High Metabolic Capacity Research Articles

Resting Metabolic Rate Does Not Predict Peak Metabolic Rate in the Glanville Fritillary Butterfly.

Peak metabolic rate reflects maximal performance and may have direct fitness consequences, whereas resting metabolic rate (RMR) represents the maintenance cost of the whole animal. These traits may be linked, which has significant implications for the evolution of both traits. In vertebrates, a positive correlation between RMR and aerobic capacity has been proposed to explain the origin of endothermy. However, as studies on the relationship between RMR and aerobic capacity have focused on vertebrates, we know much less about these traits in ectothermic insects. I measured RMR in the Glanville fritillary butterfly (Melitaea cinxia) using two configurations: one optimized for measuring flight metabolic rate and the other optimized for RMR. The relationship between RMR and body mass was similar for the two configurations. Body mass explained 82% of the variation in RMR when it was measured using the "flight" configuration at 32°C, and 91% when using the "rest" configuration at 23°C. The Q10 coefficient calculated based on the two RMR measurements was 2.8. Mass-independent RMR was positively correlated between measurements obtained using the two instrument configurations. However, neither measure of RMR was correlated with peak metabolic rate, which indicates that RMR cannot be used as a surrogate measure for aerobic capacity in the Glanville fritillary. Ectothermic insects may be able to combine high metabolic capacity with no apparent increase in maintenance cost. Even though RMR is among the most frequently measured physiological variables, it may have limited predictive power when it comes to questions related to activity or aerobic capacity, or in the case of butterflies, flight performance.

Discovery, characterization, and engineering of an advantageous Streptomyces host for heterologous expression of natural product biosynthetic gene clusters

BackgroundStreptomyces is renowned for its robust biosynthetic capacity in producing medically relevant natural products. However, the majority of natural products biosynthetic gene clusters (BGCs) either yield low amounts of natural products or remain cryptic under standard laboratory conditions. Various heterologous production hosts have been engineered to address these challenges, and yet the successful activation of BGCs has still been limited. In our search for a valuable addition to the heterologous host panel, we identified the strain Streptomyces sp. A4420, which exhibited rapid initial growth and a high metabolic capacity, prompting further exploration of its potential.ResultsWe engineered a polyketide-focused chassis strain based on Streptomyces sp. A4420 (CH strain) by deleting 9 native polyketide BGCs. The resulting metabolically simplified organism exhibited consistent sporulation and growth, surpassing the performance of most existing Streptomyces based chassis strains in standard liquid growth media. Four distinct polyketide BGCs were chosen and expressed in various heterologous hosts, including the Streptomyces sp. A4420 wild-type and CH strains, alongside Streptomyces coelicolor M1152, Streptomyces lividans TK24, Streptomyces albus J1074, and Streptomyces venezuelae NRRL B-65442. Remarkably, only the Streptomyces sp. A4420 CH strain demonstrated the capability to produce all metabolites under every condition outperforming its parental strain and other tested organisms. To enhance visualization and comparison of the tested strains, we developed a matrix-like analysis involving 15 parameters. This comprehensive analysis unequivocally illustrated the significant potential of the new strain to become a popular heterologous host.ConclusionOur engineered Streptomyces sp. A4420 CH strain exhibits promising attributes for the heterologous expression of natural products with a focus on polyketides, offering an alternative choice in the arsenal of heterologous production strains. As genomics and cloning strategies progress, establishment of a diverse panel of heterologous production hosts will be crucial for expediting the discovery and production of medically relevant natural products derived from Streptomyces.

