The Amherst
ELEMENT Volume 6, Issue 2
Spring 2014
Letter from the Editors Thank you for picking up the Spring 2014 issue of the Element! Thanks to all the writers, editors, and people who contributed in one form or another! This semester, we have a TV show review (Cosmos: The Space-Time Odyssey by Lindsey Bechen ’16), an article on the polar vortex and why our winter has been long in the leaving (If you were a squirrel by Xiao Xiao ’16), a follow-up to last semester’s kidney transplantation article (A Look at Intestinal Transplantations by Thomas Savage ’15), a “proof of concept” experiment (Monkey Avatar by Minjee Kim ’17), and two thesis interviews– one in chemistry (Interview with Christine Bierema by Conner Reilly ’16) and one in neuroscience (Interview with Shannon Townsend by Kevin Mei ’16). While the bulk of articles for The Element have been on previous research experiences, letters reflecting the scientific curiosities of the authors, and in thesis interviews, in this issue, we have our first TV show review and a piece relevant to campus life (the weather), joining the ranks of quirky features in the past including organic chemistry advice, science conference reviews, and a faux interview with Antoine Lavoisier. Although this is welcome, The Element hasn’t received as many articles this semester as in previous years. The Element continues its efforts to be the voice of the scientific community on campus but requires the involvement of students to make that community a realization. With that said, please consider writing next semester! We hope you enjoy reading this issue!
Kevin Mei Thomas Savage
Reason and Persuasion In light of recent campus “discussions” (AAS proceedings, the ban on fraternities, Dinesh D’Souza), I’ve run into an interesting frustration: can people be reasoned with? In a study by Lord, Ross, and Leper in 1979, participants who held prior beliefs in either support or opposition against the death penalty were presented with statistics either in support of (that it lowered crime rates) or against the death penalty. The study showed that people didn’t change their minds when presented with opposing evidence. Those who supported the penalty continued to believe in the penalty whether the evidence was for or against their belief. Moreover, on both sides, people became even more entrenched in their beliefs regardless of the evidence. In modern days, similar studies have been shown on the issue of climate change or vaccinations. Can people be swayed by rational arguments? Or are we only rationalizing, i.e. justifying our beliefs even in the face of opposing evidence? In his article (cited), Tom Stafford explores this issue and answers yes, we are rational. Stafford concludes, “...there’s no shortage of evidence that our intuitions, emotions, prejudices and motivations can push reason around. Good luck to you if you want to use only argument to persuade - unless you’ve got people who already like you or trust you (ideally both) you’re going to have a hard time, but amidst the storm and shouting of psychological factors, reason has a quiet power. People do change each other’s minds, and if you can demonstrate the truth of your point of view, or help someone come to realize the short-comings of theirs, maybe you can shift them along. But beware Singer’s warning - logic has its own dynamic. If you open yourself to sincerely engage in argument then it is as likely that your interlocutor will persuade you as the other way around...” This seems overly obvious. Of course Amherst students are rational and not merely rationalizing. After all, all our op-ed articles and protests operate under an assumption or hope that people can be convinced through reason if not ethos, group mentality, or other “shouting of psychological factors.” But in both casual debates and campus conversations, it can feel as if strong arguments have no persuasive power. Those who agree, already agree, and those who do not, as these psych experiments suggest, may be driven even further into their opposing viewpoints. What’s the point when discussion with rational arguments does not find common ground but furthers division? In his article, Stafford explains how reason can be persuasive, citing several tests and studies. To state some of his points, reason is effective when there is a right answer. In moral arguments, where the right answer is not clear, causal reasoning is more effective than statistics (Stafford gives the example of convincing you that you don’t catch AIDS through touching hands by arguing AIDS is transferred through bodily fluids rather than arguing that no one ever has). The way towards helping people “come to realize the short-comings of their beliefs” is by asking them what effects a particular policy may have, rather than why they support or don’t support that policy. Find his full article online... Stafford, Tom. “What’s the Evidence on Using Rational Argument to Change People’s Minds? by Tom Stafford.” Contributoria. Contributoria, May 2014. Web. 11 May 2014. Kevin Mei ‘16
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Table of Contents
The Amherst Element Staff Editors-in-Chief Kevin Mei Thomas Savage
Associate Copy Editors Lindsey Bechen Sonum Dixit David Nam
Feature Contributor Thomas Savage
Cover Feature
1 Under the Rainforest Eugene Lee ‘16 20 Zebra Finch Song Victoria Turner ‘14
Features
3 News-in-Brief Thomas Savage ‘15
Letters 5 If You Were a Squirrel Xiao Xiao ‘16 8 Cosmos: A Space-Time Odyssey Lindsey Bechen ‘16 11 A Look at Intestinal Transplants Thomas Savage ‘15 14 Monkey Avatar Minjee Kim ‘17
Thesis Research
16 Interview with Shannon Townsend Kevin Mei ‘16 18 Interview with Christine Bierema Conner Reilly ‘16
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, or age. 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.
