Fall 2011: Volume 4, Issue 1

The Amherst

ELEMENT Volume 4 Issue 1

Fall 2011

Letter from the Editors We are excited to bring you the first issue of the Amherst Element since Spring 2010. We would like to thank all of our staff writers and copy editors for joining us in our journey to revive the Element!

One of the two main goals we had in our minds as we worked with the writers this semester, was to diversify the fields of science that the Element represents. In the previous issues of the Element, articles primarily focused on Biology and Neuroscience, which are tremendously fascinating fields, but of course are not a complete representation of the wide body of scientific knowledge. We wish to make the Element inclusive of all sciences. In this issue, we sought submissions from diverse fields, including astronomy, chemistry, physics, environmental science, geology, math, computer science, and psychology. We managed to achieve a degree of success; we received articles on environmental science (Going Blue by Anna Rasmussen ‘13, and Disease at the Margins of a Species by Casey Silver ‘12 and Caitlin NiesenBlank ‘14) and computer science (Useful Tools for the Computer Scientist by Jez Ng ‘14), and about summer research experiences in various scientific fields and geographic locations. Clearly, we still have a a long way to go in terms of achieving this diversity, but we will make this our long-term goal and continue to work on it in our future issues.

In addition, we envision the Element, the only publication on campus devoted to scientific thoughts, as the voice of the science community at Amherst. Science is much more than just beakers and lab reports; it is also about the people within. The scientific network at Amherst is composed not only of faculty and students, but also of many lab technicians and department coordinators keeping the labs running smoothly behind the scenes. We want to convey this sense of community. As a part of this effort, we have launched a new section in the Element where we interview the faculty and staff members of the science departments. This issue features an interview with Professor Stephen George, who was one of the founding members of the Neuroscience program at Amherst and is now on phased retirement. We tried our best to portray his prolific career in the span of a two-page interview.

Now, enough with the boring talk. We hope you enjoy reading this issue of the Element as much as we enjoyed creating it!

Sincerely,

News-In-Brief

Haneui Bae

Sonum Dixit

Sonum Dixit ‘13 Pituitary gland in a dish!

Japanese researchers successfully grew a pituitary gland from embryonic stem cells in vitro. Unlike previous studies, Yoshiki Sasai and his team grew two types of brain tissues, then injected them with Hedgehog, a protein messenger that causes cell differentiation. The dish-grown gland contains five different types of hormone cells and when inserted into a mice kidney, secreted adrenocorticotropic hormone (ACTH). It is unknown if the gland can produce other kinds of hormones.

Moth color patterns preserved through evolution 47-million-year-old fossilized moths from the Messel Pit in Germany had the same color patterns as present-day moths. The Messel Pit is a former mining site that has now been converted to a scientific excavation site and contains many well-preserved fossils, including these moths. Moth color patterns are not derived from pigments but stacks of layers in their scales. These stacks, also known as structural colors, make eyes blue and peacock feathers radiant. The primitive moths had yellow-green wings, most likely to camouflage themselves and hide from predators.

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Cheap treatment for arthritis!

As you will read in Namyi’s article, mirror therapy is used to cure pain in amputated limbs (also known as phantom limbs).

In this particular study at University of California, San Diego, a reflection of Dr. Laura Case’s healthy hand was shown to arthritis patients in a mirror. The mirror image gave the patients an illusion that Case’s hand was theirs, and their pain dropped an average of 1.5 points (out of 10 on a self-reported pain scale). Researchers still need to determine whether this therapy will have permanent effects.

Creating a Fish Genome Database?

Certain fish species are often fraudulently mislabeled as more expensive than they actually are. The Food and Drug Administration decided to collaborate with the Smithsonian Institution’s Laboratories for Analytical Biology and the Division of Fishes to release a fish genome database on Nov. 1st. DNA sequencing techniques were used to compile this database, which allows even processed and cooked fish samples to be used for sequencing. With the new fish genome database, consumers can now file a complaint with the FDA if they believe that their fish has been mislabeled. A crustacean database is also in the works.

Table of Contents

The Amherst Element Staff Editors-in-Chief Haneui Bae Sonum Dixit

Chief Layout Editor Jez Ng

Associate Copy Editors Maile Hollinger Narendra Joshi Namyi Kang Alexander Li Alice Li Maddie Lobrano Gabi Mateo Jez Ng Anna Rasmussen Sunnii Roh Katherine Savage

Feature Contributor Haneui Bae Sonum Dixit

Layout

Terence Kim Alice Li

Get Involved!

Send questions, comments, letters, or submissions to theAmherstElement@ gmail.com.

Cover Feature 1

The Canyonlands Risalat Khan ‘13

Features

2 News-in-Brief

Sonum Dixit ‘13 30 Interview with Professor Stephen A. George

Haneui Bae ‘13 and Sonum Dixit ‘13

Letters

6 Balance, the Lost Sixth Sense

Haneui Bae ‘13 11 Going Blue

Anna Rasmussen ‘13 14 Importance of Sleep in Memory and Related Processes

Narendra Joshi ‘13 21 Phantom Limb Syndrome and Mirror Therapy

Namyi Kang ‘15 23 Useful Tools for the Computer Scientist

Jez Ng ‘14 27 Lending a Hand to the Handless

Alice Li ‘13

Summer Research

4 Visualizing Disruption of Hair Cell Signal Transduction

Feynman Liang ‘14 9 Disease at the Margins of a Species

Casey Silver ‘12 and Caitlin Niesen-Blank ‘14 16 Amherst Students Discuss their Summer Experiences 18 Preventing Neuronal Cell Death in the Presence of Methamphetamine

Maile Hollinger ‘15 25 Science Elsewhere, the ‘Deutschland’ Perspective

Gabriela Mateo ‘13 26 CGRP Receptors and Migraine

Haneui Bae ‘13

The opinions and ideas expressed in the Element are those of the individual writers and do not necessarily reflect the views of the Element or Amherst College. The editorials are a product of the opinions of the current editors-in-chief of the Element. The Element does not discriminate on the basis of gender, race, ethnicity, sexual orientation, scientific background, age, or hair color.

Research findings published in the Element are not intended for wide distribution or for the reader’s profit. As a member of the Amherst community, please use the information and data presented in the Element judiciously.

Cover Photo: “We camped at many national parks and only passed through some others. We did not spend much time at Canyonlands - but it made for a pretty impressive view for just a lunch break! We did not go into the canyon, unfortunately. But it was probably for the best, since none among us wanted to get stuck for 127 hours! ” — Risalat Khan ‘13 The Amherst Element, Vol 4, Issue 1. Fall 2011

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Summer Research

Visualizing Disruption of Hair Cell Signal Transduction Feynman Liang ‘14 Over the summer, I had the pleasure of working at the Corey lab at Har vard Medical School. I was able to find this opportunity through my aunt, a postdoc at the Har vard School of Public Health, who introduced me to Dr. Corey, an Amherst alumnus. For those of you who have taken Introduction to Neuroscience, Dr. Corey is mentioned in the textbook!

INTRODUCTION The Corey lab is interested in hair cells: sensor y peripherals for both the auditor y and vestibular systems of vertebrates. Hair cells consist of multiple ster eocilia that protr ude from the surface of the inner ear in a str ucture known as a hair bundle.

Stereocilia are arranged in order of height, and adjacent stere- ocilia are connected by a thin strand known as a tip link 2 . One end of the tip link connects to the side of the adjacent taller stereocilia and the other end is connected to the gate of an ion channel on the tip of the lower end (see Fig. 2). This allows the ion channel to be directly sensitive to mechanical stimulus, and as a result hair cell Figure 1: Fluorescent Imaging of FM1-43 Dye Uptake ion channels open and close more rapidly than any other sensory receptor avoid unblocking. FM1-43 was added (2mM, 1μL per 1mL cells. FM1-43, a styr yle fluorescent 3 dye, passes through the mechanotransductionchannel . solution) and gently shaken for 1 minute. SCAS (100μL Tubocurare, a Southern Ameri- can arrow poison, blocks per 1mL solution) was then added and soaked for 5 the ion channel 1 and BAPTA breaks tip links and closes minutes. Samples were then mounted and visualized on the channel 2 . Using FM1-43 and fluorescence microscopy, a confocal microscope. disruption of transduction after BAPTA or curare treatment can be visualized. Field Emis- sion Scanning Electron FM1-43 and Fluorescence Microscopy In all cases, the amount of fluorescence decreased, Microscopy (FE-SEM) can visualize the morphological indicating that both BAPTA and tubocurare treatment changes resulting from BAPTA cutting the tip links. disr upt the mechanotransduction channel’s ability to pass FM1-43.

PROCEDURE AND RESULTS Utricle samples were dissected from P4 mice and Scanning Electron Microscopy After BAPTA treatment, samples were immediately immediately treated. Sam- ples were first rinsed in mouse exter nal solution for 15 minutes. Samples were then fixed with 2% parafor malde- hyde. Samples were treated treated with either 5mM BAPTA or (200μM and 2mM) with Osmium-Tannic Acid, dried, and then imaged with a field scanning electron confocal microscope.

Curare for 30 minutes.

Red arrows in the control image indicate tip links.

BAPTA treated samples were first rinsed in external solution for 5 minutes before dye loading while FM1-43 The absence of tip links in the treatment group confir ms was added directly to the tubocurare treated samples to BAPTA is cutting the tip links.

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Summer Research

Figure 3: BAPTA treated hair bundle

Figure 2: Control Hair Bundle COMMENTS AND CONCLUSIONS Because SCAS binds to all extracellular FM1-43 3 , the fluorescence in the control fluorescence images is from intracellular dye passed by the ion channel. The decrease in fluorescence in the treatment groups indicate that dye is no longer passing through the ion channel and that both BAPTA and tubocurare are disrupting the channel’s ability to uptake extracellular molecules.

The tip link complex is formed by PCDH15 and CDH23 bound together by three calcium binding sites 4 . BAPTA is a chelating agent and will remove extracellular calcium, causing the tip links to break. SEM imaging confir ms the morphological changes caused by BAPTA. This experiment confir ms both BAPTA and tubocurare’s ability to disrupt transduction and illustrates BAPTA’s p hy s i o l o g i c a l e f f e c t s o n h a i r c e l l s. T h e s e two treatments are thus viable channel inhibitors with different mechanisms of action which can be used in future studies of hearing and deafness.

While at times the long hours at the lab and even longer reading lists dampened my enthusiasm, the excitement of getting results made it all worthwhile. I found it difficult at first to transition from high-school biology to a research environment, but thankfully the other researchers were more than happy to help out. I encourage ever yone who is interested in doing research to find investigators who are studying something you’re interested in and directly reach out to them.

REFERENCES 1. Alharazneh A, Luk L, Huth M, Monfared A, Steyger PS, Cheng AG, and Ricci AJ. Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity. PLoS One, 6(7):e22347, 2011.

2. Assad JA, Shepherd GM, and Corey DP. Tip-link integrity and mechanical trans- duction in vertebrate hair cells. Neuron, 7(6):985–994, 1991.

3. Meyers JR, MacDonald RB, Duggan A, Lenzi D, Standaert DG, Corwin JT, and Corey DP. Lighting up the senses: Fm1-43 loading of sensory cells through nons- elective ion channels.

Journal of Neuroscience, 23(10):4054–4065, 2003.

4. Sotomayor M, Weihofen WA, Gaudet R, and Corey DP. Structural determinants of cadherin-23 function in hearing and deafness. Neuron, 66(1):85–100, 2010. *All images were acquired by William Fowle at the Northeastern University Center for Electron Microscopy

Wo r k i n g i n t h e Corey lab has been an exhilarating yet equally challenging experience.

Figure 4: Image of Hair Bundle.

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Letters

Balance, the lost sixth sense Haneui Bae ’13

The “five senses” has become a phrase we use frequently whenever we talk about our sensory perceptions of the world. But what we do not realize is that there is another crucial sense, a sense that we are so used to having and relying on that we do not even realize its existence: the sense of balance. But when we pause for a second to imagine a world without balance, so much of our daily activities and everyday happiness depends on having a well-functioning sense of balance. Not only would you be unable to perform simple balancing tasks like walking, or even sitting without falling, but also you would not be able to have clear vision.

Patients of Vestibular Disorders At the age of 39, Cheryl Schiltz, took an antibiotic called gentamicin to treat a postoperative infection, which inadvertently destroyed most of the balance-detecting hair cells in her inner ears, along with the bacteria that it was meant to kill. Two days after gentamicin treatment ended, she woke up with her world upside down. She crumpled to the floor from her bed and despite repeated attempts she could not get herself to her feet. She only managed to call her doctor by crawling down the staircase on her rear-end. At the doctor’s office, she was diagnosed with Bilateral Vestibular Dysfunction (BVD). “It’s as if the whole world and everything in it is made out of Jell-O,” Cheryl explained. “You don’t have anything steady under your feet. And then when you hit that, the Jell-O, everything in the distance starts shaking and that’s what you see.”1 Over the next few years, Cheryl’s life began to unravel. She could no longer drive anymore and lost her job as a consequence. BVD also affected her cognitive skills. She could no longer multitask, or do simple math.

Cheryl felt like she was perpetually falling into an endless abyss.

Cheryl’s story is an extreme example showing us how having almost no balance can wreak havoc on our lives. Many words we use to describe our sense of security are related to balance, such as “well-grounded,” and “settled.” This reveals how important balance is to our psychological as well as physical well-being.

