Investigation and identification of protein γ-glutamyl carboxylation sites

<p>Abstract</p> <p>Background</p> <p>Carboxylation is a modification of glutamate (Glu) residues which occurs post-translation that is catalyzed by γ-glutamyl carboxylase in the lumen of the endoplasmic reticulum. Vitamin K is a critical co-factor in the post-translational conversion of Glu residues to γ-carboxyglutamate (Gla) residues. It has been shown that the process of carboxylation is involved in the blood clotting cascade, bone growth, and extraosseous calcification. However, studies in this field have been limited by the difficulty of experimentally studying substrate site specificity in γ-glutamyl carboxylation. <it>In silico</it> investigations have the potential for characterizing carboxylated sites before experiments are carried out.</p> <p>Results</p> <p>Because of the importance of γ-glutamyl carboxylation in biological mechanisms, this study investigates the substrate site specificity in carboxylation sites. It considers not only the composition of amino acids that surround carboxylation sites, but also the structural characteristics of these sites, including secondary structure and solvent-accessible surface area (ASA). The explored features are used to establish a predictive model for differentiating between carboxylation sites and non-carboxylation sites. A support vector machine (SVM) is employed to establish a predictive model with various features. A five-fold cross-validation evaluation reveals that the SVM model, trained with the combined features of positional weighted matrix (PWM), amino acid composition (AAC), and ASA, yields the highest accuracy (0.892). Furthermore, an independent testing set is constructed to evaluate whether the predictive model is over-fitted to the training set.</p> <p>Conclusions</p> <p>Independent testing data that did not undergo the cross-validation process shows that the proposed model can differentiate between carboxylation sites and non-carboxylation sites. This investigation is the first to study carboxylation sites and to develop a system for identifying them. The proposed method is a practical means of preliminary analysis and greatly diminishes the total number of potential carboxylation sites requiring further experimental confirmation.</p

Characterizing the Efficiency of Perovskite Solar Cells and Light-Emitting Diodes

Metal halide perovskites (MHPs) are being widely studied as a light-absorber for high-efficiency solar cells. With efforts being made throughout the globe, the power conversion efficiency of MHP solar cells has recently soared up to 25.2%. MHPs are now being spotlighted as a next-generation light-emitter as well. Their high color purity and solution-processability are of particular interest for display applications, which in general benefit from wide color gamut and low-cost high-resolution subpixel patterning. For this reason, research activities on perovskite light-emitting diodes (LEDs) are rapidly growing, and their external quantum efficiencies have been dramatically improved to over 20%. As more and more research groups with different backgrounds are working on these perovskite optoelectronic devices, the demand is growing for standard methods for accurate efficiency measurement that can be agreed upon across the disciplines and, at the same time, can be realized easily in the lab environment with due diligence. Herein, optoelectronic characterization methods are revisited from the viewpoint of MHP solar cells and LEDs. General efficiency measurement practices are first reviewed, common sources of errors are introduced, and guidelines for avoiding or minimizing those errors are then suggested to help researchers in fields develop the best measurement practice.

Postchallenge responses of nitrotyrosine and TNF-alpha during 75-g oral glucose tolerance test are associated with the presence of coronary artery diseases in patients with prediabetes

<p>Abstract</p> <p>Background</p> <p>Meta-analysis has demonstrated an exponential relationship between 2-hr postchallenge hyperglycemia and coronary artery disease (CAD). Pulsatile hyperglycemia can acutely increase proinflammatory cytokines by oxidative stress. We hypothesized that postchallenge proinflammatory and nitrosative responses after 75 g oral glucose tolerance tests (75 g-OGTT) might be associated with CAD in patients without previously recognized type 2 diabetes mellitus (T2DM).</p> <p>Methods</p> <p>Serial changes of plasma glucose (PG), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and nitrotyrosine levels were analyzed during 75 g-OGTT in 120 patients (81 male; age 62 ± 11 years) before coronary angiography. Patients were classified as normal (NGT; 42%), impaired (IGT; 34%) and diabetic (T2DM; 24%) glucose tolerance by 75 g-OGTT.</p> <p>Results</p> <p>Postchallenge hyperglycemia elicited TNF-α, IL-6 and nitrotyrosine levels time-dependently, and 2-hr median levels of TNF-α (7.1 versus 6.4 pg/ml; <it>P </it>< 0.05) and nitrotyrosine (1.01 versus 0.83 <it>μ</it>mol/l; <it>P </it>< 0.05), but not IL-6 or PG, were significantly higher in patients with CAD in either IGT or T2DM groups. After adjusting risk factors and glucose tolerance status, 2-hr nitrotyrosine in highest quartiles (OR: 3.1, <it>P </it>< 0.05) remained an independent predictor of CAD by logistic regression analysis.</p> <p>Conclusions</p> <p>These results highlight postchallenge proinflammatory and nitrosative responses by 75 g-OGTT, rather than hyperglycemia <it>per se</it>, are associated with CAD in patients without previous recognized diabetes.</p

