Journal of Biology 2015

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VOLUME XCIX | ISSUE 1 | 2015

ALSO IN THE JOURNAL

Neuroscience SPECIAL FEATURE The Year in Biology FEATURED STUDENT RESEARCH

Spinal Pulse Inducing Neuro-Electric Stimulator S.P.I.N.E.S. (Bionic Spine Connector)


"The brain is the organ of destiny. It holds within its humming mechanism secrets that will determine the future of the human race." Quote by Wilder Penfield , Penfield, W. (1963). The Second Career. Boston: Little, Brown.

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SENIOR STAFF

Jessica Ho ‘15 Yiwen Huang ‘15 Tangirul Islam ‘15 Jiayi Lily Ma ‘15 Keti Vaso ‘15 Aaron Zhang ‘15 Betty Chen ‘15

JUNIOR STAFF

Crystal Wu ‘16 Yan Zhang ‘16 FACULTY CONSULTANT

Erin O’Leary, PhD

2015 Volume XCIX

THE BRONX HIGH SCHOOL of SCIENCE 75 West 205th Street Bronx, New York 10468 Telephone: (718) 817 -7700 Fax: (718) 733 -7951 www.bxscience.edu JEAN M. DONAHUE, PhD Principal ALLISON WHEELER, PhD Assistant Principal The Journal of Biology is published annually by the students of the Bronx High School of Science

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by Jessica Ho ‘15

It can be said that neuroscience is the central science. With the central nervous system and the vast, interconnected network of the peripheral nervous system (PNS) containing billion of neurons. billions of neurons are firing away right now. They conduct messages between sensory neurons, interneurons, and motor neurons to elicit what we might perceive as simple responses that range from lighting an arm, to moving your leg, to creating feelings of joy and anger, and to controlling the beating of your heart. Neuroscience, therefore, is in no way a simple science. It is an intricate science that today, still remains enigmatic to the best scientists around the world. How does the brain enable individuals to form dreams, hopes, and nightmares? How does the circuitry of the brain contribute to the development of diseases and mental conditions? How is the brain influenced by our environment? How does neuroscience influence who we are as a person and our lifestyle? As important discoveries are made in neuroscience, we are learning more about our brain, our mind, and ourselves.

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Commentary

What is Neuroscience ?


The Table of Contents I. Overview of the Brain Tangirul Islam- Page 6 II. Interview: Dr. Gensert Keti Vaso and Yiwen Huang - Page 9 III. Neuroplasticity Jiayi Lily Ma - Page 12 IV. “Bak Yeh” Betty Chen - Page 15 V. Effect of Sleep Deprivation on Adolescent Brain and Behavior Keti Vaso- Page 17 VI. Effect of Drugs on Brain Tangirul Islam - Page 19 VII. What is schizophrenia, what underlies its etiology, and what are its current cases and research? Jessica Ho-Page 21 VII. Amnesia: Memory Loss Crystal Wu-Page 23 VIII. Brain Tumors: The Facts and the Problems Aaron Zhang- Page 25 IX. The Year in Biology Page 28 X. Featured Student Research: Spinal Pulse Inducing Neuro-Electric Stimulator (S.P.I.N.E.S.) (Bionic Spine Connector) Page 33 XI. Student Research Abstracts - Page 41

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ARTICLE

Neuroscience: Overview of the Brain

Overview of the Brain By Tangirul Islam ‘15

The brain is the focal point of all neurological activity, averaging 3 pounds and controlling all conscious and unconscious decisions. The brain is what makes us human because it enables us to read, write, speak, think rationally and so much more. Every time we walk, raise our hands, or turn our heads, it is our brain that is both simultaneously comprehending information from the environment and sending messages throughout the body to react to the environment. You may wonder what enables the brain to perform all of its intricate tasks. The brain contains a hundred billion nerve cells called neurons, which are electrically excitable cells that process and transmit information through electrochemical signals. Three major types of neurons are motor, sensory and interneurons. Motor neurons control muscle movement and sensory neurons carry messages from the outside of your body such as your skin and send it to your central nervous system. For example, your motor neurons are responsible for your reflex when your hand moves to touch a hot object and your sensory neurons are used to tell you that the object is hot, which then causes your hand to jerk away. This reaction is called a reflex. The neuron is made up of an axon that is covered in a myelin sheath. This myelin sheath consists of fat and protein that speeds up the movement of the message between neurons, through a small gap known as the synapse. Dendrites finally connect the neuron to another neuron and the process continues as such (1). In the most general terms, the brain is made up of the cerebrum, brain stem, thalamus and hypothalamus. The cerebrum is the largest part of the brain responsible for controlling

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intelligence judgement and voluntary activities such as moving your shoulders up when you don’t know something. In the back of the skull lies the cerebellum, the second largest region of the brain that is responsible for balance in the body (3). The brain stem serves as the inter connecting region of the brain that connects the brain and the rest of the spine and central nervous system for the purpose of regulating the flow of information between the brain and the rest of the body (2). It also regulates blood pressure, heart rate, breathing and swallowing.The thalamus internally receives messages from the sense organs such as the cerebrum. These messages are subsequently sent to the cerebrum in order to be interpreted. The cerebrum controls voluntary actions which is the reason humans can do hard math problems or kick a soccer ball (5). The hypothalamus is the control center for recognition and analysis of hunger, thirst, fatigue anger and body temperature.

Figure 1. A message goes to the axon terminal through the synapse onto another neuron picked up by dendrites. The messages goes from the terminal bud and then through the axon and in the synapse where they attach to receptors (1). The synapse is located between the dendrites and the previous axon terminal (2).

In order to perform everyday functions such as running, the brain must have some type of protection, and it does! The skull covered by layers of membranes called meninges (1). Meninges protect the brain from rubbing against


Neuroscience: General Overview of Brain the bones of the skull and spine. Furthermore the brain and spinal cord have cerebrospinal fluid which aids in protecting the brain from damage during accidents such as getting hit on the head by a basketball (5). Development of the Brain The first part of the brain that develops is the brainstem and midbrain which is the top and middle portion of the brain. These regions are significantly responsible for autonomic functions such as digesting food in your stomach or regulating hormones (5). When a baby is born, the lower portions of the nervous system must be well developed before the higher regions. For humans, newborn babies develop the higher portions of their brain after birth (2). The higher portion of the brain controls emotions language and abstract thought. Each region manages its assigned function through processes with chemical messenger. (neurotransmitters and hormones) to transmit info throughout the body and the rest of the brain. Conclusion The inner mechanisms of the brain are very complex. Neurologists have spent many years to figure out how it works. The brain is responsible for a persons personality, memory, movement and senses. Thanks to neuroscience research, we are able to find out specifically which part of the brain does what and how it affects our lives. Our brain is like a computer that controls every part of our body!

Figure 2: As shown in the diagram to the left, the forebrain, midbrain and the hindbrain are developed first for babies.

References: 1. David Borsook ( 2012, February. Neurological Diseases and Pain Brain. National Geographic ; 135(2): 320–3 2. Clikeman Margaret. Research in Brain Function and Learning Retrieved from <http:// www.apa.org/education/k12/brainfunction.aspx>. 3. University of Michigan. "The Human Brain." The Human Brain. N.p., n.d. Web. 01 Jan. 2014. 4. Human Brain. Digital image. Wikipedia.org. (n.d). Web. <http://upload.wikimedia.org/ wikipedia/commons/thumb/1/1a/ Gray728.svg/1024px-Gray728.svg.png>. 5. Helen Philips. (2006) The Human Brain. NewScientist.

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SPECIAL FEATURE

Interview Conducted by Keti Vaso ‘15 and Yiwen Huang ‘15

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Interview with Dr. JoAnn Gensert Dr. JoAnn Gensert: Q. Please introduce yourself and talk about your position here at Bronx Science A. My name is JoAnn Gensert, and I’m at Bronx Science as a biology teacher. I teach research projects, AP Biology, and Research Literacy. Q. What did you do before coming to Bronx Science? A. I was a research scientist. I got my doctorate at Columbia University Medical Center. I did a post doc and fellowship at NYU School of Medicine. I was also on the faculty at Cornell and I worked at a research institute as well. Q. What were you studying during college? A. Biochemistry. I did research as an undergrad as well. My research as an undergrad involved examining the function of the 5’ planking region of the estrogen gene. It had to do with manipulating a particular region of the DNA for a gene that encodes for a hormone. Q. We heard from Dr. O’Leary that you were involved with neurobiology. Could you tell us a little bit more about that? A. Certainly. I did my doctorate in the lab of the director of neuropathology at Columbia. My research is specifically in rodents, but it applies to mammals. I was the first one to identify that proliferating cells that persist in adult mammals are able to be stimulated to differentiate into a cell type called an oligodendrocyte. Oligodendrocytes actually myelinate the neurons. So, these immature dividing cells that are in the adult brain, even in your brain, are able to be induced to become oligodendrocytes and to repair lesions. The type of lesions that they can repair are those seen in diseases like multiple sclerosis. Multiple sclerosis is a disease of the brain. For example, when you touch something hot, your brain will tell you that “Its hot! Its hot!” And the brain will say “Pull your hand away,” and a healthy person will pull his/her hand away hard. In multiple sclerosis, then this breaks down so the message doesn’t go through completely, and the person can’t pull their hand away as a reflex. These cells are actually in the brain so you don’t have to put any cells into the person and there’s no rejection issues; they’re already there. So we labeled these oligodendrocytes so we created a lesion and we showed that these oligodendrocytes wereable to repair the induced lesion. Oligodendrocytes make myelin, and myelin covers the neuron so that the message can travel long distances.

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In conclusion, we showed that these cells in the brain could differentiate and mature into oligodendrocytes. They could repair lesions in a therapeutic approach. Naturally in cross-sections of post-mortem brain tissues there might be myelin on the axon liked a swirled lollipop. However in MS brain, there is some myelination, but it is not as thick with not as many swirls. Q. What kind of implications do you think your research could have in Q. Q. What kind of implications do you think your research could have in medicine or the future? A. My research employs a more therapeutic approach to MS but it is not a cure. It is a method used to enhance lesion repair so that a person would be able to regain some functions, or not lose function as quickly. However, the actual signals that cause the progenitors to mature into oliogodentrocytes are unknown. And so, these signals must be identified. Q. What made you interested in this topic? A. I love glia. There are many different types of glia, mainly micro and macro glia. Macro glia consists of astrocytes and oligodendrocytes, and hold the brain together. It these weren’t in your body, your brain would just mush and drip out of your nose. When I first started, I did a project in a lab involving glia, and I am passionate about glia. Everybody thinks that the brain as just composed neurons, but glia are also present in neuron and allow signals to travel long distances. Astrocytes, put their endfeet around a synapse to protect the communication between one neurons. Q. More generally, how did you become interested in the field of neurobiology? A. I have always been interested in science, I’ve always been interested in asking questions and trying to understand how things work. As an undergrad I didn’t do neuro initially as I did research that was more molecular in nature. I love cells and love working with whole animals because you can see the effect. I don’t know for sure why it’s neuro, but I know it is my passion. Q. What was your favorite part about being involved in neurobiology? A. Discovering something in neuroscience could make a difference in peoples lives. My thesis advisor and I had the opportunity to do things such as brain sectioning. Columbia has a brain bank where the brains are cut in half. One half is frozen and the other half is fixed in a paraformaldehyde. Some diseases are identified post mortem only, although the symptoms may point to a disease before a person passes away, you have to cut the brain and look to verify the disease. The other thing I liked is that if there was a certain incident where the physicians were removing a tumor, for example, my mentor would have to go while the person was still being operated on, my mentor would have to go and section the pieces of the tumor removed to get the edges. That is exciting to me, and I think it’s a lot of fun. The other thing I liked that I worked on in

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terms of neuro was we showed that someone did a comparison of a type of brain tumor which is glioma and normal astrocytes. And when they did that comparison, they pulled out a couple of molecules that are expressed in one part but not expressed in another. I looked at a couple of these molecules and based on DNA structure, we proposed that it may respond to certain really cheap drugs to cause the gene to be re-expressed. And when we re-express the molecule that was in one part but was missing in the tumor, the tumor stopped dividing and stopped moving around. So that can also be a possible therapeutic treatment. And that’s exciting, because to me, you take the logic, look at system, you apply simple biological concepts, ask the right questions and do the right experiments to come up with answers that can change the lives of people. Q. How did you end up from researching neurobiology to teaching at Bronx Science? A. I’ve always been a teacher. I’ve taught Sunday school, I’ve coached volleyball on a high school and college level, I’ve taught swimming and tennis from when I was in high school all the way up, and so I’ve always been a teacher. I love teaching, and believe it or not, I love kids, including high school kids. I wanted to apply what I know to a different type of atmosphere and environment. Q. Do you have any advice for students who may be interested in pursuing neuroscience in college? A. Start learning basics as early as you can. There are many students who come up to me and say they’re interested in neuroscience and biology, but they don’t understand how a neuron functions, and that is just part of the basics. There are so many things online that you can access, or get a good neuroscience book and just go through it. So my advice would be to start learning and to read as early as you can, because who knows, somebody who’s interested in neuroscience and research can be one of you guys to discover the cure for MS, for example. The cure is coming from you young people.

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Neuroscience: Neuroplasticity

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begins to process information. In a process called synaptic pruning, unused synapses are eliminated, leaving behind efficient networks of neural connections.(1) Other forms of neuroplasticity that are induced by various circumstances have similar mechanism as the one described above. These circumstances include physical changes of the body; for example, the loss of a limb or sense organ.(1) In addition, the brain employs neuroplasticity during the reinforcement of sensory information gathered through activities such as learning.(1)

Neuroplasticity By Jiayi Lily Ma ‘15

Neuroplasticity For decades, neuroscientists believed that the functions carried out by specific regions of the brain are fixed; any incidents of brain change or recovery were considered exceptions.(1) However, during the 1970’s and 80’s, scientists changed their conventional view of the brain and accepted neuroplasticity as an important characteristic of this vital organ. Neuroplasticity is the ability of neurons and neural networks in the brain to change their connections and behavior in order to adjust to new information, sensory stimulation, development, damage or dysfunction.(1) Neural networks exhibit modularity and carry out specific functions. Nevertheless, they can diverge from their regular functions and reorganize themselves when necessary.(1) Rapid alterations or reorganization of the brain’s neural networks can happen in many forms and under many circumstances. During developmental plasticity, neurons in the young brain branch out quickly and form synapses. Some of these synapses are strengthened while others are weakened as the brain

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Adult Neurogenesis The ability of the adult mammalian brain to generate new neurons from neural stem cells and progenitor cells in a process called neurogenesis is one of the most fascinating examples of neuroplasticity.(2) Neurogenesis has sparked new interest in stem cell research because of the possibility to discover ways to enhance the regeneration of neurons in adults who suffer from neurological disease and impairment, stroke, and depression. For years, scientists believed that certain cells in the body, such as brain cells, were nonrenewable. However, many later studies indicated that these cells can be regenerated from stem cells that exist throughout life. In the 1960s, Joseph Altman reported the first evidence of adult neurogenesis in rats. (3) Yet, the idea of adult neurogenesis wasn’t widely accepted until the 1990s, when researchers found self-renewing neural stem cells that could give rise to new neural cells in the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampal dentate gyrus.(3) Similar to the neurogenesis process during development, adult neurogenesis involves a multistep process that includes cell proliferation, cell cycle exit, a choice between survival and death, cell migration, cell differentiation, and cell-fate decisions.(4) Despite this similarity, there are several significant differences between the two. The most important difference is that adult neurogenesis creates fewer proliferating cells and produces limited


Neuroscience: Neuroplasticity neuronal cell classes.(4) The cause of the adult neural stem cells (NSC) to have a more restricted neurogenic potential could be the microenvironment or the “niche” of these cells. During development, embryonic NSCs originate from radial glia and neuroepithelial cells lining the neural tubes. Adult NSCs, however, come from the embryonic neuroepithelial radial glia, with a subset of cells found in highly specialized regions of the brain such as the subgranular zone and subventricular zone. (3) Implications of Adult Neurogenesis in Various Diseases and Disorders Adult neurogenesis is affected by brain injuries and neurological diseases and disorders such as traumatic brain injury and ischemic stroke. Neurodegenerative diseases like Alzheimer’s and Parkinson’s diseases; demyelinating diseases like multiple sclerosis; epilepsy and seizure; and psychiatric disorders such as depression also have an impact on adult neurogenesis.(3) The following explores several of these diseases and disorders and how they are connected with adult neurogenesis. Brain Injury Traumatic brain injury (TBI) occurs when sudden trauma causes brain injury. Generally, TBI leads to neuronal loss and neurological deficits, especially in hippocampusdependent cognitive functions.(3) Many animal studies of both focal and diffuse TBI indicate that neurogenesis is increased in the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles after TBI.(3) However, whether neurogenesis contributes to the recovery process after TBI is another question. Stroke, a leading cause of death in humans, occurs because of ischemia blockage or hemorrhage to the brain. Studies have shown that focal or global ischemia could induce neurogenesis in adult rats and monkeys. Researchers have also demonstrated functional neurogenesis in the hippocampus and discovered that “newborn” neurons in the SVZ migrate to the damaged cortex. (3) Despite these findings, the specific role

that ischemia-induced neurogenesis play in the recovery process remains unknown. Alzheimer's disease (AD) AD is a progressive neurodegenerative disease of the central nervous system; the main feature of AD includes the accumulation of plagues and tangles in the brain, especially in the hippocampus. Another characteristic of AD is the loss of connections between neurons.(5) The role that neurogenesis plays in AD is ambiguous and complicated. In some animal model of AD, increase in hippocampal neurogenesis is reported.(3) Other evidence has indicated the opposite, however. An important characteristic of AD is the reduction of overall cholinergic signaling. The loss of cholinergic signaling has been shown to decrease adult neurogenesis in the hippocampus and olfactory bulb.(3) On the other hand, treatment with cholinergic drugs that increase cholinergic signaling has been found to induce neurogenesis.(3) Amyotrophic Lateral Sclerosis (ALS) ALS is a fatal, progressive neurodegenerative disease that affects neurons and the spinal cord. It causes rapid muscle weakness, disability, and ultimately, death.(6) There is an increase in progenitor cell proliferation, migration, and neurogenesis in mice with a mutation of superoxide dismutase 1, a mutation found in rare familial patients with ALS.(3) The neurodegenerative diseases described above influence both adult neurogenesis and neural plasticity. The genes that are often involved in these diseases (Parkinson’s disease and Alzheimer’s disease) seem to play a key regulating role in adult neurogenesis, too. (3) Major Depression Disorder (MDD) MDD is a psychiatric disorder that causes low mood, low self-esteem, and a loss of interest in activities that are usually entertaining.(3) In 2000, researchers suggested that depression is linked to impaired adult neurogenesis. Many experiments have both supported and opposed this hypothesis. Patients with chronic MDD usually have smaller hippocam-

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Neuroscience: Neuroplasticity pi. The high stress and cortisol levels usually experienced by people with MDD have been shown to decrease adult hippocampal neurogenesis.(3) Conversely, antidepressants increase cell proliferation in the adult hippocampus. Recent findings suggest that impaired adult neurogenesis affect MDD patients; nevertheless, MDD is not completely caused by weakened neurogenesis. (3)

atrophy. But when similar transplanting is applied to humans with PD or HD, mixed results were found.(3) The transplanting of adult neuronal precursor cells has also been tested. When adult spinal cord stem cells were transplanted locally into the adult dentate gyrus in rats, the generation of new neurons was observed.(3) Despite these discoveries, neurotransplantation of adult or embryonic stem/ progenitor cells in humans still present chalTreatments Involving Adult Neural Stem Cells lenges to neuroscientists due to issues such as Adult neural stem cells (NSCs) are improper delivery and migration, mass effect multipotent cells that have the ability to selfand cell death, cell manufacturing problems, renew. It has been found that adult mammalian tumor formation, and adverse immune system NSCs can give rise to functional neurons and interactions.(3) glia.(3) Although it is known that adult neuroAnother promising way of treating neugenesis plays key role in maintaining homeo- rological disorders or diseases is the stimulastasis and contribute to the plasticity of the tion of endogenous neural stem or progenitor central nervous system (CNS), scientists are cells. Active adult neurogenesis is mostly constill investigating the specific role that adult fined in the SGZ and SVZ regions of the brain; neurogenesis play. however, incidence this process is also found Adult neurogenesis seems to help to throughout the CNS.(3) Consequently, recruitrepair the CNS after a brain injury or disease. ing and activating these endogenous cells Acute brain damage usually causes an accrue- could induce regeneration and healing in inment of cell proliferation temporarily; chronic jured or diseased CNS.(3) brain damage, however, leads to a decrease in adult neurogenesis overtime.(3) Studies have Conclusion indicated that in rats, NSCs are responsible for Many cells in the body have the ability replacing dying neurons caused by direct inju- to repair and self-renew because of stem cells ry or ischemic stroke.(3) In addition, in many and of various regulating mechanisms.(3) seizure models and neurodegenerative diseases Since the brain can regenerate, it may be possisuch as Alzheimer’s Disease (AD) and Hunble in the future to use NSC-based therapy to tington’s Disease (HD), cell proliferation and cure neurological diseases like AD and brain neurogenesis seems to escalate initially at the injuries . sites of damage.(3) In patients with neuroReferences: degenerative disorders, an increase in neuro1. Rugnetta, M. (2012). Neuroplasticity. In Britannica. plasticity is also found.(3) Thus, treatments Retrieved September 5, 2013 involving NSCs may be the cure for many neu- 2. Gage, F. H., Kempermann, G., & Song, H. rological disorders. (2008). Adult Neurogenesis. (p. blurb). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. ReCurrently, there are two such NSCtrieved September 6, 2013 based treatments: Transplantation of exogenous neural stem or progenitor cells and stimu- 3. Doze, V. A., & Perez, D. M. (2012, July). G-ProteinCoupled Receptors in Adult Neurogenesis [Electronic lation of endogenous neural stem or progenitor version].Pharmacological Reviews, 64(3), 645-675. cells.(3) doi:10.1124/pr.111.004762 4. Gage, F. H., Kempermann, G., & Song, H. Scientists have found some degree of success transplanting fetal neuronal precursor (2008). Adult Neurogenesis (p. 7). Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. Retrieved cells to animals with spinal cord injury, TBI, September 6, 2013 In National Institute on Aging. ReParkinson’s Disease (PD), and spinal muscular trieved September 5, 2013

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Bak Yeh (Uncle) I've always wondered deep inside how you've managed to stay so kind. Your passion to learn, to laugh and to stay firm, is definitely a mentality that many can learn from. Although we're many miles away, and our visits have been timed, each visit has surely been infinitely sublime. The things that you have shown me though are beyond the depths of this rhyme. You've taught me to stand strong, to know no limits and to be wrong. You've truly defined the quote, "It's not about the cards you're dealt, but how you play the hand." You chased after your education and worked hard conducting your job. After many years of toil, you've finally made it to the top. You've gone above and beyond your possible limits, all the while, staying vivid. Over the years, your health has greatly deteriorated. But you're still very much extraordinarily bold. As this poem is drawing to a close, one thing is for sure, ALS may be within you, but it will surely never define you.

Written by Betty Chen ‘15

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Neuroscience: ALS Disease

Neuroscience: ALS By Betty Chen ‘15

Figure 1. Normal nerve cell vs ALS nerve cells. Amyotrophic lateral sclerosis (ALS), often also known as "Lou Gehrig's Disease�, is a progressive neurodegenerative disease that targets nerve cells in the brain and the spinal cord. Motor neurons spread from the brain to the spinal cord and then to the muscles in the body. When these motor neurons begin to degenerate, they are then unable to send impulses to the muscle fibers which would normally cause muscle movement. As a result, the brain is unable to initiate and control muscle movement. Patients in the later stages of this disease are often paralyzed. However, the current cause of this disease is unknown. Symptoms of ALS include increasing muscle weakness, especially in the arms and legs, and inhibited speech and breathing. This may lead to difficulty in projecting one's voice, as well as twitching and cramping of muscles in hands and feet. Limbs also begin to look "thinner" as a result of muscle tissue atrophies, which is when the muscle tissues decrease in size since they are unable to receive messages from the motor neurons. In order to diagnose someone with ALS, a list of cumulative tests must be done, including a spinal tap, x-rays, muscle/nerve biopsy, etc. There is not one specific test or procedure to diagnose one with ALS. Many who do develop ALS are between the ages of 40 and 70, but there are also cases in those who are in their twenties and thirties. Once diagnosed with ALS, half of all people affected live at least three years or more. Twenty percent live at least five years and ten percent live more than ten years. Although there is currently no cure for this disease, there is an FDA approved drug known as Riluzole which shows clinically that it slows the progression of ALS.

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Neuroscience: Sleep Deprivation deprivation must first be considered. Sleep is crucial, especially for developing teenagers, to provide rest for the brain and ensure it works optimally. The effects of sleep By Keti Vaso ‘15 can be considered in relation to the cerebral cortex. For example, the temporal lobe of the cerebral cortex is associated with the process of language. MRI scans on subjects who are fully rested reveal very active brain activity in this region. (3) However, in sleep deprived subjects, MRI scans have shown very little to no activity occurring in the temporal lobe. These effects on the cerebral cortex are seen to greatly impact behavior as well. The inactivity in the temporal lobe is thought to be associated with the fact that, after verbal learning tests, sleep deprived subjects were seen to exhibit slurred speech patterns, as opposed to the normal speech patterns seen in the subjects who did receive sufficient sleep. Bronx Science is arguably one of the most widely known high schools in New York City. Nearly everyone who’s heard of it is aware of how hard working and motivated all of the students in our school are. But the public is not entirely familiar with a fact more widely known among the students in our school: Many Bronx Science students suffer from lack of sleep. But are those two hours of sleep lost to cram for an upcoming test really beneficial in the long run? Sleep deprivation is thought to be undermining teenagers’ health as it has negaLimited amounts of sleep not only aftive effects on the developing brain which, confect speech patterns, but also performance in sequently, affects how teenagers behave. Not only is it becoming a rising issue for students in school. In an 1998 study conducted by psychologists from the College of the Holy Cross Bronx Science, but also for high school stuand Brown University Medical School, students all around the nation. According to the National Sleep Foundation, teenagers in Ameri- dents who reported lower grades (D’s and F’s) ca are advised to sleep 9 hours every night. But were reported to receive 25 less minutes of sleep when compared to students who reported a follow up study published in the Journal of higher grades (A’s and B’s). (2) Furthermore, a Adolescent Health reveals that only 8% of teenagers in America are receiving the required connection between sleep deprivation in teens amount of sleep. (1) Even more shocking is the and decreased levels of human growth hormone has been seen. This hormone is an essential fact that as many as two thirds of American component to the physical growth, brain develteenagers get, on average, 7 hours of sleep or less. (2) But how can we stop this rising issue? opment, and maturation of the immune system In order to answer that question, the effects of in a teenager. (3) A study conducted in 2010 by the journal, Sleep, revealed that teenagers who sleep

Effect of Sleep Deprivation on Adolescent Brain and Behavior

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Neuroscience: Sleep Deprivation stay up past midnight are 24% more likely to suffer from depression and other psychological disorders. (1) Lack of sleep can affect the descisions that teenagers make. In order to cram for tests or try to stay more alert, they may rely on caffeine, energy drinks, as well as amphetamines such as Adderall, which may have severe neurologic and cardiovascular effects on a developing teen’s body.

What steps can be taken to help increase amount of sleep for teens and decrease their reliance on unhealthy habits to stay awake? It is important that teens develop a schedule to properly balance their school work and extracurricular activities, while fulfilling the necessary nine hours of sleep every night. Routines such as listening to soft music or reading, or being in an optimal environment that is cool and dark can help one fall asleep easily. Furthermore, caffeine intake should be limited after lunchtime. There is no set cut off time one should stop taking caffeine, but it is recommended that caffeine intake should be stopped four to six hours before bedtime.

