Slow Type Research Articles

Vgll2 as an integrative regulator of mitochondrial function and contractility specific to skeletal muscle.

During skeletal muscle adaptation to physiological or pathophysiological signals, contractile apparatus and mitochondrial function are coordinated to alter muscle fiber type. Although recent studies have identified various factors involved in modifying contractile proteins and mitochondrial function, the molecular mechanisms coordinating contractile and metabolic functions during muscle fiber transition are not fully understood. Using a gene-deficient mouse approach, our previous studies uncovered that vestigial-like family member 2 (Vgll2), a skeletal muscle-specific transcription cofactor activated by exercise, is essential for fast-to-slow adaptation of skeletal muscle. The current study provides evidence that Vgll2 plays a role in increasing muscle mitochondrial mass and oxidative capacity. Transgenic Vgll2 overexpression in mice altered muscle fiber composition toward the slow type and enhanced exercise endurance, which contradicted the outcomes observed with Vgll2 deficiency. Vgll2 expression was positively correlated with the expression of genes related to mitochondrial function in skeletal muscle, mitochondrial DNA content, and protein abundance of oxidative phosphorylation complexes. Additionally, Vgll2 overexpression significantly increased the maximal respiration of isolated muscle fibers and enhanced the suppressive effects of endurance training on weight gain. Notably, no additional alteration in expression of myosin heavy chain genes was observed after exercise, suggesting that Vgll2 plays a direct role in regulating mitochondrial function, independent of its effect on contractile components. The observed increase in exercise endurance and metabolic efficiency may be attributed to the acute upregulation of genes promoting fatty acid utilization as a direct consequence of Vgll2 activation facilitated by endurance exercise. Thus, the current study establishes that Vgll2 is an integrative regulator of mitochondrial function and contractility in skeletal muscle.

Genus-wide analysis of Trichoderma antagonism toward Pythium and Globisporangium plant pathogens and the contribution of cellulases to the antagonism.

Parasitism is an important lifestyle in the Trichoderma genus but has not been studied in a genus-wide way toward Pythium and Globisporangium hosts. Our approach screened a genus-wide set of 30 Trichoderma species in dual culture assays with two soil-borne Pythium and three Globisporangium plant-parasitic species and used exo-proteomic analyses, with the aim to correlate Trichoderma antagonism with potential strategies for attacking Pythium and Globisporangium. The Trichoderma spp. showed a wide range of antagonism from strong to weak, but the same Trichoderma strain showed similar levels toward all the Pythium and Globisporangium species. The Trichoderma enzymes from strong (Trichoderma asperellum, Trichoderma atroviride, and Trichoderma virens), moderate (Trichoderma cf. guizhouense and Trichoderma reesei), and weak (Trichoderma parepimyces) antagonists were induced by the autoclaved mycelia of one of the screened Pythium species, Pythium myriotylum. The variable proportions of putative cellulases, proteases, and redox enzymes suggested diverse as well as shared strategies amongst the antagonists. There was a partial positive correlation between antagonism from microscopy and the cellulase activity induced by autoclaved P. myriotylum mycelia in different Trichoderma species. The deletion of the cellulase transcriptional activator XYR1 in T. reesei led to lower antagonism toward Pythium and Globisporangium. The antagonism of Pythium and Globisporangium appears to be a generic property of Trichoderma as most of the Trichoderma species were at least moderately antagonistic. While a role for cellulases in the antagonism was uncovered, cellulases did not appear to make a major contribution to T. reesei antagonism, and other factors are also likely contributing.IMPORTANCETrichoderma is an important genus widely distributed in nature with broad ecological impacts and applications in the biocontrol of plant diseases. The Pythium and Globisporangium genera of fungus-like water molds include many important soil-borne plant pathogens that cause various diseases. Most of the Trichoderma species showed at least a moderate ability to compete with or antagonize the Pythium and Globisporangium hosts, and microscopy showed examples of parasitism (a slow type of killing) and predation (a fast type of killing). Hydrolytic enzymes such as cellulases and proteases produced by Trichoderma likely contribute to the antagonism. A mutant deficient in cellulase activity had reduced antagonism. Interestingly, Pythium and Globisporangium species contain cellulose in their cell walls (unlike true fungi such as Trichoderma), and the cellulolytic ability of Trichoderma appears beneficial for antagonism of water molds.

