Science Roundup


This month in Science Roundup:
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REPORT: Seasonal Flows on Warm Martian Slopes

Abstract: Water probably flowed across ancient Mars, but whether it ever exists as a liquid on the surface today remains debatable. Recurring slope lineae (RSL) are narrow (0.5 to 5 meters), relatively dark markings on steep (25° to 40°) slopes; repeat images from the Mars Reconnaissance Orbiter High Resolution Imaging Science Experiment show them to appear and incrementally grow during warm seasons and fade in cold seasons. They extend downslope from bedrock outcrops, often associated with small channels, and hundreds of them form in some rare locations. RSL appear and lengthen in the late southern spring and summer from 48°S to 32°S latitudes favoring equator-facing slopes, which are times and places with peak surface temperatures from ∼250 to 300 kelvin. Liquid brines near the surface might explain this activity, but the exact mechanism and source of water are not understood.
Supporting online material


REVIEW: The Future of Seawater Desalination: Energy, Technology, and the Environment

Abstract: In recent years, numerous large-scale seawater desalination plants have been built in water-stressed countries to augment available water resources, and construction of new desalination plants is expected to increase in the near future. Despite major advancements in desalination technologies, seawater desalination is still more energy intensive compared to conventional technologies for the treatment of fresh water. There are also concerns about the potential environmental impacts of large-scale seawater desalination plants. Here, we review the possible reductions in energy demand by state-of-the-art seawater desalination technologies, the potential role of advanced materials and innovative technologies in improving performance, and the sustainability of desalination as a technological solution to global water shortages.
Supporting online material


REPORT: Integrating What and When Across the Primate Medial Temporal Lobe

Abstract: Episodic memory or memory for the detailed events in our lives is critically dependent on structures of the medial temporal lobe (MTL). A fundamental component of episodic memory is memory for the temporal order of items within an episode. To understand the contribution of individual MTL structures to temporal-order memory, we recorded single-unit activity and local field potential from three MTL areas (hippocampus and entorhinal and perirhinal cortex) and visual area TE as monkeys performed a temporal-order memory task. Hippocampus provided incremental timing signals from one item presentation to the next, whereas perirhinal cortex signaled the conjunction of items and their relative temporal order. Thus, perirhinal cortex appeared to integrate timing information from hippocampus with item information from visual sensory area TE.
Supporting online material


RESEARCH ARTICLE: Epidermal Electronics

Abstract: We report classes of electronic systems that achieve thicknesses, effective elastic moduli, bending stiffnesses, and areal mass densities matched to the epidermis. Unlike traditional wafer-based technologies, laminating such devices onto the skin leads to conformal contact and adequate adhesion based on van der Waals interactions alone, in a manner that is mechanically invisible to the user. We describe systems incorporating electrophysiological, temperature, and strain sensors, as well as transistors, light-emitting diodes, photodetectors, radio frequency inductors, capacitors, oscillators, and rectifying diodes. Solar cells and wireless coils provide options for power supply. We used this type of technology to measure electrical activity produced by the heart, brain, and skeletal muscles and show that the resulting data contain sufficient information for an unusual type of computer game controller.
Supporting online material


REPORT: A Synthetic Nickel Electrocatalyst with a Turnover Frequency Above 100,000 s-1 for H2 Production

Abstract: Reduction of acids to molecular hydrogen as a means of storing energy is catalyzed by platinum, but its low abundance and high cost are problematic. Precisely controlled delivery of protons is critical in hydrogenase enzymes in nature that catalyze hydrogen (H2) production using earth-abundant metals (iron and nickel). Here, we report that a synthetic nickel complex, [Ni(PPh2NPh)2](BF4)2, (PPh2NPh = 1,3,6-triphenyl-1-aza-3,6-diphosphacycloheptane), catalyzes the production of H2 using protonated dimethylformamide as the proton source, with turnover frequencies of 33,000 per second (s-1) in dry acetonitrile and 106,000 s-1 in the presence of 1.2 M of water, at a potential of −1.13 volt (versus the ferrocenium/ferrocene couple). The mechanistic implications of these remarkably fast catalysts point to a key role of pendant amines that function as proton relays.
Supporting online material


REPORT: Viviparity and K-Selected Life History in a Mesozoic Marine Plesiosaur (Reptilia, Sauropterygia)