Vestibulo-Ocular Reflex The clear vision that we all take for granted depends on a special link between the vestibular system and the eyes called the vestibulo-ocular reflex. As you move around, your head and your eyes are bobbing up and down crazily, yet your vision remains clear and focused. This is because the vestibular system adjusts the angle of your eyes to the motion of your head so that the image can stay focused on the retina, unaffected by head motion.

You can demonstrate this to yourself with a simple test. Hold your finger in front of your face and look at it while shaking your head from side to side. Even though your head is moving, you can still see the details of your finger clearly. Now keep your head in place and start moving your finger from side to side in space. The relative motion between your head

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and your finger is the same as in the first exercise, but now you will find that the image blurs out and you cannot see your finger clearly. Vestibuloocular reflex keeps your eyes in focus in the first exercise by detecting the motions of your head, but in the second one, your vision depends only on your imperfect voluntary eye muscles to control the eye movement, causing blurry images.

This precise reflex is compromised in the patients of balance disorders.

Cheryl explained how it is like to see the world through a person with BVD. “If you were to take a video camera and put it against your chest and just walk around…that’s kind of similar to what it looks like. Things wiggle and bounce around. Your eyes are like they’re on springs; they don’t want to stay still.”1

Figure 1: Amazing things balance lets us do.

Letters

Figure 2: A depiction of the inner ear by Max Brödel Multimodality of Balance We see with our eyes, hear with our ears, but how do we sense balance? Behind our ears encased inside the temporal bone of our skull is an intricate structure collectively called the inner ear, which is composed of the auditory system and vestibular system. The auditory organ, cochlea, (shaped like a snail shell in the picture) detects the vibrations created by sound waves with tiny hair cells lining the membranes inside. (See Feynman’s article for cool pictures of the hair cells!) The vestibular system, which is physically connected to the cochlea, works in similar mechanisms. It has two parts, the semicircular canals, and the otolith organs (utricle and saccule). The three semicircular canals are oriented in orthogonal directions to detect the rotation of our head in the three directions in space, and the otolith organs detect the tilt of our head. Both of these structures are filled with a viscous liquid with a group of hair cells lining the inner surface. When you turn your head sideways to say no, the sluggish liquid in the horizontal semicircular canal, moving more slowly than the canal itself, bends the hair cells in the opposite direction. This bending causes the hair cells to fire and send out the information to the brain, which integrates all the signals sent out by the hair cells (and some others) to create a picture of how the body is oriented in space: the sense of balance.

However, unlike the other five senses which receive most of the information from one primary sensory organ, the sense of balance requires more than vestibular inputs. In fact, relying solely on the vestibular system for balance may fool us in many situations. One of the reasons is that the vestibular system detects the acceleration of our head, not velocity. For example, when we are on an airplane, we feel the acceleration as the plane lifts off, but once it reaches a constant velocity (zero acceleration), we no longer feel the movement. In addition, sometimes the otolith organs can

mistake a force as gravity. During your flight, you may have looked out the window from reading a book or watching a movie, and found that the plane was in a sharp turn, but that you did not feel it. The centrifugal force of the turn bends the hair cells on the utricle and saccule and the brain mistakes it as gravity, causing a feeling that you are upright. In fact, cacording to the Civil Aerospace Medical Institute, it is possible in certain planes to perform a full 360-degree turn without the passengers’ being aware of the turn at all.1 This unexpected unreliability of our vestibular system in flight has led to numerous accidents, collectively called “ear deaths.” For example, experts attribute John F. Kennedy Jr.’s unfortunate crash off Martha’s Vineyard in 1999 to such spatial disorientation. There was no problem with the plane itself or the fuel; there were no signs of alcohol use. The experts speculate that Kennedy, having lost the visual cues to tell him which way is up, did not notice a slight tilt of the plane. Later when he noticed an increase in airspeed, he pulled up, which normally slows the plane down, but in this case increases the speed by tightening the turn. Then the panicking pilot might have pulled on the stick even more, locking the plane into a graveyard spiral to the earth.1 The Federal Aviation Administration reported in 1983 that in the past five years more than 500 spatial disorientation accidents occurred, with a 90% fatality rate.1 But if the vestibular system is fallible and unreliable, why is it that we are not constantly running ourselves into the ground? The sense of balance is unique in that it is detected by integration of information coming from several different sensory systems. Apart from the vestibular system, there are two other primary sensors: vision and proprioception. Proprioception is the muscle sense; from the stretch of our muscles, we can get information about how our body is oriented in space. For example, the stretch on our Achilles tendons can tell us that we are leaning forward.

Vision, however, is the most significant influence in perceiving balance. The only reason why we know that we are moving in a car of constant velocity is our vision: we see the landscape outside passing by.

Especially in flight where we cannot trust the vestibular system or the proprioception (we are sitting down), vision is our primary source of balance. As long as pilots can see the horizon or other visual markers that The Amherst Element, Vol 4, Issue 1. Fall 2011

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Letters indicate the relationship of their body to the ground, they have little trouble keeping themselves level. It is only when the vision is compromised, such as at night or when the plane flies through thick clouds, life-threatening spatial disorientations occur. Sometimes vision tricks us to perceiving that we are moving when we are not. When you are temporarily parked on a hill and the cars around you start to move forward, have you ever felt a jolt of fear, thinking that you are slipping backwards, and stepped on the breaks? This phenomenon is called vection, an illusion of self-motion by visual cues.1 Cheryl was especially prone to this kind of illusion because she depended on her visions so much as a result of her compromised vestibular system. She would get very dizzy in places like shopping malls where the environment was full of visual motion. When she was typing she felt the same way, “I couldn’t take my eyes from the computer to the paper and then back up, it was awful. It would make me feel like I was falling out of my chair.”1 This suggests that the three modes of balance perception, vestibular sense, vision, and proprioception, contribute to our sense of balance in a very dynamic manner. If one input is limited in certain situations, such as in the dark (vision), in a train (proprioception), or in flight (vestibular system), the other two can take over, giving more input to the brain. This plasticity is the reason why patients of vestibular disorders like Cheryl are not completely incapacitated, because they can utilize the two other organs of balance to get a limited sense of their orientation in space. Perhaps this multimodality of the plastic nature of balance reflects its evolutionary importance to the survival of our biped ancestors.

Balance of Survival “Plants don’t have a brain because they’re not going anywhere,” said Robert Sylwester, professor of emeritus at the University of Oregon.

“And if you’re not going anywhere, you don’t even need to know where you are.”1 The consequence of animals’ ability to move was that they now had to be able to detect and assess their surrounding environments. The sense of balance is a crucial part of this sensory mechanism that evolved to enhance our survival in this world.

Let’s wander back in time about 35,000 years when our ancestors and their competing peers roamed the earth. One of the greatest mysteries to anthropologists studying this period is why the Neanderthals disappeared completely from the earth after living successfully for nearly 200,000 years, while a later species Homo sapiens survived and flourished. There are many speculations regarding this issue, and one interesting view draws attention to the differences in their vestibular system.

Figure 3 : The skulls of the Neanderthals (left) and the Sapiens (right)

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The skeletons of Neanderthals showed that they had significantly smaller semicircular canals compared to their body size than modern humans.1 The size of the vestibular apparatus compared to the body size of an organism is considered an accurate measure of its agility and movements, and this revealed that the Neanderthals had a poorer sense of balance than our ancestor Sapiens.

This difference in balance function became significant in the face of rapid climate changes about 45,000 years ago. The climate shifts wreaked havoc on the woodlands where the Neanderthals lived and hunted. They were forced to live and find food in the open plains. The open field hunting required a dramatically different set of skills which the Neanderthals lacked and the Sapiens had: running.

Running is an incredible feat of the balance system. When we are running, only one of our legs is touching the ground at one time. The balance system keeps our torso upright as the rest of our body frantically moves about us, all the while balancing on one leg. In addition, the vestibuleocular reflex adjusts our eyeballs in such minute details that our vision of the world ahead of us remains clear, despite our head bouncing up and down. This was especially important for the Sapiens when they were hurling spears at the game during hunting. Neanderthals, who were stronger but did not have the balance skills necessary for open field hunting, slowly died out while the Sapiens flourished.

The balance, the sixth sense, is often overlooked and underestimated, but it is nevertheless a crucial sense that makes everything that we have become used to possible. It is time we gave it the due appreciation that it deserves.

REFERENCES 1. McCredie, S. (2007) Balance, in Search of the Lost Sense. New York: Little, Brown and Company.

Figure 1 : http://www.aspireadvantage.com/blog/?p=517 Figure 2: The Max Brödel Archives, Department of Arts as Applied to Medicine, The Johns Hopkins University School of Medicine. http://www.hopkinsmedicine.org/medart/HistoryArchives.htm Figure 3: http://www.erichufschmid.net/Neanderthals/MoreNeanderthals-4.html

Summer Research

Disease at the Margins of a Species Casey Silver ‘12 and Caitlin Niesen-Blank ‘14 Pathogen-host relationships can be observed in nearly the impact of the Black Death on human populations of every living system in biology. From infections in humans the 14th centur y, makes it a ver y worthwhile system to and animals to crop diseases to the goldenrod galls studied study. Given that the disease is so abundant in nature, in Biolog y 181, this interaction is widely researched in it is worthwhile to explore the effects that anther-smut natural populations. Infectious disease is very influential in has on the populations it parasitizes. the ecology and evolution of new species, as organisms can In assessing the theoretical effect of disease, one must strongly select for resistance to infectious disease or other consider the mode of transmission and the str ucture of methods of evading the pathogen. However, one area that host populations. Near the limits of a host’s distribution, is not yet fully understood is the effect that disease has on populations are often less dense, which prevents the the distribution of a host population. It is this question spread of diseases that depend on direct contact between we set out to work on in the Italian Alps this for two hosts, such as anther-smut. The transmission of antherweeks this summer. With Professor Michael Hood of the smut is frequency-dependent because the pollinators that biology department, Dr. spread the disease Janis Antonovics of the will fly further University of Virgina, between plants when and other undergraduate the plants are are and g raduate students at which decreases from both the United the number of States and Italy, we spent potentially infected t e n d ay s n e a r C h i u s a plants the pollinators d e Pe s i o s e t t i n g u p a will visit in any five year study that given time period. 1 will seek to deter mine Given this behavior how disease affects of pollinators, host populations at the pathogens can the margins of species produce sur prising ranges. patter ns of disease T he study utilizes prevalence that Microbotryumand in some cases can Dianthus as a even be inversely model pathogenproportional to host interaction. the size of the Figure 1: Anther-smut on Dianthus Pavonius Microbotryum is a fungus host population2 Initial that causes anther-smut disease in over 500 plant species population surveys in the study’s two permanent transects a r o u n d th e wo r l d . W h i l e t h i s d i s e a s e i s n o t f a ta l , i t showed a high prevalence of disease at 30-40%. This sterilizes the plants and takes over their reproductive prevalence remained constant among transects, despite cycle to produce fungal spores. These spores are then the fact that host-density varied more than ten-fold. spread between host plants by insect pollinators. The Finally, there was no disease-free zone at the less-dense focal host species is Dianthuspavonius, a perennial alpine margins of the populations. carnation whose populations can often suffer epidemics This summer, one of our objectives was to set up of anther-smut in which more than half of the individuals a manipulative field experiment that would help test are affected. This is a particularly convenient system to the theorized impact of Microbotr yum on population study because diseased plants can be identified simply by d i s t r i b u t i o n s o n D i a n t h u s. H i g h u p i n t h e M a r i t i m e looking at the flowers; dark spores are easily spotted on Alps, stationed at the RifugioGarelli, a lodge reachable the anthers of the flowers, giving the flowers a “smutty” accessible only by foot (a climb in elevation over 1,000 appearance. Furthermore, the prevalence of disease, rivaling meters), we set up disease removal and control plots. We The Amherst Element, Vol 4, Issue 1. Fall 2011

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Summer Research pulled up all of the diseased plants in one 6mx6m plot, works extensively with the native plants of the region. and from a second, adjacent plot we pulled up an equal While working with Professors Hood and Antonovics, percentage of plants at random (i.e. it didn’t matter if we undergraduates lived in the Parco Naturale research they were diseased or not). This second plot ser ved as station and the RifugioGarelli. During our free time, we a control. If a disease limits the distribution of a host had oppor tunities to explore the province of Cuneo, population, then a plot from which the disease has been hike through the Maritime Alps, feast on Italian cuisine, removed should experience a greater population growth, and learn about Italian culture. Overall, we learned a lot which will be deter mined by counting plants in the plots about disease biolog y and the challenges and benefits over the remaining years of the study. associated with field work. While it is ver y relevant to Another experiment that we star ted this summer study natural populations, experiments are often difficult made use of the re plicate valley system found in the to control. For example, one day we saw a cow eating the Maritime Alps. In this system, valleys lie nearly parallel flowers in one of our plots, which, needless to say, may to each other. These valleys therefore have ver y similar influence the number of plants that we count next year. climates, weather, soil, and altitude chang e. Our g oal was to figure out the ratio of healthy to diseased plants For all of us undergraduates, this was our first exposure a l o n g a n e l e va t i o n a l g r a d i e n t . We l o o ke d a t a n t h e r- to field work, and it gave us a welcome opportunity to do s mu t o n a p p r ox i m a t e l y 1 0 s p e c i e s o f D i a n t h u s a n d research outside of a laboratory, with natural populations. the related genus Silene, most of which live at slightly Of course, the view in the Alps wasn’t too bad either. different elevations, searching for a “disease-free halo,” or a section at elevational margins of the species where disease was not found on the hosts. Our initial studies REFERENCES have shown that there is rarely an anther-smut-free zone 1. Antonovics J. 2005. Plant venereal diseases: insights at the limits of the host species populations. The parallel from a messy metaphor. New Phytologist 165: 71-80. valleys allow us to replicate this assessment under similar 2. Antonovics J. 2009. The effect of sterilizing diseases conditions, giving us more data to work with. By looking on host abundance and distribution along environmental at different species of hosts, we can deter mine if the g radients. Pr oceedings of the Royal Society Series B 276: obser ved patterns can be generalized to all plant species 1443-1448. parasitized by Microbotr yum, or if they are specific to certain species.

