Gene set of nuclear-encoded mitochondrial regulators is enriched for common inherited variation in obesity

There are hints of an altered mitochondrial function in obesity. Nuclear-encoded genes are relevant for mitochondrial function (3 gene sets of known relevant pathways: (1) 16 nuclear regulators of mitochondrial genes, (2) 91 genes for oxidative phosphorylation and (3) 966 nuclear-encoded mitochondrial genes). Gene set enrichment analysis (GSEA) showed no association with type 2 diabetes mellitus in these gene sets. Here we performed a GSEA for the same gene sets for obesity. Genome wide association study (GWAS) data from a case-control approach on 453 extremely obese children and adolescents and 435 lean adult controls were used for GSEA. For independent confirmation, we analyzed 705 obesity GWAS trios (extremely obese child and both biological parents) and a population-based GWAS sample (KORA F4, n = 1,743). A meta-analysis was performed on all three samples. In each sample, the distribution of significance levels between the respective gene set and those of all genes was compared using the leading-edge-fraction-comparison test (cut-offs between the 50(th) and 95(th) percentile of the set of all gene-wise corrected p-values) as implemented in the MAGENTA software. In the case-control sample, significant enrichment of associations with obesity was observed above the 50(th) percentile for the set of the 16 nuclear regulators of mitochondrial genes (p(GSEA,50) = 0.0103). This finding was not confirmed in the trios (p(GSEA,50) = 0.5991), but in KORA (p(GSEA,50) = 0.0398). The meta-analysis again indicated a trend for enrichment (p(MAGENTA,50) = 0.1052, p(MAGENTA,75) = 0.0251). The GSEA revealed that weak association signals for obesity might be enriched in the gene set of 16 nuclear regulators of mitochondrial genes

New mutations at the imprinted Gnas cluster show gene dosage effects of Gsα in postnatal growth and implicate XLαs in bone and fat metabolism, but not in suckling

The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLαs, XLN1, and ALEX or a double dose of maternally expressed Gsα to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsα, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsα and loss of expression of XLαs and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLαs, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLαs. This is, to our knowledge, the first report describing a role for XLαs in bone metabolism. We propose that XLαs is involved in the regulation of bone and adipocyte metabolism

Understanding and using comparative healthcare information; the effect of the amount of information and consumer characteristics and skills

<p>Abstract</p> <p>Background</p> <p>Consumers are increasingly exposed to comparative healthcare information (information about the quality of different healthcare providers). Partly because of its complexity, the use of this information has been limited. The objective of this study was to examine how the amount of presented information influences the comprehension and use of comparative healthcare information when important consumer characteristics and skills are taken into account.</p> <p>Methods</p> <p>In this randomized controlled experiment, comparative information on total hip or knee surgery was used as a test case. An online survey was distributed among 800 members of the NIVEL Insurants Panel and 76 hip- or knee surgery patients. Participants were assigned to one of four subgroups, who were shown 3, 7, 11 or 15 quality aspects of three hospitals. We conducted Kruskall-Wallis tests, Chi-square tests and hierarchical multiple linear regression analyses to examine relationships between the amount of information and consumer characteristics and skills (literacy, numeracy, active choice behaviour) on one hand, and outcome measures related to effectively using information (comprehension, perceived usefulness of information, hospital choice, ease of making a choice) on the other hand.</p> <p>Results</p> <p>414 people (47%) participated. Regression analysis showed that the amount of information slightly influenced the comprehension and the perceived usefulness of comparative healthcare information. It did not affect consumers’ hospital choice and ease of making this choice. Consumer characteristics (especially age) and skills (especially literacy) were the most important factors affecting the comprehension of information and the ease of making a hospital choice. For the perceived usefulness of comparative information, active choice behaviour was the most influencing factor.</p> <p>Conclusion</p> <p>The effects of the amount of information were not unambiguous. It remains unclear what the ideal amount of quality information to be presented would be. Reducing the amount of information will probably not automatically result in more effective use of comparative healthcare information by consumers. More important, consumer characteristics and skills appeared to be more influential factors contributing to information comprehension and use. Consequently, we would suggest that more emphasis on improving consumers’ skills is needed to enhance the use of comparative healthcare information.</p

Age-Related Attenuation of Dominant Hand Superiority

The decline of motor performance of the human hand-arm system with age is well-documented. While dominant hand performance is superior to that of the non-dominant hand in young individuals, little is known of possible age-related changes in hand dominance. We investigated age-related alterations of hand dominance in 20 to 90 year old subjects. All subjects were unambiguously right-handed according to the Edinburgh Handedness Inventory. In Experiment 1, motor performance for aiming, postural tremor, precision of arm-hand movement, speed of arm-hand movement, and wrist-finger speed tasks were tested. In Experiment 2, accelerometer-sensors were used to obtain objective records of hand use in everyday activities

Integrating livelihoods and conservation in protected areas: Understanding the role and stakeholder views on prospects for non-timber forest products, a Bangladesh case study

