This Week in Science

Science  13 Mar 2015:
Vol. 347, Issue 6227, pp. 1213
  1. Epidemiology

    Vaccinate children despite Ebola

    1. Caroline Ash

    Tanzanian mothers awaiting vaccinations


    During the medical emergency caused by the Ebola virus outbreak in West Africa, routine childhood vaccination programs have been suspended. If vaccination is not resumed soon, there could be even more deaths. Measles is highly infectious, and outbreaks are a sign of health care systems in trouble. Using mathematical modelling, Takahashi et al. estimate that about a million children across Liberia, Sierra Leone, and Guinea are vulnerable to measles. Aggressive public health programs are vital for this region to minimize harm, not only from measles but also from polio, malaria, tuberculosis, and other childhood infections.

    Science, this issue p. 1240

  2. Organic Synthesis

    A block-by-block way to manufacture molecules

    1. Jake Yeston

    Carbon-based small molecules involved in biochemistry and drug design exhibit extraordinary structural diversity. But can we come up with a general set of building blocks from which a machine could put most of them together, in assembly-line fashion? Li et al. present progress toward this goal by showcasing the range of structures available via coupling reactions of fragments bearing a specific type of boronate group. They successfully made complex polycyclic structures by stringing together a linear precursor and then coaxing it to fold back on itself. They also developed a purification method that facilitates automation of the reaction and product isolation.

    Science, this issue p. 1221

  3. Metabolic Disease

    Special delivery for fatty liver disease

    1. Paula A. Kiberstis

    Nonalcoholic fatty liver disease is one of many unwelcome consequences of the global rise in obesity rates. Fat accumulation within the liver can lead to inflammation and cirrhosis, a predisposing factor for liver cancer. Treatment options are limited. Perry et al. revisit a mitochondrial uncoupling agent (2,4-dinitrophenol) that was used as a drug for weight loss in the 1930s but was discontinued because of serious toxicities. Encouragingly, an altered formulation of the drug that ensures its controlled release at low levels ameliorated fatty liver and diabetes in rodent models, without side effects.

    Science, this issue p. 1253

  4. Lung Injury

    Exercising away the effects of lung injury

    1. Yevgeniya Nusinovich

    We all know that healthy people benefit from exercise, but recent evidence suggests that it also helps the sickest patients in the ICU. Files et al. studied mice with acute lung injury to understand why exercise is beneficial and confirmed their findings in human respiratory failure patients receiving therapeutic exercise. Exercise prevented muscle wasting and limited the number of immune cells infiltrating the lung by decreasing levels of a growth factor called G-CSF.

    Sci. Transl. Med. 7, 278ra32 (2015).

  5. Lunar Geology

    Onsite radar shows what lies beneath

    1. Margaret M. Moerchen

    China's Yutu rover on the lunar surface


    In more active periods of the Moon's history, volcanic eruptions created lava plains that formed layers of dark basalt. Without subsurface probing, we can only examine the most recent flows. After the soft landing of the Chang'E-3 spacecraft, Xiao et al. made penetrating radar measurements of the lunar crust with the Yutu rover. Several subsurface layers suggest multiple geologic processes at play throughout the crustal history, including multiple lava flows and the weathering-induced creation of dust and rocky debris.

    Science, this issue p. 1226

  6. Political Psychology

    Be mindful of a self-reported gap

    1. Gilbert Chin

    Happiness is a notoriously hard to pin down quantity possibly best described by the phrase, “I know it when I see it.” Self-reported ratings of happiness are generally higher for political conservatives in the United States than for those with more liberal leanings. Wojcik et al. examined three data sets based on behavioral measures, such as tweets and smiles. Despite self-reported claims to the contrary, liberals exhibited more happiness than their more conservative counterparts. For instance, as judged from their photographs on a business-oriented social network, more employees of the New York Times smiled genuinely than did those of the Wall Street Journal.

    Science, this issue p. 1243

  7. Circadian Rhythms

    Midnight snacks are bad for the heart

    1. L. Bryan Ray

    Circadian clocks help animals coordinate their active and rest periods with the daily cycles of light and darkness. As anyone who has suffered jet lag or worked night shifts knows, losing this coordination can have deleterious effects. Gill et al. compared fruit flies that were allowed to eat at any time with flies that were only allowed to eat during the day (when they are active). The flies with restricted feeding times slept better and had a slower decline in heart function as they aged. They also showed less weight gain, even though both groups of flies consumed about the same amount.

