Impact of steroid biosynthesis on the aerobic adaptation of eukaryotes.

Steroids are indispensable components of the eukaryotic cellular membrane and the acquisition of steroid biosynthesis was a key factor that enabled the evolution of eukaryotes. The polycyclic carbon structures of steroids can be preserved in sedimentary rocks as chemical fossils for billions of years and thus provide invaluable clues to trace eukaryotic evolution from the distant past. Steroid biosynthesis consists of (1) the production of protosteroids and (2) the subsequent modifications toward "modern-type" steroids such as cholesterol and stigmasterol. While protosteroid biosynthesis requires only two genes for the cyclization of squalene, complete modification of protosteroids involves ~10 additional genes. Eukaryotes universally possess at least some of those additional genes and thus produce modern-type steroids as major final products. The geological biomarker records suggest a prolonged period of solely protosteroid production in the mid-Proterozoic before the advent of modern-type steroids in the Neoproterozoic. It has been proposed that mid-Proterozoic protosteroids were produced by hypothetical stem-group eukaryotes that presumably possessed genes only for protosteroid production, even though in modern environments protosteroid production as a final product is found exclusively in bacteria. The host identity of mid-Proterozoic steroid producers is crucial for understanding the early evolution of eukaryotes. In this perspective, we discuss how geological biomarker data and genetic data complement each other and potentially provide a more coherent scenario for the evolution of steroids and associated early eukaryotes. We further discuss the potential impacts that steroids had on the evolution of aerobic metabolism in eukaryotes, which may have been an important factor for the eventual ecological dominance of eukaryotes in many modern environments.

Impacts of elevated temperature, decreased salinity and microfibers on the bioenergetics and oxidative stress in eastern oyster, Crassostrea virginica.

Projected increases in temperature and decreases in salinity associated with global climate change will likely have detrimental impacts on eastern oyster, Crassostrea virginica, as these variables can influence physiological processes in these keystone species. We set out to determine how the interactive effects of temperature (20 °C or 27 °C) and/or salinity (27‰ or 17‰) impacted the energetic reserves, aerobic and anaerobic metabolism, and changes to oxidative stress or total antioxidant potential as a consequence of an altered environment over a 21-day exposure. Gill and adductor muscle were used to quantify changes in total glycogen and lipid content, Electron Transport System and Citrate Synthase activities, Malate Dehydrogenase activity, Protein Carbonyl formation, lipid peroxidation, and total antioxidant potential. A second exposure was performed to determine if these environmental factors influenced the ingestion of microfibers, which are now one of the leading forms of marine debris. Elevated temperature and the combination of elevated temperature and decreased salinity led to an overall decline in oyster mass, which was exacerbated by the presence of microfibers. Changes in metabolism and oxidative stress were largely influenced by time, but exposure to elevated temperature, decreased salinity, the combination of these stressors or exposure to microfibers had small impacts on oyster physiology and survival. Overall these studies demonstrate that oyster are fairly resilient to changes in salinity in short-term exposures, and elevations in temperature or temperature combined with salinity result in changes to the oyster energetic response, which can be further impacted by the presence of microfibers.

The radical impact of oxygen on prokaryotic evolution-enzyme inhibition first, uninhibited essential biosyntheses second, aerobic respiration third.

Molecular oxygen is a stable diradical. All O2-dependent enzymes employ a radical mechanism. Generated by cyanobacteria, O2 started accumulating on Earth 2.4 billion years ago. Its evolutionary impact is traditionally sought in respiration and energy yield. We mapped 365 O2-dependent enzymatic reactions of prokaryotes to phylogenies for the corresponding 792 protein families. The main physiological adaptations imparted by O2-dependent enzymes were not energy conservation, but novel organic substrate oxidations and O2-dependent, hence O2-tolerant, alternative pathways for O2-inhibited reactions. Oxygen-dependent enzymes evolved in ancestrally anaerobic pathways for essential cofactor biosynthesis including NAD+, pyridoxal, thiamine, ubiquinone, cobalamin, heme, and chlorophyll. These innovations allowed prokaryotes to synthesize essential cofactors in O2-containing environments, a prerequisite for the later emergence of aerobic respiratory chains.

