149 research outputs found

    Modernizing Mycroft: the Future of the Area Librarian

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    Examines the changing roles of area librarians and discusses how area librarians can remain relevant in academic libraries. Jakubs assesses the current skill set of area librarians and discusses new skill sets area librarians need to acquire to keep pace with changes in academic scholarship as well as technology. Includes a literature review on area librarianship from the 1960s to present and select bibliography

    Neurogenesis and epilepsy

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    Persistent neural stem cells generate dentate granule cells (DGCs) throughout life. Evidence suggests that aberrant neurogenesis contributes to epileptic structural abnormalities, but that normally integrating adult-born DGCs may restore inhibition. Current research focuses on how epileptogenic insults alter neurogenesis, and whether restoring normal neurogenesis will attenuate epilepsy or its comorbidities. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books ).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79277/1/j.1528-1167.2010.02831.x.pd

    Acquisitions Management and Collection Development in Libraries; Acquisition Policies and Procedures (Book Review)

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    published or submitted for publicatio

    Is neurogenesis reparative after status epilepticus?

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65863/1/j.1528-1167.2007.01355.x.pd

    Functional Integration of Grafted Neural Stem Cell-Derived Dopaminergic Neurons Monitored by Optogenetics in an In Vitro Parkinson Model

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    Intrastriatal grafts of stem cell-derived dopamine (DA) neurons induce behavioral recovery in animal models of Parkinson's disease (PD), but how they functionally integrate in host neural circuitries is poorly understood. Here, Wnt5a-overexpressing neural stem cells derived from embryonic ventral mesencephalon of tyrosine hydroxylase-GFP transgenic mice were expanded as neurospheres and transplanted into organotypic cultures of wild type mouse striatum. Differentiated GFP-labeled DA neurons in the grafts exhibited mature neuronal properties, including spontaneous firing of action potentials, presence of post-synaptic currents, and functional expression of DA D2 autoreceptors. These properties resembled those recorded from identical cells in acute slices of intrastriatal grafts in the 6-hydroxy-DA-induced mouse PD model and from DA neurons in intact substantia nigra. Optogenetic activation or inhibition of grafted cells and host neurons using channelrhodopsin-2 (ChR2) and halorhodopsin (NpHR), respectively, revealed complex, bi-directional synaptic interactions between grafted cells and host neurons and extensive synaptic connectivity within the graft. Our data demonstrate for the first time using optogenetics that ectopically grafted stem cell-derived DA neurons become functionally integrated in the DA-denervated striatum. Further optogenetic dissection of the synaptic wiring between grafted and host neurons will be crucial to clarify the cellular and synaptic mechanisms underlying behavioral recovery as well as adverse effects following stem cell-based DA cell replacement strategies in PD

    An Ancient Duplication of Exon 5 in the Snap25 Gene Is Required for Complex Neuronal Development/Function

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    Alternative splicing is an evolutionary innovation to create functionally diverse proteins from a limited number of genes. SNAP-25 plays a central role in neuroexocytosis by bridging synaptic vesicles to the plasma membrane during regulated exocytosis. The SNAP-25 polypeptide is encoded by a single copy gene, but in higher vertebrates a duplication of exon 5 has resulted in two mutually exclusive splice variants, SNAP-25a and SNAP-25b. To address a potential physiological difference between the two SNAP-25 proteins, we generated gene targeted SNAP-25b deficient mouse mutants by replacing the SNAP-25b specific exon with a second SNAP-25a equivalent. Elimination of SNAP-25b expression resulted in developmental defects, spontaneous seizures, and impaired short-term synaptic plasticity. In adult mutants, morphological changes in hippocampus and drastically altered neuropeptide expression were accompanied by severe impairment of spatial learning. We conclude that the ancient exon duplication in the Snap25 gene provides additional SNAP-25-function required for complex neuronal processes in higher eukaryotes