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News-In-Brief Thomas Savage ‘15 New Evidence Supporting the Big Bang Theory Scientists say they have found new evidence that supports the Big Bang theory as the origin of the universe. Using a telescope in Antarctica, scientists studied the oldest light in the sky, the Cosmic Microwave Background (CMB), and found evidence of large gravitational waves marking the CMB. These signals could only have resulted from a dramatic increase in the size of the universe, the researchers say, providing more evidence buttressing the Big Bang theory. Regaining Life after 1500 years Scientists in the U.K. have brought back to life Antarctica moss that was frozen for 1500 years. Researchers thawed ancient vegetation, and discovered new shoots growing. While researchers have brought 250-million-year-old bacteria back to life previously, this is the first time researchers have done so for multicellular organisms frozen for longer than 20 years. This provides evidence that under the right conditions, multicellular organisms can survive for far longer than previously thought. Possible Breakthroughs in Preventing AIDS infection Since the discovery of AIDS, researchers have sought to prevent and treat it. A series of recent studies have made possible breakthroughs in preventing AIDS infection. One study in monkeys prevented the spread of AIDS from one
sexual partner to the other, using a vaginal gel containing an anti-retroviral drug, raltegravir. As it was used up to 3 hours after sex, the gel was used somewhat like a plan B contraceptive. Two other studies chose a different approach, yet this was equally effective. Researchers gave monkeys infrequent injections (monthly or every 3 months) of an anti-retroviral drug GSK744, and then simulated sex with an infected partner. None of the treated monkeys became infected with AIDS. Controversy over Groundbreaking Stem Cell Study In our last issue, we discussed the intriguing experiment done by Obokata et al. at the RIKEN institute in Japan that showed how to convert mouse blood cells to become pluripotent stem cells through a mild acid treatment. The paper held great promise for stem cell research. Other scientists have attempted to replicate the study, however, and have been unable to confirm the results. A RIKEN investigation committee concluded that two figures were falsified. One of the co-authors wants to retract the paper. Haruko Obokata, the lead author, has said that she was careless in producing the manuscript, but added that she had no intent to deceive and that she has successfully created the cells “over 200 times.” If in fact she had intentionally manipulated the data, the case would be reminiscent of the William Summerlin controversy, in which he painted black dots on white mice to show successful skin transplantation.
About the Cover Photos They’re called spectrograms. Sound goes through a Fourier transform, going from waves into these bands, so you can see frequency at a given point vs time, where frequency is no longer the wiggly cycles per second on the graph but becomes a certain height on the y axis. This also lets you see harmonics. Intensity (or loudness) is translated into the color, instead of the original waves where bigger amplitude is larger intensity. Victoria Turner ‘14 I was at the California Academy of Sciences. Eugene Lee ‘16
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Letters
If you were a squirrel‌ Xiao Xiao ‘16
Would you send in a complaint letter to the weathercontrolling deity of your preference? Just imagine the sinking feeling as you wake up from your slumber and get ready to terrorize hapless college students again, nature slaps you in the face with temperatures of 10-20o F and a snow in March. The weather on the East Coast has not been charming since the start of the New Year. If you, like the author who comes from a tropical hometown, wonders if this pattern is here to stay, then read on. Spring as the season The official first day of spring for 2014 fell on March 20th. Hence, when the author first started writing this article, we were still technically in winter. Why the late onset of the change in season? The primary reason is because in America, the system of seasonal transitions follows an astronomic convention. The vernal equinox marks the first of day of spring and likewise for the autumnal equinox. In an equinox, the North and South poles of the Earth are not slanted toward or away from the Sun. So
the length of the day is the same at all points on Earth’s surface. Usually, the vernal equinox occurs between March 19th and 22nd. This is not the only system of defining seasonal transitions. In Europe, spring is often the period between winter and summer, not so surprisingly. The three hottest months constitute summer and the three coldest months constitute winter, and the time in between becomes spring and autumn, respectively. This meteorological approach relies heavily on the average monthly temperature measured against a backdrop of historical data. The benefit of this system is its practicality. Because they depend on the temperature alone, the seasons themselves can serve as indicators of the relative climate of the month. However, the downside is that the fluctuation of temperatures every year makes it difficult to demarcate a specific time for seasonal changes. Especially in the recent case of erratic climate behavior, it is next to impossible to have a fixed transition date across the years. For instance, meteorologists in Sweden have defined the start of the spring to be when the average daytime temperature exceeds 0o C or 32o F for
Figure 1: Polar vortex explanation.
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Figure 2 (on left): Typical polar jet stream boundary. Figure 3 (on right): Abnormal polar jet stream boundary. 7 consecutive days. In addition to varying on a year-by-year basis, it will also change due to locational variables such as altitude and latitude. The other side of the problem Although having a temperature based seasonal transition is practical, problems arise when the previous winter brings the temperature below the past average. Unfortunately, this happened during the recent winter; if we were to invite our Swedish meteorologists over across the Atlantic here to Amherst, they would not be able to declare the start of spring until mid-April. After all, their standard of average daytime temperature exceeding 0o C is just that different from what we actually had this March. Beginning January 2, an arctic cold front suddenly descended upon Canada and the States, bringing along a drastic decrease in temperature and heavy precipitation. A cold front is a boundary of a massive volume of cold air. Normally, cold air stays within the polar region due to the polar jet streams–narrow streams of fast moving air that are generated from the Earth’s rotation and the temperature difference between the air above the arctic sea and the air above the warmer North American landmass. In our case, a jet stream deviated from its usual path and went south. Scientists have yet to reach a consensus on the cause of this, but the widelyaccepted theory blames a sudden stratospheric warming. Polar jets are normally found 7-12 km above sea level, in the tropopause, the boundary above the troposphere and below the stratosphere. Warming of the stratosphere introduces instabilities in the temperature of a jet stream and disrupts its flow. As the stream loses momentum, it plunges toward the warmer region down south because its flow can no longer keep it confined within its usual location.