The Changes of Amino-Acid Metabolism between Wheat and Rice during Early Growth under Flooding Stress.

Floods induce hypoxic stress and reduce wheat growth. On the other hand, rice is a semi-aquatic plant and usually grows even when partially submerged. To clarify the dynamic differences in the cellular mechanism between rice and wheat under flooding stress, morphological and biochemical analyses were performed. Although the growth of wheat in the early stage was significantly suppressed due to flooding stress, rice was hardly affected. Amino-acid analysis revealed significant changes in amino acids involved in the gamma-aminobutyric acid (GABA) shunt and anaerobic/aerobic metabolism. Flood stress significantly increased the contents of GABA and glutamate in wheat compared with rice, though the abundances of glutamate decarboxylase and succinyl semialdehyde dehydrogenase did not change. The abundance of alcohol dehydrogenase and pyruvate carboxylase increased in wheat and rice, respectively. The contents of aspartic acid and pyruvic acid increased in rice root but remained unchanged in wheat; however, the abundance of aspartate aminotransferase increased in wheat root. These results suggest that flooding stress significantly inhibits wheat growth through upregulating amino-acid metabolism and increasing the alcohol-fermentation system compared to rice. When plant growth is inhibited by flooding stress and the aerobic-metabolic system is activated, GABA content increases.

Estimating maximum oxygen uptake of fishes during swimming and following exhaustive chase - different results, biological bases and applications.

The maximum rate at which animals take up oxygen from their environment (MO2,max) is a crucial aspect of their physiology and ecology. In fishes, MO2,max is commonly quantified by measuring oxygen uptake either during incremental swimming tests or during recovery from an exhaustive chase. In this Commentary, we compile recent studies that apply both techniques to the same fish and show that the two methods typically yield different mean estimates of MO2,max for a group of individuals. Furthermore, within a group of fish, estimates of MO2,max determined during swimming are poorly correlated with estimates determined during recovery from chasing (i.e. an individual's MO2,max is not repeatable across methods). One explanation for the lack of agreement is that these methods measure different physiological states, each with their own behavioural, anatomical and biochemical determinants. We propose that these methods are not directly interchangeable but, rather, each is suited to address different questions in fish biology. We suggest that researchers select the method that reflects the biological contexts of their study, and we advocate for the use of accurate terminology that acknowledges the technique used to elevate MO2 (e.g. peak MO2,swim or peak MO2,recovery). If the study's objective is to estimate the 'true' MO2,max of an individual or species, we recommend that pilot studies compare methods, preferably using repeated-measures designs. We hope that these recommendations contribute new insights into the causes and consequences of variation in MO2,max within and among fish species.

Biosynthetic and catabolic pathways control amino acid δ2H values in aerobic heterotrophs.

The hydrogen isotope ratios (δ2HAA values) of amino acids in all organisms are substantially fractionated relative to growth water. In addition, they exhibit large variations within microbial biomass, animals, and human tissues, hinting at rich biochemical information encoded in such signals. In lipids, such δ2H variations are thought to primarily reflect NADPH metabolism. Analogous biochemical controls for amino acids remain largely unknown, but must be elucidated to inform the interpretation of these measurements. Here, we measured the δ2H values of amino acids from five aerobic, heterotrophic microbes grown on different carbon substrates, as well as five Escherichia coli mutant organisms with perturbed NADPH metabolisms. We observed similar δ2HAA patterns across all organisms and growth conditions, which-consistent with previous hypotheses-suggests a first-order control by biosynthetic pathways. Moreover, δ2HAA values varied systematically with the catabolic pathways activated for substrate degradation, with variations explainable by the isotopic compositions of important cellular metabolites, including pyruvate and NADPH, during growth on each substrate. As such, amino acid δ2H values may be useful for interrogating organismal physiology and metabolism in the environment, provided we can further elucidate the mechanisms underpinning these signals.