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If more teenagers and parents become aware of the serious health risks sleep deprivation poses, then perhaps more steps can be taken to ensure teenagers receive the amount of sleep their body really needs. References (1) Strauss, V. (2012, March 10). Sleep deprivation and teens: ‘Walking zombies’. Washington Post. Retrieved April 1, 2014, from http://www.washingtonpost.com/ blogs/answer-sheet/post/sleep-deprivation-and-teenswalking-zombies/2012/03/10/gIQAr0QP3R_blog.html (2) Carpenter, S. (2001, October 1). Sleep deprivation may be undermining teen health. http://www.apa.org. Retrieved March 31, 2014, from http://www.apa.org/ monitor/oct01/sleepteen.aspx (3) The Effects of Sleep Deprivation on Brain and Behavior. (n.d.). Serendip Studio. Retrieved March 30, 2014, from http://serendip.brynmawr.edu/exchange/node/1690


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Neuroscience: Effect of Drugs on Brain eating food or accomplishing something. Some drugs increase dopamine release which leads to By Tangirul Islam ‘15 addictions. For example, people can be addicted to candy because of dopamine (1).

Effect of Drugs on Brain

Have you ever wondered why drinking an energy drink makes you wide awake? Have you ever thought of the reasons that some drugs put you sleep? Most drugs work by enhancing or restricting the effects of natural chemicals in your body. In fact, this is the way that energy drinks, which can contain up to eighty milligrams of caffeine, work. Caffeine is a stimulant contained in these drinks and is naturally present in your body. Caffeine is chemically similar to a neurochemical called adenosine, which functions by binding to receptors to cause drowsiness. Caffeine, which neurons mistakenly identify as adenosine, enables caffeine to bind to adenosine receptors. Since caffeine has binded to all the available adenosine receptors, adenosine is unable to bind to the surface of neuron cells. The result is the feeling of alertness that you get from energy drinks (4). Some drugs can become addictive because they activate the brain’s “reward system”. The reward system in your brain releases a chemical called dopamine from neurons called the dopaminergic neurons found in the substantia nigra. Dopamine is naturally released when we do something that is pleasurable, such as

When you inhale the smoke of marijuana, chemicals such as tetrahydrocannabinol (THC) travel to the brain through the bloodstream and affect something called cannabinoid receptors. Cannabinoid receptors affect your physical and mental activities such as problem solving, short term memory loss, coordinating and learning. THC can affect the ability to carry out these essential processes. Cannabinoid receptors are activated by a neurotransmitter called anandamide, and THC, a cannabinoid chemical, interferes with this interaction (G. B. Shaw). THC as a result of its similar chemical nature to anandamide mocks the neurotransmitter. Instead of having anandamide bind to the cannabinoid receptors, THC molecules bind to these chemicals and cause the hazy and drowsy feeling that marijuana users feel when they are “high”(2). Neurotransmitters allows the neurons to communicate. They fill in the gaps between neurons and bind to protein receptors which allows functions to be carried out and it allows the body to be turned on and off (3). THC blocks the neurotransmitters actions, thus creating difficulties in the functions that need to be carried out by the body. Marijuana overactivates the endocannabinoid system, which heightens a person's appetite, pain sensation, mood and memory.

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Neuroscience: Effect of Drugs on Brain Some drugs, such as medicines, are beneficial for your health until over consumed. Drugs usually enhance or block chemicals already inside your system, or can increase, decrease the levels of certain chemicals (4). This can undeniably lead to catastrophic results to your mind and body. So please, talk to your doctor about drugs before taking them as they may have potentially harmful side effects. References (1) Vince, Gaia. (2005, December). Dopamine Blockers Lead Faithful Voles Astray. NewScientist Retrieved from http://www.newscientist.com/article/dn8412-dopamineblockers-lead-faithful-voles-astray.html. (2) Frood, Arran. (2011, October).Drug Hallucinations Look Real in the Brain. NewScientist,. (3) Nutt, D. (2008). Drugs on the brain. Live Well. Retrieved June 12, 2014, from http://www.nhs.uk/Livewell/ drugs/Pages/Dodrugsdamagebrain.aspx (4) Pubchem. Adenosine.. Retrieved June 12, 2014, from http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi? cid=60961#x281

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ARTICLE

Neuroscience: Schizophrenia What is schizophrenia, what underlies its etiology, and what are its current cases and research? By Jessica Ho‘15

Schizophrenia, literally meaning ‘split mind’, is a serious, chronic mental disorder that affects approximately 1.1% of the population in the United States. Schizophrenia most commonly develops in individuals who have reached adulthood. Individuals diagnosed with schizophrenia may find difficulties in maintaining normal lifestyles and find it harder to interact with others. In fact, those diagnosed with schizophrenia might experience what researchers and medical doctors called positive and negative symptoms. Positive symptoms include delusions, withdrawal, disorganized behavior, hallucinations, and abnormal perception of true reality. The distinction between positive and negative symptoms is that the former is primarily associated with behaviors not seen in mentally healthy individuals while the latter is more associated with disruptions of normal behavior. As such, negative symptoms of schizophrenia describe behaviors such as lack of drive or pleasure in life, and withdrawal from associating with others; in fact, when approached by others, schizophrenics tend to talk very little and even if they do, they may do so with monotony and with little emotion (called a ‘flat effect’). Paranoid, catatonic, disorganized and residual schizophrenia are the three most prominent subtypes of schizophrenia. As denoted by its name, paranoid schizophrenia is identified by a mistaken perception of reality, meaning that a paranoid schizophrenic loses touch with reality and begins to imagine things that are not really there. Moreover, the term catatonia, describing a prolonged state of stupor, or motionlessness and observed in conditions like depression, is additionally characteristic of catatonic schizophrenia. Catatonic schizophrenia is a less common subtype of schizophrenia

due to available and effective drug treatments. Individuals diagnosed with this type of schizophrenia experience vastly different episodes of emotions. For instance, a catatonic schizophrenia may be extremely silent, emotionless and catatonic one moment and in the next, become extremely erratic and disarrayed the next. These unpredictable episodes of behaviors, therefore, represent the quintessential nature of catatonic schizophrenia. The third subtype of the mental disorder is disorganized schizophrenia. Signs of this subtype include disorganized thinking and speech as well as the lack of facial expressions during speech (called the ‘flat’ or ‘blunted affect’) (2). Those with this chronic disorder may find it readily difficult to organize their thoughts and speech well enough and may capriciously jump from subject to subject. When speaking, they might do so in a monotonous voice and a stolid expression without a hint of emotion whatsoever. Those with a history of schizophrenia, but do not have current positive symptoms of schizophrenia are said to have residual schizophrenia. What are the current views on the etiology of schizophrenia? There is a much higher prevalence of schizophrenia in individuals with familial history of the disorder. Scientists currently believe that molecular and biochemical imbalances in the brain underlie the development of schizophrenia. Research has dawned light on two particular types of neurotransmitters called dopamine and serotonin, molecules that researchers have learned to be essential to the normal functioning of the brain. Dopamine is a neurotransmitter secreted by the dopaminergic neurons in the substantia nigra and has a crucial role in the brain, regulating the reward and pleasure centers part of the limbic system, which include the striatum. Dopamine transmits messages from dopaminergic neurons to its target cells by binding on their specific dopamine receptors. The binding of dopamine regulates a plethora of things such as physical movement, emotions, alertness, pleasure, and memory (3).

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Neuroscience: Schizophrenia In many individuals who have schizophrenia, additionally, seem to be hyperactive. Research has also shown that lowered levels of dopamine can cause hyperactivity, a diagnostic symptom of ADHD. Drugs such as cocaine can accelerate dopamine buildup in the brain, leading to maladaptive effects. Evidence of a positive correlation between the introduction of a dopamine antagonist (D2 antagonists) to a schizophrenic subject and the presence of dopamine’s breakdown product, called homovallinic acid, in urine, cerebrospinal fluid, and plasma support the hypothesis that abnormalities in dopamine levels contribute to the mental disorder. MRI studies have also demonstrated increased levels of dopamine co-transporters in the caudate nucleus and the putamen, two regions responsible for memory and motor functions respectively. These research findings have strengthened the assertion that dopamine level abnormalities contribute the etiology of schizophrenia (3). In addition to the dopamine hypothesis, amounting evidence over the years has led researchers to formulate the serotonin hypothesis which uses the abnormalities of serotonin levels as a possible basis for the development of schizophrenia. Serotonin comes from tryptophan, and was first hypothesized to play role in the disorder in the 1950s when researchers observed similarities between serotonin and lysergic acid. Lysergic acid, which is in higher levels at serotonin’s receptor sites, induces somewhat similar to a psychosis effect, allowing researchers to raise a possibility of whether serotonin may hold a degree of responsibility in eliciting the symptoms observed in schizophrenics. Despite having collected contradictory evidence as to serotonin’s role in schizophrenia, researchers have discovered that serotonin levels are abnormally elevated in the putamen, caudate, and the prefrontal cortex (might be due to reduced serotonin reuptake sites).

in turn regulated by an enzyme called glutamate decarboxylase (GAD). Studies have shown that decreased production of GABA promotes dopamine production, therefore possibly creating the symptoms of schizophrenia (3). Interesting Case Involving Schizophrenia Seven year old girl named Jan Shofield was different from other children the day that she was born. While other babies sleep about 16 -17 hours a day, Jani never slept for more than twenty minutes at a time and no more than four hours per day. At age 2, she began to ‘see’ and interact with her imaginary friends (hallucinations). Although it is normal for kids this age to have imaginary friends, what was different about Jani’s situation was that her interactions with her imaginary friends became violent. She felt as if her friends were ‘out to get her,’ and wanted to attack her. Episodes of violent behavior soon followed afterwards-she began to scratch and attack her parents-later on, became a danger to herself. In many situations, she would try to choke herself. In another situation, when Jani was locked in her room as punishment for trying to hurt herself, her parents found Jani attempting to jump out of the window. These instances exemplify that the symptoms of schizophrenia are in some cases, dangerous and can be developed at a very young age.

References 1. Caba, J. (2014, May 14). 'Born Schizophrenic': Jani Schofield And Her 6-Year-Old Brother May Be Suffering From The Same Mental Illness. Retrieved November 17, 2014, from http:// www.medicaldaily.com/born-schizophrenic-janischofield-and-her-6-year-old-brother-may-besuffering-same-mental-illness 2. Goldberg, J. (2013, May 1). Types of Schizophrenia: Paranoid, Residual, and More. Retrieved November 17, 2014, from http://www.webmd.com/ schizophrenia/guide/schizophrenia-types 3. Milind, P. (n.d.). Biomarkers/causative factors of Schizophrenia. International Research Journal of Pharmacy, 4(4), 78-85. Lastly, gamma-amino butyric acid (GABA) has 4. The 7-Year-Old Schizophrenic. (2009, October 6). Retrieved November 17, 2014, from http:// become of interest to researchers; the producwww.oprah.com/health/The-7-Year-Oldtion of dopamine by dopaminergic neurons are Schizophrenic/3

regulated by the GABAergic neurons, which are

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ARTICLE

Neuroscience: Amnesia caused functionally, or by the mind’s reaction. The brain has defense systems that can result in By Crystal Wu ’16 the loss of memories if the they are traumatic. The memories will then trigger the mind to defend itself by blocking out or forgetting the memories. (2) Memories can also be lost due to diseases or tumors. If the disease or tumor damages the temporal or diencephalic areas of the brain, then amnesia is a possible effect. One rare case was that of Clive Wearing, an English musician. His brain was damaged due to the encephalitis virus, resulting in an inability to make memories that last more than 7 to 30 seconds. However, he was still able play the piano and conduct a choir since these actions were procedural actions and that part of the mind responsible for this function was not damaged (3).

Amnesia: Memory Loss

What is Amnesia? Amnesia is the loss of memory and is also sometimes characterized by the difficulty to remember due to a traumatic event, injury, disease, drug abuse, or tumor. Loss of memory can be permanent, but not always. In some cases, memories can be recovered with the help of psychotherapy. These memories are usually memories of traumatic events or accidents. However, amnesia can also result in a permanent loss of memories. This can result in a lapse between two time periods. Depending on the length of the time, the person with amnesia can return to their normal lives with minimal help and treatment. (1) Causes of Amnesia Amnesia can be caused multiple ways. Two major causes are organic causes and functional causes. Organic causes include the use of sedative drugs, which are taken damaged parts of the brain that hold memories. The areas that are damaged are usually the temporal or diencephalic parts of the brain. The temporal part of the brain includes the hippocampus as well as the cortical areas that surround it. The diencephalic area consists of a group of subcortical structures that are located in the middle of the brain. Damage to these areas can also be

Symptoms of Amnesia The symptoms of amnesia include the loss of memories. People affected with amnesia might not know that they are missing memories. When they suffer memory loss, they forget the event and occurrences. If the memory is not brought to their attention, they might not even know that they are missing memories. For example, if a person encounters a traumatic incident, then forgets about it, the person would not know that anything is out of the ordinary unless someone tells them. If people with amnesia do know about the missing memory, they would not be able to remember anything that happened. Sometimes, however, people replace their forgotten memories with false ones. (4) Treatment for Amnesia Amnesia can sometimes be treated and lost memories can be restored. To make this possible, psychotherapy is often required. A psychotherapist can help people recover their memories

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Neuroscience: Amnesia by focusing on what happened before and anything that can link them to their memory. This sometimes triggers them to retrieve their memory. However, when it is not possible to get the memory back, a psychotherapist can help a person cope with the memory loss. As of today, there are no drugs or any form of medication that can cure amnesia. (5) Amnesia vs. Dementia The terms amnesia and dementia are often assumed by many to mean the same, but in actuality, they are different mental conditions that have different symptoms. However, there are differences that differentiate the two. One of the differences includes the symptoms of the two. Although both impair memory, amnesia is the loss of memories. This is different from dementia because amnesia is only the loss of memories and sometimes difficulty remembering future events while dementia can impair the ability to perform basic functions. Also, dementia can often worsen over time while amnesia usually stabilizes and does not get worse unless another problem causes it to. People with dementia have difficulties living in society without help. People with amnesia can often live normally since it is memories that are forgotten.

References (1) Web MD (2013). Retrieved from

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http://www.webmd.com/brain/tc/confusion-memory-loss -and-altered-alertness-topic-overview (2) Kwon JT, Jhang J, Kim HS, Lee S, Han JH. Brain region-specific activity patterns after recent or remote memory retrieval of auditory conditioned fear. Learning & Memory 2012;19(10):487-494. (3) Mastin, L. (2010). Retrieved from http://www.human -memory.net/disorders_amnesia.html (4) Mayo Clinic Staff. (n.d.). Mayo Clinic. Retrieved from http://www.mayoclinic.com/health/amnesia/ DS01041/DSECTION=symptoms (5) Nordqvist, C. (2014). Medical News Today. Retrieved from http://www.medicalnewstoday.com/ articles/9673.php


ARTICLE

Neuroscience: Tumors

Brain Tumors: The Facts and the Problems By Aaron Zhang ‘15

Brain tumors are the abnormal growth of cells in the brain or central nervous system. In a healthy individual, when cells age, the cells are eventually replaced with new healthy cells. Cancer prevents this natural cycle of recycling cells from happening, leading to the build up of unhealthy cells that eventually end up becoming tumors. A synonym for tumor is neoplasm, which is defined as an abnormal aggregation of tissue that results from abnormal growth patterns of cells. These abnormal growth patterns include metaplasia or dysplasia, which can lead to neoplasia. A micrograph of pancreatic acinar metaplasia is shown on the left. The former term means the abnormal growth of mature cells in order to adapt to environmental stress and if this stress is removed, the cells return to their original state. The latter term describes the abnormal growth of immature cells or developmental delay including maturation and differentiation of cells. Neoplasia is the progressed form of metaplasia or dysplasia and usually develops in malignant

cancers (1). There are two types of tumors; they are malignant tumors and benign tumors. Benign tumors are non-cancerous and not as rooted or attached onto the brain or as compared to malignant tumors, but are still dangerous since they can cause inflammation and place pressure on the surroundings. Thus, most benign tumors are surgically removed since they have clearly defined boundaries that separate the tumors from the surrounding tissues. The benign tumors also have a lower chance of relapse. Malignant tumors are the dangerous and cancerous tumors that grow faster and spread quicker as compared to benign tumors. The malignant brain tumors invade surrounding tissue in the brain and central nervous system but rarely spread to other organs. The exact cause of formation of brain cancer is unknown, which makes the disease so dangerous and hard to diagnose (2). However, there have been speculations of the cause through research. These causes include mutations in the DNA of brain cells and history of cancer, which means that cancers that occur elsewhere spread to the brain. These mutations usually occur in membranes covering the brain, cranial nerves, or glands found in the brain. This type of tumor is known as a primary brain tumor because they originate in the brain. The other cause of brain a tumor is considered a metastatic brain tumor or secondary brain tumor. This type of tumor is more common as compared to the primary brain tumor. The name metastatic brain tumor is derived from how tumors from other parts of the body “metastasizes” or spreads to the brain. The diagram to the top illustrates a tumor shown with an arrow. This tumor is a metastatic tumor in the right cerebral hemisphere originating from the lungs. The image is created using magnetic resonance imaging (MRI) technique, which is a very common method used to locate cancers and tumors around the body (3). There are five stages in cancer and many types of brain cancer fall under stage four – the final and most malignant phase. Malignant cells begin to metastasize. Stage four

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Neuroscience: Tumors cancers are a very serious problem and are extremely hard to treat even with the extensive medical knowledge available today (4). Certain stage four brain cancers include Ependymoblastoma, Glioblastoma, Medulloblastomas, and Pineoblastomas. Ependymoblastoma occurs mainly in young children and infants that usually occurs in the area of the brain that contains the cerebrospinal fluid. The cerebrospinal fluid is the bodily fluid found between the brain and the spine. Glioblastoma is a popular brain cancer that includes 12% of all brain cancer cases and is located in the cerebral hemisphere of the brain. This type of brain cancer targets astrocytes, which are the most abundant type of brain cell. The reason why this is a very dangerous cancer is because astrocytes serve a variety of functions for the brain and nervous system and making their growth abnormal is fatal for the patient. Medulloblastomas is another type of childhood brain cancer and originates in the cerebellum. This cancer metastasizes to many other parts of the body. Pineoblastomas is a type of brain cancer that occurs in the pineal gland of the brain. The pineal gland secretes the hormone melatonin, which monitors the sleep and wake cycles (or circadian cycles) and seasonal functions. The prefix of the word Pineoblastomas is “pine,” which is due to the shape of the pineal gland, which is the shape of a pinecone (5). The symptoms of these stage four brain cancers include hearing problems, loss of memory and coordination, vision problems, seizures and hallucinations, and weakness of the arms and legs. A recent case involving a stage four brain cancer is Riley Brilliant, a five year old child who was diagnosed with a stage four brain cancer since he was eight weeks old. His doctors said that Riley’s survival rate was only a mere five percent and that if he survived, he would be impaired in this ability to walk and talk. However, thanks to the doctors at St. Jude Children’s Research Hospital, Riley’s tumor in the left side of his brain was successfully removed at the expense of most of the left side of

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his brain. However, Riley is now able to talk and walk with limitations such as walking using crutches and talking with a habit of repetition. Although Riley’s story is one of happiness and success, there are still many cases of brain tumors that remain unresolved. Riley’s story raises awareness of the disastrous effects cancer has on people and their family and loved ones. This story also shows how the understanding of neurology can help more people like Riley survive (6). Riley’s treatment to his stage four brain cancer was through surgery. Today, there are many other brain cancer treatments which, which include radiation therapy, chemotherapy, proton therapy, and targeted therapies. Surgery is used to reduce tumor size or completely remove the tumor before it gets too large and malignant. Brain surgery is usually the first attempted treatment for brain cancer and little to no damage to the brain is dealt undergoing surgery. However this is not the case for many and a majority of the time, many important parts of the brain are removed or destroyed. Radiation therapy is used to target brain tumors that cannot be removed using surgery. This treatment uses radioactive rays to target and kill tumor cells. However, the therapy may also harm healthy cells. This is why radiation therapy is sometimes paired with chemotherapy to lessen the stress of healthy cells. Targeted therapies are also used to remove remaining cancer cells. Chemotherapy is sometimes also used to treat brain cancer. Chemotherapy consists of the injection or oral intake of drugs that target the tumor cells. This method is not always the best for brain cancers because the blood-brain barrier and small blood vessels in the brain prevent many chemotherapeutic drugs from entering the brain. Proton therapy is similar to radiation therapy with a few differences. In proton therapy, there are high doses of radiation targeting specific areas and deals less harmful effects to nearby healthy cells. This leads to fewer side effects. Proton therapy is also used to target sensitive areas of the brain that would normally be damaged using radiation therapy and surgery. Thus, this treatment is most suggested for


Neuroscience: Tumors children to reduce radiation to healthy parts of the brain and avoid long-term radiation problems. Targeted therapies are relatively new in that the drugs target the genes that cause the abnormal growth of cancer cells. There have been many clinical trials regarding this new type of therapy (7). As one can see, brain cancer is a very serious issue. Even with the advanced medical treatments available, there is still much that scientists and doctors do not know about this malignant disease. However, the understanding of neurology and medical science is increasing each day, and hopefully one day everybody with a brain disorder or brain cancer can be as successful as Riley Brilliant’s story.

References: (1) Abrams, G. D. (2008, August 25). DISTURBANCES OF GROWTH NEOPLASIA I. University of Michigan. Retrieved December 12, 2013, from http://open.umich.edu/sites/ default/files/082508.gabrams.neoplasiai.pdf (2) Brain Tumors (Benign and Malignant): Symptoms, Causes, Treatment. (n.d.). WebMD. Retrieved December 15, 2013, from http:// www.webmd.com/cancer/brain-cancer/braintumors-in-adults (3) Brain Tumor Treatment. (n.d.). Cancer Treatment and Cancer Research. Retrieved December 15, 2013, from http:// www.mdanderson.org/patient-and-cancerinformation/cancer-information/cancer-types/ brain-tumor/treatment/index.html (4) New Health Guide. (n.d.). Stage 4 Brain Cancer. Retrieved December 15, 2013, from http://www.newhealthguide.org/Stage-4-BrainCancer.html (5) Pineal gland (anatomy). (n.d.). Encyclopedia Britannica Online. Retrieved December 12, 2013, from http://www.britannica.com/ EBchecked/topic/460967/pineal-gland (6) Shinn, S. (2013, December 15). Diagnosed with brain cancer as infant, Riley Brilliant about to turn 5. Salisbury Post. Retrieved December 15, 2013, from http:// www.salisburypost.com/article/20131215/ SP01/131219787/1184/diagnosed-with-braincancer-as-infant-riley-brilliant-about-to-turn-5 (7) Staff, M. (2012, June 14). Definition. Mayo Clinic. Retrieved December 15, 2013, from http://www.mayoclinic.com/health/braintumor/DS00281/DSECTION=causes

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SPECIAL FEATURE

THE YEAR IN BIOLOGY Compiled by Jiayi Lily Ma '15, Aaron Zhang '15, and Yan Zhang '16

The Journal of Biology’s choice of the top 25 headlines in Biology for the year 2013.* *Stories were chosen by the junior editorial staff, using DISCOVER magazine’s 2013 “The Year In Science” issue as a primary guide.

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1

The rover Curiosity

has found convincing evidence showing that Mars was once habitable. The elements carbon, hydrogen, nitrogen, sulfur and phosphorous that constitute the key ingredients of life were found. In addition, Curiosity discovered certain chemicals like hydrogen sulfide and sulfur dioxide that could provide microorgan-

6

Journeying more than 15

billion miles in more than 35 years, Voyager 1 finally made it into the interstellar space, an area surrounded by gas ejected from other stars; Voyager 1 is the first man-made object to reach this area.

5

Biologists at the Department of Regenerative Medicine at Yokoham City University in Japan have successfully generated mini-livers or liver buds by taking stem cells from human skin and reprogram the cells to an embryonic state. When mixed with two other cell types, these newly created liver cells begin organizing themselves into threedimensional structures. These liver buds, when transplanted into mice, exhibited functions like metabolizing sugars and

2

On June 13, the Supreme Court invalidated DNA patents because DNA molecules are naturally occurring substances. This decision directly benefited many researchers and doctors. Labs can now conduct experiments and clinical testing on previously patented genes; medical professionals can provide pa-

3

On May 9, instruments on top of Hawaii’s

Mauna Loa volcano measured the atmospheric concentration of CO2 to be 400 ppm. For over 650,000 years, atmospheric CO2 has never reach above 300 ppm. However, CO2 concentration has increased drastically in the last sev-

4

Former National Security Agency

contractor Edward Snowden revealed to the public the US government’s top-secret surveillance program, Prism. Carried out by the NSA, this program gathers stored Internet communications from open sources and other social networking sites such as Google, Yahoo, and Facebook.

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7

Mathematician

Yitang Zhang of University of New Hampshire established in a proof that the difference of two successive primes does not increase toward infinity. His discovery laid the foundation for proving the famous “twin prime conjecture,” which states that there are

12

Climatologist Vladimir Lipenkov and his team successively removed the purest sample of ice from Lake Vostok, located in Antarctica. This body of water has been locked beneath thousands of feet of ice for around15 million years. Examining the clean ice sample obtained, Lipenkov sets out to find any signs of life in it. The climatologist states that it would be unusual if there is microbial life in the ice considering that Lake Vostok may hold 50 times as much oxygen per gallon as seawater.

11

After 20 years

of research, geophysicist William Sager and his team from the University of Houston discovered the underwater volcano Tamu Massif. It is located between Hawaii and Japan and is by far the largest volcano on Earth.

8

Ultramodern DNA extraction and sequencing techniques have allowed scientists to examine genetic codes of long-extinct species. Researchers in Denmark have successfully reconstructed the genome of a 700,000-year-old horse. Similarly, geneticists from Germany have made significant progress in reconstructing

9

Reports from the Centers for Disease Con-

trol and Prevention (CDC) have shown that for the first time in 30 years, obesity rates among lowincome preschool children have decreased slightly. Although the change is small, it could make big

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10

Princeton physicist Nima

Arkani-Hamed discovered a new kind of geometric shape called the amplituhedron. The shape’s dimensions represent information about colliding sub-atomic particles. The amplituhedron can also simply certain quantum equations, which could


13

18

In August, scientists of Univer-

sity of Washington announced the first successful brain-to-brain interface in humans. Wearing an electroencephalography (EEG) cap, Rajesh Rao, the research team’s leader, played a videogame with his associate Andrea Stocco. Stocco, with an electromagnetic pulsar put on top of his left motor cortex, and connected by Internet across the campus, received Rao’s command to “fire” . Rao’s brain wave was picked up by a com-

14

Han-

nah Gay and her team of researchers gave an HIVpositive baby a new combination of drugs within two days rather than just treating the baby with one specific drug. This yielded positive results as the HIX -child was declared to have no signs of HIV.

15

Gastric bypass surgery is a common procedure to prevent an obese person from becoming dangerously obese. A team of scientist had tried transferring microbes from obese mice to a group of lean mice. The results displayed that two weeks after obese mice had lost considerable amount of weight. The lean mice, on the other hand, maintained the same weight. According to Lee Kaplan of Massachusetts General Hospital, the new microbiota may have triggered weight loss by sending chemical signals. This causes the body to use their fat “reserves” , causing weight loss.

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Recently, researchers have discovered a chicken-sized fossil called the Aurornis Xui. This birdlike fossil has been claimed to be 160 million years old. However, through researcher’s perspective, it could be 35 million years younger. Despite the age, the fossil itself is used as a puzzle piece to unravel the mystery behind the evolution of birds.

17 Taking 50 million tiny patches of sky, scientists have created the highest resolution picture of the universe. This picture may allow astronomers to create a more logical theory about Big Bang. Planck’s telescope records light waves dating back to 380,000 years after the Big Bang.