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As cold air clashes with the warmer atmosphere in North America, it triggers a temperature difference that can reach up to 50o F between the warm and the cold air. For the folks living in the region where the front passes, the temperature plummets significantly. Coupled with the pressure decrease as the replaced warmer air rises, chilly winter winds exacerbate the cooling effect. The net effect is a series of record low temperatures across the nation and some happy students for their multiple snow-days-ina-row. As far as records are concerned, the coldest temperature ever reported this January was in Michigan with a low of -41o F (-40o C). The reach of the cold air was broad as it even brought Tampa, FL to an unheard-of-low of 34o F (2o C). Closer to Amherst, Boston had a record low wind chill of -20o F (-29o C) with snow over 7 inches on January 3rd. For the state of Massachusetts, the heaviest snowfall within 24 hours was in Boxford, a small town just north of Boston and roughly a 2-hour drive away from our school. It accumulated a whopping 23.8 inches (60 centimeters) of snow. How did people react to this? Letting their creativity run wild over the internet! Holed up in their homes, the number of times the polar vortex was mentioned on Twitter peaked at over 77,000 times on January 6th. A slew of memes and image macros, often involving hapless looking polar bears, popped up over popular sites such as BuzzFeed, Reddit and Jezebel. What’s in for us? The historical average low for the town of Amherst in December was 20o F (-6.7o C) with a record low of -22o F (-30o C). The average snowfall was just short of 9 inches. These pale in comparison with the numbers reported above. However, weather is just something we don’t want to worry about while being swamped
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Figure 4: North Attleboro, MA on Jan. 3rd. with papers and midterms. So, how likely will we experience the frigid cold again? Global warming takes the blame here. It reduces the sea ice volume and the snow cover in the Arctic region, hence increasing the evaporation and warming the air above. This in turn alters the pressure and temperature of the air, and hence the jet streams, destabilizing their paths of flow. However, as with all other effects of climate change, the polar vortex is just one of many reasons we may experience a particularly chilly winter. Therefore, even though the likelihood of it happening again is higher now, we won’t really know if that translates to a higher chance of a repeat of the 20132014 winter. So, rejoice for now as we welcome the warm air and sunshine while dealing with all the mud that the melting snow causes. And remember to treat the squirrels nicely because nothing is worse than not getting your food after waking up. References “U.S. polar vortex sets record low temps, kills 21”. CBC News. January 8, 2014. Preston, Jennifer (January 6, 2014). “‘Polar Vortex’ Brings Coldest Temperatures in Decades”. The Lede. The New York Times.
“N America weather: Polar vortex brings record temperatures”. BBC News - US & Canada. BBC News Online. January 6, 2014. “Polar vortex”. Glossary of Meteorology. American Meteorological Society. June 2000 Baldwin, M. P.; Dunkerton, TJ (2001). “Stratospheric Harbingers of Anomalous Weather Regimes”. Science 294 (5542): 581–4. doi:10.1126/science.1063315. Figure 1: http://en.wikipedia.org/wiki/File:Polarvortexwinter.jpg Figure 2: http://en.wikipedia.org/wiki/File:November2013_ polar_vortex_geopotentialheight_mean_Large.jpg Figure 3: http://en.wikipedia.org/wiki/File:Jan52014_polar_ vortex_geopotentialheight_mean_Large.jpg Figure 4: O’Brien, Daniel . Frozen: A firefighter surveys the former Odd Fellows Building in downtown North Attleboro, Mass., Friday, Jan. 3, 2014, after it was destroyed in an early morning multi-alarm fire. 2014. Photograph. GuardianWeb. 5 Apr 2014.
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Cosmos: A Space-Time Odyssey Lindsey Bechen ‘16
If you have ever had an interest in astronomy, you’ve probably heard of Carl Sagan’s Cosmos: A Personal Voyage. If you have never seen the TV show, the original Cosmos is a documentary series consisting of thirteen hour-long episodes, originally broadcast on PBS in 1980. It covers nearly all scales of the universe, weaving together life on earth and the observable universe into a picture showing humanity’s place in existence. Cosmos was a game changer for science documentaries because Sagan was able to capture the everyday viewers’ interest and teach them about the universe. It showed in the series’ ratings: Cosmos was the highest rated series in PBS history for a decade after being aired. 1 Carl Sagan had a lifelong passion for science and a natural talent for explaining it in words the general public could understand.2 Soon after Cosmos became popular, he wrote: “I think Figure 1 (left): Carl Sagan as he appears in Cosmos: A Personal Voyage. Figure 2 (right): Neil deGrasse Tyson, the host of Cosmos: A Space-Time Odyssey.
Figure 3: The title card for Cosmos: A Space-Time Odyssey.