Oxidative Stress Induced by Cortisol in Human Platelets.

Hypercortisolism is known to affect platelet function. However, few studies have approached the effect of exogenous cortisol on human platelets, and the results obtained are conflicting and unconvincing. In this study, the effect of exogenous cortisol on several parameters indicative of oxidative status in human platelets has been analysed. We have found that cortisol stimulates ROS production, superoxide anion formation, and lipid peroxidation, with these parameters being in strict correlation. In addition, cortisol decreases GSH and membrane SH-group content, evidencing that the hormone potentiates oxidative stress, depleting platelet antioxidant defence. The involvement of src, syk, PI3K, and AKT enzymes in oxidative mechanisms induced by cortisol is shown. The main sources of ROS in cells can include uncontrolled increase of NADPH oxidase activity and uncoupled aerobic respiration during oxidative phosphorylation. Both mechanisms seem to be involved in ROS formation induced by cortisol, as the NADPH oxidase 1 inhibitor 2(trifluoromethyl)phenothiazine, and rotenone and antimycin A, complex I and III inhibitor, respectively, significantly reduce oxidative stress. On the contrary, the NADPH oxidase inhibitor gp91ds-tat, malate and NaCN, complex II and IV inhibitor, respectively, have a minor effect. It is likely that, in human platelets, oxidative stress induced by cortisol can be associated with venous and arterial thrombosis, greatly contributing to cardiovascular diseases.

Differential changes in blood flow and oxygen utilization in active muscles between voluntary exercise and electrical muscle stimulation in young adults.

The physiological effects on blood flow and oxygen utilization in active muscles during and after involuntary contraction triggered by electrical muscle stimulation (EMS) remain unclear, particularly compared with those elicited by voluntary (VOL) contractions. Therefore, we used diffuse correlation and near-infrared spectroscopy (DCS-NIRS) to compare changes in local muscle blood flow and oxygen consumption during and after these two types of muscle contractions in humans. Overall, 24 healthy young adults participated in the study, and data were successfully obtained from 17 of them. Intermittent (2-s contraction, 2-s relaxation) isometric ankle dorsiflexion with a target tension of 20% of maximal VOL contraction was performed by EMS or VOL for 2 min, followed by a 6-min recovery period. DCS-NIRS probes were placed on the tibialis anterior muscle, and relative changes in local tissue blood flow index (rBFI), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rMRO2) were continuously derived. EMS induced more significant increases in rOEF and rMRO2 than VOL exercise but a comparable increase in rBFI. After EMS, rBFI and rMRO2 decreased more slowly than after VOL and remained significantly higher until the end of the recovery period. We concluded that EMS augments oxygen consumption in contracting muscles by enhancing oxygen extraction while increasing oxygen delivery at a rate similar to the VOL exercise. Under the conditions examined in this study, EMS demonstrated a more pronounced and/or prolonged enhancement in local muscle perfusion and aerobic metabolism compared with VOL exercise in healthy participants.NEW & NOTEWORTHY This is the first study to visualize continuous changes in blood flow and oxygen utilization within contracted muscles during and after electrical muscle stimulation (EMS) using combined diffuse correlation and near-infrared spectroscopy. We found that initiating EMS increases blood flow at a rate comparable to that during voluntary (VOL) exercise but enhances oxygen extraction, resulting in higher oxygen consumption. Furthermore, EMS increased postexercise muscle perfusion and oxygen consumption compared with that after VOL exercise.

Identification of complex III, NQR, and SDH as primary bioenergetic enzymes during the stationary phase of Pseudomonas aeruginosa cultured in urine-like conditions.

