Maximum Respiration Rate Research Articles

Cystine reduces mitochondrial dysfunction in C2C12 myotubes under moderate oxidative stress induced by H2O2

Moderate oxidative stress induces temporal impairment in mitochondrial ATP production. As glutathione (GSH) content is reduced to eliminate oxidative stress by oxidation–reduction reaction, intracellular GSH content is crucial for maintaining mitochondrial function under oxidative stress. GSH precursors such as N-acetyl cysteine (NAC) and cysteine are known to suppress oxidative stress based on the supply of cysteine residues being rate-limiting for GSH synthesis. However, it remains unclear whether cystine (Cys2) can suppress mitochondrial dysfunction under oxidative stress conditions. Therefore, we examined whether Cys2 could attenuate mitochondrial dysfunction under moderate oxidative stress without scavenging reactive oxygen species (ROS) in the medium. C2C12 myotubes were incubated for 120 min in a Cys2-supplemented medium and subsequently exposed to hydrogen peroxide (H2O2). Heme oxygenase-1 (HO-1) gene expression, intracellular cysteine and GSH content, intracellular ATP level, and maximal mitochondrial respiration were assessed. Cys2 treatment significantly increased GSH content in a dose-dependent manner under oxidative stress. Cys2 treatment significantly decreased HO-1 expression induced by H2O2 exposure. In addition, maximal mitochondrial respiration rate was decreased by H2O2 exposure, but improved by Cys2 treatment. In conclusion, Cys2 treatment mitigates oxidative stress-induced mitochondrial dysfunction by maintaining GSH content under moderate oxidative stress without scavenging ROS in the medium.

Short-term exposure to a clinical dose of metformin increases skeletal muscle mitochondrial H2O2 emission and production in healthy, older adults: A randomized controlled trial.

Metformin is the most commonly prescribed medication to treat diabetes. Emerging evidence suggests that metformin could have off target effects that might help promote healthy muscle aging, but these effects have not been thoroughly studied in glucose tolerant older individuals. The purpose of this study was to investigate the short-term effects of metformin consumption on skeletal muscle mitochondrial bioenergetics in healthy older adults. We obtained muscle biopsy samples from 16 healthy older adults previously naïve to metformin and treated with metformin (METF; 3F, 5M), or placebo (CON; 3F, 5M), for two weeks using a randomized and blinded study design. Samples were analyzed using high-resolution respirometry, immunofluorescence, and immunoblotting to assess muscle mitochondrial bioenergetics, satellite cell (SC) content, and associated protein markers. We found that metformin treatment did not alter maximal mitochondrial respiration rates in muscle compared to CON. In contrast, mitochondrial H2O2 emission and production were elevated in muscle samples from METF versus CON (METF emission: 2.59±0.72 SE Fold, P=0.04; METF production: 2.29±0.53 SE Fold, P=0.02). Furthermore, the change in H2O2 emission was positively correlated with the change in type 1 myofiber SC content and this was biased in METF participants (Pooled: R2=0.5816, P=0.0006; METF: R2=0.674, P=0.0125). These findings suggest that acute exposure to metformin does not impact mitochondrial respiration in aged, glucose-tolerant muscle, but rather, influences mitochondrial-free radical and SC dynamics. NCT03107884, clinicaltrials.gov.

Elucidation of the mechanisms of trastuzumab-induced severe cardiotoxicity using patient-derived iPSCs cardiomyocyte model.

