Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration

Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration.     

Actin Dynamics Affect Mitochondrial Quality Control and Aging in Budding Yeast

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The enzyme 3-hydroxykynurenine transaminase as potential target for 1,2,4-oxadiazoles with larvicide activity against the dengue vector Aedes aegypti

The mosquito Aedes aegypti is the vector agent responsible for the transmission of yellow fever and dengue fever viruses to over 80 million people in tropical and subtropical regions of the world. Exhaustive efforts have lead to a vaccine candidate with only 30% effectiveness against the dengue virus and failure to protect patients against the serotype 2. Hence, vector control remains the most viable route to dengue fever control programs. We have synthesized a class of 1,2,4-oxadiazole derivatives whose most biologically active compounds exhibit potent activity against Aedes aegypti larvae (ca. of 15 ppm) and low toxicity in mammals. Exposure to these larvicides results in larvae pigmentation in a manner correlated with the LC₅₀ measurements. Structural comparisons of the 1,2,4-oxadiazole nucleus against known inhibitors of insect enzymes allowed the identification of 3-hydroxykynurenine transaminase as a potential target for these synthetic larvicides. Molecular docking calculations indicate that 1,2,4-oxadiazole compounds can bind to 3-hydroxykynurenine transaminase with similar conformation and binding energies as its crystallographic inhibitor 4-(2-aminophenyl)-4-oxobutanoic acid.     

Exploring the implications of recreational disturbance on an endangered butterfly using a novel modelling approach

Site and wildlife managers globally are under increasing pressure to implement management strategies that address the negative implications of outdoor recreational activities on wildlife. For many rare and isolated species any anthropogenic activities that cause disturbance could potentially be detrimental to existing populations. Understanding how non-consumptive recreation can influence a species may therefore be critical to its preservation. We developed a novel approach to specifically address this need. Using a combination of field surveys and simulation modelling exercises, we (1) explored the responses of endangered Karner blue butterflies (Lycaeides melissa samuelis) to recreation, (2) assessed whether such responses influenced oviposition rate and/or host plant choice and (3) tested alternative management strategies that could alleviate the negative impacts of recreation. Our field surveys confirmed that Karner blues were sensitive to recreational disturbance. Butterflies flushed at similar speeds and distances from recreationists (2.2 m at 0.17 m/s), as they would from natural threats, such as predators (2.2 m at 0.19 m/s). Incorporating female response parameters into a simulation model revealed that regular disturbance could reduce egg laying potential and significantly restrict host plant choice, which in turn, could impact the butterfly’s population dynamics. However, we established that it was possible to effectively offset the implications of recreational disturbance using our simulation modelling approach. For example, extending Karner blue breeding habitat from trails and other public rights of way has the potential to alleviate such disturbance. Our study demonstrates that the potential impact of recreation on species of conservation concern should not be overlooked.     

Evaluation of the Effectiveness of Malaria Vector Control Measures in Urban Settings of Dakar by a Specific Anopheles Salivary Biomarker

Standard entomological methods for evaluating the impact of vector control lack sensitivity in low-malaria-risk areas. The detection of human IgG specific to Anopheles gSG6-P1 salivary antigen reflects a direct measure of human–vector contact. This study aimed to assess the effectiveness of a range of vector control measures (VCMs) in urban settings by using this biomarker approach. The study was conducted from October to December 2008 on 2,774 residents of 45 districts of urban Dakar. IgG responses to gSG6-P1 and the use of malaria VCMs highly varied between districts. At the district level, specific IgG levels significantly increased with age and decreased with season and with VCM use. The use of insecticide-treated nets, by drastically reducing specific IgG levels, was by far the most efficient VCM regardless of age, season or exposure level to mosquito bites. The use of spray bombs was also associated with a significant reduction of specific IgG levels, whereas the use of mosquito coils or electric fans/air conditioning did not show a significant effect. Human IgG response to gSG6-P1 as biomarker of vector exposure represents a reliable alternative for accurately assessing the effectiveness of malaria VCM in low-malaria-risk areas. This biomarker tool could be especially relevant for malaria control monitoring and surveillance programmes in low-exposure/low-transmission settings.     

Monitoring of an antigen manufacturing process

Fluorescence spectroscopy in combination with multivariate statistical methods was employed as a tool for monitoring the manufacturing process of pertactin (PRN), one of the virulence factors of Bordetella pertussis utilized in whopping cough vaccines. Fluorophores such as amino acids and co-enzymes were detected throughout the process. The fluorescence data collected at different stages of the fermentation and purification process were treated employing principal component analysis (PCA). Through PCA, it was feasible to identify sources of variability in PRN production. Then, partial least square (PLS) was employed to correlate the fluorescence spectra obtained from pure PRN samples and the final protein content measured by a Kjeldahl test from these samples. In view that a statistically significant correlation was found between fluorescence and PRN levels, this approach could be further used as a method to predict the final protein content.     