Identifying protein domain(s) and interactors necessary for Mcrip2 function in brown adipocytes

High in mitochondria and oxidative capacity, brown adipose tissue (BAT) produces heat through the process of adaptive thermogenesis. Understanding the mechanisms that enable the high oxidative metabolic capacity in BAT can provide insight into and enhance current therapeutic approaches targeting conditions of metabolic dysfunction. Recently, the Kralli lab has identified a gene implicated in BAT thermogenesis that encodes the “mitogen-activated protein kinase (MAPK)-regulated corepressor interacting protein 2” (Mcrip2). Preliminary studies show Mcrip2 regulates the mRNA levels of genes involved in oxidative metabolism, including those involved in oxidative phosphorylation ( Uqcrfs1), fatty acid oxidation ( Acat1, Cpt2), and branched-chain amino acid catabolism ( Bcat2, Bckdha, Ivd, Echs1, Pcca). Interestingly, unbiased proteomic experiments in HEK203 cells have identified multiple Mcrip2 interactors (including Ddx6, Atxn2, Atxn2l) involved in RNA processing, translation and decay, suggesting that this regulation could be post-transcriptional. However, how Mcrip2 post-transcriptionally regulates these genes and the identity of the interactors Mcrip2 constitutes its effects through remains unknown. To elucidate the mechanism of action of Mcrip2, the lab created eight C-terminal HA-tagged Mcrip2 mutant constructs, with mutations targeting different evolutionarily conserved regions of the protein. These mutants will be expressed in primary brown adipocytes lacking Mcrip2 to determine if they complement wild-type and will also be used for co-immunoprecipitation. Results from such studies may provide further insight into the role of Mcrip2 in adipocyte oxidative metabolism and, more broadly, in BAT function. NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A novel gluconeogenic route enables efficient use of erythritol in zoonotic Brucella.

Brucellosis is a worldwide extended zoonosis caused by pathogens of the genus Brucella. While most B. abortus, B. melitensis, and B. suis biovars grow slowly in complex media, they multiply intensely in livestock genitals and placenta indicating high metabolic capacities. Mutant analyses in vitro and in infection models emphasize that erythritol (abundant in placenta and genitals) is a preferred substrate of brucellae, and suggest hexoses, pentoses, and gluconeogenic substrates use in host cells. While Brucella sugar and erythritol catabolic pathways are known, growth on 3-4 carbon substrates persists in Fbp- and GlpX-deleted mutants, the canonical gluconeogenic fructose 1,6-bisphosphate (F1,6bP) bisphosphatases. Exploiting the prototrophic and fast-growing properties of B. suis biovar 5, we show that gluconeogenesis requires fructose-bisphosphate aldolase (Fba); the existence of a novel broad substrate bisphosphatase (Bbp) active on sedoheptulose 1,7-bisphosphate (S1,7bP), F1,6bP, and other phosphorylated substrates; that Brucella Fbp unexpectedly acts on S1,7bP and F1,6bP; and that, while active in B. abortus and B. melitensis, GlpX is disabled in B. suis biovar 5. Thus, two Fba-dependent reactions (dihydroxyacetone-phosphate + glyceraldehyde 3-phosphate ⇌ F1,6bP; and dihydroxyacetone-phosphate + erythrose 4-phosphate ⇌ S1,7bP) can, respectively, yield fructose 6-phosphate and sedoheptulose 7-phosphate for classical gluconeogenesis and the Pentose Phosphate Shunt (PPS), the latter reaction opening a new gluconeogenic route. Since erythritol generates the PPS-intermediate erythrose 4-phosphate, and the Fba/Fbp-Bbp route predicts sedoheptulose 7-phosphate generation from erythrose 4-phosphate, we re-examined the erythritol connections with PPS. Growth on erythritol required transaldolase or the Fba/Fbp-Bbp pathway, strongly suggesting that Fba/Fbp-Bbp works as a PPS entry for both erythritol and gluconeogenic substrates in Brucella. We propose that, by increasing erythritol channeling into PPS through these peculiar routes, brucellae proliferate in livestock genitals and placenta in the high numbers that cause abortion and infertility, and make brucellosis highly contagious. These findings could be the basis for developing attenuated brucellosis vaccines safer in pregnant animals.

