Regulation of synaptic development by astrocyte signaling factors and their emerging roles in substance abuse

Astrocytes have critical functions throughout the central nervous system (CNS) and have emerged as regulators of synaptic development and function. With their highly complex morphologies, they are able to interact with thousands of synapses via peripheral astrocytic processes (PAPs), ensheathing neuronal axons and dendrites to form the tripartite synapse. In this way, astrocytes engage in crosstalk with neurons to mediate a variety of CNS processes including the regulation of extracellular matrix protein signaling, formation and maintenance of the blood-brain barrier (BBB), axon growth and guidance, homeostasis of the synaptic microenvironment, synaptogenesis, and the promotion of synaptic diversity. In this review, we discuss several key astrocyte signaling factors (thrombospondins, netrins, apolipoproteins, neuregulins, bone morphogenetic proteins, and neuroligins) in the maintenance and regulation of synapse formation. We also explore how these astrocyte signaling factors are impacted by and contribute to substance abuse, particularly alcohol and cocaine use

Putin und Russlands gelähmte Medien

Der Kreml setzt unter Putin die Unterdrückung der Medien als festen Bestandteil einer Strategie fort, jedes Aufkommen einer glaubwürdigen Opposition zu verhindern, die das derzeitige Regime ernsthaft herausfordern könnte. Dieser Beitrag betrachtet die jüngste Entwicklung der Medien in Russland und arbeitet einige Schlüsselelemente dieser Strategie heraus. Während das Fernsehen weiterhin das wichtigste Instrument bleibt, mit dem die Regierung den Informationsraum dominiert, schenkt der Kreml dem Internet wegen dessen schnell zunehmender Bedeutung immer mehr Beachtung

Absence of force suppression in rabbit bladder correlates with low expression of heat shock protein 20

BACKGROUND: Nitroglycerin can induce relaxation of swine carotid artery without sustained reductions in [Ca(2+)](i )or myosin regulatory light chain (MRLC) phosphorylation. This has been termed force suppression and been found to correlate with ser(16)-phosphorylation of heat shock protein 20 (HSP20). We tested for the existence of this mechanism in a smooth muscle that is not responsive to nitric oxide. METHODS: Isometrically mounted mucosa free rabbit bladder strips were contracted with carbachol and relaxed with 8-Br-cGMP, forskolin, or isoprenaline. RESULTS: Contraction was associated with a highly cooperative relation between MRLC phosphorylation and force such that very small increases in MRLC phosphorylation induced large increases in force. Relaxation induced by 8-Br-cGMP, forskolin, or isoprenaline did not shift the MRLC phosphorylation-force relation from that observed with carbachol alone, i.e. there was no force suppression. HSP20 content was negligible (approximately two hundred-fold less than swine carotid). CONCLUSION: The lack of force suppression in the absence of HSP20 is consistent with the hypothesized role for HSP20 in the force suppression observed in tonic smooth muscles

Coupling of Multiple Coulomb Scattering with Energy Loss and Straggling in HZETRN

The new version of the HZETRN deterministic transport code based on Green's function methods, and the incorporation of ground-based laboratory boundary conditions, has lead to the development of analytical and numerical procedures to include off-axis dispersion of primary ion beams due to small-angle multiple Coulomb scattering. In this paper we present the theoretical formulation and computational procedures to compute ion beam broadening and a methodology towards achieving a self-consistent approach to coupling multiple scattering interactions with ionization energy loss and straggling. Our initial benchmark case is a 60 MeV proton beam on muscle tissue, for which we can compare various attributes of beam broadening with Monte Carlo simulations reported in the open literature

Differing Mechanisms Underlie Sexual Size-Dimorphism in Two Populations of a Sex-Changing Fish

Variability in the density of groups within a patchy environment lead to differences in interaction rates, growth dynamics and social organization. In protogynous hermaphrodites there are hypothesised trade-offs among sex-specific growth, reproductive output and mortality. When differences in density lead to changes to social organization the link between growth and the timing of sex-change is predicted to change. The present study explores this prediction by comparing the social organisation and sex-specific growth of two populations of a protogynous tropical wrasse, Halichoeres miniatus, which differ in density. At a low density population a strict harem structure was found, where males maintained a tight monopoly of access and spawning rights to females. In contrast, at a high density population a loosely organised system prevailed, where females could move throughout multiple male territories. Otolith microstructure revealed the species to be annual and deposit an otolith check associated with sex-change. Growth trajectories suggested that individuals that later became males in both populations underwent a growth acceleration at sex-change. Moreover, in the high density population, individuals that later became males were those individuals that had the largest otolith size at hatching and consistently deposited larger increments throughout early larval, juvenile and female life. This study demonstrates that previous growth history and growth rate changes associated with sex change can be responsible for the sexual dimorphism typically found in sex-changing species, and that the relative importance of these may be socially constrained

Assessment of the influence of intrinsic environmental and geographical factors on the bacterial ecology of pit latrines

