Solvable senescence model with positive mutations

We build upon our previous analytical results for the Penna model of senescence to include positive mutations. We investigate whether a small but non-zero positive mutation rate gives qualitatively different results to the traditional Penna model in which no positive mutations are considered. We find that the high-lifespan tail of the distribution is radically changed in structure, but that there is not much effect on the bulk of the population. Th e mortality plateau that we found previously for a stochastic generalization of the Penna model is stable to a small positive mutation rate.Comment: 3 figure

The propensity for consuming ethanol in Drosophila requires rutabaga adenylyl cyclase expression within mushroom body neurons

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92421/1/GBB_810_sm_FS1-5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/92421/2/j.1601-183X.2012.00810.x.pd

Semi-Autonomous Rodent Habitat for Deep Space Exploration

NASA has flown animals to space as part of trailblazing missions and to understand the biological responses to spaceflight. Mice traveled in the Lunar Module with the Apollo 17 astronauts and now mice are frequent research subjects in LEO on the ISS. The ISS rodent missions have focused on unravelling biological mechanisms, better understanding risks to astronaut health, and testing candidate countermeasures. A critical barrier for longer-duration animal missions is the need for humans-in-the-loop to perform animal husbandry and perform routine tasks during a mission. Using autonomous or telerobotic systems to alleviate some of these tasks would enable longer-duration missions to be performed at the Deep Space Gateway. Rodent missions performed using the Gateway as a platform could address a number of critical risks identified by the Human Research Program (HRP), as well as Space Biology Program questions identified by NRC Decadal Survey on Biological and Physical Sciences in Space, (2011). HRP risk areas of potentially greatest relevance that the Gateway rodent missions can address include those related to visual impairment (VIIP) and radiation risks to central nervous system, cardiovascular disease, as well as countermeasure testing. Space Biology focus areas addressed by the Gateway rodent missions include mechanisms and combinatorial effects of microgravity and radiation. The objectives of the work proposed here are to 1) develop capability for semi-autonomous rodent research in cis-lunar orbit, 2) conduct key experiments for testing countermeasures against low gravity and space radiation. The hardware and operations system developed will enable experiments at least one month in duration, which potentially could be extended to one year in duration. To gain novel insights into the health risks to crew of deep space travel (i.e., exposure to space radiation), results obtained from Gateway flight rodents can be compared to ground control groups and separate groups of mice exposed to simulated Galactic Cosmic Radiation (at the NASA Space Radiation Lab). Results can then be compared to identical experiments conducted on the ISS. Together results from Gateway, ground-based, and ISS rodent experiments will provide novel insight into the effects of space radiation

Multivariate character process models for the analysis of two or more correlated function-valued traits

Various methods, including random regression, structured antedependence models, and character process models, have been proposed for the genetic analysis of longitudinal data and other function-valued traits. For univariate problems, the character process models have been shown to perform well in comparison to alternative methods. The aim of this article is to present an extension of these models to the simultaneous analysis of two or more correlated function-valued traits. Analytical forms for stationary and nonstationary cross-covariance functions are studied. Comparisons with the other approaches are presented in a simulation study and in an example of a bivariate analysis of genetic covariance in age-specific fecundity and mortality in Drosophila. As in the univariate case, bivariate character process models with an exponential correlation were found to be quite close to first-order structured antedependence models. The simulation study showed that the choice of the most appropriate methodology is highly dependent on the covariance structure of the data. The bivariate character process approach proved to be able to deal with quite complex nonstationary and nonsymmetric cross-correlation structures and was found to be the most appropriate for the real data example of the fruit fly Drosophila melanogaster

Rodent Research Development for Long Duration Studies on the International Space Station

Rodent research in space is needed to advance our understanding of the health risks,consequences and possible countermeasures to protect crew during future, long duration missions. TheAnimal Enclosure Module (AEM) was designed originally to support habitation of rats and mice onrelatively short duration, Shuttle missions (<19 days). The AEM was flown previously on 27 SpaceShuttle missions, and recently was modified extensively to support future long duration space biology andbiomedical research on the International Space Station (ISS). In consultation with a Science WorkingGroup comprised of veterinarians and investigators experienced in rodent spaceflight experimentation inspace, the Rodent Habitat project team at Ames Research Center modified existing hardware, developednew hardware, operations, and science activities, and performed a series of ground-based operational andscience habitat verification tests in preparation for the first validation flight

