Lifestyle Factors, Mitochondrial Dynamics, and Neuroprotection

The brain requires vast amounts of energy to carry out neurotransmission; indeed, it is responsible for approximately one-fifth of the body’s energy consumption. Therefore, in order to understand functions of brain cells under both normal and pathological conditions, it is critical to elucidate dynamics of intracellular energy. The mitochondrion is the key intercellular organelle that controls neuronal energy and survival. Numerous studies have reported a correlation between altered mitochondrial function and brain-associated diseases; thus mitochondria may serve as a promising target for treating these conditions. In this chapter, we will discuss the mechanisms of mitochondrial production, movement, and degradation in order to understand accessibility of energy during physiological and pathological conditions of the brain. While research targeting molecular dynamics is promising, translation into clinical relevance based on bench research is challenging. For these reasons, we will also summarize lifestyle factors, including interventions and chronic comorbidities that disrupt mitochondrial dynamics. By determining lifestyle factors that are readily accessible, we can propose a new viewpoint for a synergistic and translational approach for neuroprotection

BayesMendel: An R Environment for Mendelian Risk Prediction

Several important syndromes are caused by deleterious germline mutations of individual genes. In both clinical and research applications it is useful to evaluate the probability that an individual carries an inherited genetic variant of these genes, and to predict the risk of disease for that individual, using information on his/her family history. Mendelian risk prediction models accomplish these goals by integrating Mendelian principles and state-of-the art statistical models to describe phenotype/genotype relationships. Here we introduce an R library called BayesMendel that allows implementation of Mendelian models in research and counseling settings. BayesMendel is implemented in an object--oriented structure in the language R and distributed freely as an open source library. In its first release, it includes two major cancer syndromes: the breast-ovarian cancer syndrome and the hereditary non-polyposis colorectal cancer syndrome, along with up-to-date estimates of penetrance and prevalence for the corresponding genes. Input genetic parameters can be easily modified by users. BayesMendel can also serve as a generic tool for genetic epidemiologists to flexibly implement their own Mendelian models for novel syndromes and local subpopulations, without reprogramming complex statistical analyses and prediction tools

High throughput shotgun sequencing of eRNA reveals taxonomic and derived functional shifts across a benthic productivity gradient

Benthic macrofauna is regularly used in monitoring programmes, however the vast majority of benthic eukaryotic biodiversity lies mostly in microscopic organisms, such as meiofauna (invertebrates <1 mm) and protists, that rapidly responds to environmental change. These communities have traditionally been hard to sample and handle in the laboratory, but DNA sequencing has made such work less time consuming. While DNA sequencing captures both alive and dead organisms, environmental RNA (eRNA) better targets living organisms or organisms of recent origin in the environment. Here, we assessed the biodiversity of three known bioindicator microeukaryote groups (nematodes, foraminifera, and ciliates) in sediment samples collected at seven coastal sites along an organic carbon (OC) gradient. We aimed to investigate if eRNA shotgun sequencing can be used to simultaneously detect differences in (i) biodiversity of multiple microeukaryotic communities; and (ii) functional feeding traits of nematodes. Results showed that biodiversity was lower for nematodes and foraminifera in high OC (6.2%-6.9%), when compared to low OC sediments (1.2%-2.8%). Dissimilarity in community composition increased for all three groups between Low OC and High OC, as well as the classified feeding type of nematode genera (with more nonselective deposit feeders in high OC sediment). High relative abundant genera included nematodeSabatieriaand foraminiferaElphidiumin high OC, andCryptocaryon-like ciliates in low OC sediments. Considering that future sequencing technologies are likely to decrease in cost, the use of eRNA shotgun sequencing to assess biodiversity of benthic microeukaryotes could be a powerful tool in recurring monitoring programmes.Peer reviewe

xQTL workbench: a scalable web environment for multi-level QTL analysis

Summary: xQTL workbench is a scalable web platform for the mapping of quantitative trait loci (QTLs) at multiple levels: for example gene expression (eQTL), protein abundance (pQTL), metabolite abundance (mQTL) and phenotype (phQTL) data. Popular QTL mapping methods for model organism and human populations are accessible via the web user interface. Large calculations scale easily on to multi-core computers, clusters and Cloud. All data involved can be uploaded and queried online: markers, genotypes, microarrays, NGS, LC-MS, GC-MS, NMR, etc. When new data types come available, xQTL workbench is quickly customized using the Molgenis software generator

