1,287 research outputs found

    Dynamic association between perfusion and white matter integrity across time since injury in Veterans with history of TBI.

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    ObjectiveCerebral blood flow (CBF) plays a critical role in the maintenance of neuronal integrity, and CBF alterations have been linked to deleterious white matter changes. Although both CBF and white matter microstructural alterations have been observed within the context of traumatic brain injury (TBI), the degree to which these pathological changes relate to one another and whether this association is altered by time since injury have not been examined. The current study therefore sought to clarify associations between resting CBF and white matter microstructure post-TBI.Methods37 veterans with history of mild or moderate TBI (mmTBI) underwent neuroimaging and completed health and psychiatric symptom questionnaires. Resting CBF was measured with multiphase pseudocontinuous arterial spin labeling (MPPCASL), and white matter microstructural integrity was measured with diffusion tensor imaging (DTI). The cingulate cortex and cingulum bundle were selected as a priori regions of interest for the ASL and DTI data, respectively, given the known vulnerability of these regions to TBI.ResultsRegression analyses controlling for age, sex, and posttraumatic stress disorder (PTSD) symptoms revealed a significant time since injury × resting CBF interaction for the left cingulum (p < 0.005). Decreased CBF was significantly associated with reduced cingulum fractional anisotropy (FA) in the chronic phase; however, no such association was observed for participants with less remote TBI.ConclusionsOur results showed that reduced CBF was associated with poorer white matter integrity in those who were further removed from their brain injury. Findings provide preliminary evidence of a possible dynamic association between CBF and white matter microstructure that warrants additional consideration within the context of the negative long-term clinical outcomes frequently observed in those with history of TBI. Additional cross-disciplinary studies integrating multiple imaging modalities (e.g., DTI, ASL) and refined neuropsychiatric assessment are needed to better understand the nature, temporal course, and dynamic association between brain changes and clinical outcomes post-injury

    Carbon in the Moon

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    International audienceThe Moon was once thought to be depleted in volatile elements. Analyses of the carbon contents of lunar volcanic glasses reveal that carbon monoxide degassing could have produced the fire-fountain eruptions from which these glasses were formed

    SPRITE and ASSAM: web servers for side chain 3D-motif searching in protein structures

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    Similarities in the 3D patterns of amino acid side chains can provide insights into their function despite the absence of any detectable sequence or fold similarities. Search for protein sites (SPRITE) and amino acid pattern search for substructures and motifs (ASSAM) are graph theoretical programs that can search for 3D amino side chain matches in protein structures, by representing the amino acid side chains as pseudo-atoms. The geometric relationship of the pseudo-atoms to each other as a pattern can be represented as a labeled graph where the pseudo-atoms are the graph's nodes while the edges are the inter-pseudo-atomic distances. Both programs require the input file to be in the PDB format. The objective of using SPRITE is to identify matches of side chains in a query structure to patterns with characterized function. In contrast, a 3D pattern of interest can be searched for existing occurrences in available PDB structures using ASSAM. Both programs are freely accessible without any login requirement. SPRITE is available at http://mfrlab.org/grafss/sprite/while ASSAM can be accessed at http://mfrlab.org/grafss/assam/

    Earth-Moon Impacts at ~300 Ma and ~500 Ma Ago

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    Impact events have played an important role in the evolution of planets and small bodies in the Solar System. Meteorites, lunar melt rocks, and lunar impact glasses provide important information about the geology of the parent body and the age of the impacting episodes. Over 2400 impact glasses from 4 Apollo regolith samples have been geochemically analyzed and a subset has been dated by the (40)Ar/(39)Ar method. New results, consistent with 2 break-ups in the Asteroid Belt, are presented here. Our previous study reported that (40)Ar/(39)Ar ages from 9 impact glasses showed that the Moon experienced significant impacts at approx. 800 Ma and at approx. 3800 Ma ago, somewhere in the vicinity of the Apollo 16 landing site. Additionally, reported on Apollo 12 samples with ages around 800 Ma, together implying global bombardment events. New data on 7 glasses from regolith sample 66041,127 show that the Moon also experienced impact events at approx. 300 Ma and > 500 Ma ago, which may coincide with the break-ups in the Asteroid Belt of the L- and H-chrondrite parent bodies. Since meteoritic evidence for these breakups has been found on Earth, it follows that evidence should be found in lunar samples as well. Additional information is included in the original extended abstract

