Familial congenital esophageal atresia

Summary Esophageal atresia with or without tracheoesophageal fistula (EA±TEF) usually occurs sporadically either as an isolated malformation or in conjunction with other congenital anomalies. Seventy-six familial cases are recorded in the literature. Two personal cases are additionally reported. An overview of the 33 pedigrees with familial occurence of EA is presented. All available data of relevance for genetic analysis are compiled in eight tables. Attention is given to possible heterogeneity between sporadic and familial and between isolated and associated EA. Guidelines for genetic counseling are presented. With exception of the cases where EA is part of a chromosomal or of a known monogenic or teratogenic syndrome, the recurrence risks fit into a multifactorial scheme.     

Long-term effects of ungulates on phytophagous insects

Abstract.  1. Most plants interact with a diverse suite of herbivores, allowing the opportunity for the existence of positive and negative interactions between highly dissimilar organisms. However, most studies on herbivorous interactions have been performed under the assumption that they occur mainly between similar species. Consequently, ecologists are still far from a full understanding of the ecological factors that determine insect population dynamics.
2. In this study, a 7-year field experiment was conducted that manipulated the presence of ungulates to evaluate their effects on the abundance, attack rate, and survival of four guilds of co-occurring herbivorous insects living on the same host plant: seed predators, stem borers, gall makers and sap suckers. These four guilds differed in habits and behaviour, the first three being sessile and endophytic and the last being free-living.
3. This study shows that the abundance of all four guilds was negatively affected by ungulates. However, the effect on attack rate differed among guilds, as mammals do not affect the seed predator attack rate. Ungulates also differentially affected insect survival, ingesting only seed predators and gall makers.
4. In summary, this study suggests that diverse mechanisms may affect different insect guilds in different ways. Therefore, competition between disparate herbivores appears to be complex and can be provoked by multiple mechanisms.     

Antisense RNA decreases AP33 gene expression and cytoadherence by <Emphasis Type="Italic">T. vaginalis</Emphasis>

Background  

Host parasitism by Trichomonas vaginalis is complex. Adherence to vaginal epithelial cells (VECs) is mediated by surface proteins. We showed before that antisense down-regulation of expression of adhesin AP65 decreased amounts of protein, which lowered levels of T. vaginalis adherence to VECs. We now perform antisense down-regulation of expression of the ap33 gene to evaluate and confirm a role for AP33 in adherence by T. vaginalis. We also used an established transfection system for heterologous expression of AP33 in T. foetus as an additional confirmatory approach.     

Kernel-based data fusion for gene prioritization

MOTIVATION: Hunting disease genes is a problem of primary importance in biomedical research. Biologists usually approach this problem in two steps: first a set of candidate genes is identified using traditional positional cloning or high-throughput genomics techniques; second, these genes are further investigated and validated in the wet lab, one by one. To speed up discovery and limit the number of costly wet lab experiments, biologists must test the candidate genes starting with the most probable candidates. So far, biologists have relied on literature studies, extensive queries to multiple databases and hunches about expected properties of the disease gene to determine such an ordering. Recently, we have introduced the data mining tool ENDEAVOUR (Aerts et al., 2006), which performs this task automatically by relying on different genome-wide data sources, such as Gene Ontology, literature, microarray, sequence and more. RESULTS: In this article, we present a novel kernel method that operates in the same setting: based on a number of different views on a set of training genes, a prioritization of test genes is obtained. We furthermore provide a thorough learning theoretical analysis of the method's guaranteed performance. Finally, we apply the method to the disease data sets on which ENDEAVOUR (Aerts et al., 2006) has been benchmarked, and report a considerable improvement in empirical performance. AVAILABILITY: The MATLAB code used in the empirical results will be made publicly available.     

L-arginine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells

Impairment of placental growth is a major factor contributing to intrauterine growth retardation (IUGR) in both human pregnancy and animal production. Results of recent studies indicate that administration of L-arginine (Arg) to gestating pigs or sheep with IUGR fetuses can enhance fetal growth. However, the underlying mechanisms are largely unknown. The present study tested the hypothesis that Arg stimulates the mammalian target of rapamycin (mTOR) signaling pathway and protein synthesis in porcine conceptus trophectoderm (pTr2) cells. The cells were cultured for 4 days in Arg-free Dulbecco's modified Eagle's Ham medium containing 10, 50, 100, 200, 350 or 500 μM Arg. Cell numbers, protein synthesis and degradation, as well as total and phosphorylated levels of mTOR, ribosomal protein S6 kinase 1 (p70S6K) and eukaryotic initiation factor 4E-binding protein-1 (4EBP1), were determined. The pTr2 cells exhibited time (0-6 days)- and Arg concentration (10-350 μM)-dependent increases in proliferation. Addition of 100 and 350 μM Arg to culture medium dose-dependently increased (a) protein synthesis and decreased protein degradation and (b) the abundance of total and phosphorylated mTOR, p70S6K and 4EBP1 proteins. Effects of 350 μM Arg on intracellular protein turnover were only modestly affected when nitric oxide synthesis was inhibited. Collectively, these results indicate a novel and important role for Arg in promoting growth of porcine placental cells largely via a nitric-oxide-independent pathway. Additionally, these findings help to explain beneficial effects of Arg supplementation on improving survival and growth of embryos/fetuses in mammals.     

5-sulfonyl-benzimidazoles as selective CB2 agonists-part 2

In a previous communication, the SAR of a series of potent and selective 5-sulfonyl-benzimidazole CB2-receptor agonists was described. The lack of in vivo activity of compounds from this series was attributed to their poor solubility and metabolic stability. In this Letter, we report on the further optimization of this series, leading to the relatively polar and peripherically acting CB2 agonists 41 and 49. Although both compounds were not active in acute pain models, the less selective compound 41 displayed good, sustained activity in a chronic model of neuropathic pain without the tolerance observed with morphine. In addition, both 41 and 49 delayed the onset of clinical symptoms in an experimental model for Multiple sclerosis.