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I’m able to explain things because understanding wasn’t entirely easy for me. Some things that the most brilliant students were able to see instantly I had to work to understand. I can remember what I had to do to figure it out. The very brilliant ones figure it out so fast they never see the mechanics of understanding.” 1 A few years ago, it was announced that Cosmos would receive a sequel. The team working on the new series includes Ann Druyan, who worked on the original, and Seth MacFarlane, who was essential in getting the show picked up by Fox. 3 Carl Sagan’s successor is Neil deGrasse Tyson, the current director of the Hayden Planetarium at the American Museum of Natural History. His previous work and engagement as host of NOVA ScienceNOW and StarTalk Radio make him the perfect person to carry on Carl Sagan’s legacy. 4
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Figure 4: The newly designed Spaceship of the Imagination. Living up to the high standards set by Sagan in the original Cosmos is a tall order to fill. To address this, Tyson is careful not to equate himself with Sagan. Regarding his status as Sagan’s successor, Tyson has stated: “Cosmos is more than Carl Sagan. Our capacity to decode and interpret the cosmos is a gift of the methods and tools of science. And that’s what’s being handed down from generation to generation. If I tried to fill his shoes I would just fail. But I can fill my own shoes really well.” 1
Cosmos: A Space-Time Odyssey is a thrilling new update on the original. In addition to incorporating new discoveries and special effects, the show offers an updated perspective on Earth and the universe. It does not seek to merely be a redo of the original, but instead highlights a story more specific to our times. For example, while the original series touched on themes of nuclear war, the new Cosmos has already begun to place climate change as the central challenge to humanity.
Figure 5: The cosmic calendar, updated for the new series.
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Letters While the story has been updated, certain aspects have remained. The original series heavily used the Spaceship of the Imagination as a tool for exploring the universe. Using the spaceship, Sagan was able to travel the stars and show the viewer glimpses of the past. The Spaceship of the Imagination has received a redesign for the 2014 series, evolving into a sleek metallic ship, but retaining its previous role. The cosmic calendar, a tool used to help visualize the time scale of the universe by shrinking it into a single calendar year, has also returned. The series is filled with more subtle references to the original. The opening scene of the first episode is shot on the same beach Sagan opened the original with. Tyson has also incorporated several famous lines from Sagan’s series into his narrative. Overall, Cosmos: A Space-Time Odyssey is a wonderful continuation of the original show. Existing in the space between a sequel and a remake, there is sure to be a lot more to come out of the series. You can watch Cosmos Sundays at 9pm on Fox or Mondays at 10pm on National Geographic. I highly suggest you tune in for what’s to come. References 1. Achenbach, J. (2014). Why Carl Sagan is Truly Irreplaceable. Smithsonian Magazine. Retrieved from http://www. smithsonianmag.com/science-nature/why-carl-sagan-trulyirreplaceable-180949818/ 2. Morrison, D. (2007). Carl Sagan’s Life and Legacy as Scientist, Teacher, and Skeptic. Skeptical Inquirer. 31(1). Retrieved from http://www.csicop.org/si/show/carl_sagans_life_and_legacy_ as_scientist_teacher_and_skeptic 3. Itzkoff, D. (2011). “Family Guy” Creator Part of “Cosmos” Update. The New York Times. Retrieved from http://www.nytimes. com/2011/08/05/arts/television/fox-plans-new-cosmos-withseth-macfarlane-as-a-producer.html?_r=2& 4. (n.d.) About Neil deGrasse Tyson. Retrieved from http://www. haydenplanetarium.org/tyson/profile/about-neil-degrasse-tyson Figure 1: http://static.rookiemag.com/2012/03/1331011109carls agancosmos.jpg Figure 2: http://media.npr.org/assets/img/2014/02/27/neil_ planets12b_dj1_wide-be08419127c6a21519ceeff8ebe87fbc53af1e 2c.jpg?s=6 Figure 3: http://www.slate.com/content/dam/slate/blogs/ bad_astronomy/2013/07/22/cosmos_logo.jpg.CROP.originaloriginal.jpg Figure 4: http://media.skyandtelescope.com/images/SOTI-onTitan-550px.jpg Figure 5: http://www.wired.com/images_blogs/ underwire/2014/03/3QTR-Wide-Shot-101_062_030-R2_V1.jpg
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Letters
A Look at Intestinal Transplants Thomas Savage ‘15
Some forms of organ transplantation are considered relatively common (kidney, liver, and heart among others). One reason such transplantations are frequently done is because they significantly lengthen the life of the organ recipient and allow those patients to have a relatively normal life. Small intestinal transplantations (ITx), on the other hand, are performed infrequently; only about 500 are performed annually in the U.S. Moreover, five years after the operation, half of recipients die. As with other organ transplant processes, the demand for donated organs outweighs the supply. The waiting time for transplantation is quite long (220 days on average) and for children aged 0 to 5 years on the waiting list, the mortality rate while on the waiting list is as high as 60% 1. Who might be on a waiting list for ITx? ITx is done for children who have congenital defects, such as being born with their small intestine outside of their bodies. Those children must be fed intravenously and require intestinal transplantations to survive. Adults who have had part of their small intestine removed because of disorders such as Crohn’s Disease sometimes require intestinal transplantations. Why do transplants fail? Partially because of the infrequency of the operation, little is known of the biology of ITx. The robustness of our immune systems protects us when we are healthy; for recipients of organ transplantation, however, this robustness causes their immune systems, in the form of T cells, to attack the donated organs, eventually rendering them useless. This process, known as
rejection, can happen even when the immune system is suppressed using immunosuppressive drugs. Understanding the exact process of rejection in ITx could lead to the use of more precise immunosuppression and the development of other therapeutic approaches. Recent data gathered indicate that the mechanism of rejection in ITx may have been discovered. In the epithelial layer, helper T cells are normally in very low concentration relative to cytotoxic T cells (that do the killing). In rejection, recipient helper T cells infiltrate the epithelial layer from the blood in large numbers2. They are thought to be donor specific, meaning that they recognize donor cells as foreign and will coordinate the immune response against donor cells. It is possible that these recipient helper T cells also activate donor T cells residing in the epithelial layer to kill the donor epithelial cells; this scenario would be similar to an autoimmune response, as the donor T cells would attack donor tissue. The recipient T cells implicated in rejection are identifiable by the surface molecules they display. The phenotype of these T cells (high levels of surface proteins CD28 and NKG2D, low levels of CD103) is similar to that of T cells circulating in the blood and different from normal T cells in the small intestine (low levels of CD28 and NKG2D, high levels of CD103)2. For natural physiological reasons, donor T cells in the small intestine die and are replaced by recipient T cells. Thus, the presence of recipient T cells in the epithelial layer does not by itself imply rejection; specifically, the phenotype of the recipient T cells indicates rejection.
