119 research outputs found

    Bound q2qˉ2q^2\bar q^2 states in a constituent quark model

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    We consider the existence of bound systems consisting of two quarks and two antiquarks (q2qˉ2q^2\bar q^2) within the framework of a constituent quark model. The underlying quark dynamics is described by a linear confinement potential and an effective q2qˉ2q^2\bar q^2 interaction which has its origin in instanton effects of QCD. We calculate the spectra and examine the internal structure of the states found.Comment: 11 pages, needs epsf.st

    Mutations at positions 186 and 194 in the HA gene of the 2009 H1N1 pandemic influenza virus improve replication in cell culture and eggs

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    Obtaining suitable seed viruses for influenza vaccines poses a challenge for public health authorities and manufacturers. We used reverse genetics to generate vaccine seed-compatible viruses from the 2009 pandemic swine-origin influenza virus. Comparison of viruses recovered with variations in residues 186 and 194 (based on the H3 numbering system) of the viral hemagglutinin showed that these viruses differed with respect to their ability to grow in eggs and cultured cells. Thus, we have demonstrated that molecular cloning of members of a quasispecies can help in selection of seed viruses for vaccine manufacture

    A transient homotypic interaction model for the influenza A virus NS1 protein effector domain

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    Influenza A virus NS1 protein is a multifunctional virulence factor consisting of an RNA binding domain (RBD), a short linker, an effector domain (ED), and a C-terminal 'tail'. Although poorly understood, NS1 multimerization may autoregulate its actions. While RBD dimerization seems functionally conserved, two possible apo ED dimers have been proposed (helix-helix and strand-strand). Here, we analyze all available RBD, ED, and full-length NS1 structures, including four novel crystal structures obtained using EDs from divergent human and avian viruses, as well as two forms of a monomeric ED mutant. The data reveal the helix-helix interface as the only strictly conserved ED homodimeric contact. Furthermore, a mutant NS1 unable to form the helix-helix dimer is compromised in its ability to bind dsRNA efficiently, implying that ED multimerization influences RBD activity. Our bioinformatical work also suggests that the helix-helix interface is variable and transient, thereby allowing two ED monomers to twist relative to one another and possibly separate. In this regard, we found a mAb that recognizes NS1 via a residue completely buried within the ED helix-helix interface, and which may help highlight potential different conformational populations of NS1 (putatively termed 'helix-closed' and 'helix-open') in virus-infected cells. 'Helix-closed' conformations appear to enhance dsRNA binding, and 'helix-open' conformations allow otherwise inaccessible interactions with host factors. Our data support a new model of NS1 regulation in which the RBD remains dimeric throughout infection, while the ED switches between several quaternary states in order to expand its functional space. Such a concept may be applicable to other small multifunctional proteins

    Sensorimotor Experience Influences Recovery of Forelimb Abilities but Not Tissue Loss after Focal Cortical Compression in Adult Rats

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    Sensorimotor activity has been shown to play a key role in functional outcome after extensive brain damage. This study was aimed at assessing the influence of sensorimotor experience through subject-environment interactions on the time course of both lesion and gliosis volumes as well as on the recovery of forelimb sensorimotor abilities following focal cortical injury. The lesion consisted of a cortical compression targeting the forepaw representational area within the primary somatosensory cortex of adult rats. After the cortical lesion, rats were randomly subjected to various postlesion conditions: unilateral C5–C6 dorsal root transection depriving the contralateral cortex from forepaw somatosensory inputs, standard housing or an enriched environment promoting sensorimotor experience and social interactions. Behavioral tests were used to assess forelimb placement during locomotion, forelimb-use asymmetry, and forepaw tactile sensitivity. For each group, the time course of tissue loss was described and the gliosis volume over the first postoperative month was evaluated using an unbiased stereological method. Consistent with previous studies, recovery of behavioral abilities was found to depend on post-injury experience. Indeed, increased sensorimotor activity initiated early in an enriched environment induced a rapid and more complete behavioral recovery compared with standard housing. In contrast, severe deprivation of peripheral sensory inputs led to a delayed and only partial sensorimotor recovery. The dorsal rhizotomy was found to increase the perilesional gliosis in comparison to standard or enriched environments. These findings provide further evidence that early sensory experience has a beneficial influence on the onset and time course of functional recovery after focal brain injury

