bioRxiv - Physiology最新文献

{"title":"Rapamycin increases murine lifespan but does not reduce mineral volume in the Matrix GLA Protein (MGP) knockout mouse model of medial arterial calcification.","authors":"Parya Behzadi, Rolando A. Cuevas, Alex Crane, Andrew A. Wendling, Claire C. Chu, William J. Moorhead, Ryan Wong, Mark Brown, Joshua Tamakloe, Swathi Suresh, Payam Saleh, Iris A. Jaffe, Allison L. Kuipers, Lyudmila Lukashova, Konstantinos Verdelis, Cynthia St. Hilaire","doi":"10.1101/2024.08.01.606196","DOIUrl":"https://doi.org/10.1101/2024.08.01.606196","url":null,"abstract":"Peripheral artery disease (PAD) is the narrowing of the arteries that carry blood to the lower extremities. PAD has been traditionally associated with atherosclerosis. However, recent studies have found a distinct pathology when chronic limb ischemia occurs below the knee which is characterized by medial arterial calcification (MAC) which more commonly leads to limb amputation. MAC involves calcification of the elastin fibers surrounding smooth muscle cells (SMCs) in arteries. Matrix GLA Protein (MGP) binds circulating calcium and inhibits vascular calcification. Mgp-/- mice develop severe MAC and die within 8 weeks of birth due to aortic rupture or heart failure. We previously discovered a rare genetic disease Arterial Calcification due to Deficiency in CD73 (ACDC) in which patients present with extensive MAC in their lower extremity arteries. Using a patient-specific induced pluripotent stem cell model we found that rapamycin inhibited calcification. Here we investigated whether rapamycin could reduce MAC in vivo using Mgp-/- mice as a model. Mgp+/+ and Mgp-/- mice received 5mg/kg rapamycin or vehicle. Calcification content was assessed via microCT, and vascular morphology and extracellular matrix content assessed histologically. Immunostaining and western blot analysis were used to examine SMC phenotypes and cellular functions. Rapamycin prolonged Mgp-/- mice lifespan, decreased mineral density in the arteries, and increased smooth muscle actin protein levels, however, calcification volume, vessel morphology, SMC proliferation, and autophagy flux were all unchanged. These findings suggest that effects of rapamycin in the Mgp-/- mouse are independent of the vascular phenotype.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"106 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional and Metabolic Mechanism of Carbon Dots Enhancing Rice Growth and Resistance by Promoting Root","authors":"Yadong Li, Ronghua Xu, Jingyi Qi, Shang Lei, Qianying Han, Congli Ma, Yunlong Ru, Hongjie Wang","doi":"10.1101/2024.08.01.606230","DOIUrl":"https://doi.org/10.1101/2024.08.01.606230","url":null,"abstract":"Increasing climate change and pollutant discharge induce constant challenges to crops, while crops are vulnerable to environmental and pollutant stresses. In this study, a carbon dots (CDs) was developed that significantly increased rice seedling growth, and successfully reduced the inhibition of heavy metal cadmium (Cd), salt (NaCl), and herbicide 2,4-D stresses on rice seed-ling growth by pre-spraying. The root of rice seedlings responded specifically to CDs exposure, with significant improvements in root biomass, architecture, cell wall thickness, mechanical strength, and metabolic vitality. Metabolomics and transcriptomics were combined to reveal the regulatory mechanism of CDs in rice seedlings. Transcriptome analysis indicated that CDs up-regulated genes related to cytokinin, jasmonic acid, salicylic acid, MAPK signaling pathway, calcium homeostasis, and peroxidase, and downregulated those related to auxin, abscisic acid, and ethylene. Metabolomic analysis suggested CDs improved the metabolites related to antioxidant (betalain, ascorbate, aldarate, and glutathione), formation of cell wall, plasma membrane, xylem, and root cortex (phenylpropanoids biosynthesis, stilbenoid, diarylheptanoid and gingerol biosynthesis, and sphingolipid), and energy metabolism (nicotinate, nicotinamide, glyoxylate, dicarboxylate, and nitrate cycle) in rice seedlings. Therefore, pre-spraying CDs reprogrammed stress signaling pathways and enhanced adaptive responses in rice seedlings, ultimately increasing growth potential and stress resistance. This study presents a promising nano-bio-stimulant of CDs for crop resilience in the context of increasing climate change and contributes to sustainable agriculture.