Abstract: Viviparity is known in several clades of Mesozoic aquatic reptiles, but evidence for it is lacking in the Plesiosauria. Here, we report a Late Cretaceous plesiosaur fossil consisting of a fetus preserved within an adult of the same taxon. We interpret this occurrence as a gravid female and unborn young and hence as definitive evidence for plesiosaur viviparity. Quantitative analysis indicates that plesiosaurs gave birth to large, probably single progeny. The combination of viviparity, large offspring size, and small brood number differs markedly from the pattern seen in other marine reptiles but does resemble the K-selected strategy of all extant marine mammals and a few extant lizards. Plesiosaurs may have shared other life history traits with these clades, such as sociality and maternal care.
Supporting online material


REPORT: Race, Ethnicity, and NIH Research Awards

Abstract: We investigated the association between a U.S. National Institutes of Health (NIH) R01 applicant’s self-identified race or ethnicity and the probability of receiving an award by using data from the NIH IMPAC II grant database, the Thomson Reuters Web of Science, and other sources. Although proposals with strong priority scores were equally likely to be funded regardless of race, we find that Asians are 4 percentage points and black or African-American applicants are 13 percentage points less likely to receive NIH investigator-initiated research funding compared with whites. After controlling for the applicant’s educational background, country of origin, training, previous research awards, publication record, and employer characteristics, we find that black applicants remain 10 percentage points less likely than whites to be awarded NIH research funding. Our results suggest some leverage points for policy intervention.
Supporting online material


REPORT: Graduate Students’ Teaching Experiences Improve Their Methodological Research Skills

Abstract: Science, technology, engineering, and mathematics (STEM) graduate students are often encouraged to maximize their engagement with supervised research and minimize teaching obligations. However, the process of teaching students engaged in inquiry provides practice in the application of important research skills. Using a performance rubric, we compared the quality of methodological skills demonstrated in written research proposals for two groups of early career graduate students (those with both teaching and research responsibilities and those with only research responsibilities) at the beginning and end of an academic year. After statistically controlling for preexisting differences between groups, students who both taught and conducted research demonstrate significantly greater improvement in their abilities to generate testable hypotheses and design valid experiments. These results indicate that teaching experience can contribute substantially to the improvement of essential research skills.
Supporting online material


REPORT: Rapid Range Shifts of Species Associated with High Levels of Climate Warming

Abstract: The distributions of many terrestrial organisms are currently shifting in latitude or elevation in response to changing climate. Using a meta-analysis, we estimated that the distributions of species have recently shifted to higher elevations at a median rate of 11.0 meters per decade, and to higher latitudes at a median rate of 16.9 kilometers per decade. These rates are approximately two and three times faster than previously reported. The distances moved by species are greatest in studies showing the highest levels of warming, with average latitudinal shifts being generally sufficient to track temperature changes. However, individual species vary greatly in their rates of change, suggesting that the range shift of each species depends on multiple internal species traits and external drivers of change. Rapid average shifts derive from a wide diversity of responses by individual species.
Supporting online material


REVIEW: Mitochondria and the Autophagy–Inflammation–Cell Death Axis in Organismal Aging

Abstract: Alterations of mitochondrial functions are linked to multiple degenerative or acute diseases. As mitochondria age in our cells, they become progressively inefficient and potentially toxic, and acute damage can trigger the permeabilization of mitochondrial membranes to initiate apoptosis or necrosis. Moreover, mitochondria have an important role in pro-inflammatory signaling. Autophagic turnover of cellular constituents, be it general or specific for mitochondria (mitophagy), eliminates dysfunctional or damaged mitochondria, thus counteracting degeneration, dampening inflammation, and preventing unwarranted cell loss. Decreased expression of genes that regulate autophagy or mitophagy can cause degenerative diseases in which deficient quality control results in inflammation and the death of cell populations. Thus, a combination of mitochondrial dysfunction and insufficient autophagy may contribute to multiple aging-associated pathologies.
Supporting online material


REPORT: Incipient Space Weathering Observed on the Surface of Itokawa Dust Particles

Abstract: The reflectance spectra of the most abundant meteorites, ordinary chondrites, are different from those of the abundant S-type (mnemonic for siliceous) asteroids. This discrepancy has been thought to be due to space weathering, which is an alteration of the surfaces of airless bodies exposed to the space environment. Here we report evidence of space weathering on particles returned from the S-type asteroid 25143 Itokawa by the Hayabusa spacecraft. Surface modification was found in 5 out of 10 particles, which varies depending on mineral species. Sulfur-bearing Fe-rich nanoparticles exist in a thin (5 to 15 nanometers) surface layer on olivine, low-Ca pyroxene, and plagioclase, which is suggestive of vapor deposition. Sulfur-free Fe-rich nanoparticles exist deeper inside (<60 nanometers) ferromagnesian silicates. Their texture suggests formation by metamictization and in situ reduction of Fe2+.
Supporting online material


