Global asymptotic stability of complex-valued neural networks with additive time-varying delays

In this paper, we extensively study the global asymptotic stability problem of complex-valued neural networks with leakage delay and additive time-varying delays. By constructing a suitable Lyapunov–Krasovskii functional and applying newly developed complex valued integral inequalities, sufficient conditions for the global asymptotic stability of proposed neural networks are established in the form of complex-valued linear matrix inequalities. This linear matrix inequalities are efficiently solved by using standard available numerical packages. Finally, three numerical examples are given to demonstrate the effectiveness of the theoretical results.     

Environmental Response and Genomic Regions Correlated with Rice Root Growth and Yield under Drought in the OryzaSNP Panel across Multiple Study Systems

The rapid progress in rice genotyping must be matched by advances in phenotyping. A better understanding of genetic variation in rice for drought response, root traits, and practical methods for studying them are needed. In this study, the OryzaSNP set (20 diverse genotypes that have been genotyped for SNP markers) was phenotyped in a range of field and container studies to study the diversity of rice root growth and response to drought. Of the root traits measured across more than 20 root experiments, root dry weight showed the most stable genotypic performance across studies. The environment (E) component had the strongest effect on yield and root traits. We identified genomic regions correlated with root dry weight, percent deep roots, maximum root depth, and grain yield based on a correlation analysis with the phenotypes and aus, indica, or japonica introgression regions using the SNP data. Two genomic regions were identified as hot spots in which root traits and grain yield were co-located; on chromosome 1 (39.7–40.7 Mb) and on chromosome 8 (20.3–21.9 Mb). Across experiments, the soil type/ growth medium showed more correlations with plant growth than the container dimensions. Although the correlations among studies and genetic co-location of root traits from a range of study systems points to their potential utility to represent responses in field studies, the best correlations were observed when the two setups had some similar properties. Due to the co-location of the identified genomic regions (from introgression block analysis) with QTL for a number of previously reported root and drought traits, these regions are good candidates for detailed characterization to contribute to understanding rice improvement for response to drought. This study also highlights the utility of characterizing a small set of 20 genotypes for root growth, drought response, and related genomic regions.     

Examining and elucidation of human weight cycle model adopting e-cell simulation system

Cellular rhythms regulate various physiological functions in circadian oscillatory mechanisms. Weight cycling or ‘yo-yo’ dieting is an evitable process in human, because of subsequent loss and regain of body weight due to irregular diet. Human weight cycle (HWC) is the major factor for causing global epidemic diseases in human beings. Understanding the HWC process would provide potent additional knowledge to prevent obesity. However till date, there is no study dealing with examine the HWC model using virtual cell simulation based on system biological approach. Therefore, the present study was designed to develop a computational HWC model, which was simulated using E-cell system v3.0. The developed model has the cyclic feedback reactions of three significant variables (the consecutive cycles of weight loss in continuous food intake (Q) and regain of body weight (P) at highest threshold point of cognitive restraint (R)) which are obtained by mathematical modelling. The dynamic plot results supported that the PQR variables depicted sustained oscillation with reversible modification due to protein diet. By contrast, the virtual model simulation would provide extensive information on HWC, which might provide knowledge to develop HWC linked with obesity pathway. The presents study concludes that optimization of body weight is essential to prevent the obesity based diseases.     

Heat shock protein expression analysis in canine osteosarcoma reveals HSP60 as a potentially relevant therapeutic target

Heat shock proteins (HSP) are highly conserved across eukaryotic and prokaryotic species. These proteins play a role in response to cellular stressors, protecting cells from damage and facilitating recovery. In tumor cells, HSPs can have cytoprotective effects and interfere with apoptotic cascades. This study was performed to assess the prognostic and predictive values of the gene expression of HSP family members in canine osteosarcoma (OS) and their potential for targeted therapy. Gene expressions for HSP were assessed using quantitative PCR (qPCR) on 58 snap-frozen primary canine OS tumors and related to clinic-pathological parameters. A significant increased expression of HSP60 was found in relation to shorter overall survival and an osteoblastic phenotype. Therefore, the function of HSP60 was investigated in more detail. Immunohistochemical analysis revealed heterogeneous staining for HSP60 in tumors. The highest immunoreactivity was found in tumors of short surviving dogs. Next HSP expression was shown in a variety of canine and human OS cell lines by qPCR and Western blot. In two highly metastatic cell lines HSP60 expression was silenced using siRNA resulting in decreased cell proliferation and induction of apoptosis in both cell lines. It is concluded that overexpression of HSP60 is associated with a poor prognosis of OS and should be evaluated as a new target for therapy.     

Lactobacillus fermentum MCC2759 and MCC2760 Alleviate Inflammation and Intestinal Function in High-Fat Diet-Fed and Streptozotocin-Induced Diabetic Rats

Probiotics and Antimicrobial Proteins - The growing incidence of type 2 diabetes and obesity has become a worldwide crisis with increased socio-economic burden. Changes in lifestyle and food habits...     