Effects of Aerobic Exercise On Anxiety Sensitivity

Anxiety sensitivity is a known precursor to panic attacks and panic disorder, and involves the misinterpretation of anxiety-related sensations. Aerobic exercise has been shown to reduce generalized anxiety, and may also reduce anxiety sensitivity through exposure to feared physiological sensations. Accordingly, 54 participants with elevated anxiety sensitivity scores completed six 20-min treadmill exercise sessions at either a high-intensity aerobic (n = 29) or low-intensity (n = 25) level. Self-ratings of anxiety sensitivity, fear of physiological sensations associated with anxiety, and generalized anxiety were obtained at pretreatment, post-treatment, and one-week follow-up. Results indicated that both high- and low-intensity exercise reduced anxiety sensitivity. However, high-intensity exercise caused more rapid reductions in a global measure of anxiety sensitivity and produced more treatment responders than low-intensity exercise. Only high-intensity exercise reduced fear of anxiety-related bodily sensations. The implications of these findings are discussed. (C) 2003 Elsevier Ltd. All rights reserved

Haplotype inference based on Hidden Markov Models in the QTL-MAS 2010 multi-generational dataset

<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated an approach for efficient computation of genotype probabilities, and more generally probabilities of allele inheritance in inbred as well as outbred populations. That work also included an extension for haplotype inference, or phasing, using Hidden Markov Models. Computational phasing of multi-thousand marker datasets has not become common as of yet. In this communication, we further investigate the method presented earlier for such problems, in a multi-generational dataset simulated for QTL detection.</p> <p>Results</p> <p>When analyzing the dataset simulated for the 14th QTLMAS workshop, the phasing produced showed zero deviations compared to original simulated phase in the founder generation. In total, 99.93% of all markers were correctly phased. 97.68% of the individuals were correct in all markers over all 5 simulated chromosomes. Results were produced over a weekend on a small computational cluster. The specific algorithmic adaptations needed for the Markov model training approach in order to reach convergence are described.</p> <p>Conclusions</p> <p>Our method provides efficient, near-perfect haplotype inference allowing the determination of completely phased genomes in dense pedigrees. These developments are of special value for applications where marker alleles are not corresponding directly to QTL alleles, thus necessitating tracking of allele origin, and in complex multi-generational crosses. The cnF2freq codebase, which is in a current state of active development, is available under a BSD-style license.</p

О работе конференции "Лекарственные средства Республики Беларусь"

ЗДРАВООХРАНЕНИЕ РЕСПУБЛИКИ БЕЛАРУСЬЛЕКАРСТВАКОНГРЕСС

The occurrence and characterization of Campylobacter jejuni and C. coli in organic pigs and their outdoor environment

The occurrence and species distribution of thermophilic Campylobacter was investigated in organic outdoor pigs. An increased exposure of outdoor pigs to C. jejuni from the environment may cause a shift from a normal dominance of C. coli to more C. jejuni, which may imply a concern of reduced food safety. Bacteriological methods for determination of Campylobacter excretion level were combined with colony-blot hybridization and real-time PCR for specific detection of C. jejuni in pigs. Campylobacter was isolated from pigs (n = 47), paddock environment (n = 126) and wildlife (n = 44), identified to species by real-time PCR and sub-typed by serotyping (Penner) and pulse-field gel electrophorsis (PFGE) genotyping. All pigs excreted Campylobacter (103–107 CFU g1 faeces) from the age of 8–13-weeks old. C. jejuni was found in 29% of pigs in three consecutive trials and always in minority to C. coli (0.3–46%). C. jejuni and C. coli were isolated from 10% and 29% of the environmental samples, respectively, while crow-birds and rats harboured C. jejuni. Individual pigs hosted several strains (up to nine serotypes). The paddock environment was contaminated with C. coli serotypes similar to pig isolates, while most of the C. jejuni serotypes differed. C. jejuni isolates of different origin comprised few similar serotypes, just one identical genotype was common between pigs, environment and birds. In conclusion, the occurrence of C. jejuni varied considerably between the three groups of outdoor pigs. Furthermore, transfer of C. jejuni to the outdoor pigs from the nearby environment was not predominant according to the subtype dissimilarities of the obtained isolates