Smoldering oncolysis by foamy virus carrying CD19 as a CAR target escapes CAR T detection by genomic modification

Chimeric antigen receptor (CAR) Tcells have had limited success against solid tumors. Here, we used an oncolytic foamy virus (oFV) to display a model CAR target antigen (CD19) on tumors in combination with anti-CD19 CAR Tcells. We generated oFV-Δbel2 and oFV-bel2 vectors to test the efficiency and stability of viral/CD19 spread. While both viruses conferred equal CAR T killing invitro, the oFV-Δbel2 virus acquired G-to-A mutations, whereas oFV-bel2 virus had genome deletions. In subcutaneous tumor models invivo, CAR Tcells led to a significant decrease in oFV-specific bioluminescence, confirming clearance of oFV-infected tumor cells. However, the most effective therapy was with high-dose oFV in the absence of CAR Tcells, indicating that CAR T clearance of oFV was detrimental. Moreover, in tumors that escaped CAR Tcell treatment, resurgent virus contained deletions within the oFV-CD19 transgene, allowing the virus to escape CAR T elimination. Therefore, oFV represents a slow smoldering type of oncolytic virus, whose chronic spread through tumors generates anti-tumor therapy, which is abolished by CAR T therapy. These results suggest that further development of this oncolytic platform, with additional immunotherapeutic arming, may allow for an effective combination of chronic oncolysis.

Weak Harnack inequality for doubly non-linear equations of slow diffusion type

We consider non-negative weak super-solutions u:ΩT→R≥0 to the doubly non-linear equation∂t(|u|q−1u)−divA(x,t,u,Du)=0inΩT=Ω×(0,T], where Ω is an bounded open set in RN for N≥2, T>0 and q is a non-negative parameter. Furthermore, the vector field A satisfies standard p-growth assumptions for some p>1. The main novelty of this paper is that we establish the weak Harnack inequality in the entire slow diffusion regime p−q−1>0. Additionally, we only require that the weak super-solution u is located in the function spaceCloc0([0,T];Llocq+1(Ω))∩Llocp(0,T;Wloc1,p(Ω)).

Pebble-depth

In this paper we introduce a new feasible notion of Bennett's logical depth based on pebble transducers. This notion is defined based on the difference between the minimal length descriptional complexity of prefixes of infinite sequences from the perspective of finite-state transducers and pebble transducers. Our notion of pebble-depth satisfies the four fundamental properties of depth: i.e. deep sequences exist, trivial sequences are not deep, random sequences are not deep, and the existence of a slow growth law type result. We also compare pebble-depth to other depth notions based on finite-state transducers, pushdown compressors, and the Lempel-Ziv 78 compression algorithm. We first demonstrate how there exists a normal pebble-deep sequence even though there is no normal finite-state-deep sequence. We next build a sequence that has a pebble-depth level of roughly 1, a pushdown-depth level of roughly 1/2 and a finite-state-depth level of roughly 0. We then build a sequence that has a pebble-depth level of roughly 1/2 and a Lempel-Ziv-depth level of roughly 0.

Piperine enhances contractile force in slow- and fast-twitch muscle.

Piperine has been shown to bind to myosin and shift the distribution of conformational states of myosin molecules from the super-relaxed state to the disordered relaxed state. However, little is known about the implications for muscle force production and potential underlying mechanisms. Muscle contractility experiments were performed using isolated muscles and single fibres from rats and mice. The dose-response effect of piperine on muscle force was assessed at several stimulation frequencies. The potentiation of muscle force was also tested in muscles fatigued by eccentric contractions. Potential mechanisms of force potentiation were assessed by measuring Ca2+ levels during stimulation in enzymatically dissociated muscle fibres, while myofibrillar Ca2+ sensitivity was assessed in chemically skinned muscle fibres. Piperine caused a dose-dependent increase in low-frequency force with no effect on high-frequency force in both slow- and fast-twitch muscle, with similar relative increases in twitch force, rate of force development and relaxation rate. The potentiating effect of piperine on low-frequency force was reversible, and piperine partially recovered low-frequency force in fatigued muscle. Piperine had no effect on myoplasmic free [Ca2+] levels in mouse muscle fibres, whereas piperine substantially augmented the force response to submaximal levels of [Ca2+] in rat MyHCII fibres and MyHCI fibres along with a minor increase in maximum Ca2+-activated force. Piperine enhances low-frequency force production in both fast- and slow-twitch muscle. The effects are reversible and can counteract muscle fatigue. The primary underlying mechanism appears to be an increase in Ca2+ sensitivity. KEY POINTS: Piperine is a plant alkaloid derived from black pepper. It is known to bind to skeletal muscle myosin and enhance resting ATP turnover but its effects on contractility are not well known. We showed for the first time a piperine-induced force potentiation that was pronounced during low-frequency electrical stimulation of isolated muscles. The effect of piperine was observed in both slow and fast muscle types, was reversible, and could counteract the force decrements observed after fatiguing muscle contractions. Piperine treatment caused an increase in myofibrillar Ca2+ sensitivity in chemically skinned muscle fibres, while we observed no effect on intracellular Ca2+ concentrations during electrical stimulation in enzymatically dissociated muscle fibres.

