Dark matter, the CMSSM and lattice QCD

Recent lattice measurements have given accurate estimates of the light and strange quark condensates in the proton. We use these new results to significantly improve the dark matter predictions in a set of benchmark models that represent different scenarios in the constrained minimal supersymmetric standard model (CMSSM). Because the predicted cross sections are at least an order of magnitude smaller than previously suggested, our results have significant consequences for dark matter searches.Comment: 4 pages, 4 figure

Neutralino-hadron scattering in the NMSSM

We provide a scan of the parameter space for neutralino-hadron scattering in the next-to-minimal supersymmetric standard model using an updated value for the strange quark sigma commutator. These results also take into account constraints from WMAP data on the relic density and new constraints from the Large Hadron Collider. We find that the resultant spin-independent cross sections are smaller in magnitude than those found in recent results obtained within the constrained minimal supersymmetric standard model, yet still great enough to feasibly allow for detection in the case of bino-like neutralinos.Comment: 4 pages 5 figure

Essential role for non-canonical poly(A) polymerase GLD4 in cytoplasmic polyadenylation and carbohydrate metabolism

Regulation of gene expression at the level of cytoplasmic polyadenylation is important for many biological phenomena including cell cycle progression, mitochondrial respiration, and learning and memory. GLD4 is one of the non-canonical poly(A) polymerases that regulates cytoplasmic polyadenylation-induced translation, but its target mRNAs and role in cellular physiology is not well known. To assess the full panoply of mRNAs whose polyadenylation is controlled by GLD4, we performed an unbiased whole genome-wide screen using poy(U) chromatography and thermal elution. We identified hundreds of mRNAs regulated by GLD4, several of which are involved in carbohydrate metabolism including GLUT1, a major glucose transporter. Depletion of GLD4 not only reduced GLUT1 poly(A) tail length, but also GLUT1 protein. GLD4-mediated translational control of GLUT1 mRNA is dependent of an RNA binding protein, CPEB1, and its binding elements in the 3 UTR. Through regulating GLUT1 level, GLD4 affects glucose uptake into cells and lactate levels. Moreover, GLD4 depletion impairs glucose deprivation-induced GLUT1 up-regulation. In addition, we found that GLD4 affects glucose-dependent cellular phenotypes such as migration and invasion in glioblastoma cells. Our observations delineate a novel post-transcriptional regulatory network involving carbohydrate metabolism and glucose homeostasis mediated by GLD4

Dietary energy density and growing-finishing pig performance and profitability

A retrospective analysis of 25 studies (16 at university and 9 at field research facilities) was conducted to model the response in ADG and F/G to increasing dietary energy density and its effect on profitability. Average daily feed intake in the field studies was approximately 30% lower than in the university studies, and as pigs increase in weight in the university studies they transition to a non-energy dependent phase of growth at a lighter weight than those in the field studies. The percentage response in ADG per percent added fat in the university studies was greater for the first 2.5% added fat than for higher fat levels, indicating a diminishing return. However, the percentage response in ADG was similar for both the 2.5 and 5% added fat levels in the field studies, indicating a linear response to fat additions. As expected the F/G improvement was greater in the field compared to the university studies. A five-year price series was used to determine the impact of fat additions to cornsoybean meal-based diets on profitability. For lighter weight pigs (70 to 120 lb), the net return to added fat is almost always positive, with feed cost per unit of gain being increased and deceased 50% of the time. However, the net return to added fat for heavier weight pigs (230 to 265 lb) fluctuates, with feed cost per unit of gain being increased in most scenarios. Using high energy diets for lighter weight pigs is cost effective and increases profit the majority of the time. The optimal energy density for late finishing pig diets is more dependent on the economic conditions

Historical Prediction Modeling Approach for Estimating Long-Term Concentrations of PM in Cohort Studies Before the 1999 Implementation of Widespread Monitoring