Over the next four years, a group of students will return to the Alps with Professors Hood and Antonovics each summer to continue and collect data from the experiments that we started this year. After the study is completed, we hope to have a greater understanding of the effect that disease has on the distributions of host populations. Fur ther more, we will have fostered a relationship with Italian scientists and students. While the language barrier was sometimes difficult to overcome, we found that we could easily bond with the Italian students over shared interests such as hiking, cards, and food. They taught us some Italian, and it was fascinating to learn about the differences in h ow r e s e a r ch i s c o n d u c t e d i n t h e t wo c o u n t r i e s. S t u d e n t s f r o m t h e University of Turin will participate in the research each year, and the work will be done with the Parco Naturale Alta Valle Pesio e Tanaro, a b i o l o g i c a l r e s e a r ch s t a t i o n t h a t conducts conser vation effor ts and Figure 2: Collecting field data in the Maritime Alps

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Letters

Going Blue Anna Rasmussen ’13 Salmon at Val could soon become a thing of the past. Around 90 tons of fish are harvested globally each year, and it is not enough to supply the growing demand.1 With the increased need for fish and diminishing stock populations, people are beginning to realize that our “last wild food” is in trouble.2 Several problems face fish populations, including global climate change, overfishing, habitat destruction, and pollution. According to recent reports by the Food and Agricultural Organization of the United Nations(FAO), 80% of fish stocks are either fully exploited or overexploited.3 Popular fish like salmon, cod, tuna, and sea bass are dwindling because management policies do not take into account changing ecological factors and growing consumption of fish populations.

Proper management, international cooperation, and modern research are all necessary for the fishing industry to continue supplying the world at the present rate. Fish are a renewable resource, but they will not be around forever if current policies and practices continue at sea.

Climate Change One of the main issues facing fish today is climate change. A majorstudy published this September by researchers at the University of Bristol looked at the effects of rising ocean temperatures on fish in the northeast Atlantic. It found that cold-adapted fish populations like cod and haddock are declining, while warm water species such as hake and dab are thriving.

A little over 70% of fish species showed a change in abundance in the last 28 years due to dramatically rising ocean temperatures in the region. A majority of the changes were increases in warm-water fish populations.4 Another study conducted by the National Oceanic and Atmospheric Administration (NOAA) Figure 1: Haddock used 40 years of data collected in annual bottom trawl surveys and found that species such as haddock, cod, yellowtail, and spiny dogfish have shifted northward along the Atlantic Coast of the US. By 2009, half of the 36 species studied had shifted north and many other species had moved deeper to find cooler water. In total, about 2/3 of the species had habitat changes consistent with warming patterns.5 While some fish species face shrinking or moving habitat ranges, others are thriving and expanding to new areas. Considering these effects could be useful for conserving populations that are under stress while harvesting more bountiful species. One benefit of climate change on coldwater fish has been found by research from the Norwegian Component of the Ecosystem Studies of Sub-Arctic Seas (NESSAS). In the past decade,

cod spawning has been more active in the Barents Sea. Researchers have been studying cod population cycles since the 1920s and have found that cod are typically more productive when the Northern Atlantic is slightly warmer.This is most likely to due to the bottom-up effect (more phytoplankton growth at the bottom of the food chain leads to benefits higher up). Incorporating this data into management decisions could help fisheries predict when populations will flourish.6 The changing populations from cold-water to warm-water fish present people with the opportunity to change their preferences. Most people prefer salmon, cod, and sea bass, but restaurants are offering local fish or fish farmed in sustainable ways. In New Haven, for example, Miya’s restaurant prides itself on its unconventional sushi. Miya’s does not serve fish like tuna and salmon but offers locally dishes made from farmed catfish, bycatch fish, and invasive species.7 Fishing Along with climate change, overfishing plays a key role in the decline in fish stocks. Fisheries’ data has long been used in research and in making decisions about fishing regulations, yet it can hide shrinking populations until it is too late. The overfishing of Atlantic cod occurred due to misleading data and recently, two Californian recreational fisheries collapsedfor similar reasons. California’s fisheries data did not reflect the 90% decrease in stock size of barred sand bass and kelp bass because fishermen were fishing in seasonal spawning areas where many fish congregate. This practice yields average sized catches and is referred to as the “illusion of plenty” The Amherst Element, Vol 4, Issue 1. Fall 2011

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Figure 2: Herring Fishing in Alaska because it can hide overall population decline for years. Researchers used data from a power plant generating station (which uses ocean water for cooling and must track the number of fish caught in the system) to calculate the true stock abundance, and found that the population size had been declining since the 1980s, yet catch rates remained normal until the total collapse of the populations.8 Using additional types of data is necessary to avoid future crashes and to help sustain populations.

There are several ways that people have tried to alleviate the pressures of fishing, including fish farming. Aquaculture is defined by the NOAA as the “breeding, rearing, and harvesting of plants and animals in all types of water environments� and can be carried out in natural or manmade environments.9 As of 2008, over half of fish consumed were raised in aquaculture farms.1However,aquaculture has very high environmental costs that threaten its sustainability. Disease can spread from crowded farm stock to wild fish populations and fish waste can accumulate and pollute oceans. Also, it is inefficient to raise popularly consumed carnivorous fish such as salmon and sea bass. Carnivorous fish species depend on eating other fish for growth, and usually wild fish are caught and turned into fishmeal to meet this need.1 This leads to a further depletion of wild fish populations.With more fish like anchovies, sardines, capelin, and herring used as feed for aquaculture, the bottom of the food chain is also under growing pressure. While not much is known about the effect this has on marine ecosystems, it may lead to even more problems higher up in the food chain.2 Hatchery or farm fish are also not as nutritional, with less omega-3 oils and more drugs like antibiotics pumped into their systems.1 For all of its pitfalls, there is hope for aquaculture. It is more efficient than land farms in producing protein and farmers are trying to cut down on pollution and breed more efficient fish.Some modern farms are using integrated multitrophic aquaculture (IMTA) to become more sustainable.

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These farms raise fish less densely, with seaweed and mussels. Waste acts as fertilizer for seaweed, which is then turned into fish feed. Mussels filter feed and remove waste from the water as well, further reducing the impact of fish on the surrounding environment. Another new method of fish farming is raising omnivores instead ofcarnivores at the top of the food chain. An example is Barramundi, an efficient omnivore native to Australia.

They are shown to be high in omega-3 oils and do not need nearly as much fish meal as salmon or sea bass.1 Many organizations are trying to update their regulations to get a deeper understanding of the impact of fishing on non-target or nonlanding species as well.The NOAA published its first national bycatch report this September, which compiled national commercial fisheries data on bycatch information and was conducted in an effort to understand the impact of fishing by the United States on non-target species. Bycatch includes all the unwanted catch that is discarded from the ship, or dies from fishing practices. It includes fish that are caught that are not the target fish species, seabirds, sea turtles, marine mammals, and even the incorrect sex/ size fish of the target species. About 17% of the total catch in the US was found to be bycatch using data from 2005, though sample size was limited to about 63% of all landings due to insufficient data from some fisheries.

The report showed 1,887 individual marine mammals, 7,769 individual seabirds, and 11,772 individual sea turtles were bycatch in the year 2005.

Several techniques, such as new gear regulations, smart discard practices, designated no fishing zones, and species-specific bycatch reduction devices, have been implemented and appear to have decreased bycatch.For example, all shrimp trawl gear is required to have turtle excluder devices (TEDs) that have lead to the release of 97% of turtles caught in shrimp gear since the 1990s. However,the only way to see the true impact of new regulations is to have sufficient fisheries data in the future. The report contains many

Letters there are many organizations dedicated to understanding fish populations and how to conserve them while making the fish industry grow. But it will not be easy; we need to learn to catch fish in a more informed way, which includes changing our tastes. Next time Val is serving Barramundi, try it. It could be the first step in alleviating the pressures on more popular fish species.

REFERENCES

Figure 3: Satellite Image of Phytoplankton recommendations for better bycatch data collection and estimation that could greatly help our understanding of the costs of fishing.10 The Future One new development that could help fisheries understand population growth and decline is the use of satellite data. Remotely sensed data could help fisheries manage stocks because researchers are no longer restricted to ships and can track changes in an ecosystem that affect fish recruitment.

Studies have used remote sensing of ocean color to assess phytoplankton biomass, whichis often used to measure productivity of an ecosystem because phytoplankton is at the bottom of the food chain.6, 11 Instead of relying on previous years’ data from fish catches, agencies could look at phytoplankton blooms, which can indicate quality of fish yield.12 They could also track community shifts, changes in phytoplankton types, map habitats, and spot toxic algae blooms.11 This data could be used to identify potential fishing zones and predict fish production for a given season.

Unfortunately, there is a lack of willingness by the fishing community to support remote data sensing despite its potential to make necessary data collection more efficient and effective.

With all the problems facing the fishing industry, greater changes need to be made. In his widely popular book Four Fish, Paul Greenberg suggests four ways to help stop the rapid decline in stock populations.

He proposes 1) a reduction in number of fishing fleets, 2) designation of portions if ecosystems (such as breeding and nursery grounds) as no fishing zones, 3) changes in international divisions of fishing boundaries, which do not often follow scientific reasoning and cause further depletion of fish, and 4) protection of the bottom of the food chain.2 Although these goals may not be entirely realistic, they encourage us to be aware of fishing ecosystems and the stress on fish stocks. Like any other food source, fish cannot replenish themselves indefinitely and good management practices can help maintain populations for the future.

The ocean is a complex place, and the key to not destroying marine ecosystems is incorporating more research into fishing policies. Fish has become a staple in the diets of people around the world, and if it is no longer available it will cause serious issues in feeding our planet. Fortunately,

1. Walsh, B. (2011, July 07). End of the line. Time.

Retrieved from http://www. t i m e. c o m / t i m e / h e a l t h / article/0,8599,2081796,00.html 2. Greenberg, P. (2010). Four fish. New York: The Penguin Press.

3. Food and Agricultural Organization of the United Nations, Fisheries and Aquaculture Department. (2009). The state of world fisheries and aquaculture.

Retrieved from http://www.fao.org/docrep/011/i0250e/i0250e00.htm 4. Some like it hot: University of Bristol (2011, September 19). Some like it hot: European fish stocks changing with warming seas. ScienceDaily.

Retrieved September 28, 2011, from http://www.sciencedaily.com/ releases/2011/09/110915131557.htm 5. NOAA Fisheries Northeast Fisheries Science Center (2009, November 4). North Atlantic Fish Populations Shifting As Ocean Temperatures Warm.

ScienceDaily. Retrieved September 28, 2011, from http://www.sciencedaily. com¬ /releases/2009/11/091102172247.htm 6. Norway Research Council of Norway (2010, May 5). Currents influence fish stocks: More cod in the Barents Sea. ScienceDaily. Retrieved September 28, 2011, from http://www.sciencedaily.com/releases/2010/05/100505092525. htm 7. The invasive species menu: local seafood. (n.d.). Retrieved from http:// miyassushi.com/invasive.html 8. Illusion of plenty: University of California - San Diego (2011, September 27).

‘Illusion of plenty’ masking collapse of two key Southern California fisheries.

ScienceDaily. Retrieved September 28, 2011, from http://www.sciencedaily. com/releases/2011/09/110926173139.htm 9. What is aquaculture. (2010, July 15). Retrieved from http://aquaculture. noaa.gov/what/welcome.html 10. U.S. Department of Commerce, National Oceanic and Atmospheric Administration. (2011). U.S. national bycatch report. Retrieved from http:// www.nmfs.noaa.gov/by_catch/bycatch_nationalreport.htm 11. Stuart, V., Platt, T., and Sathyendranath, S. (2011, January 17). The future of fisheries science in management: a remote-sensing perspective. ICES Journal of Marine Science, 68: 644–650.

12. Platt, T., Sathyendranath, S., and Fuentes-Yaco, C., (2007, June 12). Biological oceanography and fisheries management: perspective after 10 years. ICES Journal of Marine Science, 64: 863–869.

Figure 1- http://www.nefsc.noaa.gov/press_release/2009/SciSpot/SS0908/ Figure 2- http://scrippsblogs.ucsd.edu/cens/2011/01/12/catch-shares-

an-antidote-to-overfishing/ Figure 3- http://www.geog.ucsb.edu/events/department-news/123/ breakthrough-system-for-understanding-ocean-plant-life-announced/ The Amherst Element, Vol 4, Issue 1. Fall 2011

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Letters

Importance of sleep in memory and related processes Narendra Joshi ‘13

Though most humans—except college students—spend close to a third of their lives sleeping, we know embarrassingly little about this pleasurable state of our body and mind. Over the recent years, scientists have found evidence of the critical role sleep plays in bodily functions.

