Proceedings of the Natural Academy of Sciences

Proceedings of the National Academy of Sciences RSS feed -- current issue
  • Continental-level biodiversity collapse [Environmental Sciences]
    [Apr 2015]

    Biodiversity loss is a global phenomenon (1), with Woinarski et al. (2) providing a sobering review of the demise of the Australian native terrestrial mammal fauna. The authors’ focus is on the loss of >10% of endemic terrestrial native mammal fauna since European settlement in 1788. The extent of mammal...
    Categories: Journal Articles
  • Shapely DNA attracts the right partner [Biophysics and Computational Biology]
    [Apr 2015]

    All levels of cell activity are coordinated directly or indirectly by transcription factors (TFs). In turn, the functioning of TFs relies on their ability to recognize and bind specific DNA sequences to regulate the expression of specific genes. How exactly this specificity is achieved is still not fully understood. Although...
    Categories: Journal Articles
  • Immune activation in human Ebola virus infection [Immunology and Inflammation]
    [Apr 2015]

    Ebola viruses (EBOV) are zoonotic infectious agents that are highly pathogenic in humans, causing severe hemorrhagic fever with fatality rates of ∼50–70% (1). This genus of negative single-stranded RNA viruses consists of five known species that are part of the Filoviridae family. The current EBOV outbreak in western Africa began...
    Categories: Journal Articles
  • Renaissance of black phosphorus [Engineering]
    [Apr 2015]

    One hundred years after its first successful synthesis in the bulk form in 1914, black phosphorus (black P) was recently rediscovered from the perspective of a 2D layered material, attracting tremendous interest from condensed matter physicists, chemists, semiconductor device engineers, and material scientists. Similar to graphite and transition metal dichalcogenides...
    Categories: Journal Articles
  • Loss of imprinting in fetal overgrowth [Agricultural Sciences]
    [Apr 2015]

    Embryos generated with the use of assisted reproductive technologies (ART) can develop overgrowth syndromes. In ruminants, the condition is referred to as large offspring syndrome (LOS) and exhibits variable phenotypic abnormalities including overgrowth, enlarged tongue, and abdominal wall defects. These characteristics recapitulate those observed in the human loss-of-imprinting (LOI) overgrowth...
    Categories: Journal Articles
  • Linked topological colloids [Applied Physical Sciences]
    [Apr 2015]

    Geometric shape and topology of constituent particles can alter many colloidal properties such as Brownian motion, self-assembly, and phase behavior. Thus far, only single-component building blocks of colloids with connected surfaces have been studied, although topological colloids, with constituent particles shaped as freestanding knots and handlebodies of different genus, have...
    Categories: Journal Articles
  • {alpha}/{beta}-Peptides targeting diverse protein surfaces [Biochemistry]
    [Apr 2015]

    Peptide-based agents derived from well-defined scaffolds offer an alternative to antibodies for selective and high-affinity recognition of large and topologically complex protein surfaces. Here, we describe a strategy for designing oligomers containing both α- and β-amino acid residues (“α/β-peptides”) that mimic several peptides derived from the three-helix bundle “Z-domain” scaffold....
    Categories: Journal Articles
  • Autoinhibition of MDMX by p53 mimicry [Biochemistry]
    [Apr 2015]

    The p53 inhibitor MDMX is controlled by multiple stress signaling pathways. Using a proteolytic fragment release (PFR) assay, we detected an intramolecular interaction in MDMX that mechanistically mimics the interaction with p53, resulting in autoinhibition of MDMX. This mimicry is mediated by a hydrophobic peptide located in a long disordered...
    Categories: Journal Articles
  • Identification of ubiquitin ligase substrates [Biochemistry]
    [Apr 2015]

    The identification of substrates for ubiquitin ligases has remained challenging, because most substrates are either immediately degraded by the proteasome or processed by deubiquitinating enzymes (DUBs) to remove polyubiquitin. Although a methodology that enables detection of ubiquitinated proteins using ubiquitin Lys-ε-Gly-Gly (diGly) remnant antibodies and MS has been developed, it...
    Categories: Journal Articles
  • Phosphoinositides in phagosome-lysosome fusion [Biochemistry]
    [Apr 2015]