Assessment Of The Process Of Acetylation And Lipid Composition Of Blood In Patients With Chronic Periodontitis Against The Background Of Viral Hepatitis C

The purpose of this study was to study the relationship between alel variants of acetylation and the lipid composition of blood in patients with chronic periodontitis against the background of viral hepatitis C. Biochemical studies were carried out in 42 people aged 18-45 years (24 men and 18 women) diagnosed with chronic periodontitis against the background of chronic hepatitis C. The phenotype of acetylation in saliva and the lipid spectrum of blood were studied. The prevalence of the disease among patients with slow type of acetylation in saliva was noted at an average of 17% in the examined patients of the study group. In patients with slow type of acetylation, a high level of triglycerides was noted, which was accompanied by a low concentration of cholesterol, high and low density lipoproteins in the blood

Fiber type specific myonuclear and satellite cell content comparisons between the vastus lateralis and soleus muscles in humans

Objectives: The purpose of this study was to compare fiber type specific myonuclear and satellite cell number of the vastus lateralis and soleus muscles in humans. Hypotheses: Myonuclear number (MNN), myonuclear domain (MND), and satellite cell number (SCN) would be similar within each fiber type between the vastus lateralis and soleus. Methods: Muscle biopsies from the vastus lateralis and soleus of 24 individuals (34±7y, 24-55y) were sectioned, immunofluorescently stained, and analyzed for MNN, MND, and SCN in slow (myosin heavy chain (MHC) I) and fast (MHC IIa) muscle fibers. SCN was determined only in MHC I fibers for the soleus. MNN and MND were compared for 24 individuals, while SCN was compared for 19 individuals. Results: MNN was similar in MHC I (3.32±0.81 vs. 3.66±0.65 myonuclei/fiber, P=0.067) and IIa (3.63±0.82 vs. 3.83±0.68 myonuclei/fiber, P>0.05) fibers of the vastus lateralis and soleus. Similarly, MND was not different in MHC I (1649±305 vs. 1673±340 μm2/myonuclei, P>0.05) and IIa (1705±313 vs. 1819±394 μm2/myonuclei, P>0.05) fibers of the vastus lateralis and soleus. However, SCN was 62% higher (p<0.05) in MHC I fibers of the soleus (0.127±0.039 satellite cells/fiber) compared with MHC I fibers of the vastus lateralis (0.083±0.024 satellite cells/fiber). Conclusions: The literature is void of comparisons of myonuclei and satellite numbers across different human muscles. These initial results suggest myonuclear number and the area “governed” by each myonuclei (i.e., the myonuclear domain) appears to be similar within the two main fiber types found in the vastus lateralis and soleus muscles. Interestingly, within the same slow fiber type (i.e., MHC I fibers) across these two muscles, it appears the soleus is programmed to have a substantially higher satellite cell content. The basis for this intrinsic difference in slow myofiber satellite profile may be related to the differences in daily myocellular activity between the vastus lateralis and soleus. This research was supported by the National Aeronautics and Space Administration, NNJ06HF59G; the Institute for Translational Sciences at the University of Texas Medical Branch, supported in part by a Clinical and Translational Science Award (UR1TR000071) from the National Center for Advancing Translational Sciences, National Institutes of Health; the NASA Flight Analogs Project; and the Human Bioenergetic Program at Ball State University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Myotube growth is associated with cancer-like metabolic reprogramming and is limited by phosphoglycerate dehydrogenase and pyruvate kinase M2