    Science, this issue p. 1265

  8. Behavioral Neuroscience

    Crickets say NO to fight or flight

    1. Philip Yeagle

    In crickets, to flee or not to flee is a life-and-death decision weighed on the scales of nitric oxide (NO) signaling. Stevenson and Rillich found that the making of this critical decision in the heat of battle sums the impact of the opponent's attacks. At a threshold level, the NO signaling pathway is activated. This depresses aggression and promotes flight of the loser from the scene. Activation of the NO pathway has an aftermath. Losers avoid further battles, at least for a time.

    Sci. Adv. 10.1126/sciadv.150060 (2015).

  9. Quantum Walks

    Quantum walkers under a microscope

    1. Jelena Stajic

    Generations of physics students have been taught to think of one-dimensional random walks in terms of a drunken sailor taking random steps to the right or to the left. But that doesn't compare with the complexity of a quantum walker, who can propagate down multiple paths at the same time. Preiss et al. detected particles in single sites of an optical lattice to study the dynamics of two interacting atoms of 87Rb performing a quantum walk (see the Perspective by Widera). Depending on the initial conditions and the interaction strength between the atoms, the atoms either ignored each other, stuck to each other, or tried to get as far away from each other as possible.

    Science, this issue p. 1229; see also p. 1200

  10. Epidemiology

    Mathematical modeling of infectious diseases

    1. Caroline Ash

    The spread of infectious diseases can be unpredictable. With the emergence of antibiotic resistance and worrying new viruses, and with ambitious plans for global eradication of polio and the elimination of malaria, the stakes have never been higher. Anticipation and measurement of the multiple factors involved in infectious disease can be greatly assisted by mathematical methods. In particular, modeling techniques can help to compensate for imperfect knowledge, gathered from large populations and under difficult prevailing circumstances. Heesterbeek et al. review the development of mathematical models used in epidemiology and how these can be harnessed to develop successful control strategies and inform public health policy.

    Science, this issue 10.1126/science.aaa4339

  11. Innate Immunity

    Innate immune receptor signaling, united

    1. Kristen L. Mueller

    Innate immune receptors such as RIG-I, cGAS, and Toll-like receptors bind microbial fragments and alert the immune system to an infection. Each receptor type signals through a different adapter protein. These signals activate the protein kinase TBK1 and the transcription factor IRF3, which tells cells to secrete interferon proteins (IFNs) important for host defense. Liu et al. now report a common signaling mechanism used by all three types of innate immune receptor-adaptor protein pairs to activate IRF3 and generate IFNs. This is important because cells must regulate their IFN production carefully to avoid inflammation and autoimmunity.

    Science, this issue 10.1126/science.aaa2630

  12. Organometallics

    Taking advantage of four for a nickel

    1. Jake Yeston

    Metal atoms change their oxidation state—i.e., lose or gain electrons—relatively easily. This is a major reason why metal compounds accelerate so many chemical reactions. Camasso and Sanford now report a straightforward way to prepare complexes of nickel in the +4 oxidation state, based on careful tuning of the coordination environment around the metal center (see the Perspective by Riordan). These complexes could prove useful in coupling carbon to oxygen, nitrogen, or sulfur, and complement more traditional nickel catalysts that operate in lower oxidation states.

    Science, this issue p. 1218; see also p. 1203

  13. Chemistry

    Using chemical design to avoid regrets

    1. Julia Fahrenkamp-Uppenbrink

    In response to public health concerns, the chemical bisphenol A (BPA) has been widely replaced with the related compound bisphenol S (BPS) in consumer products such as baby bottles. Yet recent studies have shown that BPS may also be harmful to human health. In a Perspective, Zimmerman and Anastas discuss how such “regrettable substitutions” may be avoided. They chart a progression via informed chemical substitutions designed to avoid toxicity and other hazards.

    Science, this issue p. 1198

  14. Sympathetic Cooling

    Highly charged ions in cold confines

    1. Jake Yeston

    High-energy irradiation can strip many electrons away from individual atoms, producing ions with charges of +10 or more. However, many of the interesting properties of such highly charged ions are hard to study or exploit under the extreme conditions needed to prepare them. Schmöger et al. cooled down argon ions with +13 charges from the megakelvin temperatures needed for their generation to millikelvin temperatures appropriate for high-precision spectroscopy. The method relies on sympathetic cooling by a cold sample of singly charged beryllium ions and is likely to be applicable to a broad range of other elements.

