Proceedings of the Natural Academy of Sciences

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  • Role of Jagged in tip-stalk fate decision [Biophysics and Computational Biology]
    [Jul 2015]

    Angiogenesis is critical during development, wound repair, and cancer progression. During angiogenesis, some endothelial cells adopt a tip phenotype to lead the formation of new branching vessels; the trailing stalk cells proliferate to develop the vessel. Notch and VEGF signaling mediate the selection of these tip endothelial cells. However, how...
    Categories: Journal Articles
  • CynA localizes and functions at the cell rear [Cell Biology]
    [Jul 2015]

    Asymmetric protein localization is essential for cell polarity and migration. We report a novel protein, Callipygian (CynA), which localizes to the lagging edge before other proteins and becomes more tightly restricted as cells polarize; additionally, it accumulates in the cleavage furrow during cytokinesis. CynA protein that is tightly localized, or...
    Categories: Journal Articles
  • Innate drug resistance to EGFR inhibitors [Cell Biology]
    [Jul 2015]

    Nonsmall cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. About 14% of NSCLCs harbor mutations in epidermal growth factor receptor (EGFR). Despite remarkable progress in treatment with tyrosine kinase inhibitors (TKIs), only 5% of patients achieve tumor reduction >90%. The limited primary responses are attributed partly...
    Categories: Journal Articles
  • Lin28b regulates timing of cochlear development [Developmental Biology]
    [Jul 2015]

    Proper tissue development requires strict coordination of proliferation, growth, and differentiation. Strict coordination is particularly important for the auditory sensory epithelium, where deviations from the normal spatial and temporal pattern of auditory progenitor cell (prosensory cell) proliferation and differentiation result in abnormal cellular organization and, thus, auditory dysfunction. The molecular...
    Categories: Journal Articles
  • Parabiosis in the age of leptin [Genetics]
    [Jul 2015]

    In this study we set out to explain the differing effects of parabiosis with genetically diabetic (db) mice versus administration of recombinant leptin. Parabiosis of db mutant, which overexpress leptin, to wildtype (WT) or genetically obese (ob) mice has been reported to cause death by starvation, whereas leptin infusions do...
    Categories: Journal Articles
  • lncRNA regulates CD8+ T-cell immune response in TB [Immunology and Inflammation]
    [Jul 2015]

    Molecular mechanisms for T-cell immune responses modulated by T cell-inhibitory molecules during tuberculosis (TB) infection remain unclear. Here, we show that active human TB infection up-regulates CD244 and CD244 signaling-associated molecules in CD8+ T cells and that blockade of CD244 signaling enhances production of IFN-γ and TNF-α. CD244 expression/signaling in...
    Categories: Journal Articles
  • PDGFB increases bone formation and bone strength [Medical Sciences]
    [Jul 2015]

    Substantial advances have been made in the past two decades in the management of osteoporosis. However, none of the current medications can eliminate the risk of fracture and rejuvenate the skeleton. To this end, we recently reported that transplantation of hematopoietic stem/progenitor cells (HSCs) or Sca1+ cells engineered to overexpress...
    Categories: Journal Articles
  • gL dissociation from gH/gL mediated by integrins [Microbiology]
    [Jul 2015]

    Herpes simplex virus (HSV) is an important human pathogen. It enters cells through an orchestrated process that requires four essential glycoproteins, gD, gH/gL, and gB, activated in cascade fashion by receptor-binding and signaling. gH/gL heterodimer is conserved across the Herpesviridae family. HSV entry is enabled by gH/gL interaction with αvβ6-...
    Categories: Journal Articles
  • Multiple GABA signals in the circadian clock [Neuroscience]
    [Jul 2015]

    The suprachiasmatic nuclei (SCN), the central circadian pacemakers in mammals, comprise a multiscale neuronal system that times daily events. We use recent advances in graphics processing unit computing to generate a multiscale model for the SCN that resolves cellular electrical activity down to the timescale of individual action potentials and...
    Categories: Journal Articles
  • Day-length encoding by GABA coupling [Neuroscience]
    [Jul 2015]

    The mammalian suprachiasmatic nucleus (SCN) forms not only the master circadian clock but also a seasonal clock. This neural network of ∼10,000 circadian oscillators encodes season-dependent day-length changes through a largely unknown mechanism. We show that region-intrinsic changes in the SCN fine-tune the degree of network synchrony and reorganize the...
    Categories: Journal Articles
  • Altered decision-making in addiction [Neuroscience]
    [Jul 2015]