Skeletal myofiber size and oxidative metabolism are inversely related. Glycolytic fast type myofibers are larger than high high oxidative, slow type myofibers. Paradoxically, despite their lower capacity for protein synthesis (lower myonucluar density and RNA content), glycolytic, low oxidative are more responsive to an anabolic stimulus. We hypothesized that glycolytic myofibers may make use of a Warburg-like metabolic reprogramming in response to an anabolic stimulus. The Warburg effect links growth and glycolysis in tumor cells to generate glycolytic intermediates for synthesis of nucleotides and amino. The aim of this study was to test whether a similar ‘glycolysis-for-anabolism’ metabolic reprogramming also occurs in post-mitotic, hypertrophying myofibers. For this purpose, we first induced C2C12 myotube hypertrophy with IGF-1. We then added 14C glucose to the differentiation medium and measured radioactivity in isolated protein and RNA to establish whether 14C had entered anabolism. We found that especially protein became radioactive, suggesting a glucose → glycolytic intermediates → non-essential amino acid(s) → protein series of reactions, the rate of which was increased by IGF-1. Next, to investigate the importance of glycolytic flux and non-essential amino acid synthesis for myotube hypertrophy, we exposed C2C12 and primary mouse myotubes to the glycolysis inhibitor 2-Deoxy-D-glucose (2DG). We found that inhibiting glycolysis lowered C2C12 and primary myotube size. Similarly, siRNA silencing of PHGDH and PKM2, key enzymes of the Warburg-like metabolic reprogramming, reduced C2C12 and primary myotube growth; whereas retroviral PHGDH overexpression increased C2C12 myotube size. Together these results suggest that glycolysis is important for hypertrophying myotubes, which reprogramme their metabolism to facilitate anabolism, similar to cancer cells. Brendan M. Gabriel was supported by fellowships from the Novo Nordisk Foundation (NNF19OC0055072) & the Wenner-Gren Foundation, an Albert Renold Travel Fellowship from the European Foundation for the Study of Diabetes, and an Eric Reid Fund for Methodology from the Biochemical Society. Abdalla D. Mohamed was funded initially by Sarcoma UK (grant number SUK09.2015), then supported by funding from Postdoctoral Fellowship Program (Helmholtz Zentrum München, Germany), and currently by Cancer Research UK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Drivers of Macroinvertebrate Communities in Mediterranean Rivers: A Mesohabitat Approach

We investigated the relationship between benthic macroinvertebrate community attributes (richness, abundance, biodiversity, and climate-specific and resistance forms) and the physical characteristics of distinct mesohabitats (hydromorphological unit types) discretized into fast (e.g., riffles or rapids) and slow (e.g., pools or glides) flow types in four Mediterranean rivers of Spain. Key attributes of hydromorphological units, including length, width, depth, shade, substrate composition, embeddedness, abundance of aquatic vegetation, and density of woody debris, were considered. Through a comprehensive suite of multivariate analyses, we unraveled taxonomic and habitat distinctions among rivers and hydromorphological unit types, with a notable influence of spatial proximity (greater similarity within the same river basin). In slow hydromorphological units, aquatic vegetation, depth, and abundance of coarse substrate emerged as pivotal factors shaping macroinvertebrate assemblages, whereas in fast-flowing units, vegetation, substrate embeddedness, and density of woody debris were the most important. Contrary to the remaining community attributes, the studied resistance forms (absent, eggs, cocoons, and cells against desiccation and diapause) exhibited uniformity across rivers despite observed variations in macroinvertebrate communities, underscoring regional functional analogies in biological and ecological mechanisms within the investigated Mediterranean river basins. This study contributes valuable insights for anticipating the repercussions of ongoing climate change, particularly in regions where fast-flowing hydromorphological units are more susceptible to depletion during drought periods.

Apelin regulates skeletal muscle adaptation to exercise in a high-intensity interval training model.

Plasma apelin levels are reduced in aging and muscle wasting conditions. We aimed to investigate the significance of apelin signaling in cardiac and skeletal muscle responses to physiological stress. Apelin knockout (KO) and wild-type (WT) mice were subjected to high-intensity interval training (HIIT) by treadmill running. The effects of apelin on energy metabolism were studied in primary mouse skeletal muscle myotubes and cardiomyocytes. Apelin increased mitochondrial ATP production and mitochondrial coupling efficiency in myotubes and promoted the expression of mitochondrial genes both in primary myotubes and cardiomyocytes. HIIT induced mild concentric cardiac hypertrophy in WT mice, whereas eccentric growth was observed in the left ventricles of apelin KO mice. HIIT did not affect myofiber size in skeletal muscles of WT mice but decreased the myofiber size in apelin KO mice. The decrease in myofiber size resulted from a fiber type switch toward smaller slow-twitch type I fibers. The increased proportion of slow-twitch type I fibers in apelin KO mice was associated with upregulation of myosin heavy chain slow isoform expression, accompanied with upregulated expression of genes related to fatty acid transport and downregulated expression of genes related to glucose metabolism. Mechanistically, skeletal muscles of apelin KO mice showed defective induction of insulin-like growth factor-1 signaling in response to HIIT. In conclusion, apelin is required for proper skeletal and cardiac muscle adaptation to high-intensity exercise. Promoting apelinergic signaling may have benefits in aging- or disease-related muscle wasting conditions.NEW & NOTEWORTHY Apelin levels decline with age. This study demonstrates that in trained mice, apelin deficiency results in a switch from fast type II myofibers to slow oxidative type I myofibers. This is associated with a concomitant change in gene expression profile toward fatty acid utilization, indicating an aged-muscle phenotype in exercised apelin-deficient mice. These data are of importance in the design of exercise programs for aging individuals and could offer therapeutic target to maintain muscle mass.

Characterization of Skeletal Muscle Regeneration Revealed a Novel Growth Network Induced by Molecular Acupuncture-like Transfection.

The low efficiency of in vivo transfection of a few fibres revealed a novel tissue network that temporally amplified growth stimulation in the entire regenerating rat soleus muscle. This acupuncture-like effect was demonstrated when the fibres began to grow after complete fibre degradation, synchronous inflammation, myoblast and myotube formation. Neonatal sarcoplasmic/endoplasmic reticulum ATPase (SERCA1b) was first detected in this system. The neonatal, fast and slow SERCA isoforms displayed consequent changes with innervation and differentiation, recapitulating events in muscle development. In vivo transfection of myotubes with plasmids expressing dominant negative Ras or a calcineurin inhibitor peptide (Cain/cabin) proved that expression of the slow myosin heavy chain and the slow muscle type SERCA2a are differentially regulated. In vivo transfection of a few nuclei of myotubes with dnRas or SERCA1b shRNA stimulated fibre size growth in the whole regenerating muscle but only until the full size had been reached. Growth stimulation by Ras and SERCA1b antisense was abolished by co-transfection of Cain or with perimuscular injection of IL4 antibody. This revealed a novel signalling network resembling scale-free networks which, starting from transfected fibre myonuclei as "hubs", can amplify growth stimulation uniformly in the entire regenerating muscle.

Myosin heavy chain-perinatal regulates skeletal muscle differentiation, oxidative phenotype and regeneration.

Myosin heavy chain-perinatal (MyHC-perinatal) is one of two development-specific myosin heavy chains expressed exclusively during skeletal muscle development and regeneration. The specific functions of MyHC-perinatal are unclear, although mutations are known to lead to contracture syndromes such as Trismus-pseudocamptodactyly syndrome. Here, we characterize the functions of MyHC-perinatal during skeletal muscle differentiation and regeneration. Loss of MyHC-perinatal function leads to enhanced differentiation characterized by increased expression of myogenic regulatory factors and differentiation index as well as reduced reserve cell numbers in vitro. Proteomic analysis revealed that loss of MyHC-perinatal function results in a switch from oxidative to glycolytic metabolism in myofibers, suggesting a shift from slow type I to fast type IIb fiber type, also supported by reduced mitochondrial numbers. Paracrine signals mediate the effect of loss of MyHC-perinatal function on myogenic differentiation, possibly mediated by non-apoptotic caspase-3 signaling along with enhanced levels of the pro-survival apoptosis regulator Bcl2 and nuclear factor kappa-B (NF-κB). Knockdown of MyHC-perinatal during muscle regeneration in vivo results in increased expression of the differentiation marker myogenin (MyoG) and impaired differentiation, evidenced by smaller myofibers, elevated fibrosis and reduction in the number of satellite cells. Thus, we find that MyHC-perinatal is a crucial regulator of myogenic differentiation, myofiber oxidative phenotype and regeneration.

COVID-19 and outcomes in Chinese peritoneal dialysis patients.

