ABSTRACT
We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m-2) or obese (OB BMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.
Subject(s)
Autopsy , COVID-19 , Metabolome , Obesity , Humans , COVID-19/metabolism , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Obesity/metabolism , Obesity/pathology , Male , Female , Middle Aged , Retrospective Studies , Aged , SARS-CoV-2/metabolism , Adipose Tissue/metabolism , Adipose Tissue/pathology , Metabolomics/methods , Body Mass Index , Adult , Oxidative Stress , Interleukin-6/metabolismABSTRACT
ABSTRACT: Follicular dendritic cell sarcoma is a rare intermediate-grade malignancy characterized by a proliferation of ovoid to spindle-shaped cells with morphologic and immunophenotypic features similar to normal follicular dendritic cells. It may develop in lymph nodes or extranodal sites. Its presentation in extranodal tissues is a diagnostic challenge. It requires a high index of suspicion because follicular dendritic cell markers are not included in the routine immunohistochemical panels used for differential diagnosis. In an extensive review of the English literature, we found 3 cases of follicular dendritic cell sarcoma developing on the skin. We report a case of a primary cutaneous follicular dendritic cell sarcoma in a 28-year-old man, which presented as a 6-mm skin-colored nodule on the right forearm. We describe the morphologic and immunohistochemical features and a review of the literature.
Subject(s)
Dendritic Cell Sarcoma, Follicular , Male , Humans , Adult , Dendritic Cell Sarcoma, Follicular/diagnosis , Dendritic Cell Sarcoma, Follicular/pathology , Skin/pathology , Diagnosis, Differential , Lymph Nodes/pathology , ImmunophenotypingABSTRACT
The Multifactorial Memory Questionnaire (MMQ; Troyer & Rich, [2002]. Psychometric properties of a new metamemory questionnaire for older adults. The Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 57(1), P19-P27) is a widely used measure of subjective memory consisting of three scales: Satisfaction, Ability, and Strategies. Although subjective memory complaints are prevalent across different age groups, the factor structure and psychometric properties of the MMQ have yet to be examined in young adults. Here, we independently replicated the original MMQ factor structure in N = 408 young adults (YA) recruited from undergraduate courses and N = 327 older adults (OA) and, for the first time, assessed the age-invariance of the scale using measurement invariance testing. YAs made significantly higher ratings than OAs on MMQ-Satisfaction and MMQ-Strategies, indicating greater satisfaction with their memory and greater use of strategies, but the groups were similar on MMQ-Ability. The original MMQ factor structure was replicated in OAs but not in YAs, and age invariance was not supported. Future studies seeking to compare young and older adults could therefore consider either requesting modification of the MMQ for use with young adults or using a different scale.
Subject(s)
Psychometrics , Humans , Male , Female , Surveys and Questionnaires , Young Adult , Aged , Adult , Middle Aged , Adolescent , Memory , Metacognition , Aging/psychology , Aged, 80 and over , Age FactorsABSTRACT
In November 2015, a catastrophic rupture of the Fundão dam in Mariana (Brazil), resulted in extensive socio-economic and environmental repercussions that persist to this day. In response, several reforestation programs were initiated to remediate the impacted regions. However, accurately assessing soil health in these areas is a complex endeavor. This study employs machine learning techniques to predict soil quality indicators that effectively differentiate between the stages of recovery in these areas. For this, a comprehensive set of soil parameters, encompassing 3 biological, 16 chemical, and 3 physical parameters, were evaluated for samples exposed to mining tailings and those unaffected, totaling 81 and 6 samples, respectively, which were evaluated over 2 years. The most robust model was the decision tree with a restriction of fewer levels to simplify the tree structure. In this model, Cation Exchange Capacity (CEC), Microbial Biomass Carbon (MBC), Base Saturation (BS), and Effective Cation Exchange Capacity (eCEC) emerged as the most pivotal factors influencing model fitting. This model achieved an accuracy score of 92% during training and 93% during testing for determining stages of recovery. The model developed in this study has the potential to revolutionize the monitoring efforts conducted by regulatory agencies in these regions. By reducing the number of parameters that necessitate evaluation, this enhanced efficiency promises to expedite recovery monitoring, simultaneously enhancing cost-effectiveness while upholding the analytical rigor of assessments.