e24065 Background: Trastuzumab (Tmab) is a highly effective anticancer drug, but it is associated with unpredictable and non-accumulative cardiotoxicity, which can interfere with continuous treatment. In order to elucidate the mechanism of Tmab-induced cardiotoxicity, we attempted to reproduce the cardiotoxicity using disease-specific iPS cells from patients who had suffered myocardial dysfunction after Tmab administration. Methods: From 468 breast cancer patients treated with Tmab at our hospital, we selected three patients exhibiting severe cardiotoxicity (SP) with left ventricular ejection fraction reduced by more than 30% from baseline, and three non-cardiotoxic patients (NP)matched with the SP group on various clinical factors. Patient-specific iPSCs established from peripheral blood samples were differentiated to cardiomyocytes (iPSC-CMs). We evaluated contractility and intracellular metabolic function. Results: Treatment of iPSC-CMs with Tmab for 7 days reduced contraction and relaxation velocity, which were more evident in SP than in NP ( p= .032, .044, respectively). In addition, SP-iPSC-CMs showed a significant decrease in ATP ( p= .048), increase in reactive oxygen species production ( p= .046), and increase in autophagy activity ( p= .030) compared to NP-iPSC-CMs. In contrast, there was no significant difference in the suppression of mitochondrial maximal respiratory rate by Tmab between the two groups. Conclusions: We demonstrated that iPSC-CMs well recapitulate the individual differences in contractile and intracellular metabolic dysfunction caused by Tmab.

Differential hepatic mitochondrial function and gluconeogenic gene expression in 2 Holstein strains in a pasture-based system

The objective of this study was to assess hepatic ATP synthesis in Holstein cows of North American and New Zealand origins and the gluconeogenic pathway, one of the pathways with the highest ATP demands in the ruminant liver. Autumn-calving Holstein cows of New Zealand and North American origins were managed in a pasture-based system with supplementation of concentrate that represented approximately 33% of the predicted dry matter intake during 2017, 2018, and 2019, and hepatic biopsies were taken during mid-lactation at 174 ± 23 days in milk. Cows of both strains produced similar levels of solids-corrected milk, and no differences in body condition score were found. Plasma glucose concentrations were higher for cows of New Zealand versus North American origin. Hepatic mitochondrial function evaluated measuring oxygen consumption rates showed that mitochondrial parameters related to ATP synthesis and maximum respiratory rate were increased for cows of New Zealand compared with North American origin. However, hepatic gene expression of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, and pyruvate dehydrogenase kinase was increased in North American compared with New Zealand cows. These results altogether suggest an increased activity of the tricarboxylic cycle in New Zealand cows, leading to increased ATP synthesis, whereas North American cows pull tricarboxylic cycle intermediates toward gluconeogenesis. The fact that this occurs during mid-lactation could account for the increased persistency of North American cows, especially in a pasture-based system. In addition, we observed an augmented mitochondrial density in New Zealand cows, which could be related to feed efficiency mechanisms. In sum, our results contribute to the elucidation of hepatic molecular mechanisms in dairy cows in production systems with higher inclusion of pastures.

Increased HDAC1 Expression Increases Mitochondrial Dysfunction in Endothelial Cells

Endothelial dysfunction is a critical determinant of many chronic diseases including cardiovascular and kidney disease. Endothelial dysfunction is defined by a loss of NO bioavailability and increased reactive oxygen species (ROS). Previous reports show that mitochondrial‐derived ROS (mtROS) is a major source of ROS in endothelial cells. Endothelial senescence and apoptosis are regulated by mtROS and changes in mitochondrial gene expression. Histone deacetylases (HDACs) remove acetyl groups from histones epigenetically regulating gene transcription via deacetylation of histone proteins or post‐translation deacetylation of non‐histone proteins. We previously presented that increased HDAC1, a class I HDAC, expression reduces NO production and increases maximum respiratory oxygen consumption rate in endothelial cells. Reports also show HDACs function as gene silencers or activators. We hypothesized that increased HDAC1 expression in endothelial cells leads to increased mtROS and mitochondrial dysfunction via increased expression of key mitochondrial genes. Bovine aortic endothelial cells (BAECs) were transiently transfected with HDAC1. BAECs were then evaluated for mtROS by mitoSox fluorescence and mRNA expression of key mitochondrial regulatory genes, NRF2, TFAM, and PGC1a, by RT‐PCR. MitoSox fluorescence was increased in cells with HDAC1 OE as compared to vehicle transfections. Gene expression of TFAM was significantly increased (p=0.0367; n=5); NRF2 expression trended up (p=0.0746; n=5); and, PGC1a expression remained unchanged (p=0.9952; n=5) as compared to vehicle transfections (n=6). These results suggest increased HDAC1 in endothelial cells may lead to increased mtROS and alterations in mitochondrial function.

