A Systematic Review and Meta-Analysis of Proteomics Literature on the Response of Human Skeletal Muscle to Obesity/Type 2 Diabetes Mellitus (T2DM) Versus Exercise Training.

We performed a systematic review and meta-analysis of proteomics literature that reports human skeletal muscle responses in the context of either pathological decline associated with obesity/T2DM and physiological adaptations to exercise training. Literature was collected from PubMed and DOAJ databases following PRISMA guidelines using the search terms 'proteom*', and 'skeletal muscle' combined with either 'obesity, insulin resistance, diabetes, impaired glucose tolerance' or 'exercise, training'. Eleven studies were included in the systematic review, and meta-analysis was performed on a sub-set (four studies) of the reviewed literature that reported the necessary primary data. The majority of proteins (n = 73) more abundant in the muscle of obese/T2DM individuals were unique to this group and not reported to be responsive to exercise training. The main response of skeletal muscle to exercise training was a greater abundance of proteins of the mitochondrial electron transport chain, tricarboxylic acid cycle and mitochondrial respiratory chain complex I assembly. In total, five proteins were less abundant in muscle of obese/T2DM individuals and were also reported to be more abundant in the muscle of endurance-trained individuals, suggesting one of the major mechanisms of exercise-induced protection against the deleterious effects of obesity/T2DM occurs at complex I of the electron transport chain

Vatica diospyroides Symington type LS Root Extract Induces Antiproliferation of KB, MCF-7 and NCI-H187 Cell Lines

Purpose: To investigate the therapeutic efficacy of V. diospyroides Symington type LS root extract as a chemopreventive agent against various cancer cell lines.Methods: Acetone root extract was evaluated for in vitro cytotoxicity against KB (oral cavity cancer), MCF-7 (breast cancer), and NCI-H187 (small cell lung cancer), using Resazurin microplate assay (REMA). Toxicity against a representative normal cells, Vero (African green monkey kidney), was assessed using green fluorescence protein (GFP)-based assay.Results: V. diospyroides root extract showed significant cytotoxic effects on KB and MCF-7 cell lines in a dose-dependent manner with IC50 of 35.05 ± 1.45 and 36.63 ± 3.40 μg/mL, respectively. NCI-H187 was not significantly inhibited (≤ 19.39 % inhibition) at the concentrations tested. IC50 against Vero cells was outside the concentration range of 0.2 - 50 μg/mL.Conclusion: These results indicate that the root extract of V. diospyroides has in vitro cytotoxic effect on human oral cavity cancer and breast cancer cells. No toxic effect on normal cells was observed. Thus, the extract may provide bioactive substances for human cancer therapy.Keywords: Breast cancer, Oral cavity cancer, Lung cancer, Cytotoxicity, Vero cells, Vatica diospyroide

On the Rate of Synthesis of Individual Proteins within and between Different Striated Muscles of the Rat

The turnover of muscle protein is responsive to different (patho)-physiological conditions but little is known about the rate of synthesis at the level of individual proteins or whether this varies between different muscles. We investigated the synthesis rate of eight proteins (actin, albumin, ATP synthase alpha, beta enolase, creatine kinase, myosin essential light chain, myosin regulatory light chain and tropomyosin) in the extensor digitorum longus, diaphragm, heart and soleus of male Wistar rats (352 ± 30 g body weight). Animals were assigned to four groups (n = 3, in each), including a control and groups that received deuterium oxide (2H2O) for 4 days, 7 days or 14 days. Deuterium labelling was initiated by an intraperitoneal injection of 10 μL/g body weight of 99.9% 2H2O-saline, and was maintained by administration of 5% (v/v) 2H2O in drinking water provided ad libitum. Homogenates of the isolated muscles were analysed by 2-dimensional gel electrophoresis and matrix-assisted laser desorption ionisation time of flight mass spectrometry. Proteins were identified against the SwissProt database using peptide mass fingerprinting. For each of the eight proteins investigated, the molar percent enrichment (MPE) of 2H and rate constant (k) of protein synthesis was calculated from the mass isotopomer distribution of peptides based on the amino acid sequence and predicted number of exchangeable C–H bonds. The average MPE (2.14% ± 0.2%) was as expected and was consistent across muscles harvested at different times (i.e., steady state enrichment was achieved). The synthesis rate of individual proteins differed markedly within each muscle and the rank-order of synthesis rates differed among the muscles studied. After 14 days the fraction of albumin synthesised (23% ± 5%) was significantly (p < 0.05) greater than for other muscle proteins. These data represent the first attempt to study the synthesis rates of individual proteins across a number of different striated muscles

