Construction of a polycystic ovarian syndrome (PCOS) pathway based on the interactions of PCOS-related proteins retrieved from bibliomic data

Polycystic ovary syndrome (PCOS) is a complex but frequently occurring endocrine abnormality. PCOS has become one of the leading causes of oligo-ovulatory infertility among premenopausal women. The definition of PCOS remains unclear because of the heterogeneity of this abnormality, but it is associated with insulin resistance, hyperandrogenism, obesity and dyslipidaemia. The main purpose of this study was to identify possible candidate genes involved in PCOS. Several genomic approaches, including linkage analysis and microarray analysis, have been used to look for candidate PCOS genes. To obtain a clearer view of the mechanism of PCOS, we have compiled data from microarray analyses. An extensive literature search identified seven published microarray analyses that utilized PCOS samples. These were published between the year of 2003 and 2007 and included analyses of ovary tissues as well as whole ovaries and theca cells. Although somewhat different methods were used, all the studies employed cDNA microarrays to compare the gene expression patterns of PCOS patients with those of healthy controls. These analyses identified more than a thousand genes whose expression was altered in PCOS patients. Most of the genes were found to be involved in gene and protein expression, cell signaling and metabolism. We have classified all of the 1081 identified genes as coding for either known or unknown proteins. Cytoscape 2.6.1 was used to build a network of protein and then to analyze it. This protein network consists of 504 protein nodes and 1408 interactions among those proteins. One hypothetical protein in the PCOS network was postulated to be involved in the cell cycle. BiNGO was used to identify the three main ontologies in the protein network: molecular functions, biological processes and cellular components. This gene ontology analysis identified a number of ontologies and genes likely to be involved in the complex mechanism of PCOS. These include the insulin receptor signaling pathway, steroid biosynthesis, and the regulation of gonadotropin secretion among others.     

Tip60 might be a candidate for the acetylation of hepatic carbonic anhydrase I and III in mice

Molecular Biology Reports - Carbonic anhydrases (CAs) play a significant role in maintaining pH balance by catalyzing the conversion of carbon dioxide to bicarbonate. The regulation of pH is...     

Pentacyclic Triterpenoids Inhibit IKKβ Mediated Activation of NF-κB Pathway: In Silico and In Vitro Evidences

Pentacyclic Triterpenoids (PTs) and their analogues as well as derivatives are emerging as important drug leads for various diseases. They act through a variety of mechanisms and a majority of them inhibit the nuclear factor kappa-beta (NF-κB) signaling pathway. In this study, we examined the effects of the naturally occurring PTs on IκB kinase-β (IKKβ), which has great scientific relevance in the NF-κB signaling pathway. On virtual screening, 109 PTs were screened through the PASS (prediction of activity spectra of substances) software for prediction of NF-κB inhibitory activity followed by docking on the NEMO/IKKβ association complex (PDB: 3BRV) and testing for compliance with the softened Lipinski’s Rule of Five using Schrodinger (LLC, New York, USA). Out of the projected 45 druggable PTs, Corosolic Acid (CA), Asiatic Acid (AA) and Ursolic Acid (UA) were assayed for IKKβ kinase activity in the cell free medium. The UA exhibited a potent IKKβ inhibitory effect on the hotspot kinase assay with IC50 of 69 μM. Whereas, CA at 50 μM concentration markedly reduced the NF-κB luciferase activity and phospho-IKKβ protein expressions. The PTs tested, attenuated the expression of the NF-κB cascade proteins in the LPS-stimulated RAW 264.7 cells, prevented the phosphorylation of the IKKα/β and blocked the activation of the Interferon-gamma (IFN-γ). The results suggest that the IKKβ inhibition is the major mechanism of the PTs-induced NF-κB inhibition. PASS predictions along with in-silico docking against the NEMO/IKKβ can be successfully applied in the selection of the prospective NF-κB inhibitory downregulators of IKKβ phosphorylation.     

Medical Students’ Opinions About the Commercialization of Healthcare: A Cross-Sectional Survey

There are serious concerns about the commercialization of healthcare and adoption of the business approach in medicine. As market dynamics endanger established professional values, healthcare workers face more complicated ethical dilemmas in their daily practice. The aim of this study was to investigate the willingness of medical students to accept the assertions of commercialized healthcare and the factors affecting their level of agreement, factors which could influence their moral stance when market demands conflict with professional values. A cross-sectional study was conducted in three medical schools in Turkey. The study population consisted of first-, third-, and sixth-year students, and 1,781 students participated in total. Students were asked to state if they agreed with the assertions of commercialized healthcare. Of all students, 87.2 per cent agreed with at least one of the assertions, and one-fifth (20.8 per cent) of them agreed with more than half of the assertions. First-year students significantly agreed more with some assertions than third- and sixth-year students. Being female, having mid-level family income, choosing medicine due to idealistic reasons, and being in the third or sixth years of medical study increased the probability of disagreement. Also, studying in a medical school that included integrated lectures on health policies, rights related to health, and health inequities, along with early field visits, increased the probability of disagreement. This study suggests that agreement with the assertions of commercialized healthcare might be prevalent among students at a considerable level. We argue that this level of agreement is not compatible with best practice in professional ethics and indicates the need for an educational intervention in order to have physicians who give priority to patients’ best interests in the face of market demands.     

