Exclusive electroproduction of K+ Lambda and K+ Sigma^0 final states at Q^2 = 0.030-0.055 (GeV/c)^2

Cross section measurements of the exclusive p(e,e'K+)Lambda,Sigma^0 electroproduction reactions have been performed at the Mainz Microtron MAMI in the A1 spectrometer facility using for the first time the Kaos spectrometer for kaon detection. These processes were studied in a kinematical region not covered by any previous experiment. The nucleon was probed in its third resonance region with virtual photons of low four-momenta, Q^2= 0.030-0.055 (GeV/c)^2. The MAMI data indicate a smooth transition in Q^2 from photoproduction to electroproduction cross sections. Comparison with predictions of effective Lagrangian models based on the isobar approach reveal that strong longitudinal couplings of the virtual photon to the N* resonances can be excluded from these models.Comment: 16 pages, 7 figure

The Role of p300 Histone Acetyltransferase in UV-Induced Histone Modifications and MMP-1 Gene Transcription

Matrix metalloproteinase (MMP)-1 promotes ultraviolet (UV)-triggered long-term detrimental effects such as cancer formation and premature skin aging. Although histone modifications may play a crucial role in the transcriptional regulation of MMP-1, the relationship between UV-induced histone modification and MMP-1 expression is not completely understood. Here, we identify regulators of histone acetylation that may link UV-mediated DNA damage and MMP-1 induction by UV in cultured human dermal fibroblasts (HDFs) in vitro. UV irradiation of HDFs induced MMP-1 expression and increased the level of phosphorylation of H2AX (γ-H2AX), p53 and the acetylation of histone H3 (acetyl-H3). Total histone deacetylase (HDAC) enzymatic activity was decreased by UV irradiation, while histone acetyltransferase (HAT) activity was increased. Suppression of p300 histone acetyltransferase (p300HAT) activity by the p300HAT inhibitor anacardic acid (AA) or by down-regulation of p300 by siRNA prevented UV-induced MMP-1 expression and inhibited UV-enhanced γ-H2AX, p53 level, and acetyl-H3. Using chromatin immunoprecipitation assays, we observed that γ-H2AX, p53, acetyl-H3, p300 and c-Jun were consistently recruited by UV to a distinct region (−2067/−1768) adjacent to the p300 binding site (−1858/−1845) in the MMP-1 promoter. In addition, these recruitments of γ-H2AX, p53, acetyl-H3, p300 and c-Jun to the p300-2 site were significantly abrogated by post-treatment with AA. Furthermore, overexpression of p300 increased the basal and UV-induced MMP-1 promoter activity. Our results suggest that p300HAT plays a critical role in the transcriptional regulation of MMP-1 by UV

Significance of abnormal 53BP1 expression as a novel molecular pathologic parameter of follicular-shaped B-cell lymphoid lesions in human digestive tract

The digestive tract is a common site of extranodal malignant lymphomas (MLs) and benign lymphoid lesions (BLs). TP53-binding protein 1 (53BP1) expression has been widely investigated in class switch recombination but rarely in human lymphoid tissues with respect to tumorigenesis. We previously reported that immunofluorescence (IF) analysis of 53BP1 nuclear foci (NF), reflecting DNA double strand breaks, is useful for estimating genomic instability in different tumor types. In this study, we evaluated the potential of IF-based analysis of 53BP1 expression in differentiating MLs from BLs. We examined 231 biopsied tissue samples of primary MLs and BLs in the digestive tract. The 53BP1 immunoreactivity pattern was determined by multicolor IF. Compared to BLs, MLs showed a high frequency of abnormal 53BP1 expression (p < 0.0001). Statistically, abnormal 53BP1 expression is an effective test for distinguishing follicular lymphomas from BLs (specificity 98.6%, sensitivity 86.8%) and for distinguishing small B-cell lymphomas from BLs (specificity 98.3%, sensitivity 77.6%). Furthermore, a high frequency of abnormal 53BP1 expression was associated with “high-risk” MALT lymphomas, which exhibited t(11;18)(q21;21) (p = 0.0145). Collectively, these results suggest that IF-based analysis of 53BP1 expression in biopsy samples is a promising technique for diagnosing MLs in the digestive system

Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks

We thank M. Gellert, A. Singer and R. Hodes for critical comments on the manuscript. We also thank D. Sackett for assistance, Y. Pommier and P. Leder for kindly providing the ATM-deficient cells, S. Ganesan and J. Chen for kindly providing Brca1 and 53BP1 antibodies. In addition, we also thank R. Schroff and M. Lichten for sharing unpublished data.Histone H2AX is rapidly phosphorylated in the chromatin micro-environment surrounding a DNA double-strand break (DSB). Although H2AX deficiency is not detrimental to life, H2AX is required for the accumulation of numerous essential proteins into irradiation induced foci (IRIF). However, the relationship between IRIF formation, H2AX phosphorylation (gamma-H2AX) and the detection of DNA damage is unclear. Here, we show that the migration of repair and signalling proteins to DSBs is not abrogated in H2AX(-/-) cells, or in H2AX-deficient cells that have been reconstituted with H2AX mutants that eliminate phosphorylation. Despite their initial recruitment to DSBs, numerous factors, including Nbs1, 53BP1 and Brca1, subsequently fail to form IRIF. We propose that gamma-H2AX does not constitute the primary signal required for the redistribution of repair complexes to damaged chromatin, but may function to concentrate proteins in the vicinity of DNA lesions. The differential requirements for factor recruitment to DSBs and sequestration into IRIF may explain why essential regulatory pathways controlling the ability of cells to respond to DNA damage are not abolished in the absence of H2AX.S

First measurements of Lambda and Sigma0 hyperons in elementary electroproduction at MAMI

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