The comprehensive model system COSMO-ART - Radiative impact of aerosol on the state of the atmosphere on the regional scale

A new fully online coupled model system developed for the evaluation of the interaction of aerosol particles with the atmosphere on the regional scale is described. The model system is based on the operational weather forecast model of the Deutscher Wetterdienst. Physical processes like transport, turbulent diffusion, and dry and wet deposition are treated together with photochemistry and aerosol dynamics using the modal approach. Based on detailed calculations we have developed parameterisations to examine the impact of aerosol particles on photolysis and on radiation. Currently the model allows feedback between natural and anthropogenic aerosol particles and the atmospheric variables that are initialized by the modification of the radiative fluxes. The model system is applied to two summer episodes, each lasting five days, with a model domain covering Western Europe and adjacent regions. The first episode is characterised by almost cloud free conditions and the second one by cloudy conditions. The simulated aerosol concentrations are compared to observations made at 700 stations distributed over Western Europe. <br><br> For each episode two model runs are performed; one where the feedback between the aerosol particles and the atmosphere is taken into account and a second one where the feedback is neglected. Comparing these two sets of model runs, the radiative feedback on temperature and other variables is evaluated. <br><br> In the cloud free case a clear correlation between the aerosol optical depth and changes in global radiation and temperature is found. In the case of cloudy conditions the pure radiative effects are superposed by changes in the liquid water content of the clouds due to changes in the thermodynamics of the atmosphere. In this case the correlation between the aerosol optical depth and its effects on temperature is low. However, on average a decrease in the 2 m temperature is still found. <br><br> For the area of Germany we found on average for both cases a reduction in the global radiation of about 6 W m<sup>2</sup>, a decrease of the 2 m temperature of 0.1 K, and a reduction in the daily temperature range of −0.13 K

Insulin-induced Increase in Anabolic Capacity is Blunted by Autophagic Inhibition in L6 Myotubes

Insulin is an anabolic hormone that acts on skeletal muscle cells to stimulate protein synthesis, an effect that is enhanced by the availability of amino acids. While autophagy within the cell provides an intracellular source of amino acids to support anabolism, little is known about how this pathway impacts the insulin-induced increase in anabolic capacity within skeletal muscle cells. PURPOSE: The purpose of this study was to determine the impact of autophagic inhibition in cultured L6 myotubes in conjunction with insulin stimulation in vitro. METHODS: Differentiated, cultured L6 myotubes were treated for 24 hours with or without insulin (100 nM) and NSC 185058 (100 μM), a specialized inhibitor of the autophagic catabolic pathway, in media enriched with 4% deuterium. Cells were harvested from each treatment group (n=3/group) 24 hours post-deuterium enrichment and were processed for protein synthesis and western blot protein analysis. A one-way ANOVA was used to compare groups, and when significant F ratios were present, a Student’s Newman-Keuls post hoc procedure was used to test differences among group means. Alpha was set at p≤0.05 for all analyses. RESULTS: Cells treated with insulin (INS) had a higher ratio of phosphorylated to total P70S6K compared to untreated (CON) cells and those incubated with both insulin and NSC 185058 (INS+NSC; 1694% and 327%, respectively; p\u3c0.05). INS+NSC also decreased the ratio of phosphorylated to total 4EBP1 relative to CON (-51%) and INS (-49%), although these differences were not significant (p\u3e0.05). Myofibrillar protein synthesis was stimulated with INS compared to CON and INS+NSC (30.3% and 70.1% respectively; p\u3c0.05) but was lower in INS+NSC relative to CON (-23.4%; p\u3c0.05). CONCLUSION: Results from our study indicate that insulin (100 nM) stimulates anabolism in skeletal muscle cells, but that addition of the autophagic inhibitor NSC 185058 (100 μM) blunts this effect to a level similar to or less than control. Further, our data suggest that the reduction of protein synthesis is mediated through the downregulation of the mTORC1 signaling pathway. While it is widely recognized that insulin promotes anabolic activity through both the direct stimulation of mTOR signaling and extracellular amino acid uptake, our data strongly indicate that autophagic processes are necessary for full anabolic responses in muscle. This decrease in anabolic capacity supports previous literature indicating that the amino acid availability impacts the stimulatory impact of insulin on protein synthesis