Genome-wide CRISPR-Cas9 screen identifies hyperosmotic stress responsive genes in Chinese hamster ovary cells

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Navigation-Assisted Full-Endoscopic Radiofrequency Rhizotomy Versus Fluoroscopy-Guided Cooled Radiofrequency Ablation for Sacroiliac Joint Pain Treatment: Comparative Study

Objective Sacroiliac joint (SIJ) pain is a common cause of chronic low back pain. Full-endoscopic rhizotomy of lateral branches of dorsal rami innervating SIJ is a potential option for patients’ refractory to medical treatment. The full-endoscopic rhizotomy is sometimes challenging under fluoroscopic guidance. This study is to evaluate the effectiveness of the navigation-assisted full-endoscopic rhizotomy for SIJ pain. Methods The study was a retrospective match-paired study that enrolled consecutive patients undergoing navigation-assisted full-endoscopic rhizotomy for SIJ pain. The patient demographics, clinical outcomes, and operative parameters of endoscopic rhizotomy were compared with conventional cooled radiofrequency ablation (RFA) treatment. Results The study enrolled 72 patients, including 36 patients in the endoscopic group. Thirty-six patients in the cooled RFA group were matched by age as the control. The follow-up time was at least 1 year. Patient characteristics were similar between the groups. The navigation-assisted endoscopic rhizotomy operation time was significantly longer than the cooled RFA. The visual analogue scale (VAS) for pain and Oswestry Disability Index (ODI) significantly decreased after each treatment. However, the between-group comparison revealed that the VAS and ODI of the patients after endoscopic rhizotomy were significantly lower than those after the cooled RFA group. There were no postoperative complications in the study. Conclusion Navigation-assisted full-endoscopic rhizotomy is an alternative to SIJ pain treatment. Integrating intraoperative navigation can ensure accurate full-endoscopic rhizotomy to provide better durability of pain relief than the cooled RFA

(Z)3,4,5,4'-trans-tetramethoxystilbene, a new analogue of resveratrol, inhibits gefitinb-resistant non-small cell lung cancer via selectively elevating intracellular calcium level.

Calcium is a second messenger which is required for regulation of many cellular processes. However, excessive elevation or prolonged activation of calcium signaling would lead to cell death. As such, selectively regulating calcium signaling could be an alternative approach for anti-cancer therapy. Recently, we have identified an effective analogue of resveratrol, (Z)3,4,5,4′-trans-tetramethoxystilbene (TMS) which selectively elevated the intracellular calcium level in gefitinib-resistant (G-R) non-small-cell lung cancer (NSCLC) cells. TMS exhibited significant inhibitory effect on G-R NSCLC cells, but not other NSCLC cells and normal lung epithelial cells. The phosphorylation and activation of EGFR were inhibited by TMS in G-R cells. TMS induced caspase-independent apoptosis and autophagy by directly binding to SERCA and causing endoplasmic reticulum (ER) stress and AMPK activation. Proteomics analysis also further confirmed that mTOR pathway, which is the downstream of AMPK, was significantly suppressed by TMS. JNK, the cross-linker of ER stress and mTOR pathway was significantly activated by TMS. In addition, the inhibition of JNK activation can partially block the effect of TMS. Taken together, TMS showed promising anti-cancer activity by mediating calcium signaling pathway and inducing apoptosis as well as autophagy in G-R NSCLC cells, providing strategy in designing multi-targeting drug for treating G-R patients

The Role of Macrolide Antibiotics in Increasing Cardiovascular Risk

AbstractBackgroundLarge cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events.ObjectivesThis study performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause.MethodsWe performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.ResultsThirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses.ConclusionsAdministration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality