Positive psychology of Malaysian students: impacts of engagement, motivation, self-compassion and wellbeing on mental health

Malaysia plays a key role in education of the Asia Pacific, expanding its scholarly output rapidly. However, mental health of Malaysian students is challenging, and their help-seeking is low because of stigma. This study explored the relationships between mental health and positive psychological constructs (academic engagement, motivation, self-compassion, and wellbeing), and evaluated the relative contribution of each positive psychological construct to mental health in Malaysian students. An opportunity sample of 153 students completed the measures regarding these constructs. Correlation, regression, and mediation analyses were conducted. Engagement, amotivation, self-compassion, and wellbeing were associated with, and predicted large variance in mental health. Self-compassion was the strongest independent predictor of mental health among all the positive psychological constructs. Findings can imply the strong links between mental health and positive psychology, especially selfcompassion. Moreover, intervention studies to examine the effects of self-compassion training on mental health of Malaysian students appear to be warranted.N/

β-Hydroxy-β-Methylbutyrate (HMB) Normalizes Dexamethasone-Induced Autophagy-Lysosomal Pathway in Skeletal Muscle

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.This project has been funded by Abbott Nutrition R&D

A Transgenic Drosophila Model Demonstrates That the Helicobacter pylori CagA Protein Functions as a Eukaryotic Gab Adaptor

Infection with the human gastric pathogen Helicobacter pylori is associated with a spectrum of diseases including gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa–associated lymphoid tissue lymphoma. The cytotoxin-associated gene A (CagA) protein of H. pylori, which is translocated into host cells via a type IV secretion system, is a major risk factor for disease development. Experiments in gastric tissue culture cells have shown that once translocated, CagA activates the phosphatase SHP-2, which is a component of receptor tyrosine kinase (RTK) pathways whose over-activation is associated with cancer formation. Based on CagA's ability to activate SHP-2, it has been proposed that CagA functions as a prokaryotic mimic of the eukaryotic Grb2-associated binder (Gab) adaptor protein, which normally activates SHP-2. We have developed a transgenic Drosophila model to test this hypothesis by investigating whether CagA can function in a well-characterized Gab-dependent process: the specification of photoreceptors cells in the Drosophila eye. We demonstrate that CagA expression is sufficient to rescue photoreceptor development in the absence of the Drosophila Gab homologue, Daughter of Sevenless (DOS). Furthermore, CagA's ability to promote photoreceptor development requires the SHP-2 phosphatase Corkscrew (CSW). These results provide the first demonstration that CagA functions as a Gab protein within the tissue of an organism and provide insight into CagA's oncogenic potential. Since many translocated bacterial proteins target highly conserved eukaryotic cellular processes, such as the RTK signaling pathway, the transgenic Drosophila model should be of general use for testing the in vivo function of bacterial effector proteins and for identifying the host genes through which they function

Blood cultures for the diagnosis of multidrug-resistant and extensively drug-resistant tuberculosis among HIV-infected patients from rural South Africa: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The yield of mycobacterial blood cultures for multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) among drug-resistant TB suspects has not been described.</p> <p>Methods</p> <p>We performed a retrospective, cross-sectional analysis to determine the yield of mycobacterial blood cultures for MDR-TB and XDR-TB among patients suspected of drug-resistant TB from rural South Africa. Secondary outcomes included risk factors of <it>Mycobacterium tuberculosis </it>bacteremia and the additive yield of mycobacterial blood cultures compared to sputum culture.</p> <p>Results</p> <p>From 9/1/2006 to 12/31/2008, 130 patients suspected of drug-resistant TB were evaluated with mycobacterial blood culture. Each patient had a single mycobacterial blood culture with 41 (32%) positive for <it>M. tuberculosis</it>, of which 20 (49%) were XDR-TB and 8 (20%) were MDR-TB. One hundred fourteen (88%) patients were known to be HIV-infected. Patients on antiretroviral therapy were significantly less likely to have a positive blood culture for <it>M. tuberculosis </it>(p = 0.002). The diagnosis of MDR or XDR-TB was made by blood culture alone in 12 patients.</p> <p>Conclusions</p> <p>Mycobacterial blood cultures provided an additive yield for diagnosis of drug-resistant TB in patients with HIV from rural South Africa. The use of mycobacterial blood cultures should be considered in all patients suspected of drug-resistant TB in similar settings.</p