Apoptosis inducing effect of plumbagin on colonic cancer cells depends on expression of COX-2

Plumbagin, a quinonoid found in the plants of the Plumbaginaceae, possesses medicinal properties. In this study we investigated the anti-proliferative and apoptotic activity of plumbagin by using two human colonic cancer cell lines, HT29 and HCT15. IC50 of Plumbagin for HCT15 and HT29 cells (22.5 μM and 62.5 μM, respectively) were significantly different. To study the response of cancer cells during treatment strategies, cells were treated with two different concentrations, 15 μM, 30 μM for HCT15 and 50 μM, 75 μM for HT29 cells. Though activation of NFκB, Caspases-3, elevated levels of TNF-α, cytosolic Cytochrome C were seen in both HCT15 cells HT29 treated with plumbagin, aberrant apoptosis with decreased level of pEGFR, pAkt, pGsk-3β, PCNA and Cyclin D1was observed only in 15 μM and 30 μM plumbagin treated HCT15 and 75 μM plumbagin treated HT29 cells. This suggests that plumbagin induces apoptosis in both HCT15 cells and HT29 treated, whereas, proliferation was inhibited only in 15 μM and 30 μM plumbagin treated HCT15 and 75 μM plumbagin treated HT29 cells, but not in 50 μM plumbagin treated HT29 cells. Expression of COX-2 was decreased in 75 μM plumbagin treated HT29 cells when compared to 50 μM plumbagin treated HT29 cells, whereas HCT15 cells lack COX. Hence the observed resistance to induction of apoptosis in 50 μM plumbagin treated HT29 cells are attributed to the expression of COX-2. In conclusion, plumbagin induces apoptosis in colonic cancer cells through TNF-α mediated pathway depending on expression of COX-2 expression.     

Down-regulation of Tripartite-motif containing 22 expression in breast cancer is associated with a lack of p53-mediated induction

Tripartite-motif containing 22 (TRIM22) is a direct p53 target gene and inhibits the clonogenic growth of leukemic cells. Its expression in Wilms tumors is negatively associated with disease relapse. This study addresses if TRIM22 expression is de-regulated in breast carcinoma. Western blotting analysis of a panel of 10 breast cancer cell lines and 3 non-malignant mammary epithelial cell lines with a well-characterized TRIM22 monoclonal antibody showed that TRIM22 protein is greatly under-expressed in breast cancer cells as compared to non-malignant cell lines. Similarly, TRIM22 protein is significantly down-regulated in breast tumors as compared to matched normal breast tissues. Study of cell lines with methylation inhibitor and bisulfite sequencing indicates that TRIM22 promoter hypermethylation may not be the cause for TRIM22 under-expression in breast cancer. Instead, we found that TRIM22 protein level correlates strongly (R = 0.79) with p53 protein level in normal breast tissue, but this correlation is markedly impaired (R = 0.48) in breast cancer tissue, suggesting that there is some defects in p53 regulation of TRIM22 gene in breast cancer. This notion is supported by cell line studies, which showed that TRIM22 was no longer inducible by p53-activating genotoxic drugs in breast cancer cell lines and in a p53 null cell line H1299 transfected with wild type p53. In conclusion, this study shows that TRIM22 is greatly under-expressed in breast cancer. p53 dysfunction may be one of the mechanisms for TRIM22 down-regulation.     

Molecular dynamics simulation studies on structural and conformational changes in tyrosine-67 nitrated cytochrome c

Protein tyrosine nitration is well-established post-translational modification occurring in a number of diseases, viz. neurodegenerative, cardiovascular diseases, ageing, etc. Tyrosine-67 (Tyr-67) nitration of cytochrome c (cyt c) was observed under oxidative stress affecting its structure and electron transfer properties. Hence, in this study, molecular dynamics (MD) simulations were carried out at room temperature to investigate the structural and conformational changes in the nitrated cyt c's. MD results revealed that the bond between FE (Heme-105) and S (Met-80) considerably weakened, radius of gyration, backbone and Cα root-mean-square deviations decreased and hydrogen bonding increased in the nitrated cyt c's relative to wild type (WT) cyt c. Ramachandran plot analysis revealed that N- and C-terminal helices also affected by nitration at CE2 carbon atom. Furthermore, essential dynamics analysis showed that amplitude of concerted motion decreased in the nitrated cyt c's, perhaps due to the increase in the hydrogen bonding interaction. Taken together, the structural and conformational changes in the active site Tyr-67 nitrated cyt c may have implications in the loss of electron/proton transfer and gain of apoptotic properties.     

Mutational analysis of G-protein coupled receptor--FFA2

As the mitochondrion is vulnerable to oxidative stress, cells have evolved several strategies to maintain mitochondrial integrity, including mitochondrial protein quality control mechanisms and autophagic removal of damaged mitochondria. Involvement of an autophagy adaptor, Sqstm1/p62, in the latter process has been recently described. In the present study, we provide evidence that a portion of p62 directly localizes within the mitochondria and supports stable electron transport by forming heterogeneous protein complexes. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) of mitochondrial proteins co-purified with p62 revealed that p62 interacts with several oxidation-prone proteins, including a few components of the electron transport chain complexes, as well as multiple chaperone molecules and redox regulatory enzymes. Accordingly, p62-deficient mitochondria exhibited compromised electron transport, and the compromised function was partially restored by in vitro delivery of p62. These results suggest that p62 plays an additional role in maintaining mitochondrial integrity at the vicinity of target machineries through its function in relation to protein quality control.