NDRG2 promotes myoblast proliferation and caspase 3/7 activities during differentiation, and attenuates hydrogen peroxide - but not palmitate-induced toxicity

The function of the stress-responsive N-myc downstream-regulated gene 2 (NDRG2) in the control of myoblast growth, and the amino acids contributing to its function, are not well characterized. Here, we investigated the effect of increased NDRG2 levels on the proliferation, differentiation and apoptosis in skeletal muscle cells under basal and stress conditions. NDRG2 overexpression increased C2C12 myoblast proliferation and the expression of positive cell cycle regulators, cdk2, cyclin B and cyclin D, and phosphorylation of Rb, while the serine/threonine-deficient NDRG2, 3A-NDRG2, had less effect. The onset of differentiation was enhanced by NDRG2 as determined through the myogenic regulatory factor expression profiles and myocyte fusion index. However, the overall level of differentiation in myotubes was not different. While NDRG2 up-regulated caspase 3/7 activities during differentiation, no increase in apoptosis was measured by TUNEL assay or through cleavage of caspase 3 and PARP proteins. During H2O2 treatment to induce oxidative stress, NDRG2 helped protect against the loss of proliferation and ER stress as measured by GRP78 expression with 3A-NDRG2 displaying less protection. NDRG2 also attenuated apoptosis by reducing cleavage of PARP and caspase 3 and expression of pro-apoptotic Bax while enhancing the pro-survival Bcl-2 and Bcl-xL levels. In contrast, Mcl-1 was not altered, and NDRG2 did not protect against palmitate-induced lipotoxicity. Our findings show that NDRG2 overexpression increases myoblast proliferation and caspase 3/7 activities without increasing overall differentiation. Furthermore, NDRG2 attenuates H2O2-induced oxidative stress and specific serine and threonine amino acid residues appear to contribute to its function in muscle cells

Microwave Based Weed Control and Soil Treatment

Herbicide resistance has become an important constraint on modern agricultural practices. An alarming increase in weed biotypes that are resistant to herbicides has also been reported. Opportunity exists for a novel weed management technology, which is also compatible with no-till agricultural practices. Microwave heating can kill both emerged weed plants and weed seeds in the soil. When the intensity of the microwave fields is moderate, plants, which have already emerged, are susceptible to microwave treatment. If the microwave field is intense enough, very rapid volumetric heating and some thermal runaway in the plant structures cause micro-steam explosions in the plant cells, which rupture the plant structures, leading to death. Soil treatment requires significantly more energy however, there are secondary benefits for crops growing in microwave treated soil. These include: significant reduction of the dormant weed seed bank significant reduction of nematode populations significant reduction of fungal populations better availability of indigenous nitrogen for the plants more rapid humification and significant increases in crop growth and yield. Microwave weed management and soil treatment is not restricted by weather conditions therefore, the technology may offer some timeliness and environmental benefits, which are yet to be quantified in a cropping system

Microwave Based Weed Control and Soil Treatment

The Yearbook mirrors the annual activities of staff and visiting fellows of the Maimonides Centre and reports on symposia, workshops, and lectures taking place at the Centre. Although aimed at a wider audience, the yearbook also contains academic articles and book reviews on scepticism in Judaism and scepticism in general. Staff, visiting fellows, and other international scholars are invited to contribut

Microwave Based Weed Control and Soil Treatment

The Yearbook mirrors the annual activities of staff and visiting fellows of the Maimonides Centre and reports on symposia, workshops, and lectures taking place at the Centre. Although aimed at a wider audience, the yearbook also contains academic articles and book reviews on scepticism in Judaism and scepticism in general. Staff, visiting fellows, and other international scholars are invited to contribut

Desmoglein 3: a help or a hindrance in cancer progression?