On Feb. 15th, an asteroid travelling at a

speed of 42,000mph struck Chelyabinsk, Russia, creating shock wave that destroyed about 4,000 buildings and injured more than 1,500. Researchers from NASA estimated that the energy released by the asteroid was equivalent to 30 Hiroshima-style atomic bombs. atomic bomb.

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20

Researchers have new research on gene-

editing, more specifically on a biological process called Clustered regularly interspaced short palindromic repeats (CRISPR). Using CRISPR single celled organisms would recognize it as a invader hence activating proteins to tear the DNA apart. They were also concerned about how accurate the CRISPR could activate the proteins to cut out specific unwanted parts of the genes. They also wanted to insert a favored

gene in place of the cut up unwanted gene. Rodolphe Barrangou had discovered about CRISPR

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H7N9 influenza began somewhere in Mongolia or the Korean peninsula. The migration patterns of the birds allowed multiple influenza strains to swap pieces of genetic code and H7N9 was born. The H7N9 then hitched a ride onto the poultry markets of eastern China and by February it leapt onto humans. Most people reported to have H7N9 have had

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Bioengineer Jay Keasling from the University of California, Berkeley developed a way to make large-scale changes to the metabolic pathways of yeast to create artemisinic acid, which can be converted to aremisinin. This is important because a malarial vaccine depends on artemisinin, a derivative of the sweet

21

MacArthur Foun-

dation “Genius� fellowship winner Sara Seager from MIT is interested in studying the existence of exoplanets. Recent evidence show that many planets have environments suitable for habitation. The Transiting Exoplanet Survey Satellite (TESS) set to launch in 2017 will do an all-sky survey searching for rocky planets around common

22

The U.S. holds top spot in world natural gas and petroleum production, toppling Russia's reign over the industry. The secret behind the United States success is fracking, a method that punctures the ground in search for oil reserves.

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Malaria still prevails as one of the most dangerous parasitic diseases, with over half of the world at risk. Fortunately, scientists have created a new vaccine made from the sweet Wormwood plant that provides 100% protection against the parasite. The only downfall to this vaccine is the price, starting at $1,100/kg due to the time-consuming procedure to pro-


FEATURED STUDENT RESEARCH

Spinal Pulse Inducing Neuro Electric Stimulator S.P.I.N.E.S. (Bionic Spine Connector) Lakshmi Singh ‘13, Maliha Sultana ‘13, Phoebe Wong ‘13, and Zejia Yu ‘13 REGIONAL 1 Winners,2012

Abstract Paraplegia, also known as paralysis, is the complete or partial loss of muscular control, leading to the lack of feeling and mobility in the affected area. This growing problem distresses millions across the world. Although there are several types of therapy available for paraplegics, no definitive cure exists. Currently, scientists are regenerating functioning neurons using stem cells. However, due to ethical and technical concerns, these regenerations often lead to numerous detrimental side effects like scar tissues. Therefore, our proposal suggests a novel technique that uses electrical pulses to stimulate damaged neurons and muscles, enabling movement and alleviating pain in damaged areas. In a similar experiment, the paraplegic was eventually able to exhibit ambulation, showing potential in the success of electrical stimulation in spinal cord injury. Our vision is to create a wireless bionic spine that functions as a neuro-stimulator, to cure paraplegic cases concerning the body from waist-down.

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PRESENT TECHNOLOGY Currently, there are no known definitive treatment strategies that can bring a significant change to the condition of patients suffering from this injury. Although complete recovery of function in an injured spinal cord is still not possible, research is being conducted to promote regeneration and repair the interruption of impulses. Current technology has allowed for the repair of damages in the spinal cord so that patients could regain some movement. However, the repair of damaged neurons responsible for spinal cord injury remains limited to the area of stem cell research. Exoskeleton suits, bionic spinal discs and spinal cord stimulators bring new insight and possibilities. Scientists are currently in the process of researching the further use of spinal cord stimulation devices. Spinal cord stimulation devices are mostly used to relieve pains in limbs and ineffective areas affected by nerve damage. Pope et al (1) theorized that this neuro-stimulation produced from the device reflects the “gate control theory”. This states that a neuro-stimulus would cause the “gate”, which releases noxious stimuli at nerve ends to “close” and reduce the intensity of pain to a lower sensation. However, in a recent study (2) , a spinal cord stimulation device composed of 16 electrodes was surgically implanted into a paraplegic (from neck down) on key parts of his spine. After three days of therapy, the patient was capable of standing for at least four minutes and exhibits some ambulatory movements. During this process, he also regained some control of his autonomic functions of his bladder and bowel. Consequently, the electrical stimulation device may be used for more advanced techniques and devices in the future. Another present technology is a motorized exoskeleton REWALK bionic suit. (3) This technology provides an alternative to wheelchairs and enables patients to stand, walk and climb stairs. The device features a

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computer-based control system as well as DC motors at joints, rechargeable batteries and sensors. It is designed for durability of a wide array of moments so that it accommodates most of the patient's needs. Another rehabilitation method is the Functional Electrical Stimulation technique. (4) Functional Electrical Stimulation (FES) applies small electrical pulses to paralyzed muscles to restore or improve their function. FES can help some to improve bladder, bowel function, and reduce the frequency of pressure sores. An example of the FES is the Parastep method. It is a computerized “neuroprosthesis” system in which users hold on to a front-wheeled walker fitted with a keypad wired to a microprocessor on the belt. Electrodes are placed on the quadriceps, the muscles and the nerve. The user initiates ambulation by positioning muscles in the proper sequence. Stimulation of the quadriceps causes a contraction leading to a knee extension, which enables the user to stand. Some research today demonstrates that such a pattern may not even be necessary, in Summer’s case, muscle memory and spinal signals were initiated by the pressure of weight exerted on his legs which allowed him to stand on his own with just non-patterned electrical stimulus. (2) Though FES devices are known to use electrodes to stimulate certain points of the spine, the connector would be programmed to emit a pulse necessary to reach the point or enough to initiate a reaction that could relay the message through the stimulated neurons. The goal is to find a type of surgical battery that would provide the spine connector with enough energy so that it could last for a sufficient amount of time. Research indicates that the different types of implantable batteries: the implantable battery and various rechargeable batteries function in different ways to sustain a relatively long battery life. The implantable battery, usually found in pacemakers, is implanted under the skin and would


have to be eventually replaced surgically. As for rechargeable batteries, two methods exist. One requires the battery to be charged through an electrical wire that protrudes from the patient connected the battery inside the body to recharge it. A more popular approach is the use of radio waves. Radio waves would be emitted from an external source to recharge the implanted battery. Instead of using the current models we plan on adopting a battery recharged by different means. Present studies plan to develop a battery in the future that is self rechargeable or recharges by exploiting its surrounding environment , which we hope to use for our device. A possibility for such an occurrence in our device would be the dependency of the battery on the pulse generator, utilize part of the electricity to charge itself. Another change that can be incorporated into this future technology is the capability of the device to function wirelessly. Current concepts of spinal chord stimulation devices require a machine or small portable device to be connected to the patient to program and monitor the electrical pulsing pattern. We hope to create a connector device that would not disrupt the human body like the implantable pacemaker, as an abnormal device attached above the heart. Overall we are looking forward to discover the success of independent ambulation by paraplegics through our device. History: One of the most common disabilities today is paralysis: the loss of control over the movement of a part of the body due to an injury to the nerves. In fact, according to the National Injury Database, 250,000 Americans have spinal cord injuries every year, with 52% being paraplegic. (6) Paralysis can be classified as local or generalized and may even follow a particular pattern, depending on the affected area. In addition, a person can experience one of the various levels of paralysis such as spasticity and flaccidity. Spasticity is a form of paralysis which results in an increased tightness in the muscles when they are immobile

and often cause a person to display abnormal limb positions. Flaccidity, on the other hand, is a form of paralysis in which skeletal muscles become unresponsive due to a problem with communication to a somatic nerve. SCI can be described as a disconnection syndrome that disrupts the motor fibers from the motor cortex to the spinal neurons, and the ascending somatosensory fibers from the spinal cord to the brain. This disruption of electrical impulse conduction is what causes loss in lower body function in SCI. In the event of a nervous system injury, regrowth of axons is not possible because the central nervous system has multiple additional factors that act as barriers towards regeneration and renders the environment hostile to inherent regenerative ability. Paralysis had been thought to be incurable due to the aforementioned reasons. However, over the recent years, there have been developments in the treatments for paralysis. In fact, it was not until the recent few decades that spinal cord injury survivors have reached life expectancy that is in close proximity to the normal population. Yet, many still struggle with immobility and its complications such as respiratory infections, urinary tract infections, decubitus ulcers, cardiovascular diseases, etc. Depending on the level and the cause of paralysis the patient is diagnosed with, treatments vary. For example, a patient may work with an occupational therapist who focuses on training the patient in doing normal activities in order to allow him to develop basic skills for selfcare. Another form of treatment that patients have been exposed to in the past is physical therapy. A physical therapist concentrates on the patient’s mobility skills by working on the muscles that can still function. Although these techniques have often shown progress in patients’ conditions, they have not occurred at the desired rate and cases in which therapy has been able to completely cure paraplegics have been rare. Thus, research in this area is still required.

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Future Technology: Our vision is to create an implantable device that can replace damaged or missing sectors of the spine to restore control of the lower body called a “Bionic Spine Connector.� Spinal cord injury often leads to paralysis due to the damaged central nervous tissue, which does not have the capacity in self-healing, such as the tissue in the peripheral nervous system. Current studies are focused on the repairs of central nervous system; however our idea is focused on reestablishing connection of the neurons in the central nervous system to provide the ability for functional limbs again. Recently, a new technique utilizing electrical stimulus has shown to succeed in inducing nerve reactions. It gradually allowed the paraplegic to not only stand but also take a few steps following three days of use. If this concept were to be incorporated onto the spine, it would allow the nerves to connect to the nervous system with greater proximity and promote further movement. In addition, various electrical patterns created by an enhance program may be induced to regulate the type of movement, required by the user. For instance, if consecutive electrical impulses could move the leg four inches or if alternating electrical impulses would move the leg two inches. Therefore, by coordinating electrical impulse patterns with leg movement, we can know what impulse pattern should be used to induce a specific leg movement. Some research today demonstrates that such a pattern may not even be necessary, in Summer’s case (2) muscle memory and spinal signals were initiated by the pressure of weight exerted on his legs

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which allowed him to stand on his own with just non-patterned electrical stimulus. Though FES devices are known to use electrodes to stimulate certain points of the spine, the connector would be programmed to emit a pulse necessary to reach the point or enough to initiate a reaction that could relay the message through the stimulated neurons. One goal is to find a type of surgical battery that would provide the spine connector with enough energy so that it could last for a sufficient amount of time. Research indicates that the implantable battery and various rechargeable batteries function in different ways to sustain a relatively long battery life. As for rechargeable batteries, two methods exist. One requires the battery to be charged through an electrical wire that protrudes from the patient connected the battery inside the body to recharge it. A more popular approach is the use of radio waves. Radio waves would be emitted from an external source to recharge the implanted battery. Instead of using the current models we plan on adopting a battery recharged by different means. Present studies plan to develop a battery in the future that is self rechargeable or recharges by exploiting its surrounding environment , which we hope to use for our device. A possibility for such an occurrence in our device would be the dependency of the battery on the pulse generator, utilize part of the electricity to charge itself. Another change that can be incorporated into this future technology is the capability of the device to function wirelessly. Current concepts of spinal chord stimulation devices require a machine or small portable device to be connected to the patient to program and monitor the electrical pulsing pattern. We hope to create a connector device that would not disrupt the human body like the implantable pacemaker, as an abnormal device attached above the heart. Overall we are looking forward to discover the success of independent ambulation by paraplegics through our device. Breakthrough: The design for a bionic spine connector


Discussion: The nucleotide excision repair pathway was used as a marker to determine the DNA repair capacity of participants in this study. Benzo[a]pyrene diolepoxide adducts were used as a mutagen for the pathway to remove. There was no statistically significant correlation found between smoking status and DNA repair capacity. A benchmark of 30 percent for DNA repair capacity was used because 30 percent was the median DNA repair capacity found among participants. Among the mothers who smoked, their daughters had a DNA repair capacity less than 30 percent and this contradicts many findings which report a positive association between smoking and DNA repair capacof reestablishing nerve connection is essential to our project and is currently one of the most difficult topics to study since researchers of the past decade are still dealing with stem cells and electrical stimulus to attempt and repair nerves. Batteries used for current FES devices all either need to be recharged or replaced surgically, otherwise to have a battery wire extension from the patient’s back to the device. Our goal is to eliminate the need for surgical replacement of the battery or possibly to have an everlasting battery that is self-rechargeable. If the patient were to continuously replace the battery once worn through surgery, as is the current method, it would be troublesome for many who use the bionic connector. To relieve their problem, a small minute whole could be created small enough to connect to the device and change the battery when needed by using a small tool. The minute hole would be made of titanium with a closing to prevent any objects from entering the body. We proposed that the wireless controller device, usually implanted into the body, be removed to eliminate any unnecessary room or damage it may cause. It would also be much easier to control the device from outside than have to surgically operate on a patient to fix the device. If such a hand-held technological device could be made to program and communicate simultaneously to the bionic spine

connector, then the efficiency for the patient would increase and be much faster than the current “steps” that are now taken by the REWALK exoskeleton and Parastep device. The hand-held transmitter would also prove as a safety device in manual shutdown in case the product malfunctions. Obstacles faced by this procedure would be the signal transmission from the spine connector to the device that would be intercepted by the human torso. Types of frequency waves, such as radio waves, used to communicate with the device may also cause side effects that may damage the body so a safer method must be found in the communication process. Lastly, nerve reconnection is the key step for the device to function properly. Nervous tissue is known for its low capacity to self regenerate and repair. Damaged nerves hardly heal, leaving people paralyzed in certain areas. A possible function that could be achieved in the future is to create nanomachines or other substances to mimic the neurotransmitters released by nerves to relay messages allowing the entire body to move. Another approach could be to interpret the “messages” sent by the brain and either reroute the message or allow the bionic connector to interpret the movements and carry them out with electrical stimulation of the spine, Design Process: After we decided to focus on the spine we decided to find a solution to paralysis. This would be done by creating a bionic spine that would be located inside the body. This spine would be charged by a battery that would be connected to the spine. The battery, lithium iodide, would be the same as those used in pacemakers since they are currently the best known batteries of today to use in implanted devices. We realized that some people only have some ineffective spine segments and removing the entire spine of a human would be dangerous. Therefore, to adapt to all individuals, the spine connector would reconnect the separate or damaged spine segments to restore its ability to function properly. Contemporary studies have begun the experiment of using

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Schwann and stem cells in an attempt to reestablish nerve connection through differentiation. (8) We avoided the use of such developmental factors because little is known about nerve reconnection and stem cells are prone to become scarred tissue instead of a functioning nerve. This idea requires more experimenting and a risk that could not be incorporated into our design. In current studies for repair of degenerating spinal discs, Dr. Kennedy and Dr. Boyan are working to develop a bionic spine disc replacement made of hydrogel that would have the same strength and flexibility of a natural disc (9). For the design of our connector, the hydrogel discs would be placed at both ends of the bionic connector to imitate a more natural environment of the spine and protect the surrounding segments. Many therapies in the past only used titanium grafting which would be uncomfortable and not flexible considering we needed to implant it into the spine so the more advanced discs are to be used. Like pacemakers, the bionic connector would be composed of a pulse generator, lead systems, and battery. The rechargeable lithium iodide battery would be placed towards the back of the connector like a small capsule so it can be removed through a minute hole instead of having to replace it surgically. The programmed pulse generator would be monitored by an external device that would control the frequency, memory, and programming of the pulse generator. Most of the electrical pulse would be transferred to the leads that are placed on key points of the spine, depending on the type of paralysis, to stimulate the movement. A small portion of the electrical pulse would be transferred to the lithium iodide battery to recharge itself. We have also decided on having a palm monitor that controls and shows the pulses, patterns, and status of the bionic spine connector. In case of a malfunction in the connector this palm device possesses the ability to shut it off manually. Present treatment requires the monitoring device to be connected to the stim-

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ulation device resulting in a protruding wire from the person’s back which may result in several limitations for the person to live a normal, industrious life. This palm sized external aide seems fitting for current technology of iPads, iPhone, and other small electronic hand held devices. Furthermore, we hope to use other methods of telemetry other than radio-waves to establish a communication link between the palm monitor and bionic spine connector to avoid any overheating or radiation issues that are known to occur. The implantation of this device requires a surgical procedure to fix the bionic spine connector in a stable position and connect the leads from the device to key areas of the spine. A small hollow titanium tube, no more than 2 cm, would also be placed directly above the battery (if it is not everlasting/ selfrechargeable) and sealed securely to alleviate the irritating process of having to surgically remove the battery. A skin patch (like a fiber enforced water resistant medical tape) would be placed over it. This minute hole would be a backup for manual shut down, where each patient will be given a small screw-like tool the size of a key to manually shut down the battery by removing the skin patch and adjusting the battery off. Consequences: Once this technology is designed and fully perfected, the Bionic Spine Connector will be able to bring benefits to paraplegics. The 12,000 paraplegics who could benefit from this device each year significantly demonstrate the practicality of this technology. This device will be capable of facilitating and improving functions of the respiratory, sexual, bladder, bowel, and lower limb mobility that are associated with paraplegia through the application of electrically controlled stimulus to incite the paralyzed muscles to contract and to function. By restoring the damaged segment of the spine and simultaneously stimulating the spine, the device will “connect� the neurons that transmit signals up and down the spine. In doing so, the electrical stimulus will enable


messages to be sent to other parts of the body and coordinate movement. It would be convenient for the patients because it is easy to control. Once inserted, the device will function and operate on a pulse-charged battery. Using a rechargeable battery shows it is cheaper than maintaining a non-rechargeable system. In addition, because the device would be capable of functioning wirelessly, it would maximize the ease and convenience of usage to benefit thepatients. A negative effect of this experiment would be that the battery would need to be replaced about every ten years. In addition, having the water proof skin patch would make the replacement more accessible and less painful to the patient. Future research could develop this device so that it could help more than just paraplegic patients. A difficulty with the concept of the battery will be the obstruction of the minute hole in the back and the possibility that batteries may overheat during its use. References (1) Spinal Cord Stimulation Devices Peripheral Neuropathy FBSS CRPS (2010, December). In MISS Spine Brain Surgeon Neurosurgeon Sydney Australia . Retrieved December 15, 2011, from http://www.spinesurgeon.com.au/ modalities/ Spinal_Cord_Stimulation_Devices.html (2) Haugh, Thomas M. "Former Beaver regains ability to walk." Gazette Times 19 Mar. 2011. Web. 30 Jan. 2012. <http:// www.gazettetimes.com/news/local/ article_b8000682-8278-11e0-91e6001cc4c002e0.ht (3) Brand, Howard. ReWalk-Bionic Research. N.p., 18 Dec. 2010. Web. 30 Jan. 2012. <http://rewalk.us/>. (4) RégineBrissot, R., Gallien,, P., Le Bot,, M., Beaubras, A., Laisné, D., & Jocelyne, . (2000, February 15). Clinical Experience With Functional Electrical Stimulation-Assisted Gait With Parastep in Spinal Cord–Injured Patients. Spine, 25(4), 501-508. Retrieved December

20, 2011, from http://journals.lww.com/ spinejournal/Abstract/2000/02150/ Clinical_Experience_With_Functional_Electri cal.18.aspx (5) Spinal Cord Stimulation Devices (2002). In Virture Medical Centre . Retrieved December 15, 2011, from http:// www.virtualmedicalcentre.com/Devices.asp? sid=2 (6) Gilbert, Ronald R.Spinal Cord Injury Facts. Foundation for Spinal Cord Injury Prevention, C, 2001. Web. 30 Jan. 2012. <http:// www.calvin.edu/library/knightcite/index.php>. (7) Hobson, K. (2011, May 20). An Electrical Jolt for Paralysis Research . In Wall Street Journal . Retrieved December 15, 2011, from http://online.wsj.com/article/ SB10001424052748704083904576333672813 390298.html (8) Samar, H., & Hayek, R. (2008, August 2). Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: an overview. Europe Spine Journal, 17(9), 12561259. Retrieved December 21, 2011, from http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC2527422/ (9) Mallela, Venkateswara, V Ilankumaran, and N Rao. "Trends in Cardiac Pacemaker Batteries."Indian Pacing Electrophysiol Journal”4.41 Oct. (2004): 201-12. Web. 30 Jan. 2012. <http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC1502062/>. (10) Maugh, T. (2011, May 19). Former Beaver regains ability to walk. Gazette Times. Retrieved December 21, 2011, from http:// www.gazettetimes.com/news/local/ article_b8000682-8278-11e0-91e6001cc4c002e0.html (11) Kennedy, S., & Boyan, B. (2005, July 4). Bionic Spine-New Discovery to Aid Treatment [Electronic version]. Retrieved January 17, 2011 from http://www.wowt.com/news/ features/2/1658247.html (12) Ludbrook, K. (2011, October 3). Bionic Spine Enables Girl to Walk Again [Electronic version]. IOL Scitech.

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Webpage References: (1) Henry F. Duston D.D.S, M.S. Web. 30 Jan. 2012. < http://4.bp.blogspot.com/_g_KhGa4HxMw/ TQFr0oTOLNI/AAAAAAAAANM/eaqvGdIq5os/ s1600/man_fifties.casual.jpg (2) Bambi SCI Revoery Project. Web. 30 Jan. 2012. <http://www.bambi.net/bob/thesis_paraplegic.jpg >. (3) Spinal Cord Stimulator. Web. 30 Jan. 2012. <18. http://www.njsrlaserspine.com/Portals/16887/images/C-Users-dgoldberg-Desktop-eon-mini-spinal-cordstimulator-3.jpg >. (4) Spine. Web. 31 Jan. 2012. <http:// wordsandpicturesarerascals.files.wordpress.com/2011/04/spine_jpg.jpg>. (5) Medical Pace Maker. St. Jude. Web. 31 Jan. 2012. <http://upload.wikimedia.org/wikipedia/commons/8/82/ St_Jude_Medical_pacemaker_in_hand.jpg>. (6) Color Pal Multi Parameter Patient Monitor. Web. 31 Jan. 2012. <http://image.made-inchina.com/2f0j00BeKaWEnRgTob/Color-Palm-MultiParameter-Patient-Monitor-JERRY-I-.jpg>. (7) Bionic Suit. Web. 31 Jan. 2012. <http:// cdn.medgadget.com/img/robodudes.jpg>. (8) Nanomachines. Web. 31 Jan. 2012. <http://www.def -logic.com/articles/nano1.jpg>. Spinal Cord Stimulator. Web. 31 Jan. 2012. <http:// www.njsrlaserspine.com/Portals/16887/images/C--Users -dgoldberg-Desktop-eon-mini-spinal-cord-stimulator3.jpg>.

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Research

Article References

Abstracts of Student Research (‘11-’12)

cells. Results confirm that redox ratios (calculated using images obtained via MPM) are highly specific for both internal and external factors that may cause metabolic changes; additionally, this technique can be used to preBy Sahil Agrawal dict the metastatic potential of cancer cells. Thus, MPM and cancer cell metabolism have major implications in The abnormal and uncontrolled proliferation of cells is one of the hallmarks of cancer. Early detection of can- bolstering current cancer diagnosis. cerous tissue results in excellent prognosis, but if the tumor is allowed to metastasize, or proliferate, it can Exposure to a Western Type Diet Causes Cardiomyhave detrimental consequences, including death. As a opathy Characterized by Mitochondrial Dysfunction result, it is imperative that cancer be detected in its earli- Due to Impairment of Fatty Acid and Glucose Utiliest stages. However, current diagnostic techniques are zation in Young Mice limited in their ability to successfully differentiate between cancerous and non-cancerous tissue; additionally, By: Alexandru Barbulescu conventional techniques cannot reliably characterize the metastatic potential of tumors. Therefore, a technique Obesity is an independent risk factor for heart failure that can both (1) clearly differentiate between cancerous resulting from consumption of a “western”-type diet that and non-cancerous tissue and (2) provide indication of is rich in saturated fat and carbohydrates. Exposure to the metastatic potential in its earliest stages would be of an ALIOS (American lifestyle-induced obesity syngreat benefit to the medical community. One emerging drome) diet has been found in recent studies to recapitudiagnostic technique that is currently being evaluated late many of the classic findings of the human disease in involves targeting cellular metabolism as a means to mice, leading to pre-diabetes, obesity, and cardiomyopadiagnose cancer; this is accomplished by calculating the thy. Heart tissue from 4-week-old mice fed either reguoxidation-reduction ratio of NADH to FAD, key players lar or an ALIOS diet for 4-16 weeks were analyzed for in cellular metabolism. However, despite the multiple immunohistochemistry, RNA and proteins specific to applications of metabolic monitoring in disease studies, cardiac metabolism. Exposure to ALIOS diet caused a few instruments exist that can accurately characterize 40% decrease of PGC-1 mRNA, a key regulator of mitocellular metabolism. This study evaluates the applica- chondria biogenesis and metabolic pathways required tion of a novel optical technique, Multiphoton Microsco- for producing ATP. This was associated with downregpy (MPM) in determining the metabolic status of cancer ulation of mRNAs of proteins involved in fatty acid beta Assessing the use of Multiphoton Microscopy Derived Redox Ratios as a Diagnostic Tool for Cancer

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-oxidation, glucose transport, mitochondrial biogenesis by the scientific community as a legitimate scaffold for and ATP synthesis (~50% ALIOS versus control diet). transcription. Proteins that interact with the nuclear In contrast, angiotensin-converting enzyme (which matrix are thus important in developing a platform for makes angiotensin II, a potent cardiac growth factor) transcription. Some cancer cells have been shown to was increased 8-10 fold together with fetal phenotype display irregular nuclear matrixes, further implicating markers suggesting a switch from adult to fetal cardiac the role of the nuclear matrix and its proteins in mainphenotype. In conclusion, exposure to ALIOS diet caus- taining proper regulation of transcription. Therefore, es obesity, cardiomyopathy and insulin resistance due in understanding the interactions between proteins of the part to the heart’s inability to metabolize fatty acid and nuclear matrix is essential to understanding how these diseases develop. However the study of matrix proteins glucose. has been hindered by their property of binding to the insoluble nuclear matrix. Standard methods to detect The Antioxidant Potential and the Effects of Phaleria protein interactions like immunoprecipitation are unable Nisidai on Human Peripheral Blood Mononuclear to isolate protein complexes from the nuclear matrix. Cells (PBMCs) of the Immune System To overcome this problem a molecule FBA was synthesized that can target, preserve, and isolate proteinBy William Borenzweig protein interactions in the nuclear matrix. This method uses a photo-activate cross linker to tag proteins in proxPhaleria nisidai is a plant reputed by the Palauans who imity to the protein of interest. To test the effectiveness use it to stimulate the immune system, warding off flu of FBA, EZH2 (Enhancer of zeste homologue 2) was and illness. Little is known about this plant and only used as a model system to see if known interactions can one other group in the world has studied its extract’s be detected with the photo-activate cross linker system. effects. Bioactive plants often have antioxidant activity. In cells containing EZH2 with a target sequence for Using a DPPH assay, a water extract was shown to have FBA, we effectively isolated proteins know to interact antioxidant potential. To assess the immunostimulatory with EZH2. activity of the plant an ELISA assay was used to quantify the levels of IFN γ secreted by peripheral blood mononuclear cells (PBMCs) that were incubated for 72 The Effects of Elevation, Azimuth, and Year on Red hours in methanol, ethanol and water extracts. This in- Spruce Dieback in the Adirondack Mountains, New terferon stimulates macrophage response, and protects York State uninfected cells during viral invasion from natural killer By John Castro cells by increasing MHC-I surface protein expression. By carrying out an ELISA on the supernatant of treated This study assessed the overall mortality of current PBMCs, we determined that the extracts of P. nisidai year red spruce branches, as well as the previous two stimulate immune response by increasing IFN γ produc- years. It was hypothesized that the current year branchtion. The methanol extract was the most active, and was es would have a higher mortality percentage as opposed therefore selected for the first steps of bioactivity-guided to the previous two years. A previous study done to fractionation, a process that separates the extract into assess the mortality percentage of 2003 and 2004 fractions by polarity. PBMCs were then grown in the branches in the Adirondack mountain peaks was incorfractions and another ELISA was used to determine IFN porated. In review the study yielded similar results to the γ production. The butanol partition was most active, 2004 study, with a survival percentage for the “current stimulating more IFN γ than any other tested Phaleria year” of seventy percent as compared to the ninety pernisidai extract. This fraction will be separated further cent survival for the previous year branches. The curuntil the active compounds are isolated. These finding rent study further proposed climate as a major factor for are significant because they validate the traditional med- apical dieback in red spruce. Such a study depicted an icine and they suggest potential for a future im- overall 68% survival for the 2004 period which exhibitmunostimulatory drug. ed a decrease in temperature, while the 2010 current year stems had a 72% survival rate and had an increase Proximity Labeling: A Method For Detecting Protein in temperature. However, there was no significant difference between the survival percentages which exhibit-Protein Interactions ed different climate patterns, and weakens the argument of climate as a major factor. It is further suggested that By Adrian Carcamo the lower survival rate for current year’s stems may be an artificial value. The nuclear matrix is becoming more widely accepted