Pseudomonas aeruginosa is a common cause of urinary tract infections by strains that are often multidrug resistant, representing a major challenge to the world's health care system. This microorganism has a highly adaptable metabolism that allows it to colonize many environments, including the urinary tract. In this work, we have characterized the metabolic strategies used by stationary phase P. aeruginosa cells cultivated in urine-like media to understand the adaptations used by this microorganism to survive and produce disease. Our proteomics results show that cells rely on the Entner-Duodoroff pathway, pentose phosphate pathway, the Krebs cycle/ glyoxylate shunt and the aerobic oxidative phosphorylation to survive in urine-like media and other conditions. A deep characterization of the oxidative phosphorylation showed that the respiratory rate of stationary phase cells is increased 3-4 times compared to cells in the logarithmic phase of growth, indicating that the aerobic metabolism plays critical roles in the stationary phase of cells grown in urine like media. Moreover, the data show that respiratory complex III, succinate dehydrogenase and the NADH dehydrogenase NQR have important functions and could be used as targets to develop new antibiotics against this bacterium.

Metabolic responses in the gills of Yellowtail Lambari Astyanax lacustris under low- and high-temperature thermal stress.

OBJECTIVE: Ectothermic fish are directly affected by temperature changes in the environment. The aim of this study was to evaluate the metabolic responses in the gills of Yellowtail Lambari Astyanax lacustris under thermal stress. METHODS: To this end, we used spectrophotometry to evaluate the biomarkers of carbohydrate and protein metabolism, antioxidant defense, and oxidative damage in fish subjected to low (15°C) and high (31°C) temperatures, with control groups held at 23°C, for 2, 6, 12, 24, 48, and 96 h. RESULT: The results showed that cold thermal stress did not change the energy demand, and the antioxidant defense was reduced; therefore, the gills were vulnerable to the action of reactive oxygen species (ROS), presenting increased protein carbonylation at 12 h. With heat thermal stress, a higher energy demand was observed, which was verified by an increase in aerobic metabolism by glycolysis and the citric acid cycle. High-temperature stress also increased the antioxidant defenses, as verified by the increased activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. However, the antioxidant defense system could not protect tissues from the action of ROS, as protein carbonylation increased at 6 and 24 h, indicating oxidative stress. CONCLUSION: The results showed that (1) temperature variations caused metabolic adjustments in the gills of Yellowtail Lambari, (2) the adaptive responses were different for winter and summer temperatures, and (3) Yellowtail Lambari recovered homeostasis when subjected to thermal stress, even with the occurrence of oxidative stress.

Effects of substrate roughening on the swimming performance of Schizothorax wangchiachii (Fang, 1936) in the Heishui River: Implications for vertical slot fishway design.

Re-establishing the natural connectivity of rivers using fishways may mitigate the unfavourable effects of dam construction on riverine biodiversity and freshwater fish populations. Knowledge of the swimming performance of target species in specific regions is critical for designing fishways with a high passage efficiency. Substrate roughening with river stones of fishways is considered to improve fish swimming capacity by benefiting from reduced-velocity zones with lower energetic costs. However, the effectiveness of rough substrates in energy metabolism is rarely tested. We investigated the effect of substrate roughening on the swimming capacity, oxygen consumption and behaviour of Schizothorax wangchiachii from the Heishui River in a flume-type swimming respirometer. The results showed that substrate roughening improved critical and burst swimming speed by ~12.9% and ~15.0%, respectively, compared to the smooth substrate. Our results demonstrate that increased reduced-velocity zones, lowered metabolic rate and tail-beat frequency support our hypothesis that lower energetic costs improve fish swimming performance in rough substrate compared to smooth treatment. The traversable flow velocity model predicted that maximum traversable flow velocity and maximum ascent distance were higher over rough compared to smooth substrate fishways. Fishway substrate roughening may be a practical approach to improve fish swimming upstream for demersal riverine fish.

Cellular metabolic pathways of aging in dogs: could p53 and SIRT1 be at play?