Assessment of Pulmonary Function Test among Petrol Pump Workers in Bankura District

Background and Aim: Health problems posed by the pollutants at the working environment of an individual are linked to the nature and level of exposure to these hazardous chemicals. Petrol pump workers are exposed to high level of different types of air pollution along with petrol and diesel vapors exhibit a number of effects on the respiratory functions. The main objective of the study was to assess the pulmonary functions in petrol pump workers (filling attendants) who are continuously exposed to petrol/diesel vapors during duty hours and compare with the normal healthy individuals. Materials and Methods: This is a cross-sectional study was conducted at seven different petrol pumps of Bankura and 65 petrol pump workers (filling attendants) were included. Each subject’s age, smoking habits, the duration of exposure, health conditions, BMI and BP were recorded. Their PFT were assessed using spirometer and was compared with 65 normal healthy individuals. Results: A significant decrease in the values of Tidal Volume, Vital Capacity, Peak Expiratory Flow Rate, Maximum Voluntary Ventilation, Respiratory Rate and Oxygen saturation in petrol pump workers when compared to control group. Significant increase in BP was observed in case of petrol pump workers and reduction in muscle strength. Conclusion: The present findings demonstrate the adverse effects of petrol and diesel vapors and fumes, hydrocarbons markedly decreased the pulmonary functions.

Short-term Obesity Worsens Heart Inflammation and Disrupts Mitochondrial Biogenesis and Function in an Experimental Model of Endotoxemia.

Cardiomyopathy is a well-known complication of sepsis that may deteriorate when accompanied by obesity. To test this hypothesis we fed C57black/6 male mice for 6week with a high fat diet (60% energy) and submitted them to endotoxemic shock using E. coli LPS (10mg/kg). Inflammatory markers (cytokines and adhesion molecules) were determined in plasma and heart tissue, as well as heart mitochondrial biogenesis and function. Obesity markedly shortened the survival rate of mouse after LPS injection and induced a persistent systemic inflammation since TNFα, IL-1β, IL-6 and resistin plasma levels were higher 24h after LPS injection. Heart tissue inflammation was significantly higher in obese mice, as detected by elevated mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6 and TNFα). Obese animals presented reduced maximum respiratory rate after LPS injection, however fatty acid oxidation increased in both groups. LPS decreased mitochondrial DNA content and mitochondria biogenesis factors, such as PGC1α and PGC1β, in both groups, while NRF1 expression was significantly stimulated in obese mice hearts. Mitochondrial fusion/fission balance was only altered by obesity, with no influence of endotoxemia. Obesity accelerated endotoxemia death rate due to higher systemic inflammation and decreased heart mitochondrial respiratory capacity.

Establishing prediction model of community-acquired pneumonia complicated with acute respiratory distress syndrome based on artificial neural network