Reports on COVID-19 in peritoneal dialysis (PD) patients are scarce in China. This study aimed to describe the characteristics and outcomes of PD patients with COVID-19 after China abandoned the 'zero-COVID' policy. This single-centre retrospective study included patients receiving PD who underwent testing for COVID-19 infections between 7 December 2022 and 7 January 2023. Outcomes of interest included factors associated with positive COVID-19 testing result and clinical outcomes including COVID-19-related hospitalisation and severe COVID-19, which were analysed using logistic regression analyses. A total of 349 PD patients (male 53.6%, age 49 ± 13 years old) were included, and 235 patients (67.3%) were infected. There were no significant differences between COVID-19 and non-COVID-19 patients other than higher proportion of vaccinated patients and slow transporters in the patients who tested positive for COVID-19 (44.7% vs. 28.1%, p = 0.003; 8.7% vs. 1.8%, p = 0.03, respectively). Multivariate analysis showed COVID-19 was associated with vaccination (odds ratio (OR): 1.71, 95% confidence interval (CI): 1.02-2.86) and slow transport type (compared with average transport type, OR: 4.52, 95% CI: 1.01-20.21). Among the patients with infection, 38 (16.2%) patients were hospitalised, 18 (7.7%) patients had severe disease and 9 (3.8%) patients died. In multivariate logistic analysis, both age (OR: 1.04, 95% CI: 1.01-1.07; OR: 1.06, 95% CI: 1.02-1.11) and hyponatremia (OR: 5.44, 95% CI: 1.63-18.13; OR: 6.50, 95% CI: 1.77-23.85) were independent risk factors for COVID-19-related hospitalisation and severe disease. Although vaccinated patients were more likely to have tested positive for COVID-19 infection, they appeared to have less severe infection and less need for hospitalisation. Patients who were older with a history of hyponatremia were more likely to experience adverse outcomes from COVID-19.

Enhancing Hybrid Eye Typing Interfaces with Word and Letter Prediction: A Comprehensive Evaluation

Eye typing interfaces enable a person to enter text into an interface using only their own eyes. But despite the inherent advantages of touchless operation and intuitive design, such eye-typing interfaces often suffer from slow typing speeds, resulting in slow words per minute (WPM) counts. In this study, we add word and letter prediction to the eye-typing interface and investigate users’ typing performance as well as their subjective experience while using the interface. In experiment 1, we compared three typing interfaces with letter prediction (LP), letter + word prediction (L + WP), and no prediction (NoP), respectively. We found that the interface with L + WP achieved the highest average text entry speed (5.48 WPM), followed by the interface with LP (3.42 WPM), and the interface with NoP (3.39 WPM). Participants were able to quickly understand the procedural design for word prediction and perceived this function as very helpful. Compared to LP and NoP, participants needed more time to familiarize themselves with L + WP in order to reach a plateau regarding text entry speed. Experiment 2 explored training effects in L + WP interfaces. Two moving speeds were implemented: slow (6.4/s same speed as in experiment 1) and fast (10/s). The study employed a mixed experimental design, incorporating moving speeds as a between-subjects factor, to evaluate its influence on typing performance throughout 10 consecutive training sessions. The results showed that the typing speed reached 6.17 WPM for the slow group and 7.35 WPM for the fast group after practice. Overall, the two experiments show that adding letter and word prediction to eye-typing interfaces increases typing speeds. We also find that more extended training is required to achieve these high typing speeds.

Enhanced capacity for CaMKII signaling mitigates calcium release related contractile fatigue with high intensity exercise