    Professional phagocytic cells ingest microbial intruders by engulfing them into phagosomes, which subsequently mature into microbicidal phagolysosomes. Phagosome maturation requires sequential fusion of the phagosome with early endosomes, late endosomes, and lysosomes. Although various phosphoinositides (PIPs) have been detected on phagosomes, it remained unclear which PIPs actually govern phagosome maturation....
    Categories: Journal Articles
  • JAK2 JH2 ATP binding required for V617F activity [Biochemistry]
    [Apr 2015]

    Pseudokinases lack conserved motifs typically required for kinase activity. Nearly half of pseudokinases bind ATP, but only few retain phosphotransfer activity, leaving the functional role of nucleotide binding in most cases unknown. Janus kinases (JAKs) are nonreceptor tyrosine kinases with a tandem pseudokinase–kinase domain configuration, where the pseudokinase domain (JAK...
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  • Force-induced on-rate switching of VWF [Biophysics and Computational Biology]
    [Apr 2015]

    Mutations in the ultralong vascular protein von Willebrand factor (VWF) cause the common human bleeding disorder, von Willebrand disease (VWD). The A1 domain in VWF binds to glycoprotein Ibα (GPIbα) on platelets, in a reaction triggered, in part, by alterations in flow during bleeding. Gain-of-function mutations in A1 and GPIbα...
    Categories: Journal Articles
  • DNA shape-based models of TF binding specificities [Biophysics and Computational Biology]
    [Apr 2015]

    DNA binding specificities of transcription factors (TFs) are a key component of gene regulatory processes. Underlying mechanisms that explain the highly specific binding of TFs to their genomic target sites are poorly understood. A better understanding of TF−DNA binding requires the ability to quantitatively model TF binding to accessible DNA...
    Categories: Journal Articles
  • Myosin ELC defines power stroke [Biophysics and Computational Biology]
    [Apr 2015]

    We have used time-resolved fluorescence resonance energy transfer (TR-FRET) to determine the role of myosin essential light chains (ELCs) in structural transitions within the actomyosin complex. Skeletal muscle myosins have two ELC isoforms, A1 and A2, which differ by an additional 40–45 residues at the N terminus of A1, and...
    Categories: Journal Articles
  • NANOG-DNA complex structure [Cell Biology]
    [Apr 2015]

    NANOG (from Irish mythology Tír na nÓg) transcription factor plays a central role in maintaining pluripotency, cooperating with OCT4 (also known as POU5F1 or OCT3/4), SOX2, and other pluripotency factors. Although the physiological roles of the NANOG protein have been extensively explored, biochemical and biophysical properties in relation to its...
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  • Raman imaging of artificial lipid raft monolayer [Chemistry]
    [Apr 2015]

    Sphingomyelin (SM) and cholesterol (chol)-rich domains in cell membranes, called lipid rafts, are thought to have important biological functions related to membrane signaling and protein trafficking. To visualize the distribution of SM in lipid rafts by means of Raman microscopy, we designed and synthesized an SM analog tagged with a...
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  • DNA-templated multicomponent enzyme crystals [Chemistry]
    [Apr 2015]

    The ability to predictably control the coassembly of multiple nanoscale building blocks, especially those with disparate chemical and physical properties such as biomolecules and inorganic nanoparticles, has far-reaching implications in catalysis, sensing, and photonics, but a generalizable strategy for engineering specific contacts between these particles is an outstanding challenge. This...
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  • Hox genes and H3K27me3 clustering [Developmental Biology]
    [Apr 2015]

    Embryogenesis requires the precise activation and repression of many transcriptional regulators. The Polycomb group proteins and the associated H3K27me3 histone mark are essential to maintain the inactive state of many of these genes. Mammalian Hox genes are targets of Polycomb proteins and form local 3D clusters centered on the H3K27me3...
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  • Hh-Igf positive feedback loop [Developmental Biology]
    [Apr 2015]

    Hedgehog (Hh) signaling is essential for osteoblast differentiation in the endochondral skeleton during embryogenesis. However, the molecular mechanism underlying the osteoblastogenic role of Hh is not completely understood. Here, we report that Hh markedly induces the expression of insulin-like growth factor 2 (Igf2) that activates the mTORC2-Akt signaling cascade during...
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  • Mechanisms for summer Arctic sea ice extent [Earth, Atmospheric, and Planetary Sciences]
    [Apr 2015]

    Satellite observations reveal a substantial decline in September Arctic sea ice extent since 1979, which has played a leading role in the observed recent Arctic surface warming and has often been attributed, in large part, to the increase in greenhouse gases. However, the most rapid decline occurred during the recent...
    Categories: Journal Articles