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fusion. To quantify changes in nuclear size, cells with large nuclei were fused to ones with normal or small nuclei. It was observed that the average N/C ratio for the vacuolar mutants was lower than in the wild-type strain and it can thus be concluded that vacuolar size affects nuclear size, but how mating cells with nuclei of different sizes affects the nuclei of heterokaryons remains to be determined. HIFD is a Chromatin-Associated Ubiquitin Ligase By Yuwen Cheng HIFD is an orphan ubiquitin ligase. Here we show that HIFD is a nuclear protein tightly associated with chromatin that binds specifically to the phosphorylated form of H2AFX (gH2AFX), a histone variant involved in the DNA damage response (DDR). We also show that the C-terminal portion of HIFD is responsible for this interaction. We found that HIFD associates with H2AFX in a DNA-independent manner, but also interacts with other DDR proteins in a DNA-dependant way, probably through its interaction with H2AFX. In order to investigate the crucial interacting residue on H2AFX, we successfully established an inducible system allowing the expression of exogenous H2AFX and its mutants in the context of H2AFX-deficient Mouse Embryonic Fibroblasts (MEFs). We found that depletion of HIFD hinders H2AFX turnover during the DDR and hypothesize that this regulated turnover may inhibit DDR signaling after successful DNA lesion repair. Implications of Neutrophil Proliferation in DT Treated Mouse Liver Cells By Ryan Chiew Liver fibrosis is a condition of excess amounts of collagen formation in the liver causing liver inflammation. As an increasing number of people contract HBV, HCV and liver cancer, liver fibrosis has become more prevalent an issue. According to the National Institute of Diabetes and Digestive and Kidney Diseases, 20% of Americans have fatty liver and that statistic is on the rise. However, there have been many attempts by the scientific community to develop new and innovative ways in which liver fibrosis can be combated. Currently, researchers make use of animal models in order to reach success in potential treatment methods such as new antibiotic treatment methods. Although the reason is unclear, success in animal models has been far easier to achieve than in human models. Before anti-fibrotic therapies can be fully implemented, key obstacles remain to be overcome. The neutrophil is the most abun-

dant type of white blood cell in the immune system. In current experimental flow cytometric evaluations of liver fibrotic mice cells, neutrophil levels were observed. Scientific experimentation has shown that neutrophil proliferation increases when mice liver cells are treated with diphtheria toxin, resulting in dendritic cell depletion in the liver cells of mice. As a result, dendritic cell depletion results in an increased level of neutrophils in the liver. In turn, the neutrophils live for a longer period of time. Based on this finding, it was hypothesized that the lives of neutrophils are prolonged because they avoid apoptosis in the liver as a result of dendritic cell depletion caused by treatment with diphtheria toxin. Modeling Stem Cell Proliferation and Differentiation in Hybrid Spheroid Cultures of Cancer Tumors By Bhargava Chitti A mathematical model was created to guide cancer treatment from the Hybrid Spheroid Assay (HSA), an in -vitro culture of patient tumor tissue used to optimize radiation treatment. The model used four cell types, Cancer Stem Cells (CSCs), Growing and Static Amplifying Transit Cells (ATCs), and fibroblasts. Previous models did not include all four cell types; some deemed ATC proliferation insignificant – shown to be false here. Previous models were also defined in terms of physically immeasurable parameters - eliminating ability to test and verify, or use them in practice, along with several other errors - such as failing to account for cell media exhaustion and having overly high CSC fractions. This model only used physically measurable parameters, ensuring applicability to patients. Model growth rate was compared to those of experimental growth curves, by trying different values for the number of days corresponding to a single generation (generation time). With a generation time of 1.5, the model growth rate matched experimental curves, indicating that the model accurately represents HS growth. Equations written for the model ensure high precision in modeling each individual patient tumor. Calculations done to determine when model cell growth ought to cease, due to media exhaustion greed with the model, and in the future can be used to verify and implement correct generation times that result in accurate models. Insight from this model will be used to optimize HSA cancer treatment by attacking cancer when it is weakest - providing optimal and minimal radiation treatment for each individual patient. Chemotherapeutic Drugs and Glycolysis Inhibitors Function Synergistically to Kill Cancer Cells While Attenuating Side Effects of Cancer Treatment

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By Florence Dasrath The Warburg effect is a well-known characteristic of cancer cells. Usually, cancer cells rely on glycolysis as their main source of energy and undergo little to no mitochondrial respiration when compared to normal cells. This project was designed to take advantage of this characteristic and target cancer cells with a combination of chemotherapy drugs and glycolysis inhibitors. Here we show that using these two types of agents in combination effectively kills the cancer cells and significantly decreases the required concentration of each agent, demonstrating a synergistic effect. Cell proliferation assays were used to demonstrate that when the drug Doxorubicin is used in combination with either 3Bromopyruvate or 2-Deoxyglucose (two glycolysis inhibitors), the concentration of each agent required to kill almost all of the cancer cells is lowered to approximately half the value of the concentration used to kill almost all of the cancer cells when used separately. These results indicate a novel line of therapy for cancer treatment in which conventional chemotherapeutic agents and glycolysis inhibitors may be used in combination, thereby decreasing the required dose of commonly used chemotherapeutic agents and hence drastically reducing potential side effects without compromising efficacy

Analysis of Musical Preference By Matthew Eakle Music is an interesting aspect of human society in that it is so commonplace, and yet very little is known about why we enjoy it. Researchers such as Paul C. Vitz, Carol Simon, and David Huron, among others, have learned much about why people enjoy music by studying specific elements of music, such as patterning, or by studying other ways in which music can be measured. This study focuses on two elements found within musical melodies: contour (the musical shape) and interval size (the distance between consecutive notes). These elements were used to measure variation (the change in pitch) in melodies found in musical patterns by quantifying the change in intervals by half-step differences (the smallest distance between two distinct notes); a change of one halfstep was awarded one “point.” Thirty-nine original music pieces were created specifically for this study, and each subject listened to each piece two separate times. On one occasion, they rated the piece on a scale of 1 to 7 on how much they enjoyed the piece, with 1 being “dislike a lot” and 7 being “really like.” On the second occasion, the subjects rated each piece on a scale of 1 to 7 on how much variation (change in pitch or note) they thought the piece had, with 1 being “no variation” and 7

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being “a lot of variation.” The data shows there was no real trend or association between variation and enjoyment, even based on the subjects' own ratings. However, there was a correlation between the subjects' ratings of variation (“Perceived Variation”) and the variation as mathematically measured for this study (“Measured Variation”), showing that the method of measuring variation used in the study was able to somewhat model the variation as determined by the subjects. These findings seem to contradict the results of Paul C. Vitz (1964, 1966), who found a trend between variation (as measured using the information equation, H = -Σplog2p) in the shape of a bell-curve. Protein Expression of L. Monocytogenes P60 and Name Autolysins in E. coli By Aurel Frangaj Bacteria like Mycobacterium tuberculosis and Listeria Monocytogenes have been shown to infect the body by using a set of secreted proteins, known as SecA2 system autolysins, to lyse the cell walls properly for replication and to give off cell wall fragments that trigger inflammatory responses in patients which actually boost pathogenicity. These autolysins also appear to be necessary in the transfer of secondary immunity after their fragments induce dendritic cells so it is wondered what type of fragments are produced by these autolysins and which ones play a role in inferring immunity. To ready a model that could test which fragments were important, two SecA2 autolysins, one believed to be relevant to immunity, p60, and one not, NamA, were cloned into plasmids, expressed in E. coli, and purified. The research yielded proteins ready for further work in lysis of cell wall for the identification of fragments produced, and their effects on dendritic cells in vitro. This type of work could eventually lead to vaccines capable of immunizing patients of SecA2-baring bacteria with these crucial cell wall fragments. Audiovisual Integration of Words in Children By Gabrielle Frankel Summation is the combination of two separate stimuli in order to improve perception ability. The summation of audio-visual stimuli is specifically the integration of visual and auditory stimulation in the brain in order to better perceive what is being presented. The purpose of this study is to determine the degree to which children are able to summate audio-visual stimuli and compare it to a previous study done using the same methodology in adults. This was done by presenting a bimodal stimulus to children in visual and auditory noise. Noise is defined here as irrelevant and meaningless stimuli.


Children were both read and shown a four-letter word and then asked to identify the word. It was found that the index of summation, or level of k value, in children was not significantly different from that of the average index of summation in adults, supporting the theory that children and adults have the same ability to summate. The child participants in this study had an average k value of approximately 0.77. This value is extremely comparable to that of the adult summation as adults. In order to better perceive what is being presented. The purpose of this study is to determine the degree to which children are able to summate audio-visual stimuli and compare it to a previous study done using the same methodology in adults. This was done by presenting a bimodal stimulus to children in visual and auditory noise. Noise is defined here as irrelevant and meaningless stimuli. Children were both read and shown a fourletter word and then asked to identify the word. It was found that the index of summation, or level of k value, in children was not significantly different from that of the average index of summation in adults, supporting the theory that children and adults have the same ability to summate. The child participants in this study had an average k value of approximately 0.77. This value is extremely comparable to that of the adult study, with an average k value of approximately 0.75. This supports the theory that children have the same index of summation as adults. Regulation of Cancer Initiating Stem Cells through Translation Factor By Michela Garabedian Breast cancer affects millions of people worldwide. The expression of proteins that promote cell survival and metastasis are important to the breast cancer phenotype. Cells that have undergone an epithelial to mesenchymal transition (EMT), whereby cells change morphology and become more invasive, contain high levels of proteins promoting cell motility. Another important aspect of cancer initiation is the cancer stem cell (CSC) theory. The CSC theory states that a population of cells that are quiescent and evade treatment may resume uncontrolled cell division by currently unknown mechanisms. It has been hypothesized that the mTOR pathway plays a major role in the initiation of EMT and the activation of CSCs. The mTOR pathway is a nutrient-sensing pathway that regulates proteins involved in breast cancer. One downstream target of the mTOR pathway is translation factor eIF4B, which, when phosphorylated and activated, stimulates the RNA helicase activity of eIF4A which in turn affects translation initiation. As eIF4B is so heavily involved in translation initiation, it is hypothesized that manipulation of eIF4B activity through

its over-expression as well as mutation of its phosphorylation site would cause changes in phenotypic markers typically associated with EMT and the activation of CSCs. The results of this study indicate that cells overexpressing eIF4B, both wild type and mutant versions, caused significant increases in some but not all CSC and EMT markers. If eIF4B is a regulator of the CSC and EMT phenotype, it would be possible to use this translation factor as a chemotherapeutic target to inhibit cancer induction. Adenosine: a Potent Agent in Dermal Fibrosis By Enkhmad Gereltogtokh Fibrosis, a disorder of the connective tissue, is a feature of many potentially fatal diseases, such as scleroderma (SSc). Fibrotic dermal tissue of SSc patients notably exhibit dysregulated expression of friend leukemia integration factor-1 (or Fli-1), a transcription factor that regulates collagen synthesis, and elevation in the expression of the vasoconstrictive peptide endothelin-1 (or ET1). Since expression of TGF-β, a negative regulator of Fli-1, is elevated by adenosine, and antagonism of the adenosine A2A receptor prevents dermal fibrosis in a murine model of SSc, this study sought to determine whether adenosine mediates expression of Fli-1 and ET1 in dermal fibroblasts. Skin biopsies were obtained from CD39/73 knock-out (KO) mice, which are deficient in adenosine, and wild-type (WT) control mice. The tissues were fixed with 10% formaldehyde, mounted on slides, stained for Fli-1, and the Fli-1 positive cells were quantified using a light-microscope. Normal human dermal fibroblasts were also treated with adenosine receptor A2A agonist, antagonist, antagonist and agonist together, and a control. The cells were harvested after 6 hours and 12 hours of treatment, and their expression of mRNA coding for ET-1 and the associated receptors was ultimately profiled using real-time PCR. Adenosine was to found to suppress Fli-1 expression in vivo based on the significantly higher amounts of Fli-1 positive fibroblasts in the CD39/73-KO mouse tissue compared to the WT mouse tissue. Adenosine was also found to promote the expression of ET-1; the highest increase in the expression of ET-1 and its receptors was observed in the presence of the adenosine A2A receptor agonist. The inhibition of adenosine A2A receptor topically may be effective in treating dermal fibrosis associated with SSc.

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The Effect of Transmission Rate on the Evolu- time. However, this procedure resulted in a flatter length distribution of microtubules. In addition, it was found that tion of Virulence of Pseudomonas Phage Φ6 microtubules cannot be continuously disassembled and then reassembled because the tubulin is unable to polymerize after a certain number of cycles. For future research, an By Henry Groos environment containing a low tubulin concentration and The correlation of transmission rate and virulence is sup- microtubule nucleation sites can be obtained by polymerizported by the trade-off hypothesis. As the transmission rate ing tubulin for a short period of time (1-2min) and separatof a virus increases it evolves towards a lower viru- ing the small microtubule seeds from the excess tubulin lence. Basically the more viruses there are infecting a giv- using an airfuge. The microtubule seeds could then be incuen number of hosts the less progeny they will reproduce per bated with a solution containing a predetermined low tubuvirus to avoid eliminating the host. An experiment was lin concentration. designed aimed at testing the extent to which this theory was true utilizing the Pseudomonas phage Φ6 as a model. The Significance of Histidine 133 to the Structure of the Profilin-Actin Complex Pseudomonas syringae (PP) was used as the bacterial host for the Φ6 allowing for the virus to produce progeBy Andreas Hadjigeorgiou ny. Different amounts of Φ6 were added to the same amount of PP and the amounts of progeny produced were recorded. This was done over approximately 100 genera- Profilin-1 is a protein found in all eukaryotic cells and is tions in hope that final generation of the virus for each vital for the restructuring of the actin cytoskeleton, and its amount would have virulence properly adapted for it its isoform, Profilin-2, is found much less commonly and host size. The final generations of the virus were put to a mostly in neurons. The actin cytoskeleton is responsible for final test to determine whether or not they were able to major functions of the cell, including cell division, cell moevolve their virulence in a manner that would allow them to tility, and intracellular motility. Profilin releases actin at the leading edge of the cell to allow actin to polymerize and reproduce without outsourcing the PP. propagate into a microspike, which induces cell motility and allows for the restructuring of the actin cytoskeleton, Controlling the Length Distribution of Microtubules but the mechanism in which Profilin-1 or Profilin-2 releases actin is not fully understood. It was hypothesized that the Polymerized in Vitro protonation of an amino acid in Profilin-1, Histidine 133, was responsible for a structural change in Profilin-1, which By Vivek Gupta would result in actin not being able to stay bound to Profilin-1. Profilin-1 experiences this conformational change Controlling the length distribution of microtubules polwhen it approaches the leading edge of the cell, where the ymerized in vitro is necessary in order to successfully inpH level is lower than the bulk pH of the cell. The pKa corporate them into molecular shuttles, often created by value of Histidine 133 interferes with the midpoint of the adsorbing kinesin motors to a substrate while microtubules bulk pH and the pH at the leading edge of the cell, indicatglide on top of them. These molecular shuttles have iming that the amino acid is protonated at the lower acidity. mense applications in molecular transport, biosensing, ac- However, Profilin-2 contains a Tyrosine residue in place of tive self assembly, and various other subfields. In order to the Histidine residue in Profilin-1, suggesting a different create a more uniform length distribution of microtubules, mechanism to release actin. Computer simulations using tubulin dimers were polymerized in the presence of a miGROMACS were used to examine structural properties of crotubule associated protein fraction (MAPF). Increasing Profilin-1 when this amino acid is protonated, and the bindconcentrations of MAPF resulted in shorter microtubules ing site of actin on Profilin was found to be unstable and and a reduction in microtubule length variance, which is altered relative to the native state of Profilin-1, indicating a lesser affinity to bind to actin. Furthermore, the simulation highly desirable. of Profilin-2 at the pH of the leading edge of the cell, where It was hypothesized that microtubule polymerization results Histidine-133 would be protonated in Profilin-1, displays in different microtubule lengths because some microtubules that Profilin-2 does not display similar structural changes as begin to nucleate or initially grow at different times. MicroProfilin-1 does, strongly implying a different mechanism tubules were disassembled at various temperatures for varifor the release of actin. ous time periods in order to determine which method is effective in depolymerizing microtubules by length without disrupting their nucleation sites. This was done so that miA Comparison of Apical and Basal Dendritic Maturity crotubules could be shortened into nucleation sites at low and Morphology in Pyramidal Cells of Decry Deficient temperatures, and then elongated at physiological temperaMice: a Possible Role in Schizophrenia Caused by the tures (cycling between assembly and disassembly). Eventu22Q11.2 Microdeletion Syndrome ally, the tubulin concentration in solution would not be high By Anthony Hagouel enough for further microtubule nucleation to occur. At this point, all the microtubules would begin to grow at the same

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Patients with 22q11.2 Microdeletion Syndrome have been shown to have a high risk of developing schizophrenia. These patients have a deficiency of a gene, DGCR8, which is responsible for the biogenesis of microRNA (miRNA), tiny pieces of messenger RNA which play a critical role in the development of neuron differentiation, maturation, and maintenance. This study examines the effects of a mice engineered with a deficiency of Dgcr8, and compares the maturation rates of dendritic spines, or, neuron receptors spanning the first and fifth cortical layers of the prefrontal cortex. After sectioning the samples of the PFC stained with green fluorescent protein (GFP) and DAPI, images were acquired using confocal z-stacks. The images were then analyzed using a Neuronstudio software program, where the diameter of the spines was taken, as well as their distances from the branch. It was found that spines of basal dendrites in layer V were more mature in wild type mice than they were in heterozygous mice, whereas the spine maturity had no significant difference in apical dendrites of layer I of either wild type or heterozygous mice. However, it was also found that apical dendrites had spines with smaller head width than of those located on basal dendrites. The study provides evidence suggesting an important role of Dgcr8 in the maturation of dendrites located in basal dendrites located in cortical layer V, while Dgcr8 plays a lesser role in the development of apical dendritic spines in cortical layer I. This study may suggest therapies for patients with mutations of the DGCR8 gene, but also provides key information to pinpoint pathways in the brain based on new advances in electrophysiological studies of the neuron and ultimately lead to possible genetic therapy measures.

in RIT is A33, whose expression is largely restricted to colorectal tumors and colon mucosa. The purpose of the research was to develop and test a non-linear simulation study of an isotope of Iodine-124 attached to a33 mAb, to test its optimal affinity to colon tumors. This model was used to fit the tumor, normal colon, and blood kinetics measured by positron emission tomography (PET) in 11 colorectal cancer patients to a non-linear compartmental model (system of non-linear differential equations). Then to use the best-fit model for each patient to calculate the hypothetical therapeutically optimum dose (in milligrams, mg) of A33 mAb for RIT. Based on the uniformly excellent goodness of fit, this non-linear compartmental model appears to provide an accurate representation of the kinetics of radioiodinated A33 mAb in colorectal cancer patients and successfully yielded a patient-specific optimum dose of A33 mAb (in mg) for RIT. The implications present a significant advance of RIT, with its unique use of simulation models for mAB pharmacokinetics, and for future treatment of colorectal cancer. A major breakthrough for individualized cancer therapy. Iron dose not Modulate the Inflammatory Response in a Murine Macrophage Cell Line By Jinseok Hong

Cardiovascular disease is the leading cause of death in the United States. Iron overload has been associated with the risk of cardiovascular disease in the past. It has been hypothesized that iron contributes to cardiovascular disease by modulating the inflammatory response, which is the primary mechanism through which atherosclerosis contributes to cardiovascular disease. The hypothesis was tested A Computer Simulation Study of Individual Radioimby using lipopolysaccharide (LPS) to induce the inflammamunotherapy of Cancer Non-Linear Compartmental tion. Cultured RAW-Blue murine macrophage cells were Modeling-Based Determination of the Optimum Dose of treated with ferric ammonium citrate (FAC), deferoxamine A33 Monoclonal Antibody for the Treatment of Colo(DFO), both, or neither in order to affect the iron status of rectal Carcinoma the cells. The differential iron status was assessed by Western blotting, measuring the expression of ferritin, the By Hassan Hamade intracellular storage form of iron. Activation of nuclear factor (NF)-ĸB, a transcription factor involved in the inCancer remains one of the leading causes of death worldwide. It is far more difficult to control once it metastasizes flammatory response, was measured using a reporter assay. The pro-inflammatory cytokines, tumor necrosis factor and produces lesions throughout the body. Treatment of (TNF)-a and interleukin (IL)-6, were measured in culture metastatic cancer therefore requires a systemic therapy such as chemotherapy, which is often highly toxic and rare- supernatants. No significant differences were detected in ly curative. Therapies which specifically target metastatic NF-ĸB activation or pro-inflammatory cytokine secretion among the different macrophage cells containing different cancer lesions and spare normal tissues are therefore urgently needed. Monoclonal antibodies (mAbs) against tu- amounts of iron. These findings do not support the hypothmor-specific and/or tumor-associated cellular antigens hold esis that iron stores in macrophages modulate the inflammatory response to LPS. great promise for highly specific treatment of cancer. However, despite intensive research over the last several decades, the treatment of solid tumors with radiolabeled mAbs, termed “radioimmunotherapy (RIT),” has generally yielded disappointing results. This is due to the inherent antibody-combative nature of the cellular physiology. However, a promising mAb for targeting colorectal cancer

Fingerprinting Amorphous Pharmaceutical Mixtures using the Atomic Pair Distribution Function By John Hong A lot of attention has recently been given towards amor-

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phous drugs due to their high aqueous solubility. A new melt-quenching method was devised to produce amorphous drugs, and the Atomic Pair Distribution Function (PDF) was performed to analyze amorphous acetylsalicyclic acid (ASA) and amorphous acetaminophen. They were mixed in different ratios and the mixtures were fingerprinted using PDF. The level of similarity between the mixture and the pure component reveals the level of composition of the pure component in the mixture. The resulting PDF output was not detailed enough in this study to accurately fingerprint the amorphous mixtures. Inherent difficulties, such as low diffraction intensity due to the small nucleic size of elements in organic compounds, along with amorphous drugs lacking definite long-range structure were encountered. Further methods of possible improvements are discussed and suggested. Immuno Electron Microscopy of Endocytosis in the Nematode By Ayesha Hossain Endocytosis is the process by which cells are able to internalize molecules such as proteins by engulfing them. C. elegans are microscopic worms useful for studying functions of certain proteins in the endocytic pathway. It was known where most of the antibodies were to localize, with the exception of TAG-1 Rabbit 1 and TAG-81 Rabbit 2. In order to find out where they localize, C. elegans tissue embedded in plastic resin was sectioned and exposed to primary antibody and then to secondary antibody linked with gold particles. These gold particles show where the proteins have bound to in the intestine. Although the results do not show precise specific labeling, antibodies such as ARF-6 and EEA-1 localized to vesicles and areas near the basal lamina. TAG-81 Rabbit 1 and TAG-81 Rabbit 2 both localized in the lumen of the intestine and were much more concentrated in the lumen, than other places in the intestine. This probably occurred because the antibody localized to E. coli bacteria present in the lumen. The Study of the Relationship Between Aerossol Optical Depth and the Total Column Water Vapor off the Coast of Africa By Tahsina Islam High absorbing aerosol levels as well as water vapor levels were found with in West Africa, mostly due to biomass burning. Aerosols can directly change the cloud cover through direct means of radiation as well as indirectly through microphysical interactions between water droplets and aerosol particles. The semi direct effect is also a claim supported by many climate models. In this study, the correlation between aerosol optical depth and the total water column vapor is analyzed from observational data. Data taken from the OMI Aura satellite of the aerosol optical depth

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from coast of West Africa was compared to the reanalysis taken from the ECMWF station of the total column water vapor. A correlation analysis was done from various periods to understand the relationship on smaller scale. Results show very little correlation between the two factors showing a possible lack of correlation and even a lack of the semi direct effect at this scale. Bypassing- Mediated Suppression of Cell Prolifera in Cancer By Clarissa Lau Numerous common cancer cell lines including adenocarcinomic human alveolar basal epithelial (A549 cells), testicular cancer, lung cancer, bladder cancer, breast cancer, colon cancer, ovarian cancer, and cervical cancer cells (HeLa) down-regulate splicing of macroH2A1.1, a variant isoform of macroH2A1 histone or protein that compacts DNA within cell nuclei. MacroH2A1.1 considerably differs from the average H2A histone because it comprised of a macrodomain, capable of binding many metabolites, including one formed by Poly ADP ribose (PARP). Former results demonstrated that macroH2A1.1 splicing is down-regulated in order to bypass its suppressive mechanism, which was accompanied by decreasing PARP levels. However, several cancer cell lines, particularly the osteosarcoma cell line (MG-63), demonstrated high rates of macroH2A1.1 splicing. To investigate the pathway by which these outlier cancer cells bypass mH2A11.1 proliferative suppression, MG63 cells’ DNA was sequenced and gel electrophoresis using protein isolated from MG-63 and human fetal lung (IMR90) cell lines were carried out. Sequencing of MG63’s macroH2A1 exons exhibited direct correspondence between the experimental and wild-type exons, implicating that no mutations were present. However, a discrepancy did exist between MG-63 and IMR90 cell lines’ PARP levels; the absence of macroH2A1 in MG-63 did not impact PARP levels, but the removal of macroH2A1 in IMR90 caused elevated PARP levels. The pathway by which MG-63 cells bypassed macroH2A1.1-mediated proliferative suppression was therefore found. These results serve as the foundation for further research on determining the defected components of this pathway, and therefore for the development of a new cancer treatment. Inhibition of the JAK/STAT3 Leads to Increased ERK and ERB/HER Family Receptor By Shu Hui Liu Cancer is characterized as uncontrolled and irregular cell growth. Since breast cancer has the second highest diagnosed cancer in women and chemotherapy is not very effective, many new treatments are currently being developed. Like these treatments, JAK inhibitor, a known inhibitor of the JAK/Stat3 pathway, was found to be an effective treatment initially, but over time, cells soon became re-


Bacteremia: an AGR-Status Independent Infection By Samantha Lau Staphylococcus aureus is the cause of many hospitalacquired infections. When it colonizes an individual, it is usually found on the skin, in the anterior nares or in the bloodstream. It was hypothesized that the isolates in the bloodstream are of the same mutant as those in the anterior nares. To test this hypothesis, cultures from both the blood and the anterior nares of patients infected with Staphylococcus aureus bacteremia, and cultures from only the anterior nares of patients that were not infected with Staphylococcus aureus were collected. The agrstatus, mutations and repeats of the cultures collected were determined by cross-streaking colonies from diluted bacterial solutions, by extracting the DNA of the colonies, and by spa typing them to sequence the DNA. In comparing the agr-status of the cultures from the anterior nares and from the blood, it was found that the agr-status of the cultures were the same. Furthermore, it was found that mutations and repeats of the cultures from the anterior nares and from the blood were identical. Therefore, it was concluded that patients are colonized by Staphylococcus aureus strains of one mutant, and that the hypothesis that cultures in the bloodstream are derived from the isolates in the anterior nares was supported. It was also concluded that the agr-status of the strain does not affect the probability of developing a Staphylococcus aureus infection. An Analysis of the Feasibility of the Refuse Derived Fuel in New York City

waste management method of exportation. I found that RDF was a better choice than exportation, as it saved money and greatly reduced environmental impacts, especially air pollution.