Sensitivity assessment of diphacinone by pharmacokinetic analysis in invasive black rats in the Bonin (Ogasawara) Archipelago, Japan

The Bonin Archipelago is a United Nations Educational, Scientific and Cultural Organization's World Natural Heritage Site in Japan with a unique ecosystem; however, the invasive rodents preying on endemic species have been a significant concern. The anticoagulant rodenticide, diphacinone, sprayed by the Ministry of the Environment, has succeeded; however, its repeated use leads to rodenticide resistance. This study evaluated the sensitivity by in vivo pharmacokinetics/pharmacodynamics (PK/PD) analysis and physiologically-based pharmacokinetic modeling to diphacinone in black rats (Rattus rattus) captured on the Bonin Archipelago in February 2022. The Bonin rats exhibited prolonged coagulation time after diphacinone administration. They recovered earlier than susceptible black rats, indicating that Bonin rats were less susceptible, though there were no genetic mutations in Vkorc1, the target enzyme of diphacinone. After the administration of diphacinone, hepatic expression levels of Fsp1, identified as the vitamin K reductase, was decreased, however, the Bonin rats exhibited the most minor suppression. The PK analysis showed that the excretion capacity of the Bonin rats was lower than that of the resistant black rats. In the PBPK modeling, the resistant black rats showed higher clearance than the Bonin and susceptible black rats due to high hepatic metabolic capacity. The Bonin rats demonstrated slow absorption and relatively low clearance. This study highlighted the reduced rodenticide-sensitive tendency of wild black rats in the Bonin Archipelago at an in vivo phenotype level. At the same time, they do not have known rodenticide resistance mechanisms, such as hepatic metabolic enhancement or Vkorc1 mutations. It is crucial to monitor the biological levels to evaluate rodenticide sensitivity accurately.

Emerging technologies for advancing microalgal photosynthesis and metabolism toward sustainable production

Microalgae are unicellular photosynthetic microorganisms that play a vital role in primary production and have diverse applications in various industries. They have high photosynthetic and metabolic capacities and can produce a variety of valuable metabolites, such as lipids, carbohydrates, pigments, and proteins. However, practical applications of microalgae are limited to high-value products due to the high production costs. Algal biotechnology faces challenges such as low energy utilization efficiency and product yield that are currently inadequate to fulfill commercial production. To overcome these challenges, emerging technologies have shown promise to achieve higher production efficiency, including molecular manipulation of photosynthetic efficiency and metabolic activities. Here, we provided an overview of the importance, diversity, and photosynthesis of microalgae, as well as strategies for enhancing their photosynthetic efficiency. We discussed various approaches for improving microalgal photosynthesis, including strain selection and optimization, rational genetic modification, and innovative technologies such as spectral recomposition of light, nanomaterials, advanced cultivation systems, and symbiotic systems. Additionally, we summarized metabolic engineering strategies that focus on optimizing the synthesis of value-added metabolites, such as pigments, long-chain polyunsaturated fatty acids, starch, proteins, and hydrogen in microalgae. By concentrating on improving photosynthetic efficiency and the synthesis of bioactive metabolites, this review provided valuable insights into enhancing microalgae production yields. Overcoming limitations in microalgae production costs can lead to broader applications in various industries. Furthermore, we highlight the potential of these strategies in increasing the efficiency of microalgae as a sustainable source for high-value products.

Lack of Musashi-2 induces type IIa fiber-dominated muscle atrophy.

Skeletal muscle is a highly plastic tissue, adapting its structure and metabolism in response to diverse conditions such as contractile activity, nutrients, and diseases. Finding a novel master regulator of muscle mass and quality will provide new therapeutic targets for the prevention and treatment of muscle weakness. Musashi is an RNA-binding protein that dynamically regulates protein expression; it was originally discovered as a cell fate determination factor in neural cells. Here, we report that Musashi-2 (Msi2) is dominantly expressed in slow-type muscle fibers, fibers characterized by high metabolism and endurance. Msi2 knockout (KO) mice exhibited a decrease in both soleus myofiber size and number compared to control mice. Biochemical and histological analyses revealed that type IIa fibers, which are of the fast type but have high metabolic capacity, were decreased in Msi2 KO mice. The contraction force of isolated soleus muscle was lower in KO mice, and the expression of the metabolic proteins, cytochrome c oxidase and myoglobin, was also decreased in KO muscle. Our data demonstrate the critical role of Msi2 in the maintenance of normal fiber-type composition and metabolism.

