Skeletal muscle microRNA's in human cancer cachexia and type 2 diabetes

MicroRNAs are powerful post-transcriptional regulators of gene expression and are biomarkers of chronic diseases such as cancer. This thesis explores the role of microRNAs in human cancer cachexia and Type 2 diabetes. MicroRNA expression was measured in skeletal muscle biopsies using RT-qPCR. In pancreatic cancer cachexia patients, expression of microRNA-1, microRNA-133a, microRNA-133b and microRNA-206 was negatively related to weight loss. In Type 2 diabetes skeletal muscle, microRNA-133a and microRNA-206 expression was down-regulated, but there was no evidence of altered microRNA transcription or processing and target expression was unchanged. Importantly, microRNA-133a expression predicted fasting glucose, glucose tolerance and insulin resistance, and therefore may be a biomarker of Type 2 diabetes. Experimental validation of microRNA arrays was unsuccessful in identifying further novel cancer cachexia and Type 2 diabetes microRNA biomarkers. MicroRNA knockdown validated CDC42 and PTBP1 as microRNA-133a targets in myoblasts. In addition, muscle microRNA expression may be regulated by insulin and TNFa. In conclusion, microRNA-133a may be a skeletal muscle biomarker of Type 2 diabetes and cancer cachexia, microRNA-133a responds to extracellular insulin and TNFa, but it remains to be established whether microRNA-133a contributes to cancer cachexia or Type 2 diabetes pathogenesis

Uncertainty and the influence of group norms in the attitude–behaviour relationship

This is the author's post-print version of an article whose final and definitive form has been published in the British Journal of Social Psychology. Reproduced with permission from the British Journal of Social Psychology © The British Psychological Society 2007. The definitve version is available at: http://www.bpsjournals.co.uk/journals/bjsp/Two studies were conducted to examine the impact of subjective uncertainty on conformity to group norms in the attitude–behaviour context. In both studies, subjective uncertainty was manipulated using a deliberative mindset manipulation (McGregor, Zanna, Holmes, & Spencer, 2001). In Study 1 (N=106), participants were exposed to either an attitude-congruent or an attitude-incongruent in-group norm. In Study 2 (N=83), participants were exposed to either a congruent, incongruent, or an ambiguous in-group norm. Ranges of attitude–behaviour outcomes, including attitude-intention consistency and change in attitude-certainty, were assessed. In both studies, levels of group-normative behaviour varied as a function of uncertainty condition. In Study 1, conformity to group norms, as evidenced by variations in the level of attitude-intention consistency, was observed only in the high uncertainty condition. In Study 2, exposure to an ambiguous norm had different effects for those in the low and the high uncertainty conditions. In the low uncertainty condition, greatest conformity was observed in the attitude-congruent norm condition compared with an attitude-congruent or ambiguous norm. In contrast, individuals in the high uncertainty condition displayed greatest conformity when exposed to either an attitude-congruent or an ambiguous in-group norm. The implications of these results for the role of subjective uncertainty in social influence processes are discussed

Role of microRNA in muscle regeneration and diseases related to muscle dysfunction in atrophy, cachexia, osteoporosis, and osteoarthritis

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have emerged as potential predictive, prognostic, and therapeutic biomarkers, relevant to many pathophysiological conditions including limb immobilization, osteoarthritis, sarcopenia, and cachexia. Impaired musculoskeletal homeostasis leads to distinct muscle atrophies. Understanding miRNA involvement in the molecular mechanisms underpinning conditions such as muscle wasting may be critical to developing new strategies to improve patient management. MicroRNAs are powerful post-transcriptional regulators of gene expression in muscle and, importantly, are also detectable in the circulation. MicroRNAs are established modulators of muscle satellite stem cell activation, proliferation, and differentiation, however, there have been limited human studies that investigate miRNAs in muscle wasting. This narrative review summarizes the current knowledge as to the role of miRNAs in the skeletal muscle differentiation and atrophy, synthesizing the findings of published data