LIN-53 Chromatin Factor Versatility is Revealed Through Inductions f Cholinergic Neuron Cell Fate in the C.Elegans Germline via UNC-3 Expression By Christina Liao Some transcription factors, called master regulatory factors, activate genes that give a particular cell type its terminal identity. It had previously been shown in Caenorhabditis elegans, a model organism with 302 neurons and its entire genome mapped out, that RNAi knockdown of lin-53 chromatin factor, a regulator gene, allows che-1, the mass regulatory factor of ASE neuron fate, to convert other cell types into ASE-like neurons. Specifically, ASE neuron cell fate was able to be induced in the gonads of worms in which che-1 expression was ubiquitously induced. Additionally, it was also shown that unc-3, a mass regulatory factor of cholinergic motor neurons, was also able to induce expression of cholinergic markers after lin-53 knockdown. However, the inducible unc-3 used in those experiments was expressed as an extra chromosomal array. In this experiment, we successfully converted cells of the C. elegans germ line, after knockdown of lin-53, into cholinergic neurons in worms. We used a strain containing unc-3 integrated into the genome. Previously this was only demonstrated for ASE chemosensory neuron fate. These findings suggest versatility of genes, such as lin-53, identified as safeguards to cell fate.

By Annie Lee As one of the biggest cities in the world, New York City generates a total of approximately 25,000 tons of solid waste per day. After the Fresh Kills landfill in Staten Island closed in 2001, NYC has been looking for other ways to dispose of its waste. Currently, the city exports all its solid waste to other states using trucks, barges and trains. This system of waste management is highly inefficient, since one ton of waste traveling hundreds of miles creates air pollution from transportation, not to mention the lethal greenhouse gas methane generated from landfilling. A possible alternative to exporting waste would be to build a Waste to Energy (WTE) facility in the city, and dispose of the waste there. As the public would probably not be supportive of an incineration plant located nearby, a good WTE technology to use Refuse Derived Fuel (RDF). This would allow the facility to take the city’s waste and turn it into storable fuel, and ship it to coal plants as a substitute for fuel, as opposed to burning the fuel on the spot. This paper used an analysis approach to determine whether or not RDF would be a good alternative to the current

Dynamics of Blood Vessels in a Totally Vascularized COrnea By Derick Liu With the increased exposure to the different types of media in the world more people are impairing their vision resulting in increased contact lens use. The already high number of Corneal Neovascularization (NV) sufferers will only increase since a good percentage of contact lens wearers develop corneal NV. The purpose of the experiment was to find out whether the blood vessels found in a fully vascularized cornea is dynamic or static. This is an important issue because by simply finding out the answer can open the door to research on new methods of treating neovascularization and angiogenesis or it can eliminate an option allowing more focused research on other forms of treatment. The data gathered in this experiment came from pictures taken from live mice which were genetically bred to develop corneal neovascularization; the pictures were taken by a different researcher several years previous to this

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The Effects of Bezafibrate and Reseratrol on Barth Syndrome Cells By Rachel Mandelbaum Barth syndrome (BTHS) is a serious X-linked genetic disease. It is found only in males because of its genetic nature, and it is present from birth till death as there is currently no possible cure. It causes the most damage to the mitochondria of the cell, and the phenotypic effects of this disorder are mainly seen in the heart of the patient. Treatment for BTHS is possible, although it is not always effective. This is mainly because current technology is only able to treat the symptoms of the disorder, rather than fix the actual cause, which is a genetic mutation on the X chromosome. In this study FDA approved drugs were tested for their ability to treat some of the mitochondrial malfunctions caused by BTHS. The drugs tested in this study are bezafibrate and resveratrol. These drugs are known to have possible benefits to mitochondrial disorders, hence their use in this particular experiment. Effect of BDNF on Astrocytic Gap Junction Protein Connexin43(CX43) in Regard to Cerebral Ischemia By Ishita Metkar Astrocytes are cells that help neurons maintain homeostasis in the CNS. These cells form a well-connected and synchronized channel for passing substances that may aid neurons. This channel is formed through the use of gap junctions. Gap junctions form channels known as hemichannels, between cells, and coordinate cell-to-cell communication. Alterations of gap junctions during ischemia are a major source of debate in the scientific community. Some believe that these junctions allow cells to survive, while others believe that they pass along apoptotic signals and are “bystanders” to cell death. In this project, the effect of Cx43, a protein that makes up gap junctions, was studied during cerebral ischemia in astrocytes. Cx43 is also involved with cell migration; its effects on migration were studied using the wound healing model on a cell culture. It is also believed that Cx43 might be affected by a neurotrophin, BDNF, during cerebral ischemia. It has been observed that BDNF levels increase under pathological conditions and that BDNF acts as a neuroprotector, but it is not known whether it functions through increasing Cx43 levels.

Analysis of MicroRNA Sequence Variations Associated with Cancer

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By Anton Morozov MicroRNAs are short regulatory RNA molecules of 22 nucleotides in length that control gene expression by inactivating messenger RNAs (mRNA) of the target proteincoding genes. MicroRNAs play an important role in regulating many cellular functions; many of them had been shown to be involved in cancer. Recently, it was demonstrated that sequences of many microRNAs are being altered after they have been synthesized as a result of “untemplated sequence editing” (UE). In several cases it was shown that UE influences microRNA function and serves as an additional regulatory mechanism. The highthroughput analysis of microRNA sequence variations conducted in this study revealed a significant level of UE in both normal and cancer samples. For 26 microRNAs, the level of UE in cancer samples was significantly different from that in normal tissues. This suggests involvement of microRNA UE in human cancer. Some of the identified microRNAs are known to be involved in cancer, while others are new candidates for future directed experimental studies. The new information connecting UE of microRNAs with cancer will serve to further our knowledge of this disease and promote the development of a cure. Adenosine A3 Regulates Osteoclastogenesis By Yaseen Morshed Osteoclasts are multinucleated giant cells which play a key role in bone resorption. Adenosine, a purine molecule, plays a key role in several physiological processes in the body--including osteoclastogenesis (the formation of osteoclasts). Adenosine has four G-protein receptors, of which three are known to have a direct role in the regulation of osteoclasts. A3, the most recently discovered receptor, is not well known in terms of its functionality. Whether a relationship exists between A3 and osteoclast formation was observed using a highly selective A3 agonist, IB Meca, and a highly selective antagonist, MRS 1191. Using TRAP staining to observe the direct effect of the agonist and antagonist, the role of the receptor on osteoclast population was observed. NFATc1, a transcriptase factor specific to osteoclast differentiation, was also measured using a Western Blot. A decreased expression of NFATc1 and a decreased number of osteoclasts visible under TRAP staining suggested that the A3 receptor serves to inhibit osteoclastogenesis. Inhibition of the A3 receptor, therefore, can be applied to degenerative diseases as a novel therapy.


sistant. Stat3 has been found to be activated in a number of cancers, making JAK/Stat3 pathway inhibition very significant. Therefore, the goal of this study is to examine the mechanism of this resistance. This study revealed that JAK inhibitor increased erbB/Her family (EGFR, erbB2/Her2, erbB3/Her3) receptor phosphorylation in ER+/PR+ and HER2 overexpressing breast cancers. This suggests that the erbB family members and its downstream oncogenic pathway Ras/Raf/MEK/ERK may play a key role in JAK inhibitor resistance. Flow cytometry analysis indicated that there was G2/M blockage when the cells were treated with JAKi. In the Her2 overexpressing breast cancer cell line (BT474) there was a large increase in percentage of dead cells manifested by sub-G1 level with the addition of Lapatinib (known inhibitor of both EGFR and erbB2 and is clinically active against breast cancer) and this increase was significantly enhanced by combination therapy with JAK inhibition. Finally, through duolinks assay, it was revealed that this resistance may be mainly due to interaction between JAK1/2 and Her2. Therefore, further studies are warranted to test these effects in in vivo, pre-clinical experiments. FAT1 Methylation and Breast Cancer By Marina Loizou Recognizing how cancer cells spread throughout the human body can offer significant insights and lead to improved therapeutic approaches. One of the critical events that can lead to cancer development and progression is the inactivation of tumor suppressor genes. In this study, we examined the inactivation of tumor suppressor genes through epigenetic silencing, specifically DNA methylation, in the tumors of breast cancer. It is known that DNA methylation silences a gene by either completely blocking gene transcription or marking chromatin changes which are incompatible with transcription. It has also been observed that DNA methylation of tumor suppressor genes is commonly seen in cancer tissue and is frequently associated with transcriptional silencing of the involved gene, leading to tumorigenesis. A myriad of tumor suppressor genes have been found to be methylated in breast cancer. However, the FAT1 tumor suppressor gene, which has been found to be methylated in cancers such as leukemia and pancreatic cancer, has been previously found to be overexpressed in breast cancer. Different fragments of the FAT gene that were previously found to be differentially methylated between normal and tumor breast tissue using the HpaII tiny fragment Enrichment by Ligation-mediated PCR Assay were examined in this study in order to determine and validate the methylation status. The objective of this study was to determine whether the FAT1 tumor suppressor gene displays aberrant methylation patterns in breast cancer and to observe whether a link exists between FAT1 overexpression in breast cancer and DNA methylation. In this study, we have observed decreased methylation of FAT1 in the tumors of breast cancer which indicate the overexpression of the FAT1 gene is linked to DNA methylation, a novel observation of FAT1 in breast cancer. We have demon-

strated through this study that a relationship exists between the overexpression of the FAT1 gene that has been previously observed by scientists and DNA methylation and that this overexpression of the FAT1 gene is not attributed to other factors, such as alterations that result in uncontrolled cell proliferation due to deletions or point mutations. Further examination of the FAT1 gene in breast cancer in future studies must be conducted to clarify the mechanisms that account for the hypomethylation of the FAT1 gene in breast cancer. The Power of a Touch: Silencing a Gene By Erica Ma DBC2 (deleted in breast cancer 2), is a tumor suppressor gene, involved in breast cancer. There is not much about this gene’s cellular function however it was demonstrated that it suppresses breast cancer. Over the last several years, various laboratories have developed inducible systems for analyzing mammalian gene expressions. These systems are often classified based on the type of inducer that is used to regulate the system such as antibiotics, steroid hormones and IPTG. However, there are limits to these systems. Some of these inducers are toxic to mammalian cells and some systems cannot be reversed. Scientists are working to develop the ideal inducible regulatory gene system with the following characteristics. Gene expression should not produce ambiguous results or have harmful effects on the organism under study. A physiological response should be able to be studied when high levels of the inducer are present and the induction of gene expression should occur only when the inducer is present and should be specific for the target gene. The inducer should not be toxic to the cells and should not alter the expression of endogenous genes in any way. The system should be fully reversible, such that gene expression occurs at the will of the researcher and results obtained with these systems should be able to be repeated in vitro and in in vivo within the desired target tissue. My project focuses on developing my own inducible gene system and using that system for DBC2.

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Environmental Enrichment Influences Neuronal Structure well into Adulthood

Parcellation of the Amygdala Using Probabilistic Tractography By Jonah Pechenik

By Olivia Munk Numerous studies have demonstrated mitigation of functional impairment through environmental enrichment. Conversely, environmental deprivation has been shown to be detrimental to cognitive development. There appears to be a “critical period” of neuronal plasticity occurring early in life during which the brain is particularly susceptible to external stimuli. Here we show that the critical period of neuronal plasticity is not as hard-wired as once thought. In this study, we explored the limits of this “critical period” by investigating the effect of combinations of enrichment (E: toys), deprivation (D: bilateral trimming of whiskers) and control (C: standard housing) on neuronal structure. Mice were assigned to the following groups: enrichment for 60 days (EE), deprivation for 30 days followed by enrichment for 30 days (DE), deprivation (30 days) then control (30 days) (DC), enrichment (30 days) then control (30 days) conditions (EC), or control conditions for the full 60 days (C). Adult mice exposed to environmental enrichment (EE and DE) developed neurons with longer dendrites and denser spines. We show here that the window for neuronal plasticity extends well into adulthood, and that neuronal structure can be influenced in the mature brain by enrichment. Clinical Findings in Age-Related Macular Degeneration (AMD) and their Correlation to Visual Acuity Outcome After Cataract Surgery By Samriti Pal

Age-related macular degeneration (AMD) is the leading cause of blindness in the US among the elderly. Because of this, it is necessary to identify the major risk factors of AMD and determine ways to minimize their impact. The purpose of this project was to study those retinal changes and evaluate their effect on visual acuity after cataract surgery. Fundus color photos of each eye in 29 AMD patients and 28 control (non-AMD) patients were examined for the presence of types of drusen, pigment abnormalities, and geographic atrophy. Visual acuity was recorded before cataract surgery, and 1 month & 12 months after it. Control patients were more likely to regain vision than AMD patients after cataract surgery. As the results suggest, patients with significant retinal changes due to AMD should be made aware of the less favorable prognosis with regard to visual improvement following cataract surgery.

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Functional analysis of the amygdala has demonstrated parcellation on a more detailed level. The amygdala has also been linked to fear association and has demonstrated connections to the prefrontal cortex and the hippocampus. In this study, we probed the correlation between post traumatic stress disorder (PTSD) and the physiology of regions in the amygdala connected to other neural regions associated with fear. First, masks of the brain were generated and registered to diffusion weighted images of the brain. Then, Diffusion Tractography was performed to define probabilistic connections between the amygdala and other areas defined as regions of interest. Using clustering methods upon the connectivity profiles of voxels in the amygdala, 4 distinct functional regions will be defined. Results are defined as the vector representing the change a clustered PTSD amygdala undergoes to have the same dimensions as a control Amygdala. It is theorized that the volume of neurons connecting to the occipital to the prefontal cortex will be severely diminished in PTSD patients. Changes in regional functionality within the amygdala are important as they can identify neural interactions which suffer the most from PTSD, and how they are afflicted.

Estrogen Suppresses NF-KB Inflammatory activity Through Regulating the Degradation of IKBA and the Nuclear Translocation of P65 By Anne Qiu Cardiovascular disease is more prevalent in men and postmenopausal women than in premenopausal women, leading to the hypothesis that estrogen protects against these diseases. However, a mechanism through which estrogen exerts a protective effect in cardiac gender disparity diseases has yet to be clearly defined. NF-кB (nuclear factor кB) is an inducible transcription factor that promotes inflammation upon activation and is implicated in the promotion of cardiovascular diseases. In this study, a potential link between estrogen treatment and the NF-кB signaling pathway was investigated. Mouse macrophage Raw 264.7 cells were stimulated with lipopolysaccharide (LPS) to induce the NF-кB pathway activity in the presence or absence of estrogen. Various markers of NF-кB pathway activity were assayed. The results indicate that estrogen treatment inhibited LPS-induced expression of several genes known to be regulated by the presence NF-кB binding sites in their promoters, including TNF-α, IL-1β, and IL-6. This suppression of NF-кB signaling activity by estrogen was further confirmed by an NF-кB dependent reporter gene assay. Western blot analysis showed that exposure to estrogen reduced


LPS-stimulated degradation of the NF-кB inhibitor IкBα at an early time point, and also decreased the translocation of the NF-кB subunit p65 to the nucleus at a later time point. Together, these results imply that estrogen regulates NF-кB pathway activity through the regulation of IκBα degradation and p65 nuclear translocation and through a mechanism that may involve the non-genomic effects of estrogen. An Analysis o the Genetic Stability of the Drosophila Melanogaster Fly in Response to Environmental and Genetic Stresses

ing and enclosing. The flies were categorized as Tb (heterozygotes) and non-Tb (homozygotes). The homozygotes were hypothesized not to develop to adulthood because of the mutation (spz/spz) on its third chromosome; two sets of mutations on the third chromosome are usually lethal and cause the flies to die. However, the results indicated that the homozygotes developed to adulthood but at a slower rate than that of heterozygotes. The results also showed that the Tb flies developed more than the non-Tb flies, proving the hypothesis (Tb flies would develop more than the non-Tb). The next step would be to investigate cell competition in wing discs of spz mutants to see the role of spz in the development of Drosophila.

By Mohammed Rahman For an organism to survive and reproduce through several generations it needs to consistently express its genes and produce proteins required for its survival despite the slightest change in its surroundings. This experiment concerns the robustness of the Ultrabithorax (Ubx) gene of the Drosophila melanogaster fruit fly. Experiments have shown that crossing Drosophila flies of differing genotypes results in silencing of Ubxenhancers, regions of DNA which increase levels of gene transcription at the promoter, in the offspring. However, it was also observed that despite the silencing, the amount of Ubx protein produced remained unchanged and thus no phenotypic expression of the abnormal genetic background was recorded. In this experiment, the hypothesis of the inherent robustness of the Ubx gene was again affirmed through long term exposure of the fruit flies to environmental stresses (temperature variability) as they developed. Results showed that haltere size remained constant, an indicator of no change in Ubx protein levels. Moreover, in continuation with prior experiments, the effect of genetic variation on Ubx enhancer silencing was observed. In this case, however, position effect variegation (PEV) was used as a marker for change in genetic background. Although the measured change in PEV of the flies clearly showed that there had been alterations in the genome of the offspring produced by the genetic variation, it cannot be said that these changes are in any way directly linked to the silencing of the Ubx enhancers. The Role of Spaetzle Gene in Drosophila Growth, Survival, and Cell Competition in Reponse to Stress Conditions By Reshma Ravindran The purpose of the project is to study the role of Spaetzle in development. Spaetzle (spz) has shown a role in the Toll Immune Pathway as well as a role in maintaining loser status in cells during cell competition. To determine whether spz has a role in cell competition and growth of the flies, spz mutants were placed under stress conditions to see how they develop; stress is considered to be a form of cell competition. The flies were placed under 25 degrees Celsius and observed to see the number of pupae wandering, pupat-

Epigenetic Agents in Von Hippel-Lindau Activiting the Renal Cell Cancer (RCC) Pathway By Junaid Saleh Esa RCC is widely regarded by the scientific community to have poor prognosis due to the lack of identified therapeutic targets, an early diagnosis, and a lack of prevention. RCC has been associated to arise from genetic disorders, such as Brit-Hogg-Dube and von Hippel-Lindau. A further analysis into VHL, including the mutations in its nucleic acid sequence, as well as the level of methylation in the gene was conducted in order to build a stronger link between the VHL gene and RCC. It was found that point deletions in the VHL gene were significant, along with high methylation silencing VHL were present in Renal Cell Cancer cells. The Effect of the 3’ Untranslated Region of Oct. on Stel Cell Gene Expression By Brianna Saunders Embryonic stem cells are unique in the human body because they have the ability to change into multiple different specialized cells. Pluripotent, or embryonic, stem cells have the full capability to develop into cells of all three germ layers, ectoderm, mesoderm, and endoderm; whereas specialized stem cells are limited in their differentiation capacity, and may differentiate only within a specific group (Thomson et al., 1998). Certain transcriptional genes such as Oct4 (Van den Berg et al., 2010), Sox 2, and Nanog (Rodda et al., 2005; Chambers and Tomlinson, 2009) regulate pluripotency and self-renewal in stem cells and are down-regulated when a cell differentiates. Here we show that the 3’ untranslated region (UTR) of one of these genes, Oct4, is involved in this regulation as it decreases expression when cloned into an expression system. An understanding of additional genes that could be used to regulate cell fate is important because of their therapeutic value in diseases where cell division plays a role, such as cancer.

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An Optimization of the Sonogashira Process; a New Road to Heterocycles

Effect of SS31 on Cytochrome C-promoted Oxidative Stress in Mitochondria

By Andrew Shakalis

By Michelle Soto

As palladium catalysis has gained more and more popularity in organic synthesis, the need to optimize the reactions that employ it has become great. The formation of methyl 2 alkynyl-benzoate through the Sonogashira reaction was of interest due to the effects of its heterocycle derivatives. To achieve the effective formation of this product, the Sonogashira reaction’s conditions had to be modified to optimize yield. The modification of base amines and the use of copper catalysts were the major modifications researched, applied to the couplings of benzoate, benzamide, and benzoic acid with phenylacetylene. The results concluded that the inclusion of pyrrolidine and copper perfected the yield of alkynyl benzoate. The results are a possible backbone to the one pot formation of isocoumarin, whose effects on disease are noteworthy. Thus, the project focused on the efficient formation of heterocycle precursors, through an optimization of the yield of the Sonogashira reaction.

Mitochondria are essential in the conversion of food energy into ATP, a form of energy usable by cells. One mitochondrial molecule of principal importance in the production of ATP is cytochrome c. However, upon binding with cardiolipin, a phospholipid found in abundance in the inner mitochondrial membrane, cytochrome c undergoes a conformational change which leads to the peroxidation of cardiolipin, increased reactive oxygen species production, and unregulated apoptosis. SS31 is a novel cell-permeable tetrapeptide that targets the inner mitochondrial membrane to promote electron transfer. In this study, the ability of SS31 to inhibit the conformational change in cytochrome c and the peroxidase activity of the cytochrome c/cardiolipin complex was studied using spectroscopy. The results indicated that SS31 is able to prevent both cytochrome c structure change and peroxidase activity induced by the cyt c/ CL complex. This study provides compelling discoveries on the role of SS31 as a mitochondria-protective molecule. Impaired Function of Mutated Carboxyterminus of CXCR4 in Whim Sydrome

Chemical Modulation of Ciliary Dynamics and Cell Cycle By Vincent Shieh Primary cilia are hair-like organelles that extend from the plasma membrane to sense and transduce extracellular signals. Many diseases, collectively known as ciliopathies, are associated with defective ciliary formation and function. Primary cilia are displayed on quiescent (G0/G1) cells, and are resorbed as the cells re-enter the cell cycle. However, the biological relevance of these temporally coupled events was unclear for more than thirty years. Recent studies have suggested that cilium disassembly is required for cell cycle re-entry, and subsequently, cell division. Thus, we hypothesize that chemicals, which are shown to block ciliary resorption, might have an ability to inhibit cell proliferation. These chemicals might have a potential application in the treatment of cancer and other proliferative diseases. Based on this hypothesis, we have conducted small-scale screening to identify molecules that exhibit the ability to block ciliary re-sorption. Our results demonstrate methimazole has the ability to inhibit both ciliary resorption and cell division.

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By Raina Sun Chemokine receptors are important in immune disease pathology. Recently, mutations in the chemokine receptor CXCR4 were identified in an immunodeficiency disease, the WHIM syndrome. WHIM, which stands for wart, hypogammaglobulinemia, infection, and myelokathexis, is characterized by chronic noncyclic neutropenia. Studies have shown that the impaired regulation of receptor signaling is associated with the truncation of the cytoplasmic tail domain and is a crucial part of disease pathogenesis.We describe here mutation truncation (RY) and mutation without truncation (PO) of carboxy terminus of CXCR4 in response to the agonist SDF-1α. Compared to the internalization of wild type CXCR4 stimulated by SDF-1α, the lack of internalization for RY and PO cells suggest the significance of these mutation points in the development of WHIM. While CXCR4 regulates the retention of neutrophils, a related receptor, CXCR2, regulates neutrophil migration to sites of inflammation. Additionally, we studied the relationship between CXCR2 and CXCR4 and their cofunctions in mutated cells. Although there were no significant changes in the level of CXCR2 after SDF-1α stimulated internalization of CXCR4, the two receptors still may be functionally related in their downstream signaling pathways. These influences of CXCR4 and CXCR2 on their respective pathways, upon stimulation, need further study.


The Insufficiency of Biomarkers in the Identification Breast Cancer Stem Cells: Hybrid Spheroids as a Functional Assay

An Analysis of Hippocampal Astrocyte Morphology in Rat Models of Epilepsy By Diptesh Tailor

By Talal Syed Recently, modern cancer therapies have begun focusing on targeted stem cell therapies to treat and cure cancer. Cancer stem cells (CSCs), a tiny fraction of the total tumor mass, are responsible for the growth and maintenance of tumors. The hypothesis is that if all of a tumor's CSCs are sterilized, the tumor will die. Several therapies such as CSC irradiation and targeted chemotherapy are being studied to develop new treatments that target CSCs to treat and cure cancer. A major problem with modern CSC research is the method used to identify and isolate CSCs. Biomarkers, or protein markers on the surface of cells, are used to isolate what are believed to be pure CSC populations. We demonstrate using the Hybrid Spheroid Assay (HAS) on patient derived breast tumor cells that in fact only a small subset of cells (~1%) isolated using biomarkers are actually CSC that fit the functional definition of a CSC. BCSCs were enriched using biomarkers. Only 1% of these cells displayed functional CSC properties in the HSA. The Effects of a Comprehensive Family Nurture Intervention Between Mother and Preterm Infant By Sabrina Tabone The main goal of this research was to measure the effects of a multi-part intervention on the relationship between mothers and their preterm infants. The intervention was unique in that it incorporated multiple past interventions into one. It consisted of the instruction and implementation of the calming cycle, kangaroo care, odor exchange, and highly encouraged interaction. The main mechanism used to convert the qualitative outcomes of the intervention into a quantitative measurable statistic was the Revised Infant Behavior Questionnaire. Twenty-eight control mothers and thirty intervention mothers were administered the questionnaire and a score was calculated from each of their responses. It was hypothesized that as a result of this intervention mothers would become more attached to their infants and more instances of reciprocity would be evident in their interactions as measured in the Infant Behavior Questionnaire. Results of the method showed a trending difference between the standard care and intervention groups and indicate that it might take longer than 4 months for the complete effects of the intervention to be significantly different.

