IGFBP3 Colocalizes with and Regulates Hypocretin (Orexin)

Background: The sleep disorder narcolepsy is caused by a vast reduction in neurons producing the hypocretin (orexin) neuropeptides. Based on the tight association with HLA, narcolepsy is believed to result from an autoimmune attack, but the cause of hypocretin cell loss is still unknown. We performed gene expression profiling in the hypothalamus to identify novel genes dysregulated in narcolepsy, as these may be the target of autoimmune attack or modulate hypocretin gene expression. Methodology/Principal Findings: We used microarrays to compare the transcriptome in the posterior hypothalamus of (1) narcoleptic versus control postmortem human brains and (2) transgenic mice lacking hypocretin neurons versus wild type mice. Hypocretin was the most downregulated gene in human narcolepsy brains. Among many additional candidates, only one, insulin-like growth factor binding protein 3 (IGFBP3), was downregulated in both human and mouse models and coexpressed in hypocretin neurons. Functional analysis indicated decreased hypocretin messenger RNA and peptide content, and increased sleep in transgenic mice overexpressing human IGFBP3, an effect possibly mediated through decrease

Study of the K+- to pi+- gamma gamma decay by the NA62 experiment

A study of the dynamics of the rare decay $K^\pm\to\pi^\pm\gamma\gamma$ has been performed on a sample of 232 decay candidates, with an estimated background of $17.4\pm1.1$ events, collected by the NA62 experiment at CERN in 2007. The results are combined with those from a measurement conducted by the NA48/2 collaboration at CERN. The combined model-independent branching ratio in the kinematic range $z=(m_{\gamma\gamma}/m_K)^2>0.2$ is ${\cal B}_{\rm MI}(z>0.2) = (0.965 \pm 0.063) \times 10^{-6}$, and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is ${\cal B}(K_{\pi\gamma\gamma}) = (1.003 \pm 0.056) \times 10^{-6}$. A detailed comparison of the results with the previous measurements is performed.A study of the dynamics of the rare decay $K^\pm\to\pi^\pm\gamma\gamma$ has been performed on a sample of 232 decay candidates, with an estimated background of $17.4\pm1.1$ events, collected by the NA62 experiment at CERN in 2007. The results are combined with those from a measurement conducted by the NA48/2 collaboration at CERN. The combined model-independent branching ratio in the kinematic range $z=(m_{\gamma\gamma}/m_K)^2>0.2$ is ${\cal B}_{\rm MI}(z>0.2) = (0.965 \pm 0.063) \times 10^{-6}$, and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is ${\cal B}(K_{\pi\gamma\gamma}) = (1.003 \pm 0.056) \times 10^{-6}$. A detailed comparison of the results with the previous measurements is performed.A study of the dynamics of the rare decay K±→π±γγ has been performed on a sample of 232 decay candidates, with an estimated background of 17.4±1.1 events, collected by the NA62 experiment at CERN in 2007. The results are combined with those from a measurement conducted by the NA48/2 Collaboration at CERN. The combined model-independent branching ratio in the kinematic range z=(mγγ/mK)2>0.2 is BMI(z>0.2)=(0.965±0.063)×10−6 , and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is B(Kπγγ)=(1.003±0.056)×10−6 . A detailed comparison of the results with the previous measurements is performed

Early phase of plasticity-related gene regulation and SRF dependent transcription in the hippocampus

Hippocampal organotypic cultures are a highly reliable in vitro model for studying neuroplasticity: in this paper, we analyze the early phase of the transcriptional response induced by a 20 \ub5M gabazine treatment (GabT), a GABA-Ar antagonist, by using Affymetrix oligonucleotide microarray, RT-PCR based time-course and chromatin-immuno-precipitation. The transcriptome profiling revealed that the pool of genes up-regulated by GabT, besides being strongly related to the regulation of growth and synaptic transmission, is also endowed with neuro-protective and pro-survival properties. By using RT-PCR, we quantified a time-course of the transient expression for 33 of the highest up-regulated genes, with an average sampling rate of 10 minutes and covering the time interval [10 3690] minutes. The cluster analysis of the time-course disclosed the existence of three different dynamical patterns, one of which proved, in a statistical analysis based on results from previous works, to be significantly related with SRF-dependent regulation (p-value<0.05). The chromatin immunoprecipitation (chip) assay confirmed the rich presence of working CArG boxes in the genes belonging to the latter dynamical pattern and therefore validated the statistical analysis. Furthermore, an in silico analysis of the promoters revealed the presence of additional conserved CArG boxes upstream of the genes Nr4a1 and Rgs2. The chip assay confirmed a significant SRF signal in the Nr4a1 CArG box but not in the Rgs2 CArG box

Review of Kaon Physics at CERN and in Europe

The Kaon physics program at CERN and in Europe will be presented. I will first give a short review of recent results form the NA48/2 and NA62 experiments, with special emphasis to the measurement of RK , the ratio of Kaon leptonic decays rates, K → eν and K → μν, using the full minimum bias data sample collected in 2007-2008. The main subject of the talk will be the study of the highly suppressed decay K → πνν. While its rate can be predicted with minimal theoretical uncertainty in the Standard Model (BR ∼ 8 × 10−11), the smallness of BR and the challenging experimental signature make it very difficult to measure. The branching ratio for this decay is thus a sensitive probe of the flavour sector of the SM. The aim of NA62 is the measurement of the K → πνν BR with ∼ 10% precision in two years of data taking. This will require the observation of 10K decays in the experiment's fiducial volume, as well as the use of high-performance systems for precision tracking, particle identification, and photon vetoing. These aspects of the experiment will also allow NA62 to carry out a rich program of searches for lepton flavour and/or number violating K decays. Data taking will start in October 2014. The physics prospects and the status of the construction and commissioning of the NA62 experiment will be presented. In the last part of the talk I will report on Kaon physics results and prospects from other experiments at CERN (e.g. LHCb) and in Europe (e.g. KLOE and KLOE-2) and briefly mention the status in US