Enhanced mitochondrial superoxide scavenging does not Improve muscle insulin action in the high fat-fed mouse

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2(tg) mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat(tg) mice) have increased scavenging of O2(˙-) and H2O2, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat(tg) mice. The goal of the current study was to test the hypothesis that increased O2(˙-) scavenging alone or in combination with increased H2O2 scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2(tg), mcat(tg) and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2(tg) mice. Consistent with our previous work, HF-fed mcat(tg) mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O2(˙-) scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H2O2 scavenging

A survey of task-oriented crowdsourcing

Since the advent of artificial intelligence, researchers have been trying to create machines that emulate human behaviour. Back in the 1960s however, Licklider (IRE Trans Hum Factors Electron 4-11, 1960) believed that machines and computers were just part of a scale in which computers were on one side and humans on the other (human computation). After almost a decade of active research into human computation and crowdsourcing, this paper presents a survey of crowdsourcing human computation systems, with the focus being on solving micro-tasks and complex tasks. An analysis of the current state of the art is performed from a technical standpoint, which includes a systematized description of the terminologies used by crowdsourcing platforms and the relationships between each term. Furthermore, the similarities between task-oriented crowdsourcing platforms are described and presented in a process diagram according to a proposed classification. Using this analysis as a stepping stone, this paper concludes with a discussion of challenges and possible future research directions.This work is part-funded by ERDF-European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through the FCT-Fundacao para a Ciencia e a Tecnologia (Portuguese Foundation for Science and Technology) within the Ph.D. Grant SFRH/BD/70302/2010 and by the Projects AAL4ALL (QREN11495), World Search (QREN 13852) and FCOMP-01-0124-FEDER-028980 (PTDC/EEI-SII/1386/2012). The authors also thank Jane Boardman for her assistance proof reading the document.info:eu-repo/semantics/publishedVersio

Trends in suicide in a Lithuanian urban population over the period 1984–2003

BACKGROUND: Throughout the last decade of the twentieth century, Lithuania had the highest suicide rates in Europe among both men and women aged 25–64 years. The rates increased from 1986 until 1995, but later there was a slight decrease. This paper describes the trends in suicide deaths in urban population in Lithuania by gender, dates and suicide method over the period 1984–2003. METHODS: Data from the regional mortality register were used to analyze suicide deaths among all men and women aged 25–64 years in Kaunas city, Lithuania over the period 1984–2003. Age-standardized death rates per 100,000 persons (using European standard population) were calculated by gender, suicide method and dates. A joinpoint regression method was used to estimate annual percentage changes (EPACs) and to detect points where the trends changed significantly. RESULTS: The frequency of death by suicide among males was 48% higher in 1994–2003 than in 1984–1993. The corresponding increase among females was 28%. The most common methods of suicide among men were hanging, strangulation and suffocation (87.4% among all suicide deaths). The proportions of hanging, strangulation and suffocation in males increased by 6.9% – from 83.9% to 89.7% – compared to a 24.2% increase in deaths from handgun, rifle and shotgun firearm discharges and a 216.7% increase in deaths from poisoning with solvents, gases, pesticides and vapors. Among females, the most common methods of suicide were hanging, strangulation and suffocation (68.3% of all suicide deaths). The proportion of hanging deaths among females increased during the time period examined, whereas the proportion of poisonings with solid or liquid substances decreased. CONCLUSION: Suicide rates increased significantly among urban men aged 25–64 years in Lithuania throughout the period 1984–2003, whereas among women an increasing but statistically insignificant trend was observed. There were changes in the suicide methods used by both men and women. Changes in the choice of method may have contributed to the changes in suicide rates

Bayesian statistical modelling of human protein interaction network incorporating protein disorder information

<p>Abstract</p> <p>Background</p> <p>We present a statistical method of analysis of biological networks based on the exponential random graph model, namely p2-model, as opposed to previous descriptive approaches. The model is capable to capture generic and structural properties of a network as emergent from local interdependencies and uses a limited number of parameters. Here, we consider one global parameter capturing the density of edges in the network, and local parameters representing each node's contribution to the formation of edges in the network. The modelling suggests a novel definition of important nodes in the network, namely <it>social</it>, as revealed based on the local <it>sociality </it>parameters of the model. Moreover, the sociality parameters help to reveal organizational principles of the network. An inherent advantage of our approach is the possibility of hypotheses testing: <it>a priori </it>knowledge about biological properties of the nodes can be incorporated into the statistical model to investigate its influence on the structure of the network.</p> <p>Results</p> <p>We applied the statistical modelling to the human protein interaction network obtained with Y2H experiments. Bayesian approach for the estimation of the parameters was employed. We deduced <it>social </it>proteins, essential for the formation of the network, while incorporating into the model information on protein disorder. <it>Intrinsically disordered </it>are proteins which lack a well-defined three-dimensional structure under physiological conditions. We predicted the fold group (ordered or disordered) of proteins in the network from their primary sequences. The network analysis indicated that protein disorder has a positive effect on the connectivity of proteins in the network, but do not fully explains the interactivity.</p> <p>Conclusions</p> <p>The approach opens a perspective to study effects of biological properties of individual entities on the structure of biological networks.</p

Tyrphostins reduce chemotherapy-induced intestinal injury in mice: assessment by a biochemical assay

Intestinal injury that results from chemotherapy belongs to the major factors of dose-limitation in tumour therapy. The tyrphostins AG1714 and AG1801 reduce cisplatin and 5-FU-induced small intestinal mucosal damage, using a quantitative biochemical assay. The assay is based on the determination of the enzymatic activity of gamma-glutamyl transpeptidase, a marker of the brush border epithelium of the small intestine

Identifying a High Fraction of the Human Genome to be under Selective Constraint Using GERP++

Computational efforts to identify functional elements within genomes leverage comparative sequence information by looking for regions that exhibit evidence of selective constraint. One way of detecting constrained elements is to follow a bottom-up approach by computing constraint scores for individual positions of a multiple alignment and then defining constrained elements as segments of contiguous, highly scoring nucleotide positions. Here we present GERP++, a new tool that uses maximum likelihood evolutionary rate estimation for position-specific scoring and, in contrast to previous bottom-up methods, a novel dynamic programming approach to subsequently define constrained elements. GERP++ evaluates a richer set of candidate element breakpoints and ranks them based on statistical significance, eliminating the need for biased heuristic extension techniques. Using GERP++ we identify over 1.3 million constrained elements spanning over 7% of the human genome. We predict a higher fraction than earlier estimates largely due to the annotation of longer constrained elements, which improves one to one correspondence between predicted elements with known functional sequences. GERP++ is an efficient and effective tool to provide both nucleotide- and element-level constraint scores within deep multiple sequence alignments

Arsenic Exposure and Motor Function among Children in Bangladesh

Background: Several reports indicate that drinking water arsenic (WAs) and manganese (WMn) are associated with children’s intellectual function. Very little is known, however, about possible associations with other neurologic outcomes such as motor function

Long-term effect of lifestyle intervention on adiposity, metabolic parameters, inflammation and physical fitness in obese children: a randomized controlled trial

Epidemiology in Pediatrics and Child Healt

Effectiveness of Early Antiretroviral Therapy Initiation to Improve Survival among HIV-Infected Adults with Tuberculosis: A Retrospective Cohort Study

Molly Franke, Megan Murray, and colleagues report that early cART reduces mortality among HIV-infected adults with tuberculosis and improves retention in care, regardless of CD4 count