Introduction: Recent cohort studies use exposure prediction models to estimate the association between long-term residential concentrations of PM2.5 and health. Because these prediction models rely on PM2.5 monitoring data, predictions for times before extensive spatial monitoring present a challenge to understanding long-term exposure effects. The Environmental Protection Agency (EPA) Federal Reference Method (FRM) network for PM2.5 was established in 1999. We evaluated a novel statistical approach to produce high quality exposure predictions from 1980-2010 for epidemiological applications. Methods: We developed spatio-temporal prediction models using geographic predictors and annual average PM2.5 data from 1999 through 2010 from the FRM and the Interagency Monitoring of Protected Visual Environments (IMPROVE) networks. The model consists of a spatially-varying long-term mean, a spatially-varying temporal trend, and spatially-varying and temporally-independent spatio-temporal residuals structured using a universal kriging framework. Temporal trends in annual averages of PM2.5 before 1999 were estimated by using a) extrapolation based on PM2.5 data for 1999-2010 in FRM/IMPROVE, b) PM2.5 sulfate data for 1987-2010 in the Clean Air Status and Trends Network, and c) visibility data for 1980-2010 across the Weather-Bureau-Army-Navy network. We validated the resulting models using PM2.5 data collected before 1999 from IMPROVE, California Air Resources Board dichotomous sampler monitoring (CARB dichot), the Southern California Children’s Health Study (CHS), and the Inhalable Particulate Network (IPN). Results: The PM2.5 prediction model performed well across three trend estimation approaches when validated using IMPROVE and CHS data (R2= 0.84–0.91). Model performance using CARB dichot and IPN data was worse than those in IMPROVE most likely due to inconsistent sampling methods and smaller numbers of monitoring sites. Discussion: Our prediction modeling approach will allow health effects estimation associated with long-term exposures to PM2.5 over extended time periods of up to 30 years

Testing validity of FitnessGram in two samples of US adolescents (12–15 years)

Background This study examined the validity of the FitnessGram® criterion-reference cut-points for cardiorespiratory fitness (CRF) based on two samples of US adolescents (aged 12–15 years). This study also established the CRF cut-points for metabolically healthy weight status based on a recent national fitness survey for the purposes of cross-validating with pre-existing cut-points including FitnessGram. Methods Two cross-sectional data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES) (n = 378) and 2012 NHANES National Youth Fitness Survey (NNYFS) (n = 451) were used. CRF (estimated V˙ role= presentation style= box-sizing: border-box; margin: 0px; padding: 0px; display: inline-block; line-height: normal; font-size: 16.2px; word-spacing: normal; overflow-wrap: normal; white-space: nowrap; float: none; direction: ltr; max-width: none; max-height: none; min-width: 0px; min-height: 0px; border: 0px; position: relative; \u3eV˙O2max in mL/kg/min) was estimated from a submaximal exercise test. CRF categories based on FitnessGram cut-points, a clustered cardiometabolic risk factors score and weight status were used. A series of Receiver Operating Characteristic (ROC) curve analyses were conducted to identify age- and sex-specific CRF cut-points that were optimal for metabolically healthy weight status. Results Based on FitnessGram cut-points, having high risk CRF, but not low risk CRF, was associated with high cardiometabolic risk (OR = 3.17, 95% CI = 1.14–8.79) and unhealthy weight status (OR = 5.81, 95% CI = 3.49–9.68). The optimal CRF cut-points for 12-13-year-olds and 14-15-year-olds were 40 and 43 mL/kg/min in males and 39 and 34 mL/kg/min in females, respectively. Compared to meeting new CRF cut-points, not meeting new CRF cut-points was associated with higher odds of showing high cardiometabolic risk (OR = 2.91, 95% CI = 1.47–5.77) and metabolically unhealthy weight status (OR = 4.47, 95% CI = 2.83–7.05). Conclusion FitnessGram CRF cut-point itself has rarely been scrutinized in previous literature. Our findings provide partial support for FitnessGram based on two samples of US adolescents. CRF cut-points established in this study supports international criterion-referenced cut-points as well as FitnessGram cut-points only for males. FitnessGram should be continuously monitored and scrutinized using different samples

