66 research outputs found

    Using content language analysis system indexes (CLASI) in the development of English testing materials

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    Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo.

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    The blockade of phagolysosomal fusion is considered a critical mycobacterial strategy to survive in macrophages. However, viable mycobacteria have been observed in phagolysosomes during infection of cultured macrophages, and mycobacteria have the virulence determinant MarP, which confers acid resistance in vitro. Here we show in mice and zebrafish that innate macrophages overcome mycobacterial lysosomal avoidance strategies to rapidly deliver a substantial proportion of infecting bacteria to phagolysosomes. Exploiting the optical transparency of the zebrafish, we tracked the fates of individual mycobacteria delivered to phagosomes versus phagolysosomes and discovered that bacteria survive and grow in phagolysosomes, though growth is slower. MarP is required specifically for phagolysosomal survival, making it an important determinant for the establishment of mycobacterial infection in their hosts. Our work suggests that if pathogenic mycobacteria fail to prevent lysosomal trafficking, they tolerate the resulting acidic environment of the phagolysosome to establish infection.National Institutes of Health (Grant IDs: R37AI054503, R01 AI076327, 5T32HD007233, 5F30HL110455), Wellcome Trust, National Institute of Health Research Cambridge Biomedical Research CentreThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.chom.2016.07.00

    Control of Dendritic Morphogenesis by Trio in Drosophila melanogaster

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    Abl tyrosine kinase and its effectors among the Rho family of GTPases each act to control dendritic morphogenesis in Drosophila. It has not been established, however, which of the many GTPase regulators in the cell link these signaling molecules in the dendrite. In axons, the bifunctional guanine exchange factor, Trio, is an essential link between the Abl tyrosine kinase signaling pathway and Rho GTPases, particularly Rac, allowing these systems to act coordinately to control actin organization. In dendritic morphogenesis, however, Abl and Rac have contrary rather than reinforcing effects, raising the question of whether Trio is involved, and if so, whether it acts through Rac, Rho or both. We now find that Trio is expressed in sensory neurons of the Drosophila embryo and regulates their dendritic arborization. trio mutants display a reduction in dendritic branching and increase in average branch length, whereas over-expression of trio has the opposite effect. We further show that it is the Rac GEF domain of Trio, and not its Rho GEF domain that is primarily responsible for the dendritic function of Trio. Thus, Trio shapes the complexity of dendritic arbors and does so in a way that mimics the effects of its target, Rac

    Applications of cortico-cortical paired associative stimulation for age-related declines of hand function

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    Neuroplasticity is a broad term that refers to our nervous system\u27s ability to adapt and modify its function throughout life. This learning process occurs as a function of experience, pain, pharmacological intervention and more. The work by Casarotto, Dolfini, Fadiga et al. (2023) in The Journal of Physiology investigates a part of this learning process referred to as Hebbian plasticity. Briefly, Hebbian plasticity can be summarized by the statement, ‘Neurons that fire together, wire together.’ This process of learning results from modifying communication between neurons (Hebb, 1949). Further, the elucidation of this process laid the groundwork for later study of long-term potentiation which is a strengthening of neuronal connections, and long-term depression which is a weakening of neuronal connections. These general synaptic ‘learning’ rules govern the more refined version of Hebbian principles, known as spike-timing-dependent plasticity
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