Maternal inflammation at 0.7 gestation in ewes leads to intrauterine growth restriction and impaired glucose metabolism in offspring at 30 d of age

Fetal programming associated with intrauterine growth restriction (IUGR) leads to lifelong deficits in growth and metabolic function (Hales and Barker, 2013). IUGR arises when fetuses respond to poor in utero conditions by developing adaptations that repartition nutrients to critical tissues and away from skeletal muscle (Yates et al., 2012, 2018). This fetal programming is beneficial in utero but leads to persistent reductions in muscle mass and glucose homeostasis in offspring (DeFronzo et al., 1981). Recent studies by our laboratory in sheep and rats demonstrate that maternal inflammation during gestation induces fetal inflammatory adaptations that impair growth and disrupt muscle glucose metabolism (Cadaret et al., 2017, 2018). IUGR fetal skeletal muscle exhibits indicators of enhanced inflammatory sensitivity, which could disrupt glucose uptake and oxidation (Yates et al., 2016; Cadaret et al., 2018). Enhanced inflammatory responsiveness would help explain growth and metabolic deficits observed in IUGR offspring. We hypothesize that fetal programming induced by maternal inflammation persists in offspring and contributes to impaired growth and glucose metabolism at 30 d. Therefore, the objective of this study was to determine whether sustained maternal inflammation induced by bacterial endotoxin at 0.7 gestation leads to fetal programming that contributes to deficits in growth and glucose metabolism in offspring

Analysis of Diffusion of Ras2 in Saccharomyces cerevisiae Using Fluorescence Recovery after Photobleaching

Binding, lateral diffusion and exchange are fundamental dynamic processes involved in protein association with cellular membranes. In this study, we developed numerical simulations of lateral diffusion and exchange of fluorophores in membranes with arbitrary bleach geometry and exchange of the membrane localized fluorophore with the cytosol during Fluorescence Recovery after Photobleaching (FRAP) experiments. The model simulations were used to design FRAP experiments with varying bleach region sizes on plasma-membrane localized wild type GFP-Ras2 with a dual lipid anchor and mutant GFP-Ras2C318S with a single lipid anchor in live yeast cells to investigate diffusional mobility and the presence of any exchange processes operating in the time scale of our experiments. Model parameters estimated using data from FRAP experiments with a 1 micron x 1 micron bleach region-of-interest (ROI) and a 0.5 micron x 0.5 micron bleach ROI showed that GFP-Ras2, single or dual lipid modified, diffuses as single species with no evidence of exchange with a cytoplasmic pool. This is the first report of Ras2 mobility in yeast plasma membrane. The methods developed in this study are generally applicable for studying diffusion and exchange of membrane associated fluorophores using FRAP on commercial confocal laser scanning microscopes.Comment: Accepted for publication in Physical Biology (2010). 28 pages, 7 figures, 3 table

Boundary Avoidance Tracking for Instigating Pilot Induced Oscillations

In order to advance research in the area of pilot induced oscillations, a reliable method to create PIOs in a simulated environment is necessary. Using a boundary avoidance tracking task, researchers performing an evaluation of control systems were able to create PIO events in 42% of cases using a nominal aircraft, and 91% of cases using an aircraft with reduced actuator rate limits. The simulator evaluation took place in the NASA Ames Vertical Motion Simulator, a high-fidelity motion-based simulation facility

Cumulative Burden of Morbidity Among Testicular Cancer Survivors After Standard Cisplatin-Based Chemotherapy: A Multi-Institutional Study