Subchronic administration of phencyclidine produces hypermethylation in the parvalbumin gene promoter in rat brain

Aim: A deficit in parvalbumin neurons is found in schizophrenia and several animal models of the disease. In this preliminary study, we determined whether one such model, phencyclidine (PCP) administration, results in changes in DNA methylation in the rat Pvalb promoter. Materials & methods: DNA from hippocampus and prefrontal cortex from rats, which 6 weeks previously received either 2 mg/kg PCP or vehicle for 7 days, underwent bisulphite pyrosequencing to determine methylation. Results: PCP administration induced significantly greater methylation at one of two Pvalb CpG sites in both prefrontal cortex and hippocampus, while no significant difference was found in long interspersed nucleotide element-1, a global measure of DNA methylation. Conclusion: Subchronic PCP administration results in a specific hypermethylation in the Pvalb promoter which may contribute to parvalbumin deficits in this animal model of psychosis

Adaptation of rat fast-twitch muscle to endurance activity is underpinned by changes to protein degradation as well as protein synthesis.

Muscle adaptations to exercise are underpinned by alterations to the abundance of individual proteins, which may occur through a change either to the synthesis or degradation of each protein. We used deuterium oxide (2 H2 O) labeling and chronic low-frequency stimulation (CLFS) in vivo to investigate the synthesis, abundance, and degradation of individual proteins during exercise-induced muscle adaptation. Independent groups of rats received CLFS (10 Hz, 24 h/d) and 2 H2 O for 0, 10, 20, or 30 days. The extensor digitorum longus (EDL) was isolated from stimulated (Stim) and contralateral non-stimulated (Ctrl) legs. Proteomic analysis encompassed 38 myofibrillar and 46 soluble proteins and the rates of change in abundance, synthesis, and degradation were reported in absolute (ng/d) units. Overall, synthesis and degradation made equal contributions to the adaptation of the proteome, including instances where a decrease in protein-specific degradation primarily accounted for the increase in abundance of the protein

Sussing merger trees: the Merger Trees Comparison Project

Merger trees follow the growth and merger of dark-matter haloes over cosmic history. As well as giving important insights into the growth of cosmic structure in their own right, they provide an essential backbone to semi-analytic models of galaxy formation. This paper is the first in a series to arise from the Sussing Merger Trees Workshop in which 10 different tree-building algorithms were applied to the same set of halo catalogues and their results compared. Although many of these codes were similar in nature, all algorithms produced distinct results. Our main conclusions are that a useful merger-tree code should possess the following features: (i) the use of particle IDs to match haloes between snapshots; (ii) the ability to skip at least one, and preferably more, snapshots in order to recover subhaloes that are temporarily lost during merging; (iii) the ability to cope with (and ideally smooth out) large, temporary fluctuations in halo mass. Finally, to enable different groups to communicate effectively, we defined a common terminology that we used when discussing merger trees and we encourage others to adopt the same language. We also specified a minimal output format to record the results

Reliability of Protein Abundance and Synthesis Measurements in Human Skeletal Muscle.