After decades of research, we are finally beginning to get a grasp of interesting details about the relationship between sleep and memory. As our knowledge about sleep has grown, so have the concern and awareness about its importance.

In humans, sleep occurs in 90-minute cycles with two general stages: rapid eye movement (REM) sleep and non-REM sleep. On the basis of recordings of electrical activity in the brain, non-REM sleep is composed of four distinct stages. The third and fourth are the deepest stages of sleep and are together called slow-wave sleep. 1 Sleep not only regulates and restores body tissues, but it also plays an important role in brain function. The patterns of electrical activity in the brain change during different stages of sleep. These changes in activity, primarily during REM sleep and slow-wave sleep, are linked to processes such as brain plasticity and memory consolidation. Connections between

neurons in the brain are formed or broken at an elevated rate during sleep, especially in regions of brain involved in information acquisition and processing. Also, information acquired during wakefulness is thought to be transferred between regions of the brain leading to “storage” in the prefrontal cortex.

Acquired skills get incorporated into the brain during sleep2. In zebra finches, a species of songbirds commonly used to model vocal learning, songs are “replayed” in the brains of young birds during sleep. In regions of the brain involved in song production, patterns of electrical activity that occur when a bird is singing get repeated with remarkable accuracy when the bird is asleep. This phenomenon is believed to play important roles in formation and reinforcement of song memories as a young bird learns to sing by copying the song of an adult.3 Surprisingly, a study in humans has found that consolidation of learned skills and facts occurs almost exclusively during sleep and very little improvement in memory happens during waking hours.1 If more studies confirm and elaborate on this phenomenon, the results could have implications for memory improvement and cognitive rehabilitation therapies.

Figure 1: A student sleeping at the study table. A common sign of sleep deprivation.

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Figure 2: A hypnogram showing stages of sleep in humans. Each sleep cycle is about 1 hour 30 minute long.

Sometimes, sleep can be a source of profound insights. Otto Loewi, the famous pioneer of neuroscience, got the idea for one of the most classic experiments in neuroscience while he was asleep. In his dream, Loewi came up with a clever experiment to check whether or not any chemical factors are involved in the transmission of nerve impulse in the heart.

He rushed to his research lab in the middle of night and started carrying out tests. Eventually, this experiment –“conceived” in a dream- led to the discovery of the first neurotransmitter. More recently, a scientific study has shown that people who get a good night’s sleep are almost twice as likely to recognize a hidden abstract rule while solving a problem. Participants who got sleep were also significantly quicker in their responses than sleep deprived individuals. 4 Studying the effects of sleep deprivation can provide important insights into sleep’s function. It has been shown experimentally that sleep deprivation can lead to disruption in normal functioning of the brain.5 Sleep deprived individuals are likely to enter states of “semi-dreaming” during a cognitive task. In such a state, individuals might experience incoherent and sporadic thoughts passing through their conscious mind.

Sleep deprived individuals also show increased occurrence of “microsleeps” whereby individuals involuntarily undergo episodes of sleep lasting up to a few seconds.5 In rats, it has been shown that sleep deprivation can cause groups of neurons in the frontal motor cortex to turn “off ” for a while even though the brain as a whole remains awake. This leads to a decrease in performance of sleep deprived rats during a behavioral test. 6 If the neurons that get turned off are involved in critical cognitive functions, it might decrease the efficiency of mental processing. Even partial sleep deprivation has major implications for memory consolidation. Individuals who get sleep after learning a new skill show improvement but subjects who remain awake or get small amount of sleep show no significant improvement. 7 Though the signs for the critical role of sleep in memory are accumulating, conclusive links have not yet been established. In particular, the precise roles of REM sleep and slow-wave sleep are not known. Also, some memory consolidation can occur over time even without sleep, though sleep certainly facilitates the process.1 Sleep is not as critical for the use of well-established memory as it is for the consolidation of new

memories.4 Therefore, we should be cautious in assessing the role of sleep.

Overall, recent findings have indicated that sleep needs to be taken more seriously than it generally is. The fact that sleep is universal among vertebrates suggests an evolutionary basis for its indispensable role. Most studies suggest that at least 6-7 hours of sleep is necessary for most adults, though, requirements may vary in particular individuals. With rapidly growing scientific knowledge of sleep’s critical functions, especially in memory consolidation, clinicians as well as the general public are recognizing the importance of a good night’s sleep. College students too should apply these new lessons and, maybe, some incentives from their professors could help!

REFERENCES 1. Stickgold, R. Sleep-dependent memory consolidation. Nature. 2005.

437, 1272-1278 2. Karni A, Tanne D, Rubenstein BS, Askenasy JJ, Sagi D. Dependence on REM sleep of overnight improvement of a perceptual skill. Science.

1994. 265(5172):679-82.

3. Shank, S.S., Margoliash, D. Sleep and sensorimotor integration during early vocal learning in a songbird. Nature. 2009. 458, 73-77 4.Wagner U, Gais S, Haider H, Verleger R, Born J. Sleep inspires insight.

Nature. 2004. 427(6972):304-5.

5. Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation.Seminars in Neurology. 2005. 25(1):117-29.

6. Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G. Local sleep in awake rats.Nature. 2011. 472(7344): 443–447 7. Stickgold R, James L, Hobson JA. Visual discrimination learning requires sleep after training. Nature Neuroscience. 2000. 3(12):1237-1238.

Figure 1: http://en.wikipedia.org/wiki/File:Sleeping_while_studying.JPG Figure 2 : http://www.medscape.org/viewarticle/588160_2

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Summer Research

Amherst Students Discuss Qianqian Chen ‘13 Selasie Krampa ‘13 I applied to the DAAD (Deutscher Akademischer Austausch Dienst) Rise program, because I saw it as an opportunity to kill two birds with one stone: going abroad for 3 months, and having hands-on Chemistry research experience. My internship placement was at the Technische Universitat Dortmund, in Dortmund, a city in the the center of Europe and close to major destination cities like Amsterdam, Brussels and Berlin.

One thing that has really impressed me about research in Germany are the abundant research opportunities in this country.I was placed with a lab that is working on a recent field of Chemistry that actually gained ground in the late 20th century. I worked at the INFU – Institute of Environmental Research, Technische Universitat Dortmund with a diverse research group consisting of people from Syria, Turkey, Iran, India, France and Germany; my co-workers were very friendly, and they helped me blend seamlessly into German life. My group worked on Molecularly Imprinted Polymers (MIPs).

MIPs are prepared by molecular imprinting, a technique based on the system used by enzymes for substrate recognition, the “lock and key model”. It entails creating template-shaped cavities in polymer matrices with the memory of the template molecules used in molecular recognition of the template. In order to create a MIP, you need a functional monomer, template, solvent, and a cross-link agent. My research this summer involved developing refined chromogenic and fluorogenic monomers and imprinting protocols allowing to obtain robust and sensitive optical sensors for a range of high priority ionic analytes. The DAAD Rise program is a great opportunity to not only get hands-on experience, but also travel within Germany and Europe. I know from personal experience that it’s difficult for science majors to “study abroad” due to course requirements. The RISE program is a solution to this hurdle. It doesn’t matter if you speak “zero” German. Prior to my internship, the only German phrase I knew was “danke” (thank you).

I was still able to make it out of Germany alive. My summer experience in Germany was rewarding and I won’t hesitate to do it again if I had the chance.

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http://www.sxc.hu/photo/834520

I did a 8-week summer math research with Professor Robert Benedetto and three other Amherst students. Our goal was to look at certain topics in algebra and number theory and to try to generalize some theorems. It was an REU research, which means the funding was only for US citizens/residents, but I was lucky enough to have the college sponsor my research.

I wasn’t really sure what I was getting myself into because I had never done math research before and the topics were unfamiliar.

The first two weeks we had a steep learning curve. Professor Benedetto would come in every morning to give us a one to two hour long lecture on the foundation of the research, and he would assign practice problems to test our understanding.

He also provided us with a stack of Springer books and several papers as reference. The next several weeks we were given general directions and started to do programming to find evidence for our theorems. It was really cool to be on the frontier of math where there was no answer key. Professor Benedetto would say - here we know nothing, absolutely nothing. One of the many things I learned this summer is that math should be a social activity. Discussion and collaboration are great ways to solve problems, find new approaches and enhance understanding.

Also, it’s really necessary to have great work ethic. If things don’t come naturally, just continue playing with them over and over again and keep your spirits high.

Risalat Khan ‘13 As part of the “Geology of the Colorado Plateau” course taught at UMass in the spring of 2011, I went to the Colorado plateau region in the beginning of the summer with our entire class on a two week field trip. We visited ten or so national and state parks over the trip. We would camp at a park, hike and discuss geology for the day, perhaps travel to other parks in the vicinity, and then move on to camp at a different park the next day. This was my first time in the west, and it was absolutely breathtaking! I especially enjoyed Bryce Canyon and Arches, and also Grand Canyon. At Grand Canyon, I challenged myself to complete the toughest hike of my life thus far - in which we made it through 10 kilometers of distance and 1 kilometer of elevation down and then back up again. But the view of the inner gorge of the canyon made it all worth it, despite the blistering heat. Coming back after the two week trip, I felt as though a long time had passed since the spring semester ended. I returned with numerous memories, perhaps even more photos and a fuller appreciation for the grandeur of nature.

Summer Research

Their Summer Experiences Mizuho Ota ‘13

Sonum Dixit ‘13

I spent 10 weeks this summer at Mount Sinai Medical Center in New York, where I participated in a Summer Undergraduate Research Program (SURP) designed for undergraduate students considering a Ph.D. or MD/Ph.D in biomedical research. In Dr. Andrew Chess’ lab in the Developmental Biology, I conducted research on the rates of X chromosome inactivation in female autistic patients and mothers of autistic patients.

Inactivation of one of the two X chromosome occurs in all human female cells. Usually X inactivation is a random event, leading to approximately equal inactivation of both X chromosomes; however, nonrandom X inactivation is seen in about 10% of the normal human population. The aim of this project was to develop an effective set of assays to quantitate X inactivation, with the ultimate purpose being to analyze the DNA of unaffected mothers of autistic patients. Autism, a neural developmental disorder found in roughly 1 in 150 of the population, is found in a higher rate in males than in females; it is thought for this reason that there may be genetic factors or mutations on the X chromosome that contribute to autism. Hypothetically, a female carrier for such a genetic factor may be “protected” from expressing the autistic phenotype if the X chromosome carrying the deleterious mutation is preferentially inactivated.Two highly polymorphic loci, the Androgen Receptor and the Fragile X, were used to assess the methylation, and thus inactivation, status of the chromosomes by digesting the DNA with the enzyme HpaII, which cleaves DNA at these sites if the X chromosome is unmethylated.

Using methods such as gel capillary electrophoresis and microfluidic Bioanalyzers, we developed an accurate assay for quantification of cleavage by the enzyme and applied it to a number of DNA samples from mothers of autistic patients to determine if nonrandom skewing occurred in mothers of autistic patients at a higher rate than in the general population. We also isolated highly skewed individuals as candidates for exome sequencing, which may shed light on the specific mutations contributing to autism.

I spent eight weeks working at the Genomics Research Centre, which is run by Professor Lyn Griffiths in Griffith University Southport. Southport is in the Australian Gold Coast, which is an hour south of Brisbane. I genotyped single nucleotide polymorphism (SNP) rs2229094 on the Lymphotoxin Alpha (LTα) Gene, found on chromosome 6.

In a SNP, one DNA nucleotide changes in a given sequence, lending to different genotypes among individuals. The LTα gene codes for the LTα protein, which is a member of the tumor necrosis family. Tumor necrosis family proteins are usually involved in inflammatory responses, the nf-Kβ pathway mediated pain response and are linked to various diseases. In my project, I examined rs2229094’s potential link to migraines. by using High Resolution Melt (HRM), to genotype 74 healthy patients and 84 migraine patients.

HRM machines pre-amplifiy DNA and generate different melt curves for each genotype. HRM is a faster and more efficient alternative to the common technique of amplifying DNA with Polymerase Chain Reaction then genotyping using Restriction Fragment Length Polymorphism (RFLP).

Because HRM involves smaller tubes than traditional PCR, samples are more likely to be contaminated and I had to be extremely careful. I also sequenced a few samples to verify that my primers were cutting the correct sequence.

Rs2229094 did not have a significant effect on migraine, but the experience was extremely rewarding It taught me the importance of independent scientifc thinking instead of just following instructions and I was able to apply principles I learned in Molecular Genetics last fall. I met many PhD students, got an opportunity to tour the beautiful beaches, see Australian wildlife and understand Australian history and culture.

Joseph Kim ‘14 This summer I participated in a 10 week long research project as part of the Summer Science Research Fellowship Program on the Amherst campus as a MacWilliams Fellow. The fellowship involved engaging in an independent research project full-time under the guidance of an Amherst College faculty mentor, in my case Professor David Ratner. The project that Professor Ratner and I decided I should undertake was to create a vector to knockout the PKaR Regulatory Subunit gene in the social amoebae Dictyostelium discoideum. This project took the full 10 weeks to accomplish, and by the end, I had learned many laboratory research techniques. One memorable episode was when the PCR of the carboxy terminus of DNA continually yielded a mysterious product. Both Professor Ratner and I were puzzled over how this PCR product could have formed, and had to work together to figure out how to solve this puzzling stretch of DNA. The most rewarding aspect of the fellowship for me was working so closely with my faculty mentor; it’s an experience that is hard to reproduce, short of writing a thesis.

