No abstract

Although hypoxia tolerance in heterothermic mammals is well established, it is unclear whether the adaptive significance stems from hypoxia or other cellular challenge associated with euthermy, hibernation, or arousal. In the present study, blood gases, hemoglobin O 2 saturation (SO2), and indexes of cellular and physiological stress were measured during hibernation and euthermy and after arousal thermogenesis. Results show that arterial O 2 tension (PaO 2 ) and SO2 are severely diminished during arousal and that hypoxia-inducible factor (HIF)-1␣ accumulates in brain. Despite evidence of hypoxia, neither cellular nor oxidative stress, as indicated by inducible nitric oxide synthase (iNOS) levels and oxidative modification of biomolecules, was observed during late arousal from hibernation. Compared with rats, hibernating Arctic ground squirrels (Spermophilus parryii) are well oxygenated with no evidence of cellular stress, inflammatory response, neuronal pathology, or oxidative modification following the period of high metabolic demand necessary for arousal. In contrast, euthermic Arctic ground squirrels experience mild, chronic hypoxia with low SO 2 and accumulation of HIF-1␣ and iNOS and demonstrate the greatest degree of cellular stress in brain. These results suggest that Arctic ground squirrels experience and tolerate endogenous hypoxia during euthermy and arousal.torpor; ischemia; stroke; Spermophilus parryii; reperfusion; inflammation; oxidative stress HIBERNATION IS A UNIQUE PHYSIOLOGICAL STATE of prolonged periods of low body temperature, metabolism, blood flow, and other physiological processes that are disrupted by brief periodic arousal episodes when animals rewarm and reperfuse metabolically active tissues (7). During arousal thermogenesis, blood flow returns to brain and other organs in a reperfusionlike manner at a time of maximal oxygen demand (42, 58). Preservation of neuronal and other cellular morphology during low cerebral blood flow demonstrates that hibernating mammals tolerate pronounced fluctuations in blood flow (16,61). Physiological and cellular stress experienced during euthermy, hibernation, and arousal is less well characterized.Arterial oxygen tension (Pa O 2 ) and tissue lactate measurements show that hibernating ground squirrels are well oxygenated (16,20), sometimes exceeding values in the euthermic state (15). In contrast, oxygen supply may become limiting during arousal thermogenesis. Increases in brain tissue lactate levels during peak oxygen consumption during arousal from hibernation in bats suggest these animals experience oxygen deficiency during arousal and reperfusion (30). However, because tissue lactate was not reported for euthermic bats, it is unclear how brain tissue hypoxia experienced during arousal compares to the euthermic state. Moreover, Pa O 2 was not measured to address the relationship between blood and tissue oxygenation during euthermy, hibernation, and arousal. To characterize physiological challenges associated with arousal thermogenesis, we evaluated b...

Scholars view entrepreneurial orientation as an essential element of high-performing firms. The extant research has focused extensively on the construct development related to and performance implications of entrepreneurial orientation. Prior research has also identified the significant positive impact of entrepreneurial orientation on technology commercialization. The research community has, however, yet to examine critical antecedents of entrepreneurial orientation and to investigate relevant antecedents and consequences of entrepreneurial orientation in transitional settings such as that of China. Most Chinese firms are embracing significant changes in governance incentive mechanisms as China deepens the economic reform. The extant literature provides limited insight as to how incentive mechanisms such as chief executive officer (CEO) ownership and turnover may affect firm entrepreneurial orientation in China's transitional setting. Furthermore, given the significant changes and uncertainty in the market place, China provides an ideal laboratory to examine the influence of technological turbulence on the relationship between entrepreneurial orientation and technology commercialization. Aimed at filling in these glaring gaps, this study develops a conceptual model, with institutional theory as its underpinning, to examine the relationships among governance incentive mechanisms, entrepreneurial orientation, technological turbulence, and technology commercialization. The empirical results from a sample of 607 Chinese firms reveal several important findings. The CEO ownership has a significant positive effect on entrepreneurial orientation, and CEO turnover frequency has an inverse U curvilinear impact on entrepreneurial orientation. Furthermore, entrepreneurial orientation positively affects technology commercialization, with technological turbulence positively moderating this relationship. This study makes several important contributions. First, the present article brings into sharper focus the differing impacts of CEO ownership and CEO turnover on entrepreneurial orientation. The theoretical deliberation and empirical testing offer useful insights into the formation process of entrepreneurial orientation. Second, the examination of the moderating effect of technological turbulence provides additional richness to the extant literature. In addition, different from prior studies, this study was conducted under China's transitional economy context. By integrating unique institutional arrangements and the turbulent technological environment, two key characteristics of China's transitional economy setting, the study broadened and Ã