Acute-Phase CD8 T cell responses that select for escape variants are needed to control live attenuated simian immunodeficiency virus

The overall CD8 T cell response to human/simian immunodeficiency virus (HIV/SIV) targets a collection of discrete epitope specificities. Some of these epitope-specific CD8 T cells emerge in the weeks and months following infection and rapidly select forsequence variants, whereas other CD8 T cell responses develop during the chronic infection phase and rarely select for sequence variants. In this study, we tested the hypothesis that acute-phase CD8 T cell responses that do not rapidly select for escapevariants are unable to control viral replication in vivo as well as those that do rapidly select for escape variants. We created a derivative of live attenuated SIV (SIVmac239Δnef) in which we ablated five epitopes that elicit early CD8 T cell responses and rapidly accumulate sequence variants in SIVmac239-infected Mauritian cynomolgus macaques (MCMs) that are homozygous for the M3 major histocompatibility complex (MHC) haplotype. This live attenuated SIV variant was called m3KOΔnef. Viremia was significantly higher in M3 homozygous MCMs infected withm3KOΔnef than in either MHC-mismatched MCMs infected with m3KOΔ nef or MCMs infected with SIVmac239Δnef. Three CD8 T cell responses, including two that do not rapidly select for escape variants, predominated during earlym3KOΔnef infection in the M3 homozygous MCMs, but these animals were unable to control viral replication. These re-sults provide evidence that acute-phase CD8 T cell responses that have the potential to rapidly select for escape variants in the early phase ofinfection are needed to establish viral control in vivo

Deposition conditions for the indium-bearing polymetallic quartz veins at Sarvlaxviken, south-eastern Finland

Polymetallic quartz veins, with up to 1500ppm indium, have been discovered recently in the Sarvlaxviken area within the 1.64Ga anorogenic multiphase Wiborg rapakivi batholith and adjacent 1.90Ga Svecofennian crust in SE Finland. Evidence from primary fluid inclusions in the Sarvlaxviken area provides new information on the hydrothermal transport and depositional processes of metals in anorogenic granites. Fluid inclusions with variable aqueous liquid and vapour proportions (5-90vol.% vapour) occur in quartz, cassiterite and fluorite belonging to three generations of polymetallic quartz veins. Microthermometry indicates that the veins were deposited at temperatures that range from similar to 500 degrees C down to <100 degrees C and salinities from 0 to 16 eq. mass% NaCl. Fluid inclusion data show that the depositional conditions were similar regardless of vein generation. The interpreted depositional processes involve phase separation with a combination of condensation, cooling and boiling of an initially low-salinity (<3 eq. mass% NaCl) aqueous magmatic vapour phase enriched in CO2-F-Cl-S and metals. Fluid inclusions with low salinities dominate, but higher salinities are recorded in metal-rich parts of the veins. The turbulent fluid flow, with complex geometry and temperature-salinity patterns, may explain why sulfide and/or oxide opaque minerals occur irregularly, and are locally the dominating vein minerals, but disappear completely into barren parts of the quartz veins. All fluids are considered to have been generated by the F-rich Marviken granite (and related granite dykes), which show all geochemical criteria for an ore-fertile granite. The quartz veins investigated in the adjacent Svecofennian country rocks are considered to represent the very last stage of a fluid with similar characteristics to the fluid responsible for the ore formation in the Sarvlaxviken area, but that had cooled to <100 degrees C