Abstract: Growth and body size of mammals are commonly correlated with many life history strategies, including those related to survival and reproduction. However, in certain circumstances suboptimal growth rates and smaller size may be advantageous and adaptive. The water vole Arvicola amphibius is a large vole, about three times the size of a field vole Microtus agrestis, but with similar ecological and reproductive characteristics. Island populations were studied on the coast of northern Norway, just below the Arctic Circle, during 2003-2018, by capture-mark-recapture. The main aims were to study growth rates, asymptotic weight and survival, expecting that the “optimal” weight for surviving the winter would be 140-160 g. The smallest juveniles caught weighed only 21 g and were assumed, based on data from the literature, to be around 14 days old. This age was used as starting point for the growth curve. This, however, may have been about one week too early, as juveniles are more likely not fully weaned and leave their nest of birth until 30-40 g. Initial growth rates in juveniles was relatively high but declined from around 100-120 g or 40-50 days old. The asymptotic weight was not clearly defined, but its maximum was around 150-160 g. Most juveniles that survived the winter weighed between 100 and 160 g in their first summer. Large individual variations in growth rates were found. Overwintered subadults in spring weighed about the same as juveniles did in the autumn but grew quickly in April and May to reach adult size. A specific “optimal” weight for juveniles that survived the winter was not found. The range could be given as 100-160 g, too broad to define an “optimal” weight range. However, those that survived tended to be slightly heavier than those that died. Reproducing adults generally weighed 180-220 g and did not reduce their weight toward the autumn, i.e., to increase winter survival, but very few adults survived even the summer and almost none survived their second winter. Juveniles postponed reproduction until next spring, most likely to take advantage of fresh vegetation growth and less competition.
Abstract: Growth and body size of mammals are commonly correlated with many life history strategies, including those related to survival and reproduction. However, in certain circumstances suboptimal growth rates and smaller size may be advantageous and adaptive. The water vole Arvicola amphibius is a large vole, about three times the size of a field vole Mi...Show More
Abstract: Objective: Curcumin has been widely used in rheumatoid arthritis (RA) treatment and the previous study also proved its effectiveness. However, the pharmacological mechanism is still not clear. The current study intends to discuss the potential mechanism of action of curcumin in RA treatment through machine learning, network pharmacology, molecular dynamics and cellular experiments.Methods: RA-related microarray data were obtained from three GEO datasets: GSE55235, GSE55457 and GSE77298. Machine learning methods including XGBOOST, LASSO and SVM were adopted to screen out potential targets of RA pathogenesis. Online tools SwissTargetPrediction and Similarity ensemble approach were visited to predict potential targets of action of curcumin. The key target was identified via a Venn diagram and processed for molecular docking and molecular dynamics simulation with curcumin. Fibroblast-like synoviocytes (RA-FLSs) were selected to study the effect of curcumin at different concentrations (20, 40 and 80 μmol/L) on cell proliferation and apoptosis using MTT and flow cytometry assays. In addition, Western blot was used to examine the protein level.Results: Arachidonate 5-Lipoxygenase (ALOX5) was identified as a key target of RA following bioinformatics prediction. Results of molecular docking and molecular dynamics simulation demonstrated the tight binding between curcumin and ALOX5 with stable function. RA-FLSs intervened with different concentrations of curcumin (20, 40 and 80 mol/L) exhibited decreased potential in proliferation while increased apoptosis, which were in a dose-dependent manner. Additionally, with the increase of curcumin concentration, the protein level of ALOX5 gradually decreased. Conclusion: Curcumin may exert its therapeutic effects in RA treatment via down-regulating the expression of ALOX5.
Abstract: Objective: Curcumin has been widely used in rheumatoid arthritis (RA) treatment and the previous study also proved its effectiveness. However, the pharmacological mechanism is still not clear. The current study intends to discuss the potential mechanism of action of curcumin in RA treatment through machine learning, network pharmacology, molecular ...Show More