Saline Sediments as a Suitable Source for Halophilic Inoculums to Degrade Azo Dyes in Synthetic and Real Textile Wastewaters by Microbial Electrochemical Systems

The treatment of textile wastewater (TWW) loaded with recalcitrant azo dyes in bioelectrochemical systems (BES) rather than in physicochemical processes is a low-cost and environmentally friendly process. The main objective of this study is to investigate the potential of different saline sediments collected from extreme Tunisian environments for the formation of bioanodes capable ofsimultaneous azo dyes degradation and electric current generation in synthetic (STWW) and real textile wastewaters (RTWW) characterized by a varied composition of azo dyes and a high salinity. The obtained bioanodes and anolytes were studied comparatively by electrochemical, microscopic, analytical, and molecular tools.Based on the UV–visible spectra analysis, the breakdown of the azo bond was confirmed. With RTWW, the BES achieved a chemical oxygen demand (COD) abatement rate of 85%with a current density of 2.5 A/m2. Microbial community analysis indicated that a diverse community of bacteria was active for effluent treatment coupled with energy production. At the phylum level, the electrodes were primarily colonized by proteobacteria and firmicutes, which are the two phyla most involved in bioremediation. The analysis of the microbial community also showed the abundance of Marinobacter hydrocarbonoclasticus and Marinobacter sp. species characterized by their high metabolic capacity, tolerance to extremophilic conditions, and role in hydrocarbon degradation.

Dynamic changes of the contents of photoprotective substances and photosynthetic maturation during leaf development of evergreen tree species in subtropical forests.

Many studies have investigated the photoprotective and photosynthetic capacity of plant leaves, but few have simultaneously evaluated the dynamic changes of photoprotective capacity and photosynthetic maturation of leaves at different developmental stages. As a result, the process between the decline of photoprotective substances and the onset of photosynthetic maturation during plant leaf development are still poorly understood, and the relationship between them has not been quantitatively described. In this study, the contents of photoprotective substances, photosynthetic pigment content and photosynthetic capacity of leaves at different developmental stages from young leaves to mature leaves were determined by spatio-temporal replacement in eight dominant tree species in subtropical evergreen broadleaved forests. The correlation analysis found that the data sets of anthocyanins, flavonoids, total phenolics and total antioxidant capacity were mainly distributed on one side of the symmetry axis (y=x), while the data sets of flavonoids, total phenolics and total antioxidant capacity were mainly distributed on both sides of the symmetry axis (y=x). In addition, the content of photoprotective substances in plant leaves was significantly negatively correlated with photosynthetic pigment content and photosynthetic capacity but was significantly positively correlated with dark respiration rate (Rd). When chlorophyll accumulated to ~50% of the final value, the photoprotective substance content and Rd of plant leaves reached the lowest level, and anthocyanins disappeared completely; in contrast, the photosynthetic capacity reached the highest level. Our results suggest that anthocyanins mainly play a light-shielding role in the young leaves of most plants in subtropical forests. In addition, 50% chlorophyll accumulation in most plant leaves was the basis for judging leaf photosynthetic maturity. We also believe that 50% chlorophyll accumulation is a critical period in the transition of plant leaves from high photoprotective capacity (high metabolic capacity, low photosynthetic capacity) to low photoprotective capacity (low metabolic capacity, high photosynthetic capacity).

Individual response in body mass and basal metabolism to the risks of predation and starvation in passerines.

