Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function human variant (SRC-1L1376P), leptin-induced depolarization of Pomc neurons and Pomc expression are significantly reduced, and food intake and body weight are increased. In summary, we demonstrate that SRC-1 modulates the function of hypothalamic Pomc neurons, and suggest that targeting SRC-1 may represent a useful therapeutic strategy for weight loss.Peer reviewe

The UK10K project identifies rare variants in health and disease

M. Kivimäki työryhmäjäsen.The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7x) or exomes (high read depth, 80x) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.Peer reviewe

THE EFFECTS OF A DYNAMIC WARM-UP USING A RESPIRATORY TRAINING MASK ON VERTICAL JUMP PERFORMANCE

Emilee M. Bounds, John H. Sellers, Jessica A. Schnaiter, Bert H. Jacobson FACSM; Oklahoma State University, Stillwater, Oklahoma Respiratory training masks have been utilized to increase warm-up intensity via increased respiration rate, heart rate, and body temperature without inducing muscular fatigue. However, the majority of such claims appear to be based on anecdotal evidence as opposed to evidence-based research. PURPOSE: The purpose of this study was to investigate the effect of a high-intensity warm-up (HWU) using a respiratory training mask on vertical jump (VJ) performance in Division I American football athletes. METHODS: Seventeen male (mean ± SD: age = 17.94 ± .75 years, mass = 104.43 ± 23.02 kg, height 184.93 ± 7.06 cm) American football athletes from the NCAA Division I level were recruited to participate in this study from a Midwestern university. Participants were informed of risks, and after completing an informed consent form, completed two testing sessions to assess VJ performance. Prior to each testing session, a member of the university’s strength and conditioning staff led the participants through a dynamic warm-up that focused on lower body musculature. For one testing session, participants completed the warm-up (WU) without the respiratory training mask, while for the other testing session, participants completed the warm-up with the respiratory training mask. The respiratory training mask was set so as to increase the athlete’s respiratory efforts 12-fold in order to create the high-intensity warm-up (HWU). After completing the warm up, participants executed three counter-movement vertical jumps (VJ). For data analysis purposes, values from each participant’s highest VJ performance were selected from both the control (WU) and experimental (HWU) sessions. A one-way repeated measure analysis of variance (ANOVA) design was used to assess differences between control and HWU results. All statistical analyses were performed using SPSS (Version 21.0 for Windows; SPSS, Chicago, Illinois) with statistical significance set a p \u3c .05. RESULTS: No statistical difference was found (p = 0.07) between vertical jump performance using a standard warm-up and high-intensity warm up. CONCLUSION: Using a respiratory resistance mask for a warm-up does not impact vertical jump height, and practitioners should exercise caution when prescribing its use to increase performance

EFFECTS OF A DYNAMIC WARM-UP USING A RESISTANCE TRAINING MASK ON SPRINT PERFORMANCE

Jessica A. Schnaiter, John H. Sellers, Emilee M. Bounds, Bert H. Jacobson *FACSM Oklahoma State University, Stillwater, OK In recent years, coaches and athletes alike have taken a keen interest in maximizing the efficiency of a dynamic warm-up without inducing muscular fatigue. One proposed method of doing so is using a respiratory training mask to provide breathing resistance to increase the intensity of a warm-up. Though there is limited empirical evidence on the topic, many athletes have adopted this warm-up strategy, possibly due to testimonials from high-profile athletes in their respective sports. PURPOSE: The purpose of this study was to investigate the effect of a high-intensity warm-up (HWU) using a respiratory training mask on sprint performance, heart rate measures (HR), and ratings of perceived exertion (RPE) in Division I football athletes using a timing system. METHODS: Seventeen male (mean ± SD: age = 17.94 ± .75 years, weight = 104.43 ± 23.02 kg, height 184.93 ± 7.06 cm) American football athletes from a NCAA Division I level were recruited to participate in this study from a Midwestern university. Athletes were informed of risks, and upon completing an informed consent document, completed 2 testing sessions separated by 7 days. Each testing session took place on artificial turf in the university’s indoor training facility at the same time of day. Both testing sessions began with a warm-up (WU) under the instruction of a member of the university’s strength and condition staff. The WU consisted of dynamic exercises targeting the lower body musculature. During the initial visit, participants completed the dynamic WU and testing without a respiratory training mask. During the second visit, the HWU was completed with the respiratory training mask set to increase the resistance level of breathing by 12-fold. Upon completion of the HWU, participants removed the mask and performed 5 × 10-meter sprints. A one-way repeated measures analysis of variance (ANOVA) design was used to assess differences between control and experimental results. All statistical analyses were performed using SPSS (Version 21.0 for Windows; SPSS, Chicago, Illinois) with statistical significance set a p \u3c .05. RESULTS: Sprint time was not significantly different after a HAWU using a respiratory training mask (p = 0.874). CONCLUSION: These findings do not suggest the use of a respiratory resistance training mask during a dynamic warm-up is useful in increasing 10-meter sprint times for football players. Athlete’s performance on repeated sprints was not improved after using a resistance mask; however, performance was also not hindered

