High variability and non-neutral evolution of the mammalian avpr1a gene

BACKGROUND: The arginine-vasopressin 1a receptor has been identified as a key determinant for social behaviour in Microtus voles, humans and other mammals. Nevertheless, the genetic bases of complex phenotypic traits like differences in social and mating behaviour among species and individuals remain largely unknown. Contrary to previous studies focusing on differences in the promotor region of the gene, we investigate here the level of functional variation in the coding region (exon 1) of this locus. RESULTS: We detected high sequence diversity between higher mammalian taxa as well as between species of the genus Microtus. This includes length variation and radical amino acid changes, as well as the presence of distinct protein variants within individuals. Additionally, negative selection prevails on most parts of the first exon of the arginine-vasopressin receptor 1a (avpr1a) gene but it contains regions with higher rates of change that harbour positively selected sites. Synonymous and non-synonymous substitution rates in the avpr1a gene are not exceptional compared to other genes, but they exceed those found in related hormone receptors with similar functions. DISCUSSION: These results stress the importance of considering variation in the coding sequence of avpr1a in regards to associations with life history traits (e.g. social behaviour, mating system, habitat requirements) of voles, other mammals and humans in particular.

Comparison of neutral oral contrast versus positive oral contrast medium in abdominal multidetector CT

To determine whether neutral contrast agents with water-equivalent intraluminal attenuation can improve delineation of the bowel wall and increase overall image quality for a non-selected patient population, a neutral oral contrast agent (3% mannitol) was administered to 100 patients referred for abdominal multidetector row computed tomography (MDCT). Their results were compared with those of 100 patients given a positive oral contrast agent. Qualitative and quantitative measurements were done on different levels of the gastrointestinal tract by three experienced readers. Patients given the neutral oral contrast agent showed significant better qualitative results for bowel distension (P < 0.001), homogeneity of the luminal content (P < 0.001), delineation of the bowel-wall to the lumen (P < 0.001) and to the mesentery (P < 0.001) and artifacts (P < 0.001), leading to a significant better overall image quality (P < 0.001) than patients receiving positive oral contrast medium. The quantitative measurements revealed significant better distension (P < 0.001) and wall to lumen delineation (P < 0.001) for the patients receiving neutral oral contrast medium. The present results show that the neutral oral contrast agent (mannitol) produced better distension, better homogeneity and better delineation of the bowel wall leading to a higher overall image quality than the positive oral contrast medium in a non-selected patient population.

Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients

PURPOSE: Neutral endopeptidase (CD10), an ectopeptidase bound to the cell surface, is thought to be a potential prognostic marker for prostate cancer. EXPERIMENTAL DESIGN: Prostate cancer patients (N = 3,261) treated by radical prostatectomy at a single institution were evaluated by using tissue microarray. Follow-up data were available for 2,385 patients. The cellular domain (membranous, membranous-cytoplasmatic, and cytoplasmatic only) of CD10 expression was analyzed immunohistochemically and correlated with various clinical and histopathologic features of the tumors. RESULTS: CD10 expression was detected in 62.2% of cancer samples and occurred preferentially in higher Gleason pattern (P < 0.0001). CD10 expression positively correlated with adverse tumor features such as elevated preoperative prostate-specific antigen (PSA), higher Gleason score, and advanced stage (P < 0.0001 each). Survival analyses showed that PSA recurrence was significantly associated with the staining pattern of CD10 expression. Outcome significantly declined from negative over membranous, membranous-cytoplasmatic, to exclusively cytoplasmatic CD10 expression (P < 0.0001). In multivariate analysis, CD10 expression was an independent predictor for PSA failure (P = 0.0343). CONCLUSIONS: CD10 expression is an unfavorable independent risk factor in prostate cancer. The subcellular location of CD10 protein is associated with specific clinical courses, suggesting an effect on different important biological properties of prostate cancer cells. The frequent expression of CD10 in prostate cancer and the strong association of CD10 with unfavorable tumor features may qualify this biomarker for targeted therapies.

Emission cross sections for neutral xenon impacted by Xe+ and Xe2+

Ion impact emission cross sections for eleven transitions from the 5p56p configuration to the 5p56s configuration of neutral xenon occurring in the spectral region between 700 nm and 1000 nm have been measured experimentally. Collisions between both singly- and doublyionized xenon and neutral xenon have been studied. These cross sections are of primary use in the development of a spectrographic diagnostic for Hall effect thruster plasma. A detailed discussion of the experimental methods and the subsequent data reduction is included. The results are presented and the importance of these data for spectrographic emission models of Hall effect thruster plasmas is discussed.

Mineralocorticoid receptor is essential for corticosteroid-induced up-regulation of L-type calcium currents in cultured neonatal cardiomyocytes

Despite the fact that mineralocorticoid receptor (MR) antagonist drugs such as spironolactone and eplerenone reduce the mortality in heart failure patients, there is, thus far, no unambiguous demonstration of a functional role of MR in cardiac cells. The aim of this work was to investigate the activation pathway(s) mediating corticosteroid-induced up-regulation of cardiac calcium current (ICa). In this study, using neonatal cardiomyocytes from MR or glucocorticoid receptor (GR) knockout (KO) mice, we show that MR is essential for corticosteroid-induced up-regulation of ICa. This study provides the first direct and unequivocal evidence for MR function in the heart.

Stress effects on working memory, explicit memory, and implicit memory for neutral and emotional stimuli in healthy men

Stress is a strong modulator of memory function. However, memory is not a unitary process and stress seems to exert different effects depending on the memory type under study. Here, we explored the impact of social stress on different aspects of human memory, including tests for explicit memory and working memory (for neutral materials), as well as implicit memory (perceptual priming, contextual priming and classical conditioning for emotional stimuli). A total of 35 young adult male students were randomly assigned to either the stress or the control group, with stress being induced by the Trier Social Stress Test (TSST). Salivary cortisol levels were assessed repeatedly throughout the experiment to validate stress effects. The results support previous evidence indicating complex effects of stress on different types of memory: A pronounced working memory deficit was associated with exposure to stress. No performance differences between groups of stressed and unstressed subjects were observed in verbal explicit memory (but note that learning and recall took place within 1 h and immediately following stress) or in implicit memory for neutral stimuli. Stress enhanced classical conditioning for negative but not positive stimuli. In addition, stress improved spatial explicit memory. These results reinforce the view that acute stress can be highly disruptive for working memory processing. They provide new evidence for the facilitating effects of stress on implicit memory for negative emotional materials. Our findings are discussed with respect to their potential relevance for psychiatric disorders, such as post traumatic stress disorder.