Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves

Green Plants in the Red: A Baseline Global Assessment for the IUCN Sampled Red List Index for Plants

Plants provide fundamental support systems for life on Earth and are the basis for all terrestrial ecosystems; a decline in plant diversity will be detrimental to all other groups of organisms including humans. Decline in plant diversity has been hard to quantify, due to the huge numbers of known and yet to be discovered species and the lack of an adequate baseline assessment of extinction risk against which to track changes. The biodiversity of many remote parts of the world remains poorly known, and the rate of new assessments of extinction risk for individual plant species approximates the rate at which new plant species are described. Thus the question ‘How threatened are plants?’ is still very difficult to answer accurately. While completing assessments for each species of plant remains a distant prospect, by assessing a randomly selected sample of species the Sampled Red List Index for Plants gives, for the first time, an accurate view of how threatened plants are across the world. It represents the first key phase of ongoing efforts to monitor the status of the world’s plants. More than 20% of plant species assessed are threatened with extinction, and the habitat with the most threatened species is overwhelmingly tropical rain forest, where the greatest threat to plants is anthropogenic habitat conversion, for arable and livestock agriculture, and harvesting of natural resources. Gymnosperms (e.g. conifers and cycads) are the most threatened group, while a third of plant species included in this study have yet to receive an assessment or are so poorly known that we cannot yet ascertain whether they are threatened or not. This study provides a baseline assessment from which trends in the status of plant biodiversity can be measured and periodically reassessed

Prescribing patterns in premenstrual syndrome

BACKGROUND: Over 300 therapies have been proposed for premenstrual syndrome. To date there has been only one survey conducted in the UK of PMS treatments prescribed by GPs, a questionnaire-based study by the National Association of Premenstrual Syndrome in 1989. Since then, selective serotonin re-uptake inhibitors have been licensed for severe PMS/PMDD, and governmental recommendations to reduce the dosage of vitamin B6 (the first choice over-the-counter treatment for many women with PMS) have been made. This study investigates the annual rates of diagnoses and prescribing patterns for premenstrual syndrome (1993–1998) within a computerised general practitioner database. METHODS: Retrospective survey of prescribing data for premenstrual syndrome between 1993–1998 using the General Practice Research Database for the West Midlands Region which contains information on 282,600 female patients RESULTS: Overall the proportion of women with a prescription-linked diagnosis of premenstrual syndrome has halved over the five years. Progestogens including progesterone were the most commonly recorded treatment for premenstrual syndrome during the whole study period accounting for over 40% of all prescriptions. Selective serotonin-reuptake inhibitors accounted for only 2% of the prescriptions in 1993 but rose to over 16% by 1998, becoming the second most commonly recorded treatment. Vitamin B6 accounted for 22% of the prescriptions in 1993 but dropped markedly between 1997 and 1998 to 11%. CONCLUSIONS: This study shows a yearly decrease in the number of prescriptions linked to diagnoses for premenstrual syndrome. Progestogens including progesterone, is the most widely prescribed treatment for premenstrual syndrome despite the lack of evidence demonstrating their efficacy

Low urine pH and acid excretion do not predict bone fractures or the loss of bone mineral density: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The acid-ash hypothesis, the alkaline diet, and related products are marketed to the general public. Websites, lay literature, and direct mail marketing encourage people to measure their urine pH to assess their health status and their risk of osteoporosis.</p> <p>The objectives of this study were to determine whether 1) low urine pH, or 2) acid excretion in urine [sulfate + chloride + 1.8x phosphate + organic acids] minus [sodium + potassium + 2x calcium + 2x magnesium mEq] in fasting morning urine predict: a) fragility fractures; and b) five-year change of bone mineral density (BMD) in adults.</p> <p>Methods</p> <p>Design: Cohort study: the prospective population-based Canadian Multicentre Osteoporosis Study. Multiple logistic regression was used to examine associations between acid excretion (urine pH and urine acid excretion) in fasting morning with the incidence of fractures (6804 person years). Multiple linear regression was used to examine associations between acid excretion with changes in BMD over 5-years at three sites: lumbar spine, femoral neck, and total hip (n = 651). Potential confounders controlled included: age, gender, family history of osteoporosis, physical activity, smoking, calcium intake, vitamin D status, estrogen status, medications, renal function, urine creatinine, body mass index, and change of body mass index.</p> <p>Results</p> <p>There were no associations between either urine pH or acid excretion and either the incidence of fractures or change of BMD after adjustment for confounders.</p> <p>Conclusion</p> <p>Urine pH and urine acid excretion do not predict osteoporosis risk.</p

Measurement of the top quark mass using the matrix element technique in dilepton final states

We present a measurement of the top quark mass in pp¯ collisions at a center-of-mass energy of 1.96 TeV at the Fermilab Tevatron collider. The data were collected by the D0 experiment corresponding to an integrated luminosity of 9.7  fb−1. The matrix element technique is applied to tt¯ events in the final state containing leptons (electrons or muons) with high transverse momenta and at least two jets. The calibration of the jet energy scale determined in the lepton+jets final state of tt¯ decays is applied to jet energies. This correction provides a substantial reduction in systematic uncertainties. We obtain a top quark mass of mt=173.93±1.84  GeV

