Human kinesiology

This paper discusses kinesiological aspects of human locomotion in terms of the incomplete morphological adaptation of the body to current lifestyles. Modern instrumentation used for biomechanical analyses is outlined for the most part in the context of human running. Investigations of spatiotemporal and segmental measures by electronic walkways, photography, optoelectronics and angle-angle diagrams are referred to, as is electromyography and direct force measurement. Three commonly identifiable areas of applied kinesiological research, namely sport, industry and medicine, are considered with reference to the prevention, treatment and after-care of injuries whether received on the sporting field, in the work place, or in an automobile accident.     

Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

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Highlights? Snx3 is highly expressed in vertebrate hematopoietic tissues ? Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates ? Snx3 and Vps35 physically interact with Tfrc ? Snx3 is required for endosomal recycling of Tf-Tfrc complex     

The Global Epidemiology and Contribution of Cannabis Use and Dependence to the Global Burden of Disease: Results from the GBD 2010 Study

AimsEstimate the prevalence of cannabis dependence and its contribution to the global burden of disease.MethodsSystematic reviews of epidemiological data on cannabis dependence (1990-2008) were conducted in line with PRISMA and meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Culling and data extraction followed protocols, with cross-checking and consistency checks. DisMod-MR, the latest version of generic disease modelling system, redesigned as a Bayesian meta-regression tool, imputed prevalence by age, year and sex for 187 countries and 21 regions. The disability weight associated with cannabis dependence was estimated through population surveys and multiplied by prevalence data to calculate the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs). YLDs and DALYs attributed to regular cannabis use as a risk factor for schizophrenia were also estimated.ResultsThere were an estimated 13.1 million cannabis dependent people globally in 2010 (point prevalence0.19% (95% uncertainty: 0.17-0.21%)). Prevalence peaked between 20-24 yrs, was higher in males (0.23% (0.2-0.27%)) than females (0.14% (0.12-0.16%)) and in high income regions. Cannabis dependence accounted for 2 million DALYs globally (0.08%; 0.05-0.12%) in 2010; a 22% increase in crude DALYs since 1990 largely due to population growth. Countries with statistically higher age-standardised DALY rates included the United States, Canada, Australia, New Zealand and Western European countries such as the United Kingdom; those with lower DALY rates were from Sub-Saharan Africa-West and Latin America. Regular cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000 DALYs globally.ConclusionCannabis dependence is a disorder primarily experienced by young adults, especially in higher income countries. It has not been shown to increase mortality as opioid and other forms of illicit drug dependence do. Our estimates suggest that cannabis use as a risk factor for schizophrenia is not a major contributor to population-level disease burden.     

Regional Differences in Seasonal Timing of Rainfall Discriminate between Genetically Distinct East African Giraffe Taxa

Masai (Giraffa tippelskirchi), Reticulated (G. reticulata) and Rothschild''s (G. camelopardalis) giraffe lineages in East Africa are morphologically and genetically distinct, yet in Kenya their ranges abut. This raises the question of how divergence is maintained among populations of a large mammal capable of long-distance travel, and which readily hybridize in zoos. Here we test four hypotheses concerning the maintenance of the phylogeographic boundaries among the three taxa: 1) isolation-by-distance; 2) physical barriers to dispersal; 3) general habitat differences resulting in habitat segregation; or 4) regional differences in the seasonal timing of rainfall, and resultant timing of browse availability. We used satellite remotely sensed and climate data to characterize the environment at the locations of genotyped giraffes. Canonical variate analysis, random forest algorithms, and generalized dissimilarity modelling were employed in a landscape genetics framework to identify the predictor variables that best explained giraffes'' genetic divergence. We found that regional differences in the timing of precipitation, and resulting green-up associated with the abundance of browse, effectively discriminate between taxa. Local habitat conditions, topographic and human-induced barriers, and geographic distance did not aid in discriminating among lineages. Our results suggest that selection associated with regional timing of events in the annual climatic cycle may help maintain genetic and phenotypic divergence in giraffes. We discuss potential mechanisms of maintaining divergence, and suggest that synchronization of reproduction with seasonal rainfall cycles that are geographically distinct may contribute to reproductive isolation. Coordination of weaning with green-up cycles could minimize the costs of lactation and predation on the young. Our findings are consistent with theory and empirical results demonstrating the efficacy of seasonal or phenologically dictated selection pressures in contributing to the reproductive isolation of parapatric populations.     