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Atrial Natriuretic Peptide Clearance Reduces Myocardial Fibrosis and Improves Cardiac Function in Diabetic Rats","authors":"Nassim Fares, Jules Joel Bakhos, Youakim Saliba, Joelle Hajal, Guy Achkouty, Hrag Oskaridjian, Chloe Azevedo, Albert Semaan, Nadine Suffee, Elise Balse, Stephane N Hatem","doi":"10.1101/2024.08.01.606125","DOIUrl":"https://doi.org/10.1101/2024.08.01.606125","url":null,"abstract":"Background: Natriuretic peptides (NP) exert pleotropic effects through the recruitment of cGMP-signaling pathways depending on their bioavailability which is regulated by clearance receptors and peptidases. Here, we tested the hypothesis that increasing myocardial bioavailability of NP has a beneficial effect on heart failure. We studied the effects of a mutated NP, MANP, resistant to neprilysin in a model of diabetic cardiomyopathy characterized by a marked myocardial fibrosis.\u0000Methods: Natriuretic peptides as well as sacubritril were delivered via osmotic mini-pumps to high-fat/streptozotocin-induced type-2 diabetic (T2D) rats. Cardiac function was evaluated by echocardiography. Myocardial remodeling was studied by histological approaches, collagen phenotype and measurement of cGMP tissue concentration. Live-cell cGMP biosensing was conducted on cultured rat cardiac fibroblasts to investigate biological effects of NPs. cGMP signaling pathway was studied using various antibody arrays and biochemicals assays in cardiac tissue and cultured fibroblasts. Results: MANP exhibits superior efficacy than ANP in reducing left ventricular dysfunction and to reduce myocardial fibrosis with less extracellular matrix deposition. In vitro, MANP and ANP similarly generated cGMP and activated PKG signaling pathway in cardiac fibroblasts, attenuating SMAD activation, collagen secretion and cell proliferation. Nevertheless, in vivo, MANP enhanced cardiac cGMP accumulation and was more potent than ANP in activating myocardial cGMP/PKG signaling and inhibiting the profibrotic SMAD pathway. Endopeptidase inhibition using sacubitril also led to cardiac cGMP accumulation and reduced myocardial fibrosis Conclusions: Myocardial bioavailability of ANP is a major determinant of peptide efficacy in reducing cardiac fibrosis and improving pump function during diabetic cardiomyopathy.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"105 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141933610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol targets G-quadruplexes to exert its pharmacological effects","authors":"Ana Soriano-Lerma, Victoria Sanchez-Martin, Javier Murciano-Calles, Matilde Ortiz-Gonzalez, Maria J Tello-Lopez, Virginia Perez-Carrasco, Angel Linde-Rodriguez, Inmaculada Ramirez-Macias, Irene Gomez-Pinto, Inmaculada Lopez-Aliaga, Miguel Soriano, Jose A Garcia-Salcedo","doi":"10.1101/2024.07.29.605564","DOIUrl":"https://doi.org/10.1101/2024.07.29.605564","url":null,"abstract":"Resveratrol (RSV) is one of the most studied and used biomolecules, for which many pharmacological effects targeting multiple tissues have been described. However, a common underlying mechanism driving its full pharmacological activity has not been elucidated to date. G-quadruplexes (G4s) are non-canonical nucleic acid structures found in promoters and involved in controlling gene transcription. This study demonstrates a G4-dependent mode of action for RSV, explaining its multi-target traits. RSV was shown to stabilise cellular G4s, which accumulate around double strand breaks (DSBs) in the promoters of differentially expressed genes (DEGs). G4 targeting triggers DNA damage and controls gene expression. Unravelling the main mode of action of RSV will be helpful to improve its therapeutic potential in a wide variety of health scenarios.