Figure 1: In red is the donated tissue. In white are the remaining recipient organs. 1A displays an isolated ITx. 1B displays a combined intestinal and liver transplant. 1C displays a MVTx.
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Figure 2: Survival at various time points for recipients of isolated small intestinal transplant (I), liver and small intestine transplant (LI), multivisceral (stomach, pancreas, intestine) transplant (MV), and modified multivisceral transplantation without liver (MMV). Time is in months post-transplant (Reference 3). Why do transplants succeed? For patients requiring small intestinal transplantation, other organs such as the stomach, liver, and pancreas can also fail, which necessitates that those organs also be replaced. When several organs are transplanted at once, it is termed a multivisceral transplant (MVTx). Counterintuitively, MVTx has a lower rate of rejection than isolated ITx3. When transplanting organs, the donated organ is connected to the recipient’s circulatory system, which allows donor cells to circulate through the recipient’s circulatory system. In MVTx, donor T cells, as well as their progenitors, can be found in the blood of the recipient for up to a year after the transplantation4. (In isolated small intestinal transplantation, donor T cells have been found in the blood of recipients only up to three months post-transplant4.) When compared to the bone marrow (where blood stem cells differentiate, some to premature T cells), the intestine has a higher ratio of T cell progenitors5. These progenitors have been found in the blood of MVTx recipients4, suggesting that they release from the donated small intestine into the recipient bloodstream. These donor T cell progenitors then travel to the recipient’s thymus. When T cells mature in the thymus, they produce T cell
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Receptor Excision Circles (TREC). When T cells proliferate, however, they do not produce more TREC, meaning TREC becomes diluted as mature T cells divide. Thus, T cells with high levels of TREC must have recently emigrated from the thymus. Researchers have found high levels of TREC in donor T cells4, indicating the donor T cell progenitors from the intestine release to the blood, travel to and mature in the recipient’s thymus, and release back into circulation. The thymus is where T cells mature and are educated to not recognize the body’s own cells as foreign. The presence of donor T cell progenitors in the recipient thymus would have two major benefits: 1. The donor progenitors in the thymus could help educate recipient immune cells to not recognize donor cells as foreign. If the recipient T cells fail to recognize the donor cells as foreign, they will be unable to reject the donor tissue. 2. In a potentially fatal condition known as Graft-versusHost-Disease (GVHD), the donor T cells in the recipient’s blood attack the recipient because they recognize the recipient as foreign. If the donor T cells in the blood travel through the recipient’s thymus, they would be educated to not recognize the recipient’s cells as foreign. Such a scenario would prevent GVHD, which is
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Figure 3: A depiction of some of the immune cells in the small intestine and their location. Observe that an intestinal epithelial lymphocyte (IEL) is pointed out in black. IELs include T cells in the epithelial layer, which are implicated in rejection.
crucial for MVTx because of the large and sustained presence of donor T cells in the recipient’s blood. Scientists and clinicians hope to develop a procedure in which a patient is given an infusion of donor hematopoietic stem cells, which would travel to the recipient’s thymus and educate the recipient’s developing T cells to not recognize donor cells as foreign. Such a process would be a continuation of what has been observed already. This would help prevent rejection, and also eliminate the need for immunosuppression. Such a protocol has been developed and successfully studied in kidney transplantation6, but much research is still required before such a study for intestinal transplantation could be done. Research into small intestinal transplantation holds great promise. We are only beginning to touch the surface of the incredibly complicated immune system in the small intestine. This research provides a greater understanding of the healthy small intestine and more importantly, the basis on which the lives of small intestinal transplant recipients could be dramatically improved.
3. Kato, T. et al. Intestinal and Multivisceral Transplantation in Children. Annals of Surgery 243, 756–766 (2006). 4. Zuber, JG. et al. Thymic generation of donor-derived T cell from intestinal lymphoid progenitors after human small bowel transplantation. World Transplantation Congress (2014). 5. Lynch, L. et al. Detection and Characterization of Hematopoietic Stem Cells in the Adult Human Small Intestine. The Journal of Immunology 176, 5199-5204 (2006). 6. Kawai, T. et al. HLA-Mismatched Renal Transplantation without Maintenance Immunosuppression. New England Journal of Medicine 358, 353-361 (2008). Figure 1: http://www.centerspan.org/pubs/news/sp94j.htm Figure 3: Modified from figure 1 of: Abreu, MT. Toll-like receptor signaling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nature Reviews Immunology 10, 131-144 (2010).