Summer Research

The Cell Suicide Hotline: Preventing Neuronal Cell Death in the Presence of Methamphetamine Maile Hollinger ‘15 Methamphetamine is known to cause devastating brain damage to users – but a certain protein inhibitor may actually prolong neuron life during methamphetamine use.

“Here are the dr ug lockers. This one’s mine. And this is the meth itself.”

My first day at the National Institute on Dr ug Abuse in June of 2009 was interesting, to say the least. Fresh out of my home state of Hawai’i, I was more than aware of the dangers of methamphetamine – it is, after all, a widespread dr ug there – but I never imagined that I would be close enough to see the small cr ystals that could destroy lives. Despite my misgivings, I ended up diving headfirst into an internship in which I would be expected to look at the effects of methamphetamine on neuron sur vival on a daily basis—and what we could do to save those neurons.

commit a for m of suicide known as apoptosis. Since neurons don’t replicate after birth, their destr uction is detrimental to the brain; after prolonged methamphetamine abuse, for example, users’ limbs shake similarly to those of a Parkinson’s disease patient due to neural degeneration. 2 Methamphetamine, p53, and Apoptosis My lab wanted to look at the possibility of protecting these meth-damaged neurons by preventing the cell from committing suicide. T his meant blocking the “master protein” of the cell: p53. p53 is a tumor suppressor responsible for mediating DNA damag e re pair, cellcycle ar rest, and apoptosisthat interacts with over 30 genes, such as those in Figure 2—thus, it literally has the power of life and death in the cell. Since p53 is pro-apoptotic, it is reasonable to expect that inhibition of p53 will inhibit apoptosis, unless apoptosis happens through a p53-independent mechanism. In the case of p53-mediated apoptosis, p53 is activated by a trig g er such as DNA damage or excessive cell damage. p53 then activates downstream genes (in the gray box of Figure 1)that cause the mitochondrial membrane to open, thus allowing ions into the cell that destroy sensitive structures. 3

Figure 1: Methamphetamine crystals.

What is Methamphetamine?

Methamphetamine is a psychostimulant that targets t h e n e u r o n s i n t h e b r a i n t h a t p r o d u c e d o p a m i n e, a neurotransmitter (signaling chemical) that is associatedwith pleasure and reward. That said, it isn’t a surprise that 10.4 million people in the United States alone had tried methamphetamine according to a study released in 2005. 1 With pleasure, however, there is pain: repeated methamphetamine use causes per manent damage to synapses, the structures that allow neurons to pass signals to neighboring cells, and eventually causes the cell to

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Figure 2: p53 and its downstream genes. Inhibiting p53 leads to inhibition of pro-apoptotic genes, represented in red.

Summer Research Inhibition of p53 and, therefore, apoptosis would then mean that neurons exposed to methamphetamine would not commit“suicide” and would instead remain alive in culture. Therefore, the purpose of the study I worked on was to see if a p53 inhibitor known as PFTα would prevent neuron death, even in the presence of a high concentration of methamphetamine.

Finding Living Cells: Immunocytochemistry To deter mine the number of living cells in culture, we perfor med a process known as immunocytochemistry.

The primar y workhorse in immunocytochemistr y is the antibody, a protein produced by the immune system that binds to a specific molecule or cell. In the body, the primar y purpose of an antibody is to tag a molecule or cell for destr uction; in the lab, however, they are useful since their binding sites can be engineered to fit a specific protein, molecule, etc. For the purposes of immunocytochemistr y, an antibody is chosen that binds to a specific molecule in the sample. Our target molecule was a protein found in healthy neurons known as tyrosine hydroxylase. Tyrosine hydroxylase is an enzyme that is involved in dopamine production; if neurons contain t y r o s i n e hyd r ox y l a s e, t h e n t h e y a r e s t i l l f u n c t i o n i n g nor mally in their dopamine production, which would not happen if the cell were to undergo apoptosis. Therefore, marking tyrosine hydroxylase would mark neurons that were still sur viving in culture.

After plating dopaminergic (dopamine-producing) neurons from rat embr yos, we treated the neurons with an inhibitor of p53, known as PFTα, fifteen minutes after treating the neurons with a toxic (1 mM) dose of methamphetamine. After allowing the cells to g row in culture for two days, we fixed the cells to the plate and used immunocytochemistr y to tag tyrosine hydroxylase.

First, the tyrosine hydroxylase-binding antibody was added to the cultures. Then, a second antibody was added to bind to the first antibody An enzyme at the end of the secondar y antibody contained an enzyme that would fluoresce in contact with a substrate, thus identifying the antibody complex and, therefore, the target protein.

Addition of substrate then caused the cells to fluoresce under a certain wavelength of light. It is possible to take a picture of these fluorescent cells via microscopy, as well as quantify the amount of fluorescent dye in the sample as compared to the entire area of the sample via LiCor ® scan. p53 Inhibition’s Effects on Neuron Survival After analyzing the LiCor scans and fluorescent microscopy images, we found that cells treated with both methamphetamine and PFTα sur vived markedly better in the presence of methamphetamine than cells treated with a vehicle control, DMSO. The DMSO control was included to ensure that the methamphetamine, and not the solvent, was killing neurons without PFTα. In the experiment

with f luorescence microscopy, the methamphetamine was neurotoxic, as can be seen by the absence of green fluorescence in Figure 3a. However, PFTα increases the concentration of green fluorescence (Figure 3b), which means that TH and viable dopaminergic neurons are present. Qualitatively speaking, PFTα protects neurons against methamphetamine neurotoxicity.

Interestingly enough, the methamphetamine was not toxic in the LiCor ® experiment; we actually found an increase in the number of neurons (Figure 4, next page).

Although the cause for this is not known, it is entirely possible that PFTα prevented cell-cycle arrest and thus caused the cells to proliferate at a greater rate than they would have nor mally.

Figure 3: PFTα protects neurons in the presence of methamphetamine.

3(a): Neurons treated with DMSO (control) and methamphetamine.

3(b): Neurons treated with PFTα and methamphetamine.

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Summer Research and another molecule, an A3 receptoragonist (a molecule that binds to the adenosine-3 receptor to initiate varied cellular responses), had what appeared to be no effect on neuron sur vival, while inosine (a nucleoside found in tRNAs) appeared to actually harm cell survival. Science is often hailed for its ability to improve the human condition; for now, however, a quick fix to stop the damage done by the methamphetamine in that small, gray locker I met on my first day at NIDA remains as elusive as ever.

Acknowledgments The research work in this study was supported by the National Institute on Dr ug Abuse, NIH.

Figure 4: PFTα promotes survival of neurons, even in the absence of neurotoxicity. “-MA” represents the methamphetamine-negative group, while “+MA” represents the methamphetamine-positive group.

Cell Survival: Good or Bad? What does this mean for methamphetamine users— o r e ve n i n d iv i d u a l s s u f f e r i n g f r o m a p o p t o t i c - b a s e d neurodeg enerative diseases like Parkinson’s? PFTα’s ability to save methamphetamine-treated neurons from apoptosis looks promising. Also, PFTα can cross the semi-per meable blood-brain barrier (BBB), which means that the use of PFTα as a treatment would involve noninvasive introduction to the body, such as intravenous injection. However, p53’s other functions should not be neglected. Blocking apoptosis would mean that unhealthy neurons that may need to be removed from the system would linger and cause problems with signal transmission.

Further more, blocking p53 would block its DNA repair and cell cycle arrest functions, causing genomic instability, uncontrollable cell division, and even carcinog enesis; with p53 mutated or inactivated in over 55% of known cancers, its use as a therapeutic target remains uncertain; however, the use of PFTα should be investigated in more detail until a less risky therapeutic possibility becomes available.

REFERENCES 1. Methamphetamine: Abuse and Addiction. Publication no. 06-4210. 1998. National Institue on Dr ug Abuse Research Report Series. US Department of Health and Human Ser vices, 2006. Web. 13 Oct. 2011.

2. Davidson, Colin, Andrew J. Gow, Tong H. Lee, and Everett H. Ellinwood. “Methamphetamine neurotoxicity: necrotic and apoptotic mechanisms and relevance to human abuse and treatment.” Brain Research Reviews 36.1 (2001): 1-22. ScienceDirect. Web. 26 July 2010.

3. Chipuk, J. E., T. Kuwana, L. Bouchier-Hayes, N. M. Droin, D. D. Newmeyer, M. Schuler, and D. R. Green.

“Direct Activation of Bax by P53 Mediates Mitochondrial Membrane Per meabilization and Apoptosis.” Science 303.5660 (2004): 1010-014. PubMed. Web. 26 July 2010. <http://www.ncbi.nlm.nih.gov/pubmed/14963330>.

The (Not-So) Smooth Process of Lab Work As straightforward as running experiments may seem, generating conclusive results is often the exception rather than the r ule. In an eight-week program, I tested four different molecules in my experiment to see if they would be effective in blocking methamphetamine neurotoxicity.

However, the only molecule that got consistent, statistically valid results was PFTα—our positive control. The other three molecules were chosen based on their potential in rescuing brain cells from death; for example, one molecule, epigallocatechin-3-gallate (EGCG), a common compound in g reen tea, was chosen for its ability to remove free radicals, molecules that oxidize cellular str uctures and cause damage that may lead to apoptosis. However, EGCG

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Letters

Pain in an Arm That Does Not Exist: Phantom Limb Syndrome and Mirror Therapy Namyi Kang ‘15 Derek Steen lost his left arm in a motorcycle accident at the age of 18.

When he started shaving after his amputation, he noticed something very bizarre. Whenever he shaved the left side of his face, he vividly felt pain and tingling sensations in the hand that no longer existed. Steen was contacted

by Vilayanur S. Ramachandran, a neuroscientist at University of California in San Diego, to participate in Ramachandran’s research of phantom limb syndrome. Ramachandran found that when he stimulated Steen’s left cheek in various ways, Steen reported a sensation on his phantom hand identical to that on his cheek.1 What is Phantom Limb Syndrome?

Phantom limb syndrome refers to the “perception of sensation, usually including pain, in a limb that has been amputated.”2 Silas Weir Mitchell coined the term “phantom limb” in 1871. From 90 to 98% of amputees experience phantom limb syndrome, and 75% of these patients feel the phantom immediately after the loss of their limb. Although the phantom gradually disappears after a few days or weeks in many cases, some patients experience the phantom for as long as several decades. Sometimes, only a part of the phantom disappears over time; about 50% of patients with a phantom arm report that the phantom becomes shorter and shorter until eventually only the phantom hand is left dangling at a distance from the shoulder.Moreover, some individuals with congenitally missing limbs also experience phantoms just as vividly as amputees do.3 Arms and legs are not the only body parts affected by this syndrome; patients have reported phantom menstrual cramps after hysterectomy , or phantom appendix pains after appendectomy.1 Some people feel bowel movements following a removal of sigmoid colon and rectum, and some report phantom ulcer pains after partial gastrectomy. Some paraplegics and patients with amputated penises have even noted phantom erections and phantom ejaculation.3 Representation of the Body in the Brain The brain has a vertical strip of cortex called the somatal sensory cortex, which contains specific regions in the cerebral cortex, thalamus, and brainstem that process sensory information from the central nervous system .4 The somatal sensory cortex contains a representation of the entire surface of the body – what experts call “body image.” Motor movements of the left side of the body are mapped on the right side of the brain, and vice versa. Thus, every point on the surface of the body is represented on a corresponding point in the somatal sensory cortex. However, the relative locations of these points do not reflect the structure of the physical body. It turns out that the region representing the face is adjacent to that representing the hand.1

Following the amputation of a limb, the sensory pathways in the patient’s brain are reorganized. Before the loss of the arm, facial sensory stimulation only sends signals to the cortical area that corresponds to the face. After the amputation, however, the area representing the hand becomes, in a sense, “hungry for sensory input,” as expressed by Ramachandran. Therefore, stimulating the face now activates the cortical region that corresponds to the hand, causing the patient to experience sensations in his phantom. This is why Steen felt sensations in his phantom hand when he shaved the left side of his face.1

Figure 1: Somatosensory map describing different body parts’ relative sensory inputs to the brain Phantom limb syndrome has provided neuroscientists strong evidence for brain plasticity – the ability of the brain to alter its structure and neural connections even in adulthood. In a study conducted by Ramachandran et al. in 1992, a magnetoencephalogram (MEG) showed reorganization in the somatal sensory cortex in four patients who had had their lower arm amputated. Figure 2 shows how sensory input from the face and the upper arm invaded the hand territory in these patients’ body maps. It shows a combined MEG and 3-D MRI of a patient who had his lower right arm amputated at the age of eleven. The left hemisphere of the brain, representing the right side of the body, is normal; it has distinct regions for the face (red), the upper arm (blue) and the hand (green). However, the The Amherst Element, Vol 4, Issue 1. Fall 2011

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Letters left hemisphere shows that the face (red) and upper arm (blue) regions are invading into the area that should be representing the amputated hand.3 Mirror Therapy: Treating Pain in the Phantom Limb As mentioned, most amputees with phantom limb syndrome experience pain in their phantom. This raises a mind-boggling question: How do you treat pain in a body part that no longer exists?