Cross-validation of a Prediction Equation for Energy Expenditure of an Acute Resistance Exercise Bout

Previously, our laboratory introduced a regression equation for predicting net kcal consumption of a resistance exercise (RE) bout: Total net kcal = 0.874(height, cm) - 0.596(age, years) - 1.016(fat mass, kg) + 1.638(lean mass, kg) + 2.461(total volume x 10-3) - 110.742 (R2 = 0.773, SEE=28.5 kcal). PURPOSE: The purpose of this study was to validate this regression equation using the same variables as predictors. METHODS: Forty-seven healthy, active subjects (23 men, 24 women, 20-58 yrs, 173.5 ± 10.5 cm, 85.5 ± 19.0 kg, VO2max 36.0 ± 8.4 ml/kg/min) were randomly divided into validation and cross-validation groups (nv = 24, ncv = 23). The validation group’s data was used to develop an equation to predict net kcal consumption, which was applied to the cross-validation group’s data to estimate net kcal consumption. Similarly, a prediction equation was derived from the cross-validation group’s raw data and applied to that of the validation group. The strength of the relationship between each group’s measured and estimated net kcal consumption was assessed via correlational analysis. RESULTS: Multiple linear regression yielded the following estimates of net kcal consumption: validation net kcal = 1.125(height, cm) – 0.662(age, years) – 0.800(fat mass, kg) + 1.344(lean mass, kg) + 2.278(total volume x 10-3) – 144.846 (R2 = 0.751, p \u3c 0.0001, SEE=29.7 kcal); cross-validation net kcal = 0.515(height, cm) - 0.520(age, years) - 1.220(fat mass, kg) + 1.995(lean mass, kg) + 2.620(total volume x 10-3) – 59.988 (R2 = 0.823, p \u3c 0.0001, SEE=29.2 kcal). These equations had a cross-validation coefficient of 0.902 and a double cross-validation coefficient of 0.863. CONCLUSION: The strong relationship between the measured and estimated net kcal consumption of both the cross-validation and validation group lead us to conclude that the regression equation derived by this laboratory is valid for estimating net energy expenditure for a total RE bout

Significant Predictors of Nonalcoholic Fatty Liver Disease in Texas Firefighters

Risk factors for Nonalcoholic Fatty Liver Disease (NAFLD) include obesity, hypertension, dyslipidemia, and diabetes mellitus. Not only are these prevalent in the general US population, but they are also present at high rates in a specific subset responsible for public safety – firefighters. PURPOSE: The aim of the present study is to use logistic regression to predict the likelihood of occurrence of NAFLD in firefighters using a subset of health-related factors associated with common cardiometabolic risk factors. METHODS: Data were collected on 136 firefighters (128 males, 8 females; 36.3 ± 9.0 yrs; 95.7 ± 17.0 kg; 178.9 ± 7.4 cm; 29.8 ± 4.2 kg/m2) participating in FITLIFE, a university-based fitness program at Texas A&M University. Nominal logistic regression with stepwise removal was used to estimate the best model to predict fatty liver disease. Stepwise removal identified resting systolic blood pressure (RSBP, mm HG), Body Mass Index (BMI, kg/m2), visceral adipose tissue (VAT, cm2), whether or not has hypertension or is on medication (HTNMED; 0=No,1=Yes), and plasma triglyceride concentrations (TG, mg/dL) as independent predictors (p\u3c0.05). Odds ratios (OR) were calculated to determine the change in the odds of NAFLD per unit increase in each predictor. RESULTS: Logistic regression yielded the following equation to predict the probability of developing NAFLD: Logit = -22.5176 + 0.0918(RSBP) + 0.2154(BMI) + 0.0065(TG) + 0.0161(VAT) + 1.830(HTNMED) (R2 = 0.4655, p \u3c 0.001). Of the predictors, the ORs from largest to smallest were 6.235, 1.240, 1.096, 1.016, and 1.002 for HTNMED, BMI, RSBP, VAT, and TG, respectively. CONCLUSION: Using RSBP, BMI, VAT, TG, and HTNMED as predictors, this study demonstrates that the probability of developing NAFLD in Texas firefighters can be reasonably predicted. This regression model and individual predictors may be used by health practitioners as a cost-effective screening tool to identify those at higher risk for NAFLD