REPORT: Expanding the Genetic Code of Escherichia coli with Phosphoserine

Abstract: O-Phosphoserine (Sep), the most abundant phosphoamino acid in the eukaryotic phosphoproteome, is not encoded in the genetic code, but synthesized posttranslationally. Here, we present an engineered system for specific cotranslational Sep incorporation (directed by UAG) into any desired position in a protein by an Escherichia coli strain that harbors a Sep-accepting transfer RNA (tRNASep), its cognate Sep–tRNA synthetase (SepRS), and an engineered EF-Tu (EF-Sep). Expanding the genetic code rested on reengineering EF-Tu to relax its quality-control function and permit Sep-tRNASep binding. To test our system, we synthesized the activated form of human mitogen-activated ERK activating kinase 1 (MEK1) with either one or two Sep residues cotranslationally inserted in their canonical positions (Sep218, Sep222). This system has general utility in protein engineering, molecular biology, and disease research.
Supporting online material


In Science Signaling

RESEARCH ARTICLE: Quantitative Encoding of the Effect of a Partial Agonist on Individual Opioid Receptors by Multisite Phosphorylation and Threshold Detection

Abstract: In comparison to endogenous ligands of seven-transmembrane receptors, which typically act as full agonists, many drugs act as partial agonists. Partial agonism is best described as a "macroscopic" property that is manifest at the level of physiological systems or cell populations; however, whether partial agonists also encode discrete regulatory information at the "microscopic" level of individual receptors is not known. Here, we addressed this question by focusing on morphine, a partial agonist drug for µ-type opioid peptide receptors (MORs), and by combining quantitative mass spectrometry with cell biological analysis to investigate the reduced efficacy of morphine, compared to that of a peptide full agonist, in promoting receptor endocytosis. We showed that these chemically distinct ligands produced a complex and qualitatively similar mixture of phosphorylated opioid receptor forms in intact cells. Quantitatively, however, the different agonists promoted disproportionate multisite phosphorylation of a specific serine and threonine motif, and we found that modification at more than one residue was essential for the efficient recruitment of the adaptor protein β-arrestin that mediated subsequent endocytosis of MORs. Thus, quantitative encoding of agonist-selective endocytosis at the level of individual opioid receptors was based on the conserved biochemical principles of multisite phosphorylation and threshold detection.
Supplementary Materials


RESEARCH ARTICLE: Yeast Dynamically Modify Their Environment to Achieve Better Mating Efficiency

Abstract: The maintenance and detection of signaling gradients are critical for proper development and cell migration. In single-cell organisms, gradient detection allows cells to orient toward a distant mating partner or nutrient source. Budding yeast expand their growth toward mating pheromone gradients through a process known as chemotropic growth. MATα cells secrete α-factor pheromone that stimulates chemotropism and mating differentiation in MATa cells and vice versa. Paradoxically, MATa cells secrete Bar1, a protease that degrades α-factor and that attenuates the mating response, yet is also required for efficient mating. We observed that MATa cells avoid each other during chemotropic growth. To explore this behavior, we developed a computational platform to simulate chemotropic growth. Our simulations indicated that the release of Bar1 enabled individual MATa cells to act as α-factor sinks. The simulations suggested that the resultant local reshaping of pheromone concentration created gradients that were directed away from neighboring MATa cells (self-avoidance) and that were increasingly amplified toward partners of the opposite sex during elongation. The behavior of Bar1-deficient cells in gradient chambers and mating assays supported these predictions from the simulations. Thus, budding yeast dynamically remodel their environment to ensure productive responses to an external stimulus and avoid nonproductive cell-cell interactions.
Supplementary Materials


RESEARCH ARTICLE: Tumor Progression Locus 2 Mediates Signal-Induced Increases in Cytoplasmic Calcium and Cell Migration