Pain in phantom limbs is categorized as neuropathic pain – “pain that does not seem to have a physical cause because it is produced by a malfunctioning nervous system.”4 Patients of phantom limb syndrome commonly suffer from excessive clenching sensations. A possible explanation for this phenomenon may be that the brain sends signals to the phantom arm, telling it to clench. When such signals are sent to an existing arm, the arm can send signals back to the brain and stop excessive clenching. However, since the brain cannot get such feedback from a phantom limb, it continues to send more signals, essentially leading to a positive feedback loop.1

Figure 3: A man recieves mirror therapy action looking into the mirror box, he felt movement in his amputated hand that mimicked the movement of his good hand. When the mirror was removed, he no longer felt sensations in his phantom. Repeating the mirror box therapy for 10 minutes a day over the course of 3 weeks led to a complete disappearance of Steen’s phantom.3 “Reality” as a Construct of Mind As much as we would like to believe that our sense perception is reliable, phantom limb syndrome suggests that even physical pain can be a construct of our mind. Studying the brain can not only tell us how we make sense of the world around us, but also shed light on the curious discrepancies between the physical world and the sense of “reality” constructed in our brain.

Figure 2: Brain Scan of a Phantom Limb Patient Ramachandran speculated that providing the brain with visual feedback might be able to stop this loop and treat the clenching pain. For this purpose, Ramachandran invented a device called the mirror box, a box partitioned into two by a mirror. The patient would put the good arm into one compartment and the amputated arm into the other. Then, he or she would look into the compartment that contains the good arm. This would create an illusion of two arms, “visually [resurrecting] the phantom limb” as Ramachandran puts it.1 As the patient moves his good hand, the mirror would make it look as though the phantom is doing the same. Visual feedback is provided to the brain by unclenching the good hand and fooling the brain into thinking that the phantom hand is being unclenched. This action allows most patients to feel vivid sensations in their phantom handsthat mimic those in their good arms. Repeating this process over a period of time can relieve the clenching pain in the phantom.3 Ramachandran tried this therapy on Steen, and obtained results that provided evidence for a strong back-and-forth interaction between visual stimuli and tactile sensations. When Steen was asked to put his hands in the mirror box and move his good arm with his eyes closed, he did not feel any movement in his phantom. However, when he performed the same

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REFERENCES 1. Blakeslee, Sandra and Vilayanur S. Ramachandran. Phantoms in the Brain : Probing the Mysteries of the Human Mind. Harper Perennial: New York.1999.

2. Scheinberg, Dianne. “Phantom Limb Syndrome”. NYU Langone Medical Center. December 2010. October 6, 2011. <http://www.med. nyu.edu/content?ChunkIID=96857>.

3. Hirstein, William and Vilayanur S. Ramachandran. “The Perception of Phantom Limbs”. Brain. Center for Brain and Cognition, University of California, San Diego. 1998.

4. Salisbury, David F. “Neuronal Growth in the Brain May Explain Phantom Limb Syndrome”. Vanderbilt News Releases. April 26, 2000. <http://www.vanderbilt.edu/News/news/apr00/nr26.html>.

Figure 1: Bugnaski, Mark. Methamphetamine. Digital image. Mlive.com.

Michigan Live LLC, 01 Nov. 2011. Web. 18 Nov. 2011.

Letters

Useful Tools for the Computer Scientist Jez Ng ‘14

For computer scientists, our laboratory is the computer itself, and we r un experiments by writing code. Yet we often focus on the theoretic aspectswhile neglecting our ‘laboratory skills’, not realizing how improving those skills can make our lives much easier. In particular, there are a number of tools which can help us write code more quickly and with fewer er rors; version control and automated testing are two of them.

Version Control Imagine this: you have a programming assignment due tomorrow, and in your final round of testing you discover a huge bug – your code is not working in the expected fashion. You know for certain that this bug was not present two days ago, but you have modified and added more than two hundred lines of code since then. You are also working on the project with a classmate, and he has added another hundred lines himself. You have two hours; how do you find the problem?

restore your code to any of these earlier versions. By testing these earlier versions for the bug, you can figure out exactly when it originated.Since only small sections of the code get changed between successive versions, it will be easy to figure out which change caused the problem! To make your life even easier, version control systems use the diff utility to show you the differences between two files, displaying only the lines that have been changed between versions.

The behavior of diff is illustrated in Figure 2.

File 1

File 2

int a = 1; int b = 2; String c = “hi!”;

int a =1; int b =1; String c = “hello!”;

Output of diff utility <int b = 2; < String c = “hi!”; -->int b = 1; > String c = “hello!”;

Figure 2: The diff utility shows the differences between File 1 and File 2. To transform File 1 into File 2, we need to delete those lines prefixed with a ‘<’, and insert in their place the lines prefixed with ‘>’.

Figure 1: This happens when you do not use version control.

This is one of the problems that version control systems are designed to solve. As the name suggests, version control systems (VCS’s) are systems for saving incremental versions of your code. Each time you write a new function or make a small change, you should use the VCS to save a new version of the code. Now when you stumble acrossa bug, you can use the VCS as a sort of ‘time machine’ to

You might be wondering if a special program is really necessary to do the above. After all, I could simply make a backup copy of all the files each time I made a major change. In fact, I am sure that many of us have done this at some point or another. However, things start to get unwieldy after doing more than a few backups. It is annoying to have a bunch of folders titled myproject_1 to myproject_20. More importantly, it is a huge waste of storage space. Only a few lines in a handful of files are different, yet we are storing entire copies of the project!

On the other hand, while a smart VCS appears to save whole copies of your code each time, it really only saves the differences, or deltas, between each copy. Moreover, VCS’s do more than just save changes: they allowme to annotate my changes with a commit message that explains what each change is about. For instance, a commit message might read something like “This fixes the color problem, because...” Now when I look back on this historical record The Amherst Element, Vol 4, Issue 1. Fall 2011

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Letters of my changes, I can get a better idea of why the code looks the way it does.

As a nice bonus, when I am trying to find the commit responsible for causing a bug, the VCS is smart enough to do a binary search for it instead of a linear one.For instance, if I tell it that the bug originated somewhere in the last 100 commits, instead of testing commit 100, 99, 98 … up to the most recent one, it will start off with commit 50: if it is bug-free, then it knows that the error must have occurred sometime between commit 50 and the most recent one. Otherwise, if it contains the bug, then the bug must have originated sometime between commits 100 and 50. By narrowing down the range of possible culprithis manner, it can quickly locate the offender.

Collaboration I hope that by this point, you are starting to see the value of version control. But there is still more! VCS’s are also essential tools for collaboration. Suppose I am working on a project with a classmate – it is a big project, and difficult for one person to finish alone. However, most of the code lies within the same few files, and we cannot both edit the same file at once! Without version control, we would have to take turns to do the project. A VCS simplifies things by helping us to merge our changes – after we are done making our respective editsto the same file, it helps us figure out how to put those changes together.If we have both modified the exact same portion of the file, the VCS cannot know which modification was the right one. We say that it has encountered a merge conflict, and we must fix the merge manually by giving one person’s edits priority over the other’s.

Now that I have sold you on the benefits of version control, you might be wondering how to get your hands on one. Thankfully, there are two very good and free VCS’s around – Git and Mercurial. Mercurial has better support on Windows, but Git is well-supported by the popular (and free!) code hosting site called GitHub. Code hosting allows you to coordinate projects amongst multiple people: instead of sending code to your classmates, you can send it to the central repository that is hosted on GitHub. When your classmates are ready, they can obtain it from the central repository. The merging capabilities of VCS’s make this entire process easy and painless.

Automated Tests I think it is wonderful that VCS’s can help us find and fix bugs. Nonetheless, it certainly would be better to fix bugs right after we create them, instead of having to search through the history of changes in our VCS to find the piece of code responsible. Automated tests help us in that regard. When we write a function, we usually know what values we expect it to return for a variety of inputs.

Automated testing is simply writing a small program that ensures that we get exactly the values we expect. There are various libraries that aim to make this task easier; for Java

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Figure 3: This is GitHub’s mascot, the Octocat. Isn’t he cute? developers, JUnit is a pretty good bet. Automated tests also serve as a good sanity check after a complicated merge operation by the VCS; the VCS is not always smart enough to do the merge correctly, and testing helps you catch any mistakes sooner rather than later.

If you are not using these tools yet, do look into them.

They will make writing code a much more pleasurable experience. Happy coding!

Summer Research

The View from Abroad: science elsewhere,the ‘Deutschland’ Perspective Gabriela Mateo ’13

As the end of interterm approached, I was not entirely sure about my summer plans. I ended up in a completely unexpected place: Germany. As a scientist I was curious about going there, as Germany is a leading nation in many fields of science, and I feel very lucky to have had the chance to participate in this wonderful experience. I found out about the opportunity through the Neuroscience Department webpage, which had a link to various summer courses and workshops. I happened to stumble upon it one day as I desperately sought a summer experience. This seminar, offered through the College of Charleston, turned out to be enriching to me not only as a scientist, but also in many other aspects. It was a great experience that I am glad I was able to participate in and hope future Amherst students will get to enjoy.

It all started in Münich, a city with a rich history in science and technology.

Including Nobel Prize laureates like Max Planck and Albert Einstein, many important figures were born and had lived in this city. During the first two weeks we participated in a series of talks at Ludwig Maximilian Universität, which were given by professors in multiple fields. From topics such as the vestibular system to specific studies on areas like the central complex in the protocerebrum, the variety was impressive and engaging. Mario Wulliman, a professor and researcher at the school whose focus is the neuroanatomy of the zebrafish, talked to us about the evolution of vertebrate brains and, after explaining the topic and his research to us, he let us analyze some zebra fish brain slices to guess where the medulla was located. The small size of the group allowed close interaction, and question and answer sessions aided learning.

Additionally, we were allowed into the labs to observe the practical applications of what we were learning in the classroom. I got to try the patch clamping sucking tube, a device commonly used in labs to measure a neuron’s electric potential, enter a sound proof room where bat’s echolocation is experimented on, watch birds fly in a wind tunnel, and much more.

We went to seven different labs, and at the Max Planck Institute of Ornithology in Seewiesen, we saw the most interesting animal behavior experiments. The labs were equipped with high-tech devices ranging from confocal microscopes to a pipette production machine that made the finest pipette tips, to be used at the very same lab. Seeing all this equipment made me realize how well-prepared and precise the studies being practiced here in Germany can be. The university and the town really caught my attention and I hope to return at some point. Graduate school seems like a great opportunity here. The institute offers multiple master’s and doctorate’s degrees in distinct areas from computational neuroscience to neurophilosophy.

The following two weeks were somewhat different since we went to Berlin, the capital of Germany. The material we learned and the lectures we attended were still connected and complementary to what we learned before, but here in Berlin, the approach was more medical. The seminar was now in Charité Medical University, an institute about 300 years old. It is one of the largest university hospitals in Europe. Research and classes here were offered in a broad range of topics by professors from varied backgrounds, fulfilling many

Figure 1: Taxonomist Holger Hoffman explaining Mastodon Americanus molar: elephant teeth prospective students’ interests. The lectures had a historical emphasis. We went through the basics of the action potential as they were discovered in chronological order. Many of the scientists that made important contributions to the discovery and the characterization of action potential lived and worked in Berlin, and we were able to come close to their work. We saw their books, the lecture halls in which they taught, and for some of these pioneers, their statues around the city.

The city itself is a great place to learn and visit, to anybody passionate about knowledge. Berlin’s dynamic pace is enriched in artistic, historical and cultural events and places. Museum Island is a complex where five museums offer an immense variety of exhibits in all fields. There is also the Natural History Museum, which was one of my favorite parts. This museum featured over 30 million specimens and the largest mounted dinosaur skeleton, a Giraffatitan that stands 41 feet tall and 73 feet long. It was nice when we were invited to the taxonomist’s office, where we saw the skulls of multiple species, from orcas to pugs.

The course turned out to be what I was looking for: an interactive tour of neuroscience in a different nation. The journal club style writing assignments allowed me to practice my communication as well as my reading skills. The talks on development and neuroanatomy in Münich, alongside the more historyoriented and measurement-in-the-field focused approach in Berlin, provided me with an insight into each of the areas and made me realize the wide extent of neuroscience’s applications. In addition, the lab visits and demonstrations showed me the practical side of neuroscience. I realized how much science The Amherst Element, Vol 4, Issue 1. Fall 2011

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Summer Research relies on machines and how the different techniques and apparatuses are undergoing an improvement with the era of technology. Meeting people from all over the world who are moved by neuroscience as much as I am was a fantastic opportunity. The professors, interns, students and doctors I met expressed enthusiasm not only for their research and classes, but also for meeting other scientists.

The neuroscience community is spreading out all over the globe. Given this chance to learn and understand the brain from multiple perspectives in

different countries has inspired me, and someday, I hope to bring this field to my homeland, Costa Rica. This summer could not have been better and I recommend it to all of you who are curious about exploring the lab scene in other countries. Germany is a thriving nation in this aspect and it is the reason why I am returning next spring to do my semester abroad in another highly recognized institute in neuroscience: Göttingen Universität.