Subject(s)
Ecosystem , Iron Compounds , Soil/chemistry , Environmental Monitoring , Mining , Brazil , Iron/analysis , Cations , Rivers/chemistryABSTRACT
Sexual rest is a transient condition, which compromises conception rates, characterized by large volumes of ejaculate with high percentages of dead sperm observed in bulls. The biochemical mechanisms leading to this ejaculate pattern are not fully understood. Six adult resting Nellore bulls were submitted to Breeding Soundness Evaluation by four consecutive semen collections through the electroejaculation method during a 30 min period. Each ejaculate had its semen phenotypic parameters; morphology and physical aspects were evaluated. To assess enzymatic activity (superoxide dismutase, catalase, and glutathione S-transferase), lipid peroxidation (concentrations of malondialdehyde and nitric oxide), fatty acid, and proteomic profile aliquots of spermatozoa from the first and fourth ejaculates were used. All sperm parameters differed between the first and fourth ejaculates. Spermatozoa from the first ejaculate showed lower enzymatic activity and a higher concentration of lipid peroxidation markers. Among the 19 identified fatty acids, 52.7% are polyunsaturated. Relative abundance analysis showed that C12:0 and C18:0 fatty acids differed between the first and fourth ejaculates, being the fourth ejaculate richer in spermatozoa. The proteomics analysis identified a total of 974 proteins in both sample groups (first and fourth ejaculates). The majority of identified proteins are related to cellular processes and signaling. Quantitative proteomics showed 36 differentially abundant proteins, 6 up-regulated proteins in the first ejaculate, and 30 up-regulated proteins in the fourth ejaculate. Spermatozoa from bulls at sexual rest have less antioxidant capacity, causing changes in their fatty acid composition and protein profile, which generates the observed sperm pattern and lower fertilization capacity.
Subject(s)
Proteomics , Semen , Male , Cattle , Animals , Spermatozoa , Semen Analysis/veterinary , Oxidative Stress , Fatty Acids , Sperm MotilityABSTRACT
Spathaspora passalidarum is a xylose-fermenting microorganism promising for the fermentation of lignocellulosic hydrolysates. This yeast is more sensitive to ethanol than Saccharomyces cerevisiae for unclear reasons. An RNA-seq experiment was performed to identify transcriptional changes in S. passalidarum in response to ethanol and gain insights into this phenotype. The results showed the upregulation of genes associated with translation and the downregulation of genes encoding proteins involved in lipid metabolism, transporters, and enzymes from glycolysis and fermentation pathways. Our results also revealed that genes encoding heat-shock proteins and involved in antioxidant response were upregulated, whereas the osmotic stress response of S. passalidarum appears impaired under ethanol stress. A pseudohyphal morphology of S. passalidarum colonies was observed in response to ethanol stress, which suggests that ethanol induces a misperception of nitrogen availability in the environment. Changes in the yeast fatty acid profile were observed only after 12 h of ethanol exposure, coinciding with the recovery of the yeast xylose consumption ability. These findings suggest that the lack of fast membrane lipid adjustments, the halt in nutrient absorption and cellular metabolism, and the failure to induce the expression of osmotic stress-responsive genes are the main aspects underlying the low ethanol tolerance of S. passalidarum. KEY POINTS: ⢠Ethanol stress halts Spathaspora passalidarum metabolism and fermentation ⢠Genes encoding nutrient transporters showed downregulation under ethanol stress ⢠Ethanol induces a pseudohyphal cell shape, suggesting a misperception of nutrients.
ABSTRACT
BACKGROUND: Lipomas are the most frequent benign tumor. They have been described as soft, well-defined, slow-growing palpable masses, and classified as deep or superficial. PURPOSE: To present the clinical and ultrasound findings of herniated superficial subcutaneous lipoma (HSL), located in pressure/support areas, not previously described. MATERIAL AND METHODS: A seven-year retrospective review was performed. Patients with a preoperative high-resolution ultrasound (HRUS) diagnosis of HSL archived in the computational system and histological study information were selected. RESULTS: A total of 37 patients (mean age = 46 years) were recruited. The clinical diagnoses were "lipoma" or "suspected lipoma" in just 46% of the cases. This was three times more frequent in women. Tumors were located mainly in the gluteal (38%) and proximal thigh areas (35%). Clinically, all patients showed small, soft, rounded skin nodules. On HRUS, they appear as lipomatous tumors that protruded, compressed, and thinned the covering dermal layer. The subcutaneous portion was bigger than the herniated part, with an iceberg image. CONCLUSION: HSL in support areas have a special clinical ultrasound presentation, not previously described. It is important to recognize them for a proper diagnosis and treatment, especially because they clinically may present as small superficial lesions; however, they are associated with a larger subcutaneous portion (iceberg image). It is probable that an estrogen influence on the adipose tissue can be suspected because of the female predominance.