We investigated the repeatability of dynamic proteome profiling (DPP), which is a novel technique for measuring the relative abundance (ABD) and fractional synthesis rate (FSR) of proteins in humans. LC-MS analysis was performed on muscle samples taken from male participants (n = 4) that consumed 4 × 50 ml doses of deuterium oxide (2 H2 O) per day for 14 d. ABD was measured by label-free quantitation and FSR was calculated from time-dependent changes in peptide mass isotopomer abundances. One-hundred and one proteins had at least 1 unique peptide and were used in the assessment of protein ABD. Fifty-four of these proteins met more stringent criteria and were used in the assessment of FSR data. The median (M), lower- (Q1 ) and upper-quartile (Q3 ) values for protein FSR (%/d) were M = 1.63, Q1  = 1.07, Q3  = 3.24. The technical CV of ABD data had a median value of 3.6% (Q1 1.7% - Q3 6.7%), whereas the median CV of FSR data was 10.1% (Q1 3.5% - Q3 16.5%). These values compare favorably against other assessments of technical repeatability of proteomics data, which often set a CV of 20% as the upper bound of acceptability. This article is protected by copyright. All rights reserved

People with obesity exhibit losses in muscle proteostasis that are partly improved by exercise training

This pilot experiment examines if a loss in muscle proteostasis occurs in people with obesity and whether endurance exercise positively influences either the abundance profile or turnover rate of proteins in this population. Men with (n = 3) or without (n = 4) obesity were recruited and underwent a 14-d measurement protocol of daily deuterium oxide (D2 O) consumption and serial biopsies of vastus lateralis muscle. Men with obesity then completed 10-weeks of high-intensity interval training (HIIT), encompassing 3 sessions per week of cycle ergometer exercise with 1 min intervals at 100% maximum aerobic power interspersed by 1 min recovery periods. The number of intervals per session progressed from 4 to 8, and during weeks 8-10 the 14-d measurement protocol was repeated. Proteomic analysis detected 352 differences (p < 0.05, false discovery rate < 5%) in protein abundance and 19 (p < 0.05) differences in protein turnover, including components of the ubiquitin-proteasome system. HIIT altered the abundance of 53 proteins and increased the turnover rate of 22 proteins (p < 0.05) and tended to benefit proteostasis by increasing muscle protein turnover rates. Obesity and insulin resistance are associated with compromised muscle proteostasis, which may be partially restored by endurance exercise

Sussing merger trees: stability and convergence

Merger trees are routinely used to follow the growth and merging history of dark matter haloes and subhaloes in simulations of cosmic structure formation. Srisawat et al. compared a wide range of merger-tree-building codes. Here we test the influence of output strategies and mass resolution on tree-building. We find that, somewhat surprisingly, building the tree from more snapshots does not generally produce more complete trees; instead, it tends to shorten them. Significant improvements are seen for patching schemes that attempt to bridge over occasional dropouts in the underlying halo catalogues or schemes that combine the halo-finding and tree-building steps seamlessly. The adopted output strategy does not affect the average number of branches (bushiness) of the resultant merger trees. However, mass resolution has an influence on both main branch length and the bushiness. As the resolution increases, a halo with the same mass can be traced back further in time and will encounter more small progenitors during its evolutionary history. Given these results, we recommend that, for simulations intended as precursors for galaxy formation models where of the order of 100 or more snapshots are analysed, the tree-building routine should be integrated with the halo finder, or at the very least be able to patch over multiple adjacent snapshots

Sussing merger trees: the impact of halo merger trees on galaxy properties in a semi-analytic model

A halo merger tree forms the essential backbone of a semi-analytic model for galaxy formation and evolution. Recent studies have pointed out that extracting merger trees from numerical simulations of structure formation is non-trivial; different tree building algorithms can give differing merger histories. These differences should be carefully understood before merger trees are used as input for models of galaxy formation. We investigate the impact of different halo merger trees on a semi-analytic model. We find that the z = 0 galaxy properties in our model show differences between trees when using a common parameter set. The star formation history of the universe and the properties of satellite galaxies can show marked differences between trees with different construction methods. Independently calibrating the semi-analytic model for each tree can reduce the discrepancies between the z = 0 global galaxy properties, at the cost of increasing the differences in the evolutionary histories of galaxies. Furthermore, the underlying physics implied can vary, resulting in key quantities such as the supernova feedback efficiency differing by factors of 2. Such a change alters the regimes where star formation is primarily suppressed by supernovae. Therefore, halo merger trees extracted from a common halo catalogue using different, but reliable, algorithms can result in a difference in the semi-analytic model. Given the uncertainties in galaxy formation physics, however, these differences may not necessarily be viewed as significant