Autophagy, but Not Proteolysis, May Aid in Muscle Protein Synthesis

For muscle growth to occur, protein synthesis must be greater than protein degradation. However, up to this point, anabolic pathways have garnered the brunt of investigations examining anabolic capacity with little investigation into the connectedness of catabolic signaling on these anabolic targets. PURPOSE: The purpose of this study was to elucidate the contributions of proteasomal-dependent and autophagic-dependent catabolic pathways on anabolism via analysis of fractional synthetic rates (FSR) in L6 myotubes. METHODS: Differentiated, cultured L6 myoblasts were treated with media containing 4% deuterium oxide (stable isotope label) and a corresponding pharmacological treatment (NSC 185058 [autophagic inhibitor; 100 μM], MG-262 [proteasomal inhibitor; 0.01 μM] or DMSO control; n=3/group) during the final 24-hours of the differentiation period prior to harvest. The myofibrillar pellet of the processed samples was used to determine FSR via mass-spectrometry analysis. DMSO-treated myotubes served as controls, with a one-way analysis of variance and Tukey’s post-hoc test used to test for any differences among groups. RESULTS: Our results indicate that MG-262 had no impact on myofibrillar FSR when compared to DMSO control (MG-262 1.0993 %/day vs. control 1.239 %/day). However, NSC 185058 lowered myofibrillar FSR (NSC 185058 0.9009 %/day vs. control 1.239 %/day; P=0.0282). CONCLUSION: These data suggest that inhibition of autophagic machinery can impair anabolism. This may be due to autophagy’s role in increasing the amino acid pool within the cell. Further, the lack of inhibition seen from MG-262 suggests that there is a delineation of roles within the catabolic pathways in regard to their influence on anabolism in healthy, metabolically unchallenged myotubes

Autophagy is Required for the Anabolic Response to Muscle Contraction

Exercise is a key stimulus in regulating the behavior and metabolism of skeletal muscle, with exercise inducing muscular growth through activation of the anabolic mechanistic target of rapamycin kinase (mTOR). Separately, there is mounting evidence that exercise increases autophagy (one of the main routes by which intracellular proteins are degraded) and that the autophagic process may indeed be required for adaptations to exercise training. PURPOSE: To investigate the effects of autophagy inhibition on mTOR signaling and cellular anabolism after muscular contraction. METHODS: Cultured L6 myotubes were to exposed to electrical pulse stimulation using a stimulator set to deliver bipolar pulses of 30V at 100 Hz for 200 ms every fifth second for 60 minutes. Subsequently, cells received either vehicle control, or 100 μM NSC-185058, an antagonist of the key autophagy protein ATG4B and known inhibitor of autophagy. All groups were also exposed to 4% deuterium oxide, a stable isotopic tracer for measurements of protein synthesis. 24 hours post “exercise” bout, cells were lysed in ice-cold Norris buffer, and prepared for Western immunoblot of protein expression, or determination of protein fractional synthesis rate (FSR) of the myofibrillar fraction via mass-spectrometry analysis. Non-stimulated cells receiving vehicle control treatment served as controls, with a one-way analysis of variance and Tukey’s post-hoc test used to test for any differences between groups. RESULTS: We found that phosphorylation of a key downstream target of mTOR, P70S6 kinase, was roughly seven times greater in cells subjected to EPS and vehicle control (710.3%) relative to control (p0.05). While there was a trend for EPS treatment to increase expression of ATG4B, along with a reduction of ATG4B content as a result of NSC-185058 treatment, this finding did not rise to the level of statistical significance. There were no differences in FSR between cells exposed to EPS; however, NSC-185058 treatment significantly reduced FSR in EPS treated cells relative to controls (0.8712 %/hr vs 1.193 %/hr). CONCLUSION: These findings present two conclusions: high-intensity EPS as an in vitro model of exercise elevates mTOR signaling through P70S6K 24 hours post exercise, and mTOR activation as a result of muscular contraction is reliant upon autophagy in skeletal muscle. Further work will be required to elucidate the dynamics of this relationship, and the interplay between skeletal muscle autophagy and anabolism