Deriving metabolic engineering strategies from genome-scale modeling with flux ratio constraints

Optimized production of bio-based fuels and chemicals from microbial cell factories is a central goal of systems metabolic engineering. To achieve this goal, a new computational method of using flux balance analysis with flux ratios (FBrAtio) was further developed in this research and applied to five case studies to evaluate and design metabolic engineering strategies. The approach was implemented using publicly available genome-scale metabolic flux models. Synthetic pathways were added to these models along with flux ratio constraints by FBrAtio to achieve increased (i) cellulose production from Arabidopsis thaliana; (ii) isobutanol production from Saccharomyces cerevisiae; (iii) acetone production from Synechocystis sp. PCC6803; (iv) H₂ production from Escherichia coli MG1655; and (v) isopropanol, butanol, and ethanol (IBE) production from engineered Clostridium acetobutylicum. The FBrAtio approach was applied to each case to simulate a metabolic engineering strategy already implemented experimentally, and flux ratios were continually adjusted to find (i) the end-limit of increased production using the existing strategy, (ii) new potential strategies to increase production, and (iii) the impact of these metabolic engineering strategies on product yield and culture growth. The FBrAtio approach has the potential to design “fine-tuned” metabolic engineering strategies in silico that can be implemented directly with available genomic tools.     

Effects of genetic mutations and chemical exposures on Caenorhabditis elegans feeding: evaluation of a novel, high-throughput screening assay

Background

Government agencies have defined a need to reduce, refine or replace current mammalian-based bioassays with testing methods that use alternative species. Invertebrate species, such as Caenorhabditis elegans, provide an attractive option because of their short life cycles, inexpensive maintenance, and high degree of evolutionary conservation with higher eukaryotes. The C. elegans pharynx is a favorable model for studying neuromuscular function, and the effects of chemicals on neuromuscular activity, i.e., feeding. Current feeding methodologies, however, are labor intensive and only semi-quantitative.

Methodology/Principal Findings

Here a high-throughput assay is described that uses flow cytometry to measure C. elegans feeding by determining the size and intestinal fluorescence of hundreds of nematodes after exposure to fluorescent-labeled microspheres. This assay was validated by quantifying fluorescence in feeding-defective C. elegans (eat mutants), and by exposing wild-type nematodes to the neuroactive compounds, serotonin and arecoline. The eat mutations previously determined to cause slow pumping rates exhibited the lowest feeding levels with our assay. Concentration-dependent increases in feeding levels after serotonin exposures were dependent on food availability, while feeding levels decreased in arecoline-exposed nematodes regardless of the presence of food. The effects of the environmental contaminants, cadmium chloride and chlorpyrifos, on wild-type C. elegans feeding were then used to demonstrate an application of the feeding assay. Cadmium exposures above 200 µM led to a sharp drop in feeding levels. Feeding of chlorpyrifos-exposed nematodes decreased in a concentration-dependent fashion with an EC₅₀ of 2 µM.

Conclusions/Significance

The C. elegans fluorescence microsphere feeding assay is a rapid, reliable method for the assessment of neurotoxic effects of pharmaceutical drugs, industrial chemicals or environmental agents. This assay may also be applicable to large scale genetic or RNAi screens used to identify genes that are necessary for the development or function of the pharynx or other neuromuscular systems.     

Population Distribution of the Sagittal Abdominal Diameter (SAD) from a Representative Sample of US Adults: Comparison of SAD,Waist Circumference and Body Mass Index for Identifying Dysglycemia

Background

The sagittal abdominal diameter (SAD) measured in supine position is an alternative adiposity indicator that estimates the quantity of dysfunctional adipose tissue in the visceral depot. However, supine SAD’s distribution and its association with health risk at the population level are unknown. Here we describe standardized measurements of SAD, provide the first, national estimates of the SAD distribution among US adults, and test associations of SAD and other adiposity indicators with prevalent dysglycemia.

Methods and Findings

In the 2011–2012 National Health and Nutrition Examination Survey, supine SAD was measured (“abdominal height”) between arms of a sliding-beam caliper at the level of the iliac crests. From 4817 non-pregnant adults (age ≥20; response rate 88%) we used sample weights to estimate SAD’s population distribution by sex and age groups. SAD’s population mean was 22.5 cm [95% confidence interval 22.2–22.8]; median was 21.9 cm [21.6–22.4]. The mean and median values of SAD were greater for men than women. For the subpopulation without diagnosed diabetes, we compared the abilities of SAD, waist circumference (WC), and body mass index (BMI, kg/m²) to identify prevalent dysglycemia (HbA1c ≥5.7%). For age-adjusted, logistic-regression models in which sex-specific quartiles of SAD were considered simultaneously with quartiles of either WC or BMI, only SAD quartiles 3 (p<0.05 vs quartile 1) and 4 (p<0.001 vs quartile 1) remained associated with increased dysglycemia. Based on continuous adiposity indicators, analyses of the area under the receiver operating characteristic curve (AUC) indicated that the dysglycemia model fit for SAD (age-adjusted) was 0.734 for men (greater than the AUC for WC, p<0.001) and 0.764 for women (greater than the AUC for WC or BMI, p<0.001).

Conclusions

Measured inexpensively by bedside caliper, SAD was associated with dysglycemia independently of WC or BMI. Standardized SAD measurements may enhance assessment of dysfunctional adiposity.     

The Burden Attributable to Mental and Substance Use Disorders as Risk Factors for Suicide: Findings from the Global Burden of Disease Study 2010

Background

The Global Burden of Disease Study 2010 (GBD 2010) identified mental and substance use disorders as the 5^th leading contributor of burden in 2010, measured by disability adjusted life years (DALYs). This estimate was incomplete as it excluded burden resulting from the increased risk of suicide captured elsewhere in GBD 2010''s mutually exclusive list of diseases and injuries. Here, we estimate suicide DALYs attributable to mental and substance use disorders.

Methods

Relative-risk estimates of suicide due to mental and substance use disorders and the global prevalence of each disorder were used to estimate population attributable fractions. These were adjusted for global differences in the proportion of suicide due to mental and substance use disorders compared to other causes then multiplied by suicide DALYs reported in GBD 2010 to estimate attributable DALYs (with 95% uncertainty).

Results

Mental and substance use disorders were responsible for 22.5 million (14.8–29.8 million) of the 36.2 million (26.5–44.3 million) DALYs allocated to suicide in 2010. Depression was responsible for the largest proportion of suicide DALYs (46.1% (28.0%–60.8%)) and anorexia nervosa the lowest (0.2% (0.02%–0.5%)). DALYs occurred throughout the lifespan, with the largest proportion found in Eastern Europe and Asia, and males aged 20–30 years. The inclusion of attributable suicide DALYs would have increased the overall burden of mental and substance use disorders (assigned to them in GBD 2010 as a direct cause) from 7.4% (6.2%–8.6%) to 8.3% (7.1%–9.6%) of global DALYs, and would have changed the global ranking from 5^th to 3^rd leading cause of burden.

Conclusions

Capturing the suicide burden attributable to mental and substance use disorders allows for more accurate estimates of burden. More consideration needs to be given to interventions targeted to populations with, or at risk for, mental and substance use disorders as an effective strategy for suicide prevention.