Purpose In this multicenter study, we evaluated the cumulative burden of morbidity (CBM) among > 1,200 testicular cancer survivors and applied factor analysis to determine the co-occurrence of adverse health outcomes (AHOs). Patients and Methods Participants were ≤ 55 years of age at diagnosis, finished first-line chemotherapy ≥ 1 year previously, completed a comprehensive questionnaire, and underwent physical examination. Treatment data were abstracted from medical records. A CBM score encompassed the number and severity of AHOs, with ordinal logistic regression used to assess associations with exposures. Nonlinear factor analysis and the nonparametric dimensionality evaluation to enumerate contributing traits procedure determined which AHOs co-occurred. Results Among 1,214 participants, approximately 20% had a high (15%) or very high/severe (4.1%) CBM score, whereas approximately 80% scored medium (30%) or low/very low (47%). Increased risks of higher scores were associated with four cycles of either ifosfamide, etoposide, and cisplatin (odds ratio [OR], 1.96; 95% CI, 1.04 to 3.71) or bleomycin, etoposide, and cisplatin (OR, 1.44; 95% CI, 1.04 to 1.98), older attained age (OR, 1.18; 95% CI, 1.10 to 1.26), current disability leave (OR, 3.53; 95% CI, 1.57 to 7.95), less than a college education (OR, 1.44; 95% CI, 1.11 to 1.87), and current or former smoking (OR, 1.28; 95% CI, 1.02 to 1.63). CBM score did not differ after either chemotherapy regimen ( P = .36). Asian race (OR, 0.41; 95% CI, 0.23 to 0.72) and vigorous exercise (OR, 0.68; 95% CI, 0.52 to 0.89) were protective. Variable clustering analyses identified six significant AHO clusters (χ2 P < .001): hearing loss/damage, tinnitus (OR, 16.3); hyperlipidemia, hypertension, diabetes (OR, 9.8); neuropathy, pain, Raynaud phenomenon (OR, 5.5); cardiovascular and related conditions (OR, 5.0); thyroid disease, erectile dysfunction (OR, 4.2); and depression/anxiety, hypogonadism (OR, 2.8). Conclusion Factors associated with higher CBM may identify testicular cancer survivors in need of closer monitoring. If confirmed, identified AHO clusters could guide the development of survivorship care strategies

Motion-Based Piloted Simulation Evaluation of a Control Allocation Technique to Recover from Pilot Induced Oscillations

This paper describes the maturation of a control allocation technique designed to assist pilots in the recovery from pilot induced oscillations (PIOs). The Control Allocation technique to recover from Pilot Induced Oscillations (CAPIO) is designed to enable next generation high efficiency aircraft designs. Energy efficient next generation aircraft require feedback control strategies that will enable lowering the actuator rate limit requirements for optimal airframe design. One of the common issues flying with actuator rate limits is PIOs caused by the phase lag between the pilot inputs and control surface response. CAPIO utilizes real-time optimization for control allocation to eliminate phase lag in the system caused by control surface rate limiting. System impacts of the control allocator were assessed through a piloted simulation evaluation of a non-linear aircraft simulation in the NASA Ames Vertical Motion Simulator. Results indicate that CAPIO helps reduce oscillatory behavior, including the severity and duration of PIOs, introduced by control surface rate limiting

A Two-Phase Innate Host Response to Alphavirus Infection Identified by mRNP-Tagging In Vivo

A concept fundamental to viral pathogenesis is that infection induces specific changes within the host cell, within specific tissues, or within the entire animal. These changes are reflected in a cascade of altered transcription patterns evident during infection. However, elucidation of this cascade in vivo has been limited by a general inability to distinguish changes occurring in the minority of infected cells from those in surrounding uninfected cells. To circumvent this inherent limitation of traditional gene expression profiling methods, an innovative mRNP-tagging technique was implemented to isolate host mRNA specifically from infected cells in vitro as well as in vivo following Venezuelan equine encephalitis virus (VEE) infection. This technique facilitated a direct characterization of the host defense response specifically within the first cells infected with VEE, while simultaneous total RNA analysis assessed the collective response of both the infected and uninfected cells. The result was a unique, multifaceted profile of the early response to VEE infection in primary dendritic cells, as well as in the draining lymph node, the initially targeted tissue in the mouse model. A dynamic environment of complex interactions was revealed, and suggested a two-step innate response in which activation of a subset of host genes in infected cells subsequently leads to activation of the surrounding uninfected cells. Our findings suggest that the application of viral mRNP-tagging systems, as introduced here, will facilitate a much more detailed understanding of the highly coordinated host response to infectious agents

