Prepulse inhibition predicts spatial working memory performance in the inbred Roman high- and low-avoidance rats and in genetically heterogeneous NIH-HS rats: relevance for studying pre-attentive and cognitive anomalies in schizophrenia

Animal models of schizophrenia-relevant symptoms are increasingly important for progress in our understanding of the neurobiological basis of the disorder and for discovering novel and more specific treatments. Prepulse inhibition (PPI) and working memory, which are impaired in schizophrenic patients, are among the symptoms/processes modeled in those animal analogues. We have evaluated whether a genetically-selected rat model, the Roman high-avoidance inbred strain (RHA-I), displays PPI deficits as compared with its Roman low-avoidance (RLA-I) counterpart and the genetically heterogeneous NIH-HS rat stock. We have investigated whether PPI deficits predict spatial working memory impairments (in the Morris water maze; MWM) in these three rat types (Experiment 1), as well as in a separate sample of NIH-HS rats stratified according to their extreme (High, Medium, Low) PPI scores (Experiment 2). The results from Exp. 1 show that RHA-I rats display PPI and spatial working memory deficits compared to both RLA-I and NIH-HS rats. Likewise, in Exp. 2, “Low-PPI” NIH-HS rats present significantly impaired working memory with respect to “Medium-PPI” and “High-PPI” NIH-HS subgroups. Further support to these results comes from correlational, factorial and multiple regression analyses, which reveal that PPI is positively associated with spatial working memory performance. Conversely, cued learning in the MWM was not associated with PPI.Thus, using genetically-selected and genetically heterogeneous rats, the present study shows, for the first time, that PPI is a positive predictor of performance in a spatial working memory task. These results may have translational value for schizophrenia symptom research in humans, as they suggest that either by psychogenetic selection or by focusing on extreme PPI scores from a genetically heterogeneous rat stock, it is possible to detect a useful (perhaps “at risk”) phenotype to study cognitive anomalies linked to schizophrenia

Dietary Mg Supplementation Decreases Oxidative Stress, Inflammation, and Vascular Dysfunction in an Experimental Model of Metabolic Syndrome with Renal Failure

whether a dietary Mg supplementation might attenuate vascular dysfunction through the modulation of oxidative stress and inflammation in concurrent MetS and CKD. Methods: A rat model of MetS (Zucker strain) with CKD (5/6 nephrectomy, Nx) was used. Nephrectomized animals were fed a normal 0.1%Mg (MetS+Nx+Mg0.1%) or a supplemented 0.6%Mg (MetS+Nx+Mg0.6%) diet; Sham-operated rats with MetS receiving 0.1%Mg were used as controls. Results: As compared to controls, the MetS+Nx-Mg0.1% group showed a significant increase in oxidative stress and inflammation biomarkers (lipid peroxidation and aortic interleukin-1b and -6 expression) and Endothelin-1 levels, a decrease in nitric oxide and a worsening in uremia and MetS associated pathology as hypertension, and abnormal glucose and lipid profile. Moreover, proteomic evaluation revealed changes mainly related to lipid metabolism and CVD markers. By contrast, in the MetS+Nx+Mg0.6% group, these parameters remained largely similar to controls. Conclusion: In concurrent MetS and CKD, dietary Mg supplementation reduced inflammation and oxidative stress and improved vascular function

Dietary Mg Supplementation Decreases Oxidative Stress, Inflammation, and Vascular Dysfunction in an Experimental Model of Metabolic Syndrome with Renal Failure

Background: Metabolic syndrome (MetS) and chronic kidney disease (CKD) are commonly associated with cardiovascular disease (CVD) and in these patients Mg concentration is usually decreased. This study evaluated whether a dietary Mg supplementation might attenuate vascular dysfunction through the modulation of oxidative stress and inflammation in concurrent MetS and CKD. Methods: A rat model of MetS (Zucker strain) with CKD (5/6 nephrectomy, Nx) was used. Nephrectomized animals were fed a normal 0.1%Mg (MetS+Nx+Mg0.1%) or a supplemented 0.6%Mg (MetS+Nx+Mg0.6%) diet; Sham-operated rats with MetS receiving 0.1%Mg were used as controls. Results: As compared to controls, the MetS+Nx-Mg0.1% group showed a significant increase in oxidative stress and inflammation biomarkers (lipid peroxidation and aortic interleukin-1b and -6 expression) and Endothelin-1 levels, a decrease in nitric oxide and a worsening in uremia and MetS associated pathology as hypertension, and abnormal glucose and lipid profile. Moreover, proteomic evaluation revealed changes mainly related to lipid metabolism and CVD markers. By contrast, in the MetS+Nx+Mg0.6% group, these parameters remained largely similar to controls. Conclusion: In concurrent MetS and CKD, dietary Mg supplementation reduced inflammation and oxidative stress and improved vascular function

Multi-institutional expert update on the use of laparoscopic bile duct exploration in the management of choledocholithiasis: lesson learned from 3950 procedures