Aging and cancer seem to be closely associated, such that cancer is generally considered a disease of the elderly in both humans and dogs. Additionally, cancer is a metabolic shift in itself towards aerobic glycolysis. Larger dog breeds with shorter lifespans, and increased glycolytic cellular metabolic rates, die of cancer more often than smaller breeds. The tumor suppressor p53 factor is a key suppressor oncogene, and the p53 pathway arrests cellular proliferation and prevents DNA mutations from accumulating during cellular stress. The p53 pathway is also associated with the control of cellular metabolism to prevent cellular metabolic shifts common to cancerous phenotypes. SIRT1 deacetylates the p53 tumor suppressor protein, downregulating p53 via effects on stability and activity during stress. Here, we used primary fibroblast cells from small and large puppies and old dogs. Using UV radiation to upregulate the p53 system (100 J/m2), control cells and UV-treated cells were used to measure aerobic and glycolytic metabolic rates using a Seahorse XFe96 oxygen flux analyzer. We also quantified p53 expression and SIRT1 concentration in canine primary fibroblasts before and after UV treatment. We demonstrate that, due to a higher p53 nuclear to cytoplasmic ratio in large breed dogs after UV treatment, p53 could have a more regulatory effect on large breed dogs' metabolism compared with smaller breeds. Thus, there may be a link between p53 upregulation and inhibition of glycolysis in large breed dogs during times of cellular stress compared with small breed dogs. However, SIRT1 concentrations decrease with age in domestic dogs of both size classes, suggesting a possible release of inhibition of p53 through the SIRT1 pathway with age. This may lead to increased incidences of cancer, especially due to the more pronounced upregulation of p53 with cellular stress.

Preliminary study on the mechanism of halofuginone inhibiting the activity of HepG2 cells / 药学学报

This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells. HepG2 cells were used to detect the effects of halofuginone. After treatment, cell activity, cell migration, cell cycle, and cell apoptosis were detected by CCK-8, transwell, and flow cytometry, respectively. The expression levels of growth and metabolism-related factors such as citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and isocitrate deoxygenase (IDH) were detected by real-time quantitative PCR and Western blot. Compared with the control group, the activity of HepG2 cells was significantly inhibited by halofuginone (P < 0.01), the migration rate of HepG2 cells was decreased (P < 0.01), the apoptosis of HepG2 cells was induced (P < 0.01), and the cell cycle was arrested in S phase (P < 0.01). The expression levels of tricarboxylic acid key enzymes CS, IDH3, and OGDH were up-regulated, the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation. In conclusion, halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner, which may be due to the promotion of the aerobic metabolism of cells.

Application and performance of heart-rate-based methods to estimate oxygen consumption at different exercise intensities in postmenopausal women.

PURPOSE: Heart rate (HR) is a widespread method to estimate oxygen consumption ( V ˙ O2), exercise intensity, volume, and energy expenditure. Still, accuracy depends on lab tests or using indexes like HRnet and HRindex. This study addresses HR indexes' applicability in postmenopausal women (PMW), who constitute over 50% of the aging population and may have unique characteristics (e.g., heart size) affecting HR use. METHODS: Fourteen PMW underwent a cycling ramp incremental test to establish the relationships between V ˙ O2 (in MET) and absolute HR, HRnet, and HRindex. In a second group of ten PMW, population-specific and general equations were tested to predict MET and energy expenditure during six constant work exercises at various intensities. Pulmonary gas exchange and HR were continuously measured using a metabolic cart. Correlations, Bland-Altman analysis, and two-way RM-ANOVA were used to compare estimated and measured values. RESULTS: Strong linear relationships between the three HR indexes and MET were found in Group 1. In Group 2, population-specific equations showed medium-to-high correlations, precision, and no significant biases when estimating MET and energy expenditure. HRnet and HRindex outperformed absolute HR in accuracy. General HR equations had similar correlations but exhibited larger biases and imprecision. Statistical differences between measured and estimated values were observed at all intensities with general equations. CONCLUSION: This investigation confirms the suitability of HR for estimating aerobic metabolism in one of the most significant aging populations. However, it emphasizes the importance of considering individual variability and developing population-specific models when utilizing HR to infer metabolism.