Funding Information: This research received financial support from the Bill and Melinda Gates Foundation (grant number OPP52641). AWW and JP were supported by the Wellcome Trust [grant number 098051]. AWW and the Rowett Institute of Nutrition and Health, University of Aberdeen, receive core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS). UZ is funded by Natural Environment Research Council (NERC) Independent Research Fellowship (NE/L011956/1). CQ is funded through an Medical Research Council fellowship (MR/M50161X/1) as part of the MRC Cloud Infrastructure for Microbial Bioinformatics consortium (MR/L015080/1).Peer reviewedPublisher PD

Contribution of Endogenous Glucocorticoids and Their Intravascular Metabolism by 11β-HSDs to Postangioplasty Neointimal Proliferation in Mice

Exogenous glucocorticoids inhibit neointimal proliferation in animals. We aime to test the hypothesis that endogenous glucocorticoids influence neointimal proliferation; this may be mediated by effects on systemic risk factors or locally in vessels, and modulated either by adrenal secretion or by enzymes expressed in vessels which mediate local inactivation (11β-HSD2 in endothelium) or regeneration (11β-HSD1 in smooth muscle) of glucocorticoids. Femoral artery wire-angioplasty was conducted in C57Bl/6J, Apo-E(−/−), 11β-HSD1(−/−), Apo-E, 11β-HSD1(−/−) (double knockout) and 11β-HSD2(−/−) mice following glucocorticoid administration, adrenalectomy, glucocorticoid or mineralocorticoid receptor antagonism, or selective 11β-HSD1 inhibition. In C57Bl/6J mice, neointimal proliferation was reduced by systemic or local glucocorticoid administration, unaffected by adrenalectomy, reduced by the mineralocorticoid receptor antagonist eplerenone, and increased by the glucocorticoid receptor antagonist RU38486. 11β-HSD2 deletion had no effect on neointimal proliferation, with or without eplerenone. 11β-HSD1 inhibition or deletion had no effect in chow-fed C57Bl/6J mice, but reduced neointimal proliferation in Apo-E(−/−) mice on Western diet. Reductions in neointimal size were accompanied by reduced macrophage and increased collagen content. We conclude that pharmacological administration of glucocorticoid receptor agonists or of mineralocorticoid receptor antagonists may be useful in reducing neointimal proliferation. Endogenous corticosteroids induce beneficial glucocorticoid receptor activation and adverse mineralocorticoid receptor activation. However, manipulation of glucocorticoid metabolism has beneficial effects only in mice with exaggerated systemic risk factors, suggesting effects mediated primarily in liver and adipose rather than intra-vascular glucocorticoid signalling. Reducing glucocorticoid action with 11β-HSD1 inhibitors that are being developed for type 2 diabetes appears not to risk enhanced neointimal proliferation

Bulk crystal growth and surface preparation of NiSb, MnSb, and NiMnSb

Bulk single crystal and polycrystalline samples of NiSb, MnSb, and NiMnSb have been grown and characterized. The lattice parameter of NiMnSb was found to be 5.945 ± 0.001 Å, around 0.25% larger than previous reports. The surface preparation of these materials was investigated using x-ray photoelectron spectroscopy. Wet etching with HCl and argon ion sputtering were used in tandem with vacuum annealing. For both binary materials, a clean and stoichiometric surface could be regained by HCl etching and annealing alone. However, clean and stoichiometric ternary NiMnSb was not successfully prepared by these methods. The transition metal 2p and 3p levels are analyzed for all three materials

Elementary School Staff Perspectives On the Implementation of Physical activity approaches in Practice: an Exploratory Sequential Mixed Methods Study

INTRODUCTION: A whole-of-school approach is best to promote physical activity before, during, and after school. However, multicomponent programming is often complex and difficult to deliver in school settings. There is a need to better understand how components of a whole-of-school approach are implemented in practice. The objectives of this mixed methods study were to: (1) qualitatively explore physical activity approaches and their implementation in elementary schools, (2) quantitatively assess implementation levels, and (3) examine associations between school-level physical activity promotion and academic ratings. METHODS: We used an exploratory sequential mixed methods design. We conducted semi-structured qualitative interviews with elementary school staff from a Texas school district and used a directed content analysis to explore physical activity approaches and their implementation. Using qualitative findings, we designed a survey to quantitatively examine the implementation of physical activity approaches, which we distributed to elementary staff district wide. We used Pearson correlation coefficients to examine the association between the amount of physical activity opportunities present in individual schools and school-level academic ratings. RESULTS: We completed 15 interviews (7 principals/assistant principals, 4 physical educators, and 4 classroom teachers). Elementary school teachers and staff indicated PE and recess implementation was driven from the top-down by state and district policies, while implementation of classroom-based approaches, before and after school programming, and active transport were largely driven from the bottom-up by teachers and school leaders. Teachers and staff also discussed implementation challenges across approaches. Survey respondents ( CONCLUSION: Schools provided physical activity opportunities consistent with a whole-of-school approach, although there was variability between schools and implementation challenges were present. Leveraging existing school assets while providing school-specific implementation strategies may be most beneficial for supporting successful physical activity promotion in elementary schools