To investigate the independent risk factors of community-acquired pneumonia (CAP) complicated with acute respiratory distress syndrome (ARDS), and the accuracy and prevention value of ARDS prediction based on artificial neural network model in CAP patients. A case-control study was conducted. Clinical data of 414 patients with CAP who met the inclusion criteria and were admitted to the comprehensive intensive care unit and respiratory department of Changzhou Second People's Hospital Affiliated to Nanjing Medical University from February 2020 to February 2021 were analyzed. They were divided into two groups according to whether they had complicated with ARDS. The clinical data of the two groups were collected within 24 hours after admission, the influencing factors of ARDS were screened out by univariate analysis, and the artificial neural network model was constructed. Through the artificial neural network model, the importance of input layer independent variables (that was, the influence factors obtained from univariate analysis) on the output layer dependent variables (whether ARDS occurred) was drawn. The artificial neural network modeling data pairs were randomly divided into training group (n = 290) and verification group (n = 124) in a ratio of 7:3. The overall prediction accuracy of the training group and the verification group was calculated respectively. At the same time, the receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated. All 414 patients were enrolled in the analysis, including 82 patients with ARDS and 332 patients without ARDS. Univariate analysis showed that gender, age, heart rate (HR), maximum systolic blood pressure (MSBP), maximum respiratory rate (MRR), source of admission, C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), neutrophil count (NEUT), eosinophil count (EOS), fibrinogen equivalent unit (FEU), activated partial thromboplastin time (APTT), total bilirubin (TBil), albumin (ALB), lactate dehydrogenase (LDH), serum creatinine (SCr), hemoglobin (Hb) and blood glucose (GLU) were significantly different between the two groups, which might be the risk factors of CAP patients complicated with ARDS. Taking the above 19 risk factors as the input layer and whether ARDS occurred as the output layer, the artificial neural network model was constructed. Among the input layer independent variables, the top five indicators with the largest influence weight on the neural network model were LDH (100.0%), PCT (74.4%), FEU (61.5%), MRR (56.9%), and APTT (51.6%), indicating that that these five indicators had a greater impact on the occurrence of ARDS in patients with CAP. The overall prediction accuracy of the artificial neural network model in the training group was 94.1% (273/290), and that of the verification group was 89.5% (111/124). The AUC predicted by the aforementioned artificial neural network model for ARDS in CAP patients was 0.977 (95% confidence interval was 0.956-1.000). The prediction model of ARDS in CAP patients based on artificial neural network model has good prediction ability, which can be used to calculate the accuracy of ARDS in CAP patients, and specific preventive measures can be given.

Evaluation of environmental and physiological indicators in lactating dairy cows exposed to heat stress.

This study aimed to better understand environmental heat stress and physiological heat strain indicators in lactating dairy cows. Sixteen heat stress indicators were derived using microenvironmental parameters that were measured at the surrounding of cows and at usual fixed locations in the barn by using handheld and fixed subarea sensors, respectively. Twenty high-producing Holstein-Friesian dairy cows (> 30.0kg/day) from an intensive dairy farm were chosen to measure respiration rate (RR), vaginal temperature (VT), and body surface temperature of forehead (FT), eye (ET), and muzzle (MT). Our results show that microenvironments measured by the handheld sensor were slightly warmer and drier than those measured by the fixed subarea sensor; however, their derived heat stress indicators correlated equally well with physiological indicators. Interestingly, ambient temperature (Ta) had the highest correlations with physiological indicators and the best classification performance in recognizing actual heat strain state. Using segmented mixed models, the determined Ta thresholds for maximum FT, mean FT, RR, maximum ET, mean ET, VT, mean MT, and maximum MT were 24.1°C, 24.2°C, 24.4°C, 24.6°C, 24.6°C, 25.3°C, 25.4°C, and 25.4°C, respectively. Thus, we concluded that the fixed subarea sensor is a reliable tool for measuring cows' microenvironments; Ta is an appropriate heat stress indicator; FT, RR, and ET are good early heat strain indicators. The results of this study could be helpful for dairy practitioners in a similar intensive setting to detect and respond to heat strain with more appropriate indicators.

A novel approach to estimate and control denitrification performance in activated sludge systems with respirogram technology

Respirogram technology has been widely applied for aerobic process, however, the response of respirogram to anoxic denitrification is still unclear. To reveal such response may help to design a new method for the evaluation of the performance of denitrification. The size distribution of flocs measured at different denitrification moments demonstrated a clear expansion of flocs triggered by denitrification, during which higher specific endogenous and quasi-endogenous respiration rates (SOURe and SOURq) were also observed. Furthermore, SOURq increases exponentially with the specific denitrification rate (SDNR), suggesting that there should be a maximum SDNR in conventional activated sludge systems. Based on these findings, an index Rq/t, defined as the ratio of quasi-endogenous (OURq) to maximum respiration rate (OURt), is proposed to estimate the denitrification capacity that higher Rq/t indicates higher denitrification potential, which can be readily obtained without complex measurement or analysis, and it offers a novel and promising respirogram-based approach for denitrification estimation and control by taking measures to extend anoxic time to maintain its value at a high level within a certain range.

