3,118 research outputs found

    Girls Count: A Global Investment & Action Agenda

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    Explains how girls' welfare affects overall economic and social outcomes. Outlines steps to disaggregate health, education, and other data by age and gender; invest strategically in girls' programs; and ensure equitable benefits for girls in all sectors

    Regulation of Neuronal Survival and Death by E2F-Dependent Gene Repression and Derepression

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    AbstractNeuronal death induced by a variety of means requires participation of the E2F family of transcription factors. Here, we show that E2F acts as a gene silencer in neurons and that repression of E2F-responsive genes is required for neuronal survival. Moreover, neuronal death evoked by DNA damaging agents or trophic factor withdrawal is characterized by derepression of E2F-responsive genes. Such derepression, rather than direct E2F-promoted gene activation, is required for death. Among the genes that are derepressed in neurons subjected to DNA damage or trophic factor withdrawal are the transcription factors B- and C-myb. Overexpression of B- and C-myb is sufficient to evoke neuronal death. These findings support a model in which E2F-dependent gene repression and derepression play pivotal roles in neuronal survival and death, respectively

    Manipulation and Study of Gene Expression in Neurotoxin- Treated Neuronal PC12 and SH-SY5Y Cells for In Vitro Studies of Parkinson’s Disease

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    Neuronal PC12 and SH-SY5Y cells are highly suitable in vitro models for study of the neurodegenerative mechanisms occurring in Parkinson’s disease (PD). Differentiated PC12 and SH-SY5Y cells bear many similarities to the neuronal populations affected in PD, and they provide a convenient source of large amounts of homogeneous material for biochemical and molecular downstream applications. In the present review, we describe how to differentiate PC12 and SH-SY5Y cells into neuron-like cells and provide protocols for their transfection with plasmids and infection with viral particles to manipulate gene expression. We also describe how to treat neuronal PC12 and SH-SY5Y cells with the classical PD neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-pyridinium ion (MPP+). Finally, we give detailed methods for several downstream applications useful for the analysis of cell death pathways in PD

    The influence of snow depth and hardness on winter habitat selection by caribou on the southwest coast of Newfoundland

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    LaPoile Herd caribou winter in the coastal margin of their range in southwestern Newfoundland. Reduced snow depths near the coast (0-20 km inland), as a result of moderated winter temperatures and low elevations, appear to provide more favourable foraging conditions than do areas further inland. In the latter areas greatly increased snow depth and hardness combine to create very extreme winter conditions and these areas are avoided by caribou throughout the winter period

    Isolation and Culture of Post-Natal Mouse Cerebellar Granule Neuron Progenitor Cells and Neurons

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    The cerebellar cortex is a well described structure that provides unique opportunities for studying neuronal properties and development1,2. Of the cerebellar neuronal types (granule cells, Purkinje cells and inhibitory interneurons), granule neurons are by far the most numerous and are the most abundant type of neurons in the mammalian brain. In rodents, cerebellar granule neurons are generated during the first two post-natal weeks from progenitor cells in the outermost layer of the cerebellar cortex, the external granule layer (EGL). The protocol presented here describes techniques to enrich and culture granule neurons and their progenitor cells from post-natal mouse cerebellum. We will describe procedures to obtain cultures of increasing purity3,4, which can be used to study the differentiation of proliferating progenitor cells into granule neurons5,6. Once the progenitor cells differentiate, the cultures also provide a homogenous population of granule neurons for experimental manipulation and characterization of phenomena such as synaptogenesis, glutamate receptor function7, interaction with other purified cerebellar cells8,9 or cell death7

    Regression/eradication of gliomas in mice by a systemically-deliverable ATF5 dominant-negative peptide.

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    Malignant gliomas have poor prognosis and urgently require new therapies. Activating Transcription Factor 5 (ATF5) is highly expressed in gliomas, and interference with its expression/function precipitates targeted glioma cell apoptosis in vitro and in vivo. We designed a novel deliverable truncated-dominant-negative (d/n) form of ATF5 fused to a cell-penetrating domain (Pen-d/n-ATF5-RP) that can be intraperitoneally/subcutaneously administered to mice harboring malignant gliomas generated; (1) by PDGF-B/sh-p53 retroviral transformation of endogenous neural progenitor cells; and (2) by human U87-MG xenografts. In vitro Pen-d/n-ATF5-RP entered into glioma cells and triggered massive apoptosis. In vivo, subcutaneously-administered Pen-d/n-ATF5-RP passed the blood brain barrier, entered normal brain and tumor cells, and then caused rapid selective tumor cell death. MRI verified elimination of retrovirus-induced gliomas within 8-21 days. Histopathology revealed growth-suppression of intracerebral human U87-MG cells xenografts. For endogenous PDGF-B gliomas, there was no recurrence or mortality at 6-12 months versus 66% mortality in controls at 6 months. Necropsy and liver-kidney blood enzyme analysis revealed no adverse effects on brain or other tissues. Our findings thus identify Pen-d/n-ATF5-RP as a potential therapy for malignant gliomas
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