Consistent changes in muscle metabolism underlie dive performance across multiple lineages of diving ducks.

Diving animals must sustain high activity with limited O2 stores to successfully capture prey. Studies suggest that increasing body O2 stores supports breath-hold diving, but less is known about metabolic specializations that underlie underwater locomotion. We measured maximal activities of 10 key enzymes in locomotory muscles (gastrocnemius and pectoralis) to identify biochemical changes associated with diving in pathways of oxidative and substrate-level phosphorylation and compared them across three groups of ducks-the longest diving sea ducks (eight spp.), the mid-tier diving pochards (three spp.) and the non-diving dabblers (five spp.). Relative to dabblers, both diving groups had increased activities of succinate dehydrogenase and cytochrome c oxidase, and sea ducks further showed increases in citrate synthase (CS) and hydroxyacyl-CoA dehydrogenase (HOAD). Both diving groups had relative decreases in capacity for anaerobic metabolism (lower ratio of lactate dehydrogenase to CS), with sea ducks also showing a greater capacity for oxidative phosphorylation and lipid oxidation (lower ratio of pyruvate kinase to CS, higher ratio of HOAD to hexokinase). These data suggest that the locomotory muscles of diving ducks are specialized for sustaining high rates of aerobic metabolism, emphasizing the importance of body O2 stores for dive performance in these species.

Crosstalk between the Rod Outer Segments and Retinal Pigmented Epithelium in the Generation of Oxidative Stress in an In Vitro Model.

Dysfunction of the retinal pigment epithelium (RPE) is associated with several diseases characterized by retinal degeneration, such as diabetic retinopathy (DR). However, it has recently been proposed that outer retinal neurons also participate in the damage triggering. Therefore, we have evaluated the possible crosstalk between RPE and photoreceptors in priming and maintaining oxidative damage of the RPE. For this purpose, we used ARPE-19 cells as a model of human RPE, grown in normal (NG, 5.6 mM) or high glucose (HG, 25 mM) and unoxidized (UOx) or oxidized (Ox) mammalian retinal rod outer segments (OSs). ARPE-19 cells were efficient at phagocytizing rod OSs in both NG and HG settings. However, in HG, ARPE-19 cells treated with Ox-rod OSs accumulated MDA and lipofuscins and displayed altered LC3, GRP78, and caspase 8 expression compared to untreated and UOx-rod-OS-treated cells. Data suggest that early oxidative damage may originate from the photoreceptors and subsequently extend to the RPE, providing a new perspective to the idea that retinal degeneration depends solely on a redox alteration of the RPE.

No Signs of Adaptations for High Flight Intensity in the Mitochondrial Genome of Birds.

Mitochondrial genomes are expected to show adaptations for optimizing aerobic respiration in birds that make intense use of flight. However, there is limited empirical evidence of such a relationship. We here examine correlates of several mitochondrial genome characteristics and flight use across a diverse sample of 597 bird species. We developed an index of flight use intensity that ranged from 0 in flightless species to 9 in migratory hummingbirds and examined its association with nucleobase composition, amino acid class composition, and amino acid site allelic variation using phylogenetic comparative methods. We found no evidence of mitochondrial genome adaptations to flight intensity. Neither nucleotide composition nor amino acid properties showed consistent patterns related to flight use. While specific sites in mitochondrial genes exhibited variation associated with flight intensity, there was limited association between specific amino acid residues and flight intensity levels. Our findings suggest a complex genetic architecture for aerobic performance traits, where multiple genes in both mitochondria and the nucleus may contribute to overall performance. Other factors, such as gene expression regulation and anatomical adaptations, may play a more significant role in influencing flight performance than changes in mitochondrial genes. These findings highlight the need for comprehensive genomic analyses to unravel the intricate relationship between genetic variants and aerobic performance in birds.

Mitochondrial Enzyme Activities and Body Condition of Naturally Infected Sunfish (Lepomis gibbosus).