Wintering energy management in small passerines has focused on the adaptive regulation of the daily acquisition of energy reserves within a starvation-predation trade-off framework. However, the possibility that the energetic cost of living, i.e. basal metabolic rate (BMR), is being modulated as part of the management energy strategy has been largely neglected. Here, we addressed this possibility by experimentally exposing captive great tits (Parus major) during winter to two consecutive treatments of increased starvation and predation risk for each individual bird. Body mass and BMR were measured prior to and after each week-long treatment. We predicted that birds should be lighter but with a higher metabolic capacity (higher BMR) as a response to increased predation risk, and that birds should increase internal reserves while reducing their cost of living (lower BMR) when exposed to increased starvation risk. Wintering great tits kept a constant body mass independently of a week-long predation or starvation treatment. However, great tits reduced the cost of living (lower BMR) when exposed to the starvation treatment, while BMR remained unaffected by the predation treatment. Energy management in wintering small birds partly relies on BMR regulation, which challenges the current theoretical framework based on body mass regulation.

A one-year follow-up study of treatment-compliant suicide attempt survivors: relationship of CYP2D6-CYP2C19 and polypharmacy with suicide reattempts

This study of a cohort of 1-year treatment-compliant survivors of a suicide attempt examined for the first time whether a high CYP2D6-CYP2C19 metabolic capacity (pharmacogenes related to psychopathology, suicide, and attempt severity) and/or polypharmacy treatments predicted repeat suicide attempts, adjusting for sociodemographic and clinical factors as confounders. Of the 461 (63% women) consecutively hospitalized patients who attempted suicide and were evaluated and treated after an index attempt, 191 (67.5% women) attended their 6- and 12-month follow-up sessions. Clinicians were blinded to the activity scores (AS) of their genotypes, which were calculated as the sum of the values assigned to each allele (CYP2C19 *2, *17; CYP2D6 *3, *4, *4xN, *5, *6, *10, wtxN). No differences were found in polypharmacy prescription patterns and the variability of CYP2D6 and CYP2C19 genotypes between adherents and dropouts, but the formers were older, with a higher frequency of anxiety and bipolar disorders and fewer alcohol and substance use disorders. The risk of reattempts was higher for CYP2D6 ultrarapid (AS > 2) metabolizers (β = 0.561, p = 0.005) and violent suicide survivors (β = −0.219, p = 0.042) if the attempt occurred during the first 6-month period, individuals with an increased number of MINI DSM-IV Axis I mental disorders (β = 0.092, p = 0.032) during the second 6-month period and individuals with a combined high CYP2D6-CYP2C19 metabolic capacity (AS > 4) (β = 0.345, p = 0.024) and an increased use of drugs other than antidepressants, anxiolytics-depressants and antipsychotics-lithium (β = 0.088, p = 0.005) in multiple repeaters during both periods. CYP2D6 and CYP2C19 rapid metabolism and polypharmacy treatment for somatic comorbidities must be considered to prevent the severe side effects of short-term multiple suicide reattempts after a previous attempt.

Siglec-7 represents a glyco-immune checkpoint for non-exhausted effector memory CD8+ T cells with high functional and metabolic capacities.

While inhibitory Siglec receptors are known to regulate myeloid cells, less is known about their expression and function in lymphocytes subsets. Here we identified Siglec-7 as a glyco-immune checkpoint expressed on non-exhausted effector memory CD8+ T cells that exhibit high functional and metabolic capacities. Seahorse analysis revealed higher basal respiration and glycolysis levels of Siglec-7+ CD8+ T cells in steady state, and particularly upon activation. Siglec-7 polarization into the T cell immune synapse was dependent on sialoglycan interactions in trans and prevented actin polarization and effective T cell responses. Siglec-7 ligands were found to be expressed on both leukemic stem cells and acute myeloid leukemia (AML) cells suggesting the occurrence of glyco-immune checkpoints for Siglec-7+ CD8+ T cells, which were found in patients’ peripheral blood and bone marrow. Our findings project Siglec-7 as a glyco-immune checkpoint and therapeutic target for T cell-driven disorders and cancer.