Exposure assessment of PM2.5 in temple premises and crematoriums in Kanpur, India.

Regular use of incense and earthen lamps in temples leads to the release of particulate matter (PM), airborne flecks, and gaseous pollutants. Similarly, the cremation of dead bodies using timber and other accessories such as incense, organic chemicals containing carbon, and clothes generates air pollutants. It is currently unclear how much emissions and exposure these activities may lead. This work attempts to fill this gap in our understanding by assessing the associated emissions of PM2.5 and the corresponding exposure. Ten temples and two cremation grounds were considered for the sampling of PM2.5. The average PM2.5 concentration at the ten temples and the two crematoriums was found to be 658.30 ± 112.63µg/m3 and 1043.50 ± 191.63µg/m3, respectively. The range of real-time PM2.5 data obtained from the nearest twelve stations located in the vicinity was 113-191µg/m3. The exposure assessment in terms of deposition dose was carried out using the ICRP model. The maximum and minimum total respiratory deposition dose rate for PM2.5 for temples was 175.75µg/min and 101.15µg/min, respectively. For crematoriums, the maximum and minimum value of same was 252.3µg/min and 194.31µg/min, respectively, for an exposure period of 10min.

Liraglutide prevents high glucose induced HUVECs dysfunction via inhibition of PINK1/Parkin-dependent mitophagy

Functional loss of endothelial cells will lead to development and progression of atherosclerosis in diabetic patients. However, dysfunction of endothelial cells in diabetes has yet to be fully understood. We aimed to characterize the potential effects of liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, on preventing high glucose-induced endothelial dysfunction and excessive mitophagic response. Pretreatment with liraglutide prevented downregulation of eNOS phosphorylation and NO secretion, and reduced apoptosis and oxidative stress of the human umbilical vein endothelial cells (HUVECs) exposed to high glucose. We further demonstrated that liraglutide likely mediated such protective effects by reducing PINK1/Parkin mediated mitophagy. Liraglutide markedly decreased high glucose-induced mitochondrial ROS, lessened PINK1 expression and mitochondrial accumulation of Parkin, but recovered SIRT1 expression. Seahorse analysis revealed that liraglutide mitigated high glucose-induced reduction of basal and maximum respiration rates as well as spare respiration capacity. Inhibition of Parkin by RNA silencing not only resulted in increased mitochondrial and cytosolic ROS and reduced mitochondrial mass and mitochondrial membrane potential, but also led to increased apoptotic responses in high glucose treated HUVECs which were not preventable by liraglutide. Together, our study reveals that liraglutide acts upstream of the PINK1/Parkin pathway to effectively counteract high glucose induced cell dysfunction by suppression of the PINK1/Parkin-dependent mitophagy. Therefore, its use as an adjunct therapy for type 2 diabetes mellitus is warranted to reduce the risk of atherosclerosis. Further research is required to examine the exact molecules, including SIRT1, upstream of the PINK1/parkin pathway that liraglutide targets to maintain the mitochondrial homeostasis.

Outcome, Clinical Profile and Risk Factors for Mortality of Neonates Necessitating Mechanical Ventilation

Background: Assisted ventilation has turn out to be an essential part of the neonatal intensive care unit (NICU). It is one of the main methods of support in the ICU and undoubtedly influences the survival of sick newborns. Aims: 1. To investigate common indications for mechanical ventilation in newborns 2. To investigate factors influencing the outcome. Method: It is a descriptive study of 60 infants admitted to the Department of Pediatric Medicine in the ICU over a one-year period in the department of Paediatrics, Abbasi Shaheed Hospital. The information was gathered and analysed in a pre-designed format. Results: Of a total of 60 infants, 46 survived, 14 died, and one infant was discharged despite medical advice. 36 children were born vaginally, 20 were born via LSCS, and 4 via assisted delivery. Postnatal asphyxia was the most common ventilation indication in full-term newborns, while HMD was present in preterm infants. The best results were obtained in ventilated infants with MAS, with 100% survival, followed by apnoea in premature infants, perinatal asphyxia, and HMD. Pulmonary haemorrhage (48.3%) was the most common complication among deceased infants, followed by sepsis (28.3%) and shock (23.4%) with a significant p <0.05. There were no complications in 76.7% of the surviving infants. Conclusions: Among the many widely available variables studied in this study, maximum and mean peak inspiratory pressure (PIP or (PEEP), maximum respiratory rate, maximum mean airway pressure (MAP) and average ventilation demand was much greater among non-survivals in comparison to the survivors. Bicarbonate, PH and excess base have been found to be important determinants of mortality in ventilated newborns. Keywords: Indications, mechanical ventilation and Results

