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Current rodent models of menopause fail to adequately recapitulate the menopause transition. The intact aging model fails to achieve very low estrogen levels, and the ovariectomy model lacks a perimenopause phase. A new rodent model of accelerated ovarian failure (AOF) successfully replicates human perimenopause and postrnenopause, including estrous acyclicity and fluctuating, followed by undetectable, estrogen levels, and allows for the dissociation of the effects of hormone levels from the effects of aging. In this model, an ovotoxic chemical, 4-vinylcyclohexene diepoxide (VCD), selective for primary and primordial follicles, is injected intraperitonelly in animals for 15 days. As the mature follicle population is depleted through natural cycling, ovarian failure follows increasing periods of acyclity. Administered at low doses, VCD specifically causes apoptotic cell death of primordial follicles but does not affect other peripheral tissues, including the liver and spleen, nor does it affect brain inflammation markers. In addition to reducing confounds associated with genetic and surgical manipulations, the AOF model maintains the presence of ovarian tissue which importantly parallels to the menopause transition in humans. The VCD injection procedure can be applied to studies using transgenic or knockout mice strains, or in other disease-state models (e.g., ischemia, atherosclerosis, or diabetes). This AOF model of menopause will generate new insights into women's health particularly in determining the critical periods (i.e., a window of opportunity) during perimenopause for restoring ovarian hormones for the most efficacious effect on memory and mood disorders as well as other menopausal symptoms. (C) 2011 Elsevier B.V. All rights reserved.

We report a new two-color fluorescent imaging system to visualize the mosaic adult photoreceptor neurons (Pits) in real-time. Using this method, we examined a collection of 434 mutants and identified genes required for PR survival, planar cell polarity (PCP), patterning and differentiation. We could track the progression of PR degeneration in living flies. By introducing the expression of p35, a caspase inhibitor, we found mutations that specifically activate caspase-dependent death. Moreover, we showed that grh is required in R3 for correct PCP establishment. The "Tomato/GFP-FLP/FRT" method allows high-throughput, rapid and precise identification of survival and developmental pathways in living adult PRs at single-cell resolution. (C) 2011 Elsevier Inc. All rights reserved.

Medulloblastoma (MB) is the most common malignant pediatric brain tumor and is thought to arise from genetic anomalies in developmental pathways required for the normal maturation of the cerebellar cortex, notably developmental pathways for granule cell progenitor (GCP) neurogenesis. Over the past decade, a wide range of studies have identified genes and their regulators within signaling pathways, as well as noncoding RNAs, that have crucial roles in both normal cerebellar development and pathogenesis. These include the Notch, Wnt/beta-catenin, bone morphogenic proteins (Bmp) and Sonic Hedgehog (Shh) pathways. In this review, we highlight the function of these pathways in the growth of the cerebellum and the formation of MB. A better understanding of the developmental origins of these tumors will have significant implications for enhancing the treatment of this important childhood cancer.

During development, a polarized epidermal sheet undergoes stratification and differentiation to produce the skin barrier. Through mechanisms that are poorly understood, the process involves actin dynamics, spindle reorientation and Notch signalling. To elucidate how epidermal embryogenesis is governed, we conditionally targeted serum response factor (Sri), a transcription factor that is essential for epidermal differentiation. Unexpectedly, previously ascribed causative defects are not responsible for profoundly perturbed embryonic epidermis. Seeking the mechanism for this, we identified actins and their regulators that were downregulated after ablation. Without Sri, cells exhibit a diminished cortical network and in mitosis, they fail to round up, features we recapitulate with low-dose actin inhibitors in vivo and shRNA-knockdown in vitro. Altered concomitantly are phosphorylated ERM and cortical myosin-IIA, shown in vitro to establish a rigid cortical actomyosin network and elicit critical shape changes. We provide a link between these features and Sri loss, and we show that the process is physiologically relevant in skin, as reflected by defects in spindle orientation, asymmetric cell divisions, stratification and differentiation.

The increasing use of high-throughput technologies and computational modeling is revealing new levels of biological function and organization. How are these features of systems biology influencing our view of the cell?