An increase of cereal intake as an approach to weight reduction in children is effective only when accompanied by nutrition education: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The main emphasis of dietary advice for control of obesity has been on reducing dietary fat. Increasing ready to eat cereal (RTEC) consumption could be a strategy to reduce fat intake and increase carbohydrate intake resulting in a diet with lower energy density.</p> <p>Objectives</p> <p>1. To determine if an increase in RTEC intake is an effective strategy to reduce excess body weight and blood lipids in overweight or at risk of overweight children. 2. To determine if a nutrition education program would make a difference on the response to an increase in cereal intake. 3) To determine if increase in RTEC intake alone or with a nutrition education program has an effect on plasma lipid profile.</p> <p>Experimental design</p> <p>One hundred and forty seven overweight or at risk of overweight children (6–12 y of age) were assigned to one of four different treatments: a. One serving of 33 ± 7 g of RTEC for breakfast; b. one serving of 33 ± 7 g of RTEC for breakfast and another one for dinner; c. one serving of 33 ± 7 g of RTEC for breakfast and a nutrition education program. d. Non intervention, control group. Anthropometry, body composition, physical activity and blood lipids were measured at baseline, before treatments, and 12 weeks after treatments.</p> <p>Results</p> <p>After 12 weeks of intervention only the children that received 33 ± 7 g of RTEC and nutrition education had significantly lower body weight [-1.01 (-1.69, -0.34) ], p < 0.01], lower BMI [-0.95 (-1.71, -0.20), p < 0.01] and lower total body fat [-0.71 (-1.71, 0.28), p < 0.05] compared with the control group [1.19 (0.39, 1.98), 0.01 (-0.38, 0.41), 0.44 (-0.46, 1.35) respectively]. Plasma triglycerides and VLDL were significantly reduced [-20.74 (-36.44, -5.05), -3.78 (-6.91, -0.64) respectively, p < 0.05] and HDL increased significantly [6.61 (2.15, 11.08), p < 0.01] only in this treatment group. The groups that received 1 or 2 doses of RTEC alone were not significantly different to the control group.</p> <p>Conclusion</p> <p>A strategy to increase RTEC consumption, as a source of carbohydrate, to reduce obesity is effective only when accompanied by nutrition education. The need for education could be extrapolated to other strategies intended for treatment of obesity.</p> <p>Trial Registration</p> <p>Australian New Zealand Clincial Trial Registry. Request no: ACTRN12608000025336</p

Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-

We report the first observation of the baryonic flavor-changing neutral current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}. We also report the first measurement of the differential branching ratio of B_s -> phi mu+ mu- using 49 signal events. In addition, we report branching ratios for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let

MicroRNA-Integrated and Network-Embedded Gene Selection with Diffusion Distance

Gene network information has been used to improve gene selection in microarray-based studies by selecting marker genes based both on their expression and the coordinate expression of genes within their gene network under a given condition. Here we propose a new network-embedded gene selection model. In this model, we first address the limitations of microarray data. Microarray data, although widely used for gene selection, measures only mRNA abundance, which does not always reflect the ultimate gene phenotype, since it does not account for post-transcriptional effects. To overcome this important (critical in certain cases) but ignored-in-almost-all-existing-studies limitation, we design a new strategy to integrate together microarray data with the information of microRNA, the major post-transcriptional regulatory factor. We also handle the challenges led by gene collaboration mechanism. To incorporate the biological facts that genes without direct interactions may work closely due to signal transduction and that two genes may be functionally connected through multi paths, we adopt the concept of diffusion distance. This concept permits us to simulate biological signal propagation and therefore to estimate the collaboration probability for all gene pairs, directly or indirectly-connected, according to multi paths connecting them. We demonstrate, using type 2 diabetes (DM2) as an example, that the proposed strategies can enhance the identification of functional gene partners, which is the key issue in a network-embedded gene selection model. More importantly, we show that our gene selection model outperforms related ones. Genes selected by our model 1) have improved classification capability; 2) agree with biological evidence of DM2-association; and 3) are involved in many well-known DM2-associated pathways

Variations in the Hemagglutinin of the 2009 H1N1 Pandemic Virus: Potential for Strains with Altered Virulence Phenotype?

A novel, swine-origin influenza H1N1 virus (H1N1pdm) caused the first pandemic of the 21st century. This pandemic, although efficient in transmission, is mild in virulence. This atypical mild pandemic season has raised concerns regarding the potential of this virus to acquire additional virulence markers either through further adaptation or possibly by immune pressure in the human host. Using the mouse model we generated, within a single round of infection with A/California/04/09/H1N1 (Ca/04), a virus lethal in mice—herein referred to as mouse-adapted Ca/04 (ma-Ca/04). Five amino acid substitutions were found in the genome of ma-Ca/04: 3 in HA (D131E, S186P and A198E), 1 in PA (E298K) and 1 in NP (D101G). Reverse genetics analyses of these mutations indicate that all five mutations from ma-Ca/04 contributed to the lethal phenotype; however, the D131E and S186P mutations—which are also found in the 1918 and seasonal H1N1 viruses—in HA alone were sufficient to confer virulence of Ca/04 in mice. HI assays against H1N1pdm demonstrate that the D131E and S186P mutations caused minor antigenic changes and, likely, affected receptor binding. The rapid selection of ma-Ca/04 in mice suggests that a virus containing this constellation of amino acids might have already been present in Ca/04, likely as minor quasispecies