DNA methylation of loci within ABCG1 and PHOSPHO1 in blood DNA is associated with future type 2 diabetes risk

Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci in blood DNA (ABCG1, PHOSPHO1, SOCS3, SREBF1, and TXNIP), recently reported to be associated with T2D, might predict future T2D in subjects from the Botnia prospective study. We also tested if these CpG sites exhibit altered DNA methylation in human pancreatic islets, liver, adipose tissue, and skeletal muscle from diabetic vs. non-diabetic subjects. DNA methylation at the ABCG1 locus cg06500161 in blood DNA was associated with an increased risk for future T2D (OR = 1.09, 95% CI = 1.02–1.16, P-value = 0.007, Q-value = 0.018), while DNA methylation at the PHOSPHO1 locus cg02650017 in blood DNA was associated with a decreased risk for future T2D (OR = 0.85, 95% CI = 0.75–0.95, P-value = 0.006, Q-value = 0.018) after adjustment for age, gender, fasting glucose, and family relation. Furthermore, the level of DNA methylation at the ABCG1 locus cg06500161 in blood DNA correlated positively with BMI, HbA1c, fasting insulin, and triglyceride levels, and was increased in adipose tissue and blood from the diabetic twin among monozygotic twin pairs discordant for T2D. DNA methylation at the PHOSPHO1 locus cg02650017 in blood correlated positively with HDL levels, and was decreased in skeletal muscle from diabetic vs. non-diabetic monozygotic twins. DNA methylation of cg18181703 (SOCS3), cg11024682 (SREBF1), and cg19693031 (TXNIP) was not associated with future T2D risk in subjects from the Botnia prospective study.     

Differences in the Access to Sterilization between Women Living and Not Living with HIV: Results from the GENIH Study,Brazil

BackgroundIn many countries, young women of reproductive age have been especially affected by the HIV epidemic, which have fostered research to better understand how HIV infection influences and shapes women´s fertility and reproductive and sexual decisions. In Brazil, few studies have focused on the impact of the HIV epidemic on contraceptive choices among women living with HIV (WLHIV).ObjectiveThis study evaluates the impact HIV infection may have in the access to female sterilization in Brazil, using a time-to-event analysis.MethodsA cross-sectional quantitative study (GENIH study) was conducted between February 2013 and April 2014 in the city of São Paulo, comparing two probabilistic samples of 975 WLHIV and 1,003 women not living with HIV (WNLHIV) aged 18 to 49. Sexual and reproductive data was collected retrospectively in order to reconstruct women''s reproductive trajectories. Given the objectives of this study, the analysis was restricted to women with parity one or more and, in case of WLHIV, to those sterilized after HIV diagnosis and not infected through vertical transmission. The final sample analysis included 683 WNLHIV and 690 WLHIV. A series of multivariable-adjusted Cox models estimated the probability of being sterilized after HIV diagnosis, compared with WNLHIV. Models were adjusted for schooling, race/color, and stratified by parity at last delivery (1–2, 3+). Hazard ratios were calculated for female sterilization, and separately for interval and postpartum procedures (performed in conjunction with caesarean section or immediately after vaginal delivery). Additionally, information regarding unmet demand for female sterilization was also explored.FindingsNo statistical difference in the overall risk of sterilization between WLHIV and WNLHIV in the two parity-related groups is observed: HR = 0.88 (0.54–1.43) and 0.94 (0.69–1.29), respectively, among women with 1–2 children and those with three and more. However, significant differences regarding the impact of HIV infection at sterilization are observed depending on the timing and the type of sterilization procedure. The probability of obtaining an interval sterilization is significantly lower for WLHIV compared to those not living with HIV. The reverse occurs regarding postpartum sterilization. Although sterilization is mainly performed in conjunction with caesarean section in Brazil, it is evident that caesarean sections are not the sole factor increasing the risk of sterilization among WLHIV.ConclusionThe results indicate barriers in the access to services offering interval sterilization for WLHIV and certain facilitation in obtaining the procedure in conjunction with caesarean section. Health policy makers at local and national levels should promote institutional changes in order to facilitate access to interval sterilization and to confront the sensitive discussion of WLHIV’s eligibility for postpartum sterilization. It is also urgent to increase access to a wider range of contraceptive methods for WLHIV and promote dual method protection strategies. Moreover, since condom use may decrease in the future in the context of the preventive effect of antiretroviral therapy, promoting dual methods will expand the choices regarding the reproductive rights of women living with HIV.     

Inclusion of Dominance Effects in the Multivariate GBLUP Model

New proposals for models and applications of prediction processes with data on molecular markers may help reduce the financial costs of and identify superior genotypes in maize breeding programs. Studies evaluating Genomic Best Linear Unbiased Prediction (GBLUP) models including dominance effects have not been performed in the univariate and multivariate context in the data analysis of this crop. A single cross hybrid construction procedure was performed in this study using phenotypic data and actual molecular markers of 4,091 maize lines from the public database Panzea. A total of 400 simple hybrids resulting from this process were analyzed using the univariate and multivariate GBLUP model considering only additive effects additive plus dominance effects. Historic heritability scenarios of five traits and other genetic architecture settings were used to compare models, evaluating the predictive ability and estimation of variance components. Marginal differences were detected between the multivariate and univariate models. The main explanation for the small discrepancy between models is the low- to moderate-magnitude correlations between the traits studied and moderate heritabilities. These conditions do not favor the advantages of multivariate analysis. The inclusion of dominance effects in the models was an efficient strategy to improve the predictive ability and estimation quality of variance components.