Acetylation genotype and the genetic susceptibility to postate cancer in a Southern European population

Epidemiologic studies have suggested that environmental factors and diet are important risk factors in the pathogenesis of prostate cancer. The N-acetyltransferases (NAT) are important enzymes in activation and inactivation of various carcinogens, including those found in well-cooked meat and cigarette smoke. METHODS. We analyzed DNA samples from 146 prostate cancer patients and 174 healthy men. We used PCR–RFLP method to analyze NAT1 and NAT2 polymorphisms. RESULTS. We did not find statistically significant differences in NAT1 genotypes frequencies between prostate cancer patients and control group. We observed an association of the slow acetylator genotype, NAT2*6/NAT2*6 with prostate cancer protection (P¼0.017;OR¼0.31, 95% CI 0.11–0.84). Multivariate logistic regression analysis confirmed this association (0.030; OR¼0.32, 95% CI 0.12–0.89). CONCLUSIONS. Our results indicate a role of NAT2 polymorphisms in the carcinogenic pathway of prostate cancer, specifically in a population of Southern Europe

The listening talker: A review of human and algorithmic context-induced modifications of speech

International audienceSpeech output technology is finding widespread application, including in scenarios where intelligibility might be compromised - at least for some listeners - by adverse conditions. Unlike most current algorithms, talkers continually adapt their speech patterns as a response to the immediate context of spoken communication, where the type of interlocutor and the environment are the dominant situational factors influencing speech production. Observations of talker behaviour can motivate the design of more robust speech output algorithms. Starting with a listener-oriented categorisation of possible goals for speech modification, this review article summarises the extensive set of behavioural findings related to human speech modification, identifies which factors appear to be beneficial, and goes on to examine previous computational attempts to improve intelligibility in noise. The review concludes by tabulating 46 speech modifications, many of which have yet to be perceptually or algorithmically evaluated. Consequently, the review provides a roadmap for future work in improving the robustness of speech output

Low copy numbers of complement C4 and C4A deficiency are risk factors for myositis, its subgroups and autoantibodies

Background Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complement C4 in IIM pathology was unknown. Methods We elucidated the gene copy number (GCN) variations of total C4, C4A and C4B, long and short genes in 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion. Results The large study populations helped establish the distribution patterns of various C4 GCN groups. Low GCNs of C4T (C4T=2+3) and C4A deficiency (C4A=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28-2.91), p=5.0×10 -53 for C4T, and 2.82 (2.48-3.21), p=7.0×10 -57 for C4A deficiency. Contingency and regression analyses showed that among patients with C4A deficiency, the presence of HLA-DR3 became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% had HLA-DR3 with an OR of 11.02 (1.44-84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies. Conclusions C4A deficiency is relevant in dermatomyositis, HLA-DRB1∗03 is important in IBM and both C4A deficiency and HLA-DRB1∗03 contribute interactively to risk of polymyositis

Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human Brain

Context: Modafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise. Objective: To measure the acute effects of modafinil at doses used therapeutically (200 mg and 400 mg given orally) on extracellular dopamine and on dopamine transporters in the male human brain. Design, Setting, and Participants: Positron emission tomography with [11C]raclopride (D2 / D3 radioligand sensitive to changes in endogenous dopamine) and [11C]cocaine (dopamine transporter radioligand) was used to measure the effects of modafinil on extracellular dopamine and on dopamine transporters in 10 healthy male participants. The study took place over an 8-month period (2007-2008) at Brookhaven National Laboratory. Main Outcome Measures: Primary outcomes were changes in dopamine D2 / D3 receptor and dopamine transporter availability (measured by changes in binding potential) after modafinil when compared with after placebo. Results: Modafinil decreased mean (SD) [11C]raclopride binding potential in caudate (6.1% [6.5%]; 95% confidence interval [CI], 1.5% to 10.8%; P = .02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P = .002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P = .02), reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P < .001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P < .001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P = .001), reflecting occupancy of dopamine transporters. Conclusions: In this pilot study, modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens). Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations.Chemistry and Chemical Biolog

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

[Roundtable Writer's Breakfast on "How 12 Wrongly Imprisoned Men Held Onto Hope" tape 2]

Video recording from The Black Academy of Arts and Letters recorded during the roundtable writer's breakfast, "Tested: How 12 Wrongly Imprisoned Men Held Onto Hope" with Payton Budd and Dorothy Budd held on March 2nd, 2013. The footage shows the opening of the dialogue facilitated by Curtis King on the topics of psychology, crime, law, and the prison system. The footage switches to art restoration content at the 32:45 time mark

[Roundtable Writer's Breakfast on "How 12 Wrongly Imprisoned Men Held Onto Hope" tape 1 of 2]

Video recording from The Black Academy of Arts and Letters recorded during the roundtable writer's breakfast, "Tested: How 12 Wrongly Imprisoned Men Held Onto Hope" with Payton Budd and Dorothy Budd held on March 2nd, 2013. The footage shows the opening of the dialogue facilitated by Curtis King on the topics of psychology, crime, law, and the prison system