This Week in Science

Science  09 Jan 2015:
Vol. 347, Issue 6218, pp. 141
  1. Epidemiology

    Co-infection complicates treatment

    1. Caroline Ash

    Water buffalo show that curing one infection does not stop the spread of another

    PHOTOS: MINEV ET AL.; © JOHAN SWANEPOEL/ALAMY

    Infections rarely occur in isolation, and treating one pathogen may have unpredictable effects on another. Ezenwa and Jolles, working on wild African buffaloes, expected that because deworming relieves immune suppression, such treatment would lead to a drop in tuberculosis because the animals would clear the second infection without further intervention. Not so. Deworming did improve the lot of parasite-infested individuals, but it also increased the spread of tuberculosis among the population. What apparently happened is that the worm-free buffalo lived longer but stayed infected with tuberculosis and had longer to spread the infection among the herd.

    Science, this issue p. 175

  2. Earth History

    Dating the influence of Deccan Traps eruptions

    1. Nicholas S. Wigginton

    The Deccan Traps flood basalts in India represent over a million cubic kilometers of erupted lava. These massive eruptions occurred around the same time as the end-Cretaceous mass extinction some 65 million years ago, which famously wiped out all nonavian dinosaurs. Schoene et al. determined the precise timing and duration of the main phase of the eruptions, which lasted over 750,000 years and occurred just 250,000 years before the Cretaceous-Paleogene boundary. The relative contribution of these eruptions and of the Chicxulub impact in Mexico to the mass extinction remains unclear, but both provide potential kill mechanisms.

    Science, this issue p. 182

    Gases released in these lava flows in India may have aided an extinction event

    PHOTO: © DINODIA PHOTOS/ALAMY
  3. Cancer

    Going BATty to fight prostate cancer

    1. Yevgeniya Nusinovich

    Although many early cases of prostate cancer can be treated by blocking the activity of male hormones, the tumor often develops resistance and regrows. Standard hormone-based treatments, which all involve androgen deprivation, are ineffective at this stage of the disease. Now, Schweizer et al. describe an approach based on evidence that cancer cells adapted to low-androgen conditions may not tolerate high concentrations of testosterone. A clinical trial of BAT (bipolar androgen therapy), in which very high and very low concentrations of testosterone alternate in the patients' blood, showed that the regimen was well tolerated. In addition to direct anticancer effects, intermittent testosterone treatment also restored the tumors' sensitivity to anti-androgen agents, further expanding patients' treatment options.

    Sci. Transl. Med. 7, 269ra2 (2015).

  4. Quantum Gases

    Breaking the symmetry in an atomic gas

    1. Jelena Stajic

    Cooling a physical system through a phase transition typically makes it less symmetrical. If the cooling is done very slowly, this symmetry change is uniform throughout the system. For a faster cooling process, the system breaks up into domains: The faster the cooling, the smaller the domains. Navon et al. studied this process in an ultracold gas of Rb atoms near its transition to a condensed state (see the Perspective by Ferrari). The authors found that the size of the domains froze in time in the vicinity of the transition and that it depended on the cooling speed, as predicted by theory.

    Science, this issue p. 167; see also p. 127

  5. Ultrafast Dynamics

    Traveling a long way past the junction

    1. Jake Yeston

    Diodes are central components of modern electronic circuits. They essentially consist of two semiconductors sandwiched together, with one deficient in electrons (p), the other enriched (n). Najafi et al. used ultrafast electron microscopy to study the dynamics in a silicon diode on a time scale of trillionths of a second. They discovered that when light excites the diode's charge carriers, those carriers migrate much farther past the p-n junction than standard models would imply. The authors explain the results using a ballistic transport model.

    Science, this issue p. 164

  6. Gut Microbiota

    Gut microbes resist inflammation

    1. Caroline Ash

    It is vital to human well-being that our gut microbiota can be distinguished from harmful, but often very similar, organisms. Cullen et al. begin to analyze how one dominant symbiont, Bacteroidetes thetaiotaomicron, does this. Our guts release potent antimicrobial peptides when we become infected with pathogenic bacteria such as salmonella, but these symbionts make an outer lipopolysaccharide coat that differs from those of pathogens by only one phosphate molecule. Enzymatic removal of this group is enough to confer resistance to the host's immune response and allow the symbionts to escape damage.

    Science, this issue p. 170

  7. Computer Science

    I'll see your program and raise you mine

    1. Gilbert Chin

    One of the fundamental differences between playing chess and two-handed poker is that the chessboard and the pieces on it are visible throughout the entire game, but an opponent's cards in poker are private. This informational deficit increases the complexity and the uncertainty in calculating the best course of action—to raise, to fold, or to call. Bowling et al. now report that they have developed a computer program that can do just that for the heads-up variant of poker known as Limit Texas Hold 'em (see the Perspective by Sandholm).

    Science, this issue p. 145; see also p. 122

  8. DNA Repair

    A factor for repairing broken DNA

    1. Guy Riddihough

    Unprogrammed DNA double-strand breaks are extremely dangerous for genomic stability. Nonhomologous end-joining (NHEJ) repair systems are present in all domains of life and help deal with these potentially lethal lesions. Ochi et al. have discovered a new factor involved in NHEJ by searching for proteins with structural similarities to known NHEJ proteins. Specifically, PAXX, a paralog of XRCC1 and XLF, interacts with a key repair pathway protein, Ku, and helps promote ligation of the broken DNA.

