Project description:Myostatin (MSTN) and growth and differentiation factor-11 (GDF-11) are highly related TGF-β family members that have distinct biological functions. MSTN is expressed primarily in skeletal muscle and acts to limit muscle growth. GDF-11 is expressed more widely and plays multiple roles, including regulating axial skeletal patterning during development. Several MSTN and GDF-11 binding proteins have been identified, including GDF-associated serum protein-1 (GASP-1) and GASP-2, which are capable of inhibiting the activities of these ligands. Here, we show that GASP-1 and GASP-2 act by blocking the initial signaling event (namely, the binding of the ligand to the type II receptor). Moreover, we show that mice lacking Gasp1 and Gasp2 have phenotypes consistent with overactivity of MSTN and GDF-11. Specifically, we show that Gasp2(-/-) mice have posteriorly directed transformations of the axial skeleton, which contrast with the anteriorly directed transformations seen in Gdf11(-/-) mice. We also show that both Gasp1(-/-) and Gasp2(-/-) mice have reductions in muscle weights, a shift in fiber type from fast glycolytic type IIb fibers to fast oxidative type IIa fibers, and impaired muscle regeneration ability, which are the reverse of what are seen in Mstn(-/-) mice. All of these findings suggest that both GASP-1 and GASP-2 are important modulators of GDF-11 and MSTN activity in vivo.
Project description:Mood can influence behaviour and consumer choice in diverse settings. We found that such cognitive influences extend to candidate admission interviews at a Canadian medical school. We suggest that an awareness of this fallibility might lead to more reasonable medical school admission practices.
Project description:Growth and differentiation factor Associated Serum Protein (GASP) 1 and 2 are proteins known to be involved in the control of myostatin activity at least in vitro. Most deuterostome GASPs share a modular organization including WAP, follistatin/kazal, IGc2, two kunitz, and NTR domains. Based on an exon shuffling model, we performed independent phylogenetic analyses on these modules and assessed that papilin is probably a sister sequence to GASP with a divergence date estimated from the last common ancestor to bilateria. The final organization was acquired by the addition of the FS domain in early deuterostomes. Our study revealed that Gasp genes diverged during the first round of genome duplication in early vertebrates. By evaluating the substitution rate at different sites on the proteins, we showed a better conservation of the follistatin/kazal domain of GASP1 than GASP2 in mammals, suggesting a stronger interaction with myostatin. We also observed a progressive increase in the conservation of follistatin and kunitz domains from the ancestor of Ciona to early vertebrates. In situ hybridization performed on mouse embryos showed a weak Gasp1 expression in the formed somites at 10.5 dpc and in limb buds from embryonic E10.0 to E12.5. Similar results were obtained for zebrafish embryos. We propose a synthetic view showing possible interactions between GASP1 and myostatin and highlighting the role of the second kunitz domain in preventing myostatin proteolysis.
Project description:BackgroundUnfavourable changes occur in children's health behaviours and outcomes during the summer holidays. This systematic review aimed to determine the effectiveness of summer holiday programs in mitigating these changes.MethodsSix databases (MEDLINE, JBI, PsychINFO, Embase, ERIC and Scopus) were systematically searched for experimental controlled studies that investigated programs of at least 5 days' duration conducted exclusively during the summer holiday period on school-aged children (5-18 years). Primary outcomes were moderate-vigorous physical activity and energy intake. Secondary outcomes were sedentary behavior, diet quality, adiposity, and cardiorespiratory fitness. Risk of Bias was assessed using the PEDro tool. Effect sizes were calculated using random-effects meta-analysis with narrative synthesis of effects by student or program characteristics.ResultsTen studies (two randomised controlled trials, and eight non-randomised controlled trials) involving 1,446 participants were included. Summer programs had a significant moderate effect on reducing sedentary behaviour (g= -0.59, 95%CI= -1.16, -0.03) and significant small effects on improving moderate-to-vigorous physical activity (g = 0.35, 95%CI = 0.02, 0.67) and adiposity (g= -0.25, 95% CI = -0.39, -0.10). No significant change was detected for cardiorespiratory fitness (g = 0.43, 95%CI= -0.32, 1.17), energy intake (g= -0.06, 95% CI -2.33, 2.22), or diet quality (g = 0.20, 95%CI= -0.43, 0.83). Summer program effectiveness did not appear to differ by child sociodemographic or program characteristics. Concerns regarding bias and high heterogeneity impacted results.ConclusionsSummer programs show potential in promoting healthier movement behaviours in children and supporting healthy body weight during the summer months. Although evidence from the included studies has limitations, these programs produced small to moderate effect sizes and present promising health intervention opportunities for children. Future research with more rigorous study designs and comprehensive reporting is needed to confirm these findings and better understand the impact of summer programs on children's health.Prospero registrationCRD42023409795.
Project description:Osteoporosis related fractures contribute to morbidity and mortality in U.S. patients, placing a heavy financial burden on society. Randomized clinical trials involving over 30,000 subjects have established bisphosphonates' efficacy in reducing the incidence of fragility fractures. However, as bisphosphonates are retained for years in the skeleton, reports of adverse events from prolonged use are surfacing in the literature, namely, esophageal cancer, atrial fibrillation, osteonecrosis of the jaw, and atypical fracture development. The concept of a drug holiday has been proposed to potentially reduce incidence of these adverse events. This review will highlight the benefits and risks of bisphosphonate therapy and discuss the extension data available from the bisphosphonate trials. As randomized clinical trial evidence is not yet available on who may qualify for drug holiday, this review will provide suggestions for clinicians on identification of possible candidates and monitoring during a bisphosphonate drug holiday.
Project description:Anthropogenic emissions are generally lower during holidays than they are on workdays, this pattern is expected to result in temperature variations. Variations in the daily maximum (Tmax), mean (Tmean) and minimum (Tmin) air temperatures and the diurnal temperature range (DTR) during the Chinese New Year holiday are evaluated with two methods using daily meteorological observations collected at 2200 stations in China from 1961 to 2015. These two methods yield nearly equivalent results that reflect strong variations in the defined holiday effects. During the period from 1961 to 1980, Tmean, Tmax, Tmin and the DTR all exhibit cooling holiday effects, this effect as measured by the DTR disappears during the period from 1981 to 2000. However, during the period from 2001 to 2015 warming holiday effects are observed for Tmax and the DTR. The evaluation shows that the holiday effect is neither unique nor statistically significant. These results indicate that the holiday effect is primarily caused by natural atmospheric oscillations, because ΔT oscillates noticeably with periods of approximately 7.1 days, 8.5 days and 16.2 days, and these oscillations can account for approximately 75.6% of the variance in ΔT. The oscillation identified here is consistent with the fundamental theory of Rossby wave in the atmosphere.