BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection

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Temperature and the tropical tortoise Kinixys spekii: tests of thermoregulation

The mean body temperature (T_b) of active Kinixys spekii did not vary with sex or type of activity, or between hot days (maximum ambient temperature T_a > 29°C) and cool days. On hot days, T_b increased rapidly in the morning, and was constant during the late afternoon after midday inactivity. On cool days, T_b increased more slowly in the morning, and decreased during the afternoon. The slopes of T_b on T_a overall, and on hot days, were close to one, suggesting that tortoises were thermoconformers; the slope was greater than one on cool days. In a second test of thermoregulation, T_bs were compared with temperatures of null models (T_m). Tortoises were clearly thermoregulators compared to 'active-all-day' models. 'Activity-time' models had T_m more similar to T_b. Nevertheless, detailed comparison showed that tortoises were thermoregulating in the late morning, and that this was by choice of microenvironment, rather than ceasing activity when T_b reached a high level. These results are discussed in relation to E, a measure of the effectiveness of thermoregulation based on comparison of T_b and T_m with the set point range (T_set) selected in a thermal gradient. A set of three indices, which separate the variability of T_b, the difference between T_b and T_m, and between T_b and T_set, is suggested as a more generally applicable summary of thermoregulation in ectotherms.     

Metabolic effects of physiological levels of caffeine in myotubes

Caffeine has been shown to stimulate multiple major regulators of cell energetics including AMP-activated protein kinase (AMPK) and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII). Additionally, caffeine induces peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial biogenesis. While caffeine enhances oxidative metabolism, experimental concentrations often exceed physiologically attainable concentrations through diet. This work measured the effects of low-level caffeine on cellular metabolism and gene expression in myotubes, as well as the dependence of caffeine’s effects on the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPARβ/δ). C2C12 myotubes were treated with various doses of caffeine for up to 24 h. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Cellular metabolism was determined via oxygen consumption and extracellular acidification rate. Caffeine significantly induced regulators of mitochondrial biogenesis and oxidative metabolism. Mitochondrial staining was suppressed in PPARβ/δ-inhibited cells which was rescued by concurrent caffeine treatment. Caffeine-treated cells also displayed elevated peak oxidative metabolism which was partially abolished following PPARβ/δ inhibition. Similar to past observations, glucose uptake and GLUT4 content were elevated in caffeine-treated cells, however, glycolytic metabolism was unaltered following caffeine treatment. Physiological levels of caffeine appear to enhance cell metabolism through mechanisms partially dependent on PPARβ/δ.     

Diazepam in Labour: Its Metabolism and Effect on the Clinical Condition and Thermogenesis of the Newborn

Following the administration of diazepam to mothers in labour the clinical effects, changes in thermogenesis, and metabolism of the drug in the newborn were observed under carefully controlled conditions. A total maternal dose of 30 mg or less in the 15 hours before delivery had little effect on the infants'' state. Larger doses, however, were accompanied by low Apgar scores at birth, apnoeic spells, hypotonia, reluctance to feed, and an impaired metabolic response to a cold stress. Measurement of plasma levels of diazepam and its active metabolite showed that both products were detectable in significant concentrations in some infants for up to eight days. We conclude that greater care should be taken in the use of this otherwise effective drug for the treatment of pre-eclampsia.