Subject(s)
Lipoma , Soft Tissue Neoplasms , Humans , Female , Middle Aged , Male , Thigh/diagnostic imaging , Lipoma/diagnostic imaging , Lipoma/pathology , Diagnosis, Differential , Ultrasonography , Retrospective Studies , Soft Tissue Neoplasms/pathologyABSTRACT
Inspiratory muscle training (IMT) is known to promote physiological benefits and improve physical performance in endurance sports activities. However, the metabolic adaptations promoted by different IMT prescribing strategies remain unclear. In this work, a longitudinal, randomized, double-blind, sham-controlled, parallel trial was performed to investigate the effects of 11 weeks (3 days·week-1) of IMT at different exercise intensities on the serum metabolomics profile and its main regulated metabolic pathways. Twenty-eight healthy male recreational cyclists (30.4 ± 6.5 years) were randomized into three groups: sham (6 cm·H2O of inspiratory pressure, n = 7), moderate-intensity (MI group, 60% maximal inspiratory pressure (MIP), n = 11) and high-intensity (HI group, 85-90% MIP, n = 10). Blood serum samples were collected before and after 11 weeks of IMT and analyzed by 1H NMR and UHPLC-HRMS/MS. Data were analyzed using linear mixed models and metabolite set enrichment analysis. The 1H NMR and UHPLC-HRMS/MS techniques resulted in 46 and 200 compounds, respectively. These results showed that ketone body metabolism, fatty acid biosynthesis, and aminoacyl-tRNA biosynthesis were upregulated after IMT, while alpha linolenic acid and linoleic acid metabolism as well as biosynthesis of unsaturated fatty acids were downregulated. The MI group presented higher MIP, Tryptophan, and Valine levels but decreased 2-Hydroxybutyrate levels when compared to the other two studied groups. These results suggest an increase in the oxidative metabolic processes after IMT at different intensities with additional evidence for the upregulation of essential amino acid metabolism in the MI group accompanied by greater improvement in respiratory muscle strength.
Subject(s)
Breathing Exercises , Serum , Humans , Male , Breathing Exercises/methods , Chromatography, High Pressure Liquid , Muscle Strength/physiology , Proton Magnetic Resonance Spectroscopy , Respiratory Muscles , Longitudinal StudiesABSTRACT
Episodic memory is vulnerable to aging and may be influenced by age-related decline in the neurotransmitter acetylcholine. We probed this relation using a novel, minimally invasive transcranial magnetic stimulation marker of brain acetylcholine: short-latency afferent inhibition (SAI). We used neuropsychological testing to construct a composite score of episodic memory in N = 19 community-dwelling older adults, and stratified older adults into Higher- (N = 9) versus Lower-memory (N = 10) groups before SAI. The Higher-memory group showed significantly stronger SAI than the Lower-memory group, indicating an association between higher brain acetylcholine levels and better episodic memory. The two memory groups were equivalent in the potential confounds of age, education, mood, subjective sleep quality, and executive function. These data converge with others to suggest that episodic memory is related to acetylcholine in older adults. This relation should be further investigated, especially with pharmacology and neuroimaging.
Subject(s)
Memory, Episodic , Acetylcholine , Aged , Aging , Brain/diagnostic imaging , Cholinergic Agents , Humans , Neuropsychological Tests , Transcranial Magnetic Stimulation/methodsABSTRACT
BACKGROUND AND AIMS: Obesity affects metabolism, increasing the risk of developing non-communicable diseases in adolescence, due to excess adipose tissue and low cardiorespiratory fitness (CRF). The metabolomics approach allows the elucidation of metabolites, which may have the concentrations altered by several factors, such as body composition (BC). We aimed to analyze the metabolomic profile of normal-weight and overweight adolescents and associate the metabolites with clinical markers related to BC, insulin resistance (IR), and CRF. METHODS AND RESULTS: The sample was composed of 57 adolescents and divided into two groups: the normal-weight group (NWG, n = 24) and the overweight group (OWG, n = 33). They underwent blood collection and anthropometric, BC, and CRF assessment. Blood serum samples were analyzed by 1H-NMR spectroscopy (600 MHz). The OWG presented higher values of body weight (BW), body mass index (BMI), waist circumference (WC), fasting glucose, insulin, IR, cholesterol, and percentage of fat mass (%FM) and lower levels of peak oxygen consumption (VO2 peak) compared with the NWG. The OWG presented lower concentrations of 3-hydroxyisovalerate, glutamate, and methionine as well as higher concentrations of aspartate, asparagine, creatine, glycerol, myo-inositol, proline, pyruvate, tyrosine, and valerate compared with the NWG. The concentrations of glutamate, myo-inositol, creatine, methionine, and valerate correlated with %FM; pyruvate and valerate positively correlated with IR; and glutamate, tyrosine, and valerate negatively correlated with CRF. CONCLUSION: Changes in the BC lead to changes in the metabolomic profile of adolescents, and the altered metabolites are associated with increased IR and low CRF. These results indicate new targets for health monitoring and prevention of cardiovascular and metabolic diseases in adolescents.