    Singing the same tune? International continuities and discontinuities in how police talk about using force

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    This article focuses on a research project conducted in six jurisdictions: England, The Netherlands, Germany, Australia, Venezuela, and Brazil. These societies are very different ethnically, socially, politically, economically, historically and have wildly different levels of crime. Their policing arrangements also differ significantly: how they are organised; how their officers are equipped and trained; what routine operating procedures they employ; whether they are armed; and much else besides. Most relevant for this research, they represent policing systems with wildly different levels of police shootings, Police in the two Latin American countries represented here have a justified reputation for the frequency with which they shoot people, whereas at the other extreme the police in England do not routinely carry firearms and rarely shoot anyone. To probe whether these differences are reflected in the way that officers talk about the use of force, police officers in these different jurisdictions were invited to discuss in focus groups a scenario in which police are thwarted in their attempt to arrest two youths (one of whom is a known local criminal) by the youths driving off with the police in pursuit, and concludes with the youths crashing their car and escaping in apparent possession of a gun, It might be expected that focus groups would prove starkly different, and indeed they were, but not in the way that might be expected. There was little difference in affirmation of normative and legal standards regarding the use of force. It was in how officers in different jurisdictions envisaged the circumstances in which the scenario took place that led Latin American officers to anticipate that they would shoot the suspects, whereas officers in the other jurisdictions had little expectation that they would open fire in the conditions as they imagined them to be

    (Putative) sex differences in neuroimmune modulation of memory

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134408/1/jnr23921.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134408/2/jnr23921_am.pd

    Neuroinflammation, Neuroautoimmunity, and the Co-Morbidities of Complex Regional Pain Syndrome

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    Synaptic Integration of Hippocampal Neurons Generated in the Adult Brain: Influence of a Pathological Environment

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    The adult brain constantly produces new neurons from endogenous neural progenitor cells located in at least two regions, the subgranular zone (SGZ) in dentate gyrus of the hippocampus, and the subventricular zone (SVZ). Major efforts are underway to discover the functional significance of new neurons in the adult brain. Several studies have indicated a relationship exists between newborn hippocampal neurons and learning and memory, suggesting that the new neurons have a physiological role within the established circuitry. Individual newborn hippocampal neurons develop into functional dentate granule cells and integrate normally into the hippocampal circuitry. They develop electrophysiological properties that are indistinguishable from the granule cells that were formed during early development. Adult neurogenesis may provide the possibility for neuronal replacement therapy. Several brain pathologies have been shown increase or decrease the magnitude of neurogenesis in the dentate gyrus. However, we do not know how the new neurons function when they are born in a pathological environment. This information is crucial for potential neuronal repair strategies utilizing endogenous neural progenitor cells. In this thesis, we used electrophysiological techniques to study the functional integration of new neurons born in a pathological environment. In the first study, we used an animal model of temporal lobe epilepsy, status epilepticus (SE), characterized by abnormal seizure activity, cell death and inflammation. In the second study we caused inflammation by intrahippocampal administration of lipopolysaccharide (LPS), which induced a strong inflammatory response but no seizure activity or cell death. After the insult, the new cells were labeled with a retrovirus tagged with green fluorescent protein (GFP), which incorporates into dividing cells and the protein is expressed throughout the cell body and processes.The new cells were identified in acute brain slices based on their GFP expression and subjected whole-cell patch-clamp recordings. We found that after SE the synaptic properties of the newborn neurons were consistent with enhanced inhibition and reduced excitation, indicating they may act to attenuate the hyperexcitability caused by epilepsy. After the LPS-induced inflammation, the new neurons also received enhanced inhibitory input. Our findings indicate that the environment in which new neurons are born dramatically influences their synaptic integration into the circuitry. The overall functional significance is not known, and further studies are warranted in order to understand underlying mechanisms. Such investigations may lead to potential neuronal replacement strategies harnessing endogenous neural progenitor cells
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