Attenuating Effect of Vigorous Physical Activity on the Risk for Inherited Obesity: A Study of 47,691 Runners

Objective: Physical activity has been shown to attenuate the effect of the FTO polymorphism on body weight, and the heritability of body weight in twin and in family studies. The dose-response relationship between activity and the risk for inherited obesity is not well known, particularly for higher doses of vigorous exercise. Such information is needed to best prescribe an exercise dose for obesity prevention in those at risk due to their family history. Design: We therefore analyzed self-reported usual running distance, body mass index (BMI), waist circumference, and mother’s and father’s adiposity (1 = lean, 2 = normal, 3 = overweight, and 4 = very overweight) from survey data collected on 33,480 male and 14,211 female runners. Age-, education-, and alcohol-adjusted regression analyses were used to estimate the contribution of parental adiposities to the BMI and waist circumferences in runners who ran an average of,3, 3–6, 6–9, $9 km/day. Results: BMI and waist circumferences of runners who ran,3 km/day were significantly related to their parents adiposity (P,10 215 and P,10 211, respectively). These relationships (i.e., kg/m 2 or cm per increment in parental adiposity) diminished significantly with increasing running distance for both BMI (inheritance6exercise interaction, males: P,10 210; females: P,10 25) and waist circumference (inheritance6exercise interaction, males: P,10 29; females: P = 0.004). Compared to,3 km/day, the parental contribution to runners who averaged$9 km/day was diminished by 48 % for male BMI, 58 % for female BMI, 55 % for male waist circumference, and 58 % for female waist circumference. These results could not b

FOXO Regulates Organ-Specific Phenotypic Plasticity In Drosophila

Phenotypic plasticity, the ability for a single genotype to generate different phenotypes in response to environmental conditions, is biologically ubiquitous, and yet almost nothing is known of the developmental mechanisms that regulate the extent of a plastic response. In particular, it is unclear why some traits or individuals are highly sensitive to an environmental variable while other traits or individuals are less so. Here we elucidate the developmental mechanisms that regulate the expression of a particularly important form of phenotypic plasticity: the effect of developmental nutrition on organ size. In all animals, developmental nutrition is signaled to growing organs via the insulin-signaling pathway. Drosophila organs differ in their size response to developmental nutrition and this reflects differences in organ-specific insulin-sensitivity. We show that this variation in insulin-sensitivity is regulated at the level of the forkhead transcription factor FOXO, a negative growth regulator that is activated when nutrition and insulin signaling are low. Individual organs appear to attenuate growth suppression in response to low nutrition through an organ-specific reduction in FOXO expression, thereby reducing their nutritional plasticity. We show that FOXO expression is necessary to maintain organ-specific differences in nutritional-plasticity and insulin-sensitivity, while organ-autonomous changes in FOXO expression are sufficient to autonomously alter an organ's nutritional-plasticity and insulin-sensitivity. These data identify a gene (FOXO) that modulates a plastic response through variation in its expression. FOXO is recognized as a key player in the response of size, immunity, and longevity to changes in developmental nutrition, stress, and oxygen levels. FOXO may therefore act as a more general regulator of plasticity. These data indicate that the extent of phenotypic plasticity may be modified by changes in the expression of genes involved in signaling environmental information to developmental processes

Response to first-line treatment and histology are associated with achieving complete remission after the first salvage high-dose chemotherapy in relapsing germ cell tumor patients

Sequential high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is a curative option in relapsing germ cell tumor (GCT) patients, and complete remission (CR) after the first ASCT (early CR2) is associated with favorable outcome. Prognostic factors predicting early CR2 have not been investigated so far. We analyzed consecutive patients with a first relapse of GCT treated with three sequential cycles of carboplatin/etoposide-based HDCT with ASCT in the two largest academic centers in Switzerland. The cohort comprised 96 relapsing GCT patients, with 19 (19.8%) patients achieving early CR2 after the first HDCT cycle. The median progression-free survival and overall survival were not reached in patients achieving early CR2, whereas they were 9.6 months (P = 0.0301) and 34.8 months (P = 0.0684) for patients missing early CR2. Patients with early CR2 more often had CR1 after first-line bleomycin, etoposide, and cisplatin chemotherapy (68.4 vs. 31.6%; P = 0.0037) and an interval longer than 2 years between initial diagnosis and first HDCT (36.8 vs. 15.6%; P = 0.0373), but less often a histology of mixed nonseminomatous tumor (46.8 vs. 21.1%; P = 0.0418). These data suggest that response to first-line chemotherapy, late relapse, and histology are associated with achieving early CR2 after a first HDCT with ASCT in relapsing GCT patients

A hybrid life cycle assessment of public transportation buses with alternative fuel options

Purpose: Alternative fuel options are gaining popularity in the vehicle market. Adopting alternative fuel options for public transportation compared to passenger vehicles contributes exponentially to reductions in transportation-related environmental impacts. Therefore, this study aims to present total air pollutant emissions and water withdrawal impacts through the lifetime of a transit bus with different fuel options. Methods: In consideration of market share and future development trends, diesel, biodiesel, compressed natural gas (CNG), liquefied natural gas (LNG), hybrid (diesel-electric), and battery electric (BE) transit buses are analyzed with an input-output (IO)-based hybrid life cycle assessment (LCA) model. In order to accommodate the sensitivity of total impacts to fuel economy, three commonly used driving cycles are considered: Manhattan, Central Business District (CBD), and Orange County Transit Authority (OCTA). Fuel economy for each of these driving cycles varies over the year with other impacts, so a normal distribution of fuel economy is developed with a Monte Carlo simulation model for each driving cycle and corresponding fuel type. Results and discussion: Impacts from a solar panel (photovoltaic, PV) charging scenario and different grid mix scenarios are evaluated and compared to the nation’s average grid mix impacts from energy generation to accommodate the lifetime electricity needs for the BE transit bus. From these results, it was found that the BE transit bus causes significantly low CO2 emissions than diesel and other alternative fuel options, while some of the driving cycles of the hybrid-powered transit bus cause comparable emissions to BE transit bus. On the other hand, lifetime water withdrawal impacts of the diesel and hybrid options are more feasible compared to other options, since electricity generation and natural gas manufacturing are both heavily dependent on water withdrawal. In addition, the North American Electricity Reliability Corporation’s (NERC) regional electricity grid mix impacts on CO2 emissions and water withdrawal are presented for the BE transit bus. Conclusions: As an addition of current literature, LCA of alternative fuel options was performed in this paper for transit buses with the consideration of a wide variety of environmental indicators. Although the results indicate that BE and hybrid-powered buses have less environmental emissions, the US’s dependency on fossil fuel for electricity generation continues to yield significant lifetime impacts on BE transit bus operation. With respect to water withdrawal impacts, we believe that the adoption of BE transit buses will be faster and more environmentally feasible for some NREC regions than for others