Long-term creatine supplementation does not significantly affect clinical markers of health in athletes

Creatine has been reported to be an effective ergogenic aid for athletes. However, concerns have been raised regarding the long-term safety of creatine supplementation. This study examined the effects of long-term creatine supplementation on a 69-item panel of serum, whole blood, and urinary markers of clinical health status in athletes. Over a 21-month period, 98 Division IA college football players were administered in an open label manner creatine or non-creatine containing supplements following training sessions. Subjects who ingested creatine were administered 15.75 g/day of creatine monohydrate for 5 days and an average of 5 g/day thereafter in 5–10 g/day doses. Fasting blood and 24-h urine samples were collected at 0, 1, 1.5, 4, 6, 10, 12, 17, and 21 months of training. A comprehensive quantitative clinical chemistry panel was determined on serum and whole blood samples (metabolic markers, muscle and liver enzymes, electrolytes, lipid profiles, hematological markers, and lymphocytes). In addition, urine samples were quantitatively and qualitative analyzed to assess clinical status and renal function. At the end of the study, subjects were categorized into groups that did not take creatine (n = 44) and subjects who took creatine for 0–6 months (mean 4.4 ± 1.8 months, n = 12), 7–12 months (mean 9.3 ± 2.0 months, n = 25), and 12–21 months (mean 19.3 ± 2.4 months, n = 17). Baseline and the subjects' final blood and urine samples were analyzed by MANOVA and 2 × 2 repeated measures ANOVA univariate tests. MANOVA revealed no significant differences (p = 0.51) among groups in the 54-item panel of quantitative blood and urine markers assessed. Univariate analysis revealed no clinically significant interactions among groups in markers of clinical status. In addition, no apparent differences were observed among groups in the 15-item panel of qualitative urine markers. Results indicate that long-term creatine supplementation (up to 21-months) does not appear to adversely effect markers of health status in athletes undergoing intense training in comparison to athletes who do not take creatine.     

The Hsp110 molecular chaperone stabilizes apolipoprotein B from endoplasmic reticulum-associated degradation (ERAD)

Apolipoprotein B (apoB) is the most abundant protein in low density lipoproteins and plays key roles in cholesterol homeostasis. The co-translational degradation of apoB is controlled by fatty acid levels in the endoplasmic reticulum (ER) and is mediated by the proteasome. To define the mechanism of apoB degradation, we employed a cell-free system in which proteasome-dependent degradation is recapitulated with yeast cytosol, and we developed an apoB yeast expression system. We discovered that a yeast Hsp110, Sse1p, associates with and stabilizes apoB, which contrasts with data indicating that select Hsp70s and Hsp90s facilitate apoB degradation. However, the Ssb Hsp70 chaperones have no effect on apoB turnover. To determine whether our results are relevant in mammalian cells, Hsp110 was overexpressed in hepatocytes, and enhanced apoB secretion was observed. This study indicates that chaperones within distinct complexes can play unique roles during ER-associated degradation (ERAD), establishes a role for Sse1/Hsp110 in ERAD, and identifies Hsp110 as a target to lower cholesterol.     

THRUMIN1 is a light-regulated actin-bundling protein involved in chloroplast motility

Chloroplast movement in response to changing light conditions optimizes photosynthetic light absorption. This repositioning is stimulated by blue light perceived via the phototropin photoreceptors and is transduced to the actin cytoskeleton. Some actin-based motility systems use filament reorganizations rather than myosin-based translocations. Recent research favors the hypothesis that chloroplast movement is driven by actin reorganization at the plasma membrane, but no proteins affecting chloroplast movements have been shown to associate with both the plasma membrane and actin filaments in vivo. Here we identified THRUMIN1 as a critical link between phototropin photoreceptor activity at the plasma membrane and actin-dependent chloroplast movements. THRUMIN1 bundles filamentous actin in vitro, and it localizes to the plasma membrane and displays light- and phototropin-dependent localization to microfilaments in vivo. These results suggest that phototropin-induced actin bundling via THRUMIN1 is important for chloroplast movement. A mammalian homolog of THRUMIN1, GRXCR1, has been implicated in auditory responses and hair cell stereocilla development as a regulator of actin architecture. Studies of THRUMIN1 will help elucidate the function of this family of eukaryotic proteins.     

Design and initial characterization of the SC-200 proteomics standard mixture

High-throughput (HTP) proteomics studies generate large amounts of data. Interpretation of these data requires effective approaches to distinguish noise from biological signal, particularly as instrument and computational capacity increase and studies become more complex. Resolving this issue requires validated and reproducible methods and models, which in turn requires complex experimental and computational standards. The absence of appropriate standards and data sets for validating experimental and computational workflows hinders the development of HTP proteomics methods. Most protein standards are simple mixtures of proteins or peptides, or undercharacterized reference standards in which the identity and concentration of the constituent proteins is unknown. The Seattle Children's 200 (SC-200) proposed proteomics standard mixture is the next step toward developing realistic, fully characterized HTP proteomics standards. The SC-200 exhibits a unique modular design to extend its functionality, and consists of 200 proteins of known identities and molar concentrations from 6 microbial genomes, distributed into 10 molar concentration tiers spanning a 1,000-fold range. We describe the SC-200's design, potential uses, and initial characterization. We identified 84% of SC-200 proteins with an LTQ-Orbitrap and 65% with an LTQ-Velos (false discovery rate?=?1% for both). There were obvious trends in success rate, sequence coverage, and spectral counts with protein concentration; however, protein identification, sequence coverage, and spectral counts vary greatly within concentration levels.     

EvoS: A Prescription for What Ails Pre-Medical Education?

Pre-medical students are certainly a widely varied group, with different motivations and experiences, different skills sets and interests. However, they often tend to approach their undergraduate education as a necessary evil that they must endure in order to achieve their ultimate goals. This article summarizes recent literature addressing some of the questions that have been raised regarding pre-medical education programs. Are students prepared for the intellectual, emotional, and even physical challenges of medical training? What deficiencies are commonly seen in entering medical students? What are students’ perceptions of how well their pre-medical studies helped them? Many of these studies have resulted in a call for more science training, while some have advocated for less, but with an enhanced focus on humanistic studies. We supply a brief outline of our Evolutionary Studies (EvoS) program and reflect upon how participation in this program can enhance pre-medical students’ education. Importantly, we argue that EvoS can expand students’ depth of understanding of science, as well as nurture their ability to think about the needs of their patients and the context of their medical practice.