An hourglass mechanism controls torpor bout length in hibernating garden dormice

Hibernating mammals drastically lower their rate of oxygen consumption and body temperature (Tb) for up to several weeks, but regularly rewarm and stay euthermic for brief periods (< 30 h). It has been hypothesized that these periodic arousals are driven by the development of a metabolic imbalance during torpor, that is, the accumulation or the depletion of metabolites or the accrual of cellular damage that can be eliminated only in the euthermic state. We obtained oxygen consumption (as a proxy of metabolic rate) and Tb at 7-minute intervals over entire torpor-arousal cycles in the garden dormouse (Eliomys quercinus). Torpor bout duration was highly dependent on mean oxygen consumption during the torpor bout. Oxygen consumption during torpor, in turn, was elevated by Tb, which fluctuated only slightly in dormice kept at∼3-8°C. This corresponds to a well-known effect of higher Tb on shortening torpor bout lengths in hibernators. Arousal duration was independent from prior torpor length, but arousal mean oxygen consumption increased with prior torpor Tb. These results, particularly the effect of torpor oxygen consumption on torpor bout length, point to an hourglass mechanism of torpor control, i.e., the correction of a metabolic imbalance during arousal. This conclusion is in line with previous comparative studies providing evidence for significant interspecific inverse relationships between the duration of torpor bouts and metabolism in torpor. Thus, a simple hourglass mechanism is sufficient to explain torpor/arousal cycles, without the need to involve non-temperature-compensated circadian rhythms.

Traumatic Brain Injury and Mountains

Today, the traumatic epidemic is gaining momentum around the world. Having a complex pathogenesis, many aspects of the development and impact of traumatic brain injury (TBI) on the body remain undescribed. In particular, there is practically no information about the state of the body after a traumatic brain injury received in the highlands. The aim of the study is to establish the features of animal behavior, homeostatic blood parameters and functional morphology of the cerebellum in TBI in the highlands. The work was performed on 46 white male mongrel rats. The low-mountain series of experiments was modeled at an altitude of 760 m above sea level (Kyrgyzstan, Bishkek), the high-mountain series — at the Tuya-Ashu pass — 3200 m above sea level (Kyrgyzstan). The Weight Drop Method shock model was used to reproduce a traumatic brain injury. The ethology of animals was evaluated in the Open Field test. The lactic acid level was determined in the AQUA LAB (Bishkek). The microcirculation of the cerebellum was examined under the Olympus B×40 microscope (Japan). Statistical data processing was carried out in the SPSS 16.0 program. The visit to the outer squares of the field during TBI decreases (P<0.001) regardless of the height of the experiments, the number of racks in the highlands decreases by 60% (P < 0.001), the number of peeks into minks — by 76 % (P<0.01). The number of acts of defecation after TBI increases. The biochemical parameters of blood in TBI are characterized by an increase in the deficit of buffer bases to −3.8 mmol/l, a drop in the rate of oxygen consumption to 2.5 ml/min, an increase in the ratio between the rate of oxygen transport by arterial blood and the rate of its consumption to 4.8 rel. unit, and the concentration of lactic acid in the blood is up to 5 mmol/l. The microcirculatory bed of the cerebellum in TBI in the highlands is characterized by increased tortuosity, the appearance of swellings and interceptions along the course of blood vessels, activation of anastomoses, increased vascular porosity, hypercapillarization with erythrocyte sludge, parietal standing of leukocytes, the formation of blood clots in all parts of the vascular bed. There is vasogenic swelling of the cerebellum with the phenomena of dislocation of layers.