Subject(s)
Cardiorespiratory Fitness , Insulin Resistance , Adolescent , Body Mass Index , Humans , Overweight/diagnosis , Serum , Waist CircumferenceABSTRACT
The study aimed to identify and quantify the metabolites profile and metabolic pathways in human muscle tissue engaged during exhaustive high-intensity cycling exercise. Seven healthy physically active men performed a graded exercise test and an exhaustive supramaximal effort at 115% of maximal aerobic power with muscles biopsies performed in rest and immediately after exhaustion for quantifying of muscle metabolites changes by 1 H-NMR spectroscopy. The time until exhaustion (tlim) recorded was 224.7 ± 35.5 s whereas the muscle pH at exhaustion was 6.48 ± 0.05. A total of 54 metabolites were identified and quantified. The most enriched and impacted pathways included: beta oxidation of very long chain fatty acids, mitochondrial electron transport chain, alanine aspartate, and glutamate metabolism, citric acid cycle, arginine biosynthesis, propanoate metabolism, threonine and 2-oxobutanoate degradation and pyruvate metabolism. In addition, the muscle concentrations in Post exercise, compared to Pre increased significantly (p < 0.0398) for fumarate (42.0%), succinate (101.2%), glucose (249.7%), lactate (122.8%), O-acetylcarnitine (164.7%), glycerol (79.3%), AMP (288.2%), 2-oxobutyrate (121.0%), and methanol (58.5%), whereas decreased significantly (p < 0.010) for creatine phosphate (-70.2%), ADP (-56.5%), carnitine (-33.5%), and glutamate (-42.3%). Only the succinate was significantly correlated with tlim (r = -0.76; p = 0.0497). Besides the classical expected contribution of glycolytic and phosphagen energetic pathways, it was demonstrated that the high-intensity exercise is also associated with pathways indicatives of amino acid and fatty acid oxidation metabolisms, highlighting the inverse relation between changes in the intramuscular succinate levels and tlim.
Subject(s)
Exercise , Muscle, Skeletal , Bicycling , Exercise Test , Humans , Male , MetabolomicsABSTRACT
Collision tumours are a random association of two or more neoplasms arising in the same anatomical site. Dilated pore of Winer (DPW) - an adnexal tumour of pilar origin - has been described in collisions with basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and trichoblastoma. We present a literature review of melanoma-associated skin lesions and describe the first collision of a DPW with a melanoma in situ (MIS) and the sequential dermoscopic examination for diagnosis.
Subject(s)
Hair Diseases/pathology , Hair Follicle/pathology , Melanoma/pathology , Skin Neoplasms/pathology , Aged, 80 and over , Female , HumansABSTRACT
Studies of risk perception and risk communication concerning the nuclear area are quite common in scientific literature. However, though numerous studies on this topic point to the importance of scientific and technological knowledge in facilitating the reduction of perceived risks, there are few papers that effectively discuss the role of education in risk communication on the subject, particularly in Brazil. The objective of the present work was to reflect on this problem by analyzing the results obtained from two case studies on the implementation of the Brazilian Multipurpose Reactor, in the city of Iperó, in the state of São Paulo, Brazil. As was verified in the investigation, most participants of the study had high perception of risk with respect to the implementation of the reactor. Nevertheless, although important in the project of the reactor implementation, it was verified that the state, municipal and community schools of the city of Iperó had not participated, in the public hearings nor had they discussed the issue inside the school community, until the moment of the research.