Epilepsy is a chronic disease characterized by recurrent seizures. One of the most afflicted regions of the brain is the Hippocampus, which plays a significant role in learning, memory, and emotional functions. Normally, specialized nervous system cells known as astrocytes maintain nervous system homeostasis by performing essential functions. However, neurological trauma, such as seizures, has been associated with changes in astrocyte morphology which may disrupt proper astrocyte function. In this study, astrocyte morphology was studied in a rat epilepsy model to further understand the post-epileptic scenario. First, seizures were induced in rats and rated based on severity via a modified Racine Scale. Next, a Morris Water Maze and a Light-Dark Exploration behavioral test were conducted. Then, rat brain tissue was extracted, prepared, and examined under the microscope. Hippocampal astrocytes were traced using Neurolucida software and analyzed via Branched Structure Analysis. For the behavioral tests, it was found that rats with mild seizures exhibited healthier memory and learning abilities, as well as innate anxiety behaviors, than rats with more severe, status epilepticus seizures. Furthermore, rats with mild seizures had hippocampal astrocytes which exhibited less morphological hypertrophy and complexity than rats with status epilepticus seizures. Although analyses showed a direct correlation between seizure severity and behavioral and morphological alterations, a quantitative, statistical significance of p<0.05 was not established for these findings, most likely the result of a variety of experimental limitations. For example, a noseizure rat group was not able to be analyzed in this study due to the small sample size. Future directions include the addition of more animals, which will increase the power of analysis and allow for additional comparisons. Neural Induction By Abshaar Taj The mammalian central nervous system is a complex system that has developed through the coordinated actions of proteins and molecules during embryogenesis. Much progress has been made toward identifying and understanding many of the key signaling pathways involved in the process of neural induction, however, current protocols for generating fully differentiated forebrain neurons from embryonic stem cells (ESCs) has lagged behind that from more caudal regions of the neuroaxis. Forebrain neurons such as cortical interneurons are of particular importance because they have been implicated in a number of neuropsychological diseases. The remarkable ability of embryonic stem cell derived interneurons to survive and migrate extensively upon transplantation has made them an attractive candidate as a therapeutic treatment for these diseases. However, in

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order to achieve this goal we must improve upon the efficiency of current protocols. In this study, we attempt to better understand the temporal and spatial expression patterns that promote neural induction of forebrain progenitors by manipulating exogenous exposure to morphogens Shh, FGF, IGF, and Wnt Antagonist and increasing surface area of mouse embryonic stem cells exposed to neuralizing factors at an early stage of the differentiation protocol. Investigation of the Mechanisms Behind Nuchal Edema in Aneuploidic Fetuses By Qian Kun Tan Lymphatic malformations during development are extremely harmful to fetuses, as the lymphatic system has many roles, such as fluid homeostasis and immune functions. Lymphatic malformations can cause devastating effects and increases the risk of mortality in fetuses. Often times, fetuses with aneuploidies such as Turner syndrome and Trisomy 21 exhibit increased nuchal edema as a result of lymphatic defects from altered development of the vasculature. Although Turner syndrome fetuses and Trisomy 21 fetuses exhibit the same entity of nuchal edema, previous research has found that there are differences in the morphology of their lymphatic vasculatures, which may mean that the mechanisms causing the lymphatic malformations that lead to nuchal edema may be different. This investigation aims to evaluate the lymphatic vascular defects and the mechanisms behind the severe edema that many of those affected by chromosomal abnormalities suffer from. From immunohistochemical processing, image documentation, and analysis of tissue samples from fetuses with Turner syndrome, the results show that there may be a spectrum of aberrancies associated with lymphatic defects and severe edema, including smooth muscle cell defects and morphological defects. However, there is much more to be studied about the lymphatic vasculature in chromosomally abnormal fetuses, in hopes that there may be ways to improve their conditions.

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Is NSC606985 an Androgen Agonist? By Ryan Tang The Purpose: Prostate cancer is a significant health problem. Currently there is no treatment or cure to combat the disease, once it has metastasized. Thus, the development of new therapeutic agents to treat prostate cancer is imperative. In the present study, the androgenic activity of NSC606985 (NSC), a camptothecin analog, was evaluated towards characterizing its promise as a treatment for prostate cancer. Methods: African green monkey kidney cells were cotransfected with a PSA promoter–directed luciferase reporter construct and an androgen receptor expressing vector. Transfected cells were treated with various doses of NSC and/or 10 nM of the androgen dihydrotestosterone (DHT). Luciferase activity was determined, normalized to an internal control, and expressed as relative luciferase units (RLU). Results: Treatment with 10 nM DHT resulted in a 6-fold induction of PSA promoter-directed luciferase activity, as expected. Treatment with NSC alone at either 50 nM or 100 nM induced PSA promoter activity approximately 3fold indicating that at these concentrations, NSC may have some androgen-agonist characteristics. The combination of DHT with 50 nM NSC resulted in an 8-fold increase in PSA promoter activity, suggesting a possible additive effect. In contrast, the combination of DHT with 100 nM NSC yielded a 5-fold increase in PSA promoter activity, suggesting that at higher concentrations NSC may act as an inhibitor to androgen signaling. Conclusion: The current study demonstrated that NSC by itself is able to induce PSA promoter-directed gene expression, suggesting an androgenic activity. However, at higher concentrations, NSC may inhibit androgen-dependent transcription, suggesting that NSC can also have an inhibitory effect on androgen signaling. A Comparative Study of the Routes of Heavy Metal Uptake in Grass Shrimp (Palaemoonetes Pugio) From Meadow Lake, Queens NY By Matias Tong When toxic heavy metals enter aquatic ecosystems, they pose a continual threat to the fragile system and its inhabitants. Uptake of these metals in grass shrimp primarily involves heavy metals that are bound to sediment particles, incorporated into detritus or other food source, or dissolved in the water column. Grass shrimp, water, and sediment were taken from Meadow Lake, a man-made lake that has historically been subject to heavy pollution, and used to compare the relative importance of re-suspended sediment and polluted water in the overall uptake of Cu, Zn, and Pb in grass shrimp (Palaemonetes pugio). The shrimp were

allowed to empty gut content for several days before reexposing them to polluted sediment and water for three weeks. Inductively Coupled Plasma Optical Emission Spectroscopy (IC-POES) was used to measure heavy metal concentration in the grass shrimp after each subsequent week. Heavy metal concentrations for treatments with polluted sediment and polluted water were not significantly different from those without, suggesting that in the short term, polluted sediment and water may not play as important a role in heavy metal uptake than other sources like contaminated food. Although the sediment contained the highest heavy metal concentrations, the heavy metals were not necessarily in bioavailable form and readily assimilated by the grass shrimp. Additionally, the results for Cu, Zn, and Pb indicate regulatory mechanisms for Cu and Zn which are absent for Pb. This is thought to have been due to the importance of Cu and Zn in biological activity as essential trace elements.

The Development of a Prospective Treatment for Post Traumatic Stress Disorder: Transcranial Direct Current Stimulation By Andrew Vogel The efficacy of transcranial direct current stimulation (tDCS) of the medial prefrontal cortex was investigated for use on patients with post-traumatic stress disorder (PTSD). Based on the results of studies using repetitive transcranial magnetic stimulation (rTMS), a type of electrotherapy stimulation similar to tDCS, for PTSD, a tDCS device was designed to apply stimulation to similar regions used in the studies with rTMS. However, being that tDCS is portable and rTMS is not, the former may be able to treat PTSD sooner and prevent the neurological damage from manifesting. The device will output a constant current of 1.5 mA across the brain as its resistance changes from 20kΩ to 4kΩ. It is theorized that, since rTMS shows therapeutic effects on PTSD and tDCS has similar results to rTMS in other studies, tDCS should hold similar effects on PTSD before it develops.

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Structural and Functional Studies of Linker Histone H1 in Drosophila Developement By Catherine Wang Histones are proteins that impact gene expression and regulate DNA structure in the chromosome. Histone H1 is a linker protein that binds to the nucleosome and DNA to stabilize the structure, thus it is crucial for the compaction of chromosomes. Previous experiments have shown that H1 is essential for the normal development and survival in higher eukaryotes, such as in mice and in Drosophila flies. This experiment attempts to address the question of which regions of the H1 linker histone protein are responsible for linker histone function, and whether the function of H1 is conserved across closely related species. RNA interference was used to deplete fruit flies of 90% of their endogenous H1, resulting in developmental defects and lethality. In one set of experiments, transgenes encoding a series of Cterminal deletions of H1 were introduced into the knock down flies to assess their ability to rescue the loss of wild type H1. In another set of experiments, full length H1 from Drosophila yakuba, Drosophila ananassae, and Drosophila willistoni were introduced into the knock down flies to test whether or not H1 function is conserved across these species. It was found that shorter C-terminal deletions of H1 correlated with better rescue ability. However, there was a much more significant success rescue rate when the flies were injected with full length H1 from the foreign species. The purpose of this work is to gain a better understanding of the functional domains of the H1 proteins. Knowing this would contribute to our general knowledge of epigenetics and may have implications for processes such as differentiation and development.

Pathway-Based Approach to Analyze Genome-Wide Association Study of Pancreatic Adenocarcinoma Survival Using Pre-Defined Gene Sets and Pathway Analysis Software By Jeanette Wong Genome wide association studies (GWAS) have identified single-loci markers and SNPs to be associated with pancreatic cancer; however, complex diseases such as pancreatic cancer develop due to multiple rare genetic mutations or variations, rather than by a single SNP or gene mutation. Pathway analyses provide supplemental information from GWAS results to further analyze and understand disease etiology. With the use of two publicly-available pathway analysis software programs, GSA-SNP and ICSNPathway, standard parameters are set and data is analyzed with the use of computational algorithms. The goal of this research is to assess results from GWAS of pancreatic cancer survival data to identify pathways associated to disease progression in addition to locate genetic mutations that predispose some individuals to pancreatic cancer and influence a patient’s overall prognosis. Results from this study provide insight to mechanisms of pancreatic cancer and their relationship to candidate pathways derived from pathway analyses. A literature survey confirms the significance and relevance of candidate pathways to pancreatic cancer. Re-Evaluation of Fuzeon, The First Peptide Anti-HIV Drug, Reveals a Novel Mechanism of Action By TongZhu Xu

This paper describes a previously undiscovered and novel two-step mechanism of action for Fuzeon. Fuzeon (Enfuvirtide, also known as T20) is the first FDA-approved peptide anti- HIV drug targeting the HIV-1 envelope glycoBy Lucia Wang protein (Env) transmembrane subunit gp41. T20 was proposed to inhibit HIV fusion with the target cell by blocking Proteinuria is a common effect of nephrotic syndromes. It formation of the six-helix bundle (6HB) core between the N- and C-terminal heptad repeats (NHR and CHR) in gp41. is caused by a damaged or nonexistent filtration barrier in However, previous studies using the monoclonal antibody the kidney. This filtration barrier is the slit diaphragm, a (mAb) NC-1 that binds to 6HB and NHR suggest that T20 gap regulated by transmembrane proteins located between is not able to inhibit 6HB formation. In this study, the mAb podocytes in the kidney glomerulus. Previous studies have 2G8 that specifically binds to only 6HB and not NHR, was demonstrated that Nephrin (NPHS1) and Neph1 are two used to determine the interaction of T20 with viral gp41 major transmembrane proteins of the slit diaphragm. In NHR domain or NHR peptides at different stages of the this study, the exact interaction between these two proteins 6HB formation and viral fusion. It is found here that T20 could inhibit 6HB formation in the early fusion stage, but, is examined through a fly model. When expressed in with the progression of time, the effect of T20 on 6HB deneighboring cells, they are expected to bind together and creased concomitant with increased interaction with the localize at the border. However, when each is expressed in fusion peptide (FP) region of gp41 that is located near the neighboring cells, they are expected to be scattered and not NHR. Taken together, these results suggest a model in bind or localize at the border. Results so far have shown which T20 inhibits cell- cell fusion through a two-step procorrespondence with the hypothesis that NPHS1 and Neph1 cess: (1) interaction with the NHR to block 6HB formation at the early stage and (2) binding to the FP to suppress FPare heterophilic. If the hypothesis is further proven to be mediated membrane fusion at the late stage. Therefore, this true, it could provide a molecular basis for therapeutic study elucidates the mechanism of action of T20 as being a treatments towards nephrotic syndromes. two-stop process. This provides a model for new strategies Nephrin and Neph1 Mediated Protein-Protein Interactions

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upon which to base design and development of novel and more effective HIV inhibitors. The Duel Agent: HC1270 Inherits the Double Functions of Hc Fragment of Tetanus Toxin By Adela Yang The development of an effective therapy to help lessen the severity of Sandhoff disease was necessary. Due to the inefficiency of Enzyme Replacement Therapy and Hematopoietic Stem Cell Replacement Therapy, new methods of supplying deficient cells with enzymes were of utmost importance. The C fragment of tetanus toxin may be the answer for supplying Sandhoff neurons that are deficient of hexβ. The heavy chain of tetanus toxin serves as a vehicle that can transport the hexβ fragment past the obstacles such as the Blood Brain Barrier. At the same time, it can also enhance uptake and binding to neurons and localized in lysosomes. The sequence of Hc1270 will be fused with flexlinker3-hexb to create a chimeric protein. It will then be tested to see it retains both the hexosaminidase activity and binding and localization properties. The expected result is that Hc1270 will incorporate more localization than Hc1282 and more binding and uptake of Hc1120. Activation of Dre-1 Gene Inhibits Function of Hermaphrodite Specific Neurons to Regulate Egg-Laying Expression By Michelle Yu

Corrosive Killers: Effects of SGI-1776 and Bicaultamide on Androgen Dependent Prostate Cancer By Xida Zou Prostate cancer is one of the leading causes of death in men. The high expression level of the androgen receptor (AR) by androgens is one of the major causes of the development of prostate cancer. The signaling of the AR and androgens allows for the prostate growth to grow and progress. Because prostate cancers can develop from androgen dependent to androgen independent cases, new treatment approaches are desperately needed. Many studies have indicated a high expression of the AR and an overexpression of the Pim1 oncogene in cases of prostate cancer. The family of Pims (Pims1-3) was first identified in murine leukemia virus induced lymphomas. However, new scientific results have indicated the Pim family to play a large part in prostate cancer as well. Numerous experiments have identified the overexpressed Pim1 gene to be phosphorlyating and increasing the levels of AR in prostate cancer. Studies have demonstrated Pim1 to be working through the regulations of c-myc transcriptional activity, cap-dependent protein translation, cell cycle progression and the survival signaling by phosphorylation of BAD. As a result, Pim1 has recently become a new field of interest for developing new treatment approaches for prostate cancer. Pim1 inhibitors have been used in chemotherapy treatments to try to regulate the expression levels of AR with the hope to reduce and prevent the development of tumors.

Consisting of seven transmembrane receptors and associated heterotrimeric binding proteins, serotonin (5-HT) has been proposed to play a key role in regulating the activity of various neurons and muscles. Previous studies have characterized the 5-HT physiological function in the Caenorhabditis elegans using a G protein called Go. Mutations in the goa-1 gene can cause behavioral defects similar to those observed in mutants that cannot express 5-HT. These mutants display abnormalities in locomotion, feeding, and egg laying behaviors. However, in nonmutants, all behaviors are regulated by the uptake of 5-HT. In this study, we sought to identify a gene like goa-1 involved in a pathway that regulates its egg laying behavior using a mutant worm. We used methods, including complementation testing for standard genetic analysis and fluorescence microscopy to characterize defective gene expression of the mutant being studied. The results indicate that a gene called dre-1, encodes for the serotonin neurotransmitter. An abnormality in such a gene can prevent hermaphrodite specific neurons to regulate the egg laying behavior. This information can help encode for new targets in the treatment of serotonin deficient disorders such as schizophrenia; providing clues to molecular pathways that function to modulate those neurochemical signals.

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Research

Article References

Abstracts of Student Research (‘12-’13)

Knockdown of c-Myc in Rhabdoid Tumor Cells Inhibits Cell Growth By Anna Bao Rhabdoid tumor (RT) is a rare and lethal pediatric cancer. INI1/hSNF5, a component of the chromatin remodeling SWI/SNF complex, is a tumor suppressor deleted in RT. Our lab had demonstrated that Cyclin D1 and Aurora A are the direct downstream targets of INI1 and that INI1 interacts with cMYC, an oncogene in many types of cancer, including lymphoma and breast cancer and regulates cMYC-mediated transcription. Interestingly, previous experiments shown that there is an overexpression of cMYC, Cyclin D1 and Aurora A in RT cells and that Aurora A is upregulated by cMYC in B-cell lymphoma and cMYC transcriptionally activates Cyclin D1. The association of cMYC with INI1 suggests its possible involvement in affecting Cyclin D1 and Aurora A transcription in RT and thereby affecting cell proliferation. To determine the role of cMYC in RT, knockdown of cMYC were performed in RT cells and its effect on tumor cell growth was determined. Western blot was used to confirm that cMYC was knocked-down. The proliferation assay indicated that complete cMYC knockdown inhibits RT cell growth and western blot confirmed that knockdown of cMYC was successful. These results suggested that knockdown of cMYC inhibits Rhabdoid tumor cell growth. Therefore, cMYC is an oncogene necessary for RT cell survival and may be

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a potential drug target. No Double Strand Breaks induced after 1900 MHz (cell phone) Irradiation in Saccharomyces cerevisiae By: Tyler Bell As human exposure to cell phones has increased, the public has expressed concerns with the possible effects, the most detrimental being the development of cancer. The effect of cell phone radiation on DNA integrity in Saccharomyces cerevisiae was measured in live cells in this study using two assays: Rad52 protein localization and Sml1 protein degradation. Results from both assays suggest that the low frequency radiation emitted by cell phones does not damage DNA. The effect of cisplatin on DNA integrity in S. cerevisiae was also measured using a Rad52 protein localization assay. Cisplatin is a cross-linking agent commonly used for chemotherapy. This study confirmed that the repair pathway of the DNA interstrand crosslinks and intrastrand crosslinks formed by cisplatin utilize homologous recombination proteins as the assay showed an increase in Rad52 foci. Furthermore, damage is seen within just a few hours of cisplatin treatment. This work is important to understanding the potential dangers of cell phone usage and towards understanding how the cisplatin chemotherapy drug works.


A Structural Analysis of a Novel Dendrite Arborization Regulator Menorin in the Nematode C. elegans By: Shyam Bhatt The novel protein Menorin was identified through chemical mutagenesis and an SNP mapping strategy as an important factor in dendrite development and structuring in the nematode Caenorhabditis elegans. The protein is encoded for by the gene mnr-1, an ortholog of the human genes FAM151A and FAM151B. The protein Menorin contains two domains, a DUF domain that is conserved throughout all orthologs of the gene in different species. The question asked was if the DUF domain alone could do the job of guiding dendrite arbors of the worm neuron PVD into the hypodermis where they belong, and maintain their "menorah" structure as in wild type. A truncated form of mnr-1 was inserted into mutant worms deficient for Menorin. This produced a truncated form of the protein Menorin that was expressed in the hypodermis (where Menorin is normally expressed) due to the help of a dumpy-7 promoter. A GFP promoter was added to the worms to enable visibility of dendritic branching patterns in PVD and it was observed that the truncated form of Menorin does not rescue the phenotype of normal arborization in PVD. The same phenotype of abnormal branching was observed as in the Menorin deficient mutants. Assessing Anxiety and Depression in ?9Tetrahydrocannabinol Treated Adolescent Rats Using an Elevated Plus Maze and Forced Swim Test By: Rita Black The rate of teenaged adolescents abusing illicit substances, most notably of marijuana, has been rising steadily over the past decade. Previous studies on marijuana (?9Tetrahydrocannabinol) abuse have remained primarily focused on the repercussions to the cognitive abilities of adults but have overlooked adolescents as a significant marijuanauser group. As a result, it is imperative that the effects of the abuse of this substance on adolescents be assessed. However, current behavioral studies are limited in their ability to adequately collect data from consenting human subjects through “check-in� reports and unreliable, personal information. Additionally, behavioral studies involving adolescents are often not feasible due to the age of the participants not allowing for consent. Therefore, a behavioral study that can (1) perform as a rigidly controlled experiment to yield consistent results and (2) measure the effects of marijuana use on mental health during adolescence specifically would be of considerable value to the scientific community. The techniques of behavioral testing that evaluate comprehensive mental disorders involve exposing the animal test subjects to engineered stresses in the form an elevated plus maze (EPM) and a forced swim test (FST). The elevated plus maze acts as an assessor of anxiety whereas the forced swim test analyzes depressive symptoms. This

study evaluates the application of these behavioral tasks in determining the consequences of marijuana abuse on the mental stability, relating to anxiety disorders and depression, of adolescent aged Sprague Dawley rats. Results affirm that ?9-Tetrahydrocannabinol presents both anxietyrelated and depressive symptoms specifically in female rats more so than male rats. Thus, behavioral testing in rat test subjects to assess anxiety and depressive symptoms following drug abuse has significant implications in reinforcing current marijuana research pertaining to adolescents. Hermaphroditism and Social Evolution in Synalpheus Snapping Shrimp By: Gillian Carling Social behavior in the sponge-dwelling snapping shrimp Synalpheus includes asociality, communal living, and eusociality. Through examining the distribution of hermaphroditism among communal, eusocial, and asocial species of shrimp, it may be possible to find out if hermaphroditism and social structure have a connection. The two alternative hypotheses addressed in this investigation were (1) hermaphroditism will be more prevalent in asocial species than social species due to the nature of asocial living, or, (2) hermaphroditism will be more prevalent in social species than asocial species due to competition between shrimp in a colony. Samples from 28 species of Synalpheus were dissected and sexed through the position of gonopores, or sexual ducts, on the pereopods of the shrimp. We found that hermaphroditism was most common among social species of Synalpheus, with a 50% rate of hermaphroditism among communal species and a 43% rate of hermaphroditism among eusocial species. Asocial species only had an 11% rate of hermaphroditism. This indicated that hermaphroditism is correlated with social behavior in general rather than a particular social structure. This supported the second hypothesis, that hermaphroditism will be more prevalent in social species than asocial species due to competition between shrimp in a colony. The combination of very diverse social systems and ecological uniformity found among Synalpheus makes these shrimp an ideal model for studying how hermaphroditism evolved with social structure Investigating the Role of Microtubules in Vertebrate Cardiac Development By: Jessica (Mei Wai) Chan Cardiogenesis, the development of the embryonic heart, is a process investigated in a variety of organisms but particularly suited for this developmental study is the specimen zebra fish. In the zebra fish, key steps in heart development have been largely understood through studies over the years but despite knowledge of these basic steps, understanding of the mechanisms controlling the process remains vague. The goal of experimentation is to assess the role of microtubules in cardiac development. Microtubules, the largest compo-

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nent of the cytoskeleton is known to aid during mitosis as well as support cell form and cell migration. Drug treatments with the drug Colchicine, a drug known to disrupt microtubule formation by binding to tubulin, allowed its role to be assessed. From preliminary data from the lab, it was expected that the groups affected by the tubulin- binding drug would result in trumpet shaped hearts. Results from the experiments indicated a mild version of what was anticipated, demonstrating a slightly flared cardiac tube. It was also observed that the drug-treated embryonic hearts experienced a lack of cellular migration leftward, and forwards in the heart, relative to the control embryos at 24 hours post fertilization (hpf). These findings suggest the lack of microtubules result in a defective heart lacking proper cellular migration and cell formation at the 24 hpf. These results are beneficial in filling the gaps of knowledge in the cardiac process and may lead to future diagnosis of congenital heart disease.

in the last few million years. We used the C01 genes of 25 sister species of sharks and rays from the Indo?Pacific Region. The C01 sequences of these species were obtained from the database Genbank and were aligned on a program called Geneious. MTML?msBayes, a program that analyzes data from multiple species and examines it under a hierarchal model, was used. Two pulses (times when many divergences occurred simultaneously) were confirmed for the 18 sister species pairs that had detectable pair?wise differences. The first pulse contained 12 sister species, and occurred near present daytime. The second pulse occurred 2?4 mya (million years ago), and contained six sister species pairs. The results support allopatric speciation. The divergences correspond to the closing of the Indonesian seaway 3?4 mya. The data supports the Center of Origin hypothesis for the IMPA (Indo?Malay Archipelago) because more of the species pairs that diverged a few million years ago converged at the IMPA than the species pairs that have recently diverged near present daytime.

Compounds Extracted from Dianthus Superbus (Qu Mai) Inhibit B-cell Lymphocyte Production of Immunoglobulin-E

APOBEC1-mediated Editing of Amyloidogenic RNA Transcripts in Microglia

By: Vincent Chan

By: Yashaswini Chittampalli

An increase in the frequency of food allergies in recent times, sometimes life threatening, behooves us to find better treatments for those who suffer. The immunoglobulin E (IgE) antibody is one of the main proteins involved in allergic reactions to food. In a previous study, whole extracts of the Chinese medicinal herb Dianthus superbus (Qu Mai) were shown to inhibit IgE production in human Blymphocytes in culture and to inhibit peanut specific IgE in whole mice, causing reduced allergic reaction. The purpose of this study was to more specifically identify the compounds in D. superbus responsible for inhibition of IgE production toward finding a treatment for food allergies. Compounds found in D. superbus were separated from each other through extraction with dichloromethane followed by silica gel chromatography. The resulting fractions were then analyzed by high-pressure liquid chromatography and then tested for their ability to inhibit IgE production in human lymphocytic cells. One fraction isolated here was able to inhibit IgE production, and it will serve as the basis for further characterization of the specific active compounds. Identification of these compounds would help develop a general treatment for patients suffering from many types of food allergy.

Microglia, the immune cells of the brain, plays a crucial, though controversial role in the central nervous system. Microglia trim synapses, a process important for learning. However, defective microglia can cause neurological disorders, such as Alzheimer’s disease (AD). This study focuses on three genes of microglia: beta 2-microglobulin (B2M), amyloid precursor protein (APP), and a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). These genes are involved in the creation of amyloid plaques—the hallmark AD. It was hypothesized that Apolipoprotein B-editing enzyme, catalytic polypeptide-1 (APOBEC1)—a cytidine deaminase—edits the 3' UTRs of these transcripts of microglia. By means of RNA and DNA isolation, cDNA synthesis, PCR amplification, bacterial transformation, DNA purification, gel electrophoresis and sequence analysis using the MacVector program, we have concluded that APOBEC1 is responsible for editing of APP in murine microglia from brain tissue, and that cytidine-touridine (C to U) RNA editing occurs in the 3’ UTRs of B2M, APP and ADAM10 in an immortalized, murine, microglial cell line (BV2). It is likely that APOBEC1 is responsible for the editing present in the BV2 cell line, because the sites edited correspond with the editing preferences of APOBEC1.

Testing the Geographic Mode of Speciation in IndoPacific Chondrichthyes By: Andrew Chen

Dynamics of Emulsion Separation: A Microscopic Investigation at the Interface

By: Daniel Donenfeld The Indo?Pacific region, especially the Coral Triangle, contains the largest amount of marine biodiversity. In this This study examined the dynamics of phospholipidstudy, we are trying to determine the mode of speciation that stabilized emulsions, and how the emulsion dynamics affect sharks and rays in the Indo?Pacific region have undertaken self-assembly of the phospholipid. An emulsion droplet of

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water and 3-hexanol was imaged using fluorescence microscopy to observe activity on the air/water interface. An experimental system was designed with a hydrophobic substrate and control over the humidity, early stage coalescence, and ambient light using a vacuum grease sealant and a cover. We obtained data on the spreading of the oil phase and assembly of the phospholipid from the interfacial activity. Our data suggests that the emulsion separates in two ways, coalescence, and creaming, which correspond to different rates of 3-hexanol spreading on the interface. Creaming is also coupled with free lipid going to the interface and slowing down of the spreading of the oil phase. Previous studies have examined the stability of phospholipidstabilized emulsions, and this research looks at the microscopic dynamics involved. This could allow for a more tailored design of industrial emulsions through knowledge of emulsion separation. The results of this research could be used in designing future food products and pharmaceuticals with phospholipid surfactants as stabilizers. Application of Carcinoma Precursors and Cell Polarity in Intestinal Epithelium By: Timothy Gao In recent years, the study of cell polarity has increased, due to discoveries linking the change in polarity of certain proteins to tumorigenesis. Epithelial cell polarity, defined as the formation of distinct apical and basolateral domains, causes proteins to localize in specific areas of the cell; this often leads to a change in the role that a protein may play within its cellular surroundings. Proteins, TGF-? receptor, TNF-? receptor, and ErbB2, have all exhibited signs of tumor initiation in previous studies. While they are prominently known in their research as tumor suppressors, evidence has proven that they can sometimes become tumor promoters in later stages of development; we believe that the reason for this change in function is caused by cell polarity. The implementation of AP1B, a major basolateral protein sorter that is found only in epithelial cells, is a possible player in sorting these three proteins mentioned to abnormal areas of the cell when it is abnormally expressed. As a result, we hypothesize that TGF-? receptor, TNF-? receptor, and ErbB2 are basolaterally expressed in enterocytes because they are AP1B cargo. Based on this hypothesis, immunohistochemistry was performed on intestinal and kidney sections obtained from mus musculus to be analyzed via confocal microscopy and morphological identification. Staining cells of the MDCK cell line and the MDCK ¾1BKD cell line of AP1B presence was also attempted. Results demonstrate that TGF-? receptor, TNF-? receptor, and ErbB2 polarize distinctively in the intestinal epithelium, as a possible result of AP1B’s sorting ability.

