11,553 research outputs found

    Regulation of brain endothelial barrier function by microRNAs in health and neuroinflammation

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    Brain endothelial cells constitute the major cellular element of the highly specialized blood–brain barrier (BBB) and thereby contribute to CNS homeostasis by restricting entry of circulating leukocytes and blood-borne molecules into the CNS. Therefore, compromised function of brain endothelial cells has serious consequences for BBB integrity. This has been associated with early events in the pathogenesis of several disorders that affect the CNS, such as multiple sclerosis, HIV-associated neurologic disorder, and stroke. Recent studies demonstrate that brain endothelial microRNAs play critical roles in the regulation of BBB function under normal and neuroinflammatory conditions. This review will focus on emerging evidence that indicates that brain endothelial microRNAs regulate barrier function and orchestrate various phases of the neuroinflammatory response, including endothelial activation in response to cytokines as well as restoration of inflamed endothelium into a quiescent state. In particular, we discuss novel microRNA regulatory mechanisms and their contribution to cellular interactions at the neurovascular unit that influence the overall function of the BBB in health and during neuroinflammatio

    A GEANT4 Study of a Gamma-ray Collimation Array

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    Proton beam therapy uses high-energy protons to destroy cancer cells which are still uncertain about where in the body they hit. A possible way to answer this question is to detect the gamma rays produced during the irradiation and determine where in the body they are produced. This work investigates the use of collimators to determine where the proton interactions occur. GEANT4 is used to simulate the gamma production of a source interacting with a collimator. Each event simulates a number of gammas obtained as a function of the position along the detector. Repeating for different collimator configurations can thus help determine the best characteristics of a detector device

    The effects of advanced maternal age on T- cell subsets at the maternal- fetal interface prior to term labor and in the offspring: a mouse study

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155904/1/cei13437.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155904/2/cei13437_am.pd

    Relativistic Klein-Gordon charge effects by information-theoretic measures

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    The charge spreading of ground and excited states of Klein-Gordon particles moving in a Coulomb potential is quantitatively analyzed by means of the ordinary moments and the Heisenberg measure as well as by use of the most relevant information-theoretic measures of global (Shannon entropic power) and local (Fisher's information) types. The dependence of these complementary quantities on the nuclear charge Z and the quantum numbers characterizing the physical states is carefully discussed. The comparison of the relativistic Klein-Gordon and non-relativistic Schrodinger values is made. The non-relativistic limits at large principal quantum number n and for small values of Z are also reached.Comment: Accepted in New Journal of Physic

    CD71+ erythroid cells from neonates born to women with preterm labor regulate cytokine and cellular responses

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    Neonatal CD71+ erythroid cells are thought to have immunosuppressive functions. Recently, we demonstrated that CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor (PTL) are reduced to levels similar to those of term neonates; yet, their functional properties are unknown. Herein, we investigated the functionality of CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm or term labor. CD71+ erythroid cells from neonates born to women who underwent PTL displayed a similar mRNA profile to that of those from term neonates. The direct contact between preterm or term neonatal CD71+ erythroid cells and maternal mononuclear immune cells, but not soluble products from these cells, induced the release of proinflammatory cytokines and a reduction in the release of TGFâ β. Moreover, PTLâ derived neonatal CD71+ erythroid cells (1) modestly altered CD8+ T cell activation; (2) inhibited conventional CD4+ and CD8+ Tâ cell expansion; (3) suppressed the expansion of CD8+ regulatory T cells; (4) regulated cytokine responses mounted by myeloid cells in the presence of a microbial product; and (5) indirectly modulated Tâ cell cytokine responses. In conclusion, neonatal CD71+ erythroid cells regulate neonatal Tâ cell and myeloid responses and their direct contact with maternal mononuclear cells induces a proinflammatory response. These findings provide insight into the biology of neonatal CD71+ erythroid cells during the physiologic and pathologic processes of labor.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142950/1/jlb10051_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142950/2/jlb10051-sup-0003-TableS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142950/3/jlb10051-sup-0002-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142950/4/jlb10051-sup-0001-Figures.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142950/5/jlb10051.pd

    Molecular and Biochemical Methods Useful for the Epigenetic Characterization of Chromatin-Associated Proteins in Bivalve Molluscs

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    Bivalve molluscs constitute a ubiquitous taxonomic group playing key functions in virtually all ecosystems, and encompassing critical commercial relevance. Along with a sessile and filter-feeding lifestyle in most cases, these characteristics make bivalves model sentinel organisms routinely used for environmental monitoring studies in aquatic habitats. The study of epigenetic mechanisms linking environmental exposure and specific physiological responses (i.e., environmental epigenetics) stands out as a very innovative monitoring strategy, given the role of epigenetic modifications in acclimatization and adaptation. Furthermore, the heritable nature of many of those modifications constitutes a very promising avenue to explore the applicability of epigenetic conditioning and selection in management and restoration strategies. Chromatin provides a framework for the study of environmental epigenetic responses. Unfortunately, chromatin and epigenetic information are very limited in most non-traditional model organisms and even completely lacking in most environmentally and ecologically relevant organisms. The present work aims to provide a comprehensive and reproducible experimental workflow for the study of bivalve chromatin. First, a series of guidelines for the molecular isolation of genes encoding chromatin-associated proteins is provided, including information on primers suitable for conventional PCR, Rapid Amplification of cDNA Ends (RACE), genome walking and quantitative PCR (qPCR) experiments. This section is followed by the description of methods specifically developed for the analysis of histone and SNBP proteins in different bivalve tissues, including protein extraction, purification, separation and immunodetection. Lastly, information about available antibodies, their specificity and performance is also provided. The tools and protocols described here complement current epigenetic analyses (usually limited to DNA methylation) by incorporating the study of structural elements modulating chromatin dynamics

    Standardised description of health and social care: A systematic review of use of the ESMS/DESDE (European Service Mapping Schedule/Description and Evaluation of Services and DirectoriEs)

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    Background: Evidence-informed planning and interpretation of research results both require standardised description of local care delivery context. Such context analysis descriptions should be comparable across regions and countries to allow benchmarking and organizational learning, and for research findings to be interpreted in context. The European Service Mapping Schedule (ESMS) is a classification of adult mental health services that was later adapted for the assessment of health and social systems research (Description and Evaluation of Services and DirectoriEs - DESDE). The aim of the study was to review the diffusion and use of the ESMS/DESDE system in health and social care and its impact in health policy and decision-making. Method: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (1997–2018). Results: Out of 155 papers mentioning ESMS/DESDE, 71 have used it for service research and planning. The classification has been translated into eight languages and has been used by seven international research networks. Since 2000, it has originated 11 instruments for health system research with extensive analysis of their metric properties. The ESMS/DESDE coding system has been used in 585 catchment areas in 34 countries for description of services delivery at local, regional and national levels. Conclusions: The ESMS/DESDE system provides a common terminology, a classification of care services, and a set of tools allowing a variety of aims to be addressed in healthcare and health systems research. It facilitates comparisons across and within countries for evidence-informed planning

    Amniotic fluid neutrophils can phagocytize bacteria: A mechanism for microbial killing in the amniotic cavity

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138926/1/aji12723_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138926/2/aji12723.pd
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