Radionuclide imaging of spinal infections

Background: The diagnosis of spinal infection, with or without implants, has been a challenge for physicians for many years. Spinal infections are now being recognised more frequently, owing to aging of the population and the increasing use of spinal-fusion surgery. Discussion: The diagnosis in many cases is delayed, and this may result in permanent neurological damage or even death. Laboratory evidence of infection is variable. Conventional radiography and radionuclide bone imaging lack both sensitivity and specificity. Neither in vitro labelled leucocyte scintigraphy nor 99mTc-anti-granulocyte antibody scintigraphy is especially useful, because of the frequency with which spinal infection presents as a non-specific photopenic area on these tests. Sequential bone/gallium imaging and 67Ga-SPECT are currently the radionuclide procedures of choice for spinal osteomyelitis, but these tests lack specificity, suffer from poor spatial resolution and require several days to complete. [ 18F]Fluoro-2-deoxy-D-glucose (FDG) PET is a promising technique for diagnosing spinal infection, and has several potential advantages over conventional radionuclide tests. Results: The study is sensitive and is completed in a single session, and image quality is superior to that obtained with single-photon emitting tracers. The specificity of FDG-PET may also be superior to that of conventional tracers because degenerative bone disease and fractures usually do not produce intense FDG uptake; moreover, spinal implants do not affect FDG imaging. However, FDG-PET images have to be read with caution in patients with instrumented spinal-fusion surgery since non-specific accumulation of FDG around the fusion material is not uncommon. Conclusion: In the future, PET-CT will likely provide more precise localisation of abnormalities. FDG-PET may prove to be useful for monitoring response to treatment in patients with spinal osteomyelitis. Other tracers for diagnosing spinal osteomyelitis are also under investigation, including radiolabelled antibiotics, such as 99mTc-ciprofloxacin, and radiolabelled streptavidin-biotin complex. Antimicrobial peptides display preferential binding to microorganisms over human cells and perhaps new radiopharmaceuticals will be recruited from the array of human antimicrobial peptides/proteins. In experiments with Tc-ubiquicidin-derived peptides, radioactivity at the site of infection correlated well with the number of viable bacteria present. Finally, radiolabelled antifungal tracers could potentially distinguish fungal from bacterial infections. © 2006 Springer-Verlag.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Determinants of Peak Bone Mass Acquisition

Peak bone mass (PBM) is an important determinant of osteoporotic fracture risk later in life. Bone mineral mass accumulation from infancy to postpuberty is a complex process implicating interactions of genetic, endocrine, mechanical, and nutritional factors. PBM is attained in the axial skeleton and in the proximal femur by the end of the second decade of life. The increase in mass and strength is essentially due to an increment in bone size, with volumetric bone mineral density (BMD) changing very little during growth. In adult women, an increase of PBM by 10%, that is, by approximately 1 standard deviation (SD), could decrease the risk of fragility fracture by 50% or be equivalent to retarding menopause by 14 years. Bone mineral mass during growth follows a trajectory. The main influencing factor is genetics. Increasing calcium intake or mechanical loading can shift upward the age-bone mass trajectory, while chronic diseases and their treatment can shift it downward. Prepuberty appears to be an opportune time for obtaining a substantial benefit of increasing physical activity with appropriate intakes of calcium and proteins