Desmoglein 3 is one of seven desmosomal cadherins that mediate cell-cell adhesion in desmosomes. Desmosomes are the intercellular junctional complexes that anchor the intermediate filaments of adjacent cells and confer strong cell adhesion thus are essential in the maintenance of tissue architecture and structural integrity. Like adherens junctions, desmosomes function as tumour suppressors and are down regulated in the process of epithelial-mesenchymal transition and in tumour cell invasion and metastasis. However, recently several studies have shown that various desmosomal components, including desmoglein 3, are up-regulated in cancer with increased levels of expression correlating with the clinical stage of malignancy, implicating their potentiality to serve as a diagnostic and prognostic marker. Furthermore, in vitro studies have demonstrated that overexpression of desmoglein 3 in cancer cell lines activates several signal pathways that have an impact on cell morphology, adhesion and locomotion. These additional signalling roles of desmoglein 3 may not be associated to its adhesive function in desmosomes but rather function outside of the junctions, acting as a key regulator in the control of actin based cellular processes. This review will discuss recent advances which support the role of desmoglein 3 in cancer progression.The authors would like to thank Medical Research Council, British Skin Foundation and Institute of Dentistry, School of Medicine and Dentistry, Queen Mary University of London for support to the work in the authors’ lab

Nutraceutical properties of chestnut flours: beneficial effects on skeletal muscle atrophy

Plants contain a wide range of non-nutritive phytochemicals, many of which have protective or preventive properties for human diseases. The aim of the present work has been to investigate the nutraceutical properties of sweet chestnut flour extracts obtained from fruits collected from 7 geographic areas of Tuscany (Italy), and their ability in modulating skeletal muscle atrophy. We found that the cultivars from different geographic areas are characterized by the composition and quantity of various nutrients and specific bioactive components, such as tocopherols, polyphenols and sphingolipids. The nutraceutical properties of chestnut sweet flours have been evaluated in C2C12 myotubes induced to atrophy by serum deprivation or dexamethasone. We found that the pretreatment with both total extracts of tocopherols and sphingolipids is able to counterbalance cell atrophy, reducing the decrease in myotube size and myonuclei number, and attenuating protein degradation and the increase in expression of MAFbx/atrogin-1 (a muscle-specific atrophy marker). By contrast, polyphenol extracts were not able to prevent atrophy. Since we also found that γ-tocopherol is the major form of tocopherol in sweet flour and its content differs depending on the procedure of sweet flour preparation, the mechanisms by which γ-tocopherol as well as sphingolipids affect skeletal muscle cell atrophy have been also investigated. This is the first evidence that chestnut sweet flour is a natural source of specific bioactive components with a relevant role in the prevention of cell degeneration and maintenance of skeletal muscle mass, opening important implications in designing appropriate nutritional therapeutic approaches to skeletal muscle atrophy

Acute molecular responses to concurrent resistance and high-intensity interval exercise in untrained skeletal muscle

Concurrent training involving resistance and endurance exercise may augment the benefits of single-mode training for the purpose of improving health. However, muscle adaptations, associated with resistance exercise, may be blunted by a subsequent bout of endurance exercise, via molecular interference. High-intensity interval training (HIIT), generating similar adaptations to endurance exercise, may offer an alternative exercise mode to traditional endurance exercise. This study examined the influence of an acute HIIT session on the molecular responses following resistance exercise in untrained skeletal muscle. Ten male participants performed resistance exercise (4 9 8 leg extensions, 70% 1RM, (RE)) or RE followed by HIIT (10 x 1 min at 90% HRmax, (RE+HIIT)). Muscle biopsies were collected from the vastus lateralis before, 2 and 6 h post-RE to determine intramuscular protein phosphorylation and mRNA responses. Phosphorylation of Akt (Ser473) decreased at 6 h in both trials (P < 0.05). Phosphorylation of mTOR (Ser2448) was higher in RE+HIIT (P < 0.05). All PGC-1a mRNA variants increased at 2 h in RE+HIIT with PGC-1a and PGC-1a-ex1b remaining elevated at 6 h, whereas RE-induced increases at 2 and 6 h for PGC-1a-ex1b only (P < 0.05). Myostatin expression decreased at 2 and 6 h in both trials (P < 0.05). MuRF-1 was elevated in RE+HIIT versus RE at 2 and 6 h (P < 0.05). Atrogin-1 was lower at 2 h, with FOXO3A downregulated at 6 h (P < 0.05). These data do not support the existence of an acute interference effect on protein signaling and mRNA expression, and suggest that HIIT may be an alternative to endurance exercise when performed after resistance exercise in the same training session to optimize adaptations

