FGF2 is expressed in human and murine embryonic choroid plexus and affects choroid plexus cell behaviour

<p>Abstract</p> <p>Background</p> <p>Although fibroblast growth factor (Fgf) signalling plays crucial roles in several developing and mature tissues, little information is currently available on expression of Fgf2 during early choroid plexus development and whether Fgf2 directly affects the behaviour of the choroid plexus epithelium (CPe). The purpose of this study was to investigate expression of Fgf2 in rodent and human developing CPe and possible function of Fgf2, using <it>in vitro </it>models. The application of Fgf2 to brain <it>in vivo </it>can affect the whole tissue, making it difficult to assess specific responses of the CPe.</p> <p>Methods</p> <p>Expression of Fgf2 was studied by immunohistochemistry in rodent and human embryonic choroid plexus. Effects of Fgf2 on growth, secretion, aggregation and gene expression was investigated using rodent CPe vesicles, a three-dimensional polarized culture model that closely mimics CPe properties <it>in vivo</it>, and rodent CPe monolayer cultures.</p> <p>Results</p> <p>Fgf2 was present early in development of the choroid plexus both in mouse and human, suggesting the importance of this ligand in Fgf signalling in the developing choroid plexus. Parallel analysis of Fgf2 expression and cell proliferation during CP development suggests that Fgf2 is not involved in CPe proliferation <it>in vivo</it>. Consistent with this observation is the failure of Fgf2 to increase proliferation in the tri-dimensional vesicle culture model. The CPe however, can respond to Fgf2 treatment, as the diameter of CPe vesicles is significantly increased by treatment with this growth factor. We show that this is due to an increase in cell aggregation during vesicle formation rather than increased secretion into the vesicle lumen. Finally, Fgf2 regulates expression of the CPe-associated transcription factors, <it>Foxj1 </it>and <it>E2f5</it>, whereas transthyretin, a marker of secretory activity, is not affected by Fgf2 treatment.</p> <p>Conclusion</p> <p>Fgf2 expression early in the development of both human and rodent choroid plexus, and its ability to modulate behaviour and gene expression in CPe, supports the view that Fgf signalling plays a role in the maintenance of integrity and function of this specialized epithelium, and that this role is conserved between rodents and humans.</p

Black hole quasinormal modes using the asymptotic iteration method

In this article we show that the asymptotic iteration method (AIM) allows one to numerically find the quasinormal modes of Schwarzschild and Schwarzschild de Sitter (SdS) black holes. An added benefit of the method is that it can also be used to calculate the Schwarzschild anti-de Sitter (SAdS) quasinormal modes for the case of spin zero perturbations. We also discuss an improved version of the AIM, more suitable for numerical implementation.Comment: 10 pages, LaTeX; references added; substantially expanded versio

Graviton emission from simply rotating Kerr-de Sitter black holes: Transverse traceless tensor graviton modes

In this article we present results for tensor graviton modes (in seven dimensions and greater, $n\geq 3$) for greybody factors of Kerr-dS black holes and for Hawking radiation from simply rotating (n+4)-dimensional Kerr black holes. Although there is some subtlety with defining the Hawking temperature of a Kerr-dS black hole, we present some preliminary results for emissions assuming the standard Hawking normalization and a Bousso-Hawking-like normalization.Comment: 12 pages, 18 figure

Angular Eigenvalues of Higher-Dimensional Kerr-(A)dS Black Holes with Two Rotations

In this paper, following the work of Chen, L\"u and Pope, we present the general metric for Kerr-(A)dS black holes with two rotations. The corresponding Klein-Gordon equation is separated explicitly, from which we develop perturbative expansions for the angular eigenvalues in powers of the rotation parameters with $D\geq 6$.Comment: 10 pages, no figures. To appear in the proceedings of 2011 Shanghai Asia-Pacific School and Workshop on Gravitatio

Bulk dominated fermion emission on a Schwarzschild background

Using the WKBJ approximation, and the Unruh method, we obtain semi-analytic expressions for the absorption probability (in all energy regimes) for Dirac fermions on a higher dimensional Schwarzschild background. We present an analytic expression relating the absorption probability to the absorption cross-section, and then use these results to plot the emission rates to third order in the WKBJ approximation. The set-up we use is sufficiently general such that it could also easily be applied to any spherically symmetric background in $d$-dimensions. Our results lead to the interesting conclusion that for $d>5$ bulk fermion emission dominates brane localised emission. This is an example contrary to the conjecture that black holes radiate mainly on the brane.Comment: 13 pages, 3 figure