    Patients suffering from neuropsychiatric disorders such as substance-related and addictive disorders exhibit altered decision-making patterns, which may be associated with their behavioral abnormalities. However, the neuronal mechanisms underlying such impairments are largely unknown. Using a gambling test, we demonstrated that methamphetamine (METH)-treated rats chose a high-risk/high-reward option more frequently and...
    Categories: Journal Articles
  • Structure of LacY/{alpha}-substituted galactoside [Biochemistry]
    [Jul 2015]

    The X-ray crystal structure of a conformationally constrained mutant of the Escherichia coli lactose permease (the LacY double-Trp mutant Gly-46→Trp/Gly-262→Trp) with bound p-nitrophenyl-α-d-galactopyranoside (α-NPG), a high-affinity lactose analog, is described. With the exception of Glu-126 (helix IV), side chains Trp-151 (helix V), Glu-269 (helix VIII), Arg-144 (helix V), His-322 (helix...
    Categories: Journal Articles
  • Viral nuclear egress complex subunit structure [Biophysics and Computational Biology]
    [Jul 2015]

    Herpesviruses require a nuclear egress complex (NEC) for efficient transit of nucleocapsids from the nucleus to the cytoplasm. The NEC orchestrates multiple steps during herpesvirus nuclear egress, including disruption of nuclear lamina and particle budding through the inner nuclear membrane. In the important human pathogen human cytomegalovirus (HCMV), this complex...
    Categories: Journal Articles
  • Anomalous water inside the SecY translocon [Biophysics and Computational Biology]
    [Jul 2015]

    The heterotrimeric SecY translocon complex is required for the cotranslational assembly of membrane proteins in bacteria and archaea. The insertion of transmembrane (TM) segments during nascent-chain passage through the translocon is generally viewed as a simple partitioning process between the water-filled translocon and membrane lipid bilayer, suggesting that partitioning is...
    Categories: Journal Articles
  • Conformation changes of cytochrome P450cam [Biophysics and Computational Biology]
    [Jul 2015]

    The energy landscapes of proteins are highly complex and can be influenced by changes in physical and chemical conditions under which the protein is studied. The redox enzyme cytochrome P450cam undergoes a multistep catalytic cycle wherein two electrons are transferred to the heme group and the enzyme visits several conformational...
    Categories: Journal Articles
  • Structure of IgG Fc-protein A complex [Biophysics and Computational Biology]
    [Jul 2015]

    Staphylococcal protein A (SpA) is an important virulence factor from Staphylococcus aureus responsible for the bacterium’s evasion of the host immune system. SpA includes five small three-helix–bundle domains that can each bind with high affinity to many host proteins such as antibodies. The interaction between a SpA domain and the...
    Categories: Journal Articles
  • NF1 hyperpigmentation modeling using hESCs [Cell Biology]
    [Jul 2015]

    “Café-au-lait” macules (CALMs) and overall skin hyperpigmentation are early hallmarks of neurofibromatosis type 1 (NF1). One of the most frequent monogenic diseases, NF1 has subsequently been characterized with numerous benign Schwann cell-derived tumors. It is well established that neurofibromin, the NF1 gene product, is an antioncogene that down-regulates the RAS...
    Categories: Journal Articles
  • A lipid-binding domain in the ATP13A2 N terminus [Cell Biology]
    [Jul 2015]

    ATP13A2 is a lysosomal P-type transport ATPase that has been implicated in Kufor–Rakeb syndrome and Parkinson’s disease (PD), providing protection against α-synuclein, Mn2+, and Zn2+ toxicity in various model systems. So far, the molecular function and regulation of ATP13A2 remains undetermined. Here, we demonstrate that ATP13A2 contains a unique N-terminal...
    Categories: Journal Articles
  • Spatiotemporal variations in surface reactivity [Chemistry]
    [Jul 2015]

    For the practical application of nanocatalysts, it is desirable to understand the spatiotemporal fluctuations of nanocatalytic activity at the single-nanoparticle level. Here we use time-lapsed superresolution mapping of single-molecule catalysis events on individual nanoparticles to observe time-varying changes in the spatial distribution of catalysis events on Sb-doped TiO2 nanorods and...
    Categories: Journal Articles
  • Maximum likelihood refinement for small datasets [Chemistry]
    [Jul 2015]

    The crystallographic reliability index Rcomplete is based on a method proposed more than two decades ago. Because its calculation is computationally expensive its use did not spread into the crystallographic community in favor of the cross-validation method known as Rfree. The importance of Rfree has grown beyond a pure validation...
    Categories: Journal Articles