Mathematical modelling of autophagy pathway.

A system modelling autophagy is a new area of research. Current understanding of each step in this biochemical pathway is limited. The study of this mechanism is interesting in several aspects: autophagy plays an important role in physiological cellular processes, is a survival mechanism under external stress and is also connected with cancer and neurodegenerative diseases [Cuervo, 2004; Kondo et al., 2005; Levine, 2007; Pan et al., 2008]. Autophagy is the pathway for degradation of redundant or faulty cell components. This important mechanism occurs in all eukaryotic cells as a part of cell’s everyday activities and plays an important role in cell growth and development (cellular differentiation, immunity, cellular homeostasis). This work proposes a simple mathematical model of autophagy pathway as a system with feedback, which controls the level of the total amino acid pool. Feedback comes from the amino acids which are produced during the autophagy mechanism which is induced as a result of starvation or rapamycin treatment

Chlorophyll fluorescence in two strawberry (Fragaria x ananassa Duch.) cultivars

The study of chlorophyll fluorescence (CF) parameters conducted in two strawberry. Measurements of their values were done twice: in an early autumn and late spring. Fluorescence of five dark-adapted mature leaves derived from each was measured in the laboratory at room temperature with the use of a portable pulse amplitude modulation (PAM) in 15. replicates for each parameter. Statistical analysis of the obtained results showed significant differences between values of CF parameters in both

The effects of prostaglandin E-2 treatment on the secretory function of mare corpus luteum depends on the site of application : an in vivo study

Research Areas: Veterinary SciencesWe examined the effect of prostaglandin (PG) E2 on the secretory function of equine corpus luteum (CL), according to the application site: intra-CL injection vs. an intrauterine (intra-U) administration. Moreover, the effect of intra-CL injection vs. intra-U administration of both luteotropic factors: PGE2 and human chorionic gonadotropin (hCG) as a positive control, on CL function was additionally compared. Mares were assigned to the groups (n = 6 per group): (1) an intra-CL saline injection (control); (2) an intra-CL injection of PGE2 (5 mg/ml); (3) an intra-CL injection of hCG (1,500 IU/ml); (4) an intra-U saline administration (control); (5) an intra-U administration of PGE2 (5 mg/5 ml); (6) an intra-U administration of hCG (1,500 IU/5 ml). Progesterone (P4) and PGE2 concentrations were measured in blood plasma samples collected at −2, −1, and 0 (pre-treatment), and at 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after treatments. Moreover, effects of different doses of PGE2 application on the concentration of total PGF2α (PGF2α and its main metabolite 13,14-dihydro-15-keto-prostaglandin F2α– PGFM) was determined. The time point of PGE2, hCG, or saline administration was defined as hour “0” of the experiment. An intra-CL injection of PGE2 increased P4 and PGE2 concentrations between 3 and 4 h or at 3 and 12 h, respectively (p < 0.05). While intra-U administration of PGE2 elevated P4 concentrations between 8 and 24 h, PGE2 was upregulated at 1 h and between 3 and 4 h (p < 0.05). An intra-CL injection of hCG increased P4 concentrations at 1, 6, and 12 h (p < 0.05), while its intra-U administration enhanced P4 and PGE2 concentrations between 1 and 12 h or at 3 h and between 6 and 10 h, respectively (p < 0.05). An application of PGE2, dependently on the dose, supports equine CL function, regardless of the application site, consequently leading to differences in both P4 and PGE2 concentrations in blood plasmainfo:eu-repo/semantics/publishedVersio

Quantifying the impact of novel metastatic cancer therapies on health inequalities in survival outcomes

Background: Novel therapies in metastatic cancers have contributed to improvements in survival outcomes, yet real-world data suggest that improvements may be mainly driven by those patient groups who already had the highest survival outcomes. This study aimed to develop and apply a framework for quantifying the impact of novel metastatic cancer therapies on health inequalities in survival outcomes based on published aggregate data.Methods: Nine (N = 9) novel therapies for metastatic breast cancer (mBC), metastatic colorectal cancer (mCRC), and metastatic non–small cell lung cancer (mNSCLC) were identified, 3 for each cancer type. Individual patient data (IPD) for overall survival (OS) and progression-free survival (PFS) were replicated from published Kaplan-Meier (KM) curves. For each cancer type, data were pooled for the novel therapies and comparators separately and weighted based on sample size to ensure equal contribution of each therapy in the analyses. Parametric (mixture) distributions were fitted to the weighted data to model and extrapolate survival. The inequality in survival was defined by the absolute difference between groups with the highest and lowest survival for 2 stratifications: one for which survival was stratified into 2 groups and one using 5 groups. Additionally, a linear regression model was fitted to survival estimates for the 5 groups, with the regression coefficient or slope considered as the inequality gradient (IG). The impact of the pooled novel therapies was subsequently defined as the change in survival inequality relative to the pooled comparator therapies. A probabilistic analysis was performed to quantify parameter uncertainty.Results: The analyses found that novel therapies were associated with significant increases in inequalities in survival outcomes relative to their comparators, except in terms of OS for mNSCLC. For mBC, the inequalities in OS increased by 13.9 (95% CI: 1.4; 26.6) months, or 25.0%, if OS was stratified in 5 groups. The IG for mBC increased by 3.2 (0.3; 6.1) months, or 24.7%. For mCRC, inequalities increased by 6.7 (3.0; 10.5) months, or 40.4%, for stratification based on 5 groups; the IG increased by 1.6 (0.7; 2.4) months, or 40.2%. For mNSCLC, inequalities decreased by 14.9 (−84.5; 19.0) months, or 12.2%, for the 5-group stratification; the IG decreased by 2.0 (−16.1; 5.1) months, or 5.5%. Results for the stratification based on 2 groups demonstrated significant increases in OS inequality for all cancer types. In terms of PFS, the increases in survival inequalities were larger in a relative sense compared with OS. For mBC, PFS inequalities increased by 8.7 (5.9; 11.6) months, or 71.7%, for stratification based on 5 groups; the IG increased by 2.0 (1.3; 2.6) months, or 67.6%. For mCRC, PFS inequalities increased by 5.4 (4.2; 6.6) months, or 147.6%, for the same stratification. The IG increased by 1.3 (1.1; 1.6) months, or 172.7%. For mNSCLC, inequalities increased by 18.2 (12.5; 24.4) months, or 93.8%, for the 5-group stratification; the IG increased by 4.0 (2.8; 5.4) months, or 88.1%. Results from the stratification based on 2 groups were similar.Conclusion: Novel therapies for mBC, mCRC, and mNSCLC are generally associated with significant increases in survival inequalities relative to their comparators in randomized controlled trials, though inequalities in OS for mNSCLC decreased nonsignificantly when stratified based on 5 groups. Although further research using real-world IPD is warranted to assess how, for example, social determinants of health affect the impact of therapies on health inequalities among patient groups, the proposed framework can provide important insights in the absence of such data

Periodization and self-regulation in action sports: Coping with the emotional load

Action sports usually include some danger and personal challenge. The levels of both are often further increased when the sport is placed in a competitive environment. In this paper, we consider the Olympic disciplines of freeskiing and snowboarding in park and pipe. We consider some pertinent theoretical perspectives, then offer some insights on their operation using a range of data from ongoing research and support work. Finally, we offer a number of practical steps which can be taken to optimize performance, both in learning and practicing new tricks and in executing them under the pressures of competition