BackgroundWe tested whether enhancing the capacity for calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling would delay fatigue of excitation-induced calcium release and improve contractile characteristics of skeletal muscle during fatiguing exercise. MethodsFast and slow type muscle, gastrocnemius medialis (GM) and soleus (SOL), of rats and mouse interosseus (IO) muscle fibers, were transfected with pcDNA3-based plasmids for rat α and β CaMKII or empty controls. Levels of CaMKII, its T287-phosphorylation (pT287-CaMKII), and phosphorylation of components of calcium release and re-uptake, ryanodine receptor 1 (pS2843-RyR1) and phospholamban (pT17-PLN), were quantified biochemically. Sarcoplasmic calcium in transfected muscle fibers was monitored microscopically during trains of electrical excitation based on Fluo-4 FF fluorescence (n = 5–7). Effects of low- (n = 6) and high- (n = 8) intensity exercise on pT287-CaMKII and contractile characteristics were studied in situ. ResultsCo-transfection with αCaMKII-pcDNA3/βCaMKII-pcDNA3 increased α and βCaMKII levels in SOL (+45.8 %, +250.5 %) and GM (+40.4 %, +89.9 %) muscle fibers compared to control transfection. High-intensity exercise increased pT287-βCaMKII and pS2843-RyR1 levels in SOL (+269 %, +151 %) and GM (+354 %, +119 %), but decreased pT287-αCaMKII and p17-PLN levels in GM compared to SOL (−76 % vs. +166 %; 0 % vs. +128 %). α/β CaMKII overexpression attenuated the decline of calcium release in muscle fibers with repeated excitation, and mitigated exercise-induced deterioration of rates in force production, and passive force, in a muscle-dependent manner, in correlation with pS2843-RyR1 and pT17-PLN levels (|r| > 0.7). ConclusionEnhanced capacity for α/β CaMKII signaling improves fatigue-resistance of active and passive contractile muscle properties in association with RyR1- and PLN-related improvements in sarcoplasmic calcium release.

Correlation analysis of structural characteristics of table tennis players' hitting movements and hitting effects based on data analysis

The increase in table tennis ball size and the decrease in table tennis ball speed and rotation speed in recent years have brought new challenges to the body strength of table tennis players and put new tests on the physical fitness and stability of the hitting action of the players. Improving the body strength can accelerate the rotation speed of the ball, improve the body quality and stability, and improve the accuracy of the ball. Basic skills training is a new method of modern sports training. After scientists studied it, they played a positive role in table tennis. The purpose of the paper is to discuss the impact of table tennis basic skills training, provide more space for the development of physical fitness training, provide the best training tools, and provide ways to improve the impact of hitting. The purpose of this document is to use the sports capture system to collect data from the structural characteristics of table tennis players, analyze the impact of various structural characteristics of the ball, and analyze the impact of various factors affecting table tennis players. In the process of a table tennis player's frontal downward spin stroke, the structure types of the player's frontal downward spin stroke were divided into two types: fast type and slow type according to the different lengths of the three stages of the player's stroke action. The experimental results proved that the optimized model applied to the correlation analysis between the structural characteristics of the stroke action and the stroke effect was stronger, and the accuracy was improved by nearly 5%, achieving the hypothesized goal.

Resolving heterogeneity in Alzheimer's disease based on individualized structural covariance network

The heterogeneity of Alzheimer's disease (AD) poses a challenge to precision medicine. We aimed to identify distinct subtypes of AD based on the individualized structural covariance network (IDSCN) analysis and to research the underlying neurobiology mechanisms. In this study, 187 patients with AD (age = 73.57 ± 6.00, 50% female) and 143 matched normal controls (age = 74.30 ± 7.80, 44% female) were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI) project database, and T1 images were acquired. We utilized the IDSCN analysis to generate individual-level altered structural covariance network and performed k-means clustering to subtype AD based on structural covariance network. Cognition, disease progression, morphological features, and gene expression profiles were further compared between subtypes, to characterize the heterogeneity in AD. Two distinct AD subtypes were identified in a reproducible manner, and we named the two subtypes as slow progression type (subtype 1, n = 104, age = 76.15 ± 6.44, 42% female) and rapid progression type (subtype 2, n = 83, age = 71.98 ± 8.72, 47% female), separately. Subtype 1 had better baseline visuospatial function than subtype 2 (p < 0.05), whereas subtype 2 had better baseline memory function than subtype 1 (p < 0.05). Subtype 2 showed worse progression in memory (p = 0.003), language (p = 0.003), visuospatial function (p = 0.020), and mental state (p = 0.038) than subtype 1. Subtype 1 often shared increased structural covariance network, mainly in the frontal lobe and temporal lobe regions, whereas subtype 2 often shared increased structural covariance network, mainly in occipital lobe regions and temporal lobe regions. Functional annotation further revealed that all differential structural covariance network between the two AD subtypes were mainly implicated in memory, learning, emotion, and cognition. Additionally, differences in gray matter volume (GMV) between AD subtypes were identified, and genes associated with GMV differences were found to be enriched in the terms potassium ion transport, synapse organization, and histone modification and the pathways viral infection, neurodegeneration-multiple diseases, and long-term depression. The two distinct AD subtypes were identified and characterized with neuroanatomy, cognitive trajectories, and gene expression profiles. These comprehensive results have implications for neurobiology mechanisms and precision medicine.

