Experimental demonstration of prenatal programming of mitochondrial aerobic metabolism lasting until adulthood

It is increasingly being postulated that among-individual variation in mitochondrial function underlies variation in individual performance (e.g. growth rate) and state of health. Environmental conditions experienced before birth have been suggested to programme postnatal mitochondrial biology, but the hypothesis that early-life conditions induce consistent and long-lasting differences in mitochondrial function among individuals remains mostly untested. We tested this hypothesis in an avian model by experimentally manipulating prenatal conditions (incubation temperature and stability), then measuring mitochondrial aerobic metabolism in blood cells from the same individuals during postnatal growth and at adulthood. Mitochondrial aerobic metabolism changed markedly across life stages, and part of these age-related changes were influenced by the prenatal experimental conditions. A high incubation temperature induced a consistent and long-lasting increase in mitochondrial aerobic metabolism, while unstable incubation conditions had a delayed effect, with an increased metabolism only being observed at adulthood. While we detected significant within-individual consistency in mitochondrial aerobic metabolism across life-stages, the prenatal temperature regime only accounted for a relatively small proportion (<20%) of the consistent among-individual differences we observed. Our results demonstrate that prenatal conditions can program consistent and long-lasting differences in mitochondrial function, which could potentially underly among-individual variation in performance and health state.

Elasmobranch Responses to Experimental Warming, Acidification, and Oxygen Loss—A Meta-Analysis

Despite the long evolutionary history of this group, the challenges brought by the Anthropocene have been inflicting an extensive pressure over sharks and their relatives. Overexploitation has been driving a worldwide decline in elasmobranch populations, and rapid environmental change, triggered by anthropogenic activities, may further test this group's resilience. In this context, we searched the literature for peer-reviewed studies featuring a sustained (&gt;24 h) and controlled exposure of elasmobranch species to warming, acidification, and/or deoxygenation: three of the most pressing symptoms of change in the ocean. In a standardized comparative framework, we conducted an array of mixed-model meta-analyses (based on 368 control-treatment contrasts from 53 studies) to evaluate the effects of these factors and their combination as experimental treatments. We further compared these effects across different attributes (lineages, climates, lifestyles, reproductive modes, and life stages) and assessed the direction of impact over a comprehensive set of biological responses (survival, development, growth, aerobic metabolism, anaerobic metabolism, oxygen transport, feeding, behavior, acid-base status, thermal tolerance, hypoxia tolerance, and cell stress). Based on the present findings, warming appears as the most influential factor, with clear directional effects, namely decreasing development time and increasing aerobic metabolism, feeding, and thermal tolerance. While warming influence was pervasive across attributes, acidification effects appear to be more context-specific, with no perceivable directional trends across biological responses apart from the necessary to achieve acid-base balance. Meanwhile, despite its potential for steep impacts, deoxygenation has been the most neglected factor, with data paucity ultimately precluding sound conclusions. Likewise, the implementation of multi-factor treatments has been mostly restricted to the combination of warming and acidification, with effects approximately matching those of warming. Despite considerable progress over recent years, research regarding the impact of these drivers on elasmobranchs lags behind other taxa, with more research required to disentangle many of the observed effects. Given the current levels of extinction risk and the quick pace of global change, it is further crucial that we integrate the knowledge accumulated through different scientific approaches into a holistic perspective to better understand how this group may fare in a changing ocean.

Rewarming With Closed Thoracic Lavage Following 3-h CPR at 27°C Failed to Reestablish a Perfusing Rhythm

Introduction: Previously, we showed that the cardiopulmonary resuscitation (CPR) for hypothermic cardiac arrest (HCA) maintained cardiac output (CO) and mean arterial pressure (MAP) to the same reduced level during normothermia (38°C) vs. hypothermia (27°C). In addition, at 27°C, the CPR for 3-h provided global O2 delivery (DO2) to support aerobic metabolism. The present study investigated if rewarming with closed thoracic lavage induces a perfusing rhythm after 3-h continuous CPR at 27°C.Materials and Methods: Eight male pigs were anesthetized, and immersion-cooled. At 27°C, HCA was electrically induced, CPR was started and continued for a 3-h period. Thereafter, the animals were rewarmed by combining closed thoracic lavage and continued CPR. Organ blood flow was measured using microspheres.Results: After cooling with spontaneous circulation to 27°C, MAP and CO were initially reduced by 37 and 58% from baseline, respectively. By 15 min after the onset of CPR, MAP, and CO were further reduced by 58 and 77% from baseline, respectively, which remained unchanged throughout the rest of the 3-h period of CPR. During CPR at 27°C, DO2 and O2 extraction rate (VO2) fell to critically low levels, but the simultaneous small increase in lactate and a modest reduction in pH, indicated the presence of maintained aerobic metabolism. During rewarming with closed thoracic lavage, all animals displayed ventricular fibrillation, but only one animal could be electro-converted to restore a short-lived perfusing rhythm. Rewarming ended in circulatory collapse in all the animals at 38°C.Conclusion: The CPR for 3-h at 27°C managed to sustain lower levels of CO and MAP sufficient to support global DO2. Rewarming accidental hypothermia patients following prolonged CPR for HCA with closed thoracic lavage is not an alternative to rewarming by extra-corporeal life support as these patients are often in need of massive cardio-pulmonary support during as well as after rewarming.

