Myostatin induces mitochondrial metabolic alteration and typical apoptosis in cancer cells

Myostatin, a member of the transforming growth factor-β superfamily, regulates the glucose metabolism of muscle cells, while dysregulated myostatin activity is associated with a number of metabolic disorders, including muscle cachexia, obesity and type II diabetes. We observed that myostatin induced significant mitochondrial metabolic alterations and prolonged exposure of myostatin induced mitochondria-dependent apoptosis in cancer cells addicted to glycolysis. To address the underlying mechanism, we found that the protein levels of Hexokinase II (HKII) and voltage-dependent anion channel 1 (VDAC1), two key regulators of glucose metabolisms as well as metabolic stress-induced apoptosis, were negatively correlated. In particular, VDAC1 was dramatically upregulated in cells that are sensitive to myostatin treatment whereas HKII was downregulated and dissociated from mitochondria. Myostatin promoted the translocation of Bax from cytosol to mitochondria, and knockdown of VDAC1 inhibited myostatin-induced Bax translocation and apoptosis. These apoptotic changes can be partially rescued by repletion of ATP, or by ectopic expression of HKII, suggesting that perturbation of mitochondrial metabolism is causally linked with subsequent apoptosis. Our findings reveal novel function of myostatin in regulating mitochondrial metabolism and apoptosis in cancer cells.     

RhoGAPs Attenuate Cell Proliferation by Direct Interaction with p53 Tetramerization Domain

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Numerical Modelling of Electroosmotic Driven Flow in Nanoporous Media by Lattice Boltzmann Method

The lattice Boltzmann method was employed to simulate electroosmotic driven flow and Debye layer screening in conducting electrolyte around a porous structure with average size of 40 nm. The charge screening around the nanopores was investigated by solving the vector-superpositioned potential equilibrium distribution function and adding electro-kinetic force term to the evolution equation. In this intermediate case of moderate Debye length, the electrophoresis problem becomes complicated. The motion of the particles distorts the screening cloud, which becomes asymmetric, resulting in very complex interactions between the electrolyte, the screening cloud and the particle; but the Electroosmotic Flow (EOF) behaviour was still considered based on the Helmoholtz-Smoluchowski model with adaptation to fit nanoporous flow in the porous structure. In the present approach, the flow in the nanopores is directly modelled; the detailed flow information can be obtained by simplifying the repeated macrostructure. Due to the symmetry of the domain, the size of computational domain can be largely reduced by less repeated spherical nanoparticles. Each pore of the medium contains several lattice nodes on the simplified curved edges and potential gradients are produced by adjusting the zeta potential value. The velocity results for pressure-driven and EOF flows agree well with the analytical solutions and recent experimental results. In particular, the interface between solid particles and fluids, the influences of porosity, solid particle diameter, yield stress and electric parameters in EOF were investigated. The anti-adhesion effect of electroosmotic pumping effect was evaluated, and the pulsed DC was applied in order to enhance the performance of the electroosmotic pumping. The results demonstrate that the present lattice Boltzmann model is capable of modelling flow through nanoporous media at certain restrictions while some results deviate from the predictions based on the macroscopic theories.     

Fusion Tensor Subspace Transformation Framework

Tensor subspace transformation, a commonly used subspace transformation technique, has gained more and more popularity over the past few years because many objects in the real world can be naturally represented as multidimensional arrays, i.e. tensors. For example, a RGB facial image can be represented as a three-dimensional array (or 3rd-order tensor). The first two dimensionalities (or modes) represent the facial spatial information and the third dimensionality (or mode) represents the color space information. Each mode of the tensor may express a different semantic meaning. Thus different transformation strategies should be applied to different modes of the tensor according to their semantic meanings to obtain the best performance. To the best of our knowledge, there are no existing tensor subspace transformation algorithm which implements different transformation strategies on different modes of a tensor accordingly. In this paper, we propose a fusion tensor subspace transformation framework, a novel idea where different transformation strategies are implemented on separate modes of a tensor. Under the framework, we propose the Fusion Tensor Color Space (FTCS) model for face recognition.     

Decreased Serum Hepcidin Concentration Correlates with Brain Iron Deposition in Patients with HBV-Related Cirrhosis

Purpose

Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level.

Methods

Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters.

Results

Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients.

Conclusions

Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential.     

Methionine Synthase A2756G Polymorphism and Risk of Colorectal Adenoma and Cancer: Evidence Based on 27 Studies

Methionine synthase (MTR), which plays a central role in maintaining adequate intracellular folate, methionine and normal homocysteine concentrations, was thought to be involved in the development of colorectal cancer (CRC) and colorectal adenoma (CRA) by affecting DNA methylation. However, studies on the association between MTR A2756G polymorphism and CRC/CRA remain conflicting. We conducted a meta-analysis of 27 studies, including 13465 cases and 20430 controls for CRC, and 4844 cases and 11743 controls for CRA. Potential sources of heterogeneity and publication bias were also systematically explored. Overall, the summary odds ratio of G variant for CRC was 1.03 (95% CI: 0.96–1.09) and 1.05 (95% CI: 0.99–1.12) for CRA. No significant results were observed in heterozygous and homozygous when compared with wild genotype for these polymorphisms. In the stratified analyses according to ethnicity, source of controls, sample size, sex, and tumor site, no evidence of any gene-disease association was obtained. Results from the meta-analysis of four studies on MTR stratified according to smoking and alcohol drinking status showed an increased CRC risk in heavy smokers (OR = 2.06, 95% CI: 1.32–3.20) and heavy drinkers (OR = 2.00, 95% CI: 1.28–3.09) for G allele carriers. This meta-analysis suggests that the MTR A2756G polymorphism is not associated with CRC/CRA susceptibility and that gene-environment interaction may exist.     

Diet Shift and Its Impact on Foraging Behavior of Siberian Crane (Grus Leucogeranus) in Poyang Lake

The study of habitat selection and diet has a long history in ecology. This is often used to assess the functional roles of wetland in biodiversity conservation. Shifting habitat and diet may be one of the survival strategies during extremely adverse conditions. Therefore, sudden changes in habitat selection may indicate the deterioration of the habitat quality, and management interventions are necessary. Siberian crane (Grus leucogeranus) became critically endangered due to loss of habitat, and is currently a global conservation focus. Every winter, more than 95% of the species'' global population congregates at Poyang Lake, and feeds on tubers of Vallisneria spiralis in shallow water and mudflat habitat. In this study, we reported the first sighting of large numbers of Siberian cranes foraging at wet meadows, where they fed on a different plant, Potentilla limprichtii due to extreme scarcity of their preferred tuber. To understand how well the cranes adapted to such unusual habitat, field surveys to assess the distribution of cranes across different habitats, and food availability in each habitat were carried out in the winter of 2011. Field observations on crane behaviors at different habitats were also conducted. Results show that cranes displayed significantly different behavior patterns when using the wet meadow, compared to the crane''s optimal habitat - shallow water and mudflat. Both juveniles and adults spent significantly less time foraging, and more time alerting in meadows than in shallow waters and mudflats. These results indicated that the meadow might be a suboptimal wintering ground for Siberian crane, which helped the cranes survive from extreme unfavorable conditions. To some degree, this finding alleviates the general concern over the fluctuating of its food resources which was caused by hydrological disturbances. However, more studies are needed to assess the consequences of such diet and habitat shift for crane survival.