The signatures of Anthropocene defaunation: cascading effects of the seed dispersal collapse

Anthropogenic activity is driving population declines and extinctions of large-bodied, fruit-eating animals worldwide. Loss of these frugivores is expected to trigger negative cascading effects on plant populations if remnant species fail to replace the seed dispersal services provided by the extinct frugivores. A collapse of seed dispersal may not only affect plant demography (i.e., lack of recruitment), but should also supress gene flow via seed dispersal. Yet little empirical data still exist demonstrating the genetic consequences of defaunation for animal-dispersed plant species. Here, we first document a significant reduction of seed dispersal distances along a gradient of human-driven defaunation, with increasing loss of large- and medium-bodied frugivores. We then show that local plant neighbourhoods have higher genetic similarity and smaller effective population sizes when large seed dispersers become extinct (i.e., only small frugivores remain) or are even partially downgraded (i.e., medium-sized frugivores providing less efficient seed dispersal). Our results demonstrate that preservation of large frugivores is crucial to maintain functional seed dispersal services and their associated genetic imprints, a central conservation target. Early signals of reduced dispersal distances that accompany the Anthropogenic defaunation forecast multiple, cascading effects on plant populations

Disease-associated alleles in genome-wide association studies are enriched for derived low frequency alleles relative to HapMap and neutral expectations

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies give insight into the genetic basis of common diseases. An open question is whether the allele frequency distributions and ancestral vs. derived states of disease-associated alleles differ from the rest of the genome. Characteristics of disease-associated alleles can be used to increase the yield of future studies.</p> <p>Methods</p> <p>The set of all common disease-associated alleles found in genome-wide association studies prior to January 2010 was analyzed and compared with HapMap and theoretical null expectations. In addition, allele frequency distributions of different disease classes were assessed. Ages of HapMap and disease-associated alleles were also estimated.</p> <p>Results</p> <p>The allele frequency distribution of HapMap alleles was qualitatively similar to neutral expectations. However, disease-associated alleles were more likely to be low frequency derived alleles relative to null expectations. 43.7% of disease-associated alleles were ancestral alleles. The mean frequency of disease-associated alleles was less than randomly chosen CEU HapMap alleles (0.394 vs. 0.610, after accounting for probability of detection). Similar patterns were observed for the subset of disease-associated alleles that have been verified in multiple studies. SNPs implicated in genome-wide association studies were enriched for young SNPs compared to randomly selected HapMap loci. Odds ratios of disease-associated alleles tended to be less than 1.5 and varied by frequency, confirming previous studies.</p> <p>Conclusions</p> <p>Alleles associated with genetic disease differ from randomly selected HapMap alleles and neutral expectations. The evolutionary history of alleles (frequency and ancestral vs. derived state) influences whether they are implicated in genome-wide assocation studies.</p

Disinhibition: its effects on appetite and weight regulation.

yesOver the past 30 years, the understanding of eating behaviour has been dominated by the concept of dietary restraint. However, the development of the Three Factor Eating Questionnaire introduced two other factors, Disinhibition and Hunger, which have not received as much recognition in the literature. The objective of this review was to explore the relationship of the Disinhibition factor with weight regulation, food choice and eating disorders, and to consider its aetiology. The review indicates that Disinhibition is an important eating behaviour trait. It is associated not only with a higher body mass index and obesity, but also with mediating variables, such as less healthful food choices, which contribute to overweight/obesity and poorer health. Disinhibition is also implicated in eating disorders and contributes to eating disorder severity. It has been demonstrated that Disinhibition is predictive of poorer success at weight loss, and of weight regain after weight loss regimes and is associated with lower self-esteem, low physical activity and poor psychological health. Disinhibition therefore emerges as an important and dynamic trait, with influences that go beyond eating behaviour and incorporate other behaviours which contribute to weight regulation and obesity. The characteristics of Disinhibition itself therefore reflect many components representative of a thrifty type of physiology. We propose that the trait of Disinhibition be more appropriately renamed as ¿opportunistic eating¿ or ¿thrifty behaviour¿