References 1. Testa, G. et al. Living Related Small Bowel Transplantation. Annals of Surgery 240, 779-784 (2004). 2. Shonts, BA. et al. Unpublished data. The Amherst Element, Vol 6, Issue 2. Spring 2014
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Letters
A Monkey Avatar Minjee Kim ‘17
What would happen if you could control the movements of another being, such as in the movie Avatar? When a person has an injury to the central nervous system, comprised of the brain and the spinal cord, one of the most common harmful effects is loss of motor function. Researchers have long tried to restore the motor function in people with central nervous system paralysis. Previous therapies have used a braincomputer interface, in which external computers read brain signals, moving robots or cursors on a screen (Ethier et al). Many of these therapies are limited, however, because the patients only move an external machine, not their own limbs. In a study done at Cornell University, researchers have shown the possibility of moving one’s own limbs by demonstrating the possibility of moving a living, non-mechanical object. Using two monkeys as their subjects, the researchers showed that one monkey was able to control the other monkey’s movements. What is BMI (Brain-Machine Interface)? BMI is a communication pathway between a patient’s brain and external machines. Neurons in our brains send electrical signals to each other. These electrical signals can be measured in a BMI. There are two types of BMI: noninvasive and invasive. In noninvasive BMI, electrodes are placed on the scalp and measure the brain’s electrical signals by measuring the minute differences in voltage between neurons. In invasive BMI, the electrodes are
implanted into the grey matter of the brain through surgery. Compared to non-invasive BMI, invasive BMI is more precise in the recognition of the electrical signals and more accurate. In non-invasive BMI, the scalp often blocks signals and causes the electrode to read multiple layers of electrical activity; this problem is eliminated in invasive BMI (Lebedev et al). This electrical activity is then translated by a computer, which coordinates motion in an external machine such as a robot or a computer cursor. Application of BMI in Moving an Avatar The goal of BMI has been to move a person’s own limbs instead of machines. One challenge facing researchers is that the exact muscle contractions and relaxations needed to generate arm movement are unknown; unlike computer cursors, which only move up, down, left, and right, the combination of human muscle movement that generates a particular motion remains elusive (Shanechi et al). In this study by Sanechi et al, instead of trying to discover the particular combination of muscle movements, the researchers focused on the intended targets, or the target location the monkey wanted to move to. These intended targets are all connected to particular brain signals, and therefore the brain signals can be translated to the locations to which the monkeys wanted to move to. In the study, the researchers used two Rhesus monkeys, one as the “master” and the other as the “avatar”. They implanted
Figure 1: The master monkey, on top, has an electrode in the brain. The master monkey was trained with the joystick and his neural spiking patterns recorded. After the training, the joystick was taken away from the master monkey and given to the sedated “avatar” monkey. The intended target of movement from the master’s neural signals was transferred to the electrodes implanted in the avatar monkey’s spinal cord. Stimulating the avatar monkey’s nervous system in the same pattern as the master monkey used to move the joystick, allowed the sedated “avatar” monkey to move the joystick.
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Letters
Figure 2: The avatars’ movement from one target circle to another by movement of a joystick. The blue and green line represents upward movements and the red and black line represents downward movements.
electrodes into the brain, muscle, and cervical spinal cord of both monkeys. They then sedated the avatar monkey and gave the master monkey control of the avatar monkey’s movements by sending the master monkey’s brain’s electrical signals to the avatar monkey’s spinal cord and muscle electrodes, through a BMI. After monitoring more than 150 neurons in the monkeys, they matched the electrical neural signals to limb movements toward intended targets. In testing whether external limb control was possible, the researchers attached the avatar monkey’s limbs to a joystick and the movements of the joystick were made visible on a screen to the master monkey. The master monkey was shown two small circular targets with the goal of moving the joystick from one circle to the other. The results showed that the sedated avatar monkey moved the joystick to the target in 84 ± 14% of the 561 trials. Therefore, for the majority of the trials, the master monkey controlled the movement of the avatar. This study has ethical complications because a large number of electrodes need to be implanted into the monkeys, which is an invasive procedure. However, despite the ethical issues, I found the work fascinating. The study is still preliminary, having only been conducted on two monkeys, but it is a proof of concept experiment (research that lays the ground for further research) showing the possibility of paralyzed individual being able to control his or her own limb movement. In the study, the sedated monkey played the part of the paralyzed portion of a body. For a paraplegic or quadriplegic, electrodes could be placed into his or her brain and spinal cord and a computer could coordinate these two electrodes to control the person’s muscles and movement. One in fifty people are paralyzed in the United States and these results could provide hope for those who want to free themselves from paralysis. References http://www.nature.com/ncomms/2014/140218/ncomms4237/ full/ncomms4237.html http://cs.rochester.edu/~kautz/Courses/290Bspring2008/ NeuroRobots/TiNS_2006.pdf http://computer.howstuffworks.com/brain-computer-interface. htm/printable http://www.nature.com/nature/journal/v485/n7398/full/ nature10987.html
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Thesis Research