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Challenges in multidisciplinary cancer care among general surgeons in Canada

<p>Abstract</p> <p>Background</p> <p>While many factors can influence the way that cancer care is delivered, including the way that evidence is packaged and disseminated, little research has evaluated how health care professionals who manage cancer patients seek and use this information to identify whether and how this could be supported. Through interviews we identified that general surgeons experience challenges in coordinating care for complex cancer patients whose management is not easily addressed by guidelines, and conducted a population-based survey of general surgeon information needs and information seeking practices to extend these findings.</p> <p>Methods</p> <p>General surgeons with privileges at acute care hospitals in Ontario, Canada were mailed a questionnaire to solicit information needs (task, importance), information seeking (source, frequency of and reasons for use), key challenges and suggested solutions. Non-responders received up to three reminder packages. Significant differences among sub-groups (age, setting) were examined statistically (Kruskal Wallis, Mann Whitney, Chi Square). Standard qualitative methods were used to thematically analyze open-ended responses.</p> <p>Results</p> <p>The response rate was 44.2% (170/385) representing all 14 health regions. System resource constraints (60.4%), comorbidities (56.4%) and physiologic factors (51.8%) were top-ranked issues creating information needs. Local surgical colleagues (84.6%), other local colleagues (82.2%) and the Internet (81.1%) were top-ranked sources of information, primarily due to familiarity and speed of access. No resources were considered to be highly applicable to patient care. Challenges were related to limitations in diagnostics and staging, operative resources, and systems to support multidisciplinary care, together accounting for 76.0% of all reported issues. Findings did not differ significantly by surgeon age or setting of care.</p> <p>Conclusion</p> <p>General surgeons appear to use a wide range of information resources but they may not address the complex needs of many cancer patients. Decision-making is challenged by informational and logistical issues related to the coordination of multidisciplinary care. This suggests that limitations in system capacity may, in part, contribute to variable guideline compliance. Further research is required to evaluate the appropriateness of information seeking, and both concurrent and consecutive mechanisms by which to achieve multidisciplinary care.</p

Does Glycine max leaves or Garcinia Cambogia promote weight-loss or lower plasma cholesterol in overweight individuals: a randomized control trial

<p>Abstract</p> <p>Background</p> <p>Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing <it>Glycine max </it>leaves extract (EGML) or <it>Garcinia cambogia </it>extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles.</p> <p>Methods</p> <p>Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants.</p> <p>Results</p> <p>EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group.</p> <p>Conclusions</p> <p>Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis.</p

Copy Number Variation and Transposable Elements Feature in Recent, Ongoing Adaptation at the Cyp6g1 Locus

The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation mediated by cis-regulatory change. A fragment of an Accord transposable element inserted upstream of the Cyp6g1 gene is causally associated with resistance and has spread to high frequencies in populations around the world since the 1940s. Here we report the existence of a natural allelic series at this locus of D. melanogaster, involving copy number variation of Cyp6g1, and two additional transposable element insertions (a P and an HMS-Beagle). We provide evidence that this genetic variation underpins phenotypic variation, as the more derived the allele, the greater the level of DDT resistance. Tracking the spatial and temporal patterns of allele frequency changes indicates that the multiple steps of the allelic series are adaptive. Further, a DDT association study shows that the most resistant allele, Cyp6g1-[BP], is greatly enriched in the top 5% of the phenotypic distribution and accounts for ∼16% of the underlying phenotypic variation in resistance to DDT. In contrast, copy number variation for another candidate resistance gene, Cyp12d1, is not associated with resistance. Thus the Cyp6g1 locus is a major contributor to DDT resistance in field populations, and evolution at this locus features multiple adaptive steps occurring in rapid succession

The Epidemiology, Genetics and Future Management of Syndactyly

Syndactyly is a condition well documented in current literature due to it being the most common congenital hand defect, with a large aesthetic and functional significance

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe