Shape based virtual screening and molecular docking towards designing novel pancreatic lipase inhibitors

Increase in obesity rates and obesity associated health issues became one of the greatest health concerns in the present world population. With alarming increase in obese percentage there is a need to design new drugs related to the obesity targets. Among the various targets linked to obesity, pancreatic lipase was one of the promising targets for obesity treatment. Using the in silico methods like structure based virtual screening, QikProp, docking studies and binding energy calculations three molecules namely zinc85531017, zinc95919096 and zinc33963788 from the natural database were reported as the potential inhibitors for the pancreatic lipase. Among them zinc95919096 presented all the interactions matching to both standard and crystal ligand and hence it can be further proceeded to drug discovery process.     

Sprint interval training (SIT) is an effective method to maintain cardiorespiratory fitness (CRF) and glucose homeostasis in Scottish adolescents

The present study examined the physiological impact of a school based sprint interval training (SIT) intervention in replacement of standard physical education (SPE) class on cardio-respiratory fitness (CRF) and glucose homeostasis during the semester following summer vacation. Participants (n=49) were randomly allocated to either intervention (SIT; n=26, aged 16.9 ± 0.3 yrs) or control group who underwent standard physical education (SPE; n=23, aged 16.8 ± 0.6 yrs). CRF (VO₂max) and glucose homeostasis were obtained prior-to and following 7 weeks of SIT exercise. Significant group x time interaction was observed for CRF (P < 0.01) with non-significant trends for fasting insulin (P= 0.08), and HOMA-IR (P=0.06). CRF decreased (P < 0.01) in SPE such that POST intervention CRF was significantly lower (P< 0.05) in SPE. Fasting plasma glucose (P < 0.01), insulin (P< 0.01) and HOMA-IR (P< 0.01) increased significantly amongst SPE. The main finding of the present study is that 7-weeks of SIT exercise is an effective method of maintaining (but not improving) CRF and fasting insulin homeostasis amongst school-going adolescents. SIT exercise demonstrates potential as a time efficient physiological adjunct to standard PE class in order to maintain CRF during the school term.     

Exercise training in heart failure

Chronic heart failure (CHF) is a common condition with a poor prognosis. It is associated with poor exercise tolerance and debilitating symptoms. These symptoms appear to be associated with pathophysiological changes that occur systemically in the patient with CHF. Exercise training in carefully selected patients has been shown to be safe and to improve exercise capacity. Many of the pathophysiological abnormalities of CHF are improved by training. Some studies have suggested a possible improvement in morbidity and mortality with training. This review analyzes the controlled clinical trials of exercise training in CHF published to date.     

Spatial and temporal expression of histone demethylase,Kdm2a,during murine molar development

The histone demethylase, lysine (K)-specific demethylase 2A (Kdm2a), is highly conserved and expressed ubiquitously. Kdm2a can regulate cell proliferation and osteo/dentinogenic, adipogenic and chondrogenic differentiation of mesenchymal stem cells (MSCs) derived from dental tissue. We used quantitative real-time RT-PCR analysis and immunohistochemistry to detect Kdm2a expression during development of the murine molar at embryonic days E12, E14, E16 and E17 and postnatal days P3 and P14. Immunohistochemistry results showed no positive staining of Kdm2a at E12. At E14, Kdm2a was expressed weakly in the inner enamel epithelium, stellate reticulum cells and dental sac. At E16, Kdm2a was expressed mainly in the inner and outer enamel epithelium, stratum intermedium and dental sac, but weaker staining was found in cervical loop and dental papilla cells adjacent to the basement membrane. At E17, the strongest Kdm2a staining was detected in the ameloblasts and stronger Kdm2a staining also was detected in the stratum intermedium, outer enamel epithelium and dental papilla cells compared to the expression at E16. Postnatally, we found that Kdm2a was localized in secretory and mature ameloblasts and odontoblasts, and dentin was unstained. Real-time RT-PCR showed that Kdm2a mRNA levels in murine germ cells increased from E12 to E14 and from E14 to E16; no significant change occurred at E16, E17 or P3, then the levels decreased at P14 compared to P3. Kdm2a expression may be closely related to cell proliferation, to ameloblast and odontoblast differentiation and to the secretion of extracellular enamel and dentin during murine tooth development.     

Phylogenomics and Coalescent Analyses Resolve Extant Seed Plant Relationships

The extant seed plants include more than 260,000 species that belong to five main lineages: angiosperms, conifers, cycads, Ginkgo, and gnetophytes. Despite tremendous effort using molecular data, phylogenetic relationships among these five lineages remain uncertain. Here, we provide the first broad coalescent-based species tree estimation of seed plants using genome-scale nuclear and plastid data By incorporating 305 nuclear genes and 47 plastid genes from 14 species, we identify that i) extant gymnosperms (i.e., conifers, cycads, Ginkgo, and gnetophytes) are monophyletic, ii) gnetophytes exhibit discordant placements within conifers between their nuclear and plastid genomes, and iii) cycads plus Ginkgo form a clade that is sister to all remaining extant gymnosperms. We additionally observe that the placement of Ginkgo inferred from coalescent analyses is congruent across different nucleotide rate partitions. In contrast, the standard concatenation method produces strongly supported, but incongruent placements of Ginkgo between slow- and fast-evolving sites. Specifically, fast-evolving sites yield relationships in conflict with coalescent analyses. We hypothesize that this incongruence may be related to the way in which concatenation methods treat sites with elevated nucleotide substitution rates. More empirical and simulation investigations are needed to understand this potential weakness of concatenation methods.     

Plasma protein profiling reveals protein clusters related to BMI and insulin levels in middle-aged overweight subjects

BACKGROUND: Biomarkers that allow detection of the onset of disease are of high interest since early detection would allow intervening with lifestyle and nutritional changes before the disease is manifested and pharmacological therapy is required. Our study aimed to improve the phenotypic characterization of overweight but apparently healthy subjects and to identify new candidate profiles for early biomarkers of obesity-related diseases such as cardiovascular disease and type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: In a population of 56 healthy, middle-aged overweight subjects Body Mass Index (BMI), fasting concentration of 124 plasma proteins and insulin were determined. The plasma proteins are implicated in chronic diseases, inflammation, endothelial function and metabolic signaling. Random Forest was applied to select proteins associated with BMI and plasma insulin. Subsequently, the selected proteins were analyzed by clustering methods to identify protein clusters associated with BMI and plasma insulin. Similar analyses were performed for a second population of 20 healthy, overweight older subjects to verify associations found in population I. In both populations similar clusters of proteins associated with BMI or insulin were identified. Leptin and a number of pro-inflammatory proteins, previously identified as possible biomarkers for obesity-related disease, e.g. Complement 3, C Reactive Protein, Serum Amyloid P, Vascular Endothelial Growth Factor clustered together and were positively associated with BMI and insulin. IL-3 and IL-13 clustered together with Apolipoprotein A1 and were inversely associated with BMI and might be potential new biomarkers. CONCLUSION/ SIGNIFICANCE: We identified clusters of plasma proteins associated with BMI and insulin in healthy populations. These clusters included previously reported biomarkers for obesity-related disease and potential new biomarkers such as IL-3 and IL-13. These plasma protein clusters could have potential applications for improved phenotypic characterization of volunteers in nutritional intervention studies or as biomarkers in the early detection of obesity-linked disease development and progression.