By: John Gilheany When T cells are activated, they proliferate and undergo a massive expansion that increases the potency of the immune response. Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) is a protein that has regulatory effects on the immune system and it can be spliced to give rise to three different unique isoforms: full length (fl), soluble (s), and a CTLA-4 isoform with only exons 1 and 4 (1/4). The purpose of the experiment was to see if there is any difference in the relative levels of each isoform in a T cell prior to and after activation. Primers were designed to detect each variant accurately, T cells were cultured with anti-CD3, RNA was isolated and reverse transcriptase done. A semiquantitative PCR was then run, to compare splice variant expression levels between the activated and non-activated cells. In the end, after activation of the T cell, it was concluded that flCTLA-4 expression increased, while sCTLA-4 and 1/4 CTLA-4 expression decreased; there was a clear preferential splicing of full length CTLA-4 over the others when the cell was activated. This could be because flCTLA -4 is a strong immune regulator, and as the only splice variant with a trans membrane domain, it can regulate the immune system the quickest and most effectively. My results will be applied and compared to the case of ipilimumab patients, where their T cells are activated. In ipilimumab, a recent melanoma therapy drug, an antibody blocks CTLA-4 on the surface of the cell to indirectly activate the immune system. The purpose of the project was to see if there was any correlation between expression of CTLA-4 splice variants, and patients who respond to treatment. In total, it can also help us understand more about T cell activity after activation, regulation of T cells by CTLA-4, and selective splicing. Testing the Interactions of Drugs and Modulators in a Neuromuscular System of Aplysia By: Joshua glynn

Neuromodulators are a primary component of the nervous system in biological organisms. They are responsible for not only the neural development of the organism, but also for mediating specific muscle activities by forming specific motor neuron outputs that regulate muscle activity. Neuromodulators are very difficult to study, as their effects can be unpredictable when combining different neuromodulators in various concentrations are to form different cocktails. This project addresses the validity of a mathematical combinatorial algorithm that is proposed to be able to define the function of each neuromodulator. The combinations tested in this experiment were successful in indicating what factors of modulatory systems we need to pay attention to. Data from physiological experiments suggests that there are two main factors that should be taken into account: (1) the order in Preferential Splicing of Full Length CTLA-4 in Activat- which individual modulators are applied and (2) the number of modulators interacting in any given scenario. Focusing ed, Cultured T Cells on these particular aspects in depth in future experiments

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will undoubtedly allow for better insight into the dynamics of these modulatory systems. Location of HIVAN Susceptibility Gene in HIVAN Locus By: Ekramul Gofur HIV-Associated Nephropathy (HIVAN) is a relatively recently discovered which leads to end stage renal disease. The disease results from HIV-1 infection of renal epithetical cells and podocytes. The prevalent form of treatment currently for HIVAN is highly active antiretroviral therapy. HIVAN primarily occurs in people of African descent; approximately 90% of known HIVAN cases are from people of African descent. Previous studies in mice using genetic linkage have shown four loci, which could potentially have a susceptibility gene leading to the infection of HIVAN. This project focuses on determining the location of a susceptibility gene in the HIVAN 1 locus. Comparing the genotypes of three individual mice strains to the control FVB strain on the SubIII region (subsection of the entire locus) of the HIVAN 1 locus shows that the mutation for susceptibility to HIVAN does not exist as a single nucleotide polymorphism (SNP) but could still exist as an insertion/deletion. Assessing DNA Transcription in an HPV 11 Upstream Regulatory Region (URR) Using a Reporter Construct Mutated in the AP1 Sites By: Lubaina Haider

By: Daniel Huang Umbilical cord blood (CB) contains primitive hematopoietic stem cells. It has become an alternative to bone marrow for stem cell transplantation therapy to reconstitute the hematopoietic system in patients with malignant and nonmalignant, or other disorders. Success of bone marrow transplantation is hampered by high rate of graft-versus-host disease (GVHD) which may lead to death of patients. Finding an appropriate donor to reduce chance of GVHD is very hard, and waiting period is too long for some patients with life threatening diseases. GVHD after CB transplantation is lower partly due to immaturity of T cells and relatively higher frequency of regulatory T cells (T regs) in CB. CD 4 T regs have been well studied, and their existence in CB has been documented. CD8 T regs are less characterized; their existence in CB has been suggested. In this study CD8 T cells was first determined to have suppression function in CB only after they are stimulated with allogeneic antigen presenting cells (APC). Then CD8 T regs were molecularly characterized CD8 from CB. It showed that CD8 T regs from CB expressed higher level of BCL6 gene, which is a molecular marker for CD8 T regs induced from adult peripheral blood (AB). It also further showed that the level of micro-RNA (miRNA)-30b, which inhibits BCL6 gene, was lower than the control. These results indicate that CD8 T regs in CB may play a role in low rate of GVHD in CB transplantation, and they may be used in cell therapy to further reduce GVHD in CB transplantation if they can be expanded in large quantity.

An Evaluation of Langerhans Cell Chimerism after Gender-Mismatched Allogeneic Hematopoietic Stem Cell Recurrent Respiratory Papillomatosis (RRP) is a disease Transportation caused by the human papilloma virus (HPV). The upstream regulatory region (URR) of the HPV genome contains sevBy: Martin John eral regulatory sites, which control transcription of specific proteins that directly cause RRP. Our experiment attempts to figure out whether the AP1d and/or the AP1p site are/is For patients with hematologic and lymphoid malignancies, important in HPV DNA transcription. To test the AP1 sites, allogeneic hematopoietic stem cell transplants (allo-HSCT), mutant plasmids were produced and transfected into HeLa also known as bone marrow transplants, often offer a curacells. A luciferase assay was used to determine whether the tive treatment option beyond what chemotherapy alone can AP1 sites promote or inhibit transcription of DNA. The provide. However, graft-versus-host disease (GVHD) is a results showed that the AP1d site is a negative regulator of potentially serious complication that can occur when transE6 and E7 because the luciferase levels were higher in the planted donor cells recognize host cells as foreign, despite HeLa cells transfected with the AP1d mutant rather than the matching for the major human leukocyte antigens (HLA). HeLa cells transfected with the 311 DNA, which was not Doctors believe the recent success of donor T-cell depleted mutated. These results are reliable because the same trend allo-HSCT is the result of host antigen presenting cells was seen in four other HeLa cell transfections. To confirm (APCs) changing to donor over time. Yet, mouse studies these results, the JNK pathway was inhibited to test for tran- have shown that precursors of host LCs are long-lived and scription of DNA in HPV. The results from the inhibitor can self-renew in skin, unless the net egress of LCs to skinresearch confirmed the results from the mutational study, draining lymph nodes exceeds the capacity of local progeniwhich means that the results presented in this report, are tors to replenish them. Skin biopsy sections were used to valid; therefore, inhibition of the JNK pathway is not a good examine expression of donor sex chromosomes in recipient Langerhans cells (LCs), a type of dendritic cell that resides therapeutic target. in the skin and is important for initiating immune responses Characterization of CD8 Regulatory T Cells in Umbili- by donor T cells. Using fluorescence in situ hybridization (FISH), sex chromosomes were highlighted in cells of skin cal Cord Blood biopsy sections, which were co-stained with fluorescent

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antibodies to distinguish LCs from other cells in the epidermis. The skin biopsies were collected from two patients with GVHD and two patients without GVHD. Results shown that mixed LC chimerism were examined in the skin of all four patients, and a pattern can be seen between genders, rather than between those with GVHD and those without. Furthermore, the mixed chimerism observed suggest that not all host APCs in the patients are changing into donor following allo-HSCT, though host cells are changing into host only within the blood. High Preservation of CpG Methylation Patterns in the Liver of Aging Mus musculus musculus Mitochonadrial Genome By: Hyewon Kang Epigenetic modification is heritable state of gene expression that can contribute to age-related physical invalidity or diseases such as cancer or depression. A significant aspect of epigenetics is the methylation status of Cytosine-Guanine (CpG) dinucleotides in the five position of the genomic DNA regulation by interfering with the binding of transcription factors to promoter regions in the gene. The mitochondrial DNA (mtDNA) is prone to mutation, single-nucleotide mutation rate ranging from 2.7x10(-8) per mtDNA for brain to 3.2x10(-9) per mtDNA for the liver. However, most of the studies on methylation were done on the nuclear genome while the mitochondrial DNA was not explored because the mtDNA was believed to be unmethylated. Recently methylation sites were found in the mitochondrial genome in global assessment. To investigate the mouse liver at an epigenetic level, the experiment aimed to find how unstable the mtDNA in the mouse liver really is. Methylation in mtDNA of the liver from young and old mice were analyzed using noble sodium bisulfite conversion approaches which change the DNA sequence depending on the methylation status of cytosine residues. All the cytosine in the bisulfate treated CG sites was converted into uracil, which showed up as thymine in the PCR. The results indicate that the mitochondrial DNA is hypomethylated both in young and old mice samples in the liver, and is surprisingly very stable in epigenetic marks. The experiment thereby suggests that there may be a repair system for epigenetic marks in the mitochondrial genome and may have further implications in studying aging and its related diseases.

attempted to, using the transcript of a Presidential or VicePresidential debate, predict the winner of the debate as told by polling. Chi-squared feature selection identified features correlated with debate success. These features gave insight into the distinct importance of discussing war and national defense the modern American political system. Although the extremely limited corpus size restricted both the training and significance of the predictive models, with a set of surface-level lexical features from historical debates the winners of presidential debates can be predicted with 60-80% accuracy. Determination of the Role of CBX3 in the Chemoresistance of Relapse Pediatric Acute Lymphoblastic Leukemia By: Rana Lamisa Although there have been significant improvements in the survival rate of childhood acute lymphoblastic leukemia (ALL), the outcome for relapse patients is still poor. CBX3 is a missense mutation that could possibly change the function of a protein. CBX3 encodes for the heterochromatin protein HP1y that is responsible for binding the trimethylated lysine 9 residues on histone H3. In previous research, it has been shown that CBX3 is mutated in one pediatric relapse ALL patient sample. One objective of this study is to understand whether CBX3 binds to H3K9Me3, the protein this gene encodes, and by what mechanisms. Another objective is to find the cellular functions CBX3 alters, and the mechanisms it uses to do so. The third objective is to understand whether CBX3 causes Chemoresistance. Of all the experiments done, results showed that CBX3 mutant does bind to the histone H3K9Me3 more readily than the CBX3 wild type does. All other results show that there is no change between the mutant and the wild type. Our results indicate that further experiments must be done to understand the cellular activity of the cell when CBX3 is mutated. In addition, CBX3 may be a passenger mutation and does not play a major role in Chemoresistance of relapse ALL. Comparing the Efficacies of Different Incubation Methods for Common Snapping Turtle (Chelydra Serpentina) Eggs from the Bronx River By: Candace Lee

Using Lexical Features to Predict Winners of U.S. Presi- As part of conservation efforts for common snapping turtles (Chelydra serpentina), their eggs have traditionally been dential and Vice-Presidential Debates collected from nests during the nesting period in late spring and incubated in direct contact with vermiculite in sweater By: Ian Kaplan boxes. Squamata Concepts LLC has standardized new SusAn investigation of lexical, transcript based, features of pended Incubation Method (S.I.M.) using suspended conAmerican Presidential and Vice-Presidential debates that tainers with vermiculite, but minimal research has been may correlate with personally appealing or politically per- done to compare S.I.M. containers with the traditional methsuasive language facilitates the discovery of the features of od for incubating the eggs of this species. The success of personally appealing and politically persuasive language. traditional incubation was compared with that of the S.I.M. The investigation involved predictive models created that container under various environmental conditions. Success

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was measured in terms of the number of hatchlings, incubation period, hatchling mass, and size of the carapace and plastron. Each clutch was divided into S.I.M. containers and sweater boxes. Those collected in 2011 were placed in two incubators (25°C and 30°C) in a nursery and those in 2012 were placed in an outside garage under fluctuating temperatures that corresponded with the environment’s changing temperature. Weekly, lost water weight in sweater boxes was compensated for by adding water to the vermiculite and S.I.M. containers were aired. The S.I.M. containers produced larger hatchlings after shorter incubation times and were suggested to be better at producing more hatchlings than sweater boxes at constant temperatures in the nursery. The sweater box produced hatchlings with greater masses and larger sizes at fluctuating temperatures in the garage, but at the expense of longer incubation times. The results correspond with those of past studies done by scientists such as Yntema, Spotila, Steyermark, Baumer, Andrews, Bauwens, and Garel, who experimented on the effects of various factors during incubation on hatchlings of reptile species, including snapping turtles.

(Geochelone nigra microphyes) and its application when training. The hypothesis states that the color targets can be utilized as a training tool. Operant and classical conditioning were used alongside clicker and target training to test color recognition and differentiation. Individuals were conditioned to a specific color (red, orange, black, or white) and assessed using trials in which the color target each subject selected was recorded. The results supported an inclination toward red colors in this species and suggested that although differentiation between colors is evident, differentiation between similar colors is not. These findings can be applied to improve training approaches of zoo and medical staff when conducting standard veterinary protocols, especially in cases where multiple animals are involved. It is also the onset of future research regarding the natural selection and the conservation of the renowned Galapagos tortoise species. Investigation of Relationship Between Math Anxiety and Math Ability in Different Ethnicities

By: Syeda Malliha Conditions for Turing Pattern Formation in Electrically Although policies such as affirmative action aim to equalize Coupled Networks of Neurons the disparity of educational opportunities in the United By: Fred Lin States between different ethnicities, it is clear that contrasts still exist. This study aims to identify how different ethniciNeurons in the brain communicate by a combination of ties perform with their respective math abilities and anxiechemical and electrical signals. Certain combinations of ties, and if other prominent differences exist. It does so these two types of signals could create Turing patterns, spa- through a questionnaire including measures for mathematics tially periodic oscillations, which are ubiquitous in biology. anxiety, math ability, and relevant factors such as ethnicity. However, the biological mechanism by which Turing pat- The questionnaire was distributed among 160 students of terns could occur in a group of neurons is not well under- Hunter College and revealed a significant contrast between stood. Gap junctions electrically couple many types of cells the way Caucasians and Asians correlate math anxiety with in the brain and can coordinate inhibitory neuron firing. math ability and the way African Americans and Hispanics Moreover, conductance through gap junctions depends on correlate math anxiety with math ability, but none concernneural activity and intracellular signaling. Here, we use a ing general anxiety and neuroticism. It has traditionally computational model to show that gap junctions could link been noted that math anxiety is negatively correlated with chemical and electrical signaling in the brain to produce math ability. However, through an ANOVA (using means Turing patterns. The strength of activity of gap junctions for math ability and math anxiety) it was found that math required is biologically plausible. ability has predictably a negative correlation with math anxiety in Caucasians and Asians (meaning the higher one’s The Ability of Color Recognition and Distinction in Ga- math ability, the lower his math anxiety), whereas in African Americans and Hispanics math ability has a positive lapagos Tortoises (Geochelone nigra microphyes) correlation with math anxiety (meaning the higher one’s math ability, the higher his math anxiety) - a very unexBy: Catherine Louie pected phenomenon. In essence, this implies that math anxThe subspecies of Galapagos tortoises have morphological iety cannot be blamed on math ability alone, and there is characteristics that vary from different islands of the Gala- another unknown factor that is essential in the causation of pagos archipelago. These variations are the results of adap- math anxiety. This study highlights this critical difference tations that may include certain visual abilities because of and opens the door to future research investigating why this the species’ heavy reliance on their vision to forage. The difference exists. The next steps entail lab experiments and potential to see color and even differentiate between colors further questionnaires testing the accuracy of trends discovhas not been a subject of much research. Color vision and ered within this questionnaire and begin to delve into the differentiation is important because husbandry-training reasons as to why this trend exists. By discovering common methods can use colored targets for minimizing stress in the causes for math anxiety, methods of standard education can animals during medical procedures. This experiment ex- be adjusted to prevent math anxiety among all races, and plored the visual capabilities of the Galapagos tortoise thus produce a more mathematically able population.

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The Effect of Socioeconomic Enviroment on Birth Outcomes of Women in the South Bronx: A Proposal By: Maribel Maria Preterm pregnancy is an enduring issue in the United States despite the advances in technology geared towards aiding in the delivery of children. The actual causes of preterm pregnancy remain unclear to this day. However, factors are known to exist which influence the outcome of a pregnancy. A potentially influential factor may be the socioeconomic environment, such as the perceived safety in the community, in which a woman lives in during the time of her pregnancy. It could be predicted that African American and Hispanic women in the South Bronx are negatively impacted by their socioeconomic environment and are thus likely to give birth prematurely. Further investigation into the issue would be necessary to determine if socioeconomic environmental factors do affect the pregnancy outcomes of African American and Hispanic women. This study proposes to investigate and evaluate the causes of preterm birth in the population of African American and Hispanic women, in the South Bronx.

is a significant step towards the ultimate goal of explaining how these neurons do the visual computation that is seeing. Molecular Identification and Functional Characterization of fried, a Gene Required for Growth and Fertility in Drosophila 2010-2013 By: Sharon Migdal Fried is a mutant gene known to cause defects in the ovaries and larvae of drosophila. Two alleles of the gene were identified and named fried150 and fried212. Using a genetic trick known as the flp-FRT system, we were able to study the physical and behavioral effects of the gene by producing a homozygous mutant and observe the mutation in the eyes of the drosophila. White stops indicated the fried allele. Fried mutants demonstrated defective behaviors in comparison to wild type larvae, which include precocious wandering, early lethality, extensive melanization and an overall smaller body mass. A Survey of Juvenile Horseshoe Crabs (Limulus polyphemus) along Plumb Beach, Brooklyn By: Lawrence Moy

The Number of Cortical Neurons Used to See By: Krisha Mehta

All organisms are part of a food web and play a unique role in the ecosystem they live in. Like all organisms within a food web, American horseshoe crabs are important and vital for the survival of their ecosystem. American horseshoe crabs exhibit spawning during the spring in areas such as Plumb Beach in Brooklyn, New York. Unfortunately, horseshoe crab populations are on the decline. These declines could have an impact on local food webs and on species that rely on horseshoe crabs to survive. In this study to examine changes in spawning activity of horseshoe crabs, Plumb Beach was used as the research site. The East and West mudflats of the beach were surveyed in the experiment. Transects were used to box off regions within the areas. In each boxed off region, the top portion of the sand was filtered and the contents left over were examined for horseshoe crab hatchlings. No juvenile horseshoe crabs were found in either location, but other marine wildlife was. Sheddings of horseshoe crab juveniles and adult carcasses were also found on the east side. None of these were found on the west side. As expected, no juveniles were found in the surveys since the spawning season has been over for quite some time. Future research will examine changes in juvenile counts during the spawning season along with changes in horseshoe crab populations over a longer period of time and the effect of these changes on local shorebirds.

A neuron’s receptive field is the area in the visual field in which it responds to light. A neuron has one cell body and many dendrites. Physiologically, the integration occurs as the signals from the many dendrites converge on the cell body. The integrated input signals cause the cell to fire, i.e. produce an action potential. The cell firing stimulates the dendrites of other neurons. The integration is linear (weighted averaging) even though the cell firing depends nonlinearly on that weighted average. The main nonlinearity is a threshold. The cell does not fire if the weighted average is less than the neuron’s threshold. Thus, although a complete mathematical model of the neuron would include the nonlinearity of the cell’s response, the spatial integration by the cell’s receptive field (or dendrites) is a simple sum, a linear weighted average. That weighted average is a sample of the image in the visual field of the observer. The weighting functions that produce these samples have been extensively studied in individual neuraons in fish, cats, and monkeys, but very little is known about how these animals and people use multiple neurons to see. There are hundreds of millions of neurons in the visual cortex, but so little is known that previously studied performance of human observers might be accounted for by using a single cortical neuron. Here a new technique, based on a new mathemati- Optimized Conditions of Genome-Wide Screening for cal theorem, allows non-invasive visual tests to demonstrate Genes Correlated with Regulatory B Cell Biogenesis that people use a large number of neurons. More specifically, findings show that observers are using a maximum of By: Ujwalla Murthy about 100 receptive fields, a new upper bound never before found in neural studies. Saying how many neurons are used The B cell is widely recognized for its role in producing

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antibodies to protect the body from invaders and pathogens. It is known also for its ability to present pathogens to killeror helper T cells. Recently, interest in a little understood subset of B cells, regulatory B cells (Bregs), has emerged. Bregs can secrete interleukin-10 (IL-10), an antiinflammatory cytokine involved in suppressing the inflammatory immune response, important in autoimmune diseases and inflammatory disorders. How a B cell becomes a Breg remains unknown. Identification of genes involved in Breg formation would have therapeutic value in inflammatory and autoimmune diseases. Here I describe the optimization of conditions for a genome-wide screen of genes associated with Breg formation. Employing a strategy in which target genes in mammalian B cell lines and cultures are silenced, activating B cells (Bregs) and measuring IL-10 production, would enable identification of potential genes responsible for Breg formation. The silenced genes would cause a decrease in IL-10 production. These genes would be identified as putative regulatory genes. Here, an appropriate cell line, virus dilution, experimental design, and cell density were determined in preparation for these future experiments. I found that the CH12F3 cell line, 1:1000 virus dilution, and a plating density of 2.92 Ă— 105 cells/cm2 were conditions suitable for genome-wide screens, through which genes involved in Breg formation could be identified. As possible therapeutic targets, the identified genes would facilitate the effort to create novel therapies for autoimmune diseases and inflammatory disorders. Purification of Beta Cells in a Heterogeneous Population for the Treatment of Diabetes Mellitus By: Pratyusha Mutyala Over 130 million people worldwide are afflicted with Diabetes mellitus. The current treatment for this disease involves insulin-injection and glucose monitoring; however, there is no cure. A cure for this disease can be achieved through beta cell replacement therapy. A viable population of beta cells can be acquired through differentiating human embryonic stem cells. In this research, fluorescence staining, cell screening, and FACS were used to isolate beta cells in a mixed human islet cell population. Highly fluorescent cells were separated from less fluorescent cells on the cell sorter. This helped us to identify several potential candidates for cell surface markers among which, surface marker CDXX held the most promise. CDXX was incubated with single cells dissociated from human pancreatic islets and identified to potentially recognize the insulin-positive cells. The cells were tested for the expression of insulin using RTPCR and qRT-PCR. The highly fluorescent cell population was enriched fifty-eight-fold for insulin-containing beta cells, indicating that islet beta cells are relatively enriched in CDXX antigen and can be partially purified in a heterogeneous stem cell population by this method. In the future, this purification method can facilitate beta cell replacement therapy to potentially cure patients with Diabetes mellitus.

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Enviroment Affects Cell Proliferation in Offspring By: Chirilien Pang There are many factors that may influence development in offspring, including different proteins that are in the mother. Previous studies have shown that maternal TNFa plays a role in altering offspring memory. However, there still remains a question about whether the effect on offspring memory occurs prenatally, postnatally, or a combination of the two. We found that foster mothers that express less or no TNFa positively influence memory in offspring. Whereas foster mothers that do have TNFa negatively influence memory in offspring. Proliferation of cells in the dentate gyrus of the hippocampus (as indicated by BrdU incorporation) was used as a measure of spatial memory. Our data demonstrate how crucial and impressionable the postnatal environment is to the offspring. Furthermore, we examined whether the mother’s milk was an underlying mechanism in which the foster mother affected offspring memory. Our data show that lactating mothers in whom TNFa was neutralized fostered offspring with increased spatial memory as measured by proliferation in the dentate gyrus of the hippocampus. These results are significant because they show the effect of the postnatal environment on memory. Initial In-silico Docking of M.Tuberculosis BetaLactamase By: Shivam Patel Tuberculosis is a bacterial infection, which deals with the lungs but has the ability to worsen and move throughout the body. Currently, most cases of tuberculosis are able to be treated with the regular strain; however there is a stronger strain which is resistant to the penicillin. M. tuberculosis beta-lactamase is the enzyme which will be used during this experiment. This is because of the intrinsic resistance which had developed for the enzyme to the illness; however the enzyme does not always bind properly. The techniques may be sufficient but the actual compound does not seem to fulfill the needed requirements. We are looking for a compound which is able to destroy the strain which is at hand, as well as keep the bacteria from leaving its dormant stage. If no longer dormant or if present again, there can is strength attained in the strain which will be able to cause more damage to the person who is experiencing the bacteria. By using in-silico doc king; we are using a cost effective method as well as using a method which does not prove to be too tedious. The results which are attained here can be taken a step further and put into experimentation. Certain compounds have been proven to be better at this then others such as a present carboxyl group, along with the presence of Clavulanic acid and sulbactam. These specific components seem to better the compounds affinity to bind with the enzyme.


Effect of Medial Dorsal Thalamic Lesions on the Development of the Prefrontal Cortex By: Ian Persaud Gap junctions connect many types of cells, including neurons. Diffusion of ions through gap junctions can coordinate neuronal activity, hence influencing information propagation and processing. However, exactly how diffusion affects information processing remains poorly understood. By modifying gap junctions, we examined how different diffusion conditions affect sub-threshold oscillation in a 2 dimensional (2D) population of neurons. Here we describe the derivation of those conditions under which diffusion of ions through gap junctions allows Turing patterns- spatial oscillations of ion concentration, which directly affects action potential generation and other neuronal processes. We derived these conditions for a sheet of neurons represented by a system of linked reaction-diffusion equations. If gap junctions slow the diffusion of inhibition below a critical rate, Turing patterns cannot occur in sub-threshold neural oscillations. At biologically plausible values of diffusion, if the rate of diffusion is independent of space and time, Turing patterns occur. The spatial oscillations that Turing patterns create occurs with a spatial frequency that depends on the strength of diffusion. Our analysis show that recurrent inhibitory neurons must scale to excitatory for Turing patterns to occur. We also determined the effect of space, or distance, between cells on Turing patterns of neuronal populations, a novel finding. We anticipate that our model will lead to more sophisticated models of neural population interaction. For example, modeling of neuron populations with fluctuating thresholds or neuron populations with spiking activity, even a 3D model of neuronal interaction are plausible extensions of our model. Furthermore, since many neurons perform functions in sub-threshold oscillation, an understanding of the patterns associated with such functions is essential to our understanding the neural system.

seen expressed in the spermatogonia of the testis. In general, that would be the outline of the seminiferous tubules (basement membrane). If this proved to work then there would be proof of our hypothesis that there is a better way to stain for this marker. The UTF-1 was expressed so far with the basic protocol. The basis of this particular experiment was to see the best staining. To find the best results, the experiment, and the protocol was to be optimized so that the best possible results were produced. The idea was to prove that there is a connection between UTF-1 and spermatogonial self-renewal into various types of cells (pluripotency). Overall then, that would mean that it was expected that the marker is expected to work in the staining but the following steps were taken take are to achieve the best staining in the human testis samples. The Interaction between the Ubiquitin/Proteasome System and the AMP-regulated Kinase Snf1 By: Anahi Potrero The ubiquitin proteasome system (UPS) is the major proteolytic system in the cytoplasm and nuclei of eukaryotic cells. Many cellular functions are regulated via regulated turnover of proteins by the proteasome and dysfunction of this system is observed in many human diseases such as cancer and in aging processes. To prevent unspecific protein degradation, proteasome activity is tightly controlled. Previous reports indicate that the AMP regulated kinase Snf1/AMPK, a regulator of energy levels in the cell, might functionally interact with the UPS due to its UBA domain. In this work, mutant and tagged Snf1 strains were created which allowed the investigation of this interaction. The strains were purified and proteins that interact with the new strains will be identified using mass spectrometry. This method will present first evidence that the UPS interacts genetically with SNF1 and that Snf1 itself is not a UPS target.