THU658 My Giant Calves Gave Up My Diagnosis: An Extreme Manifestation Of A Very Rare Syndrome With A Severe Elevation Of Tsh Levels

Abstract Disclosure: E.E. Castro Feliu: None. A. Ludena De Freitas: None. A. Torres Rodríguez: None. G. Irizarry: None. Hoffmann’s Syndrome is a rare type of hypothyroidism myopathy in adults that classically presents with muscle cramps, weakness, muscle stiffness, hyporeflexia, delay deep tendon reflexes and pseudohypertrophy. This is the case of a 55-year-old male with history of poorly controlled hypothyroidism and medication non-compliance who was admitted to our institution for non-purulent cellulitis. Vital signs were within normal limits and Body Mass Index was 41.1. Upon physical examination flat affect, periorbital edema, moon facies features and macroglossia were distinguished. Skin had a doughy texture with areas of ichthyosis at upper and lower extremities. Goiter was absent. The most remarkable finding was bilateral calf hypertrophy, with measurements of 56 cm and 55.5 cm in diameter of right and left calves respectively. There was no tenderness to calf palpation and Homan’s sign was absent. Laboratories revealed dyslipidemia with a cholesterol of 308 mg/dL, triglycerides of 782 mg/dL, HDL of 26 mg/dL and LDL of 216 mg/dL with elevated inflammatory markers including sedimentation rate of 77 mm/hr and C-reactive protein of 6.45 mg/dL. Hypothyroidism was suspected therefore thyroid studies were ordered, which was compatible with severe hypothyroidism demonstrated by a record level TSH of 523 lU/ml. Other reported levels were Free T3 0.94pg/ml, total T3 0.5 ng/ml, free thyroxine &amp;lt;0.07 ng/dL, thyroid peroxidase &amp;lt;4, and thyroglobulin AB 19 IU/ml. Hoffmann’s Panel was confirmatory for this diagnosis reporting elevated levels of CPK 1509 U/L, LDH serum of 383 U/L and aldolase of 9.2 u/L. Ultrasound of the neck was non-contributory. Patient received antibiotic therapy for his skin infection and was also treated with IV Levothyroxine, which was prescribed orally upon discharge. Myopathy may be present in patients with longstanding untreated hypothyroidism in which pseudohypertrophy may occur, sometimes involving calf muscles (gastrocnemius). Hoffmann’s Syndrome is associated with changes in muscle fiber type from fast twitch type II to slow twitch type I and alteration of oxidative muscle enzyme activity with deceased calcium ATPase activity of fast twitch type II fibers leading to delayed relaxation. Biopsy of the affected muscle may reveal fiber necrosis, atrophy, hypertrophy with increased number of nuclei and increased connective tissue. Most cases of Hoffmann’s Syndrome improve after treatment with Levothyroxine, therefore, implementing this management on time can be curative. This case highlights the importance of considering this diagnosis when muscle dystrophies are studied and myopathic disorders are suspected, even in the absence of overt manifestations of hypothyroidism. Presentation: Thursday, June 15, 2023

Thoughts on Integrating Evolutionary Analysis into Sociological Action Theory

It is explored if and to what extent two approaches in behavioral sciences, which are promising with respect to an evolutionary grounded, integrative action theory, are actually compatible. These two approaches are, on the one hand, evolutionary psychology, which conceptualizes human nature as a collection of evolved psychological mechanisms, each being functionally specialized with respect to a specific problem of adaptation. And on the other hand, the dual-process perspective, which holds that human behavior is driven by the interplay of two qualitatively distinct types of cognitive processes: Autonomous, fast, and associative Type 1 processes, which operate outside of the consciousness of the actor, on the one hand, and controlled, slow, and rule-based Type 2 processes of which the actor is aware. Notably, both of these approaches have descendants in modern sociological action theory, i.e., goal-framing theory (Lindenberg 2008, 2009) and the model of frame-selection (Esser 2001; Kroneberg 2011). It is argued that evolutionary psychology and the dual-process perspective are largely compatible, thereby giving rise to an evolutionary grounded, integrative action theory. Accordingly, Type 1 processes can be traced back to evolutionary old cognitive modules, which humans share with other species and which are highly efficient at solving specific problems of adaptation in a stable environment. In contrast, Type 2 processes of higher cognition are distinctly developed in humans and highly effective at dealing with a rapidly changing life space.