    The benefits of strength training on musculoskeletal system health: practical applications for interdisciplinary care

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    Global health organizations have provided recommendations regarding exercise for the general population. Strength training has been included in several position statements due to its multi-systemic benefits. In this narrative review, we examine the available literature, first explaining how specific mechanical loading is converted into positive cellular responses. Secondly, benefits related to specific musculoskeletal tissues are discussed, with practical applications and training programmes clearly outlined for both common musculoskeletal disorders and primary prevention strategies

    Le <i>controlling</i> dans la planification directrice cantonale

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    La pratique actuelle de l'orientation de la planification implique un retoilettage complet de celle-ci à chaque décennie. Le degré d'efficacité de la planification directrice ne peut être évalué qu'approximativement avant l'évolution suivante, dans la mesure où celle-ci n'est entreprise que très peu de temps avant la révision générale. Dans beaucoup de cas un aperçu des développements ou effets, souhaités ou non, des mesures envisagées pour la réalisation des objectifs du plan, fait défaut. C'est pourquoi il n'est pas possible d'introduire des corrections dans l'évolution du développement spatial. Une évolution fondée sur le principe du développement durable requiert toutefois de telles possibilités d'intervention. II importe de mettre au point des démarches susceptibles de constater en temps utile les éventuelles déviations et de rectifier le cours de la planification. II existe des instruments qui permettent de surveiller et d'orienter la mise en &oelig;uvre des objectifs et mesures des plans cantonaux. Ils peuvent aussi contribuer à l'évaluation du degré de réalisation des objectifs définis par la planification. II est ainsi possible de déceler en temps opportun les développements non durables et de procéder aux correctifs nécessaires. Ces instruments s'appellent monitoring, controlling et benchmarking; ils sont sous-tendus par des indicateurs. L'instrument central de ce système, le controlling, est présénte dans notre étude; son degré d'efficacité dans la planification cantonale directrice donne lieu à une analyse critique. Le recours au monitoring, au controlling et au benchmarking est indispensable pour un développement durable et une planification volontariste dynamique

    Sustainable Urban Development in Gaborone, Botswana: Synthesis Report, Draft Final

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    Mitochondrial dysfunction in astrocytes impairs the generation of reactive astrocytes and enhances neuronal cell death in the cortex upon photothrombotic lesion.

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    Mitochondria are key organelles in regulating the metabolic state of a cell. In the brain, mitochondrial oxidative metabolism is the prevailing mechanism for neurons to generate ATP. While it is firmly established that neuronal function is highly dependent on mitochondrial metabolism, it is less well-understood how astrocytes function rely on mitochondria. In this study, we investigate if astrocytes require a functional mitochondrial electron transport chain (ETC) and oxidative phosphorylation (oxPhos) under physiological and injury conditions. By immunohistochemistry we show that astrocytes expressed components of the ETC and oxPhos complexes in vivo. Genetic inhibition of mitochondrial transcription by conditional deletion of mitochondrial transcription factor A (Tfam) led to dysfunctional ETC and oxPhos activity, as indicated by aberrant mitochondrial swelling in astrocytes. Mitochondrial dysfunction did not impair survival of astrocytes, but caused a reactive gliosis in the cortex under physiological conditions. Photochemically initiated thrombosis induced ischemic stroke led to formation of hyperfused mitochondrial networks in reactive astrocytes of the perilesional area. Importantly, mitochondrial dysfunction significantly reduced the generation of new astrocytes and increased neuronal cell death in the perilesional area. These results indicate that astrocytes require a functional ETC and oxPhos machinery for proliferation and neuroprotection under injury conditions
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