Proceedings of the Natural Academy of Sciences

Proceedings of the National Academy of Sciences RSS feed -- current issue
  • Stochastic epigenetic variation and evolution [Evolution]
    [Apr 2014]

    Evolution by gene duplication is generally accepted as one of the crucial driving forces for the gain of new complexity and functions, but the formation of pseudogenes remains a problem for this mechanism. Here we expand on earlier ideas that epigenetic modifications can drive neo- and subfunctionalization in evolution by...
    Categories: Journal Articles
  • Partner choice in an ancient defensive symbiosis [Evolution]
    [Apr 2014]

    Many insects rely on symbiotic microbes for survival, growth, or reproduction. Over evolutionary timescales, the association with intracellular symbionts is stabilized by partner fidelity through strictly vertical symbiont transmission, resulting in congruent host and symbiont phylogenies. However, little is known about how symbioses with extracellular symbionts, representing the majority of...
    Categories: Journal Articles
  • Uridylation of miRNAs and 5' cleavage products [Genetics]
    [Apr 2014]

    In plants, methylation catalyzed by HEN1 (small RNA methyl transferase) prevents microRNAs (miRNAs) from degradation triggered by uridylation. How methylation antagonizes uridylation of miRNAs in vivo is not well understood. In addition, 5′ RNA fragments (5′ fragments) produced by miRNA-mediated RNA cleavage can be uridylated in plants and animals. However,...
    Categories: Journal Articles
  • Optical control of T-cell migration [Immunology]
    [Apr 2014]

    Adoptive cell transfer of ex vivo-generated immune-promoting or tolerogenic T cells to either enhance immunity or promote tolerance in patients has been used with some success. However, effective trafficking of the transferred cells to the target tissue sites is the main barrier to achieving successful clinical outcomes. Here we developed...
    Categories: Journal Articles
  • Stretched cell cycle model [Immunology]
    [Apr 2014]

    Stochastic variation in cell cycle time is a consistent feature of otherwise similar cells within a growing population. Classic studies concluded that the bulk of the variation occurs in the G1 phase, and many mathematical models assume a constant time for traversing the S/G2/M phases. By direct observation of transgenic...
    Categories: Journal Articles
  • EphB4 and PDGFR{beta} in alveolar rhabdomyosarcoma [Medical Sciences]
    [Apr 2014]

    Alveolar rhabdomyosarcoma (aRMS) is an aggressive myogenic childhood malignancy, not infrequently presenting as incurable metastatic disease. To identify therapeutic targets, we performed an unbiased tyrosine kinome RNA interference screen in primary cell cultures from a genetically engineered, conditional mouse model of aRMS. We identified ephrin receptor B4 (EphB4) as a...
    Categories: Journal Articles
  • TrpC5-containing EVs and chemoresistance [Medical Sciences]
    [Apr 2014]

    A critical challenge for chemotherapy is the development of chemoresistance in breast cancer. However, the underlying mechanisms and validated predictors remain unclear. Extracellular vesicles (EVs) have gained attention as potential means for cancer cells to share intracellular contents. In adriamycin-resistant human breast cancer cells (MCF-7/ADM), we analyzed the role of...
    Categories: Journal Articles
  • Genetic determinants of PI3K isoform dependency [Medical Sciences]
    [Apr 2014]

    There has been increasing interest in the use of isoform-selective inhibitors of phosphatidylinositide-3-kinase (PI3K) in cancer therapy. Using conditional deletion of the p110 catalytic isoforms of PI3K to predict sensitivity of cancer types to such inhibitors, we and others have demonstrated that tumors deficient of the phosphatase and tensin homolog...
    Categories: Journal Articles
  • Preventing influenza by targeting host receptors [Microbiology]
    [Apr 2014]

    There is a need for new approaches for the control of influenza given the burden caused by annual seasonal outbreaks, the emergence of viruses with pandemic potential, and the development of resistance to current antiviral drugs. We show that multivalent biologics, engineered using carbohydrate-binding modules specific for sialic acid, mask...
    Categories: Journal Articles
  • Regulation of bacterial glycan chain length [Microbiology]
    [Apr 2014]

    The lengths of bacterial polysaccharides can be critical for their biological function. Unlike DNA or protein synthesis, where polymer length is implicit in the nucleic acid template, the molecular mechanisms for regulating polysaccharide length are poorly understood. Two models are commonly cited: a “molecular clock” regulates length by controlling the...
    Categories: Journal Articles
  • HCV-induced mitochondrial fission [Microbiology]
    [Apr 2014]

