This review outlines current concepts and hypotheses on ENaC phylogeny and discusses the emergence of regulation-defining sequence motifs in the context of osmoregulatory adaptations during tetrapod terrestrialization. In light of the distinct regulation and expression of ENaC isoforms in tetrapod vertebrates, we discuss the potential significance of ENaC orthologs in osmoregulation of fishes as well as the putative fates of atypical channel isoforms in mammals. We hypothesize that ancestral proton-sensitive ENaC orthologs might have aided the osmoregulatory adaptation to freshwater environments whereas channel regulation by proteases evolved as a molecular adaptation to lung liquid homeostasis in terrestrial tetrapods.Hibernators suppress physiological processes when expressing torpor, yet little is known about the effects of torpor on male reproductive physiology. Studies of hibernating mammals suggest that deep torpor negatively impacts spermatogenesis and that transitions between torpor and euthermic arousals increase cellular oxidative stress, with potentially damaging effects on sperm. Here, we hypothesize that variation in torpor expression affects the reproductive readiness of hibernators by impacting their sperm production. To test this, we examined the relationship between torpor expression and spermatogenesis in captive eastern chipmunks (Tamias striatus). https://www.selleckchem.com/products/triparanol-mer-29.html We determined torpor depth with temperature data loggers and assessed its relationship with spermatogenesis by examining spermatogenic progression, cell division, sperm counts, sperm maturity, and DNA damage. We show that deep hibernators (high levels of torpor) largely halted spermatogenesis in late hibernation in comparison with shallow hibernators (low levels of torpor), where ongoing spermatogenesis was observed. Despite these differences in spermatogenic state during hibernation, spermatogenic progression, sperm numbers, and maturity did not differ in spring, potentially reflecting similar degrees of reproductive readiness. Interestingly, shallow hibernators exhibited higher rates of DNA damage in spermatogenic cells during hibernation, with this trend reversing in spring. Our results thus indicate that once heterothermy is terminated, deep hibernators resume spermatogenesis but are characterized by higher rates of DNA damage in spermatogenic cells at the seasonal stage when spring mating commences. Therefore, our study confirmed posthibernation recovery of sperm production but also a potential impact of deep torpor expression during winter on DNA damage in spring.Planarians are widely used animal models for studies in regeneration, developmental biology, neurobiology, and behavior. However, surprisingly little is known about other aspects of their basic biology, even though such information might help validate these flatworms as a general animal model. We hypothesized that planaria, although dependent on simple diffusion of O2 across the integument for O2 uptake, would nonetheless show changes in oxygen consumption (V̇o2) associated with reproductive mode (sexual or asexual), feeding (specific dynamic action; SDA), temperature (Q10 values), and photoperiod typical of those responses of more complex invertebrates. In the current experiments, routine V̇o2 was measured over the range of 13-28°C in Schmidtea mediterranea and Girardia dorotocephala. At the long-term maintenance temperature of 18°C, routine V̇o2 was ~13 µL O2·g-1·h-1 in the two asexual strains, but approximately twice as high (27 µL O2·g-1·h-1) in the sexual strain of S. mediterranea, suggesting a metabolic cost for sexual reproduction. Metabolic temperature sensitivity, measured by Q10, was about one to three for all three groups. All three groups showed a large (~2- to 3-fold) increase in V̇o2 within a day following feeding, suggesting a large SDA effect. Starvation, causing "degrowth" in some planaria, resulted in a loss of one-third of body mass in sexual S. mediterranea but no body mass loss in either asexual strains. Collectively, these data indicate that, while being a relatively simple flatworm with no dedicated respiratory or circulatory system, their metabolic physiological responses are quite similar to those shown by more complex invertebrates and vertebrates, contributing to their validation as an animal model. Obesity, race/ethnicity, and other correlated characteristics have emerged as high-profile risk factors for adverse coronavirus disease 2019 (COVID-19)-associated outcomes, yet studies have not adequately disentangled their effects. To determine the adjusted effect of body mass index (BMI), associated comorbidities, time, neighborhood-level sociodemographic factors, and other factors on risk for death due to COVID-19. Retrospective cohort study. Kaiser Permanente Southern California, a large integrated health care organization. Kaiser Permanente Southern California members diagnosed with COVID-19 from 13 February to 2 May 2020. Multivariable Poisson regression estimated the adjusted effect of BMI and other factors on risk for death at 21 days; models were also stratified by age and sex. Among 6916 patients with COVID-19, there was a J-shaped association between BMI and risk for death, even after adjustment for obesity-related comorbidities. Compared with patients with a BMI of 18.5 to 24 kg/m , those with BMIs of 40 to 44 kg/m and greater than 45 kg/m had relative risks of 2.68 (95% CI, 1.43 to 5.04) and 4.18 (CI, 2.12 to 8.26), respectively. This risk was most striking among those aged 60 years or younger and men. Increased risk for death associated with Black or Latino race/ethnicity or other sociodemographic characteristics was not detected. Deaths occurring outside a health care setting and not captured in membership files may have been missed. Obesity plays a profound role in risk for death from COVID-19, particularly in male patients and younger populations. Our capitated system with more equalized health care access may explain the absence of effect of racial/ethnic and socioeconomic disparities on death. Our data highlight the leading role of severe obesity over correlated risk factors, providing a target for early intervention. Roche-Genentech. Roche-Genentech.