Interview With Shannon Townsend Kevin Mei ‘16 Introduction Late nights and weekends, Shannon Townsend can be found in McGuire, working with large, albino, Norwegian rats. Shannon is a Neuroscience major who has spent a large portion of her time at Amherst handling rats. She started in the fall of 2012 as a research assistant in Professor Baird’s lab, learning the technique of handling the animal: how to care for them, hold them, make injections, and perform surgeries and dissections on them. Now, Shannon is conducting her senior thesis in the Turgeon lab. The Turgeon lab used to research the effects of the chemical phenylcyclidine (PCP) in rat models of schizophrenia, but now studies the impact of caffeine on the brain. Shannon is interested in neuroscience and psychology, particularly abnormal psychology: depression, anxiety disorders, autism, Alzheimer’s, and so on. Besides the insight offered into the mind, psychology interests Shannon because her mother is a psychologist and her aunt has schizophrenia. For her thesis, Shannon studied the effects of caffeine on locomotion in adolescent rats. Effects of Caffeine on Locomotion in Adolescent Rats The scientific literature shows that in adult rats, caffeine coupled with an amphetamine challenge (being injected with amphetamine) causes an increase in motor activity. This is because caffeine is known to influence dopamine signaling in the brain and dopamine plays a integral role in regulating motor function. Dopamine signaling in the nigrostriatal pathway of the brain allows people to fine-tune motor movements and damage to the nigrostraital pathway is often associated with Parkinson’s disease. Amphetamine is a drug that causes greater dopamine release and is used with caffeine to see if caffeine has sensitized dopaminergic neurons to other drugs. While caffeine has been shown to cause an increase in motor activity in adult rats, the same hasn’t been studied in adolescent rats. Adolescents have greater brain plasticity (ability to change and adapt) and changing neuronal circuitry in the brain, perhaps allowing them to better adapt to caffeine. Does caffeine similarly affect dopamine signaling and locomotion in adolescent rats? To test this, Shannon used six groups of eight adolescent rats (28 days after being born), with each group broken down as follows: 1. Male, on caffeine, injected with amphetamine 2. Male, on caffeine, no amphetamine 3. Female, on caffeine, injected with amphetamine 4. Female, on caffeine, no amphetamine
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5. Male, no caffeine, injected with amphetamine 6. Male, no caffeine, no amphetamine 7. Female, no caffeine, injected with amphetamine 8. Female, no caffeine, no amphetamine Rats on caffeine had caffeine powder put into their drinking water for two weeks (chronic caffeine intake). Every day, Shannon would measure how much water the rats drank to record caffeine intake. To measure effects on locomotion, rats were put onto one side of an open field (a fishtank). Shannon measured for an hour how many times the rats crossed the midline of the field (crosses) and how many times rats got up on their hindlegs (rears). What she found was rather suprising: females showed no differences across treatments, but males with no caffeine and with amphetamine had more rears compared to males with caffeine and amphetamine. Based on 6 trials, her result was statistically significant– males with no caffeine but with amphetamine showed around two times more rearing in all 6 trials. This goes against Shannon’s null hypothesis that caffeine would cause a greater motor response to amphetamine, as in adults. Instead, it seems as if caffeine caused less activity in adolescent males, after an amphetamine challenge. It might be that because adolescents have greater brain plasticity, they are able to downregulate to stronger signals, Shannon muses. Thus, if they were being given chronic caffeine, perhaps less receptors for caffeine are being produced or the existing receptors become less sensitive to caffeine. Another interesting note is that the result was only shown for adolescent males when Shannon might’ve expected adolescent females to be able to downregulate. In all animal studies, it’s been shown that females are more sensitive
Thesis Research to drugs of abuse. Adult females always show a higher response to drugs than males, while adolescent females somehow compensate and have a lower response. This may be related to hormones in females; when females have their ovaries removed, they become less sensitive and responsive to drugs. Future Directions Shannon feels at ease in the lab– there’s autonomy and purposiveness. And she’s good at it (author’s perspective): “You hold the rat by its armpits and doop, make an injection.” She describes playing with newly born rats and letting them crawl up her arm a few weeks after they are born. Shannon says animal research can be upsetting but ultimately, it’s for a good cause: advancing human health and understanding. Mice, hamsters, guinea pigs, and other rodents are “little soldiers of science.” Her favorite part of the thesis were her results– there were no good or bad results. If her hypothesis had been confirmed, she would have shown something about caffeine effects in adolescent rats. If the results had not conformed to her hypothesis, as they hadn’t, it would also have provided insightful information and motivation for more interesting research. Shannon’s advice to scientists is to go into research with an open mind and not be discouraged by unexpected results. Shannon hopes to go into teaching and research, citing encouragement from mentors she’s worked with as motivation. Starting this June after her graduation, Shannon will be at the Valenzuela lab at the National Institute of Allergy and Infectious Diseases of the NIH, using hamsters as a model to develop a vaccine against Leishmaniasis. Leishmaniasis is a gruesome and common disease globally, caused by Leishmania parasites that are transferred through sandflies. Symptoms include skin ulcers and sores, and enlargement of internal organs, notably the spleen and liver. Rather than play a supporting role as a laboratory technician, Shannon would prefer to conduct in-depth research after she graduates (“a large scale thesis”) and intends to spend a few years at the Valenzuela lab before moving onto graduate school.