Hydrocarbonoclastic activity in bacterial biofilms: A systematic study emphasizing pseudomonads

Pseudomonas aeruginosa is a ubiquitous fluorescent, rod-shaped pseudomonad, with a high metabolic capacity, and potential for application in processes to remove recalcitrant compounds such as petroleum hydrocarbons (PHC) from the environment. The bacterium persists in sites with highly selective pressures such as those contaminated by PHC. One of the bacterium's strategies is to colonize biofilms which enhance its protection from toxic compounds and favor oil uptake. It is the most prevalent microbe at sites impacted by PHC owing to the use of aliphatic hydrocarbons to form biofilms and other metabolites crucial for the uptake and degradation of crude oil. P. aeruginosa could be useful in biofilm-mediated bioremediation; however, it has been poorly explored in the last ten years. This systematic study addresses recent research on the application of P. aeruginosa/pseudomonads biofilms in bioremediation The studies come from Asia and Africa and emphasized the formation of biofilm by P. aeruginosa and other pseudomonads as crucial elements in the detoxification process of the environment.

Photobacterium arenosum WH24, Isolated from the Gill of Pacific Oyster Crassostrea gigas from the North Sea of Germany: Co-cultivation and Prediction of Virulence

Cream colored bacteria from marine agar, strain WH24, WH77, and WH80 were isolated from the gill of the Crassostrea gigas a Pacific oyster with a filter-feeding habit that compels accompanying bacteria to demonstrate a high metabolic capacity, has proven able to colonize locations with changing circumstances. Based on the 16S rRNA gene sequence, all strains had high similarity to Photobacterium arenosum CAU 1568T (99.72%). This study involved phenotypic traits, phylogenetic analysis, antimicrobial activity evaluation, genome mining, Co-cultivation experiments, and chemical studies of crude extracts using HPLC and LC-HRESIMS. Photobacterium arenosum WH24 and Zooshikella harenae WH53Twere co-cultivated for 3 days in a rotary shaker at 160 rpm at 30 °C, and LC-MS monitored the chemical profiles of the co-cultures on the third day. The UV chromatograms of the extracts of the co-cultivation experiments show that Zooshikella harenae WH53T could be inhibited by strain WH24. The high virulence of Photobacterium arenosum WH24 was confirmed by genome analysis. Gene groups with high virulence potential were detected: tssA (ImpA), tssB (ImpB/vipA), tssC (ImpC/vipB), tssE, tssF (ImpG/vasA), tssG (ImpH/vasB), tssM (IcmF/vasK), tssJ (vasD), tssK (ImpJ/vasE), tssL (ImpK/vasF), clpV (tssH), vasH, hcp, lapP, plpD, and tpsB family.

A feeder cell-free activation and expansion strategy to generate memory-like NK cells sufficient for off-the-shelf multi-dose adoptive cell therapy.

Abstract Adoptive cell therapy (ACT) using NK cells is a promising armament in the fight against cancer. Cytokine induced memory like (CIML) NK cells have been shown in clinical studies to have potent antitumor activity with superior in vivo persistence. Currently, the expansion of NK cells for clinical development is mainly based on feeder cells, which imposes significant regulatory hurdles and increases the costs for manufacturing. We have developed fusion proteins, HCW9201 and HCW9206 comprising of IL-15/IL-18/IL-12 and IL15/IL-7/IL-21, respectively, capable of priming memory-like differentiation and expanding CIML NK cell products without using feeder cells. This “Kick and Expand” strategy allows greater than 100x expansion of CIML NK cells from donor PBMCs in as little as 14 days without the use of exogenous feeder cells. Continued expansion can yield sufficient CIML NK cells for cryopreservation and multiple ACT infusions. The NK cells generated have bona fide memory-like properties: enhanced antitumor activity across multiple cancer cell lines, higher metabolic capacity, stable epigenetic demethylation of the IFN-γ promoter and increased persistence in NSG mice, when compared to conventional NK cells. In conclusion, this “Kick and Expand” process supports generation of abundant CIML NK cells for multiple ACT infusions and provides simpler, more regulatory friendly, off-the-shelf platform for generating NK cell products, including those with chimeric antigen receptor (CAR) constructs.

