The conserved C-terminus of the PcrA/UvrD helicase interacts directly with RNA polymerase

Copyright: © 2013 Gwynn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a Wellcome Trust project grant to MD (Reference: 077368), an ERC starting grant to MD (Acronym: SM-DNA-REPAIR) and a BBSRC project grant to PM, NS and MD (Reference: BB/I003142/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

C9orf72 Expansion Disrupts ATM-mediated Chromosomal Break Repair

A hexanucleotide repeat expansion represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, though the mechanisms by which the expansion cause neurodegeneration are poorly understood. We report elevated levels of DNA/RNA hybrids (R-loops) and double-strand breaks (DSBs) in rodent neurons, human cells, and in C9orf72-ALS patient spinal cord tissues. Accumulation of endogenous DNA damage is concomitant with defective ATM-mediated DNA repair signalling and accumulation of protein-linked DNA breaks. We further reveal that defective ATM-mediated DNA repair is a consequence of p62 accumulation, which impairs H2A ubiquitylation and perturbs ATM signalling. Adeno-associated virus- mediated expression of C9orf72-related RNA and dipeptide repeats in the murine central nervous system causes elevated DSBs, ATM defects, and triggers neurodegeneration. These findings identify R-Loops, DSBs, and defective ATM-mediated repair as pathological consequences of C9orf72 expansions, and suggest that C9orf72-linked neurodegeneration is driven, at least in part, by genomic instability

Seasonal variation of suspended particulate matter in two-layered Izmit Bay, Turkey

The spatial and temporal distribution of suspended particulate matter (SPM) concentration in Izmit Bay (Sea of Marmara) were studied in order to examine the prevailing transport mechanisms under varying seasonal hydrographical conditions. The prevailing current system of the Bay occurs in two opposite directions and changes seasonally, flowing into the Bay as a lower layer and flowing out to the Sea of Marmara as an upper layer in autumn and winter. SPM concentrations and distribution pattern of both upper and lower water layers display variations throughout the year, reflecting a seasonal cycle and variability of the circulation and stratification of two water layers seems to control the vertical and spatial distribution of SPM in Izmit Bay. The SPM concentration of the lower layer is higher than that of the upper layer with an increase in intensity of the pycnocline in summer. Homogeneous vertical distribution of SPM during February and March is supported by the weak stratification of the two layers. SPM transportation from Izmit Bay to the open sea occurs in winter, whereas it is carried to interior of the Bay from central to eastern basins in summer. Both the grain size distribution of the bottom sediments and the temporal-spatial variation of SPM content of the water column indicate that the transportation and depositional conditions are different in the three basins. Predominantly fine-grained-sized bottom sediments are deposited in the central and eastern basins due to the reduced current velocities in the lower layer. The western basin is subjected to deposition of sediments with various size, from both the central basin and the Sea of Marmara. (C) 1999 Academic Press

Effects of Mast-Cell Stabilization in Cerulein-Induced Acute Pancreatitis in Rats.

Acute pancreatitis is characterized by inflammationof the pancreas that ranges from mild inflammationto severe necrotizing pancreatitis (1-3).Several factors can initiate a cascade of pathologic events that results in AP (4). A key feature in thispathogenesis is inflammatory reaction. However,causes of exaggerated inflammatory reaction are notwell understood (4,5). Since the pathogenesis of pancreatitisis still unclear, most of the treatment modalitiesare largely supportive and independent of thepathogenesis (1,2)

Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment

Objective: To determine whether first-voided urinary LH (FV-ULH) - level measurement can adequately assess pubertal suppression as much as standard tests can. Subjects and methods: The study group included patients with central precocious puberty and rapidly progressing early puberty who received up to 3 - 4 doses of GnRHa therapy monthly and did not have adequate hormonal suppression after GnRH stimulation (90-minute LH level > 4 IU/L). Design: All of the participants underwent an LHRH test just after admission to the study. According to the stimulated peak LH levels, the patients were divided into 2 groups and followed until the end of the first year of treatment.The concordance between FV-ULH and stimulated LH levels was assessed. Results: The FV-ULH levels in patients with inadequate hormonal suppression were significantly high compared to patients with adequate hormonal suppression. FV-ULH levels were very strongly correlated with stimulated LH levels (r = 0.91). Its correlation with basal LH levels was significant (r = 0.65). However, this positive correlation was modestly weakened after the first year of treatment.The cutoff value for FV-ULH of 1.01 mlU/mL had the highest sensitivity (92.3\%) and specificity (100\%). Conclusion: FV-ULH levels, using more reliable and sensitive assay methods, can be used to monitor the adequacy of GnRHa therapy