AbstractParasites can affect host behavior, cognition, locomotion, body condition, and many other physiological traits. Changes to host aerobic metabolism may be responsible for these parasite-induced performance alterations. Whole-organism metabolic rate is underpinned by cellular energy metabolism driven most prominently by mitochondria. However, few studies have explored how mitochondrial enzymatic activity relates to body condition and parasite infection, despite it being a putative site for metabolic disruptions related to health status. We studied correlations among natural parasite infection, host body condition, and activity of key mitochondrial enzymes in target organs from wild-caught pumpkinseed sunfish (Lepomis gibbosus) to better understand the cellular responses of fish hosts to endoparasite infection. Enzymatic activities in the gills, spleen, and brain of infected fish were not significantly related to parasite infection or host body condition. However, the activity of cytochrome c oxidase, an enzyme involved in oxidative phosphorylation, in fish hearts was higher in individuals with a lower body condition. Activities of citrate synthase, electron transport system (complexes I and III), and carnitine palmitoyltransferase were also significantly different among organ types. These results provide preliminary information regarding the likely mitochondrial pathways affecting host body condition, the maintenance energetic requirements of different organs, and the organs' specific dependency on particular mitochondrial pathways. These results help pave the way for future studies on the effects of parasite infection on mitochondrial metabolism.

Effect of Polarized Training on Cardiorespiratory Fitness of Untrained Healthy Young Adults: A Randomized Control Trial with Equal Training Impulse.

To explore the effects of 8-week polarized training (POL), high-intensity interval training (HIIT), and threshold training (THR) interventions on the cardiorespiratory fitness (CRF) of untrained healthy young adults. This study recruited 36 young adults and randomly assigned them to POL, HIIT, THR, or control (CG) groups to undergo an 8-week training intervention. The training impulse applied to all three intervention groups was identical. The training intensity was divided into Zone 1, 2, and 3 (Z1, Z2 and Z3) on the basis of the ventilatory thresholds (VT). The weekly training intensity distribution for POL was 75% of Z1 and 25% of Z3; HIIT was 100% of Z3 and THR was 50% of Z1 and 50% of Z2. Each group underwent Bruce protocol testing and supramaximal testing before, during, and after the intervention; relevant CRF parameters were assessed. 8 weeks of POL and HIIT significantly increased VT2 (p < 0.05); 8 weeks of POL, HIIT, THR and significantly increased VO2max and TTE (p < 0.05). The effect size of POL in relation to VO2max and TTE improvements was greater than that of HIIT and THR (g = 2.67 vs. 1.26 and 1.49; g = 2.75 vs. 2.05 and 1.60). Aerobic training models with different intensity distributions have different time effects on improving CRF. Relative to HIIT and THR, POL improved more variables of CRF. Therefore, POL is a feasible aerobic training method for improving CRF.

Altered Mitochondrial Dynamic in Lymphoblasts and Fibroblasts Mutated for FANCA-A Gene: The Central Role of DRP1.

Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure and aplastic anemia. So far, 23 genes are involved in this pathology, and their mutations lead to a defect in DNA repair. In recent years, it has been observed that FA cells also display mitochondrial metabolism defects, causing an accumulation of intracellular lipids and oxidative damage. However, the molecular mechanisms involved in the metabolic alterations have not yet been elucidated. In this work, by using lymphoblasts and fibroblasts mutated for the FANC-A gene, oxidative phosphorylation (OxPhos) and mitochondria dynamics markers expression was analyzed. Results show that the metabolic defect does not depend on an altered expression of the proteins involved in OxPhos. However, FA cells are characterized by increased uncoupling protein UCP2 expression. FANC-A mutation is also associated with DRP1 overexpression that causes an imbalance in the mitochondrial dynamic toward fission and lower expression of Parkin and Beclin1. Treatment with P110, a specific inhibitor of DRP1, shows a partial mitochondrial function recovery and the decrement of DRP1 and UCP2 expression, suggesting a pivotal role of the mitochondrial dynamics in the etiopathology of Fanconi anemia.