Modeling an immune response to influenza A virus infection in alveolar epithelial cells

Influenza A viruses (IAV) have been the cause of several influenza pandemics in history and are a significant threat for the next global pandemic. Hospitalized influenza patients often have excess interferon production and a dysregulated immune response to the IAV infection. Obtaining a better understanding of the mechanisms of IAV infection that induce these harmful effects would help drug developers and health professionals create more effective treatments for IAV infection and improve patient outcomes. IAV stimulates viral sensors and receptors expressed by alveolar epithelial cells, like RIG-I and toll-like receptor 3 (TLR3). These two pathways coordinate with one another to induce expression of type III interferons to combat the infection. Presented here is a queuing theory-based model of these pathways that was designed to analyze the timing and amount of interferons produced in response to IAV single stranded RNA and double-stranded RNA detection. The model accurately represents biological data showing the necessary coordination of the RIG-I and TLR3 pathways for effective interferon production. This model can serve as the framework for future studies of IAV infection and identify new targets for potential treatments.     

Volatile oils of mature and juvenile leaves of Juniperus horizontalis: Chemosystematic significance

Comparison of 39 terpenoids between young (juvenile) foliage and mature (adult) foliage from naturally growing plants of Juniperus horizontalis revealed no significant differences. Canonical variate analysis of the terpenoids of J. scopulorum and J. virginiana along with the mature foliage of J. horizontalis and co-plotting juvenile foliage showed a slight loosening of the J. horizontalis group but not enough to blur taxonomic distinctions. These results stand in sharp contrast with the previous work on J. scopulorum and appear to be due to the indeterminant growth pattern seen in J. horizontalis.     

Wood construction more strongly shapes deadwood microbial communities than spatial location over 5 years of decay

Diverse communities of fungi and bacteria in deadwood mediate wood decay. While rates of decomposition vary greatly among woody species and spatially distinct habitats, the relative importance of these factors in structuring microbial communities and whether these shift over time remains largely unknown. We characterized fungal and bacterial diversity within pieces of deadwood that experienced 6.3–98.8% mass loss while decaying in common garden ‘rotplots’ in a temperate oak-hickory forest in the Ozark Highlands, MO, USA. Communities were isolated from 21 woody species that had been decomposing for 1–5 years in spatially distinct habitats at the landscape scale (top and bottom of watersheds) and within stems (top and bottom of stems). Microbial community structure varied more strongly with wood traits than with spatial locations, mirroring the relative role of these factors on decay rates on the same pieces of wood even after 5 years. Co-occurring fungal and bacterial communities persistently influenced one another independently from their shared environmental conditions. However, the relative influence of wood construction versus spatial locations differed between fungi and bacteria, suggesting that life history characteristics of these clades structure diversity differently across space and time in decomposing wood.     

The Yeast Oxysterol Binding Protein Kes1 Maintains Sphingolipid Levels

The oxysterol binding protein family are amphitropic proteins that bind oxysterols, sterols, and possibly phosphoinositides, in a conserved binding pocket. The Saccharomyces cerevisiae oxysterol binding protein family member Kes1 (also known as Osh4) also binds phosphoinositides on a distinct surface of the protein from the conserved binding pocket. In this study, we determine that the oxysterol binding protein family member Kes1 is required to maintain the ratio of complex sphingolipids and levels of ceramide, sphingosine-phosphate and sphingosine. This inability to maintain normal sphingolipid homeostasis resulted in misdistribution of Pma1, a protein that requires normal sphingolipid synthesis to occur to partition into membrane rafts at the Golgi for its trafficking to the plasma membrane.     

Constant light alters serum hormone levels related to thyroid function in male CD-1 mice

ABSTRACT

Disruptions to the circadian rhythm can lead to altered metabolism. Modification of thyroid function may be a reason why circadian misalignment may contribute to future metabolic disorders. We investigated whether circadian disruption through constant light (LL) can lead to variations in hormone levels associated with thyroid function. Mice were exposed to LL or a 12:12 Light:Dark (LD) cycle for 6 weeks; then glucose tolerance and thyroid hormone levels were measured at ZT 6 and ZT 18. There was day/night variation in glucose tolerance, but LL had no effect. LL reduced TSH, increased fT4, and abolished day/night variation in fT3 and leptin. These findings illustrate that LL alters thyroid-related hormones, providing evidence of a link between circadian disruption and thyroid function.     