Mitochondrial function in heart failure: The impact of ischemic and non-ischemic etiology

Background Although cardiac mitochondrial dysfunction is associated with heart failure (HF), this is a complex syndrome with two predominant etiologies, ischemic HF (iHF) and non-ischemic HF (niHF), and the exact impact of mitochondrial dysfunction in these two distinct forms of HF is unknown. Methods and results To determine the impact of HF etiology on mitochondrial function, respiration was measured in permeabilized cardiac muscle fibers from patients with iHF (n = 17), niHF (n = 18), and healthy donor hearts (HdH). Oxidative phosphorylation capacity (OXPHOS), assessed as state 3 respiration, fell progressively from HdH to niHF, to iHF (Complex I + II: 54 ± 1; 34 ± 4; 27 ± 3 pmol·s− 1·mg− 1) as did citrate synthase activity (CSA: 206 ± 18; 129 ± 6; 82 ± 6 nmol·mg− 1·min− 1). Although still significantly lower than HdH, normalization of OXPHOS by CSA negated the difference in mass specific OXPHOS between iHF and niHF. Interestingly, Complex I state 2 respiration increased progressively from HdH, to niHF, to iHF, whether or not normalized for CSA (0.6 ± 0.2; 1.1 ± 0.3; 2.3 ± 0.3; pmol·mg− 1·CSA), such that the respiratory control ratio (RCR), fell in the same manner across groups. Finally, both the total free radical levels (60 ± 6; 46 ± 4 AU) and level of mitochondrial derived superoxide (1.0 ± 0.2; 0.7 ± 0.1 AU) were greater in iHF compared to niHF, respectively. Conclusions Thus, the HF-related attenuation in OXPHOS actually appears to be independent of etiology when the lower mitochondrial content of iHF is taken into account. However, these findings provide evidence of deleterious intrinsic mitochondrial changes in iHF, compared to niHF, including greater proton leak, attenuated OXPHOS efficiency, and augmented free radical levels

Altered skeletal muscle mitochondrial phenotype in COPD: disease vs. disuse

Patients with chronic obstructive pulmonary disease (COPD) exhibit an altered skeletal muscle mitochondrial phenotype, which often includes reduced mitochondrial density, altered respiratory function, and elevated oxidative stress. As this phenotype may be explained by the sedentary lifestyle that commonly accompanies this disease, the aim of this study was to determine whether such alterations are still evident when patients with COPD are compared to control subjects matched for objectively measured physical activity (PA; accelerometry). Indexes of mitochondrial density [citrate synthase (CS) activity], respiratory function (respirometry in permeabilized fibers), and muscle oxidative stress [4-hydroxynonenal (4-HNE) content] were assessed in muscle fibers biopsied from the vastus lateralis of nine patients with COPD and nine PA-matched control subjects (CON). Despite performing similar levels of PA (CON: 18 ± 3, COPD: 20 ± 7 daily minutes moderate-to-vigorous PA; CON: 4,596 ± 683, COPD: 4,219 ± 763 steps per day, P \u3e 0.70), patients with COPD still exhibited several alterations in their mitochondrial phenotype, including attenuated skeletal muscle mitochondrial density (CS activity; CON 70.6 ± 3.8, COPD 52.7 ± 6.5 U/mg, P \u3c 0.05), altered mitochondrial respiration [e.g., ratio of complex I-driven state 3 to complex II-driven state 3 (CI/CII); CON: 1.20 ± 0.11, COPD: 0.90 ± 0.05, P \u3c 0.05), and oxidative stress (4-HNE; CON: 1.35 ± 0.19, COPD: 2.26 ± 0.25 relative to β-actin, P \u3c 0.05). Furthermore, CS activity (r = 0.55), CI/CII (r = 0.60), and 4-HNE (r = 0.49) were all correlated with pulmonary function, assessed as forced expiratory volume in 1 s (P \u3c 0.05), but not PA (P \u3e 0.05). In conclusion, the altered mitochondrial phenotype in COPD is present even in the absence of differing levels of PA and appears to be related to the disease itself