CGRP Receptors and Migraine Haneui Bae ‘13 Over the summer I participated in a 10-week research program offered by the Center for Neuroscience in the University of Pittsburgh (CNUP). I worked with Dr. Carey D. Balaban, whose lab studies various aspects of the vestibular system, including the detrimental effects of vibrational shock waves in the inner ear and neural circuits connecting the vestibular nuclei and the amygdala.

I focused on a protein called Calcitonin Gene-Related Peptide, or CGRP. Vestibular symptoms, such as vertigo, often occur in association with migraine, a condition termed “migrainous vertigo.” This comorbidity may reflect similar pathogenic mechanisms between the trigeminal pain pathways and the vestibular system. CGRP, a vasodilator neuropeptide, was recently found to play an important role in migraine headache. CGRP levels increase during acute migraine attacks, and intravenous infusion of CGRP has been found to trigger migraine-like headaches. Following the discoveries in research, new migraine treatments using CGRP antagonists, such as Telcagepant (Merck), have been developed and are undergoing clinical trials.

Given the comorbid symptoms, a natural question arises: Does CGRP play a role in migrainous vertigo, and could a CGRP antagonist also be effective in treating the vestibular symptoms? In previous studies, CGRP was found in human vestibular efferents making synaptic connections with the sensory hair cells of vestibular epithelia. The aim of my project over the summer was to find the potential sites of action of CGRP antagonists by localizing CGRP receptor subunits in the monkey vestibular system.

I used specific antibodies against CGRP receptor subunits, CRLR and RAMP1, for immunohistochemical staining of decalcified, paraffin embedded monkey temporal bone sections. CRLR and RAMP1 immunoreactivity was found on certain vestibular ganglion cells as well as on cell bodies and processes of the vestibular epithelia. Fluorescent double-staining showed co-localization of CRLR and RAMP1 in some vestibular ganglion cells, indicating the presence of CGRP receptors. These results show that CGRP may be the common factor causing comorbid symptoms of migraine and vestibular dysfunction, suggesting new directions for the treatment of both disorders.

The whole research experience was stressful at times but very gratifying overall. Being new to the techniques of histology and immunohistochemistry, the primary techniques used in the Balaban lab, as well as the workings of the vestibular system (which my Intro to Neuroscience class unfortunately chose to skip over...), I was initially very overwhelmed with the bombardment of

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Figure 1: RAMP1-immunopositive vestibular ganglion cells. new information. However after weeks of honing my skills on free-floating tissue mounting and coverslipping, as well as lugging through stacks of primary literature, I was surprised by how much I learned in such a short period of time.

Aside from research, I also enjoyed my conversations with Dr. Balaban.

In addition to neuroscience, he also had a strong background in physics, engineering, and anatomy, which led to his very interdisciplinary interests.

All throughout the summer, he had numerous brainstorming meetings with scholars and businessmen from all over the nation, on projects that pool expertise from diverse fields of science. For example, one of these projects aimed to develop a device that vaporizes small portions of a tissue and analyzes the protein content using a mass spectrometer. After these meetings he would excitedly return to the lab, grab anybody who was near him and start talking about the progress they made and amazing potential the project has. I was usually the one to fall victim to these enthusiastic—and often lengthy— speeches, some of which were very abstruse. But I found his projects immensely fascinating, and I realized the importance of interdisciplinary thought processes that allow us to think outside of box.

Letters

Lending a Hand to the Handless The New Face of Transplantation Alice Li ’13

On September 23, 1998, Clint Hallam was the first patient order for the nerves to regenerate, which would eventually allow for to receive a hand transplant, a radical new solution to the ancient the dexterity and tactile sensation the prosthetics are unable to provide. problem of amputated hands. Yet, while the surgery was successful, While hand transplants have become more common in recent the transplanted hand was amputated in 2001 at Hallam’s own request. years, face transplants remain experimental, last resort procedures. Far What should have been a revolutionary new method to increase the from being cosmetic surgery, facial transplantation is for patients who quality of life for amputees ended in failure and media controversy. have lost critical functions due to severe disfiguration.3 Face transplants So much of our everyday lives revolve around touching and have suffered more setbacks than hand transplants, as two patients manipulating things, from holding a pencil, to using a keyboard, to who received new faces have died after the operation. Nevertheless, playing a musical instrument. The loss of even one hand is devastating, for those who no longer have the ability to speak, smell, eat or drink, both for carrying out daily activities and for the joys of touch that we face transplants represent their only hope to regain their former senses. often take for granted. For many years, patients without hands have Such procedures sound like a dream come true, but as with all had to rely on prosthetics. While advances have been made in the past pioneering medical procedures, hand and face transplantation are not several years, prosthetics are not as easy to move as actual human hands free of problems. One of the most formidable challenges to VCA, as and still cannot restore patients’ sense of touch. to transplantation in general, lies in rejection of the transplanted tissue.

New advances in the field of transplantation, however, may But in order to understand rejection, we must first understand how offer a solution to patients in the form of hand transplants, such as the immune system works.

Clint Hallam’s. Hand transplantation, along with face transplantation, is a form of Vascularized Composite Allotransplantation (VCA). The Immune System and the Problem of Unlike organ transplantation, VCA involves the transplantation of Rejection: How to Treat the Other as Self Imagine a multiple tissues, such warzone.

The as muscle, bone, invading army nerve, and skin, as a has infiltrated the functional unit.1 As country, and now with other forms that country’s of transplantation, defenders are hands and faces can scrambling to be obtained from mobilize against a donor, who is the threat. Scouts matched for blood identify who is foe type, but also for from who is friend, size, gender, skin while heavy-hitting tone, race, and age. missiles hone in on The process for those who have hand transplantation been pegged for is similar to the destruction. surgical reattachment Now imagine of a severed hand: that this warzone doctors connect is inside your the severed bones body.

In fact, this and stitch together is the kind of tendons, nerves, 2 war that goes on arteries, and veins. within you every After the procedure, Figure 1: 3D diagram showing the nerves, veins, tendons, and arteries that need to be reattime you get sick. physical therapy and tached in hand transplantation.

The invaders are time are required in The Amherst Element, Vol 4, Issue 1. Fall 2011

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Letters pathogens, bacteria and viruses that range from the common cold to the chicken pox, while the defenders are the cells, tissues, and proteins that make up your immune system. Without an immune system, we would not be able to survive.

A complex network of cells is involved in eliminating foreign invaders. Many of the cells in this network are specialized types of white blood cells, and among the major players are macrophages, which engulf and digest microorganisms;B cells, which produce specialized proteins called antibodies, that bind to nonself substances; T cells, which learn the art of self defense in the thymus and kill virus-infected cells; and natural killer (NK) cells, which attack and lyse virus-infected or cancerous body cells.4 Crucial to the function of the immune system is the differentiation

by T cells and B cells between cells and tissue that are part of the “self,” that is, part of the body, from those that are “nonself,” foreign entities such as bacteria and viruses. When a nonself antigen is recognized in the body, B cells manufacture antibodies specific to that antigen that bind to it, allowing for attack by T cells or NK cells. In this way, the immune system can successfully tell a friend from foe and unleash its full destructive power on potential threats.

Transplantation, however, poses a problem for the immune system. Although a transplanted organ may keep a patient alive in the short term, it is often not long before the immune system recognizes the donor organ as “foreign” and begins to tear it apart. This forms one of the most troublesome paradoxes in medicine: our immune system, which has been programmed to destroy all non-self entities in order to keep us alive, can destroy the transplanted organs that are also necessary for human life.

Current solutions to this problem involve patients taking drugs that suppress the immune system, also known as immunosuppressants, for life. There are a variety of immunosuppressants that act on the immune system in different ways, though they can be classified into four major categories: cyclosporins, which inhibit T-cell activation and prevent T-cells from attacking; azathioprines, which disrupt DNA and RNA synthesis, as well as cell division; monoclonal antibodies, which slow down T-cell production; and corticosteroids, which suppress the inflammation associated with transplant rejection.5 These drugs prevent the organ from being destroyed immediately, but are only a temporary solution that delay rather than prevent the destruction of transplanted organs. Aside from causing greater vulnerability to other illnesses through repression of normal immune function, a host of unpleasant side effects can occur, including damage to the liver and kidneys and an increased risk of cancer.6 Oftentimes, patients also must take additional pills in order to counteract the side effects of immunosuppressants. Hand and face transplantation similarly involves the taking of immunosuppressants in order to prevent rejection of the transplanted tissue throughout the patient’s life, and Clint Hallam’s voluntary cessation of taking immunosuppressants was a key factor in the eventual amputation of the transplanted hand. However, in cases of organ transplantation—for example, a heart transplant—the

patient will die without a new heart, and so he or she has no choice but to take the immunosuppressants. A patient without one or both hands, however, is perfectly capable of surviving—no matter how inconvenient such a life may be—and thus taking immunosuppressants poses a risk to his or her health without necessarily guaranteeing the survival of the transplanted hand.

For years, researchers have worked on circumventing the

“This forms one of the most troublesome paradoxes in medicine: our immune system, which has been programmed to destroy all non-self entitites in order to keep us alive, can destroy the transplanted organs that are also necessary for human life.”

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aggressiveness of the immune system in cases of transplantation. Aside from efforts to increase the efficiency of immunosuppressive drugs while reducing their side effects, scientists have courted the possibility of “re-educating” the immune system. Because B cells mature in the bone marrow, where they learn to produce antibodies for nonself antigens, a bone marrow transplant from the same donor who provided the transplanted tissue will result in new B cells’ acceptance of tissue from that donor as part of the “self.”

Although such research holds promise for a better survival rate of transplanted organs without having to depend so heavily on immunosuppressant drugs, scientists still do not fully understand the recognition mechanisms that the immune system uses to distinguish self from nonself entities. As of yet, there are still no developed treatments that can dispense completely with immunosuppressants.

Figure 2: T-cell microscopy image.

Ethical Considerations: Whose Face Is This, Anyway?

While organ transplantation in the twenty-first century has widespread support, hand and face transplants remain the subject of ethical debates. Some have argued that, because the lack of hands or a face is not life-threatening, the risks associated with the surgery itself and with the subsequent need to take immunosuppressants are not worth the enhancement of life quality. Others have argued that the invaluable improvement in the quality of life afforded by hand and

Letters face transplants outweigh such concerns.

Furthermore, there are possible psychological consequences to receiving hand and face transplants. Unlike organ transplants, which do not affect a patient’s outward appearance, the face in particular is an integral part of a person’s identity. Hand transplants can also have psychological ramifications: Clint Hallam, for example, reported feeling “mentally detached” from his transplanted hand and eventually begged surgeons to amputate it.7 Surgeons now recognize the importance of body image and psychological acceptance of another person’s hands, and hand transplantation procedures include both a mandatory preoperative psychiatric evaluation to determine whether the patient is eligible for a hand transplant and post-operative psychiatric support when necessary.

Conclusion: VCA – Imperfect, But More Than a Pipe Dream The myriad risks and uncertainty of success remain formidable obstacles for those who seek hand and face transplants. Not all cases of hand transplants are successful. While surgeries may have been successful, some patients still suffer from reduced finger function afterwards,8 and the danger of immune rejection has still not entirely gone away. More research must be done into alternative methods of preventing immune rejection. Still, reports by the International Registry of Hand and Composite Tissue Transplantation have shown that hand transplants have greatly improved the quality of life for many patients.9 Though we may continue to debate the necessity of a new hand or face versus the negativeeffects of immunosuppression, it seems unlikely that those without hands or a face will ever settle for less than a full restoration of a body part that is so vital to everyday life and experience.

REFERENCES 1. American Society of Transplantation. “Vascularized Composite Allotransplantation (VCA) Research.” http://www.a-s-t.org/publicpolicy/vascularized-composite-allotransplantation-vca-research. Last modified June 1, 2011.

2. Shari Roan, Los Angeles Times. “UCLA surgeons perform first hand transplant in California.” http://articles.latimes.com/2011/mar/07/ health/la-he-hand-transplant-20110307. Last modified March 7, 2011.

3. Kevin B. O’Reilly, American Medical News. “Face transplants starting to gain acceptance.” http://www.ama-assn.org/amednews/2011/09/19/ prl20919.htm. Last modified September 19, 2011.

4. Sadava, David, Craig Heller, Gordon Orians, Bill Purves, and David Hills. “Immunology: Gene Expression and Natural Defense Systems.”

In Life: The Science of Biology. Sunderland, MA: Sinauer Associates, Inc., 2008.

5. Encyclopedia of Surgery. “Immunosuppressant Drugs.” http:// www.surgeryencyclopedia.com/Fi-La/Immunosuppressant-Drugs. html. Accessed October 24, 2011.

6. Brown University. “Transplant Rejection Therapy.” http://biomed. brown.edu/Courses/BI108/BI108_2004_Groups/Group04/Side_ Effects.htm. Accessed October 16, 2011.

7. BBC News. “Surgeons sever transplant hand.” http://news.bbc. co.uk/2/hi/europe/1151553.stm. Last modified February 3, 2001.

8. Madison Park, CNN. “One year after double hand transplant, progress elusive.” http://www.cnn.com/2010/HEALTH/08/26/ double.hand.transplant/index.html. Last modified August 30, 2011.

9. Amer, Hatem, Brian Carlsen, Jennifer Dusso, Brooks Edwards, and Steven Moran. “Hand Transplantation.” http://www. minnesotamedicine.com/tabid/3764/Default.aspx. Last modified May 2011.

