Crosstalk between transcription factors and microRNAs in human protein interaction network

<p>Abstract</p> <p>Background</p> <p>Gene regulatory networks control the global gene expression and the dynamics of protein output in living cells. In multicellular organisms, transcription factors and microRNAs are the major families of gene regulators. Recent studies have suggested that these two kinds of regulators share similar regulatory logics and participate in cooperative activities in the gene regulatory network; however, their combinational regulatory effects and preferences on the protein interaction network remain unclear.</p> <p>Methods</p> <p>In this study, we constructed a global human gene regulatory network comprising both transcriptional and post-transcriptional regulatory relationships, and integrated the protein interactome into this network. We then screened the integrated network for four types of regulatory motifs: single-regulation, co-regulation, crosstalk, and independent, and investigated their topological properties in the protein interaction network.</p> <p>Results</p> <p>Among the four types of network motifs, the crosstalk was found to have the most enriched protein-protein interactions in their downstream regulatory targets. The topological properties of these motifs also revealed that they target crucial proteins in the protein interaction network and may serve important roles of biological functions.</p> <p>Conclusions</p> <p>Altogether, these results reveal the combinatorial regulatory patterns of transcription factors and microRNAs on the protein interactome, and provide further evidence to suggest the connection between gene regulatory network and protein interaction network.</p

Glycemia and peak incremental indices of six popular fruits in Taiwan: healthy and Type 2 diabetes subjects compared

The aim of this study was to evaluate the glycemic index and peak incremental indices of six popular fruits in Taiwan, comparing healthy subjects (n = 20) and patients with Type 2 diabetes (n = 17). The six kinds of fruits tested were grapes, Asian pears, guavas, golden kiwifruit, lychees and bananas. Glycemic index values were tested according to the standard glycemic index testing protocol. The glycemic index and peak incremental indices were calculated according to published formulas. In Type 2 diabetes subjects, the glycemic index values of grapes, Asian pears, guavas, golden kiwifruit, lychees and bananas were 49.0 ± 4.5, 25.9 ± 2.9, 32.8 ± 5.2, 47.0 ± 6.5, 60.0 ± 8.0 and 41.3 ± 3.5. In healthy subjects, the glycemic index values were 49.1 ± 7.3, 18.0 ± 5.4, 31.1 ± 5.1, 47.3 ± 12.1, 47.9 ± 6.8 and 35.1 ± 5.6. There was no significant difference in glycemic index values between healthy and Type 2 diabetes subjects. There was also no significant difference in PII when comparing healthy subjects and subjects with Type 2 diabetes. In conclusion, glycemic index and peak incremental indices in healthy subjects can be approximately the same for Type 2 diabetes

IS SUICIDE MORTALITY ASSOCIATED WITH METEOROLOGICAL AND SOCIO-ECONOMIC FACTORS? AN ECOLOGICAL STUDY IN A CITY IN TAIWAN WITH A HIGH SUICIDE RATE

Background: Keelung City has the highest suicide rate in Taiwan. This study aimed to determine whether meteorological and socio-economic factors are associated with suicide mortality in Keelung City, by gender and by means of suicide. Subjects and methods: Data on suicides between January 2006 and December 2010 were provided by the Department of Health, Keelung City Government. The suicide victims were categorized into non-violent and violent groups, based on the International Classification of Disease, Ninth Revision. Meteorological data were obtained from the Central Weather Bureau of Taiwan. Socioeconomic data were gathered from the Accounting and Statistics Office, Keelung City Government. Multiple linear regression analysis with backward elimination was performed to determine the model that was most effective in predicting dependent variables. Results: During the 5-year study period, the overall suicide mortality rate was negatively associated with ambient temperature. Male suicide mortality was positively correlated with unemployment, and negatively correlated with ambient temperature, barometric pressure, rainy days, family income and number of holidays. Female suicide mortality and violent suicide mortality were not significantly correlated with any meteorological or socio-economic factors. Non-violent suicide mortality was positively correlated with unemployment, and negatively correlated with ambient temperature, barometric pressure and family income. Conclusions: Suicide is a complex psychopathological phenomenon. Further studies with individual data are warranted to confirm how meteorological and socio-economic conditions influence ones’ suicidal behaviour

GPER-induced signaling is essential for the survival of breast cancer stem cells.