    An interdomain sector mediating allostery in Hsp70 molecular chaperones

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    The Hsp70 family of molecular chaperones provides a well defined and experimentally powerful model system for understanding allosteric coupling between different protein domains.New extensions to the statistical coupling analysis (SCA) method permit identification of a group of co-evolving amino-acid positions—a sector—in the Hsp70 that is associated with allosteric function.Literature-based and new experimental studies support the notion that the protein sector identified through SCA underlies the allosteric mechanism of Hsp70.This work extends the concept of protein sectors by showing that two non-homologous protein domains can share a single sector when the underlying biological function is defined by the coupled activity of the two domains

    Structure and mechanism of acetolactate decarboxylase

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    Acetolactate decarboxylase catalyzes the conversion of both enantiomers of acetolactate to the (R)-enantiomer of acetoin, via a mechanism that has been shown to involve a prior rearrangement of the non-natural (R)-enantiomer substrate to the natural (S)-enantiomer. In this paper, a series of crystal structures of ALDC complex with designed transition state mimics are reported. These structures, coupled with inhibition studies and site-directed mutagenesis provide an improved understanding of the molecular processes involved in the stereoselective decarboxylation/protonation events. A mechanism for the transformation of each enantiomer of acetolactate is proposed

    Attributing scientific and technical progress: the case of holography

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    Holography, the three-dimensional imaging technology, was portrayed widely as a paradigm of progress during its decade of explosive expansion 1964–73, and during its subsequent consolidation for commercial and artistic uses up to the mid 1980s. An unusually seductive and prolific subject, holography successively spawned scientific insights, putative applications and new constituencies of practitioners and consumers. Waves of forecasts, associated with different sponsors and user communities, cast holography as a field on the verge of success—but with the dimensions of success repeatedly refashioned. This retargeting of the subject represented a degree of cynical marketeering, but was underpinned by implicit confidence in philosophical positivism and faith in technological progressivism. Each of its communities defined success in terms of expansion, and anticipated continual progressive increase. This paper discusses the contrasting definitions of progress in holography, and how they were fashioned in changing contexts. Focusing equally on reputed ‘failures’ of some aspects of the subject, it explores the varied attributes by which success and failure were linked with progress by different technical communities. This important case illuminates the peculiar post-World War II environment that melded the military, commercial and popular engagement with scientific and technological subjects, and the competing criteria by which they assessed the products of science

    Structural and functional characterization of Pseudomonas aeruginosa CupB chaperones

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    Pseudomonas aeruginosa, an important human pathogen, is estimated to be responsible for,10% of nosocomial infections worldwide. The pathogenesis of P. aeruginosa starts from its colonization in the damaged tissue or medical devices (e. g. catheters, prothesis and implanted heart valve etc.) facilitated by several extracellular adhesive factors including fimbrial pili. Several clusters containing fimbrial genes have been previously identified on the P. aeruginosa chromosome and named cup [1]. The assembly of the CupB pili is thought to be coordinated by two chaperones, CupB2 and CupB4. However, due to the lack of structural and biochemical data, their chaperone activities remain speculative. In this study, we report the 2.5 A crystal structure of P. aeruginosa CupB2. Based on the structure, we further tested the binding specificity of CupB2 and CupB4 towards CupB1 (the presumed major pilus subunit) and CupB6 (the putative adhesin) using limited trypsin digestion and strep-tactin pull-down assay. The structural and biochemical data suggest that CupB2 and CupB4 might play different, but not redundant, roles in CupB secretion. CupB2 is likely to be the chaperone of CupB1, and CupB4 could be the chaperone of CupB4:CupB5:CupB6, in which the interaction of CupB4 and CupB6 might be mediated via CupB5
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