High Energetic Demand of Elite Rowing – Implications for Training and Nutrition

Purpose: Elite rowers have large body dimensions, a high metabolic capacity, and they realize high training loads. These factors suggest a high total energy requirement (TER), due to high exercise energy expenditure (EEE) and additional energetic needs. We aimed to study EEE and intensity related substrate utilization (SU) of elite rowers during rowing (EEEROW) and other (EEENON-ROW) training. Methods: We obtained indirect calorimetry data during incremental (N = 174) and ramp test (N = 42) ergometer rowing in 14 elite open-class male rowers (body mass 91.8 kg, 95% CI [87.7, 95.9]). Then we calculated EEEROW and SU within a three-intensity-zone model. To estimate EEENON-ROW, appropriate estimates of metabolic equivalents of task were applied. Based on these data, EEE, SU, and TER were approximated for prototypical high-volume, high-intensity, and tapering training weeks. Data are arithmetic mean and 95% confidence interval (95% CI). Results: EEEROW for zone 1 to 3 ranged from 15.6 kcal·min−1, 95% CI [14.8, 16.3] to 49.8 kcal·min−1, 95% CI [48.1, 51.6], with carbohydrate utilization contributing from 46.4%, 95% CI [42.0, 50.8] to 100.0%, 95% CI [100.0, 100.0]. During a high-volume, a high-intensity, or a taper week, TER was estimated to 6,775 kcal·day−1, 95% CI [6,651, 6,898], 5,772 kcal·day−1, 95% CI [5,644, 5,900], or 4,626 kcal∙day−1, 95% CI [4,481, 4,771], respectively. Conclusion: EEE in elite open-class male rowers is remarkably high already during zone 1 training and carbohydrates are dominantly utilized, indicating relatively high metabolic stress even during low intensity rowing training. In high-volume training weeks, TER is presumably at the upper end of the sustainable total energy expenditure. Periodized nutrition seems warranted for rowers to avoid low energy availability, which might negatively impact performance, training, and health.

Perspectives on the Structure and Function of the Avian Respiratory System: Functional Efficiency Built on Structural Complexity

Among the air-breathing vertebrates, regarding respiratory efficiency, the avian respiratory system rests at the evolutionary zenith. Structurally, it is separated into a lung that serves as a gas exchanger and air sacs that mechanically ventilate the lung continuously and unidirectionally in a caudocranial direction. Largely avascular, the air sacs are delicate, transparent, compliant and capacious air-filled spaces that are not meaningfully involved in gas exchange. The avian lungs are deeply and firmly attached to the vertebrae and the ribs on the dorsolateral aspects, rendering them practically rigid and inflexible. The attachment of the lung to the body wall allowed extreme subdivision of the exchange tissue into minuscule and stable terminal respiratory units, the air capillaries. The process generated a large respiratory surface area in small lungs with low volume density of gas exchange tissue. For the respiratory structures, invariably, thin blood-gas barrier, large respiratory surface area and large pulmonary capillary blood volume are the foremost adaptive structural features that confer large total pulmonary morphometric diffusing capacities of O2. At parabronchial level, the construction and the arrangement of the airway- and the vascular components of the avian lung determine the delivery, the presentation and the exposure of inspired air to capillary blood across the blood-gas barrier. In the avian lung, crosscurrent-, countercurrent- and multicapillary serial arterialization systems that stem from the organization of the structural parts of the lung promote gas exchange. The exceptional respiratory efficiency of the avian respiratory system stems from synergy of morphological properties and physiological processes, means by which O2uptake is optimized and high metabolic states and capacities supported. Given that among the extant animal taxa insects, birds and bats (which accomplished volancy chronologically in that order) possess structurally much different respiratory systems, the avian respiratory system was by no means a prerequisite for evolution of powered flight but was but one of the adaptive solutions to realization of an exceptionally efficient mode of locomotion.