Split fermion quasi-normal modes

In this paper we use the conformal properties of the spinor field to show how we can obtain the fermion quasi-normal modes for a higher dimensional Schwarzschild black hole. These modes are of interest in so called split fermion models, where quarks and leptons are required to exist on different branes in order to keep the proton stable. As has been previously shown, for brane localized fields, the larger the number of dimensions the faster the black hole damping rate. Moreover, we also present the analytic forms of the quasi-normal frequencies in both the large angular momentum and the large mode number limits.Comment: 11 pages, 7 figures, version 2 added reference

The predominant relationship between sexual environment characteristics and HIV-serodiscordant condomless anal sex among HIV-positive men who have sex with men (MSM)

In some studies, situational factors have been shown to be stronger predictors of condomless sex than individual risk factors. Cross-sectional relationships between condomless anal sex (CAS) with HIV-serodiscordant partners and risk factors across ecological levels (individual, sexual environment) were examined using a sample (N = 60) of HIV-positive men who have sex with men (MSM) who reported multiple recent episodes of CAS. Negative binomial regressions were used to evaluate the association of contextual risk factors (e.g., substance use during sex, transactional sex, public sex, sex at a sex party) with recent condomless sex, controlling for demographics and mental health. Results demonstrated that sexual environment factors, particularly sex under the influence of drugs or alcohol (B = .019, p < .05), transactional sex (B = .035, p < .01), and public sex (B = .039, p < .01) explained a large proportion of the variance in CAS. Only sex at a sex party was not related to CAS (p = .39). For each additional sexual environment in which men engaged, their rates of CAS increased (B = .39, p < .01). Secondary prevention interventions that are tailored to the proximal sexual environment could be maximally effective, particularly if they address substance use and other challenging sexual situations.We are very grateful to the participants for their time and efforts in the study. Support for the current study came from a feasibility grant (PI: Conall O'Cleirigh) from the Harvard University Center for AIDS Research (Parent Grant: P30AI060354, PI: Bruce Walker, MD) awarded to Dr. Conall O'Cleirigh. Investigator support for Dr. Steven Safren also came from NIH Grant K24MH094214. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. (P30AI060354 - Harvard University Center for AIDS Research; K24MH094214 - NIH)Accepted manuscrip

Common CHD8 Genomic Targets Contrast With Model-Specific Transcriptional Impacts of CHD8 Haploinsufficiency.

The packaging of DNA into chromatin determines the transcriptional potential of cells and is central to eukaryotic gene regulation. Case sequencing studies have revealed mutations to proteins that regulate chromatin state, known as chromatin remodeling factors, with causal roles in neurodevelopmental disorders. Chromodomain helicase DNA binding protein 8 (CHD8) encodes a chromatin remodeling factor with among the highest de novo loss-of-function mutation rates in patients with autism spectrum disorder (ASD). However, mechanisms associated with CHD8 pathology have yet to be elucidated. We analyzed published transcriptomic data across CHD8 in vitro and in vivo knockdown and knockout models and CHD8 binding across published ChIP-seq datasets to identify convergent mechanisms of gene regulation by CHD8. Differentially expressed genes (DEGs) across models varied, but overlap was observed between downregulated genes involved in neuronal development and function, cell cycle, chromatin dynamics, and RNA processing, and between upregulated genes involved in metabolism and immune response. Considering the variability in transcriptional changes and the cells and tissues represented across ChIP-seq analysis, we found a surprisingly consistent set of high-affinity CHD8 genomic interactions. CHD8 was enriched near promoters of genes involved in basic cell functions and gene regulation. Overlap between high-affinity CHD8 targets and DEGs shows that reduced dosage of CHD8 directly relates to decreased expression of cell cycle, chromatin organization, and RNA processing genes, but only in a subset of studies. This meta-analysis verifies CHD8 as a master regulator of gene expression and reveals a consistent set of high-affinity CHD8 targets across human, mouse, and rat in vivo and in vitro studies. These conserved regulatory targets include many genes that are also implicated in ASD. Our findings suggest a model where perturbation to dosage-sensitive CHD8 genomic interactions with a highly-conserved set of regulatory targets leads to model-specific downstream transcriptional impacts