High Fat Relative to Low Fat Ground Beef Consumption Lowers Blood Pressure and Does Not Negatively Alter Arterial Stiffness

Beef consumption has been stigmatized as an unhealthy dietary choice. However, randomized control trials to support this claim are lacking. PURPOSE: To examine the effect of low-fat (5%) and high-fat (25%) ground beef consumption on blood pressure (BP) and carotid-femoral pulse wave velocity (PWV).METHODS: Twenty-three male subjects (age 40±11 yrs, height 177.4±6.7 cm, weight 97.3±25.0 kg, lean mass 64.5±9.5 kg, fat mass 30.6±19.1 kg) volunteered to participate in this cross-over design study. Each participant completed two, 5-week ground beef interventions in a randomized order with a 4-week washout period in-between. All participants visited the lab four times after an overnight fast. Each visit to the lab consisted of supine BP, dual energy x-ray absorptiometry (DXA) scan to assess body composition, and PWV analysis. The PWV recording was assessed on the right carotid and femoral arteries. The distance used for the PWV calculation was 80% of the actual distance between carotid and femoral sites. All PWV measures were completed according to previously published procedures (Van Bortel, 2011). BP and PWV results were analyzed separately via 2x2 repeated measures ANOVA. RESULTS: Our results indicate there was a significant decrease in systolic BP (p=0.01) following the high-fat ground beef intervention compared to the low-fat. The BP values for low-fat beef and high-fat beef are 120/74 and 116/73 mmHg, respectively. Further, there were no significant differences between the PWV measures. CONCLUSION: Based on our results, high fat ground beef favorably alters systolic BP and does not negatively affect PWV measures

The global aerosol-climate model ECHAM6.3-HAM2.3-Part 2: Cloud evaluation, aerosol radiative forcing, and climate sensitivity

