529 research outputs found

    World Health Organization Ranking of Antimicrobials According to Their Importance in Human Medicine: A Critical Step for Developing Risk Management Strategies for the Use of Antimicrobials in Food Production Animals

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    The use of antimicrobials in food animals creates an important source of antimicrobial-resistant bacteria that can spread to humans through the food supply. Improved management of the use of antimicrobials in food animals, particularly reducing the usage of those that are "critically important” for human medicine, is an important step toward preserving the benefits of antimicrobials for people. The World Health Organization has developed and applied criteria to rank antimicrobials according to their relative importance in human medicine. Clinicians, regulatory agencies, policy makers, and other stakeholders can use this ranking when developing risk management strategies for the use of antimicrobials in food production animals. The ranking allows stakeholders to focus risk management efforts on drugs used in food animals that are the most important to human medicine and, thus, need to be addressed most urgently, such as fluoroquinolones, macrolides, and third- and fourth-generation cephalosporin

    The Role of Bilayer Tilt Difference in Equilibrium Membrane Shapes

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    Lipid bilayer membranes below their main transition have two tilt order parameters, corresponding to the two monolayers. These two tilts may be strongly coupled to membrane shape but only weakly coupled to each other. We discuss some implications of this observation for rippled and saddle phases, bilayer tubules, and bicontinuous phases. Tilt difference introduces a length scale into the elastic theory of tilted fluid membranes. It can drive an instability of the flat phase; it also provides a simple mechanism for the spontaneous breaking of inversion symmetry seen in some recent experiments.Comment: Latex file; .ps available at http://dept.physics.upenn.edu/~nelson/saddle.p

    A test of the core process account of psychopathology in a heterogenous clinical sample of anxiety and depression: A case of the blind men and the elephant?

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    Many cognitive and behavioral processes, such as selective attention to threat, self-focused attention, safety-seeking behaviors, worry and thought suppression, have their foundations in research on anxiety disorders. Yet, they are now known to be transdiagnostic, i.e. shared across a wide range of psychological disorders. A more pertinent clinical and theoretical question is whether these processes are themselves distinct, or whether they reflect a shared 'core' process that maintains psychopathology. The current study utilized a treatment-seeking clinical adult sample of 313 individuals with a range of anxiety disorders and/or depression who had completed self-report measures of widely ranging processes: affect control, rumination, worry, escape/avoidance, and safety-seeking behaviors. We found that only the first factor extracted from a principal components analysis of the items of these measures was associated with symptoms of anxiety and depression. Our findings supported the 'core process' account that had its origins in the field of anxiety disorders, and we discuss the implications for theory, clinical practice and future research across psychological disorders

    Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes

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    The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3\u27UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3sigma) to be similarly regulated by Nup98. The expression of Nup98 is reduced in murine and human hepatocellular carcinomas (HCCs) and correlates with p21 expression in HCC patients. Our study elucidates a previously unrecognized function of wild-type Nup98 in regulating select p53 target genes that is distinct from the well-characterized oncogenic properties of Nup98 fusion proteins

    Investigating goal conflict as a source of mixed emotions

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    This research investigated whether (1) the experience of mixed emotions is a consequence of activating conflicting goals and (2) mixed emotions are distinct from emotional conflict. A preliminary experiment (Study 1, N = 35) showed that an elicited goal conflict predicted more mixed emotions than a condition where the same goals were not in conflict. The second experiment was based on naturally occurring goal activation (Study 2, N = 57). This illustrated that mixed emotions were experienced more following conflicting goals compared with a facilitating goals condition—on both a direct self-report measure of mixed emotions and a minimum index measure. The results also showed that mixed emotions were different to emotional conflict. Overall, goal conflict was found to be a source of mixed emotions, and it is feasible that such states have a role in resolving personal dilemmas

    Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

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    The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

    Dyadic Interaction: Greater than the Sum of its Parts?

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    The study of dyadic interaction plays a major role in infancy research. To advance conceptually-informed measurement of dyadic interaction and integration across studies, we examined factor structure of individual parents’ and infants’ measures and dyadic measures from face-to-face interactions in two samples of 6-mo-old infants and their parents: mothers from a demographically heterogeneous sample (N = 164) and mothers and fathers (N = 156) from a Caucasian middle-class sample. Results suggested: a) individual and dyadic measures, and parents’ and infants’ behaviors contribute independent information, b) measures of both valence and process are needed, c) there are context-general and context-specific qualities, and d) structure of dyadic interaction is more similar among mother-infant dyads from independent samples than between mother- and father-infant dyads within the same sample. Future research should use multiple measures incorporating valence, temporal processes, contextual influences, and behaviors of individual partners along with dyadic measures to adequately assess the quality of dyadic interaction
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