A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2 with serum creatinine level

<p>Abstract</p> <p>Background</p> <p>Serum creatinine (S_CR) is the most important biomarker for a quick and non-invasive assessment of kidney function in population-based surveys. A substantial proportion of the inter-individual variability in S_CRlevel is explicable by genetic factors.</p> <p>Methods</p> <p>We performed a meta-analysis of genome-wide association studies of S_CRundertaken in five population isolates ('discovery cohorts'), all of which are part of the European Special Population Network (EUROSPAN) project. Genes showing the strongest evidence for an association with S_CR(candidate loci) were replicated in two additional population-based samples ('replication cohorts').</p> <p>Results</p> <p>After the discovery meta-analysis, 29 loci were selected for replication. Association between S_CRlevel and polymorphisms in the collagen type XXII alpha 1 (<it>COL22A1</it>) gene, on chromosome 8, and in the synaptotagmin-1 (<it>SYT1</it>) gene, on chromosome 12, were successfully replicated in the replication cohorts (p value = 1.0 × 10^-6and 1.7 × 10^-4, respectively). Evidence of association was also found for polymorphisms in a locus including the gamma-aminobutyric acid receptor rho-2 (<it>GABRR2</it>) gene and the ubiquitin-conjugating enzyme E2-J1 (<it>UBE2J1</it>) gene (replication p value = 3.6 × 10^-3). Previously reported findings, associating glomerular filtration rate with SNPs in the uromodulin (<it>UMOD</it>) gene and in the schroom family member 3 (<it>SCHROOM3</it>) gene were also replicated.</p> <p>Conclusions</p> <p>While confirming earlier results, our study provides new insights in the understanding of the genetic basis of serum creatinine regulatory processes. In particular, the association with the genes <it>SYT1 </it>and <it>GABRR2 </it>corroborate previous findings that highlighted a possible role of the neurotransmitters GABA_Areceptors in the regulation of the glomerular basement membrane and a possible interaction between GABA_Areceptors and synaptotagmin-I at the podocyte level.</p

Genetic Effects at Pleiotropic Loci Are Context-Dependent with Consequences for the Maintenance of Genetic Variation in Populations

Context-dependent genetic effects, including genotype-by-environment and genotype-by-sex interactions, are a potential mechanism by which genetic variation of complex traits is maintained in populations. Pleiotropic genetic effects are also thought to play an important role in evolution, reflecting functional and developmental relationships among traits. We examine context-dependent genetic effects at pleiotropic loci associated with normal variation in multiple metabolic syndrome (MetS) components (obesity, dyslipidemia, and diabetes-related traits). MetS prevalence is increasing in Western societies and, while environmental in origin, presents substantial variation in individual response. We identify 23 pleiotropic MetS quantitative trait loci (QTL) in an F16 advanced intercross between the LG/J and SM/J inbred mouse strains (Wustl:LG,SM-G16; n = 1002). Half of each family was fed a high-fat diet and half fed a low-fat diet; and additive, dominance, and parent-of-origin imprinting genotypic effects were examined in animals partitioned into sex, diet, and sex-by-diet cohorts. We examine the context-dependency of the underlying additive, dominance, and imprinting genetic effects of the traits associated with these pleiotropic QTL. Further, we examine sequence polymorphisms (SNPs) between LG/J and SM/J as well as differential expression of positional candidate genes in these regions. We show that genetic associations are different in different sex, diet, and sex-by-diet settings. We also show that over- or underdominance and ecological cross-over interactions for single phenotypes may not be common, however multidimensional synthetic phenotypes at loci with pleiotropic effects can produce situations that favor the maintenance of genetic variation in populations. Our findings have important implications for evolution and the notion of personalized medicine