Molecular docking analysis of compounds from Justica adhatoda L with the MUC1 oncoprotein

The MUC1 oncoprotein is known to be linked with different types of cancer. Therefore, it is of interest to document the molecular docking analysis of compounds from Justica adhatoda L with the MUC1 oncoprotein. We report the structure based molecular binding features compounds such as amrinone, ethambutol, pyrazinamide and vasicoline the MUC1 oncoprotein for further consideration in drug discovery.     

Meta-analysis identified the TNFA -308G > A promoter polymorphism as a risk factor for disease severity in patients with rheumatoid arthritis

Introduction

The goal of this study is to investigate whether the -308G > A promoter polymorphism in the tumor necrosis factor alpha (TNFA) gene is associated with disease severity and radiologic joint damage in a large cohort of patients with rheumatoid arthritis (RA).

Methods

A long-term observational early RA inception cohort (n = 208) with detailed information about disease activity and radiologic damage after 3, 6 and 9 years of disease was genotyped for the TNFA -308G > A promoter polymorphism (rs1800629). A longitudinal regression analysis was performed to assess the effect of genotype on RA disease severity and joint damage. Subsequently, a meta-analysis, including all publically available data, was performed to further test the association between joint erosions and the TNFA polymorphism. To learn more about the mechanism behind the effect of the polymorphism, RNA isolated from peripheral blood from RA patients (n = 66) was used for TNFA gene expression analysis by quantitative PCR.

Results

Longitudinal regression analysis with correction for gender and disease activity showed a significant difference in total joint damage between GG and GA+AA genotype groups (P = 0.002), which was stable over time. The meta-analysis, which included 2,053 patients, confirmed an association of the genetic variant with the development of erosions (odds ratio 0.78, 95% CI 0.62, 0.98). No significant differences in TNFA gene expression were observed for the different genotypes, confirming earlier findings in healthy individuals.

Conclusions

Our data confirm that the TNFA -308G > A promoter polymorphism is associated with joint damage in patients with RA. This is not mediated by differences in TNFA gene expression between genotypes.     

Simulation of stent deployment in a realistic human coronary artery

Background  

The process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis.     

Trehalose Increases Freeze-Thaw Damage in Liposomes Containing Chloroplast Glycolipids

Chloroplast thylakoids contain three classes of glycolipids, monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG), and sulfoquinovosyldiacylglycerol (SQDG). We have investigated the stability of large unilamellar vesicles made from egg phosphatidylcholine (EPC) and different chloroplast glycolipids during freezing to -18 degreesC, as a function of the presence of three sugars: glucose, sucrose, or trehalose. Contrary to the situation in thylakoids, where cryoprotection increases from glucose < sucrose < trehalose, liposomes containing 50% DGDG showed the opposite behavior. In fact, carboxyfluorescein leakage increased over the control values (freezing in the absence of sugar) in the presence of trehalose. This effect was not seen in vesicles made from pure EPC, or a mixture of EPC and MGDG, or EPC and SQDG. Liposomes made from mixtures of all three glycolipids, however, showed even more leakage in the presence of trehalose than liposomes containing only DGDG and EPC. Copyright 1998 Academic Press.     

Lack of geographic variation in anonymous nuclear polymorphisms in the American oyster, Crassostrea virginica

Comparing geographic variation of noncoding nuclear DNA polymorphisms, which presumably are neutral to natural selection, with geographic variation of allozymes is potentially a good way to detect the effects of selection on allozyme polymorphisms. A previous study of four anonymous nuclear markers in the American oyster, Crassostrea virginica, found dramatic differences in allele frequency between the Gulf of Mexico and the Atlantic Ocean. In contrast, 14 allozyme polymorphisms were fairly uniform in frequency between the two areas. This led to the conclusion that all of the allozyme polymorphisms were kept uniform in frequency by balancing selection. To test the robustness of this pattern, six additional anonymous nuclear DNA polymorphisms were surveyed in oysters from Panacea, Fla, and Charleston, S.C. on the Gulf and Atlantic coasts, respectively. Unlike the previously studied DNA markers, the six DNA polymorphisms examined here show geographic variation that is not significantly greater than that of allozymes. The reason for the discrepancy between the two sets of DNA polymorphisms is unclear.      

