Genomic landscape of rat strain and substrain variation

Background: Since the completion of the rat reference genome in 2003, whole-genome sequencing data from more than 40 rat strains have become available. These data represent the broad range of strains that are used in rat research including commonly used substrains. Currently, this wealth of information cannot be used to its full extent, because the variety of different variant calling algorithms employed by different groups impairs comparison between strains. In addition, all rat whole genome sequencing studies to date used an outdated reference genome for analysis (RGSC3.4 released in 2004). Results: Here we present a comprehensive, multi-sample and uniformly called set of genetic variants in 40 rat strains, including 19 substrains. We reanalyzed all primary data using a recent version of the rat reference assembly (RGSC5.0 released in 2012) and identified over 12 million genomic variants (SNVs, indels and structural variants) among the 40 strains. 28,318 SNVs are specific to individual substrains, which may be explained by introgression from other unsequenced strains and ongoing evolution by genetic drift. Substrain SNVs may have a larger predicted functional impact compared to older shared SNVs. Conclusions: In summary we present a comprehensive catalog of uniformly analyzed genetic variants among 40 widely used rat inbred strains based on the RGSC5.0 assembly. This represents a valuable resource, which will facilitate rat functional genomic research. In line with previous observations, our genome-wide analyses do not show evidence for contribution of multiple ancestral founder rat subspecies to the currently used rat inbred strains, as is the case for mouse. In addition, we find that the degree of substrain variation is highly variable between strains, which is of importance for the correct interpretation of experimental data from different labs

Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update

Large amounts of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2005. These include long-term follow-up studies in large community-based cohorts or asymptomatic subjects with chronic HBV infection, further studies on the role of HBV genotype/naturally occurring HBV mutations, treatment of drug resistance and new therapies. In addition, Pegylated interferon α2a, entecavir and telbivudine have been approved globally. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings were discussed and debated. The earlier “Asian-Pacific consensus statement on the management of chronic hepatitis B” was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, special indications for liver biopsy in patients with persistently normal alanine aminotransferase, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune-suppressive medications or chemotherapy and patients in the setting of liver transplantation, are also included

The experimental analysis of the interruptive, interfering, and identity-distorting effects of chronic pain

Pain is an unpleasant sensory and emotional experience urging the individual to take action to restore the integrity of the body. The transition from a common episode of acute pain to a state of intermittent or chronic pain has been a constant preoccupation of researchers and clinicians alike. In this review, we approach chronic pain from a modern learning perspective that incorporates cognitive, affective, behavioral and motivational aspects. We view pain as a biologically hard-wired signal of bodily harm that competes with other demands in the person’s environment. The basic tenet is that pain urges people to interrupt ongoing activity, elicits protective responses that paradoxically increase interference with daily activities, and compromises the sense of self. Here we briefly summarize existing evidence showing how pain captures attention, and how attention for pain can be controlled. We also consider pain as a strong motivator for learning, and review the recent evidence on the acquisition and generalization of pain-related fear and avoidance behavior, which are likely to interfere with daily life activities. We highlight the paradoxical effects of pain avoidance behavior, and review treatment effects of exposure in vivo. A generally neglected area of research is the detrimental consequences of repeated interference by pain with daily activities on one’s sense of “self”. We end this review with a plea for the implementation of single-case experimental designs as a means to help customize and develop novel cognitive-behavioral treatments for individuals for chronic pain aimed at reducing the suffering of this large group of individuals

APPROVAL

of a thesis submitted b

The Hierarchy of Probe Interval, Tolerance, and Interval k-Graphs

We introduce a series of generalizations of probe interval graphs called t-probe interval graphs, (a probe interval graph is a 1-probe interval graph) and show, via a method similar to graph homomorphism, that each class, including the class of probe interval graphs, is contained in the class of interval k-graphs. Any probe interval graph is clearly a tolerance graph, but for some t\u3e1 this relationship fails. We wish to determine this t. Also, the interval k-graphs whose complement describes a poset are believed to have a nice characterication via forbidden subgraphs, and we give the conjecture here, and a new description of these interval k-graphs that is similar to the salient property of function graphs

The sequenced rat brain transcriptome – its use in identifying networks predisposing alcohol consumption

Artículo de publicación ISIA quantitative genetic approach, which involves correlation of transcriptional networks with the phenotype in a recombinant inbred (RI) population and in selectively bred lines of rats, and determination of coinciding quantitative trait loci for gene expression and the trait of interest, has been applied in the present study. In this analysis, a novel approach was used that combined DNA-Seq data, data from brain exon array analysis of HXB/BXH RI rat strains and six pairs of rat lines selectively bred for high and low alcohol preference, and RNA-Seq data (including rat brain transcriptome reconstruction) to quantify transcript expression levels, generate co-expression modules and identify biological functions that contribute to the predisposition of consuming varying amounts of alcohol. A gene co-expression module was identified in the RI rat strains that contained both annotated and unannotated transcripts expressed in the brain, and was associated with alcohol consumption in the RI panel. This module was found to be enriched with differentially expressed genes from the selected lines of rats. The candidate genes within the module and differentially expressed genes between high and low drinking selected lines were associated with glia (microglia and astrocytes) and could be categorized as being related to immune function, energy metabolism and calcium homeostasis, as well as glial-neuronal communication. The results of the present study show that there are multiple combinations of genetic factors that can produce the same phenotypic outcome. Although no single gene accounts for predisposition to a particular level of alcohol consumption in every animal model, coordinated differential expression of subsets of genes in the identified pathways produce similar phenotypic outcomesNIAAA/NIH R24AA013162 U01AA016649 U01AA016663 AA006420 AAU01 T32AA007464 NHLBI/NIH HL35018 Banbury Fund Pearson Center for Alcoholism and Addiction Researc