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative lifespan and healthspan of nonhuman primate species common to biomedical research","authors":"Hillary F Huber, Hannah C Ainsworth, Ellen E Quillen, Adam Salmon, Corinna Ross, Adinda D Azhar, Karen Bales, Michele A Basso, Kristine Coleman, Ricki Colman, Huda S Darusman, Bill Hopkins, Charlotte E Hotchkiss, Matthew J Jorgensen, Kylie Kavanagh, Cun Li, Julie A Mattison, Peter W Nathanielsz, Suryo Saputro, Diana G Scorpio, Paul-Michael Sosa, Eric J Vallender, Yaomin Wang, Caroline J Zeiss, Carol A Shively, Laura A Cox","doi":"10.1101/2024.07.31.606010","DOIUrl":"https://doi.org/10.1101/2024.07.31.606010","url":null,"abstract":"There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Accurate measures of chronological aging are essential for inferences into genetic, demographic, and physiological variables driving differences in NHP lifespan within and between species. Understanding NHP lifespans is relevant to public health because unraveling the demographic, molecular, and clinical bases of health across the life course in translationally relevant NHP species is fundamentally important to the study of human aging. Data from more than 110,000 captive individual NHP were contributed by 15 major research institutions to generate sex-specific Kaplan-Meier survival curves using uniform methods in 12 translational aging models: Callithrix jacchus (common marmoset), Chlorocebus aethiops sabaeus (vervet/African green), Macaca fascicularis (cynomolgus macaque), M. fuscata (Japanese macaque), M. mulatta (rhesus macaque), M. nemestrina (pigtail macaque), M. radiata (bonnet macaque), Pan troglodytes spp. (chimpanzee), Papio hamadryas spp. (baboon), Plecturocebus cupreus (coppery titi monkey), Saguinus oedipus (cotton-top tamarin), and Saimiri spp. (squirrel monkey). After employing strict inclusion criteria, primary analysis results are based on 12,269 NHP that survived to adulthood and died of natural/health-related causes. A secondary analysis was completed for 32,616 NHP that died of any cause. For the primary analyses, we report ages of 25th, 50th, 75th, and 85th percentiles of survival, maximum observed ages, rates of survivorship, and sex-based differences captured by quantile regression models and Kolmogorov-Smirnov tests. Our findings show a pattern of reduced male survival among catarrhines (African and Asian primates), especially macaques, but not platyrrhines (Central and South American primates). For many species, median lifespans were lower than previously reported. An important consideration is that these analyses may offer a better reflection of healthspan than lifespan. Captive NHP used in research are typically euthanized for humane welfare reasons before their natural end of life, often after diagnosis of their first major disease requiring long-term treatment with reduced quality of life (e.g., endometriosis, cancer, osteoarthritis). Supporting the idea that these data are capturing healthspan, for several species typical age at onset of chronic disease is similar to the median lifespan estimates. This data resource represents the most comprehensive characterization of sex-specific lifespan and age-at-death distributions for 12 biomedically relevant species, to date. The results clarify the relationships among NHP ages and will provide a valuable resource for the aging research community, improving human-NHP age equivalencies, informing investigators of the expected survival rates of NHP assigned to studies, providing a metric for compa","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose colchicine treatment improves vasorelaxation, reduces arterial remodeling and attenuates blood pressure increases in spontaneously hypertensive rats","authors":"Samuel N Baldwin, Joakim A. Bastrup, Jennifer van der Horst, Antonella M G Formento, Magdalena Dubik, Olga S Kudryavtseva, Arnela Saljic, Salome Rognant, Johs Dannesboe, Anthony M Mozzicato, Thomas Jespersen, Jesper Bonnet Moeller, Jean-Claude Tardif, Morten B Thomsen, Thomas A Jepps","doi":"10.1101/2024.07.31.604256","DOIUrl":"https://doi.org/10.1101/2024.07.31.604256","url":null,"abstract":"Colchicine, a microtubule depolymerizing agent, is an effective therapy for the secondary prevention of cardiovascular disease and has been approved recently as a novel treatment for atherosclerosis associated with coronary artery disease. Hypertension is a leading cause of cardiovascular disease, yet