The effects of different levels of systemic hypoxia on hormonal responses, strength, and body composition to 5-week resistance training were investigated. Twenty-five male subjects were randomly assigned into 3 experimental groups that performed 10 sessions (2 sessions per week) of barbell back squat (10 repetitions, 5 sets, 70% 1 repetition maximum [RM]) under normoxia (NR, FiO2 = 21%) and hypoxia (HL, FiO2 = 16%; HH, FiO2 = 12.6%). Serum growth hormone (GH), testosterone (T), and cortisol (C) concentrations were measured before (Pre) and at 0 (T-0), 15 (T-15), 30 (T-30) minutes after exercise in the first and last training sessions. One repetition maximum, isometric knee extension, isometric leg press (LP), and body composition were evaluated before and after the protocol. In the first session, GH of HH (p < 0.01) and HL (p < 0.01) was higher than NR at T-0. In the last session, only GH of HH was higher than NR at T-0 (p ≤ 0.05); meanwhile, T/C ratio of HH was higher than NR at Pre (p < 0.01), T-0 (p < 0.01), and T-15 (p ≤ 0.05). Following the training protocol, HH showed greater (p ≤ 0.05) improvement of isometric LP strength compared with NR; lean body mass was increased in the hypoxia groups only. Moderate-intensity resistance training performed in severe hypoxia (FiO2 = 12.6%) induced greater GH responses and isometric strength gains in LP than that in NR. FiO2 of 12.6% was recommended when performing the moderate-intensity resistance training under systemic hypoxia.

Oral microbial dysbiosis is known to increase susceptibility of an individual to develop rheumatoid arthritis (RA). Individuals at-risk of RA may undergo different phases of disease progression. In this study, we aim to investigate whether and whereby the oral microbiome communities alter prior to symptoms of RA. Seventy-nine saliva samples were collected from 29 high-risk individuals, who were positive for anti-citrullinated protein antibodies (ACPA) and have no clinical arthritis, 27 RA patients and 23 healthy controls (HCs). The salivary microbiome was examined using 16S ribosomal RNA gene sequencing. Alpha and beta diversity analysis and the linear discriminant analysis were applied to examine the bacterial diversity, community structure and discriminatory taxa between three groups, respectively. The correlation between salivary bacteria and autoantibodies were analyzed. In the "pre-clinical" stages, salivary microbial diversity was significantly reduced comparing to RA patients and HCs. In contrast to HCs, like RA patients, individuals at high-risk for RA showed a reduction in the abundance of genus Defluviitaleaceae_UCG-011 and the species Neisseria oralis, but an expansion of Prevotella_6. Unexpectedly, the relative abundance of Porphyromonas gingivalis, reported as opportunistic pathogens for RA development, was significantly decreased in high-risk individuals. Additionally, we identified four genera in the saliva from high-risk individuals positively correlated with serum ACPA titers, and the other two genera inversely displayed. In summary, we observed a characteristic compositional change of salivary microbes in individuals at high-risk for RA, suggesting that oral microbiota dysbiosis occurs in the "pre-clinical" stage of RA and are correlated with systemic autoimmune features.