Proceedings of the Natural Academy of Sciences

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  • Substrate recognition by MMPs [Biochemistry]
    [Oct 2014]

    Genomic sequencing and structural genomics produced a vast amount of sequence and structural data, creating an opportunity for structure–function analysis in silico [Radivojac P, et al. (2013) Nat Methods 10(3):221–227]. Unfortunately, only a few large experimental datasets exist to serve as benchmarks for function-related predictions. Furthermore, currently there are no...
    Categories: Journal Articles
  • H-NOX activation [Biochemistry]
    [Oct 2014]

    Heme-nitric oxide/oxygen (H-NOX) binding domains are a recently discovered family of heme-based gas sensor proteins that are conserved across eukaryotes and bacteria. Nitric oxide (NO) binding to the heme cofactor of H-NOX proteins has been implicated as a regulatory mechanism for processes ranging from vasodilation in mammals to communal behavior...
    Categories: Journal Articles
  • Modeling cancer-immunity interplay with exosomes [Biophysics and Computational Biology]
    [Oct 2014]

    Development of effective strategies to mobilize the immune system as a therapeutic modality in cancer necessitates a better understanding of the contribution of the tumor microenvironment to the complex interplay between cancer cells and the immune response. Recently, effort has been directed at unraveling the functional role of exosomes and...
    Categories: Journal Articles
  • Dissecting cadherin binding affinity determinants [Biophysics and Computational Biology]
    [Oct 2014]

    Type I cadherin cell-adhesion proteins are similar in sequence and structure and yet are different enough to mediate highly specific cell–cell recognition phenomena. It has previously been shown that small differences in the homophilic and heterophilic binding affinities of different type I family members can account for the differential cell-sorting...
    Categories: Journal Articles
  • Dual mode activation of BubR1 by Bub3 [Cell Biology]
    [Oct 2014]

    The mitotic checkpoint (also known as the spindle assembly checkpoint) prevents premature anaphase onset through generation of an inhibitor of the E3 ubiquitin ligase APC/C, whose ubiquitination of cyclin B and securin targets them for degradation. Combining in vitro reconstitution and cell-based assays, we now identify dual mechanisms through which...
    Categories: Journal Articles
  • Defective autophagy causes preterm labor [Developmental Biology]
    [Oct 2014]

    Autophagy is an important cellular process that serves as a companion pathway to the ubiquitin-proteasome system to degrade long-lived proteins and organelles to maintain cell homeostasis. Although initially characterized in yeast, autophagy is being realized as an important regulator of development and disease in mammals. Beclin1 (Becn1) is a putative...
    Categories: Journal Articles
  • Abating ground-level ozone through reforestation [Environmental Sciences]
    [Oct 2014]

    High ambient ozone (O3) concentrations are a widespread and persistent problem globally. Although studies have documented the role of forests in removing O3 and one of its precursors, nitrogen dioxide (NO2), the cost effectiveness of using peri-urban reforestation for O3 abatement purposes has not been examined. We develop a methodology...
    Categories: Journal Articles
  • Adult OPC gliomagenesis by multistep reactivation [Genetics]
    [Oct 2014]

    How malignant gliomas arise in a mature brain remains a mystery, hindering the development of preventive and therapeutic interventions. We previously showed that oligodendrocyte precursor cells (OPCs) can be transformed into glioma when mutations are introduced perinatally. However, adult OPCs rarely proliferate compared with their perinatal counterparts. Whether these relatively...
    Categories: Journal Articles
  • Mechanism of translation initiation in E. coli [Genetics]
    [Oct 2014]

    Initiator tRNAs are special in their direct binding to the ribosomal P-site due to the hallmark occurrence of the three consecutive G-C base pairs (3GC pairs) in their anticodon stems. How the 3GC pairs function in this role, has remained unsolved. We show that mutations in either the mRNA or...
    Categories: Journal Articles
  • L(3)mbt requires Myb-MuvB complex for recruitment [Genetics]
    [Oct 2014]

    Lethal malignant brain tumors (lmbt) result from the loss of the conserved transcriptional repressor l(3)mbt, in Drosophila melanogaster. Similar mutations in the human homolog L3MBTL1 correlate with some cancers. The protein’s C-terminal MBT repeats bind mono and dimethylated histones in vitro, which could influence recruitment of L3MBTL1 to its target...
    Categories: Journal Articles
  • DNA-repair factor TDP2 in HBV cccDNA biogenesis [Microbiology]
    [Oct 2014]

    Hepatitis B virus (HBV), the causative agent of chronic hepatitis B and prototypic hepadnavirus, is a small DNA virus that replicates by protein-primed reverse transcription. The product is a 3-kb relaxed circular DNA (RC-DNA) in which one strand is linked to the viral polymerase (P protein) through a tyrosyl–DNA phosphodiester...
    Categories: Journal Articles
  • IpaH7.8 targets GLMN to activate inflammasomes [Microbiology]
    [Oct 2014]

    When nucleotide-binding oligomerization domain–like receptors (NLRs) sense cytosolic-invading bacteria, they induce the formation of inflammasomes and initiate an innate immune response. In quiescent cells, inflammasome activity is tightly regulated to prevent excess inflammation and cell death. Many bacterial pathogens provoke inflammasome activity and induce inflammatory responses, including cell death, by...
    Categories: Journal Articles
  • Domain selectivity in human entorhinal cortex [Neuroscience]
    [Oct 2014]

    Recent models of episodic memory propose a division of labor among medial temporal lobe cortices comprising the parahippocampal gyrus. Specifically, perirhinal and lateral entorhinal cortices are thought to comprise an object/item information pathway, whereas parahippocampal and medial entorhinal cortices are thought to comprise a spatial/contextual information pathway. Although several studies...
    Categories: Journal Articles
  • {alpha}-Synuclein multimerizes on membranes [Neuroscience]
    [Oct 2014]

    Physiologically, α-synuclein chaperones soluble NSF attachment protein receptor (SNARE) complex assembly and may also perform other functions; pathologically, in contrast, α-synuclein misfolds into neurotoxic aggregates that mediate neurodegeneration and propagate between neurons. In neurons, α-synuclein exists in an equilibrium between cytosolic and membrane-bound states. Cytosolic α-synuclein appears to be natively...
    Categories: Journal Articles
  • Europeans occupied a cold steppe 43,500 years ago [Anthropology]
    [Oct 2014]

    The first settlement of Europe by modern humans is thought to have occurred between 50,000 and 40,000 calendar years ago (cal B.P.). In Europe, modern human remains of this time period are scarce and often are not associated with archaeology or originate from old excavations with no contextual information. Hence,...
    Categories: Journal Articles
  • Collapse of an ecological network in Ancient Egypt [Anthropology]
    [Oct 2014]

    The dynamics of ecosystem collapse are fundamental to determining how and why biological communities change through time, as well as the potential effects of extinctions on ecosystems. Here, we integrate depictions of mammals from Egyptian antiquity with direct lines of paleontological and archeological evidence to infer local extinctions and community...
    Categories: Journal Articles
  • 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...
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  • 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...
    Categories: Journal Articles