G-Protein Coupled Receptor Signaling Architecture of Mammalian Immune Cells

A series of recent studies on large-scale networks of signaling and metabolic systems revealed that a certain network structure often called “bow-tie network” are observed. In signaling systems, bow-tie network takes a form with diverse and redundant inputs and outputs connected via a small numbers of core molecules. While arguments have been made that such network architecture enhances robustness and evolvability of biological systems, its functional role at a cellular level remains obscure. A hypothesis was proposed that such a network function as a stimuli-reaction classifier where dynamics of core molecules dictate downstream transcriptional activities, hence physiological responses against stimuli. In this study, we examined whether such hypothesis can be verified using experimental data from Alliance for Cellular Signaling (AfCS) that comprehensively measured GPCR related ligands response for B-cell and macrophage. In a GPCR signaling system, cAMP and Ca2+ act as core molecules. Stimuli-response for 32 ligands to B-Cells and 23 ligands to macrophages has been measured. We found that ligands with correlated changes of cAMP and Ca2+ tend to cluster closely together within the hyperspaces of both cell types and they induced genes involved in the same cellular processes. It was found that ligands inducing cAMP synthesis activate genes involved in cell growth and proliferation; cAMP and Ca2+ molecules that increased together form a feedback loop and induce immune cells to migrate and adhere together. In contrast, ligands without a core molecules response are scattered throughout the hyperspace and do not share clusters. G-protein coupling receptors together with immune response specific receptors were found in cAMP and Ca2+ activated clusters. Analyses have been done on the original software applicable for discovering ‘bow-tie’ network architectures within the complex network of intracellular signaling where ab initio clustering has been implemented as well. Groups of potential transcription factors for each specific group of genes were found to be partly conserved across B-Cell and macrophage. A series of findings support the hypothesis

PGC-1 alpha and PGC-1 beta increase protein synthesis via ERR alpha in C2C12 myotubes

The transcriptional coactivators peroxisome proliferator-activated receptor-&gamma; coactivator-1&alpha; (PGC-1&alpha;) and PGC-1&beta; are positive regulators of skeletal muscle mass and energy metabolism; however, whether they influence muscle growth and metabolic adaptations via increased protein synthesis is not clear. This study revealed PGC-1&alpha; or PGC-1&beta; overexpression in C2C12 myotubes increased protein synthesis and myotube diameter under basal conditions and attenuated the loss in protein synthesis following the treatment with the catabolic agent, dexamethasone. To investigate whether PGC-1&alpha; or PGC-1&beta; signal through the Akt/mTOR pathway to increase protein synthesis, treatment with the PI3K and mTOR inhibitors, LY294002 and rapamycin, respectively, was undertaken but found unable to block PGC-1&alpha; or PGC-1&beta;&rsquo;s promotion of protein synthesis. Furthermore, PGC-1&alpha; and PGC-1&beta; decreased phosphorylation of Akt and the Akt/mTOR substrate, p70S6K. In contrast to Akt/mTOR inhibition, the suppression of ERR&alpha;, a major effector of PGC-1&alpha; and PGC-1&beta; activity, attenuated the increase in protein synthesis and myotube diameter in the presence of PGC-1&alpha; or PGC-1&beta; overexpression. To characterize further the biological processes occurring, gene set enrichment analysis of genes commonly regulated by both PGC-1&alpha; and PGC-1&beta; was performed following a microarray screen. Genes were found enriched in metabolic and mitochondrial oxidative processes, in addition to protein translation and muscle development categories. This suggests concurrent responses involving both increased metabolism and myotube protein synthesis. Finally, based on their known function or unbiased identification through statistical selection, two sets of genes were investigated in a human exercise model of stimulated protein synthesis to characterize further the genes influenced by PGC-1&alpha; and PGC-1&beta; during physiological adaptive changes in skeletal muscle