Proceedings of the Natural Academy of Sciences

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  • Substrate stiffness mediates platelet physiology [Applied Physical Sciences]
    [Oct 2014]

    As platelets aggregate and activate at the site of vascular injury to stem bleeding, they are subjected to a myriad of biochemical and biophysical signals and cues. As clot formation ensues, platelets interact with polymerizing fibrin scaffolds, exposing platelets to a large range of mechanical microenvironments. Here, we show for...
    Categories: Journal Articles
  • Tuning without resonance in a fluid waveguide [Applied Physical Sciences]
    [Oct 2014]

    This study analyzes a waveguide consisting of two parallel fluid-filled chambers connected by a narrow slit that is spanned by two coupled elastic beams. A stiffness gradient exists in the longitudinal direction. This simple linear system, which contains no lumped mass, is shown to act as a spectral analyzer. Fluid...
    Categories: Journal Articles
  • Blocking mitochondrial protein import in PH1 [Biochemistry]
    [Oct 2014]

    Primary hyperoxaluria 1 (PH1; Online Mendelian Inheritance in Man no. 259900), a typically lethal biochemical disorder, may be caused by the AGTP11LG170R allele in which the alanine:glyoxylate aminotransferase (AGT) enzyme is mistargeted from peroxisomes to mitochondria. AGT contains a C-terminal peroxisomal targeting sequence, but mutations generate an N-terminal mitochondrial targeting...
    Categories: Journal Articles
  • Cardiac TnI[1-37] positions TnC regulatory domain [Biochemistry]
    [Oct 2014]

    The cardiac isoform of troponin I (cTnI) has a unique 31-residue N-terminal region that binds cardiac troponin C (cTnC) to increase the calcium sensitivity of the sarcomere. The interaction can be abolished by cTnI phosphorylation at Ser22 and Ser23, an important mechanism for regulating cardiac contractility. cTnC contains two EF–hand...
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  • Mechanism of a translational GTPase [Biochemistry]
    [Oct 2014]

    GTP hydrolysis by elongation factor Tu (EF-Tu), a translational GTPase that delivers aminoacyl-tRNAs to the ribosome, plays a crucial role in decoding and translational fidelity. The basic reaction mechanism and the way the ribosome contributes to catalysis are a matter of debate. Here we use mutational analysis in combination with...
    Categories: Journal Articles
  • RIPK1 inhibits RIPK3 to maintain hematopoiesis [Cell Biology]
    [Oct 2014]

    Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is recruited to the TNF receptor 1 to mediate proinflammatory signaling and to regulate TNF-induced cell death. RIPK1 deficiency results in postnatal lethality, but precisely why Ripk1−/− mice die remains unclear. To identify the lineages and cell types that depend on RIPK1 for survival, we...
    Categories: Journal Articles
  • Gelsolin confers chemoresistance [Cell Biology]
    [Oct 2014]

    Chemoresistance is a major hurdle in cancer treatment. Down-regulation of apoptosis pathways is one of the key determinants for chemoresistance. Here, we report higher gelsolin (GSN) levels in chemoresistant gynecological cancer cells compared with their sensitive counterparts. cis-Diammine dichloroplatinium (II) (CDDP)-induced GSN down-regulation is associated with its cleavage and apoptosis....
    Categories: Journal Articles
  • Memory in chemotaxis [Cell Biology]
    [Oct 2014]

    Natural chemical gradients to which cells respond chemotactically are often dynamic, with both spatial and temporal components. A primary example is the social amoeba Dictyostelium, which migrates to the source of traveling waves of chemoattractant as part of a self-organized aggregation process. Despite its physiological importance, little is known about...
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  • Transcription defects in Cockayne syndrome [Cell Biology]
    [Oct 2014]

    Cockayne syndrome (CS) is a multisystem disorder with severe neurological symptoms. The majority of CS patients carry mutations in Cockayne syndrome group B (CSB), best known for its role in transcription-coupled nucleotide excision repair. Indeed, because various repair pathways are compromised in patient cells, CS is widely considered a genome...
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  • Compound from Hoodia activates GPR119 [Chemistry]
    [Oct 2014]

