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news briefsBAX, the potency of the peptide has been adjusted so that it is strong enough to bind to BAX, but a bit slower at activating it so that the interaction can actually be studied (2). The group also used nuclear magnetic resonance spectroscopy (NMR) to study the arrangement of atoms in the protein. The subset of amino acids that are part of BAX which shifted upon exposure to the peptide re-vealed a completely unanticipated location on BAX (2)—the discovery of a switch that turns BAX on. This has immense implications for the develop-ment of new pharmacologic agents. Drugs can potentially be developed to directly activate BAX to kill diseased cells for cancer treatment. Similarly, BAX blocking drugs could potentially prevent unwanted cell death, perhaps thwarting some of the terrible effects of heart attacks, strokes, and neurodegeneration (1, 2). —Pushan S. Dasgupta ‘10

Identifi cation of a Cell Death Protein’s Switch

1.Gavathiotis, E., Suzuki, M., Davis, M. L., Pitter, K., Bird, G. H., Katz, S. G., Tu, H., Kim, H., Cheng, E., Tjandra, N., & Walensky, L. D. BAX activation is initiated at a novel interaction site. Nature 455, 1076-1081 (2008).2.Saltus, Richard. “Scientists unlock secret of death protein’s ac-tivation.” Harvard Science . URL: <http://harvardscience.harvard.edu/foundations/articles/scientists-unlock-secret-death-protein-s-activation>. Accessed 7 November 2008.

Harvard Medical School scientists at Dana-Farber Cancer Institute have identifi ed a trigger point on a special protein called BAX. BAX is a naturally occurring protein that can cause a cell to go through a process called apoptosis or pro-grammed cell death (1). BAX helps the body get rid of unwanted or diseased cells. It belongs to a group of proteins called the BCL-2 family. These proteins interact in many different ways resulting in either cell survival or cell death. Cancer cells have an imbalance of BCL-2 family signals that causes them to survive instead of dying on com-mand (2). Normally BAX is predominantly in the cytosol of the cell when it is not activated. Then upon cellular stress and subsequent activation, BAX translocates to the mitochondria which are essentially the cell’s power plants. BAX then pokes holes in the mitochondria’s membranes, increas-ing their permeability and ultimately leading to apoptosis. The scientists at Dana-Farber have made a peptide, or protein subunit, that matches the shape of the newly found trigger site. Docking of the peptide into the binding site causes BAX to become activated, directly resulting in cell death. In order to study the interaction of the peptide with

It’s generally accepted that fi ngertips act to increase friction and to provide greater tacticle perception of the world. However, the study by Debrégeas et al indicates that fi ngerprints may also be used to selectively amplify tactile information, which presumably allows the brain to interpret informa-tion more effi ciently. Though the consequences of this fi nding have yet to be fully explored, it seems as though fi ngerprints may have evolved for much more complicated purposes than were previously known. —Daniel O’Leary ‘09

Fingerprints may be useful for more than just identifi cation of suspects by the po-lice. In a recent study by Debrégeas et al, scientists in Paris at the École Normale

Supérieure used a biomimetric tactile sensor to test what range of vibrations could be detected by human fi ngertips. The study found that when the sensor mimicked the pattern of ridges found in a typical fi ngerprint the vibration spectrum pro-duced by the sensor was largely limited to the op-timal range for interpretation by the human brain.

Fingerprints Increase Fingers’ Tactile Sensitivity

Fingerprints may be useful for more than just identifi cation of suspects by the po-lice. In a recent study by Debrégeas et al, scientists in Paris at the École Normale

1. Scheibert, J., Leurent, S., Prevost, A. & Debrégeas, G. “The Role of Fingerprints in the Coding of Tactile Information Probed with aBiomimetic Sensor.” Science advance online publication (2009).