Factors Governing Biodegradability of Dissolved Natural Organic Matter in Lake Water

Dissolved Natural Organic Matter (DNOM) is a heterogeneous mixture of partly degraded, oxidised and resynthesised organic compounds of terrestrial or aquatic origin. In the boreal biome, it plays a central role in element cycling and practically all biogeochemical processes governing the physico-chemistry of surface waters. Because it plays a central role in multiple aquatic processes, especially microbial respiration, an improved understanding of the biodegradability of the DNOM in surface water is needed. Here the current study, we used a relatively cheap and non-laborious analytical method to determine the biodegradability of DNOM, based on the rate and the time lapse at which it is decomposed. This was achieved by monitoring the rate of oxygen consumption during incubation with addition of nutrients. A synoptic method study, using a set of lake water samples from southeast Norway, showed that the maximum respiration rate (RR) and the normalised RR (respiration rate per unit of carbon) of the DNOM in the lakes varied significantly. This RR is conceived as a proxy for the biodegradability of the DNOM. The sUVa of the DNOM and the C:N ratio were the main predictors of the RR. This implies that the biodegradability of DNOM in these predominantly oligotrophic and dystrophic lake waters was mainly governed by their molecular size and aromaticity, in addition to its C:N ratio in the same manner as found for soil organic matter. The normalised RR (independently of the overall concentration of DOC) was predicted by the molecular weight and by the origin of the organic matter. The duration of the first phase of rapid biodegradation of the DNOM (BdgT) was found to be higher in lakes with a mixture of autochthonous and allochthonous DNOM, in addition to the amount of biodegradable DNOM.

The Effect of Crank Arm Length on Cycling Economy and Performance in Triathlon

Given the nature of a triathlon race, the cycling distance is typically much longer than swimming and running across race distances from sprint to Ironman. Besides, triathletes should try to not only maintain a certain level of cycling power but also consider cycling economy to make a better performance in both the cycling portion and the overall race (Bonacci et al., 2013; Sleivert & Rowland, 1996; Swinnen et al., 2018). The cycling economy is an important indicator to predict cycling performance in terms of time to complete a certain distance. Both cycling economy and performance are determined by the interaction between mechanical output and physiological input (Barratt et al., 2016; Korff et al., 2007; Sunde et al., 2010). Theoretically, improving cycling economy elicits a better cycling time trial performance and/or less physiological demands (e.g., rate of oxygen consumption: V̇O2, heart rate) to complete at a given distance. The crank arm length (CAL) is one of the important factors among many variables that affect the economy and performance in cycling (McDaniel et al., 2002). Therefore, the appropriate selection of CAL may play a key role in improving the cycling portion of the race and entire triathlon performance. The purpose of this review is to identify the effects of acute changing CAL on physiological and biomechanical responses during cycling.

Is hypoxia vulnerability in fishes a by-product of maximum metabolic rate?

ABSTRACT The metabolic index concept combines metabolic data and known thermal sensitivities to estimate the factorial aerobic scope of animals in different habitats, which is valuable for understanding the metabolic demands that constrain species' geographical distributions. An important assumption of this concept is that the O2 supply capacity (which is equivalent to the rate of oxygen consumption divided by the environmental partial pressure of oxygen: ) is constant at O2 tensions above the critical O2 threshold (i.e. the where O2 uptake can no longer meet metabolic demand). This has led to the notion that hypoxia vulnerability is not a selected trait, but a by-product of selection on maximum metabolic rate. In this Commentary, we explore whether this fundamental assumption is supported among fishes. We provide evidence that O2 supply capacity is not constant in all fishes, with some species exhibiting an elevated O2 supply capacity in hypoxic environments. We further discuss the divergent selective pressures on hypoxia- and exercise-based cardiorespiratory adaptations in fishes, while also considering the implications of a hypoxia-optimized O2 supply capacity for the metabolic index concept.