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs

Extensive hepatic infarction in severe preeclampsia as part of the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): Evolution of CT findings and successful treatment with plasma exchange therapy

AbstractObjectiveWe describe the serial computed tomography (CT) findings of extensive hepatic infarction and successful plasma exchange therapy in a severe preeclamptic woman with postpartum HELLP syndrome.Case ReportA 38 year-old woman presented with elevated blood pressure of 140–180/90–120 mmHg and 3+ proteinuria at 28 weeks of gestation. Two days after admission, the patient suddenly complained of severe epigastric pain and headache. Her blood pressure rose sharply to 195/120 mmHg. A 980 g female was delivered by emergency cesarean section. Following delivery, the patient's clinical condition and laboratory values deteriorated, with progressive liver insufficiency (peak AST level = 4246 IU/L, ALT = 3685 IU/L, LDH = 6237 IU/L, platelets = 72,000/mm3). Two consecutive plasma exchanges (PEX) were undertaken on the 3rd and 4th postpartum day. A contrast-enhanced CT of the abdomen performed 8 days postpartum showed geographically wedge-shaped areas of low attenuation, with a mottled appearance in the right hepatic lobe. Shortly thereafter, the patient recovered and all laboratory parameters gradually normalized 3 weeks after delivery. Follow-up CT-scan of the liver 2 months postpartum showed no evidence of infarction, with complete recovery.ConclusionWe recommend that severely ill patients with HELLP syndrome having epigastric pain should undergo CT imaging of the liver. A trial of postpartum PEX therapy should be considered for treatment of the HELLP syndrome complicated with hepatic infarction, which is recalcitrant to conventional medical management, and fails to abate within 72–96 hours of delivery

Simple and Specific Dual-Wavelength Excitable Dye Staining for Glycoprotein Detection in Polyacrylamide Gels and Its Application in Glycoproteomics

In this study, a commercially available fluorescent dye, Lissamine rhodamine B sulfonyl hydrazine (LRSH), was designed to specifically stain the glycoproteins in polyacrylamide gels. Through the periodate/Schiff base mechanism, the fluorescent dye readily attaches to glycoproteins and the fluorescence can be simultaneously observed under either 305 nm or 532 nm excitation therefore, the dye-stained glycoproteins can be detected under a regular UV transilluminator or a more elegant laser-based gel scanner. The specificity and detection limit were examined using a standard protein mixture in polyacrylamide gels in this study. The application of this glycoprotein stain dye was further demonstrated using pregnancy urine samples. The fluorescent spots were further digested in gel and their identities confirmed through LC-MS/MS analysis and database searching. In addition, the N-glycosylation sites of LRSH-labeled uromodulin were readily mapped via in-gel PNGaseF deglycosylation and LC-MS/MS analysis, which indicated that this fluorescent dye labeling does not interfere with enzymatic deglycosylation. Hence, the application of this simple and specific dual-wavelength excitable dye staining in current glycoproteome research is promising

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and risk of arsenic-induced urothelial carcinoma in residents of southwestern Taiwan

<p>Abstract</p> <p>Background</p> <p>Arsenic exposure is an important public health issue worldwide. Dose-response relationship between arsenic exposure and risk of urothelial carcinoma (UC) is consistently observed. Inorganic arsenic is methylated to form the metabolites monomethylarsonic acid and dimethylarsinic acid while ingested. Variations in capacity of xenobiotic detoxification and arsenic methylation might explain individual variation in susceptibility to arsenic-induced cancers.</p> <p>Methods</p> <p>To estimate individual susceptibility to arsenic-induced UC, 764 DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and arsenic methylation enzymes including GSTO1 and GSTO2 were genotyped.</p> <p>Results</p> <p>The GSTT1 null was marginally associated with increased urothelial carcinoma (UC) risk (HR, 1.91, 95% CI, 1.00-3.65), while the association was not observed for other GSTs. Among the subjects with cumulative arsenic exposure (CAE) ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased cancer risk (RR, 3.25, 95% CI, 1.20-8.80). The gene-environment interaction between the GSTT1 and high arsenic exposure with respect to cancer risk was statistically significant (multiplicative model, <it>p </it>= 0.0151) and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22). The genetic effects of GSTO1/GSTO2 were largely confined to high arsenic level (CAE ≥ 20). Diplotype analysis showed that among subjects exposed to high levels of arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2 5'UTR (-183)A/G, and GSTO2 Asn142Asp was associated with an increased cancer risk (HRs, 4.91, 95% CI, 1.02-23.74) when compared to the all-wildtype reference, respectively.</p> <p>Conclusions</p> <p>The GSTs do not play a critical role in arsenic-induced urothelial carcinogenesis. The genetic effects of GSTT1 and GSTO1 on arsenic-induced urothelial carcinogenesis are largely confined to very high exposure level.</p