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news briefsScientists at UCLA have demonstrated that peel-ing adhesive tape in a near-vacuum can generate X-ray emission. This phenomenon is an extreme example of tribioluminescence, in which visible light is emitted from two surfaces rub-bing against each other. The scientists have proposed a model in which the peeling tape induces a separation of charge, with the sticky part gaining positive charge and the other (polyethylene) side of the tape gaining nega-tive charge. Once the resulting electric field becomes strong enough, the tape discharges and electrons accelerate from the negative to the positive side. This electron acceleration is intense enough to generate Bremsstrahlung radiation (radiation from accelerating charge) in the X-ray part of the spectrum. The scien-tists have measured a peak X-ray energy of 15 keV, intense enough for this technique to be used

as X-ray photography; in fact, the scientists have already taken an X-ray (see figure) [1].

—Tim Hsieh‘10

X-Rays from Tape

the rapidity with which Tsein was able to alter memo-ries surprised other scientists in the field. According to Todd Sacktor of State University of New York Down-state Medical Cen-ter, Tsein’s research represents part of “a big paradigm shift in how people think about how long-term memories are stored.” The biggest challenge will be how to successfully apply this research to human models in order to treat psychiatric disorders [1].

—Joshua Feblowitz ‘09

By administering specific drugs to genetically engineered mice, scientists have been able to se-lectively erase certain long-term memories. This discovery raises the possibility of developing new, more effective treatments for psychiatric condi-tions such as post-traumatic stress disorder.The research, which was conducted by Joe Tsein at the Medical College of Georgia in Augusta, cen-ters on the manipulation of an enzyme known as αCAMKII. Lab mice were genetically engineered to produce excess of this enzyme and were then administered drugs in order to regulate its produc-tion. The mice were given water laced with the in-hibiting drugs and were taught to associate certain stimuli with electric shocks. As long as the mice had normal levels of αCAMKII, they remembered these associations. However, when the research-ers later withheld the inhibitors and allowed the αCAMKII to flood their brains, the mice forgot any of the associations that were recalled during this period. The simplicity of the αCAMKII mechanism and

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1. Camara, C.G., et al. “Correlation between nanosecond X-ray flashes and stick-slip friction in peeling tape.” 2008, Nature. 455, 7216.

1. Miller, Greg. “Thanks for Erasing the Memories.” ScienceNOW Daily News. http://sciencenow.sciencemag.org/cgi/content/full/2008/1023/1, October 23, 2008.

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An x-ray of a capacitor, tak-en using X-rays generated by tape (1).

Spotless Mind: Scientists Erase Select Memories in Mice

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Sweeter Pill Helps Children Combat Malaria

1.Abdulla, Salim., et al. “Efficacy and safety of artmether-lume-fantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomized, single-blind, multicentre trial.” 2008, The Lancet, Early Online Publication.

too large to be ingested by small children. This poses a serious issue in a region where children are at extremely high risk of contracting malaria. Dr. Abdulla et al set out to remedy this issue by developing a cherry-flavored alternative for young children in a dispersible tablet form. These dis-persible tablets are as easy to ingest as crushed tablets and don’t run the risk of lowering drug dosage (as crushed tablets do). Dr. Abdulla et al found that their tasty and edible tablets were just as effective as the original, less appealing version [1]. Though these changes may seem small, they can be critical when it comes to providing good care to a large group of people who cannot be constantly supervised by medical officials. —Daniel O’Leary ‘09

Most people have had the experience of being forced to take nasty-tasting medicine at some point in their childhood. Taking medicine is often akin to eating vegetables in the mind of a child; neither has clear enough benefits to be worth the terrible taste. Kids (as well as adults) often don’t recognize the importance of taking medicine on a regular

basis. In wealthy countries that have eradicated many diseases, forgetting to take medicine typi-cally results in an extended cold or cough. In less wealthy areas of the world like sub-Saharan Africa it can result in morbidity or death from ubiquitous malarial infections. Unfortunately the only accepted tablet for preventing and combating malaria, artemether-lumefantrine, has a taste as unappealing as its name and is only available in tablet form, which can be