This is the final version. Available on open access from European Geosciences Union via the DOI in this recordCode availability. The ECHAM-HAMMOZ model is made freely available to the scientific community under the HAMMOZ Software License Agreement, which defines the conditions under which the model can be used. More information can be found at the HAMMOZ website (https://redmine.hammoz.ethz.ch/projects/hammoz, last access: 13 August 2019). Scripts can be found at https://doi.org/10.5281/zenodo.2553891 (Neubauer et al., 2019a).Data availability. Data can be found at https://doi.org/10.5281/zenodo.2541936 (Neubauer et al., 2019b). ESA cloud CCI data can be downloaded from http://www.esa-cloud-cci.org/?q=data_download (Poulsen et al., 2017; Stengel et al., 2017b). MODIS products are available for download from Level 1 and the Atmosphere Archive and Distribution System (LAADS) at https://ladsweb.modaps.eosdis.nasa.gov/search/ (Platnick, 2017). ISCCP histogram data and the CALIPSO-GOCCP product can be obtained from http://climserv.ipsl.polytechnique.fr/cfmip-obs/ (Zhang et al., 2012; Pincus et al., 2012). Cloud-top CDNC can be downloaded from https://doi.org/10.15695/vudata.ees.1 (Bennartz and Rausch, 2016). MAC-LWP data are available at the Goddard Earth Sciences Data and Information Services Center (GES DISC; current hosting: http://disc.sci.gsfc.nasa.gov, Elsaesser et al., 2016). CERES satellite data can be obtained from the NASA Langley Research Center Atmospheric Science Data Center at https://ceres.larc.nasa.gov/order_data.php (last access: 12 February 2018). The IWP satellite data from Li et al. (2012) were obtained from the authors. GPCP Precipitation data provided by the NOAA/OAR/ESRL PSD, Boulder, Colorado, USA, from their Web site at https://www.esrl.noaa.gov/psd/ (last access: 16 September 2017).The global aerosol-climate model ECHAM6.3-HAM2.3 (E63H23) as well as the previous model versions ECHAM5.5-HAM2.0 (E55H20) and ECHAM6.1-HAM2.2 (E61H22) are evaluated using global observational datasets for clouds and precipitation. In E63H23, the amount of low clouds, the liquid and ice water path, and cloud radiative effects are more realistic than in previous model versions. E63H23 has a more physically based aerosol activation scheme, improvements in the cloud cover scheme, changes in the detrainment of convective clouds, changes in the sticking efficiency for the accretion of ice crystals by snow, consistent ice crystal shapes throughout the model, and changes in mixed-phase freezing; an inconsistency in ice crystal number concentration (ICNC) in cirrus clouds was also removed. Common biases in ECHAM and in E63H23 (and in previous ECHAM-HAM versions) are a cloud amount in stratocumulus regions that is too low and deep convective clouds over the Atlantic and Pacific oceans that form too close to the continents (while tropical land precipitation is underestimated). There are indications that ICNCs are overestimated in E63H23. Since clouds are important for effective radiative forcing due to aerosol-radiation and aerosol-cloud interactions (ERFariCaci) and equilibrium climate sensitivity (ECS), differences in ERFariCaci and ECS between the model versions were also analyzed. ERFariCaci is weaker in E63H23 (-1:0 W m-2) than in E61H22 (-1:2 W m-2) (or E55H20;-1:1 W m-2). This is caused by the weaker shortwave ERFariCaci (a new aerosol activation scheme and sea salt emission parameterization in E63H23, more realistic simulation of cloud water) overcompensating for the weaker longwave ERFariCaci (removal of an inconsistency in ICNC in cirrus clouds in E61H22). The decrease in ECS in E63H23 (2.5 K) compared to E61H22 (2.8 K) is due to changes in the entrainment rate for shallow convection (affecting the cloud amount feedback) and a stronger cloud phase feedback. Experiments with minimum cloud droplet number concentrations (CDNCmin) of 40 cm-3 or 10 cm-3 show that a higher value of CDNCmin reduces ERFariCaci as well as ECS in E63H23.Swiss National Science FoundationEuropean Union FP7European Research Council (ERC)Academy of Finlan

ASPP: a new family of oncogenes and tumour suppressor genes

The apoptosis stimulating proteins of p53 (ASPP) family consists of three members, ASPP1, ASPP2 and iASPP. They bind to proteins that are key players in controlling apoptosis (p53, Bcl-2 and RelA/p65) and cell growth (APCL, PP1). So far, the best-known function of the ASPP family members is their ability to regulate the apoptotic function of p53 and its family members, p63 and p73. Biochemical and genetic evidence has shown that ASPP1 and ASPP2 activate, whereas iASPP inhibits, the apoptotic but not the cell-cycle arrest function of p53. The p53 tumour suppressor gene, one of the most frequently mutated genes in human cancer, is capable of suppressing tumour growth through its ability to induce apoptosis or cell-cycle arrest. Thus, the ASPP family of proteins helps to determine how cells choose to die and may therefore be a novel target for cancer therapy