    African cactiform Hoodia gordonii (Asclepiadaceae) has been used for thousands of years by Xhomani Bushmen as an anorexant during hunting trips and has been proposed as a new agent for the management of body weight. However, its in vivo targets and molecular mechanisms remain elusive. GPR119, a G protein-coupled receptor...
    Categories: Journal Articles
  • Mosquito-specific microRNA [Developmental Biology]
    [Oct 2014]

    Lineage-specific microRNAs (miRNAs) may contribute to functions specific to hematophagous mosquitoes and, as such, have potential for contributing to the development of future mosquito control approaches. Here we report that the mosquito- and gut-specific miRNA, miR-1174, is required for proper sugar absorption, fluid excretion, blood intake, and, consequently, egg maturation...
    Categories: Journal Articles
  • Ebf2 expression identifies brown preadipose cells [Developmental Biology]
    [Oct 2014]

    Brown adipocytes and muscle and dorsal dermis descend from precursor cells in the dermomyotome, but the factors that regulate commitment to the brown adipose lineage are unknown. Here, we prospectively isolated and determined the molecular profile of embryonic brown preadipose cells. Brown adipogenic precursor activity in embryos was confined to...
    Categories: Journal Articles
  • Soil communities and ecosystem multifunctionality [Ecology]
    [Oct 2014]

    Ecosystem management policies increasingly emphasize provision of multiple, as opposed to single, ecosystem services. Management for such “multifunctionality” has stimulated research into the role that biodiversity plays in providing desired rates of multiple ecosystem processes. Positive effects of biodiversity on indices of multifunctionality are consistently found, primarily because species that...
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  • Theory of development resilience [Economic Sciences]
    [Oct 2014]

    We advance a theory of resilience as it applies to the challenges of international development. The conceptualization we advance for development resilience focuses on the stochastic dynamics of individual and collective human well-being, especially on the avoidance of and escape from chronic poverty over time in the face of myriad...
    Categories: Journal Articles
  • Structural adaptations in beetle horns [Evolution]
    [Oct 2014]

    The shapes of sexually selected weapons differ widely among species, but the drivers of this diversity remain poorly understood. Existing explanations suggest weapon shapes reflect structural adaptations to different fighting styles, yet explicit tests of this hypothesis are lacking. We constructed finite element models of the horns of different rhinoceros...
    Categories: Journal Articles
  • Divergent adaptation to drought in conifers [Evolution]
    [Oct 2014]

    Water stress is one of the primary selective forces in plant evolution. There are characters often cited as adaptations to water stress, but links between the function of these traits and adaptation to drying climates are tenuous. Here we combine distributional, climatic, and physiological evidence from 42 species of conifers...
    Categories: Journal Articles
  • Alternating drugs constrains paths to resistance [Evolution]
    [Oct 2014]

    Alternating antibiotic therapy, in which pairs of drugs are cycled during treatment, has been suggested as a means to inhibit the evolution of de novo resistance while avoiding the toxicity associated with more traditional combination therapy. However, it remains unclear under which conditions and by what means such alternating treatments...
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  • Symbiotic complementary substrate decomposition [Evolution]
    [Oct 2014]

    Termites normally rely on gut symbionts to decompose organic matter but the Macrotermitinae domesticated Termitomyces fungi to produce their own food. This transition was accompanied by a shift in the composition of the gut microbiota, but the complementary roles of these bacteria in the symbiosis have remained enigmatic. We obtained...
    Categories: Journal Articles
  • NK- and T-cell responses to influenza in pregnancy [Immunology and Inflammation]
    [Oct 2014]

    Pregnant women experience increased morbidity and mortality after influenza infection, for reasons that are not understood. Although some data suggest that natural killer (NK)- and T-cell responses are suppressed during pregnancy, influenza-specific responses have not been previously evaluated. Thus, we analyzed the responses of women that were pregnant (n =...
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  • Insulin/IGF1 receptors and imprinted genes [Medical Sciences]
    [Oct 2014]

    In addition to signaling through the classical tyrosine kinase pathway, recent studies indicate that insulin receptors (IRs) and insulin-like growth factor 1 (IGF1) receptors (IGF1Rs) can emit signals in the unoccupied state through some yet-to-be-defined noncanonical pathways. Here we show that cells lacking both IRs and IGF1Rs exhibit a major...
    Categories: Journal Articles