The potential of prodigiosin for control of Prorocentrum donghaiense blooms: Algicidal properties and acute toxicity to other marine organisms at various trophic levels

Prorocentrum donghaiense, a marine dinoflagellate, causes harmful algal blooms (HABs) characterised by the highest outbreak frequency and most extensive coverage among similar species in the East China Sea. Highly efficient and ecofriendly biocontrol strategies should be developed for HAB control. Prodigiosin is an efficient biological algicide that demonstrated strong algicidal activity towards P. donghaiense. However, the mechanism of its toxicity to P. donghaiense is unknown. These factors were investigated to evaluate potential use of prodigiosin for control of P. donghaiense blooms. Photosynthetic electron transport rate, maximum quantum yield and respiration rate of P. donghaiense decreased significantly upon exposure to prodigiosin, indicating that prodigiosin rapidly exerted adverse effects on the chloroplasts and mitochondria. Furthermore, a significant increase in dichlorofluorescein fluorescence intensity indicated an overproduction of reactive oxygen species (ROS). The antioxidant system of P. donghaiense scavenged ROS; however, an increase in malondialdehyde concentrations indicated that excessive ROS were still able to initiate lipid peroxidation. Thus, ROS production resulted in the formation of lipids with a reduced degree of unsaturation. Lipid peroxidation decreased lipid fluidity and rigidified the membrane system, causing serious functional destruction of the membrane. Flow cytometry analysis indicated that prodigiosin arrested the cell cycle of P. donghaiense. However, surviving algal cells were able to repair the damaged functions and resume the cell cycle after prodigiosin was removed by photodegradation. Otherwise, P. donghaiense cells lost their membrane integrity and died. To begin an evaluation of ecological safety of prodigiosin, we tested four marine organisms at various trophic levels. The results of these tests indicated that Chlorella vulgaris, Photobacterium phosphoreum, Artemia salina and Lateolabrax japonicus were less sensitive to prodigiosin than P. donghaiense. Toxicity to all five organisms declined after prodigiosin was exposed to sunlight for 6 h. Considering the toxic doses of prodigiosin to various organisms and its photodegradation characteristics, we suggest that prodigiosin has potential in controlling P. donghaiense blooms but should be applied at night, in small doses, with multiple applications.

Limiting factors for panicle photosynthesis at the anthesis and grain filling stages in rice (Oryza sativa L.).

Panicle photosynthesis is crucial for grain yield in cereal crops; however, the limiting factors for panicle photosynthesis are poorly understood, greatly impeding improvement in this trait. In the present study, pot experiments were conducted to investigate the limiting factors for panicle photosynthesis at the anthesis stage in seven rice genotypes and to examine the temporal variations in photosynthesis during the grain filling stage in the Liangyou 287 genotype. At the anthesis stage, leaf and panicle photosynthesis was positively correlated with stomatal conductance and maximum carboxylation rate, which were in turn associated with hydraulic conductance and nitrogen content, respectively. Panicle hydraulic conductance was positively correlated with the area of bundle sheaths in the panicle neck. During grain filling, leaf and panicle photosynthesis remained constant at the early stage but dramatically decreased from 8 to 9 days after anthesis. The trends of variations in panicle photosynthesis were consistent with those in stomatal conductance but not with those in maximum carboxylation rate. At first, the maximum carboxylation rate and respiration rate in the panicle increased, through elevated panicle nitrogen content, but then drastically decreased, as a result of dehydration. The present study systematically investigated the limiting factors for panicle photosynthesis, which are vital for improving photosynthesis and crop yield.