the impact of colchicine on hypertension has not been studied. We hypothesized that low-dose colchicine could be used to treat hypertension to reduce cardiovascular disease risk. The aim of this study was to administer daily, low dose (0.05 mg/kg/day) oral colchicine for 4 weeks to spontaneously hypertensive rats (SHR) and normotensive controls (WKY) and determine the effect on blood pressure, vascular reactivity, remodeling and inflammation, and left ventricular hypertrophy. Daily blood pressure measurements recorded by telemetry in conscious rats showed colchicine prevented increases in mean arterial pressure observed in the SHRs receiving vehicle over the 4-week treatment period. After the 4-weeks of treatment, 3rd order mesenteric artery vasorelaxations to isoproterenol, sodium nitroprusside and the Kv7.2-5 channel activator, ML213, were enhanced in the SHRs receiving colchicine compared to vehicle. The improved isoproterenol-mediated relaxation was also observed in WKY rats receiving colchicine, and in both the SHR and WKY, this improved effect was attenuated by the β2 adrenoceptor antagonist, ICI118,551. Proteomic analysis of the mesenteric arteries by mass spectrometry revealed that colchicine treatment prevented changes observed when comparing the SHR vehicle group with the WKY vehicle group in proteins associated with extracellular matrix pathways. Immunostaining of 3rd order mesenteric arteries with Sirius red found that colchicine treatment attenuated the increased media thickness of the artery wall observed in SHRs receiving vehicle. Multiplex immunoassay and Western blots revealed colchicine reduced certain inflammatory mediators in the wall of the SHR mesenteric arteries, particularly the nucleotide-binding domain and leucine-rich repeat pyrin containing protein-3 (NLRP3), IL-18, CXCL10, and CXCL2, as well as reducing phosphorylated STAT3. Finally, in the left ventricle of the SHR, colchicine treatment attenuated a number of inflammatory mediators, including NLRP3, IL-1beta, and IL-18, and reduced fibrosis and cell size, which are indicative of left ventricular hypertrophy. Overall, we show colchicine has the potential to elicit cardiovascular protective effects in hypertension by targeting multiple cell types.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"184 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central activation of catecholamine-independent lipolysis drives the end-stage catabolism of all adipose tissues","authors":"Xiao Zhang, Anurag Majumdar, Clara Kim, Brian Kleiboeker, Kristann L Magee, Brian S Learman, Steven A Thomas, Irfan J Lodhi, Ormond A MacDougald, Erica L Scheller","doi":"10.1101/2024.07.30.605812","DOIUrl":"https://doi.org/10.1101/2024.07.30.605812","url":null,"abstract":"Several adipose depots, including constitutive bone marrow adipose tissue (cBMAT), resist conventional lipolytic cues, making them metabolically non-responsive. However, under starvation, wasting, or cachexia, the body can eventually catabolize these stable adipocytes through unknown mechanisms. To study this, we developed a mouse model of brain-evoked depletion of all fat, including cBMAT, independent of food intake. Genetic, surgical, and chemical approaches demonstrated that depletion of stable fat required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system, and catecholamines. Instead, concurrent hypoglycemia and hypoinsulinemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent lipolysis via downregulation of cell-autonomous lipolytic inhibitors Acvr1c, G0s2, and Npr3. This was also sufficient to delipidate classical adipose depots. Overall, this work defines unique adaptations of stable adipocytes to resist lipolysis in healthy states while isolating a potent in vivo neurosystemic pathway by which the body can rapidly catabolize all adipose tissues.