Multiple Sclerosis (MS) is a neurodegenerative disease consisting of two distinct phases: early and late. In the early phase, the body of the patient mounts an allergic response to its own white matter in the brain and spinal cord. Symptoms from this stage include blurred vision and difficulty walking. In the late stage, patients suffer irreversible nerve cell damage leading to symptoms of fatigue, loss of balance and coordination, as well as changes in perception (1). Because the early stage of MS inevitably leads to the late stage, treatments often focus on preventing the symptoms of early-phase MS from worsening. A recent study at the University of Cam-bridge tested a new drug containing alemtuzumab (marketed as Campath-1H), an artificial human antibody, which inactivates the immune cells that

attack white matter in early-phase MS. Three years of medical trials for the alemtuzumab drug showed very promising results compared to conventional drug used for early-phase MS (interferon beta-1a). While patients who used the conventional drug became more disabled on average, many patients who used the alemtuzumab drug actually recovered from some of their debilitating symptoms. This also suggests that alemtuzumab may be very effec-tive in constraining the onset of the much more serious (and irreversible) late-phase MS (1). The alemtuzumab drug, however, has its caveats: in certain individuals, very severe side ef-fects were observed. Six of the 223 (3%) patients tested developed an illness called ITP (Immune Thrombocytopenic Purpura), a potentially-fatal condition in which damaged blood vessels to leak

A mosquito biting a hu-man. Mosquitos are the vecor that transmit ma-laria.

A Hopeful but Troubled Drug for MS

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6 Harvard Science Review • fall 2008

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proposed a new model to explain the nonlinear behavior, which they analogized to “mass bouncing on a trampoline.” According to this model, soil experiences compressional stress during extreme ground motion and behaves elastically. While fall-ing back down, cohesion between soil particles is reduced, so the force of gravity takes over. This is similar to jumping on a trampoline, when the repellent, upward force of the trampoline can exceed the downward force of gravity. The authors note that the trampoline model may be an oversimplification of ground behavior, but their findings have important implications for assessing and preventing earthquake hazards. Quake-proof buildings usually only take horizontal shaking into account, but the Iwate-Miyagi earth-quake showed that vertical movement can also wreak havoc. Better models could help engineers build structures that can survive stronger earth-quakes.

The Iwate-Miyagi earthquake shook the Tōhoku region of Japan on June 14, 2008, set-ting off landslides and injuring more than 300 residents. The earthquake scored a magnitude of 6.9 on the Richter scale— it is on par with the 1989 earthquake that struck San Francisco. Earthquakes are not uncommon in the country, but researchers at the Institute for Earth Science and Disaster Prevention in Tsukuba, Japan, found an unprecedented result when they analyzed the records. Seismologists usually focus on horizon-tal ground motion when assessing the hazardous impact of an earthquake, but Aoi et al. measured that the ground exhibited a vertical acceleration of roughly 4g (four times that of gravity), far exceed-ing the horizontal acceleration of only 1.5g. Even more surprising was the asymmetry in the vertical movement: the ground sprang upward with larger acceleration than what it exhibited when falling back down [1]. Existing models of ground motion could not explain this movement, so the researchers

Insights from Earthquakes into Designing Quake Proof Buildings

1. Aoi S et al. Trampoline Effect in Extreme Ground Motion. Science 322: 727-730 (2008).

1. Spiesel, Sydney. “The Good News and Bad News About MS.” Updated 31 Oct. 2008. <http://www.slate.com/id/2203429/>. Cited 1 Nov. 2008. 2. CAMMS223 Trial Investigators, et al. Alemtuzumab vs. inter-feron beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801.

Protein structure of the monoclonal antibody alem-tuzumab, a possible treat-ment for multiple scle-rosis.

large amounts of blood. Other patients developed auto-allergic thyroid illnesses, which only exacerbate the allergic problems of Multiple Sclerosis (2). Because of these potentially life-threatening side effects, alemtuzumab will most likely not become mainstream medication for early-phase MS. Its encouraging benefits, however, may lead some doctors to prescribe alemtuzumab drugs “off label,” since the drug has already been approved for leukemia therapy. The question MS patients must face now is whether they would be willing to take the short-term risk with alemtuzumab to po-tentially avoid the long-term degenerating effects of Multiple Sclerosis. —Lisa N. Chen ‘12

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