Protected areas (PAs) represent a key global strategy in biodiversity conservation. In tropical developing countries, the management of PAs is a great challenge as many contain resources on which local communities rely. Collection and trading of non-timber forest products (NTFPs) is a well-established forest-based livelihood strategy, which has been promoted as a potential means for enhanced conservation and improved rural livelihoods in recent years, even though the sustainability or ecological implications have rarely been tested. We conducted an exploratory survey to understand the role and stakeholder views on conservation prospects and perceived ecological feasibility of NTFPs and harvesting schemes in a northeastern PA of Bangladesh, namely the Satchari National Park. Households (n = 101) were interviewed from three different forest dependency categories, adopting a stratified random sampling approach and using a semi-structured questionnaire. The study identified 13 locally important NTFPs, with five being critically important to supporting local livelihoods. Our study suggests that collection, processing and trading in NTFPs constitutes the primary occupation for about 18% of local inhabitants and account for an estimated 19% of their cash annual income. The household consensus on issues relating to NTFPs and their prospective role in conservation was surprisingly high, with 48% of respondents believing that promotion of NTFPs in the PA could have positive conservation value. The majority (71%) of households also had some understanding of the ecological implications of NTFP harvesting, sustainability (53%) and possible management and monitoring regimes (100%). With little known about their real application in the field, our study suggests further investigations are required to understand the ecological compatibility of traditional NTFP harvesting patterns and management. © 2010 Taylor & Francis

Anti-malarial activity of Holarrhena antidysenterica and Viola canescens, plants traditionally used against malaria in the Garhwal region of north-west Himalaya

<p>Abstract</p> <p>Background</p> <p>The increasing number of multidrug-resistant <it>Plasmodium </it>strains warrants exploration of new anti-malarials. Medicinal plant research has become more important, particularly after the development of Chinese anti-malarial drug artemisnin from <it>Artemisia annua</it>. The present study shows evaluation of anti-malarial effects of two plants commonly used against malaria in the Garhwal region of north-west Himalaya, in order to discover the herbal-based medicine.</p> <p>Methods</p> <p><it>In vitro </it>anti-plasmodial sensitivity of plant extracts was assessed using schizont maturation and parasite lactate dehydrogenase (pLDH) assay. Cytotoxic activities of the examined extracts were determined on L-6 cells of rat skeletal muscle myoblast. The 4-day test for anti-malarial activity against a chloroquine sensitive <it>Plasmodium berghei </it>NK65 strain in Swiss albino mice was used for monitoring <it>in vivo </it>activity of plant extracts.</p> <p>Results</p> <p>Chloroform extract of <it>H. antidysenterica </it>(HA-2) and petroleum ether extract of <it>V. canescens </it>(VC-1) plants significantly reduced parasitaemia in <it>P. berghei </it>infected mice. The extract HA-2 showed <it>in vitro </it>anti-plasmodial activity with its IC₅₀value 5.5 μg/ml using pLDH assay and ED₅₀value 18.29 mg/kg in <it>P. berghei </it>infected Swiss albino mice. Similarly petroleum ether extract of <it>V. canescens </it>(VC-1) showed <it>in vitro </it>anti-plasmodial activity with its IC₅₀value 2.76 μg/ml using pLDH assay and ED₅₀15.8 mg/kg in <it>P. berghei </it>infected mice. The extracts coded as HA-2 at 30 mg/kg and VC-1 at 20 mg/kg exhibited parasite inhibition in mice: 73.2% and 63.0% respectively. Of these two plant extracts, petroleum ether extract of <it>V. canescens </it>was found slightly cytotoxic.</p> <p>Conclusion</p> <p>The present investigation reflects the use of these traditional medicinal plants against malaria and these plants may work as potential source in the development of variety of herbal formulations for the treatment of malaria.</p

Relevant Assay to Study the Adhesion of Plasmodium falciparum-Infected Erythrocytes to the Placental Epithelium

In placental malaria, Plasmodium falciparum-infected erythrocytes adhere to the apical plasma membrane of the placental epithelium, triggering an impairment of placental function detrimental to the fetus. The design of anti-adhesion intervention strategies requires a detailed understanding of the mechanisms involved. However, most adhesion assays lack in vivo relevance and are hardly quantitative. Here, we describe a flow cytometry-based adhesion assay that is fully relevant by using apical epithelial plasma membrane vesicles as the adhesion matrix, and being applicable to infected erythrocytes directly isolated from patients. Adhesion is measured both as the percentage of pathogens bound to epithelial membrane vesicles as well as the mean number of vesicles bound per infected erythrocytes. We show that adhesins alternative to those currently identified could be involved. This demonstrates the power of this assay to advance our understanding of epithelial adhesion of infected erythrocytes and in the design of intervention strategies

Machupo Virus Glycoprotein Determinants for Human Transferrin Receptor 1 Binding and Cell Entry

Machupo virus (MACV) is a highly pathogenic New World arenavirus that causes hemorrhagic fever in humans. MACV, as well as other pathogenic New World arenaviruses, enter cells after their GP1 attachment glycoprotein binds to their cellular receptor, transferrin receptor 1 (TfR1). TfR1 residues essential for this interaction have been described, and a co-crystal of MACV GP1 bound to TfR1 suggests GP1 residues important for this association. We created MACV GP1 variants and tested their effect on TfR1 binding and virus entry to evaluate the functional significance of some of these and additional residues in human and simian cells. We found residues R111, D123, Y122, and F226 to be essential, D155, and P160 important, and D114, S116, D140, and K169 expendable for the GP1-TfR1 interaction and MACV entry. Several MACV GP1 residues that are critical for the interaction with TfR1 are conserved among other New World arenaviruses, indicating a common basis of receptor interaction. Our findings also open avenues for the rational development of viral entry inhibitors