Effects of rewarming with extracorporeal membrane oxygenation to restore oxygen transport and organ blood flow after hypothermic cardiac arrest in a porcine model

We recently documented that cardiopulmonary resuscitation (CPR) generates the same level of cardiac output (CO) and mean arterial pressure (MAP) during both normothermia (38 °C) and hypothermia (27 °C). Furthermore, continuous CPR at 27 °C provides O2 delivery (ḊO2) to support aerobic metabolism throughout a 3-h period. The aim of the present study was to investigate the effects of extracorporeal membrane oxygenation (ECMO) rewarming to restore ḊO2 and organ blood flow after prolonged hypothermic cardiac arrest. Eight male pigs were anesthetized and immersion cooled to 27 °C. After induction of hypothermic cardiac arrest, CPR was started and continued for a 3-h period. Thereafter, the animals were rewarmed with ECMO. Organ blood flow was measured using microspheres. After cooling with spontaneous circulation to 27 °C, MAP and CO were initially reduced to 66 and 44% of baseline, respectively. By 15 min after the onset of CPR, there was a further reduction in MAP and CO to 42 and 25% of baseline, respectively, which remained unchanged throughout the rest of 3-h CPR. During CPR, ḊO2 and O2 uptake (V̇O2) fell to critical low levels, but the simultaneous small increase in lactate and a modest reduction in pH, indicated the presence of maintained aerobic metabolism. Rewarming with ECMO restored MAP, CO, ḊO2, and blood flow to the heart and to parts of the brain, whereas flow to kidneys, stomach, liver and spleen remained significantly reduced. CPR for 3-h at 27 °C with sustained lower levels of CO and MAP maintained aerobic metabolism sufficient to support ḊO2. Rewarming with ECMO restores blood flow to the heart and brain, and creates a “shockable” cardiac rhythm. Thus, like continuous CPR, ECMO rewarming plays a crucial role in “the chain of survival” when resuscitating victims of hypothermic cardiac arrest.

Soil Candidate Phyla Radiation Bacteria Encode Components of Aerobic Metabolism and Co-occur with Nanoarchaea in the Rare Biosphere of Rhizosphere Grassland Communities

Here, we investigated overlooked microbes in soil, candidate phyla radiation (CPR) bacteria and Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, and Nanohaloarchaeota (DPANN) archaea, by size fractionating small particles from soil, an approach typically used for the recovery of viral metagenomes. Concentration of these small cells (<0.2 μm) allowed us to identify these organisms as part of the rare soil biosphere and to sample genomes that were absent from non-size-fractionated metagenomes.

Temperature, osmotic and acidic activity of infusion solutions as an integral part of their mechanism of action

A review of the literature shows that the physical-chemical properties of infusion solutions can be an integral part of the mechanism of their local action on the routes of administration. This new scientific and practical direction in clinical pharmacology was born at the end of the 20th century in Russia. Initially, it was found that isotonic solutions of glucose, mannitol, and sodium chloride with different temperatures have different local effects on the metabolism and viability of isolated biological objects such as mitochondria and blood plasma. At the same time, it was shown that increasing the temperature of solutions from +37 to +45C accelerates the metabolism of these biological objects, increases their reactivity and enhances their response to the action of many drugs-activators of metabolism and function. And vice versa, lowering the temperature of these solutions from +37 to +20C and below (up to 0C) slows down their metabolism, reduces their reactivity, weakens their response to the action of drugs-activators of metabolism and function, and also increases survival in conditions of ischemia and hypoxia. These results allowed us to recommend warm infusion solutions as universal means of activating aerobic metabolism in tissues and the response of tissues to drugs with local physical-chemical action, and cold infusion solutions as universal means of inhibiting aerobic metabolism in tissues and increasing the resistance of tissues to the action of drugs on them. Following this, it was shown that many infusion solutions do not have isoosmotic activity, since the osmotic activity of drugs is not controlled. Therefore, one part of the solutions has hypotonic activity, and the other part has hypertonic activity. Therefore, sometimes the infusion solution can increase the hypoosmotic or hyperosmotic activity of the blood plasma. Then it was shown that the absolute majority of infusion solutions do not have a pH of 7.4. At the same time, very many infusion solutions have acidic activity, so they have an acidifying effect on the blood. The chronology of the development of inventions based on the achievements of the physical-chemical pharmacology of infusion agents is shown.

Dual sensor measurement shows that temperature outperforms pH as an early sign of aerobic deterioration in maize silage

High quality silage containing abundant lactic acid is a critical component of ruminant diets in many parts of the world. Silage deterioration, a result of aerobic metabolism (including utilization of lactic acid) during storage and feed-out, reduces the nutritional quality of the silage, and its acceptance by animals. In this study, we introduce a novel non-disruptive dual-sensor method that provides near real-time information on silage aerobic stability, and demonstrates for the first time that in situ silage temperature (Tsi) and pH are both associated with preservation of lactic acid. Aerobic deterioration was evaluated using two sources of maize silage, one treated with a biological additive, at incubation temperatures of 23 and 33 °C. Results showed a time delay between the rise of Tsi and that of pH following aerobic exposure at both incubation temperatures. A 11 to 25% loss of lactic acid occurred when Tsi reached 2 °C above ambient. In contrast, by the time the silage pH had exceeded its initial value by 0.5 units, over 60% of the lactic acid had been metabolized. Although pH is often used as a primary indicator of aerobic deterioration of maize silage, it is clear that Tsi was a more sensitive early indicator. However, the extent of the pH increase was an effective indicator of advanced spoilage and loss of lactic acid due to aerobic metabolism for maize silage.