Advances in Rodent Research Missions on the International Space Station

A Research platform for rodent experiment on the ISS is an essential tool for advancing biomedical research in space. The Rodent Research allows for experiments of much longer duration that experiments on the Shuttle. NASAs Rodent Research (RR)-1 mission was successfully completed, including post-flight analysis and achieved a number of objectives including validation of flight hardware, on-orbit operations, and science capabilities that were developed at the NASA Ames Research Center. Briefly, twenty C57BL/6J adult female mice were launched on the SpX4 Dragon vehicle, which thrived for up to 37 days in microgravity. Daily health checks of the mice were performed during the mission via downlinked video; all animals were healthy and displayed normal behavior without any significant signs of stress. Behavioral analysis demonstrated that Flight and Ground Control mice exhibited the same range of behaviors, including eating, drinking, exploratory behavior, self- and allo-grooming, and social interactions indicative of healthy animals. The animals were euthanized and select tissues were collected from some of the mice on orbit to assess the long-term sample storage capabilities of the ISS. The data obtained from the flight mice were comparable to those from the 3 groups of control mice (baseline, vivarium and ground controls), suggesting that the ISS has adequate capability to support long-duration rodent experimentations. We recovered over 35 tissues from 40 RR1 frozen carcasses, yielded over 3200 aliquots of tissues, and distributed to the scientific community, including NASAs GeneLab and scientists in the U.S. through Biospecimen Sharing Program via Ames Life Science Data Archive. Tissues were also distributed to Russian research colleagues at the Institute for Biomedical Problems. The expression levels of select genes including albumin, catalase, GAPDH, HMGCoA Reductase, and IGF1 were determined using RNA isolated from the livers by qPCR and no significant differences by one factor ANOVA were found between flight and ground control groups. In addition, some of the liver samples were subject to transcriptomics, epigenomics and proteomics. The data are now available to the scientific community through GeneLabs open science data website. Since the RR1 mission, another long duration mission (Rodent Research-2) was completed on the ISS in 2015 in which 20 female C57 BL/6J mice were successfully maintained on the ISS for varying time points, with the last group of 5 animals being on-orbit for 54 days. This second Rodent Research flight expanded the programs capabilities with the introduction of new technologies including blood collection and separation and bone densitometry scanning. Furthermore, we have continued to expand the ISSs capabilities by running a series of ground-based verification testing using male mice. Our next step is to fly male mice for Rodent Research-4 on SpaceX-10 to study the effects of microgravity on bone healing and regeneration. It will be the first long-duration mission using male mice using Rodent Hardware. In addition, the number of mice will increase from 20 mice (on RR-1 and RR-2) to 40 for RR-4. When samples return to Earth, a number of tissues will be dissected from the frozen carcasses and select tissue samples will become available to the scientific community via BSP. Altogether, we have continued to expand our capabilities for performing long-duration missions on the ISS as emphasized in the National Research Councils Decadal Survey released in 2011 and to maximize science return from each mission

Analytical solution of a generalized Penna model

In 1995 T.J.Penna introduced a simple model of biological aging. A modified Penna model has been demonstrated to exhibit behaviour of real-life systems including catastrophic senescence in salmon and a mortality plateau at advanced ages. We present a general steady-state, analytic solution to the Penna model, able to deal with arbitrary birth and survivability functions. This solution is employed to solve standard variant Penna models studied by simulation. Different Verhulst factors regulating both the birth rate and external death rate are considered.Comment: 6 figure

Associations of Blood Pressure and&nbsp;Cholesterol Levels During Young&nbsp;Adulthood With Later&nbsp;Cardiovascular Events.

BackgroundBlood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified.ObjectiveThe authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures.MethodsThe authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke.ResultsA total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL&nbsp;≥100&nbsp;mg/dl (compared with&nbsp;&lt;100&nbsp;mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP&nbsp;≥130&nbsp;mm&nbsp;Hg (compared with&nbsp;&lt;120&nbsp;mm&nbsp;Hg) was associated with a 37% increased risk for HF, and young adult DBP&nbsp;≥80&nbsp;mm&nbsp;Hg (compared with&nbsp;&lt;80&nbsp;mm&nbsp;Hg) was associated with a 21% increased risk.ConclusionsCumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with&nbsp;increased CVD risks in later life, independent of later adult exposures

Nighttime Blood Pressure Dipping in Young Adults and Coronary Artery Calcium 10-15 Years Later: The Coronary Artery Risk Development in Young Adults Study

Nighttime blood pressure (BP) dipping can be quantified as the ratio of mean nighttime (sleep) BP to mean daytime (awake) BP. People whose dipping ratio is 0.90 have been referred to as nondippers, and nondipping is associated with cardiovascular disease events. We examined the relationship between systolic nighttime BP dipping in young adults and presence of coronary artery calcium (CAC) 10-15 years later using data from the ambulatory BP monitoring substudy of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Among 239 participants with adequate measures of both nighttime and daytime readings and coronary artery calcium, the systolic BP dipping ratio ranged from 0.72 to 1.24 (mean 0.88, SD 0.06), and CAC was present 10 to 15 years later in 54 participants (22.6%). Compared to those whose systolic BP dipping ratio ranged from 0.88 to 0.92 (Quartile 3), the 57 participants (23.9%) with less pronounced or absent dipping (ratio 0.92 to 1.24, Quartile 4) had an unadjusted odds ratio of 4.08 (95% CI 1.48-11.2) for presence of CAC. The 60 participants (25.1%) with a more pronounced dipping (ratio 0.72 to 0.85, Quartile 1) also had greater odds for presence of CAC (OR 4.76; 95% CI 1.76-12.9). When modeled as a continuous predictor, a U-shaped relationship between systolic BP dipping ratio and future CAC was apparent, and persisted after adjustment for multiple potential confounders (