MicroRNA-101-3p Modulates Mitochondrial Metabolism via the Regulation of Complex II Assembly

MicroRNA-101-3p (miR-101-3p) is a tumour suppressor that regulates cancer proliferation and apoptotic signalling. Loss of miR-101-3p increases the expression of the Polycomb Repressive Complex 2 (PRC2) subunit enhancer of zeste homolog 2 (EZH2), resulting in alterations to the epigenome and enhanced tumorigenesis. MiR-101-3p has also been shown to modulate various aspects of cellular metabolism, however little is known about the mechanisms involved.To investigate the metabolic pathways that are regulated by miR-101-3p, we performed transcriptome and functional analyses of osteosarcoma cells transfected with miR-101-3p. We found that miR-101-3p downregulates multiple mitochondrial processes, including oxidative phosphorylation, pyruvate metabolism, the citric acid cycle and phospholipid metabolism. We also found that miR-101-3p transfection disrupts the transcription of mitochondrial DNA (mtDNA) via the downregulation of the mitochondrial transcription initiation complex proteins TFB2M and Mic60. These alterations in transcript expression disrupt mitochondrial function, with significant decreases in both basal (54%) and maximal (67%) mitochondrial respiration rates. Native gel electrophoresis revealed that this diminished respiratory capacity was associated with reduced steady-state levels of mature succinate dehydrogenase (complex II), with a corresponding reduction of complex II enzymatic activity. Furthermore, miR-101-3p transfection reduced the expression of the SDHB subunit, with a concomitant disruption of the assembly of the SDHC subunit into mature complex II.Overall, we describe a new role for miR-101-3p as a modulator of mitochondrial metabolism via its regulation of multiple mitochondrial processes, including mtDNA transcription and complex II biogenesis.

SOIL MICROBIAL ACTIVITY AS BIOINDICATORS DURING THE DECOMPOSITION OF GRASS RESIDUES IN SANDY CLAY LOAM SOIL

Assessing the quality of the soil is an important method in determining the sustainability and environmental impact of agricultural ecosystems. Soil microbial indices like microbial biomass and microbial activity are important criteria for the determination of soil quality. Laboratory incubation study was undertaken to examine the influence of 2 grass residues on changes in soil microbial indices {(microbial (Cmic: Corg), metabolic (qCO2), carbon mineralization (qM) and microbial biomass change rate (qC) quotients)} in a sandy clay loam soil. Both P.maximum and D.horizontalis amended soil showed maximum soil respiration rate (11.90 mgCO2-C g-1 soil) while P.maximum had maximum cumulative respiration rate (199.90 mgCO2-C g-1 soil) .Microbial biomass C was significantly improved by both P.maximum and D.horizontalis residues under study (158.08 and 162 mg/g respetively). The qCO2 among different grass residues ranged from 1.23 to 1.24μg CO2- C μg-biomass-C -1 on the 82nd day. The results showed that incorporation of both grass residues impacted a positive effect on microbial flora and their activity. The study suggests that the despite the high C:N ratio of grasses, its seems to be of advantage in the maintenance of soil quality in a sandy clay loam soil.

High Leaf Respiration Rates May Limit the Success of White Spruce Saplings Growing in the Kampfzone at the Arctic Treeline.