Endoplasmic reticulum−mitochondria coupling increases during doxycycline-induced mitochondrial stress in HeLa cells

Subcellular organelles communicate with each other to regulate function and coordinate responses to changing cellular conditions. The physical-functional coupling of the endoplasmic reticulum (ER) with mitochondria allows for the direct transfer of Ca2+ between organelles and is an important avenue for rapidly increasing mitochondrial metabolic activity. As such, increasing ER−mitochondrial coupling can boost the generation of ATP that is needed to restore homeostasis in the face of cellular stress. The mitochondrial unfolded protein response (mtUPR) is activated by the accumulation of unfolded proteins in mitochondria. Retrograde signaling from mitochondria to the nucleus promotes mtUPR transcriptional responses aimed at restoring protein homeostasis. It is currently unknown whether the changes in mitochondrial−ER coupling also play a role during mtUPR stress. We hypothesized that mitochondrial stress favors an expansion of functional contacts between mitochondria and ER, thereby increasing mitochondrial metabolism as part of a protective response. Hela cells were treated with doxycycline, an antibiotic that inhibits the translation of mitochondrial-encoded proteins to create protein disequilibrium. Treatment with doxycycline decreased the abundance of mitochondrial encoded proteins while increasing expression of CHOP, C/EBPβ, ClpP, and mtHsp60, markers of the mtUPR. There was no change in either mitophagic activity or cell viability. Furthermore, ER UPR was not activated, suggesting focused activation of the mtUPR. Within 2 h of doxycycline treatment, there was a significant increase in physical contacts between mitochondria and ER that was distributed throughout the cell, along with an increase in the kinetics of mitochondrial Ca2+ uptake. This was followed by the rise in the rate of oxygen consumption at 4 h, indicating a boost in mitochondrial metabolic activity. In conclusion, an early phase of the response to doxycycline-induced mitochondrial stress is an increase in mitochondrial−ER coupling that potentiates mitochondrial metabolic activity as a means to support subsequent steps in the mtUPR pathway and sustain cellular adaptation.

A Method for Estimating the Velocity at Which Anaerobic Metabolism Begins in Swimming Fish

Anaerobic metabolism begins before fish reach their critical swimming speed. Anaerobic metabolism affects the swimming ability of fish, which is not conducive to their upward tracking. The initiation of anaerobic metabolism therefore provides a better predictor of flow barriers than critical swimming speed. To estimate the anaerobic element of metabolism for swimming fish, the respiratory metabolism and swimming performance of adult crucian carp (Carassius auratus, mass = 260.10 ± 7.93, body length = 19.32 ± 0.24) were tested in a closed tank at 20 ± 1 °C. The swimming behavior and rate of oxygen consumption of these carp were recorded at various swimming speeds. Results indicate (1) The critical swimming speed of the crucian carp was 0.85 ± 0.032 m/s (4.40 ± 0.16 BL/s). (2) When a power function was fitted to the data, oxygen consumption, as a function of swimming speed, was determined to be AMR = 131.24 + 461.26Us1.27 (R2 = 0.948, p < 0.001) and the power value (1.27) of Us indicated high swimming efficiency. (3) Increased swimming speed led to increases in the tail beat frequency. (4) Swimming costs were calculated via rate of oxygen consumption and hydrodynamic modeling. Then, the drag coefficient of the crucian carp during swimming was calibrated (0.126–0.140), and the velocity at which anaerobic metabolism was initiated was estimated (0.52 m/s), via the new method described herein. This study adds to our understanding of the metabolic patterns of fish at different swimming speeds.

Zero Echo Time 17O-MRI Reveals Decreased Cerebral Metabolic Rate of Oxygen Consumption in a Murine Model of Amyloidosis

The cerebral metabolic rate of oxygen consumption (CMRO2) is a key metric to investigate the mechanisms involved in neurodegeneration in animal models and evaluate potential new therapies. CMRO2 can be measured by direct 17O magnetic resonance imaging (17O-MRI) of H217O signal changes during inhalation of 17O-labeled oxygen gas. In this study, we built a simple gas distribution system and used 3D zero echo time (ZTE-)MRI at 11.7 T to measure CMRO2 in the APPswe/PS1dE9 mouse model of amyloidosis. We found that CMRO2 was significantly lower in the APPswe/PS1dE9 brain than in wild-type at 12–14 months. We also estimated cerebral blood flow (CBF) from the post-inhalation washout curve and found no difference between groups. These results suggest that the lower CMRO2 observed in APPswe/PS1dE9 is likely due to metabolism impairment rather than to reduced blood flow. Analysis of the 17O-MRI data using different quantification models (linear and 3-phase model) showed that the choice of the model does not affect group comparison results. However, the simplified linear model significantly underestimated the absolute CMRO2 values compared to a 3-phase model. This may become of importance when combining several metabolic fluxes measurements to study neuro-metabolic coupling.