Immunostaining of UTF-1

Pharmacological Dissociation of Smoking and Reward in Schizophrenic Patients

By: Anjali Pillai

By: Mousumi Reja

The purpose of this experiment is to use an immunostaining method utilizing antibodies and antigen-retrieval to get the best kind of staining of the marker UTF-1 (undifferentiated embryonic cell transcription factor 1) that can be achieved. UTF-1 is known for being a marker for pluripotency. It is also known to be found to be expressed mainly in spermatogonia. Therefore, the hypothesis is that if properly stained, UTF-1 will be expressed in the basement membrane of the seminiferous tubules, where the spermatogonia are located. The first part of the experiment involved going through the typical protocol for immunostaining. This involves preparing the slides with testis samples for the antigen-retrieval and addition of antibodies prior to the outcome of the staining itself. The slides were then stained to find where exactly this transcription factor was seen. UTF-1 is thought to be

A high percentage of schizophrenics are smokers. This study analyzes what happens in the brain when nicotine is introduced in the brains of individuals, specifically schizophrenics. When nicotine is introduced into the brain, there is a large stimulation of receptor activity and large release of acetylcholine. Glutamate is another neurotransmitter released in large amounts both because of the introduction of nicotine in the brain and in schizophrenic patients. This neurotransmitter is involved with memory, learning, and enhances the reward system. This chemical activity within the brain was studied in brains of schizophrenic smokers and non-smokers. This study analyzed what happens in the brains of schizophrenics when NMDA receptors are blocked, a known consequence of nicotine use. Ketamine, a phencyclidine hydrochloride derivative and NMDA antago-

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nist was used to block receptor activity. A release of acetylcholine is accompanied with the release of glutamate in smokers. When the level of glutamate increases, so does the level of acetylcholine. Results showed that in schizophrenics who were nicotine dependent, psychosis was a response and patients had more cravings for nicotine. Schizophrenics who were not nicotine dependent experienced positive-like symptoms of schizophrenia, such as delusions, thought disorders, and hallucinations. Healthy controls experienced negative symptoms similar to those caused by schizophrenia and were negatively affected by the inducement of nicotine in their brains. This showed that ketamine blocks NMDA receptors from binding with glutamate so that the reward system is not activated, but that schizophrenic patients have more cravings for nicotine. Prevalence of Parkinson’s Disease Mutation in Males and Females: A Proposal By: Martin Ridge Parkinson's Disease is a neurodegenerative disorder that affects over seven million people worldwide. The disease ultimately leads to death, and can induce bradykinesia (among other symptoms). Familial Parkinson's Disease is an inherited form of the disease in which certain mutations affect neural development. The most prevalent of these mutations occurs in the Park8 gene, which encodes the protein Leucine-Rich Repeat-Kinase 2 (LRRK2). The mutation creates a G2019S abnormality in the enzyme, causing it to over-phosphorylate ERM Proteins in the dendrites. It has been shown in mice that this over-activity of LRRK2 leads to increased dendritic length and decreased dendritic branching in early developmental milestones. In addition, Parkinson's Disease has been shown repeatedly to have a predilection for affecting males (in some studies, the rate of incidence of Parkinson’s Disease in males exceeded that of females by over 90%). This project aims to ascertain the relationship, if any, between the effects of LRRK2 G2019S and gender. We expect to find lower rates of dendritic branching in male mice compared to female G2019S mice and control, along with lower dendritic lengths. The results will show whether or not the increased prevalence of Parkinson’s Disease in males is correlated with the effects of LRRK2 operation, or a more phenotypical set of stimuli. If the results show that LRRK2 G2019S indeed affects dendritic branching in males more than in than females, then we may proceed with testing the relationship between Parkinson's Disease and testosterone. A therapeutic method of addressing this correlation would then be in reach.

er, in all patients’ newly developing lymphocytes do not develop into mature cells, but stay as immature cells called lymphoblasts. The immune system recognizes foreign substances via antigen receptors to elicit an antibody response. The collection of antibody specificities an individual has is known as the antibody or immunoglobulin repertoire. The number of antibody specificities is limited by the total number of B cells in an individual. V(D)J recombination is the process by which the variability and diversity of antigen receptors is generated. Since patients with ALL do not properly develop B cells, their immunoglobulin repertoire is very limited. Lymphocytes have unique receptors, which enable recognition of almost any foreign substance. These receptors are specialized and only match to one specific antigen. B lymphocytes develop in the bone marrow and produce receptors via V(D)J recombination. This process increases the variety of receptors of lymphocytes. V(D)J recombination, is a mechanism of genetic recombination in the early stages of immunoglobulin (Ig) and T cell receptor production. This process primarily takes place in the primary lymphoid tissue; the bone marrow for B cells, and Thymus for T cells. The formation of an antigen receptor is categorized by the combination of the Variable, Diverse, and Joining gene segments of vertebrates is a site-specific process. Since the process of antigen receptor variability joins segments and different genes almost randomly, the receptors produced are able to diversely encode proteins to match antigens from bacteria to tumor cells to pollen (Malu et al., 2012). V(D)J recombination is initiated by the lymphoid-specific Rag1 and Rag2 proteins, which cooperate to make double-strand breaks at specific recognition sequences (Gomez et al., 2000). Evidence of Hybrization in Camponotus pennsylvanicus By: Sameer Sabharwal-Siddiqi The purpose of the study was to test for the incidence of hybridization in two species of hymenopterans: Dorylus (Anomma) molestus and Dorylus (Anomma) wilverthi. This study used morphometric and phylogenetic analysis to identify hybridization. Morphometric data was collected quantitatively by measuring the posterior head lengths, and phylogenetic analysis was conducted through gene extraction, PCR, and genotyping. Youth-Generated Programs: Evaluating the Impact of Project STEP-UP By: Shyam Bhatt

The Modulating Effect of Pax5 on V(D)J Recombination Many adolescents in inner-city communities struggle in school and in life, however, not much is done to help them. Step-Up, a youth intervention stationed in two schools in Acute lymphoblastic leukemia (ALL) is a cancer of the lym- NYC, fills this void. The program assesses and addresses phocytes and is found to be prevalent in children. Normal- mental health difficulties and provides opportunities for ly, lymphocytes fight bacterial and viral infections; howev- increasing youths’ social problem solving and life skills. By: Amanda Ruiz

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We hypothesized that Step-Up youth would evidence increases in GPA and high school graduation rates that exceeded national and NYC rates of youth with mental health difficulties, and that the more contextual stressors (i.e. race, gender, who the youth live with, if they participate in out of school activities) a Step-Up youth faces, the lower the GPA and the more depressed he or she would be. All of the participants completed surveys before and after the intervention. The results from these surveys were analyzed using SPSS. It was found that the program did not necessarily increase the GPAs and decrease the CDI scores of the students. However, it did maintain them (Mean GPA before=68.94, after=70.52; Mean CDI before=12.70, after=12.91). Since most of them were on a downward slope, the fact that their situations did not become worse demonstrates the success of the program. We also found that only gender was a good predictor for post-intervention GPA, and that none of the contextual stressors were good predictors for post-intervention CDI results. This information can be used to improve the Step-Up intervention and develop more like it.

humans. Each bacterium has unique abilities to adapt and become resistant to conventional antibiotics, making treatment difficult for clinicians. This is evident in the rise of antibiotic-resistant strains of both bacteria. It is believed that besides resistance via genotypic changes, the ability of both of these bacteria to form complex communities that function to prevent antimicrobial treatment is key in their virulence. Biofilms, defined by J.W. Costerton to be a microniche of bacteria enveloped in an exopolysaccharide matrix, pose a threat because of their shield- like properties to bacteria. It is also a problem that biofilms do not usually exist as single species because this makes them more difficult to treat. Polymicrobial infections are commonly found in humans and often the culprits are combinations of S. aureus and E. faecalis. Current therapies have been shown to be limited in combating these poly- microbial threats. The treatment of S. aureus and E. faecalis biofilms by Daptomycin and CF- 301is focused on in this paper. Daptomycin is a broad- spectrum antibiotic most commonly used on forms of S. aureus and E. faecalis that are not in biofilms. CF-301 is a lysin, which has been shown to break through the cell membrane through the process of lysis and has been shown Toxoplasma gondii Genes Regulated by Apetala 2 Tran- to have anti-biofilm properties and successfully kill bacteria scription Factors Through Protein DNA Binding Motifs grown in biofilms. The results of this experiment show that the use of Daptomycin and CF- 301 together can successfuland Transcription Start Sites ly treat Polymicrobial biofilms. By: Lakshmi Devi Singh An Intervention to Control Vasomotor Symptoms for vToxoplasma gondii, an Apicomplexan parasite carried by Advanced Prostate Cancer Patients on Hormone Theracats, can infect humans and currently affects about one-third py of the world’s population. The infection causes significant brain inflammation, altered brain chemistry, and blindness, By: Maliha Sultana which is of particular concern for susceptible populations like AIDS, transplant and pregnant patients. Previous re- The research conducted in this study attempts to use modern search has found Apetala 2 (AP2) binding domains to be technology to propose a treatment for one of the side effects prevalent in the genome of Apicomplexan parasites, includ- resulting from androgen deprivation therapy, paced breathing Toxoplasma. This study focused on determining which ing, for prostate cancer patients. Because vasomotor sympToxoplasma genes have AP2 binding domains on their pro- toms yielded a significant decrease in hot flash episodes moter region. This was accomplished by creating a special- with menopausal women with similar experiences, it was ized computer program using two Bioconductor packages - hypothesized that perhaps prostate cancer patients with simChIPpeakAnno and Biostrings—to analyze the data of AP2- ilar episodes would have similar results. In order to faciliGST fusion protein binding capabilities to DNA sequences tate these trials, researchers in this study used iPods, intein Protein Binding Microarrays. The targeted approach of grating modern technology in the research; this is different the computer program was able to identify 116 genes in from other oncological research in not only does it incorpoToxoplasma that have domains in their promoter region for rate modern technology as a form of individual treatments, AP2 TF to initiate and promote transcription. These results but it focuses on current ways of dealing with those with the will facilitate in the understanding of gene regulation in disease already rather than depending on molecular sciences Toxoplasma gondii, which can be translated into advancing to prevent the disease. The results have shown that patients the development of more effective treatments for infected appreciated this program and that further improvements in patients. the final version would most likely be successful. The Effect of CF-301 and Daptomycin on Polymicrobial Biofilms By: Elias Strizower

Suppression of Prion Toxicity in Yeast by Deletion of Ubiquitin Ligases Correclates with Decreased Sizes of Protein Aggregates

By: Sarah Sutto-Plunz Staphylococcus aureus and Enterococcus faecalis are pathogens that are leading causes of nosocomial infections in Neurodegenerative disorders such as Alzheimer’s, Parkin-

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son’s, and Huntington’s disease affect millions of people worldwide. Each of these disorders has in common the intracellular accumulation of misfolded and aggregated proteins that are insoluble and are associated with cell toxicity. These toxic compounds are known as prion proteins. Similar toxic accumulated proteins are found in the model eukaryotic organism yeast. RNQ1 is a yeast protein that, in its prion form, leads to cell death. Toxicity is thought to be due to a failure or overloading of protein quality control pathways in the cell. This idea is supported by the observation that overexpressing a second protein that misfolds, Ste11? NK444R, in the RNQ1 prion background further increases protein aggregation and toxicity. The purpose of the experiments presented here was to investigate the effects of Ste11? NK444R expression on RNQ1 toxicity in yeast toward better understanding the role of different protein quality control pathways in protecting cells. In a cell viability assay, it was found that loss of the Ubr1 and Ltn1 ubiquitin ligases that target misfolded proteins to the proteasome suppressed toxicity. As shown by Western blot analysis and microscopy, reduced toxicity in the ubr1? strains correlated with reduced number and size of protein aggregates, despite the total amount of Ste11?NK444R RNQ1 protein in the cell being the same as compared to wild type. Furthermore, the results of a semi-denaturing gel suggested that there is a relationship between a decrease in toxicity and decrease in polymer size in the aggregates. This suggests that the yeast strains surviving exposure to the toxic aggregates may have survived by altering polymer and aggregate size. This work has important implications for possibly finding a drug that would aid quality control pathways to eliminate the toxic compounds, or even prevent their formation, and using it to cure the aforementioned neurodegenerative diseases, helping save millions of lives. Phosphodiesterase Inhibitors Reduce Proliferation in Malignant Gliomas By: Philip To Malignant Gliomas are a deadly form of cancer with very poor prognosis. Current available chemotherapies for treating malignant Gliomas result in significant adverse effects indicating the necessity of novel less toxic treatments. Previous studies have shown that activation of the Protein Kinase A/ Cyclic AMP responsive element binding protein (PKA/CREB) pathway results in a decrease in proliferation of Gliomas cells due to the induction of cellular differentiation state. The PKA/CREB pathway is activated by increases in levels of the small second messenger cyclic AMP (cAMP). In this project, the effects of specific inhibitors on Phosphodiesterase (PDEs), the enzymes that degrade cAMP, on CREB activation are computationally modeled and then experimentally validated to determine their ability to prevent proliferation of Gliomas cells. First, an ordinary differential equation based model of the kinetic reactions of the PKA/CREB pathway was constructed to predict the contribution of each individual PDE to PKA/CREB activation.

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Next, the effect of targeting specific PDEs with inhibitors was measured experimentally via a CREB activation assay and expression of a glial cell differentiation marker in a Gliomas cell line. These data were used to refined the computational model, and improve its predictive power. Based on the simulation results, predictions on the anti-proliferation potential of single PDE inhibitors and combinations of PDE inhibitors were made. Lastly, the anti-proliferating effects of PDE inhibitors in Gliomas cells were tested experimentally. It was found that targeted inhibition of PDE3, PDE4, and PDE7 in the Gliomas cell line U87 results in increased activation of CREB and decreased cell proliferation. The targeted single PDE3 inhibitor displayed the most prodifferentiation and anti- proliferation potential in U87 cells. This is the first systematic study comparing the contribution of multiple PDEs to the differentiation process in Gliomas cells, and highlighting PDE3 inhibition as a novel therapeutic approach to treat malignant Gliomas. Co-immunoprecipitation Reveals an Interaction between Human Factor P53 and Dengue Viral Protease NS2B/3 By: Pablo Vasquez Dengue Virus is the most common mosquito-borne viral disease in the world, with about 50 million cases of infection each year and is usually isolated in tropical environments where mosquitoes thrive. Because dengue virus evades the innate immunity of the body, it can lead to several severe manifestations such as Dengue Hemorrhagic Fever (DHF) or Dengue Shock Syndrome (DDS). Not all manifestations of dengue virus are as severe, however. There are no vaccines or antibiotics for dengue and treatment focuses on treating symptoms. For instance, if dengue is diagnosed early, it can be treated for by administering electrolytes. The non-structural dengue protein NS2B/3 has been implicated in interactions with host-cell proteins and it is possible that those interactions help the Dengue virus evade the innate immunity of the body. NS2B/3 has been shown to prefer cleaving quartets of amino acids with the P1 site being either Arginine or Lysine. The quartet follows the pattern of two basic amino acids, followed by two small amino acids. A pull down assay of NS2B/3 in a transfected cell revealed over 300 potential specific binding partners. Proteins selected fulfilled three criteria: 1.The proteins were present in the initial pull down assay. 2. The proteins are involved in the immune system in some way. 3. The protein has a potential NS2B/3 cleavage site. Likely host-protein candidates include human proteins: PI3K, NIRF, DDX (17/39/60), P53 and the TRIP. Understanding which proteins, both viral and human immune cell proteins, interact with which, is necessary in order to understand how the dengue virus evades the innate immune response. This study will use transfections, and if necessary, co-immunoprecipitation to determine if the given proteins interact with the NS2B/3 and further our understanding of the innate immune response evasion. AMPure beads: Size-Selection of DNA


By: Navya Voleti

By: Phoebe Wong

DNA Sequencing has become evident over the years, and scientists have even been successful in sequencing the whole human genome. In order for the DNA to be prepared before it is sequenced, depending on the size of the DNA fragments, because certain types of sequencing must be done. In order to select the size of the DNA, gel electrophoresis is used. However, it is very time-consuming and requires techniques that are more complex than that of using AMPure beads, which are magnetic beads that attach to the DNA, so that the DNA that is attached can be taken out, using a magnet. However, the use of AMPure beads is very new and had to be tested in order to find an effective concentration that would yield the best results. The testing of AMPure beads was done in order to find a better concentration of the beads that would yield a higher amount of the target DNA size. AMPure beads are magnetic beads that bind to the DNA. When these magnetic beads bind to the DNA, it allows us to separate the DNA from the enzymes and reagents. This is more efficient than running gel electrophoresis, since this takes about an hour, versus 3 hours for gel electrophoresis. It was concluded that the concentration of 1.5X would yield the highest amount of the target size of DNA. Knowing this increases efficiency because it lets us know the correct concentration at which we can use these magnetic beads to obtain the DNA fragments that we need.

Cartilage and tendons are one of the most difficult tissues to repair due to lower metabolic rates and tearing post-repair. A new look at therapy reveals stem cells, cells capable of differentiating into various tissues, may be the key to repair. This study focuses on comparing stem cell populations from gingival and dermal sources, cultured with and without transforming growth factor beta-3 (TGF-?3), to determine the extent of chondrogenesis or tendogenesis in an in vitro culture. TGF-?3 is a growth factor used for studies of Mesenchymal stem cells (MSCs), due to its proliferative and differentiative effect on cells. Rabbit gingival and dermal fibroblasts were cultured with/without TGF-?3. They were examined with Safranin O/Fastgreen stains and qRT-PCR with Collagen I, Collagen II, and Aggrecan, Decorin, and Tenomodulin gene markers. Results showed TGF-?3 increased proliferation and gene expression (except tenomodulin) of both cell types. In addition, all samples were more inclined for chondrogenesis than tendogenesis, because all genes except tenomodulin (the only marker for tendogenesis) were expressed. The gingival MSCs were larger, had higher levels of extracellular matrix, and attained more significant gene expression values than that of the dermal fibroblasts. All qualitative and quantitative results indicated that gingiva is a finer source than dermal for harvesting stem cells, and that TGF-?3 effectively enhances cartilage tissue formation of MSCs.

Regulation of Root Plasticity in Arabidopsis thaliana By: Vinesh Vora A major problem that we face today is a shortage of food due to the decrease in crop output. This inadequate food supply is the result of the changing climate that causes unfavorable environments for the plants to thrive in. Plant root system has major impact on plant survival, and it is regulated by myriads of internal and external factors. Understanding how the root plasticity is regulated in different environments would be beneficial in crop production. Here we intend to apply a combinatorial method utilizing 5 different signals, known to regulate root plasticity, two Nitrogen signals (NO3-, NH4+) and three hormone signals (Auxin-IAA, Cytokinins-CK and Abscisic Acid-ABA), to quantify root development (Trait) and gene expression (Gene). We then correlate Trait-to-Gene and use network analysis to identify novel candidate genes regulating root plasticity. Finally, we validate our hypothesis and identified a protein, the K+ protein channel that has a direct role in regulating the movement of the stomata and transpiration rate, and potential regulator of root development. We tested knockout mutant line of this gene, and identified root phenotype in six root traits. Potential application of this finding could be genetic manipulation of this gene, thus allowing the plants to survive in the harsh environments.

Various Agents Induce Encystment in the Protozoan Parasite Giaradia By: Jeffrey Wu Giardia intestinalis, a protist that causes the diarrheal disease giardiasis, kills 1.8 million people each year, worldwide. Giardia has two forms: trophozoite and cyst. Trophozoites feed and reproduce in the intestine, causing disease, and are shed in feces. Trophozoites do not exist long outside hosts. Cysts develop from trophozoites in the host, are shed in feces, and can survive hardily outside. Cysts are responsible for rapid spread of the parasite from host to host. Bile, produced by the liver and an emulsifier of fats, is an inducement factor of cysts in the host. It was hypothesized that the ability of bile to induce cysts is due to its detergent-like properties. The effect of detergent on cyst formation in Giardia was tested in vitro. This research is important because it will help people understand how to control the spread of giardiasis. Inhibiting cyst formation would help prevent host shedding of cysts in feces. If the host only sheds trophozoites that cannot survive outside the host long, the Giardia would likely die before reaching another host. Identifying Novel Function of Let-7 miRNA in Promoting Nephron Formation

Characterization of Novel Stem Cell Population By: Carly (Yue) Yu

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other associated metabolic disorders in patients with SCI. Kidney failure, one of the most severe health disorders today, afflicts over 26 million American adults. The ultimate cure is kidney transplantation. However, as recorded by the U.S Renal Data System, approximately twelve patients die every day amongst 100,000 others while waiting for an organ donor. Therefore, widely available bio-artificial kidneys, which require a comprehensive understanding of kidney development to build, will become crucial in future treatment. Previous research has acknowledged that Mesenchymal Epithelial Transition (MET), in which the mesenchyme differentiates into divergent cell types to form nephron, is essential during kidney growth. One regulator of epithelial development is miRNA, which are small genes that modulate organogenesis. We hypothesize that miRNA may function in the MET process during which essential internal structures of the kidney develop. To test our hypothesis, the miRNA expression profile during MET was screened, and 20 up regulated miRNA including the Let-7 family were found. Through Let-7f targeting by antagomir, we have discovered that down regulation of Let-7f inhibits ureteric bud branching and greatly reduces nephron growth, which allows us to draw the conclusion that Let-7f miRNA is a key player during kidney development. Thus, understanding the mechanism of Let-7f miRNA in a functional kidney promotes groundbreaking advancement in engineering a feasible, replacement bio-artificial transplant kidney.

WNT Signaling Protein LEF1 in Prostate Cancer Metastasis By: Valerio Zhang

?-catenin is a cadherin and a transcription co-factor that plays a large role in the growth, invasion, and metastasis of prostate cancer (PCa). ?-catenin during the Wnt signaling pathway can be either degraded or partake as a downstream effector for lymphoid binding-enhancer factor (LEF)1. LEF1 in previous research has been identified as a mediator in the Wnt/?-Catenin pathway (coordinating with AndrogenReceptor (AR)) and regulator for cell growth and fate. In this project we cultured PCa cell lines LNCaP, LNCaPAI, LNCaP-Lef1OE, LNCaP-AI-Lef1KD. The cells were run through a 4% acrylamide gel electrophoresis detecting for ?-catenin and 14-3-3?. A cell fractionation of the four lines was run through a 10% acrylamide gel electrophoresis detecting changes in the expression of ?-catenin and 14-33?. The results showed 14-3-3? to have higher concentrations in the cytoplasm of the four cell lines and ?-catenin to be found more concentrated in the nucleus than the cytoplasm with the presence of 14-3-3?. When 14-3-3? was knocked down with siRNA, ?-catenin had a significantly lower concentration in the nucleus than the cytoplasm. To confirm these Assessment of Effect of Exercise on Body Composition results, we used immunofluorescence microscopy with fluorescent-dyes specific to ?-catenin, LEF1, and 14-3-3?. Changes Following Spinal Cord Injury In this experiment, we identified 14-3-3? as a chaperone By: Zejia Yu for ?-catenin and aids translocation of ?-catenin to and from the nucleus. In addition, we will determine the cellular loPersons with spinal cord injury (SCI) may become wholly calization of both ?-catenin and 14-3-3? in multiple prostate or partially paralyzed. Muscle atrophy, because of immobilization and lack of exercise induces dramatic changes in cancer cell lines body composition. In the able-bodied population, exercise programs are crucial in the prevention and control of many Reactive Oxygen Species Elicit Renin Release from Mast Cells metabolic syndrome-related disorders, such as carbohydrate and lipid metabolism. To date, no standard guidelines have By: Qinru Zou been developed about exercise in the SCI population. In addition, there have been no studies that examine the existing literature in order to summarize the relationship between Mast cells are present in myocardial tissue in close vicinity insulin sensitivity and exercise in those with spinal cord to myocytes and nerve endings. Though these cells are best injury. The goal of this comprehensive review was to exam- known for their role in allergic reactions, research has ine the existing literature in the field of SCI medicine and shown these cells are pivotal in the activation of a local carrehabilitation and to determine the variables reported that diac renin angiotensin system, a hormone system that is best may be associated with insulin resistance in the SCI popula- known for its regulation of blood pressure and water baltion. It is hypothesized that there will be a direct relation- ance. Evidence suggests that mast cells constitute an addiship identified between body composition changes, duration tional source of renin in the heart. Human mastocytoma of exercise, type and intensity of exercise and the degree of cells and murine bone marrow-derived mast cells were incuinsulin sensitivity, or conversely lack of exercise, increased bated with H2O2 to mimic ischemic conditions in the heart. fat mass, and/or loss of lean mass with insulin resistance. As a function of its concentration, H2O2 elicited mast cell The review study thus implicates that activity training with degranulation, as evidenced by the release of ?duration from 8-52 weeks using the functional electrical hexosaminidase, which was associated with a release of stimulation (FES) aerobic training method increases glucose renin. In the heart, released renin would be likely to convert metabolism and insulin sensitivity, as well as prevents the angiotensin I to angiotensin II, which is capable of releasing progression of insulin resistance to diabetes mellitus and norepinephrine from sympathetic nerve terminals causing

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(13) Biomaterial of the Month. (2007, June 1). Society for Biomaterials. Retrieved December 21, 2011 (14) Hamilton, M. (n.d.). In What is an EMS Muscle Stimulator Unit and How Does It Work?. Retrieved January 3, 2012, from http:// www.lgmedsupply.com/whisemsmusta.html (15) Hornberger, J, K Kumar, E Verhulst, MA Clark, and J Hernandez. "Rechargeable spinal cord stimulation versus non-rechargeable system for patients with failed back surgery syndrome: a cost-consequences analysis."Clinical Journal of Pain� 24.3 Apr. (2008): 244-52. Web. 30 Jan. 2012. <http://www.ncbi.nlm.nih.gov/ pubmed/18287831>.

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Award Winners in Biology 2012 American Academy of Neurology Neuroscience Prize Vincent Shieh Intel Science Talent Search Semi-Finalists Award Sahil Agrawal, Bhargava Chitti, Olivia Munk, Talal Syed, Qian Kun Tan, Catherine Wang ISEF Finalists Shu Hui Liu, Talal Syed Junior Science and Humanities Symposium (JSHS) Finalists Bhargava Chitti, Christina Liao, Qian Kun Tan, Tongzhu Xu New York City Science and Engineering Fair Finalists Sahil Agrawal, Yuwen Cheng, Bhargava Chitti, Florence Dasrath, Matthew Eakle, Gabrielle Frenkel, Michela Garabedian, Enkhmend Gereltogtokh, Vivek Gupta, Andreas Hadjigeorgiou, Anthony Hagouel, John Hong, Tahsina Islam, Christina Liao, Shu Hui Liu, Anton Morozov, Yaseen Morshed, Olivia Munk, Anne Qiu, Brianna Saunders, Andrew Shakalis, Vincent Shieh, Talal Syed, Diptesh Tailor, Qian Kun Tan, Matias Tong, Tongzhu Xu Siemens-Westinghouse Contest Finalist: Yuwen Cheng Semi-finalists: Anthony Hagouel, Vincent Shieh

Award Winners in Biology 2013 Intel Science Talent Search Semi-Finalists Award Yashaswini Chittampalli, Daniel Donenfeld, Amanda Ruiz ISEF Finalists Shu Hui Liu, Talal Syed Junior Science and Humanities Symposium (JSHS) Finalists Lubaina Haider New York City Science and Engineering Fair Finalists Tyler Bell, Daniel Donenfeld, Ekramul Gofur, Daniel Huang, Ian Kaplan, Rana Lamisa, Fred Lin, Pratyusha Mutyala, Chirlien Pang, Ian Persaud, Elias Strizower, Maliha Sultana, Philip To Siemens-Westinghouse Contest Semifinalist Sarah Sutto-Plunz

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Photo Credit: : Shutterstock / Sebastian Kaulitzki The Journal of Biology is published annually by the Students of the Bronx High School of Science. The Bronx High School of Science The Journal of Biology, Rm 329D 75 West 205th Street Bronx, NY, 10468

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