We report the first observation of two Cabibbo-suppressed decay modes of the B-s(0) meson. Using a sample of p (p) over bar collisions at root s = 1.96 TeV corresponding to 5: 9 fb(-1) of integrated luminosity collected with the CDF II, the collider detector at the Fermilab Tevatron, we search for new B-s(0) decay modes in a sample of events containing J/psi -> mu(+)mu(-) decays. We reconstruct a B-s(0) -> J/psi K*(892)(0) 0 signal with K*(892)(0) -> K+ pi(-), observing a yield of 151 +/- 25 events with a statistical significance of 8.0 sigma. We also reconstruct a B-s(0) -> J/psi K-s(0) signal with K-s(0) -> pi(+)pi(-) , observing a yield of 64 +/- 14 events with a statistical significance of 7.2 sigma. From these yields, we extract the branching ratios B(B-s(0) -> J/psi K* (892)(0) = (8.3 +/- 3.8) X 10(-5) and B(B-s(0) -> J/psi K-0) = (3.5 +/- 0.8) X 10(-5), where statistical, systematic, and fragmentation-fraction uncertainties are included in the combined uncertainty.

Background: The nosocomial prevalence of methicillin resistant Staphylococcus aureus (MRSA) in Portugal remains one of highest in Europe and is currently around 50%. Transmission of S. aureus, including MRSA, occurs principally by direct human-to-human skin contact. However, S. aureus can survive for long periods on inanimate objects, which may represent an important reservoir for dissemination as well. Methodology/Principal Findings: Between May 2009 and February 2010, handrails of 85 public urban buses circulating in Oporto, Portugal, were screened for the occurrence of MRSA. Twenty-two (26%) buses showed MRSA contamination. The molecular characterization of a total of 55 MRSA, by pulsed-field gel electrophoresis (PFGE), staphylococcal cassette chromosome (SCC) mec typing, spa typing, and multilocus sequence typing (MLST), clustered the isolates into three clonal types. However, the overwhelming majority (n = 50; 91%) of the isolates belonged to a single clone (PFGE A, spa types t747, t032, t025 or t020, ST22, SCCmec type IVh) that exhibits the characteristics of the pandemic EMRSA-15, currently the major lineage circulating in Portuguese hospitals, namely in the Oporto region. Two additional clones were found but in much lower numbers: (i) PFGE B, ST5, spa type t002, SCCmec IVa (n = 3), and (ii) PFGE C, spa type t008, ST8, SCCmec IVa (n = 2). None of the 55 isolates was PVL positive. Conclusions/Significance: Public buses in Oporto seem to be an important reservoir of MRSA of nosocomial origin, providing evidence that the major hospital-associated MRSA clone in Portugal is escaping from the primary ecological niche of hospitals to the community environment. Infection control measures are urgently warranted to limit the spread of EMRSA-15 to the general population and future studies are required to assess the eventual increase of MRSA in the Portuguese community, which so far remains low.

Bioorthogonal chemical reporters are useful tools for visualizing and identifying post-translational modifications on proteins. Here we report the proteomic analysis of mammalian proteins targeted by a series of fatty acid chemical reporters ranging from myristic to stearic acid. The large-scale analysis of total cell lysates from fully solubilized Jurkat T cells identified known fatty-acylated proteins and many new candidates, including nuclear proteins and in particular histone H3 variants. We demonstrate that histones H3.1, H3.2, and H3.3 are modified with fatty acid chemical reporters and identify the conserved cysteine 110 as a new site of S-acylation on histone H3.2. This newly discovered modification of histone H3 could have implications for nuclear organization and chromatin regulation. The unbiased proteomic analysis of fatty-acylated proteins using chemical reporters has revealed a greater diversity of lipid-modified proteins in mammalian cells and identified a novel post-translational modification of histones. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.001198, 1-16, 2011.

A search for microscopic black hole production and decay in pp collisions at a center-of-mass energy of 7 TeV has been conducted by the CMS Collaboration at the LHC, using a data sample corresponding to an integrated luminosity of 35 pb(-1). Events with large total transverse energy are analyzed for the presence of multiple high-energy jets, leptons, and photons, typical of a signal expected from a microscopic black hole. Good agreement with the standard model backgrounds, dominated by QCD multijet production, is observed for various final-state multiplicities and model-independent limits on new physics in these final states are set. Using simple semi-classical approximation, limits on the minimum black hole mass are derived as well, in the range 3.5-4.5 TeV. These are the first direct limits on black hole production at a particle accelerator. (c) 2011 CERN. Published by Elsevier B.V. All rights reserved.