244 research outputs found

    Identification of H3K4me1-associated proteins at mammalian enhancers.

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    Enhancers act to regulate cell-type-specific gene expression by facilitating the transcription of target genes. In mammalian cells, active or primed enhancers are commonly marked by monomethylation of histone H3 at lysine 4 (H3K4me1) in a cell-type-specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals is unclear. In this study, we conducted SILAC mass spectrometry experiments with mononucleosomes and identified multiple H3K4me1-associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments association of the chromatin-remodeling complex BAF to enhancers in vivo and that, in vitro, H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of the BAF component BAF45C indicate that monomethylation, but not trimethylation, is accommodated by BAF45C's H3K4-binding site. Our results suggest that H3K4me1 has an active role at enhancers by facilitating binding of the BAF complex and possibly other chromatin regulators

    Neuronal circuitry for pain processing in the dorsal horn

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    Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

    Evolutionary and Experimental Assessment of Novel Markers for Detection of Xanthomonas euvesicatoria in Plant Samples

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    BACKGROUND: Bacterial spot-causing xanthomonads (BSX) are quarantine phytopathogenic bacteria responsible for heavy losses in tomato and pepper production. Despite the research on improved plant spraying methods and resistant cultivars, the use of healthy plant material is still considered as the most effective bacterial spot control measure. Therefore, rapid and efficient detection methods are crucial for an early detection of these phytopathogens. METHODOLOGY: In this work, we selected and validated novel DNA markers for reliable detection of the BSX Xanthomonas euvesicatoria (Xeu). Xeu-specific DNA regions were selected using two online applications, CUPID and Insignia. Furthermore, to facilitate the selection of putative DNA markers, a customized C program was designed to retrieve the regions outputted by both databases. The in silico validation was further extended in order to provide an insight on the origin of these Xeu-specific regions by assessing chromosomal location, GC content, codon usage and synteny analyses. Primer-pairs were designed for amplification of those regions and the PCR validation assays showed that most primers allowed for positive amplification with different Xeu strains. The obtained amplicons were labeled and used as probes in dot blot assays, which allowed testing the probes against a collection of 12 non-BSX Xanthomonas and 23 other phytopathogenic bacteria. These assays confirmed the specificity of the selected DNA markers. Finally, we designed and tested a duplex PCR assay and an inverted dot blot platform for culture-independent detection of Xeu in infected plants. SIGNIFICANCE: This study details a selection strategy able to provide a large number of Xeu-specific DNA markers. As demonstrated, the selected markers can detect Xeu in infected plants both by PCR and by hybridization-based assays coupled with automatic data analysis. Furthermore, this work is a contribution to implement more efficient DNA-based methods of bacterial diagnostics

    A 119-125 GeV Higgs from a string derived slice of the CMSSM

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    The recent experimental hints for a relatively heavy Higgs with a mass in the range 119-125 GeV favour supersymmetric scenarios with a large mixing in the stop mass matrix. It has been shown that this is possible in the constrained Minimal Super-symmetric Standard Model (CMSSM), but only for a very specific relation between the trilinear parameter and the soft scalar mass, favouring A ≈ −2m for a relatively light spectrum, and sizable values of tan β. We describe here a string-derived scheme in which the first condition is automatic and the second arises as a consequence of imposing radiative EW symmetry breaking and viable neutralino dark matter in agreement with WMAP constraints. More specifically, we consider modulus dominated SUSY-breaking in Type II string compactifications and show that it leads to a very predictive CMSSM-like scheme, with small departures due to background fluxes. Imposing the above constraints leaves only one free parameter, which corresponds to an overall scale. We show that in this construction A=−3/2–√m≃−2mA=−3/2m≃−2m and in the allowed parameter space tan β ≃ 38 − 41, leading to 119 GeV < mh  < 125 GeV. The recent LHCb results on BR(Bs → μ+μ−) further constrain this range, leaving only the region with mh ~ 125. GeV. We determine the detectability of this model and show that it could start being probed by the LHC at 7(8) TeV with a luminosity of 5(2) fb−1, and the whole parameter space would be accessible for 14 TeV and 25 fb−1. Furthermore, this scenario can host a long-lived stau with the right properties to lead to catalyzed BBN. We finally argue that anthropic arguments could favour the highest value for the Higgs mass that is compatible with neutralino dark matter, i.e., mh-125 GeV
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