A life in progress: motion and emotion in the autobiography of Robert M. La Follette

This article is a study of a La Follette’s Autobiography, the autobiography of the leading Wisconsin progressive Robert M. La Follette, which was published serially in 1911 and, in book form, in 1913. Rather than focusing, as have other historians, on which parts of La Follette’s account are accurate and can therefore be trusted, it explains instead why and how this major autobiography was conceived and written. The article shows that the autobiography was the product of a sustained, complex, and often fraught series of collaborations among La Follette’s family, friends, and political allies, and in the process illuminates the importance of affective ties as well as political ambition and commitment in bringing the project to fruition. In the world of progressive reform, it argues, personal and political experiences were inseparable

Maternal inflammation at 0.7 gestation in ewes leads to intrauterine growth restriction and impaired glucose metabolism in offspring at 30 d of age

Fetal programming associated with intrauterine growth restriction (IUGR) leads to lifelong deficits in growth and metabolic function (Hales and Barker, 2013). IUGR arises when fetuses respond to poor in utero conditions by developing adaptations that repartition nutrients to critical tissues and away from skeletal muscle (Yates et al., 2012, 2018). This fetal programming is beneficial in utero but leads to persistent reductions in muscle mass and glucose homeostasis in offspring (DeFronzo et al., 1981). Recent studies by our laboratory in sheep and rats demonstrate that maternal inflammation during gestation induces fetal inflammatory adaptations that impair growth and disrupt muscle glucose metabolism (Cadaret et al., 2017, 2018). IUGR fetal skeletal muscle exhibits indicators of enhanced inflammatory sensitivity, which could disrupt glucose uptake and oxidation (Yates et al., 2016; Cadaret et al., 2018). Enhanced inflammatory responsiveness would help explain growth and metabolic deficits observed in IUGR offspring. We hypothesize that fetal programming induced by maternal inflammation persists in offspring and contributes to impaired growth and glucose metabolism at 30 d. Therefore, the objective of this study was to determine whether sustained maternal inflammation induced by bacterial endotoxin at 0.7 gestation leads to fetal programming that contributes to deficits in growth and glucose metabolism in offspring

Population Density Estimates and Growth Rates of Eleutherodactylus coqui in Hawaii

The Puerto Rican terrestrial frog (Eleutherodactylus coqui) has received considerable attention in Hawaii because of its rapid spread, loud mating calls, and its potential threat to native species. Thus far, its invasion potential on the Island of Hawaii remains poorly understood. Critical components for determining this potential are robust estimates of abundance and vital rates across habitat types. To address this lack of information, we used mark-recapture methods to estimate E. coqui survival and abundance, determine growth rates of adult male and female frogs, and relate densities to elevation, snout–vent length (SVL), habitat structure, and invertebrate abundance. Mean adult E. coqui density across eight sites was 62 ± 12 adults/100 m2 and ranged from 6-138 adults/100 m2. Our three-year mean adult density estimates were three times greater at three of our study sites (100 adults/100 m2) than the highest long-term estimates from Puerto Rico (33 adults/100 m2). Mean individual growth rates were 0.0078 mm/day (± 0.007 SD, N = 87) for males and 0.0097 mm/day (± 0.009 SD, N = 11) for females. Frogs of similar size were found to be growing slower in Hawaii than Puerto Rico. We found no relationship between elevation and E. coqui density or elevation and SVL or between invertebrate abundance and E. coqui density. However, there was a positive relationship between understory structure and E. coqui density. This relationship suggests that removing understory structure could reduce E. coqui densities, although other potential implications of this management treatment should be considered