Female parity, male aggression, and the Challenge Hypothesis in wild chimpanzees

The Challenge Hypothesis proposes that testosterone mediates aggression during periods of heightened conflict between males, especially episodes that have important fitness consequences. Considerable evidence from seasonally breeding species provides support for this hypothesis, but few data exist in animals that mate year-round. We tested predictions generated by the Challenge Hypothesis in chimpanzees, a non-seasonally breeding primate, through a study of individuals living in an exceptionally large community at Ngogo, Kibale National Park, Uganda. Results indicated that dominance rank had no influence on testosterone levels. Instead of rank influencing testosterone production, additional analyses revealed an important role for reproductive competition. Male chimpanzees displayed more aggression when they were in the same party as parous estrous females than when reproductively active females were unavailable. Male chimpanzees competed more intensely for mating opportunities with parous females than with nulliparas, and as a consequence, males displayed more aggression around the former than the latter. When males accompanied parous estrous females, their urinary testosterone concentrations were significantly higher than baseline concentrations. In contrast, urinary testosterone concentrations did not exceed baseline when males associated with nulliparous estrous females. These differences in testosterone levels could not be attributed to mating per se because males copulated equally often with parous and nulliparous females. Furthermore, variation in testosterone concentrations were not due to males gathering together in large parties, as their levels in these situations did not exceed baseline. Taken together, these findings, derived from a relatively large sample of males and estrous females, replicate those from a prior study and furnish additional support for the Challenge Hypothesis. Our results suggest that the Challenge Hypothesis is likely to be broadly applicable to chimpanzees and increase our understanding of the physiological costs to males who compete for estrous females.     

Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice

While reports suggest a single dose of senolytics may improve vasomotor function, the structural and functional impact of long‐term senolytic treatment is unknown. To determine whether long‐term senolytic treatment improves vasomotor function, vascular stiffness, and intimal plaque size and composition in aged or hypercholesterolemic mice with established disease. Senolytic treatment (intermittent treatment with Dasatinib + Quercetin via oral gavage) resulted in significant reductions in senescent cell markers (TAF⁺ cells) in the medial layer of aorta from aged and hypercholesterolemic mice, but not in intimal atherosclerotic plaques. While senolytic treatment significantly improved vasomotor function (isolated organ chamber baths) in both groups of mice, this was due to increases in nitric oxide bioavailability in aged mice and increases in sensitivity to NO donors in hypercholesterolemic mice. Genetic clearance of senescent cells in aged normocholesterolemic INK‐ATTAC mice phenocopied changes elicited by D+Q. Senolytics tended to reduce aortic calcification (alizarin red) and osteogenic signaling (qRT–PCR, immunohistochemistry) in aged mice, but both were significantly reduced by senolytic treatment in hypercholesterolemic mice. Intimal plaque fibrosis (picrosirius red) was not changed appreciably by chronic senolytic treatment. This is the first study to demonstrate that chronic clearance of senescent cells improves established vascular phenotypes associated with aging and chronic hypercholesterolemia, and may be a viable therapeutic intervention to reduce morbidity and mortality from cardiovascular diseases.     

Late‐life time‐restricted feeding and exercise differentially alter healthspan in obesity

Aging and obesity increase multimorbidity and disability risk, and determining interventions for reversing healthspan decline is a critical public health priority. Exercise and time‐restricted feeding (TRF) benefit multiple health parameters when initiated in early life, but their efficacy and safety when initiated at older ages are uncertain. Here, we tested the effects of exercise versus TRF in diet‐induced obese, aged mice from 20 to 24 months of age. We characterized healthspan across key domains: body composition, physical, metabolic, and cardiovascular function, activity of daily living (ADL) behavior, and pathology. We demonstrate that both exercise and TRF improved aspects of body composition. Exercise uniquely benefited physical function, and TRF uniquely benefited metabolism, ADL behavior, and circulating indicators of liver pathology. No adverse outcomes were observed in exercised mice, but in contrast, lean mass and cardiovascular maladaptations were observed following TRF. Through a composite index of benefits and risks, we conclude the net healthspan benefits afforded by exercise are more favorable than those of TRF. Extrapolating to obese older adults, exercise is a safe and effective option for healthspan improvement, but additional comprehensive studies are warranted before recommending TRF.     

Looking to the future: key points for sustainable management of northern Great Plains grasslands

The grasslands of the northern Great Plains (NGP) region of North America are considered endangered ecosystems and priority conservation areas yet have great ecological and economic importance. Grasslands in the NGP are no longer self‐regulating adaptive systems. The challenges to these grasslands are widespread and serious (e.g. climate change, invasive species, fragmentation, altered disturbance regimes, and anthropogenic chemical loads). Because the challenges facing the region are dynamic, complex, and persistent, a paradigm shift in how we approach restoration and management of the grasslands in the NGP is imperative. The goal of this article is to highlight four key points for land managers and restoration practitioners to consider when planning management or restoration actions. First, we discuss the appropriateness of using historical fidelity as a restoration or management target because of changing climate, widespread pervasiveness of invasive species, the high level of fragmentation, and altered disturbance regimes. Second, we highlight ecosystem resilience and long‐term population persistence as alternative targets. Third, because the NGP is so heavily impacted with anthropogenic chemical loading, we discuss the risks of ecological traps and extinction debt. Finally, we highlight the importance of using adaptive management and having patience during restoration and management. Consideration of these four points will help management and restoration of grasslands move toward a more successful and sustainable future. Although we specifically focus on the NGP of North America, these same issues and considerations apply to grasslands and many other ecosystems globally.