Contribution of inter-site variations in architecture to trabecular bone apparent yield strains

Apparent yield strains for trabecular bone are uniform within an anatomic site but can vary across site. The overall goal of this study was to characterize the contribution of inter-site differences in trabecular architecture to corresponding variations in apparent yield strains. High-resolution, small deformation finite element analyses were used to compute apparent compressive and tensile yield strains in four sites (n = 7 specimens per site): human proximal tibia, greater trochanter, femoral neck, and bovine proximal tibia. These sites display differences in compressive, but not tensile, apparent yield strains. Inter-site differences in architecture were captured implicitly in the model geometries, and these differences were isolated as the sole source of variability across sites by using identical tissue properties in all models. Thus, the effects inter-site variations in architecture on yield strain could be assessed by comparing computed yield strains across site. No inter-site differences in computed yield strains were found for either loading mode (p > 0.19), indicating that, within the context of small deformations, inter-site variations in architecture do not affect apparent yield strains. However, results of ancillary analyses designed to test the validity of the small deformation assumption strongly suggested that the propensity to undergo large deformations constitutes an important contribution of architecture to inter-site variations in apparent compressive yield strains. Large deformations substantially reduced apparent compressive, but not tensile, yield strains. These findings indicate the importance of incorporating large deformation capabilities in computational analyses of trabecular bone. This may be critical when investigating the biomechanical consequences of trabecular thinning and loss.     

Levels of Selected Trace Elements, Phytohormones, and Sugars in Pseudomonas-Infected Lycopersicum esculantum Mill Plants

The present study investigated the levels of trace elements (Zn, Cu, Fe, Pb, and Cd), major elements (Ca and K), phytohormones (trans-Zeatin [t-Z] and gibberellic acid [GA]), and sugars (sucrose and glucose) following inoculation with Pseudomonas syringae pv. tomato strain. The results of the trace elements analysis showed that Fe (in the first, fourth, eighth, and tenth study days), Cd (in the fourth, eighth, and tenth study days), Cu (in the fourth and eighth study days), and Zn (in the eighth and tenth study days) increased in bacterium-infected tomato plants, compared to healthy plants. The levels of Pb, Ca, and K did not meaningfully determine a change after inoculation with pathogen. In this vein, the increase accumulation rates of Cu, Zn, and Fe in the injured plants can be an important indicator for the plant defense processes towards pathogen attack. Furthermore, in the first, fourth, eighth, and tenth study days, the glucose and sucrose contents crucially decreased in bacterium-infected plants compared to the control groups. The lowest level of sucrose in bacterium-infected plants was observed on the first day. The findings displayed that, when endogenous t-Z levels did not change after inoculation with virulent bacterium strain, there was a reduction in the first, fourth, eighth, and tenth days in the level of GA when compared with the control group levels. Therefore, there may be a link between lower GA level and enhancement in the expression of defense-related genes. The results of this study showed that there are complex relationships among levels of sugar, trace element, and endogenous phytohormone in the regulation of defense mechanisms against bacterial pathogen attacks.     

A global metagenomic map of urban microbiomes and antimicrobial resistance

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The impact of water quality on the Asian clam,Corbicula fluminea,distribution in Pergau Lake,Kelantan, Malaysia

In the present study described the impact of water quality on the Asian clam, Corbicula fluminea, distribution in man – made Pergau Lake was carried out. Recently, Pergau Lake was gazette as state park and any activities related to fishery and agricultural were not allowed in the park. Subsequently, the nearby lake community was affected as many of them earn a living by carrying fisheries activity in the lake especially harvesting Asian clam. 10 sampling sites were selected in the lake to monitor water quality and Asian clam distribution. Water parameters data were also subjected to cluster analysis by using Ward’s method with squared Euclidean distances as a measure of similarity and a dendrogram was successfully generated. The water quality of the lake is under good condition and suitable to carry fishery activities by referred to Malaysia National Water Quality Standards (NWQS). The dendrogram revealed that the sampling sites can be divided into 2 clusters where Location 1 alone in its own cluster. Another cluster possesses 2 sub-clusters where Location 2 and 3 shared similar sub cluster. Another sub-cluster has two groups namely Location 5, 6 and 8 in one group whereas Location 4, 7, 9 and 10 shared similar group. The findings of the present study showed most of sampled Asian clam in Pergau Lake was semi mature indicating highly exploitation of Asian clam in the Lake. Furthermore, there were no correlation was detected between the population of Asian clam and water quality of the lake. Hence, we suggest that seasonal harvesting Asian clam should be implemented in order to conserve the population of Asian clam in the lake at the mean time the community to continue earn a living through carrying fishery activities in the lake.