    Science, this issue p. 1233

  15. Oceanography

    Connecting orbit to the ocean floor

    1. Brent Grocholski

    The amount of magma erupted at mid-ocean ridges can be modified by periodic ice ages that alter sea level. Crowley et al. analyzed high-resolution ocean depth data across the Australian-Antarctic ocean ridge (see the Perspective by Conrad). The results revealed 23-, 41-, and 100-thousand-year periodicity. These periods are similar to the well-known Milankovitch cycles associated with ice ages that are triggered by changes in Earth's orbit. Decreasing sea levels decrease the overlying pressure, thereby increasing the amount of erupted magma. The cyclic nature of glaciations and sea level creates a series of spaced topographic highs along the sea floor. Thus, Earth's atmosphere and mantle are coupled on a glacial time scale.

    Science, this issue p. 1237; see also p. 1204

  16. Human Paleoecology

    Pleistocene humans in tropical rainforest

    1. Andrew M. Sugden

    The tropical rainforest environment is nutritionally poor and tricky to navigate as compared to open habitats. This poses challenges for human subsistence. There has been little evidence to suggest that human populations relied on rainforest resources before the start of the Holocene, 10,000 years ago. Roberts et al. analyzed earlier fossil human and animal tooth enamel from Sri Lanka. The diet of these humans suggests rainforest rather than open-habitat foraging. Thus, humans were effectively exploiting rainforests in Sri Lanka since at least 20,000 years ago throughout periods of considerable climatic and environmental flux.

    Science, this issue p. 1246

  17. Protein Stability

    The N-end rule finds a physiological function

    1. Stella M. Hurtley

    The N-end–rule pathway for protein degradation is a canonical degradation pathway discovered in the 1980s. In recent years, studies have focused on finding novel variant pathways of N-end recognition. The “classical” pathway is blocked by N-terminal acetylation of the substrate. However, in yeast, N-terminal acetylation need not block degradation, because a second pathway can act on acetylated N-termini. But is this alternate pathway a major player in the physiology of mammals? Park et al. now confirm the existence of the alternate pathway in mammalian cells. Most notably, patient-derived point mutations thought to confer hypertension in humans affect susceptibility to this pathway for the encoded protein substrate, Rgs2.

    Science, this issue p. 1249

  18. Ion Channels

    A sensitive regulator of cellular potassium

    1. Valda Vinson

    A class of potassium channels called K2P channels modulates resting membrane potential in most cells. The channels are regulated by multiple ligands, including the antidepressant drug Prozac, as well as factors such as mechanical stretch and voltage. Dong et al. determined the structure of the human K2P channel, TREK-2, in two conformations and bound to a metabolite of Prozac. The structures show how ligand binding or mechanical stretch might induce switching between the states. Although both states have open channels, one appears primed for gating. A Prozac metabolite binds to the primed state and prevents conformational switching. K2P channels are not a target of Prozac, but their inhibition may contribute to side effects.

    Science, this issue p. 1256

  19. Sepsis

    A new therapeutic target for sepsis

    1. Kristen L. Mueller

    Infections can sometimes unleash powerful immune responses that careen out of control, leading to sepsis, organ failure, and death. Although antibiotics can help to quash the infection, sepsis patients also need therapies that will rein in the immune response. Weber et al. now identify one potential target, the secreted protein interleukin-3 (IL-3) (see the Perspective by Hotchkiss). In sepsis patients, higher serum concentrations of IL-3 were correlated with higher rates of mortality. In septic mice, IL-3 caused the immune system to produce large amounts of cells called monocytes and neutrophils, which secrete highly inflammatory proteins. Blocking IL-3 protected mice from sepsis-induced death.

    Science, this issue p. 1260; see also p. 1201

  20. Structural Biology

    Lighting up rhodopsin movement

    1. Nancy R. Gough

    One of the fastest signaling events is the eye's response to light, which is detected by the G protein–coupled receptor rhodopsin. In contrast to the majority of structural analyses that have been done with this and other G protein–coupled receptors, Malmerberg et al. determined light-induced conformational changes in rhodopsin in its native membrane environment. Within a few milliseconds, rhodopsin adopted a stable active conformation that was associated with the movement of portions of two adjacent transmembrane domains. These movements were considerably larger and implied a more extended conformational change in the light activation of rhodopsin than was suggested by crystal structures of activated rhodopsin.

    Sci. Signal. 8, ra26 (2015).