Abstract: The mitogen-activated protein kinase kinase kinase (MAPKKK or MAP3K) tumor progression locus 2 (Tpl2) is required for the transduction of signals initiated by the thrombin-activated G protein–coupled receptor (GPCR) protease-activated receptor-1 (PAR1), which promote reorganization of the actin cytoskeleton and cell migration. Here, we show that Tpl2 is activated through Gαi2-transduced GPCR signals. Activated Tpl2 promoted the phosphorylation and activation of phospholipase C–β3 (PLCβ3); consequently, Tpl2 was required for thrombin-dependent production of inositol 1,4,5-trisphosphate (IP3), IP3-mediated cytoplasmic calcium ion (Ca2+) signals, and the activation of classical and novel members of the protein kinase C (PKC) family. A PKC-mediated feedback loop facilitated extracellular signal–regulated kinase (ERK) activation in response to Tpl2 and contributed to the coordinate regulation of the ERK and Ca2+ signaling pathways. Pharmacological and genetic studies revealed that stimulation of cell migration by Tpl2 depends on both of these pathways. Tpl2 also promoted Ca2+ signals and cell migration from sphingosine 1-phosphate–responsive GPCRs, which also couple to Gαi; from Wnt5a; and from the interleukin-1β (IL-1β) receptor, a member of the Toll–IL-1R (TIR) domain family. Our data provide new insights into the role of Tpl2 in GPCR-mediated Ca2+ signaling and cell migration.
Supplementary Materials


RESEARCH ARTICLE: Rational Design of a Meningococcal Antigen Inducing Broad Protective Immunity

Abstract: The sequence variability of protective antigens is a major challenge to the development of vaccines. For Neisseria meningitides, the bacterial pathogen that causes meningitis, the amino acid sequence of the protective antigen factor H binding protein (fHBP) has more than 300 variations. These sequence differences can be classified into three distinct groups of antigenic variants that do not induce cross-protective immunity. Our goal was to generate a single antigen that would induce immunity against all known sequence variants of N. meningitides. To achieve this, we rationally designed, expressed, and purified 54 different mutants of fHBP and tested them in mice for the induction of protective immunity. We identified and determined the crystal structure of a lead chimeric antigen that was able to induce high levels of cross-protective antibodies in mice against all variant strains tested. The new fHBP antigen had a conserved backbone that carried an engineered surface containing specificities for all three variant groups. We demonstrate that the structure-based design of multiple immunodominant antigenic surfaces on a single protein scaffold is possible and represents an effective way to create broadly protective vaccines.
Supplementary material


In Science Translational Medicine

RESEARCH ARTICLE: Targeting GLUT1 and the Warburg Effect in Renal Cell Carcinoma by Chemical Synthetic Lethality

Abstract:Identifying new targeted therapies that kill tumor cells while sparing normal tissue is a major challenge of cancer research. Using a high-throughput chemical synthetic lethal screen, we sought to identify compounds that exploit the loss of the von Hippel–Lindau (VHL) tumor suppressor gene, which occurs in about 80% of renal cell carcinomas (RCCs). RCCs, like many other cancers, are dependent on aerobic glycolysis for ATP production, a phenomenon known as the Warburg effect. The dependence of RCCs on glycolysis is in part a result of induction of glucose transporter 1 (GLUT1). Here, we report the identification of a class of compounds, the 3-series, exemplified by STF-31, which selectively kills RCCs by specifically targeting glucose uptake through GLUT1 and exploiting the unique dependence of these cells on GLUT1 for survival. Treatment with these agents inhibits the growth of RCCs by binding GLUT1 directly and impeding glucose uptake in vivo without toxicity to normal tissue. Activity of STF-31 in these experimental renal tumors can be monitored by [18F]fluorodeoxyglucose uptake by micro–positron emission tomography imaging, and therefore, these agents may be readily tested clinically in human tumors. Our results show that the Warburg effect confers distinct characteristics on tumor cells that can be selectively targeted for therapy.
Supplementary material


PERSPECTIVE: The Emergence of Genome-Based Drug Repositioning

Abstract: In a pair of papers in this issue of Science Translational Medicine, Butte et al. provide a concrete example of how reinterpreting and comparing genome-wide metrics allows us to effectively hypothesize which drugs from one disease-indication can be repurposed for another disease. The shift toward integrative genome-wide computational approaches has precedence in insightful scalar theories of biological information. Here, we discuss how this recent work in drug repurposing adheres to and takes advantage of the concepts surrounding this information paradigm.


COMMENTARY: Herding CATS

Abstract:The U.S. National Institutes of Health’s new National Center for Advancing Translational Sciences (NCATS) should be refocused to spur innovation and renamed in a way that doesn’t further polarize the scientific community. This Commentary offers some suggestions for both types of transformations.

Sponsored by:

AAAS + U = Δ

Give your friend or loved one the gift of Science and a AAAS Membership!
Includes 51 issues of Science, Science Online, and all AAAS member benefits.

When you give someone the gift of a AAAS membership, they get a subscription to Science, and so much more. Your gift goes to support real-world programs that are making an impact in areas including science policy, diplomacy, public engagement and dialogue, workforce development and diversity, and education.