Subject(s)
Communication , Perception , Brazil , Cities , HumansABSTRACT
Aging process is characterized by a progressive decline of several organic, physiological, and metabolic functions whose precise mechanism remains unclear. Metabolomics allows the identification of several metabolites and may contribute to clarifying the aging-regulated metabolic pathways. We aimed to investigate aging-related serum metabolic changes using a metabolomics approach. Fasting blood serum samples from 138 apparently healthy individuals (20−70 years old, 56% men) were analyzed by Proton Nuclear Magnetic Resonance spectroscopy (1H NMR) and Liquid Chromatography-High-Resolution Mass Spectrometry (LC-HRMS), and for clinical markers. Associations of the metabolic profile with age were explored via Correlations (r); Metabolite Set Enrichment Analysis; Multiple Linear Regression; and Aging Metabolism Breakpoint. The age increase was positively correlated (0.212 ≤ r ≤ 0.370, p < 0.05) with the clinical markers (total cholesterol, HDL, LDL, VLDL, triacylglyceride, and glucose levels); negatively correlated (−0.285 ≤ r ≤ −0.214, p < 0.05) with tryptophan, 3-hydroxyisobutyrate, asparagine, isoleucine, leucine, and valine levels, but positively (0.237 ≤ r ≤ 0.269, p < 0.05) with aspartate and ornithine levels. These metabolites resulted in three enriched pathways: valine, leucine, and isoleucine degradation, urea cycle, and ammonia recycling. Additionally, serum metabolic levels of 3-hydroxyisobutyrate, isoleucine, aspartate, and ornithine explained 27.3% of the age variation, with the aging metabolism breakpoint occurring after the third decade of life. These results indicate that the aging process is potentially associated with reduced serum branched-chain amino acid levels (especially after the third decade of life) and progressively increased levels of serum metabolites indicative of the urea cycle.
Subject(s)
Aspartic Acid , Isoleucine , Male , Humans , Young Adult , Adult , Middle Aged , Aged , Female , Leucine , Metabolomics/methods , Metabolome/physiology , Aging , Biomarkers , Valine , Ornithine , UreaABSTRACT
Intrinsic cardiorespiratory fitness (iCRF) indicates the CRF level in the sedentary state. However, even among sedentary individuals, a wide interindividual variability is observed in the iCRF levels, whose associated molecular characteristics are little understood. This study aimed to investigate whether serum and skeletal muscle metabolomics profiles are associated with iCRF, measured by maximal power output (MPO). Seventy sedentary young adults were submitted to venous blood sampling, a biopsy of the vastus lateralis muscle and iCRF assessment. Blood serum and muscle tissue samples were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Metabolites related to iCRF were those supported by three levels of evidence: (1) correlation with iCRF, (2) significant difference between individuals with low and high iCRF, and (3) metabolite contribution to significant pathways associated with iCRF. From 43 serum and 70 skeletal muscle analyzed metabolites, iCRF was positively associated with levels of betaine, threonine, proline, ornithine, and glutamine in serum and lactate, fumarate, NADP+, and formate in skeletal muscle. Serum betaine and ornithine and skeletal muscle lactate metabolites explained 31.2 and 16.8%, respectively, of the iCRF variability in addition to body mass. The results suggest that iCRF in young adults is positively associated with serum and skeletal muscle metabolic levels, indicative of the amino acid and carbohydrate metabolism.
Subject(s)
Cardiorespiratory Fitness , Humans , Magnetic Resonance Spectroscopy , Metabolomics , Muscle, Skeletal , Serum , Young AdultABSTRACT
The yeast Spathaspora passalidarum is able to produce ethanol from D-xylose and D-glucose. However, it is not clear how xylose metabolism is affected by D-glucose when both sugars are available in the culture medium. The aims of this work were to evaluate the influence of D-glucose on D-xylose consumption, ethanol production, gene expression, and the activity of key xylose-metabolism enzymes under both aerobic and oxygen-limited conditions. Ethanol yields and productivities were increased in culture media containing D-xylose as the sole carbon source or a mixture of D-xylose and D-glucose. S. passalidarum preferentially consumed D-glucose in the co-fermentations, which is consistent with the reduction in expression of genes encoding the key xylose-metabolism enzymes. In the presence of D-glucose, the specific activities of xylose reductase (XR), xylitol dehydrogenase (XDH), and xylulokinase (XK) were lower. Interestingly, in accordance with other studies, the presence of 2-deoxyglucose (2DG) did not inhibit the growth of S. passalidarum in culture medium containing D-xylose as the sole carbon source. This indicates that a non-canonical repression pathway is acting in S. passalidarum. In conclusion, the results suggest that D-glucose inhibits D-xylose consumption and prevents the D-xylose-mediated induction of the genes encoding XR, XDH, and XK.
Subject(s)
Saccharomycetales , Xylose , Glucose , Saccharomyces cerevisiaeABSTRACT
We present a 12-year-old girl with multiple geographic capillary malformations in a segmental distribution over the left trunk and arm that were present at birth and evolved over years with ulceration, atrophy, and subsequent scarring. Our case is clinically consistent with the recently described entity "multifocal capillary malformation with segmental distribution and central atrophy." To our knowledge, our patient is the oldest reported to date.
Subject(s)
Arteriovenous Malformations , Vascular Malformations , Arteriovenous Malformations/pathology , Atrophy/pathology , Capillaries/abnormalities , Capillaries/pathology , Child , Female , Humans , Infant, Newborn , Vascular Malformations/diagnosis , Vascular Malformations/pathologyABSTRACT
Lin28a/miRNA let-7b-5p pathway has emerged as a key regulators of energy homeostasis in the skeletal muscle. However, the mechanism through which this pathway is regulated in the skeletal muscle has remained unclear. We have found that 8 wk of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) increased its expression. Conversely, Lin28a expression, a well-known inhibitor of let-7b-5p, was induced by Tr and decreased by Hfd. Similarly, in human muscle biopsies, Tr increased LIN28 expression and decreased let-7b-5p expression. Bioinformatics analysis of LIN28a DNA sequence revealed that its enrichment in peroxisome proliferator-activated receptor delta (PPARδ) binding sites, which is a well-known metabolic regulator of exercise. Treatment of primary mouse skeletal muscle cells or C2C12 cells with PPARδ activators GW501516 and AICAR increased Lin28a expression. Lin28a and let-7b-5p expression was also regulated by PPARδ coregulators. While PPARγ coactivator-1α (PGC1α) increased Lin28a expression, corepressor NCoR1 decreased its expression. Furthermore, PGC1α markedly reduced the let-7b-5p expression. PGC1α-mediated induction of Lin28a expression was blocked by the PPARδ inhibitor GSK0660. In agreement, Lin28a expression was downregulated in PPARδ knocked-down cells leading to increased let-7b-5p expression. Finally, we show that modulation of the Lin28a-let-7b-5p pathway in muscle cells leads to changes in mitochondrial metabolism in PGC1α dependent fashion. In summary, we demonstrate that Lin28a-let-7b-5p is a direct target of PPARδ in the skeletal muscle, where it impacts mitochondrial respiration.
Subject(s)
Mitochondria/metabolism , Muscle, Skeletal/metabolism , PPAR delta/metabolism , RNA-Binding Proteins/genetics , Animals , Cell Line , Down-Regulation , Mice , Muscle Fibers, Skeletal/metabolism , PPAR delta/geneticsABSTRACT
Increasing psychological distance is an established method for improving children's performance in a number of self-regulation tasks. For example, using a delay of gratification (DoG) task, Prencipe and Zelazo (Psychological Science, 2005, Vol. 16, pp. 501-505) showed that 3-year-olds delay more for "other" than they do for "self," whereas 4-year-olds make similar choices for self and other. However, to our knowledge, no work has manipulated language to increase psychological distance in children. In two experiments, we sought to manipulate psychological distance by replicating Prencipe and Zelazo's age-related findings and extending them to older children (Experiment 1) and also sought to manipulate psychological distance using the auxiliary verbs "want" and "should" to prime more impulsive preference-based decisions or more normative optimal decisions (Experiment 2). In Experiment 1, 96 3- to 7-year-olds showed age-related improvements and interactive effects between age and perspective on DoG performance. In Experiment 2, 132 3- to 7-year-olds showed age-related improvements and a marginal interaction between age and perspective on DoG performance, but no effect of auxiliary verbs was detected. Results are discussed in terms of differing developmental trajectories of DoG for self and other due to psychological distancing, and how taking another's perspective may boost DoG in younger children but not older children.
Subject(s)
Child Development/physiology , Delay Discounting/physiology , Language , Adolescent , Age Factors , Child , Child, Preschool , Female , Humans , MaleABSTRACT
There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability.In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels-a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.