DYNAMICS OF THE INDICATORS OF MICROCIRCULATOR-TISSUE SYSTEMS WITH THE COMBINED USE OF PROTEOLYTIC COLLAGENASIS ULTRAPHONOPHORESIS AND METHODS FRACTIONAL LASER THERAPY IN TREATMENT SCARLIFIC SKIN CHANGES IN PATIENTS WITH METABOLIC SYNDROME

В статье анализируется роль микроциркуляторных нарушений в патогенезе рубцовых изменений кожи, в том числе у пациентов с проявлениями метаболического синдрома. Исходные показатели микроциркуляторно-тканевых систем у пациентов с метаболическим синдромом свидетельствуют о более низких значениях уровня общей перфузии, чем у пациентов без признаков метаболических нарушений, что свидетельствует об угнетающем влиянии инсулинорезистентности на микроциркуляцию. Выявленная положительная динамика показателей микроциркуляторно-тканевой системы при проведении ультрафонофореза ферменкола в сочетании с методикой фракционной лазерной терапии позволяет рассматривать сосуды микроциркуляторного звена в качестве основной мишени при проведении коррекции рубцовых изменений кожи. Наблюдаемое через 4 недели после заключительной процедуры усиление нутритивного компонента кровотока и связанного с ним повышения скорости потребления кислорода и уровня окислительного метаболизма указывает на формирование пролонгированного эффекта. Преимущественное влияние рассмотренного способа коррекции рубцо-измененной кожи на отдельные компартменты микроциркуляторно-тканевой системы свидетельствует об эффективности технологии комплексного применения фракционного фототермолиза и ультрафонофореза коллагеназ, обладающей патогенетически ориентированным терапевтическим действием. Наличие в качестве фонового заболевания метаболического синдрома существенно ограничивает выраженность корригирующего эффекта, что обуславливает необходимость применения средств и методов из арсенала восстановительной медицины на основе преимущественного использования немедикаментозных лечебных факторов, которые, обладая выраженным саногенетическим потенциалом, позволяют максимально полно восстановить нарушенные функции при метаболическом синдроме и улучшить качество жизни человека The article analyzes the role of microcirculatory disorders in the pathogenesis of cicatricial changes in the skin, including in patients with manifestations of metabolic syndrome. The initial parameters of microcirculatory-tissue systems in patients with metabolic syndrome indicate lower values of the level of general perfusion than in patients without signs of metabolic disorders, which indicates the inhibitory effect of insulin resistance on microcirculation. The revealed positive dynamics of the indicators of the microcirculatory-tissue system during ultraphonophoresis of fermencol in combination with the method of fractional laser therapy allows us to consider the vessels of the microcirculatory link as the main target when correcting cicatricial changes in the skin. The increase in the nutritional component of the blood flow and the associated increase in the rate of oxygen consumption and the level of oxidative metabolism observed 4 weeks after the final procedure indicates the formation of a prolonged effect. The predominant influence of the considered method of correction of scar-altered skin on individual compartments of the microcirculatory-tissue system indicates the effectiveness of the technology of complex application of fractional photothermolysis and ultraphonophoresis of collagenases, which has a pathogenetically oriented therapeutic effect. The presence of metabolic syndrome as a background disease significantly limits the severity of the corrective effect, which necessitates the use of means and methods from the arsenal of restorative medicine based on the predominant use of non-drug therapeutic factors, which, having a pronounced sanogenetic potential, allow the most complete restoration of impaired functions in MS and improve the quality human life