CYP450 Metabolism of a Semisynthetic Naphthoquinone, an Anticancer Drug Candidate, by Human Liver Microsomes

CNFD (6b,7-dihydro-5H-cyclopenta[b]naphtho[2,1-d]furan-5,6(9aH)-dione) is a semisynthetic naphthoquinone derived from lawsone that has cytotoxic action in different tumor lines and anticancer activity in vivo. Therefore, this molecule is a relevant candidate for drug development, but there is still no information on its human metabolism and systemic elimination. This study aimed to investigate the in vitro metabolism of this naphthoquinone by human liver microsomes. Initially, in order to determine the in vitro enzymatic kinetic parameters, a high performance liquid chromatography (HPLC) method to quantify the CNFD was developed and validated. In addition, the enzymatic kinetic data, the predicted pharmacokinetic in vivo parameters and the phenotyping study were presented. The main metabolism sites and metabolites have been suggested in silico. The developed HPLC method was linear, reproducible, selective, accurate, and stable. The enzymatic kinetic parameters revealed a sigmoidal profile. In vitro to in vivo extrapolation hepatic metabolic clearance was 10.39 mL min-1 kg-1 protein and the liver extraction rate was 51%. The clearance in vivo associated with a hepatic extraction ratio indicates that the hepatic metabolism is the main route of elimination. Although all cytochrome P450 enzymes evaluated metabolized CNFD, CYP2C9 and CYP3A4 showed higher metabolic capacity. For the first time, metabolism studies of CNFD were demonstrated.

High stability and metabolic capacity of bacterial community promote the rapid reduction of easily decomposing carbon in soil

Irreversible climate change alters the decomposition and sequestration of soil carbon (C). However, the stability of C components in soils with different initial organic matter contents and its relationship with the response of major decomposers to climate warming are still unclear. In this study, we translocated Mollisols with a gradient of organic matter (OM) contents (2%–9%) from in situ cold region to five warmer climatic regions to simulate climate change. Soil C in C-rich soils (OM >5%) was more vulnerable to translocation warming than that in C-poor soils (OM ≤ 5%), with a major loss of functional groups like O-alkyl, O-aryl C and carboxyl C. Variations of microbial β diversity with latitude, temperature and precipitation indicated that C-rich soils contained more resistant bacterial communities and more sensitive fungal communities than C-poor soils, which led to strong C metabolism and high utilization ability of the community in C-rich soils in response to translocation warming. Our results suggest that the higher sensitivity of soils with high organic matter content to climate change is related to the stability and metabolic capacity of major bacterial decomposers, which is important for predicting soil-climate feedback.

Mix-cultured aerobic denitrifying bacterial communities reduce nitrate: Novel insights in micro-polluted water treatment at lower temperature

Three mix-cultured aerobic denitrifiers were screened from a source water reservoir and named HE1, HE3 and SU4. Approximately 72.9%, 68.6% and 66.2% of nitrate were effectively removed from basal medium, respectively, after 120 h of cultivation at 8 °C. The nitrogen balance analysis revealed about one-fifth of the initial nitrogen was converted into gaseous denitrification products. According to the results of Biolog, the three microfloras had high metabolic capacity to carbon sources. The dominant genera were Pseudomonas and Paracoccus in these bacterial communities based on nirS gene sequencing. Response surface methodology elucidated that the denitrification rates of identified bacteria reached the maximum under the following optimal parameters: C/N ratio of 7.51–8.34, pH of 8.03–8.09, temperature of 18.03–20.19 °C, and shaking speed of 67.04–120 rpm. All results suggested that screened aerobic denitrifiers could potentially be applied to improve the source water quality at low temperature.