Interaction of specialist root and shoot herbivores of Alliaria petiolata and their impact on plant performance and reproduction

Abstract.  1. This study explored interactions of two spatially and temporally separated weevils and their impact on Alliaria petiolata (garlic mustard) survival, growth, and reproduction at different herbivore densities.
2. The root-mining weevil Ceutorhynchus scrobicollis attacks A. petiolata rosettes from October to April, and larvae complete development in May. The shoot-mining weevil Ceutorhynchus alliariae attacks bolting plants in April/May with larvae completing development in June–July. Priority effects were expected, with early attack of C. scrobicollis affecting the later attacking C. alliariae , mediated through changes in plant growth or chemistry.
3. Attack by C. scrobicollis significantly increased plant mortality and changed plant architecture, while C. alliariae only significantly reduced plant height. Attack by C. scrobicollis also increased nitrogen content of stems.
4. Root feeding by C. scrobicollis affected the feeding niche of C. alliariae , but increased stem nitrogen content did not result in increased stem miner survival. While reduced height and stem diameters as a result of C. scrobicollis attack reduced C. alliariae attack at the stem level, attack at plant level and recruitment was unaffected.
5. Weevil density had no effect on plant performance, most likely due to strong intraspecific competition, and there were no synergistic effects between the two herbivores.
6. Overall, attack by C. scrobicollis was more detrimental to A. petiolata growth, seed output, and survival than attack by C. alliariae . Consequently, C. scrobicollis has been prioritised as a potential biocontrol agent for control of A. petiolata in North America.     

Direct effects of temperature on forest nitrogen cycling revealed through analysis of long‐term watershed records

The microbial conversion of organic nitrogen (N) to plant available forms is a critical determinant of plant growth and carbon sequestration in forests worldwide. In temperate zones, microbial activity is coupled to variations in temperature, yet at the ecosystem level, microbial N mineralization seems to play a minor role in determining patterns of N loss. Rather, N losses often appear to vary with seasonality in hydrology and plant demand, while exports over longer periods are thought to be associated with increasing rates of anthropogenic N deposition. We analyzed long‐term (21–32 years) time series of climate and stream and atmospheric chemistry from two temperate deciduous forest watersheds in the southeastern USA to understand the sensitivity of internal forest N cycles to climate variation and atmospheric deposition. We evaluated the time series with a simple analytical model that incorporates key biotic constraints and mechanisms of N limitation and cycling in plant–soil systems. Through maximum likelihood analysis, we derive biologically realistic estimates of N mineralization and its temperature sensitivity (Q₁₀). We find that seasonality and long‐term trends in stream nitrate (NO₃) concentrations can in large part be explained by the dynamics of internal biological cycling responding to climate rather than external forcing from atmospheric chemistry. In particular, our model analysis suggests that much of the variation in N cycling in these forests results from the response of microbial activity to temperature, causing NO₃ losses to peak in the growing season and to accelerate with recent warming. Extrapolation of current trends in temperature and N deposition suggests that the upturn in temperature may increase future N export by greater than threefold more than from increasing deposition, revealing a potential direct effect of anthropogenic warming on terrestrial N cycles.     

Monitoring diabetes in patients with and without rheumatoid arthritis: a Medicare study

Introduction

Diabetes mellitus is a key predictor of mortality in rheumatoid arthritis (RA) patients. Both RA and diabetes increase the risk of cardiovascular disease (CVD), yet understanding of how comorbid RA impacts the receipt of guideline-based diabetes care is limited. The purpose of this study was to examine how the presence of RA affected hemoglobin A1C (A1c) and lipid measurement in older adults with diabetes.

Methods

Using a retrospective cohort approach, we identified beneficiaries ≥65 years old with diabetes from a 5% random national sample of 2004 to 2005 Medicare patients (N = 256,331), then examined whether these patients had comorbid RA and whether they received guideline recommended A1c and lipid testing in 2006. Multivariate logistic regression was used to examine the effect of RA on receiving guideline recommended testing, adjusting for baseline sociodemographics, comorbidities and health care utilization.

Results

Two percent of diabetes patients had comorbid RA (N = 5,572). Diabetes patients with comorbid RA were more likely than those without RA to have baseline cardiovascular disease (such as 17% more congestive heart failure), diabetes-related complications including kidney disease (19% higher), lower extremity ulcers (77% higher) and peripheral vascular disease (32% higher). In adjusted models, diabetes patients with RA were less likely to receive recommended A1c testing (odds ratio (OR) 0.84, CI 0.80 to 0.89) than those without RA, but were slightly more likely to receive lipid testing (OR 1.08, CI 1.01 to 1.16).

Conclusions

In older adults with diabetes, the presence of comorbid RA predicted lower rates of A1c testing but slightly improved lipid testing. Future research should examine strategies to improve A1c testing in patients with diabetes and RA, in light of increased CVD and microvascular risks in patients with both conditions.