    Mitochondrial dynamics is crucial for the regulation of cell homeostasis. Our recent findings suggest that hepatitis C virus (HCV) promotes Parkin-mediated elimination of damaged mitochondria (mitophagy). Here we show that HCV perturbs mitochondrial dynamics by promoting mitochondrial fission followed by mitophagy, which attenuates HCV-induced apoptosis. HCV infection stimulated expression of...
    Categories: Journal Articles
  • Acetyl-CoA cleavage and CO release in D. mccartyi [Microbiology]
    [Apr 2014]

    The acetyl-CoA “Wood–Ljungdahl” pathway couples the folate-mediated one-carbon (C1) metabolism to either CO2 reduction or acetate oxidation via acetyl-CoA. This pathway is distributed in diverse anaerobes and is used for both energy conservation and assimilation of C1 compounds. Genome annotations for all sequenced strains of Dehalococcoides mccartyi, an important bacterium...
    Categories: Journal Articles
  • Tetherin antagonism by Vpu protects HIV from ADCC [Microbiology]
    [Apr 2014]

    Tetherin is an IFN-inducible transmembrane protein that inhibits the detachment of enveloped viruses from infected cells. HIV-1 overcomes this restriction factor by expressing HIV-1 viral protein U (Vpu), which down-regulates and degrades tetherin. We report that mutations in Vpu that impair tetherin antagonism increase the susceptibility of HIV-infected cells to...
    Categories: Journal Articles
  • LRP1 is a host cell receptor for TpeL toxin [Microbiology]
    [Apr 2014]

    Large glycosylating toxins are major virulence factors of various species of pathogenic Clostridia. Prototypes are Clostridium difficile toxins A and B, which cause antibiotics-associated diarrhea and pseudomembranous colitis. The current model of the toxins’ action suggests that receptor binding is mediated by a C-terminal domain of combined repetitive oligopeptides (CROP)....
    Categories: Journal Articles
  • Phagosome to vacuole invasion by T. gondii [Microbiology]
    [Apr 2014]

    Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites...
    Categories: Journal Articles
  • Applying constellation pharmacology to the CNS [Neuroscience]
    [Apr 2014]

    Previously we defined neuronal subclasses within the mouse peripheral nervous system using an experimental strategy called “constellation pharmacology.” Here we demonstrate the broad applicability of constellation pharmacology by extending it to the CNS and specifically to the ventral respiratory column (VRC) of mouse brainstem, a region containing the neuronal network...
    Categories: Journal Articles
  • Optogenetically evoked aversion via D2 receptors [Neuroscience]
    [Apr 2014]

    Dopamine (DA) transmission from the ventral tegmental area (VTA) is critical for controlling both rewarding and aversive behaviors. The transient silencing of DA neurons is one of the responses to aversive stimuli, but its consequences and neural mechanisms regarding aversive responses and learning have largely remained elusive. Here, we report...
    Categories: Journal Articles
  • Protection of spine deterioration by PAK inhibitor [Neuroscience]
    [Apr 2014]

    Drug discovery in psychiatry has been limited to chemical modifications of compounds originally discovered serendipitously. Therefore, more mechanism-oriented strategies of drug discovery for mental disorders are awaited. Schizophrenia is a devastating mental disorder with synaptic disconnectivity involved in its pathophysiology. Reduction in the dendritic spine density is a major alteration...
    Categories: Journal Articles
  • Object attention in visual and frontal cortex [Neuroscience]
    [Apr 2014]

    Models of visual attention hold that top-down signals from frontal cortex influence information processing in visual cortex. It is unknown whether situations exist in which visual cortex actively participates in attentional selection. To investigate this question, we simultaneously recorded neuronal activity in the frontal eye fields (FEF) and primary visual...
    Categories: Journal Articles
  • Mesocircuit dysfunction after severe brain injury [Neuroscience]
    [Apr 2014]

    Although disorders of consciousness (DOCs) demonstrate widely varying clinical presentations and patterns of structural injury, global down-regulation and bilateral reductions in metabolism of the thalamus and frontoparietal network are consistent findings. We test the hypothesis that global reductions of background synaptic activity in DOCs will associate with changes in the...
    Categories: Journal Articles