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Thesis Research
Interview with Christine Bierema Conner Reilly ‘16 Which professor are you doing your thesis with? Professor Ball in the Chemistry Department. Can you tell me a little bit about your thesis? My thesis is on organometallic chemistry, specifically involving the synthesis of sulfones. Sulfones have a wide array of practical applications. They are used in plastics (a specific example would be an iPhone case) and in several drugs in medicine including antibiotics, anti-leprosy drugs, and anti-glaucoma drugs. However, current syntheses of sulfones are hazardous and expensive, and few researchers are looking for new ways to create these molecules. Therefore, I am looking to develop ways of making sulfones that are more environmentally friendly, more efficient, and cheaper. Very cool. So, how do you go about trying to make “sulfones”? What is a sulfone? Well, a sulfone is just a molecule that has a sulfur atom with two oxygens and two other atoms/molecules attached to it (see Figure 1), and they just happen to have a lot of applications. To come up with new ways to make sulfones, I generally take reactions that are already known and try to make modifications to these reactions to see which molecules we can make and whether we can make these molecules in high yield. The basic idea of my research is to develop a cheaper, safer, and generalizable way to synthesize sulfones. Ideally, we would like to develop conditions that allow us to attach any carbon-containing compound that we want to the sulfur atom in sulfur dioxide. This is the long-term goal of Professor Ball’s research. As of right now, I have only been able to synthesize one desired sulfone product (see Figure 2) using reaction conditions from a paper that was published a couple of years ago (see Figure 3). However, the yield for this sulfone was only 6%. Therefore, right now I am focused on finding out if other conditions (e.g. a higher temperature) can increase the yield of this reaction. So let’s say that tomorrow you find a better way to create sulfones. What would the implications of this be? Well, first we (Professor Ball and I) would publish our results, and then we would hope that the paper gets some attention. However, the expectation would be that if we can find a better way (cheaper, faster, and safer) to synthesize sulfones, then pharmaceuticals would adopt this new method in place of the existing methods. How long will this project continue for? Can you pass this project down to future students? It’s difficult to say exactly how long the project will continue for – that is really up to Professor Ball. Even if we find a better way to create sulfones tomorrow, there would still be work to do (optimizing the The Amherst Element, Vol 6, Issue 2. Spring 2014
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reaction, finding other plausible conditions). Therefore, yes, there is a LOT of work that can be done and that will be done by future students. Professor Ball currently has two students working in his lab, and for next year he is taking on two thesis students. I imagine that in the near future, these students will focus on optimizing the synthesis that we have already discovered. However, they may want to try different things, for example, new catalysts (a catalyst is a compound that helps the reaction proceed). Right now I am using palladium as our catalyst, but in the future, students may want to try using copper or nickel. One of the disadvantages of synthesis using a palladium catalyst is that the reaction must take place under nitrogen gas, because palladium gets oxidized in the open air. However, copper reactions can take place in the open air, so if we could find a reaction pathway using copper as the catalyst, that would be very advantageous. So now that we have the basic details of your thesis topic why did you choose to write a thesis? Why in organometallic chemistry? I chose organometallic chemistry because Professor Ball’s because it is an extremely powerful branch of chemistry. Using organometallic reagents we can synthesize molecules that are entirely inaccessible through traditional methods of organic synthesis, and the idea of researching this type of system appealed greatly to me. As far as why I chose to write a thesis in the first place, I thought overall it would be a valuable experience to have. It’s very rewarding to work on something for eight months and then have a tangible product (my thesis paper) that I can call my own at the end. Also, I thought that the great amount of work that I would have to put into my thesis would help prepare me for medical school, which I plan on attending next fall. Do you have any regrets about writing your thesis? Writing my thesis was obviously a lot of work, but I don’t regret it all. However, I do sort of wish that I took more time earlier in the year to step back and look at data that I had collected in the summer. Having never done research before, it took me awhile to realize that the solution or possible solution is not always entirely apparent. This statement sounds very cliche, but when you are researching a certain topic it’s very easy to just keep running
Thesis Research different experiments, hoping that the solution will present itself, when most of the time it’s definitely better to stop and say “Okay, I haven’t been getting the results I want, so I’m going to step back and take a close look at the data I have and see if there is anything there.” Had I done this more often earlier in the play, I think I would have come up with better ideas about which directions to go in. But, part of the research experience is finding out what works and what doesn’t work, and I now realize that charging ahead full speed with ideas you already have probably isn’t the best way to go about research. Do you have any tips for future research students? If you are going to do a thesis, you absolutely need to be passionate about what you are writing about. There are many different motivations for writing a thesis (to get experience in research, to pad medical school applications, etc.), but whatever your motivations are, you must, must, must be interested in what you’re writing about, or else it is going to be a very long year for you. Basically, when you commit to a thesis, you are committing to thinking about something for at least 8 months, so in order to stay motivated you must be truly interested in what it is you are researching. I was ecstatic when I was placed with Professor Ball because, as I mentioned earlier, organometallic catalysis is an extremely powerful (and relatively new) branch of chemistry, and I really was excited to learn about past research in the field and the possible directions that we could go in. As it turned out, we weren’t able to get the results we wanted (i.e. a high-yielding sulfone reaction), but it was really incredible immersing myself in such a rich and complex field of chemistry. In summary I’d say that if you do want to do research, DEFINITELY go ahead and give it a try. If you’re like me and you don’t end up continuing with research then, oh well, but experiencing and watching and being part of the scientific process is really a valuable experience and I’d even go so far to say one that it is essential to living in the modern world. Science is based on making logical deductions from careful observations, and whether or not you continue with research these skills are incredibly valuable. So, yes, if you have even the slightest inclination to do research, go try it! What are your plans for the future? I am going to go to medical school starting in August. I don’t know where I’m going yet – I really have no idea right now. My plan is to focus on underserved medicine, meaning that I hope to work in areas that don’t have easy access to primary healthcare. As far as future research goes, I don’t see myself doing research again in the near future, first because I’m going to medical school next fall and won’t be doing any research there and second because once I graduate from med school I plan on focusing mostly on clinical work. However, if it turns out that I want to do research later in my career, I think that this experience will have prepared me very well for that.
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