Figure 1 : http://www.handtransplant.com/portals/0/hand_off.jpg Figure 2 : http://www.aai.org Figure 3 : http://science.howstuffworks.com/environmental/life/ human-biology/face-transplant.htm

Figure 3: Rabbit with a face transplant from China.

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Interview

Interview with Professor Stephen A. George Haneui Bae ’13 and Sonum Dixit ‘13

Amherst College is known for its oldest undergraduate Neuroscience program in the nation, and Professor Stephen A. George has been with the program since its very beginning in 1973. He has been the director of the Neuroscience program for 36 years, stepping down just two years agoin the face of his looming retirement in 2013. We met him at his office one day and talked about his life as a pioneer, both in the field of science and at Amherst.

Q. How did your life as a neuroscientist begin?

A. When I was studying in college, in the 1960’s, there was no such thing as “neuroscience.” I started out as a math and physics major, as many future neuroscientists did back then, at University of British Columbia. But I became interested in biophysics during my graduate studies, and earned a Ph. D in biophysics at John Hopkins University. I did electrophysiological experiments, recording from frog visual systems. Like this, what we call neuroscience now was a part of other fields of science, and that’s how I initially started.

It was in the early 1970’s that “neuroscience” began to be thought of as a field on its own. The Society for Neuroscience, the biggest and oldest academic community for neuroscientists,was founded in 1970. At that time though, it was just an interdisciplinary interest by scientists from other established fields. Though I saw an immense potential in this new field, I never knew it would be as big as it is right now. Now Neuroscience is a distinct area of study, and a flourishing department in many universities.

Very different from when it all first started.

Q. What brought you to Amherst College?

A. After getting a Ph. D, I got my first job at the University of Maryland Baltimore County (UMBC), teaching biology classes in the Biology Department. Though I enjoyed the job, the teaching environment was completely different from what it is like in Amherst. The primary role assigned to all faculty members by the University was research.I remember one day, I was talking to a student in the hallway answering questions about the class material. After the student left, one senior faculty member who saw me talking to the student came and told me not to waste so much time talking to students, and focus on my research. That was the general attitude of the university toward teaching, which was a little sad for me because I loved to interact with students. This is one of the reasons why I decided to apply for this job at Amherst College when the opportunity arose.

I actually had never heard of Amherst College before graduate school. There were a lot of students at the school who had graduated from Amherst, all of whom were very smart! Then, I started wondering where and what this place called “Amherst College” was.In the early 1970’s, Amherst College was looking for new faculty members to help launch a new interdisciplinary neuroscience program on campus. Surprisingly, I got the job to represent the Biology aspect of the joint effort, working

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alongside two other faculty members— from Psychology and Chemistry departments, both of whom are no longer at Amherst.

I started working in 1973. So did the new Neuroscience program.

The next year, we had our first Neuroscience graduates: 2 students! But the numbers grew rapidly, and in 1976, we had 16 graduates. An interesting fact about the early Neuroscience graduates is that there were not a lot of women. The first one was Karen Carbone in 1978 and even after her there were many years when we did not have women graduates. This has changed completely in the recent years; now, about two thirds of the neuroscience majors are women. Sometimes old alumni come back for reunions and are amazed that there are so many women neuroscience majors!

Q. Tell us about your research interests!

A. Well, my recent research has been on the visual plasticity of frogs.

Visual deprivation causes changes in the head and eye movements of frogs, and I measured the protein component differences in the diencephalon of the frog brain, equivalent to human lateral geniculate nucleus. When I was in China during my three sabbaticals, I worked with Dr. Shu-Rong Wang, a visual physicist whom I had a previous acquaintance with, on the binocular vision of geckos.

I also ventured out to other fields. One of the works that I am most proud of was on ion channel gating using quantum tunneling. In this study we showed that it is plausible for the activation of ion channels that underlie nerve impulses to occur by quantum tunneling, rather than by classical transitions. “Big” objects, like a transmembrane segment of a channel protein that consists of something like 2400 atomic mass units, seem unusually massive to behave non-classically, but the way this part of the protein interacts with the rest of the channel and with the environment around it makes it possible for quantum mechanical transitions to happen as our work showed. This may or may not be important in how the brain works –most neuroscientists seem more comfortable explaining neural function using non-quantum processes, but maybe that’s because those classical processes are more familiar and easier to understand. Time will tell—my guess is that quantum processes will have their day in the future!

Q. Any funny episodes during your career at Amherst?

A. In the mid 1990’s, the Society for Neuroscience annual meetingsused to be closer by in Boston. I arranged for myNeurobiology class to attend for a day—normally attendees have to pay a big fee for the whole meeting, but I knew the officers of the conference and got a special 1-day deal for the students. After the conference, I planned to take the class to Legal Seafoods for dinner, checking first to make sure the Neuroscience Program could afford it. I found out the cost of a “Fisherman’s Platter,” which I thought was the most expensive item on the menu, and calculated that the department can afford

Interview it. So at the dinner I told the class, “Order anything you want!” What I didn’t realize was that there was a special “Double 2-Pound Lobster Feast” on the menu that cost many times the cost of the Fisherman’s Platter. The entire class ordered it except for one vegetarian in the group, and it basically bankrupted the Neuroscience program for the entire year.

Q. What do you love about teaching and research at Amherst?

A. Of course, the teaching and the interaction with students. But what some people do not realize is that teaching can influence your research just as much as your research can influence the teaching. This actually happened to me at Amherst. My research on ion channels was initially inspired by a class that I taught, which investigated the new pioneering research on ion channels. That class changed the directions of my interests and research.

Teaching forces you to peek out of your comfort zones, branch out into different fields, and explore new areas. Through this exploration, you can integrate information to create new ideas that would beimpossible to conceive if you just stay in your narrow research area.

Aside from the traditional roles of a professor, I also really enjoyed the fact that I could participate in the decision making processes of the college much more than I would have if I were in a bigger university. For example, I was part of the presidential search committee last year, for which I went on “secret mission” trips all over the nation to interview potential presidential candidates.

Q. Any words of advice for fledging scientists?

A. I want to stress the importance of exploring the different areas of science, different areas of biology and techniques before making up your mind to settle down in one field. Some people just decide early on that they want to do certain research and dig their noses down into that field without looking up to see where they are or what other fields exist. The sciences are becoming increasing integrative and interdisciplinary, and it is becoming more and more necessary to have knowledge of other fields of science besides your own specialty. Extensive cooperation with experts of others fields towards a shared goal is now becoming very common. Studying at a place like Amherst is tremendously helpful in this respect; all Amherst students are encouraged and trained to explore out and integrate knowledge from different fields. In this sense, you guys are very well-equipped for the future direction of academic science.

Q. Finally, do you read the Amherst Element? :D A. Yes, I do! I have read every issue ever since it started a few years ago. It is great to read about what students are passionate about. I would recommend everyone, students and faculty, to read it. *Photograph by Jeong Eun Lee ‘13

Thesis Research

Science at amherst: Interterm courses

The victims of Microbotryum fall predominantly into a multiple, even hundreds, of seasons, lying dormant beneath the family of wildflowers known as the Caryophyllaceae. Within this surface during the winter and re-emerging with each new growing family, plant species of the genus Silene are particularly afflicted season. An annual plant, on the other hand, has a very short life by anther-smut disease. Several Silene species grow in the Pioneer span, growing and setting seed in a single season before dying with Valley, and our very own bike path is home to at least a few species the onset of winter. Because Microbotryum cannot live outside (Figure 2). You would be unlikely to see signs of anther-smut of a host, it has been speculated that a population of annual plants disease, however, as the pathogen is quite rare in our area. cannot sustain an infection. Any annuals that have contracted the Microbotryum is an ideal organism to work with for a variety of fungus will die at the end of their first growing season. The fungus reasons. As a plant pathogen, it cannot infect humans, so instead of dies with them, removing any possible source of infection for next conducting my research behind an air-lock in a full body suit, I can year’s newborns.

Wind Turbine Seminar and .field trip perform my experiments safely in the greenhouse Furthermore, Based upon this information, I hypothesize that annual Microbotryum can be easily maintained and manipulated in a lifestyles are a means of escaping anther-smut disease, an idea that Henry Parker Hirschel laboratory setting.

To determine levels of biological resistance my preliminary investigations have supported. As shown in Figure Department of Astronomy, Amherst College of Silene species, I have inoculated approximately three thousand 6, comparing disease rates between a random selection of annuals Sunday 15th / Field East Turbine) January 16th plants with Seminar: a variety of strainsJanuary of Microbotryum andTrip am (Berkshire in the and perennials shows that perennials are diseased ten times more Location: 220 in the greenhouse (Figure 3). frequently than annuals. A literature survey found a similar result, process of rearing themMerrill to adulthood I will conclude this large-scale experiment when the plants flower with mention of disease on perennials being five times more and reveal themselves Navigation as either healthy or diseased, evidenced by frequent than that on annuals [3]. And yet, annuals, when directly Celestial the characteristic dark, spore-filled anthers. The proportion of exposed to Microbotryum, display little resistance. Thus far, my Henry Parker Hirschel healthy individuals will indicate the relative resistance of a species. inoculation experiments support this low resistance. Low rates of Astronomy, College of of infection in natural populations coupled with low physiological A finalDepartment advantage of MicrobotryumAmherst is the presence an historicalTuesday record of its whereabouts.

Beginning theclass earlySunday), resistance, as pm seen- 3:00 thus am far in annual Silene species, correspond January 3 - Tuesday January 10in(no 12:30 1800s, botanists and general plant enthusiasts began collecting and to my initial characterization of organisms that have successfully Location: Merrill 220 preserving plants, indicating the date and location of collection. escaped a disease.

This activity gradually declined in popularity in the late 1900s, but I have applied this same approach to two other categories Mapping Knowledge with Geographic information systems the result of two hundred years of collection is millions of plant of host traits, demography and migration. Demography refers specimens, Andy housedAnderson in herbaria all over the world. Conveniently to the structure of a population and the spatial relationships of for Microbotryum researchers, the unusual anthers of anther-smut individuals within and between populations. These factors bear Academic Technology Services infection are recognizable even on ancient, preserved plants (Figure relevance to disease prevalence because they define a pathogen’s Monday January 9 - Friday JanuaryProfessor 13, 1:00 pm - 3:00transmission am 4). A group of scientists, including my advisor Hood, opportunities. Typically, hosts must be of a great Location: Merrill 209 in a quest for Microbotryum. enough number and density in order to provide a pathogen with a have surveyed over 28,000 specimens The preliminary data indicate where Microbotryum has traveled sustainable level of transmission between individuals. over the pastIntroduction two hundred years andto provide estimates of Practices, To investigate relevance of host of demography to disease An therough Principles, andtheProcedures Turbine the rates at which different species are infected by anther-smut prevalence, I have focused on rare and endangered Silene species, diseaseFlight (Figure 5) which tend to have unique population structures. Unfortunately, Henry Hirschel To return to Parker the topic of resistance, potential hosts of quite a few Silenes carry the classification of endangered; nearly Microbotryum exhibit a variety of defensesAmherst against the fungus. A one-third of North American species are regarded as threatened or Department of Astronomy, College study isolated anti-fungal compounds from the nectar of a Silene worse–[4] (Figure field 7). I trips hypothesize in contrast January 11 - 21 (no class Sunday or MLK Day), 12:30pm 3:00pm, (2) willthat be endangerment, all day species and speculated that at least some of these compounds target to its many disadvantages, is a manner of escaping Microbotryum Location: Merrill has 220also been repeatedly correlated because of the reduced number of hosts and high degree of Microbotryum [2]. Resistance with shorter flowering periods and diminished flower production. fragmentation within a population that characterize such species.

These EMT traits limit pollinator visits, reducing the probability of a The existence of fewer and more spatially separate hosts may Course plant contacting infectious spores. the number January 4 - 24,Microbotryum Monday-Friday, 4:00pm - 10:30pm & reduce Weekends, 9:00amof- different 5:00pm plants pollinators visit and in turn

the number of hosts to which the fungus is transmitted. As for Location: Merrill 4 Escape Tactics annual species, my expectation is that rare and endangered species My study addresses three types of host traits that are speculated will have lower disease rates and lower physiological resistance to serve as resistance by facilitating escape from(and Microbotryum. than their more common counterparts, whose higher density and The physics of “Futurama” other cartoons) To begin, the term “life-history strategy” refers to an organism’s population make them more hospitable to infection. Preliminary Michael Stage unique allocation of resources. It includes a consideration of an data from herbarium surveys support this idea in showing uniquely January 16-19, 2pm production - 4pm organism’s age at sexual maturity, of offspring, and life low disease prevalence among endangered Silene (Figure 6).

Location: Williston Observatory, Holyoke CollegeFinally, the category of migration refers to a host’s escape span. A pathogen must be compatible with its Mount host’s life-history strategy in order to yield a sustainable infection. from disease by physically moving to a region beyond the reach of To address the importance of life-history strategies to disease, a pathogen. This phenomenon is best modeled by invasive species, my research compares the resistance of annual and perennial which, in moving from their native range to their new, introduced Silene species to Microbotryum. A perennial plant lives through range, leave behind the specific predators and pathogens that

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The Amherst Element, Vol 1, Issue 2. February 25th, 2008