Cytosolic SYT/SS18 Isoforms Are Actin-Associated Proteins that Function in Matrix-Specific Adhesion

SYT (SYnovial sarcoma Translocated gene or SS18) is widely produced as two isoforms, SYT/L and SYT/S, that are thought to function in the nucleus as transcriptional coactivators. Using isoform-specific antibodies, we detected a sizable pool of SYT isoforms in the cytosol where the proteins were organized into filamentous arrays. Actin and actin-associated proteins co-immunoprecipitated with SYT isoforms, which also co-sedimented and co-localized with the actin cytoskeleton in cultured cells and tissues. The association of SYT with actin bundles was extensive yet stopped short of the distal ends at focal adhesions. Disruption of the actin cytoskeleton also led to a breakdown of the filamentous organization of SYT isoforms in the cytosol. RNAi ablation of SYT/L alone or both isoforms markedly impaired formation of stress fibers and focal adhesions but did not affect formation of cortical actin bundles. Furthermore, ablation of SYT led to markedly impaired adhesion and spreading on fibronectin and laminin-111 but not on collagen types I or IV. These findings indicate that cytoplasmic SYT isoforms interact with actin filaments and function in the ability cells to bind and react to specific extracellular matrices

Distance decay in delivery care utilisation associated with neonatal mortality. A case referent study in northern Vietnam

BACKGROUND: Efforts to reduce neonatal mortality are essential if the Millennium Development Goal (MDG) 4 is to be met. The impact of spatial dimensions of neonatal survival has not been thoroughly investigated even though access to good quality delivery care is considered to be one of the main priorities when trying to reduce neonatal mortality. This study examined the association between distance from the mother's home to the closest health facility and neonatal mortality, and investigated the influence of distance on patterns of perinatal health care utilisation. METHODS: A surveillance system of live births and neonatal deaths was set up in eight districts of Quang Ninh province, Vietnam, from July 2008 to December 2009. Case referent design including all neonatal deaths and randomly selected newborn referents from the same population. Interviews were performed with mothers of all subjects and GIS coordinates for mothers' homes and all health facilities in the study area were obtained. Straight-line distances were calculated using ArcGIS software. RESULTS: A total of 197 neonatal deaths and 11 708 births were registered and 686 referents selected. Health care utilisation prior to and at delivery varied with distance to the health facility. Mothers living farthest away (4th and 5th quintile, ≥1257 meters) from a health facility had an increased risk of neonatal mortality (OR 1.96, 95% CI 1.40 - 2.75, adjusted for maternal age at delivery and marital status). When stratified for socio-economic factors there was an increased risk for neonatal mortality for mothers with low education and from poor households who lived farther away from a health facility. Mothers who delivered at home had more than twice as long to a health facility compared to mothers who delivered at a health care facility. There was no difference in age at death when comparing neonates born at home or health facility deliveries (p = 0.56). CONCLUSION: Distance to the closest health facility was negatively associated with neonatal mortality risk. Health care utilisation in the prenatal period could partly explain this risk elevation since there was a distance decay in health system usage prior to and at delivery. The geographical dimension must be taken into consideration when planning interventions for improved neonatal survival, especially when targeting socio-economically disadvantaged groups

A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer

ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional approach was performed to select 28 single nucleotide polymorphisms (SNPs) that were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In addition, six potentially functional SNPs were genotyped in 3,662 German subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T alleles had an increased risk for CRC (Ptrend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (Ptrend = 0.022). We sought to replicate the most significant results in an independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls carried out in the North of Germany. None of the SNPs tested were significantly associated with CRC risk in the replication study. In conclusion, in this study of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a minor role in the susceptibility to CRC

Windbreaks in North American Agricultural Systems

Windbreaks are a major component of successful agricultural systems throughout the world. The focus of this chapter is on temperate-zone, commercial, agricultural systems in North America, where windbreaks contribute to both producer profitability and environmental quality by increasing crop production while simultaneously reducing the level of off-farm inputs. They help control erosion and blowing snow, improve animal health and survival under winter conditions, reduce energy consumption of the farmstead unit, and enhance habitat diversity, providing refuges for predatory birds and insects. On a larger landscape scale windbreaks provide habitat for various types of wildlife and have the potential to contribute significant benefits to the carbon balance equation, easing the economic burdens associated with climate change. For a windbreak to function properly, it must be designed with the needs of the landowner in mind. The ability of a windbreak to meet a specific need is determined by its structure: both external structure, width, height, shape, and orientation as well as the internal structure; the amount and arrangement of the branches, leaves, and stems of the trees or shrubs in the windbreak. In response to windbreak structure, wind flow in the vicinity of a windbreak is altered and the microclimate in sheltered areas is changed; temperatures tend to be slightly higher and evaporation is reduced. These types of changes in microclimate can be utilized to enhance agricultural sustainability and profitability. While specific mechanisms of the shelter response remain unclear and are topics for further research, the two biggest challenges we face are: developing a better understanding of why producers are reluctant to adopt windbreak technology and defining the role of woody plants in the agricultural landscape

Resveratrol Inhibits Protein Translation in Hepatic Cells

Resveratrol is a plant-derived polyphenol that extends lifespan and healthspan in model organism. Despite extensive investigation, the biological processes mediating resveratrol's effects have yet to be elucidated. Because repression of translation shares many of resveratrol's beneficial effects, we hypothesized that resveratrol was a modulator of protein synthesis. We studied the effect of the drug on the H4-II-E rat hepatoma cell line. Initial studies showed that resveratrol inhibited global protein synthesis. Given the role of the mammalian Target of Rapamycin (mTOR) in regulating protein synthesis, we examined the effect of resveratrol on mTOR signaling. Resveratrol inhibited mTOR self-phosphorylation and the phosphorylation of mTOR targets S6K1 and eIF4E-BP1. It attenuated the formation of the translation initiation complex eIF4F and increased the phosphorylation of eIF2α. The latter event, also a mechanism for translation inhibition, was not recapitulated by mTOR inhibitors. The effects on mTOR signaling were independent of effects on AMP-activated kinase or AKT. We conclude that resveratrol is an inhibitor of global protein synthesis, and that this effect is mediated through modulation of mTOR-dependent and independent signaling

A randomized, controlled trial of 3.0 mg of liraglutide in weight management

BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P<0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)

Methyl methacrylate and respiratory sensitization: A Critical review

Methyl methacrylate (MMA) is a respiratory irritant and dermal sensitizer that has been associated with occupational asthma in a small number of case reports. Those reports have raised concern that it might be a respiratory sensitizer. To better understand that possibility, we reviewed the in silico, in chemico, in vitro, and in vivo toxicology literature, and also epidemiologic and occupational medicine reports related to the respiratory effects of MMA. Numerous in silico and in chemico studies indicate that MMA is unlikely to be a respiratory sensitizer. The few in vitro studies suggest that MMA has generally weak effects. In vivo studies have documented contact skin sensitization, nonspecific cytotoxicity, and weakly positive responses on local lymph node assay; guinea pig and mouse inhalation sensitization tests have not been performed. Cohort and cross-sectional worker studies reported irritation of eyes, nose, and upper respiratory tract associated with short-term peaks exposures, but little evidence for respiratory sensitization or asthma. Nineteen case reports described asthma, laryngitis, or hypersensitivity pneumonitis in MMA-exposed workers; however, exposures were either not well described or involved mixtures containing more reactive respiratory sensitizers and irritants.The weight of evidence, both experimental and observational, argues that MMA is not a respiratory sensitizer