A single nucleotide polymorphism in the promoter region of the human gene for osteoprotegerin is related to vascular morphology and function

Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor receptor family, and has previously been shown to regulate bone mass by inhibiting osteoclast differentiation and activation. Recent evidence indicates that OPG also plays a role in the vascular system, since ablation of the OPG gene in mice results in calcification of the aorta and renal arteries, and association has been found between serum levels of OPG and cardiovascular mortality. This study presents a novel single nucleotide polymorphism, a T/C transition located 129 bp upstream the TATA-box of the human OPG gene, detected by sequence analysis. The OPG genotype was determined by restriction fragment length polymorphism in a cohort consisting of 59 healthy subjects. The intima-media thickness (IMT) in the common carotid artery and maximal post-ischemic forearm blood flow (FBF) were investigated. Subjects with the CC genotype showed a significantly increased IMT (p<0.05) and a concommitantly reduced maximal FBF (p<0.01) as compared to those with the T allele. Thus, our results show that the polymorphism in the promoter region of OPG is associated with both vascular morphology and function in apparently healthy subjects.     

Ghrelin stimulates motility in the small intestine of rats through intrinsic cholinergic neurons

BACKGROUND AND PURPOSE: Ghrelin is a peptide discovered in endocrine cells of the stomach. Since ghrelin mRNA expression and plasma levels are elevated in the fasting state, we investigated the effects of ghrelin on the interdigestive migrating myoelectric complex (MMC) in the small intestine in vivo and compared with motor effects of ghrelin in vitro. Methods: Sprague-Dawley rats were supplied with a venous catheter and bipolar electrodes in the duodenum and jejunum for electromyography of small intestine in awake rats. In organ baths, isometric contractions of segments of rat jejunum were studied. RESULTS: Ghrelin dose-dependently shortened the MMC cycle length at all three recording points. At the duodenal site, the interval shortened from 17.2+/-2.0 to 9.9+/-0.8 min during infusion of ghrelin (1000 pmol kg(-1) min(-1)) and at the jejunal site from 17.5+/-2.2 to 10.5+/-0.8 min. Ghrelin contracted the muscle strips with a pD2 of 7.97+/-0.47. Atropine (10(-6) M) in vitro and (1 mg kg(-1)) in vivo blocked the effect of ghrelin. CONCLUSION: Ghrelin stimulates interdigestive motility through cholinergic neurons. Ghrelin also stimulates motility, in vitro, suggesting that ghrelin receptors are present in the intestinal neuromuscular tissue and mediate its effects via cholinergic mechanisms.     

Profiling and identification of eubacteria in the stomach of Mongolian gerbils with and without Helicobacter pylori infection

Background. Mongolian gerbils are frequently used to study Helicobacter pylori‐induced gastritis and its consequences. The presence of an indigenous bacterial flora with suppressive effect on H. pylori may cause difficulties with establishing this experimental model. Aim. The aim of the present study was to determine bacterial profiles in the stomach of Mongolian gerbils with and without (controls) H. pylori infection. Methods. Gastric tissue from H. pylori ATCC 43504 and CCUG 17874 infected and control animals were subjected to microbial culturing and histology. In addition, gastric mucosal samples from H. pylori ATCC 43504 infected and control animals were analyzed for bacterial profiling by temporal temperature gradient gel electrophoresis (TTGE), cloning and pyrosequencing of 16S rDNA variable V3 region derived PCR amplicons. Results. Oral administration of H. pylori ATCC 43504, but not CCUG 17874, induced colonization and gastric inflammation in the stomach of Mongolian gerbils. Temporal temperature gradient gel electrophoresis (TTGE) and partial 16S rDNA pyrosequencing revealed the presence of DNA representing a mixed bacterial flora in the stomach of both H. pylori ATCC 43504 infected and control animals. In both cases, lactobacilli appeared to be dominant. Conclusion. These findings suggest that indigenous bacteria, particularly lactobacilli, may have an impact on the colonization and growth of H. pylori strains in the stomach of Mongolian gerbils.     

Three-Dimensional Cost-Matrix Optimization and Maximum Cospeciation

In recent years, event-based approaches have been gaining ground in coevolutionary and biogeographical inference. Unlike pattern-based methods, event-based protocols deal directly with evolutionary events, such as dispersals and host switches. Three protocols have been proposed to date: (1) a coevolutionary method based on optimization of a standard two-dimensional cost matrix; (2) dispersal–vicariance analysis, based on optimization of a three-dimensional cost matrix; and (3) the maximum cospeciation method, thus far not considered a cost matrix method. I describe here general three-dimensional cost matrix optimization algorithms and how they can be applied to the maximum cospeciation problem. The new algorithms demonstrate that all existing event-based protocols, as well as possible future methods based on more complicated process models, can be incorporated into the three-dimensional cost matrix optimization framework.     

Spite and the scale of competition in Pseudomonas aeruginosa

Scale of competition has been shown to be an important factor in shaping the evolution of social interactions. Although many theoretical and experimental studies have examined its effect on altruistic cooperation, relatively little research effort has been focused on spiteful behaviors--actions that harm both the actor and the recipient. In this study, we expand on existing theory by investigating the importance of the global frequency of spiteful alleles, and we determine experimentally how the scale of competition affects selection for spite in the bacterial pathogen Pseudomonas aeruginosa under high and intermediate spatial relatedness. Consistent with our theoretical results, we found in our experiments that spiteful genotypes are more favored under local (rather than global) competition and intermediate (rather than high) spatial relatedness, conditions that have been shown to select against indiscriminate altruism.     

Synthesis and evaluation of 2-pyridylbenzothiazole, 2-pyridylbenzoxazole and 2-pyridylbenzofuran derivatives as 11C-PET imaging agents for β-amyloid plaques

The syntheses and SAR of new series of β-amyloid binding agents are reported. The effort to optimize signal-to-background ratios for these ligands are described. Compounds 8, 21 and 30 displayed desirable lipophilicity and pharmacokinetic properties. Compounds 8 and 21 were evaluated with in vitro autoradiographic studies and in vivo in APP/PS1 transgenic mice. It is shown that it was possible to increase the signal-to-background ratios compared to PIB 1, as demonstrated by compounds 8 and 21.     

Growth and survival trade-offs and outbreeding depression in rainbow trout (Oncorhynchus mykiss)

The purpose of this study was to examine, using a rainbow trout (Oncorhynchus mykiss) model system, the fitness consequences of three generations of introgression of genotypes adapted to two different environments (culture and nature). The experiments also isolated the influence of competitive interactions and risk of predation on the relative growth and survival of the wild and backcrossed lines. Line crosses representing fast-growing pure domestic (D), slow-growing pure wild (W), domestic x wild hybrids (F1), F1 x wild backcrosses (B1), and B1 x wild backcrosses (B2) were generated and reared under (1) culture conditions, (2) seminatural conditions with competition among genotypes, and (3) seminatural conditions under risk of predation. Survival of the fry in a seminatural environment with competition fit an additive model of gene action with the domestic fish having the highest survival and the wild fish the lowest, but under risk of predation outbreeding depression was suggested by low survival of the B2 lines. Evidence of a trade-off in growth and survival under risk of predation along with observations of genetically determined behavioral differences among the strains may provide some explanation for the observed differences in survival among the strains. This information is relevant to improving our evolutionary understanding of the interaction among genomes, and the influence of environment, during hybridization events. Results from this experiment indicate that alteration of phenotype likely played a prominent role in the reduced fitness experienced by progeny produced after three generations of introgression, supporting the theory that disruption of genotypes selected for adaptation to local conditions may be a primary cause of outbreeding depression in species such as salmon.