Background: Recently there has been a growing interest in the laparoscopic management of common bile duct stones with gallbladder in situ (LBDE), which is favoring the expansion of this technique. Our study identified the standardization factors of LBDE and its implementation in the single-stage management of choledocholithiasis. Methods: A retrospective multi-institutional study among 17 centers with proven experience in LBDE was performed. A cross-sectional survey consisting of a semi-structured pretested questionnaire was distributed covering the main aspects on the use of LBDE in the management of choledocholithiasis. Results: A total of 3950 LBDEs were analyzed. The most frequent indication was jaundice (58.8%). LBDEs were performed after failed ERCP in 15.2%. The most common approach used was the transcystic (63.11%). The overall series failure rate of LBDE was 4% and the median rate for each center was 6% (IQR, 4.5-12.5). Median operative time ranged between 60-120 min (70.6%). Overall morbidity rate was 14.6%, with a postoperative bile leak and complications ≥3a rate of 4.5% and 2.5%, respectively. The operative time decreased with experience (P =.03) and length of hospital stay was longer in the presence of a biliary leak (P =.04). Current training of LBDE was defined as poor or very poor by 82.4%. Conclusion: Based on this multicenter survey, LBDE is a safe and effective approach when performed by experienced teams. The generalization of LBDE will be based on developing training programs

A resource for the simultaneous high-resolution mapping of multiple quantitative trait loci in rats: The NIH heterogeneous stock

The laboratory rat (Rattus norvegicus) is a key tool for the study of medicine and pharmacology for human health. A large database of phenotypes for integrated fields such as cardiovascular, neuroscience, and exercise physiology exists in the literature. However, the molecular characterization of the genetic loci that give rise to variation in these traits has proven to be difficult. Here we show how one obstacle to progress, the fine-mapping of quantitative trait loci (QTL), can be overcome by using an outbred population of rats. By use of a genetically heterogeneous stock of rats, we map a locus contributing to variation in a fear-related measure (two-way active avoidance in the shuttle box) to a region on chromosome 5 containing nine genes. By establishing a protocol measuring multiple phenotypes including immunology, neuroinflammation, and hematology, as well as cardiovascular, metabolic, and behavioral traits, we establish the rat HS as a new resource for the fine-mapping of QTLs contributing to variation in complex traits of biomedical relevance

Contributions of allochthonous inputs of food to the diets of benthopelagic fish over the northwest Mediterranean slope (to 2300 m)

14 pages, 4 figures, 6 tablesThe contributions of allochthonous inputs of food (food falls, plastics and other anthropogenic remains) in the diets of large fish (6 teleosteans, 3 sharks) were analyzed for depths between 500 and 2300 m in the deep Balearic basin (western Mediterranean). The analyses were based on gut contents. The identification was based on a multi-analytic approach, comprising morphological features (including morphometric analysis) and molecular genetics (DNA barcoding method). Remains of a number of anthropogenic, inorganic materials (microplastic fibres, plastic bags and cartons) appeared regularly in the guts of deep-sea fish (e.g., in Trachyrhynchus scabrus and Mora moro), though always at low occurrence (9.1% of fish at most) and negligible weights (< 2%W of diet). In our sampling, covering an area of ca. 12 km2, large food falls contribute only a little to fish diets by weight, W, e.g., in shark diets they represented 4.5%W for Centroscymnus coelolepis and 11%W for Galeus melastomus. However, the importance of food falls (e.g., cetacean blubber and carcharhinid shark remains) was substantial locally (up to 70.8%W of C. coelolepis diet) particularly near canyons. The arrival of livestock remains (beef flesh, goat ribs and vertebrae) was shown by molecular analyses to contributed to deep-sea shark diets (ca. 5.5%W) comparably to natural food falls. These remains, which originate from human activity, may locally alter the food webs of oligotrophic environments like that of the deep Mediterranean. Food falls of both natural and anthropogenic origin were mainly found in fish collected close to canyon axes. The only cetacean fall documented in the deep Balearic Basin was also near a canyon, the carcass of a small (ca. 1.2 m) striped dolphin, Stenella coeruleoalba, collected in a haul at 1750 m off BarcelonaPeer Reviewe

Combined sequence-based and genetic mapping analysis of complex traits in outbred rats

<p>Genetic mapping on fully sequenced individuals is transforming understanding of the relationship between molecular variation and variation in complex traits. Here we report a combined sequence and genetic mapping analysis in outbred rats that maps 355 quantitative trait loci for 122 phenotypes. We identify 35 causal genes involved in 31 phenotypes, implicating new genes in models of anxiety, heart disease and multiple sclerosis. The relationship between sequence and genetic variation is unexpectedly complex: at approximately 40% of quantitative trait loci, a single sequence variant cannot account for the phenotypic effect. Using comparable sequence and mapping data from mice, we show that the extent and spatial pattern of variation in inbred rats differ substantially from those of inbred mice and that the genetic variants in orthologous genes rarely contribute to the same phenotype in both species.</p>

Homomorphisms and Ramsey properties of antimatroids

SIGLEBibliothek Weltwirtschaft Kiel C132,202 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

haplotype_dosages_Rnor50.tar.gz

Probabilities of descent (haplotype dosages) of 1,407 Heterogenous Stock rat from each of the eight progenitors of the Stock, at each locus in the genom