Short‐term calorie restriction ameliorates genomewide,age‐related alterations in DNA methylation

DNA methylation plays major roles in many biological processes, including aging, carcinogenesis, and development. Analyses of DNA methylation using next‐generation sequencing offer a new way to profile and compare methylomes across the genome in the context of aging. We explored genomewide DNA methylation and the effects of short‐term calorie restriction (CR) on the methylome of aged rat kidney. Whole‐genome methylation of kidney in young (6 months old), old (25 months old), and OCR (old with 4‐week, short‐term CR) rats was analyzed by methylated DNA immunoprecipitation and next‐generation sequencing (MeDIP‐Seq). CpG islands and repetitive regions were hypomethylated, but 5′‐UTR, exon, and 3′‐UTR hypermethylated in old and OCR rats. The methylation in the promoter and intron regions was decreased in old rats, but increased in OCR rats. Pathway enrichment analysis showed that the hypermethylated promoters in old rats were associated with degenerative phenotypes such as cancer and diabetes. The hypomethylated promoters in old rats related significantly to the chemokine signaling pathway. However, the pathways significantly enriched in old rats were not observed from the differentially methylated promoters in OCR rats. Thus, these findings suggest that short‐term CR could partially ameliorate age‐related methylation changes in promoters in old rats. From the epigenomic data, we propose that the hypermethylation found in the promoter regions of disease‐related genes during aging may indicate increases in susceptibility to age‐related diseases. Therefore, the CR‐induced epigenetic changes that ameliorate age‐dependent aberrant methylation may be important to CR's health‐ and life‐prolonging effects.     

Studies on Enhancement of Anti-microbial Activity of Pristine MWCNTs Against Pathogens

Carbon nanotubes (CNTs), owing to their inherently unique properties in the domain of biomedical sciences including drug delivery, offer an exciting platform to the researchers. Of late, their applications have also been successfully established. Recently, single-walled CNTs (SWCNTs) have been explored for antibacterial efficacy, but naïve multi-walled CNTs (MWCNTs) still remained unearthed. The present studies endeavor the investigation of the potential of various non-ionic surfactants in solubility enhancement of MWCNTs and their subsequent antibacterial efficacy against Escherichia coli and Staphylococcus aureus. Polysorbates offer more solubility to MWCNTs vis-à-vis the phospholipids. However, the antibacterial effect was found to be less influenced by solubility but significantly determined by the type of surfactant. Transmission electron photomicrographs confirmed significant adhesion of MWCNTs to the bacterial walls only in the presence of unsaturated phospholipids and this was expressed in the form of lowest minimum inhibitory concentration (MIC) values of MWCNTs dispersed with the same. The findings are unique as MWCNTs were found to be active against both Gram-negative and Gram-positive bacteria to a similar extent, though somewhat milder than SWCNTs. However, when dispersed with unsaturated phospholipids, the former offer almost comparable antibacterial effects to that of the latter. The study opens a new research domain to further explore the antibacterial effects of non-functionalized and relatively safer MWCNTs, accentuating the importance of biocomponents like unsaturated phospholipids in this purview.     

QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil

The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T _60%?>?6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T _max, K _a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.     

Patellofemoral cartilage stresses are most sensitive to variations in vastus medialis muscle forces

The purpose of this study was to evaluate the effects of variations in quadriceps muscle forces on patellofemoral stress. We created subject-specific finite element models for 21 individuals with chronic patellofemoral pain and 16 pain-free control subjects. We extracted three-dimensional geometries from high resolution magnetic resonance images and registered the geometries to magnetic resonance images from an upright weight bearing squat with the knees flexed at 60°. We estimated quadriceps muscle forces corresponding to 60° knee flexion during a stair climb task from motion analysis and electromyography-driven musculoskeletal modelling. We applied the quadriceps muscle forces to our finite element models and evaluated patellofemoral cartilage stress. We quantified cartilage stress using an energy-based effective stress, a scalar quantity representing the local stress intensity in the tissue. We used probabilistic methods to evaluate the effects of variations in quadriceps muscle forces from five trials of the stair climb task for each subject. Patellofemoral effective stress was most sensitive to variations in forces in the two branches of the vastus medialis muscle. Femur cartilage effective stress was most sensitive to variations in vastus medialis forces in 29/37 (78%) subjects, and patella cartilage effective stress was most sensitive to variations in vastus medialis forces in 21/37 (57%) subjects. Femur cartilage effective stress was more sensitive to variations in vastus medialis longus forces in subjects classified as maltrackers compared to normal tracking subjects (p?=?0.006). This study provides new evidence of the importance of the vastus medialis muscle in the treatment of patellofemoral pain.     

Effect of Vanadium Supplementation on Production Performance,Nutrient Utilization,Plasma Mineral Concentration,and Mineral Balance in Lactating Goats

Biological Trace Element Research - Vanadium (V) has not been elucidated as an essential mineral in ruminants, though in lower organisms and rat model, its role is well known as insulin—a...     

Mapping quantitative trait loci associated with southern leaf blight resistance in maize (Zea mays L.)

Southern leaf blight (SLB) caused by the fungus Cochliobolus heterostrophus (Drechs.) Drechs. is a major foliar disease of maize worldwide. Our objectives were to identify quantitative trait loci (QTL) for resistance to SLB and flowering traits in recombinant inbred line (RIL) population derived from the cross of inbred lines LM5 (resistant) and CM140 (susceptible). A set of 207 RILs were phenotyped for resistance to SLB at three time intervals for two consecutive years. Four putative QTL for SLB resistance were detected on chromosomes 3, 8 and 9 that accounted for 54% of the total phenotypic variation. Days to silking and anthesis–silking interval (ASI) QTL were located on chromosomes 6, 7 and 9. A comparison of the obtained results with the published SLB resistance QTL studies suggested that the detected bins 9.03/02 and 8.03/8.02 are the hot spots for SLB resistance whereas novel QTL were identified in bins 3.08 and 8.01/8.04. The linked markers are being utilized for marker‐assisted mobilization of QTL conferring resistance to SLB in elite maize backgrounds. Fine mapping of identified QTL will facilitate identification of candidate genes underlying SLB resistance.