Investigation of the biomechanical effect of variable stiffness shoe on external knee adduction moment in various dynamic exercises

10.1186/1757-1146-6-39Journal of Foot and Ankle Research61

Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation

The second extracellular loop (EL2) of rhodopsin forms a cap over the binding site of its photoreactive 11-cis retinylidene chromophore. A crucial question has been whether EL2 forms a reversible gate that opens upon activation or acts as a rigid barrier. Distance measurements using solid-state 13C NMR spectroscopy between the retinal chromophore and the β4 strand of EL2 show that the loop is displaced from the retinal binding site upon activation, and there is a rearrangement in the hydrogen-bonding networks connecting EL2 with the extracellular ends of transmembrane helices H4, H5 and H6. NMR measurements further reveal that structural changes in EL2 are coupled to the motion of helix H5 and breaking of the ionic lock that regulates activation. These results provide a comprehensive view of how retinal isomerization triggers helix motion and activation in this prototypical G protein-coupled receptor. © 2009 Nature America, Inc. All rights reserved

Hippocampal metabotropic glutamate receptor long-term depression in health and disease: focus on mitogen-activated protein kinase pathways

YesGroup I metabotropic glutamate receptor (mGluR) dependent long-term depression (LTD) is a major form of synaptic plasticity underlying learning and memory. The molecular mechanisms involved in mGluR-LTD have been investigated intensively for the last two decades. In this 60th anniversary special issue article, we review the recent advances in determining the mechanisms that regulate the induction, transduction and expression of mGluR-LTD in the hippocampus, with a focus on the mitogen-activated protein kinase (MAPK) pathways. In particular we discuss the requirement of p38 MAPK and extracellular signal-regulated kinase 1/2 (ERK 1/2) activation. The recent advances in understanding the signaling cascades regulating mGluR-LTD are then related to the cognitive impairments observed in neurological disorders, such as fragile X syndrome and Alzheimer's disease

Low potency toxins reveal dense interaction networks in metabolism

Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. Results Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. Conclusions The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved

Generation of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II) peptide-pulsed DCs

Optimal techniques for DC generation for immunotherapy in cancer are yet to be established. Study aims were to evaluate: (i) DC activation/maturation milieu (TNF-α +/- IFN-α) and its effects on CD8+ hTERT-specific T cell responses to class I epitopes (p540 or p865), (ii) CD8+ hTERT-specific T cell responses elicited by vaccination with class I alone or both class I and II epitope (p766 and p672)-pulsed DCs, prepared without IFN-α, (iii) association between circulating T regulatory cells (Tregs) and clinical responses

Genetics of ischaemic stroke among persons of non-European descent: a meta-analysis of eight genes involving approximately 32,500 individuals

BACKGROUND: Ischaemic stroke in persons of European descent has a genetic basis, but whether the stroke-susceptibility alleles, the strength of any association, and the extent of their attributable risks are the same in persons of non-European descent remains unanswered. Whether ethnicity itself has a relevant or substantial contribution on those effect estimates is controversial. Comparative analyses between the ethnic groups may allow general conclusions to be drawn about polygenic disorders. METHODS AND FINDINGS: We performed a literature-based systematic review of genetic association studies in stroke in persons of non-European descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for each gene-disease association using fixed and random effect models. We further performed a comparative genetic analysis across the different ethnic groups (including persons of European descent derived from our previous meta-analysis) to determine if genetic risks varied by ethnicity. Following a review of 500 manuscripts, eight candidate gene variants were analysed among 32,431 individuals (12,883 cases and 19,548 controls), comprising mainly Chinese, Japanese, and Korean individuals. Of the eight candidate genes studied, three were associated with ischaemic stroke: the angiotensin I converting enzyme (ACE) insertion/deletion (I/D) polymorphism with a mean OR of 1.90 (95% CI 1.23-2.93) in the Chinese and 1.74 (95% CI 0.88-3.42) in the Japanese; the summary OR for the C677T variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) was 1.18 (95% CI 0.90-1.56) in Chinese and 1.34 (95% CI 0.87-2.06) in Koreans; and the pooled OR for the apolipoprotein E (APOE) gene was 2.18 (95% CI 1.52-3.13) in Chinese and 1.51 (95% CI 0.93-2.45) in Japanese. Comparing the commonly investigated stroke genes among the Asian groups against studies in persons of European descent, we found an absence of any substantial qualitative or quantitative interaction for ORs by ethnicity. However, the number of individuals recruited per study in the studies of persons of non-European descent was significantly smaller compared to studies of persons of European descent, despite a similar number of studies conducted per gene. CONCLUSIONS: These data suggest that genetic associations studied to date for ischaemic stroke among persons of non-European descent are similar to those for persons of European descent. Claims of differences in genetic effects among different ethnic populations for complex disorders such as stroke may be overstated. However, due to the limited number of gene variants evaluated, the relatively smaller number of individuals included in the meta-analyses of persons of non-European descent in stroke, and the possibility of publication bias, the existence of allele variants with differential effects by ethnicity cannot be excluded

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants

BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence—defined as fasting plasma glucose of 7·0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs—in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. FINDINGS: We used data from 751 studies including 4 372 000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4·3% (95% credible interval 2·4–7·0) in 1980 to 9·0% (7·2–11·1) in 2014 in men, and from 5·0% (2·9–7·9) to 7·9% (6·4–9·7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28·5% due to the rise in prevalence, 39·7% due to population growth and ageing, and 31·8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust

Remediation of salt-affected soil by the addition of organic matter: an investigation into improving glutinous rice productivity

Soil salinity may limit plant growth and development, and cause yield loss in crop species. This study aimed at remediating saline soil using organic matter (OM) treatment, before the cultivation of RD6 rice (Oryza sativa L. spp. indica). Physiological and morphological characters of rice plants, as well as crop yield, were evaluated from salt-affected soil with varying levels of salinity. The chlorophyll a and total chlorophyll pigments of rice plants grown in salt-affected soil (2% salt level) with the application of OM were maintained better than in plants grown without OM treatment. The degree of reduced photosynthetic pigments in rice plants was dependent on the level of salt contamination. Pigment content was positively related to maximum quantum yield of PSII (Fv/Fm) and quantum efficiency of PSII (ΦPSII), leading to reduced net photosynthetic rate (Pn) and reduced total grain weight (TGW). Photosynthetic abilities, including chlorophyll a and total chlorophyll pigments and ΦPSII, in rice plants grown with OM treatment were greater than in those cultivated in soil without the OM treatment, especially in high salt levels (1-2% salt). The remediation of salt-affected soil in paddy fields using OM should be applied further, as an effective way of enhancing food crop productivity

Antihyperglycemic and Antioxidative Effects of Hydroxyethyl Methylcellulose (HEMC) and Hydroxypropyl Methylcellulose (HPMC) in Mice Fed with a High Fat Diet

The effect of dietary feeding of hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) on the glucose metabolism and antioxidative status in mice under high fat diet conditions was investigated. The mice were randomly divided and given experimental diets for six weeks: normal control (NC group), high fat (HF group), and high fat supplemented with either HEMC (HF+HEMC group) or HPMC (HF+HPMC group). At the end of the experimental period, the HF group exhibited markedly higher blood glucose and insulin levels as well as a higher erythrocyte lipid peroxidation rate relative to the control group. However, diet supplementation of HEMC and HPMC was found to counteract the high fat-induced hyperglycemia and oxidative stress via regulation of antioxidant and hepatic glucose-regulating enzyme activities. These findings illustrate that HEMC and HPMC were similarly effective in improving the glucose metabolism and antioxidant defense system in high fat-fed mice and they may be beneficial as functional biomaterials in the development of therapeutic agents against high fat dietinduced hyperglycemia and oxidative stress

Radiographic knee osteoarthritis in ex-elite table tennis players

<p>Abstract</p> <p>Background</p> <p>Table tennis involves adoption of the semi-flexed knee and asymmetrical torsional trunk movements creating rotational torques on the knee joint which may predispose players to osteoarthritis (OA) of the knee. This study aims to compare radiographic signs of knee OA and associated functional levels in ex-elite male table tennis players and control subjects.</p> <p>Methods</p> <p>Study participants were 22 ex-elite male table tennis players (mean age 56.64 ± 5.17 years) with 10 years of involvement at the professional level and 22 non-athletic males (mean age 55.63 ± 4.08 years) recruited from the general population. A set of three radiographs taken from each knee were evaluated by an experienced radiologist using the Kellgren and Lawrence (KL) scale (0-4) to determine radiographic levels of OA severity. The intercondylar distance was taken as a measure of lower limb angulation. Participants also completed the pain, stiffness, and physical function categories of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) 3.1 questionnaire.</p> <p>Results</p> <p>The results showed 78.3% of the ex-elite table tennis players and 36.3% of controls had varying signs of radiographic knee OA with a significant difference in the prevalence levels of definite radiographic OA (KL scale > 2) found between the two groups (<it>P </it>≤ 0.001). Based on the WOMAC scores, 68.2% of the ex-elite table tennis players reported symptoms of knee pain compared with 27.3% of the controls (<it>p </it>= 0.02) though no significant differences were identified in the mean physical function or stiffness scores between the two groups. In terms of knee alignment, 73.7% of the ex-elite athletes and 32% of the control group had signs of altered lower limb alignment (genu varum) (<it>p </it>= 0.01). Statistical differences were found in subjects categorized as having radiographic signs of OA and altered lower limb alignment (<it>p </it>= 0.03).</p> <p>Conclusions</p> <p>Ex-elite table tennis players were found to have increased levels of radiological signs of OA in the knee joint though this did not transpire through to altered levels of physical disability or knee stiffness in these players when compared with subjects from the general population suggesting that function in these players is not severely impacted upon.</p