Arctic Treeline is the transition from the boreal forest to the treeless tundra and may be determined by growing season temperatures. The physiological mechanisms involved in determining the relationship between the physical and biological environment and the location of treeline are not fully understood. In Northern Alaska, we studied the relationship between temperature and leaf respiration in 36 white spruce (Picea glauca) trees, sampling both the upper and lower canopy, to test two research hypotheses. The first hypothesis is that upper canopy leaves, which are more directly coupled to the atmosphere, will experience more challenging environmental conditions and thus have higher respiration rates to facilitate metabolic function. The second hypothesis is that saplings [stems that are 5–10cm DBH (diameter at breast height)] will have higher respiration rates than trees (stems ≥10cm DBH) since saplings represent the transition from seedlings growing in the more favorable aerodynamic boundary layer, to trees which are fully coupled to the atmosphere but of sufficient size to persist. Respiration did not change with canopy position, however respiration at 25°C was 42% higher in saplings compared to trees (3.43±0.19 vs. 2.41±0.14μmolm−2 s−1). Furthermore, there were significant differences in the temperature response of respiration, and seedlings reached their maximum respiration rates at 59°C, more than two degrees higher than trees. Our results demonstrate that the respiratory characteristics of white spruce saplings at treeline impose a significant carbon cost that may contribute to their lack of perseverance beyond treeline. In the absence of thermal acclimation, the rate of leaf respiration could increase by 57% by the end of the century, posing further challenges to the ecology of this massive ecotone.

Snoring Remediation with Oral Appliance Therapy Potentially Reverses Cognitive Impairment: An Intervention Controlled Pilot Study.

Respiration rate (RR) dynamics entrains brain neural networks. RR differences between mild cognitive impairment (MCI) and Alzheimer’s disease (AD) in response to oral appliance therapy (OAT) are unknown. This pilot study investigated if RR during stable sleep shows a relationship to pathological severity in subjects with MCI and AD who snore and if RR is influenced following stabilization of the upper airway using OAT. The study cohort was as follows: cognitively normal (CN; n = 14), MCI (n = 14) and AD (n = 9); and a sub-population receiving intervention, CN (n = 5), MCI (n = 7), AD (n = 6) subjects. The intervention used was an oral appliance plus a mouth shield (Tx). RR maximum (max) rate (breaths/minute) and RR fluctuation during 2116 stable sleep periods were measured. The Montreal cognitive assessment (MoCA) was administered before and after 4 weeks with Tx. Baseline data showed significantly higher RR fluctuation in CN vs. AD (p < 0.001) but not between CN vs. MCI (p = 0.668). Linear mixed model analysis indicated Tx effect (p = 0.008) for RR max. Tx after 4 weeks lowered the RR-max in MCI (p = 0.022) and AD (p < 0.001). Compared with AD RR max, CN (p < 0.001) and MCI (p < 0.001) were higher with Tx after 4 weeks. Some MCI and AD subjects improved executive and memory function after 4 weeks of Tx.

Blood cell respiration rates and mtDNA copy number: A promising tool for the diagnosis of mitochondrial disease

Human mitochondrial diseases are a group of heterogeneous diseases caused by defects in oxidative phosphorylation, due to mutations in mitochondrial (mtDNA) or nuclear DNA. The diagnosis of mitochondrial disease is challenging since mutations in multiple genes can affect mitochondrial function, there is considerable clinical variability and a poor correlation between genotype and phenotype. Herein we assessed mitochondrial function in peripheral blood mononuclear cells (PBMCs) and platelets from volunteers without known metabolic pathology and patients with mitochondrial disease. Oxygen consumption rates were evaluated and respiratory parameters indicative of mitochondrial function were obtained.A negative correlation between age and respiratory parameters of PBMCs from control individuals was observed. Surprisingly, respiratory parameters of PBMCs normalized by cell number were similar in patients and young controls. Considering possible compensatory mechanisms, mtDNA copy number in PBMCs was quantified and an increase was found in patients with respect to controls. Hence, respiratory parameters normalized by mtDNA copy number were determined, and in these conditions a decrease in maximum respiration rate and spare respiratory capacity was observed in patients relative to control individuals.In platelets no decay was seen in mitochondrial function with age, while a reduction in basal, ATP-independent and ATP-dependent respiration normalized by cell number was detected in patients compared to control subjects.In summary, our results offer promising perspectives regarding the assessment of mitochondrial function in blood cells for the diagnosis of mitochondrial disease, minimizing the need for invasive procedures such as muscle biopsies, and for following disease progression and response to treatments.