    Science, this issue p. 185

  9. Vascular Biology

    Peroxidized lipids dilate blood vessels

    1. Wei Wong

    Cerebral arteries must maintain constant blood flow to the brain even though blood pressure fluctuates constantly. Sullivan et al. characterized a signaling pathway that is specific to the endothelial cells that line cerebral arteries. Reactive oxygen species (ROS) cause lipid peroxidation. In endothelial cells in cerebral arteries, locally produced ROS oxidized lipids, which triggered calcium influx through the ion channel TRPA1. In turn, this calcium influx activated a potassium-permeable channel, resulting in the dilation of cerebral arteries.

    Sci. Signal. 8, ra3 (2014).

  10. RNA Splicing

    Predicting defects in RNA splicing

    1. Guy Riddihough

    Most eukaryotic messenger RNAs (mRNAs) are spliced to remove introns. Splicing generates uninterrupted open reading frames that can be translated into proteins. Splicing is often highly regulated, generating alternative spliced forms that code for variant proteins in different tissues. RNA-binding proteins that bind specific sequences in the mRNA regulate splicing. Xiong et al. develop a computational model that predicts splicing regulation for any mRNA sequence (see the Perspective by Guigó and Valcárcel). They use this to analyze more than half a million mRNA splicing sequence variants in the human genome. They are able to identify thousands of known disease-causing mutations, as well as many new disease candidates, including 17 new autism-linked genes.

    Science, this issue 10.1126/science.1254806; see also p. 124

  11. Batteries

    Watching the silver lining inside

    1. Marc S. Lavine

    Some types of batteries contain both a transition metal reducible metal, such as the cathode material Ag2VP2O8. During operation, both Ag and V ions are reduced, and the Ag atoms can form wires to enhance the internal conductivity. Kirshenbaum et al. probe the discharge of a battery at different rates and track the formation of Ag atoms using in situ energy-dispersive x-ray diffraction (see the Perspective by Dudney and Li). They show how the discharge rate affects whether the Ag or V is preferentially reduced and also the distribution of the Ag atoms, and then correlate this to the loss of battery capacity at higher discharge rates.

    Science, this issue p. 149; see also p. 131

  12. Materials Science

    Popping materials and devices from 2D into 3D

    1. Marc S. Lavine

    Curved, thin, flexible complex three-dimensional (3D) structures can be very hard to manufacture at small length scales. Xu et al. develop an ingenious design strategy for the microfabrication of complex geometric 3D mesostructures that derive from the out-of-plane buckling of an originally planar structural layout (see the Perspective by Ye and Tsukruk). Finite element analysis of the mechanics makes it possible to design the two 2D patterns, which is then attached to a previously strained substrate at a number of points. Relaxing of the substrate causes the patterned material to bend and buckle, leading to its 3D shape.

    Science, this issue p. 154; see also p. 130

  13. Biomaterials

    Mechanically soft neural implants

    1. Marc S. Lavine

    When implanting a material into the body, not only does it need the right functional properties, but it also needs to have mechanical properties that match the native tissue or organ. If the material is too soft, it will be mechanically degraded, and if it is too hard it may get covered with scar tissue or it may damage the surrounding tissues. Starting with a transparent silicone substrate, Minev et al. patterned microfluidic channels to allow for drug delivery, and soft platinum/silicone electrodes and stretchable gold interconnects for transmitting electrical excitations and transferring electrophysiological signals. In tests of spinal cord implants, the soft neural implants showed biointegration and functionality within the central nervous system.

    Science, this issue p. 159

  14. Metabolism

    Getting specific about amino acid sensing

    1. L. Bryan Ray

    The protein kinase complex mTORC1 regulates growth and metabolism, and its activity is controlled in response to the abundance of cellular amino acids. Jewell et al. report that control of mTORC1 in response to glutamine does not require the Rag guanosine triphosphatase (GTPase) implicated in the sensing of other amino acids such as leucine (see the Perspective by Abraham). For sensing of glutamine, another GTPase, Arf1, was required. Distinct mechanisms thus appear to couple various amino acids to signaling by the mTORC1 complex.

    Science, this issue p. 194; see also p. 128

  15. Structural Biology

    Dueling dimers serve dual purposes

    1. Nicholas S. Wigginton

    Both bacteria and mitochrondria produce NADPH for amino acid biosynthesis and to remove reactive oxygen species. The enzyme that makes NADPH must translocate a proton across the membrane and transfer a hydride from NADH to NADP+—processes that happen some 40 Å apart. To understand this complex geometry, Leung et al. solved the structures of the entire transhydrogenase enzyme and the membrane domain from the bacterium Thermus thermophilus (see the Perspective by Krengel and Törnroth-Horsefield). The entire enzyme exists as a dimer, with the two membrane domains in alternate orientations. One of the membrane domains interacts with the membrane component for proton translocation, whereas the other domain exchanges hydride with NAD(H) in another large soluble domain.

    Science, this issue p. 178; see also p. 125

  16. Metabolism

    Sensing amino acids at the lysosome

    1. L. Bryan Ray

    The mTORC1 protein kinase is a complex of proteins that functions to regulate growth and metabolism. Activity of mTORC1 is sensitive to the abundance of amino acids, but how the sensing of amino acids is coupled to the control of mTORC1 has been unclear. Wang et al. searched for predicted membrane proteins that interacted with regulators of mTORC1. They identified a protein currently known only as SLC38A9. Interaction of SLC38A9 with mTORC1 regulators was sensitive to the presence of amino acids. SLC38A9 has sequence similarity to amino acid transporters. Effects of modulation of SLC38A9 in cultured human cells indicate that it may be the sensor that connects the abundance of arginine and leucine to mTORC1 activity.

    Science, this issue p. 188

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