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of RREB1 reduces adipogenesis and improves insulin sensitivity in mouse and human adipocytes","authors":"Grace Z Yu, Nicole A. J. Krentz, Liz Bentley, Meng Zhao, Keanu Paphiti, Han Sun, Julius Honecker, Marcus Nygard, Hesam Dashti, Ying Bai, Madeleine Reid, Swaraj Thaman, Martin Wabitsch, Varsha Rajesh, Jing Yang, Katia K Mattis, Fernando Abaitua, Ramon Casero, Hans Hauner, Joshua W Knowles, Joy Y Wu, Susanne Mandrup, Melina Claussnitzer, Katrin J Svensson, Roger D Cox, Anna L Gloyn","doi":"10.1101/2024.07.30.605923","DOIUrl":"https://doi.org/10.1101/2024.07.30.605923","url":null,"abstract":"There are multiple independent genetic signals at the Ras-responsive element binding protein 1 (RREB1) locus associated with type 2 diabetes risk, fasting glucose, ectopic fat, height, and bone mineral density. We have previously shown that loss of RREB1 in pancreatic beta cells reduces insulin content and impairs islet cell development and function. However, RREB1 is a widely expressed transcription factor and the metabolic impact of RREB1 loss in vivo remains unknown. Here, we show that male and female global heterozygous knockout (Rreb1+/-) mice have reduced body length, weight, and fat mass on high-fat diet. Rreb1+/- mice have sex- and diet-specific decreases in adipose tissue and adipocyte size; male mice on high-fat diet had larger gonadal adipocytes, while males on standard chow and females on high-fat diet had smaller, more insulin sensitive subcutaneous adipocytes. Mouse and human precursor cells lacking RREB1 have decreased adipogenic gene expression and activated transcription of genes associated with osteoblast differentiation, which was associated with Rreb1+/- mice having increased bone mineral density in vivo. Finally, human carriers of RREB1 T2D protective alleles have smaller adipocytes, consistent with RREB1 loss-of-function reducing diabetes risk.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"152 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CHANGES IN MUSCLE QUALITY FOLLOWING SHORT-TERM RESISTANCE TRAINING IN OLDER ADULTS: A COMPARISON OF ECHO INTENSITY AND TEXTURE ANALYSIS","authors":"Kevan S Knowles, Jason I Pagan, Jonathan P Beausejour, Scott J Mongold, Abigail W Anderson, Jeffrey R Stout, Matt S Stock","doi":"10.1101/2024.07.30.605815","DOIUrl":"https://doi.org/10.1101/2024.07.30.605815","url":null,"abstract":"Background: Skeletal muscle echo intensity (EI) is associated with functional outcomes in older adults, but resistance training interventions have shown mixed results. Texture analysis has been proposed as a novel approach for assessing muscle quality, as it captures spatial relationships between pixels. Purpose: To examine changes in first-order (EI) and second-order (texture) features of muscle quality following lower-body resistance training in older adults. Methods: Twelve older adults (2 males, 10 females; mean age = 70 years) completed 6 weeks of progressive resistance training, consisting of twice-weekly sessions at 85% of estimated 1RM. Pre- and post-intervention assessments included ultrasound imaging of the rectus femoris (RF) and vastus lateralis (VL), 5-repetition maximum (5RM) leg extension strength, and maximal voluntary isometric contraction (MVIC) force. Ultrasound images were analyzed for EI and texture features using gray-level co-occurrence matrix (GLCM) analysis. Results: Large improvements were observed in 5RM leg extension strength (p < 0.001, d = 2.09), MVIC force (p = 0.006, d = 0.969), and RF EI (uncorrected: p = 0.003, d = 0.727; corrected: p = 0.012, d = 0.864). No significant changes were observed in muscle size, VL EI, or texture features for either muscle. Conclusions: Short-term resistance training improved strength and RF muscle quality as measured by EI. However, texture analysis features were not sensitive to changes following training. These findings suggest that traditional EI measures may be more appropriate than texture analysis for tracking changes in muscle quality following resistance training in older adults.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"212 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MLCK/MLCP regulates mammalian axon regeneration via the redistribution of the growth cone F-actin","authors":"Saijilafu None, Weihua Wang, Jinjin Ma, Yin Yin, Yanxia Ma","doi":"10.1101/2024.07.30.605892","DOIUrl":"https://doi.org/10.1101/2024.07.30.605892","url":null,"abstract":"Axon regrowth is a key determinant of the restoration of the biological function of the nervous system after trauma. However, mature mammalian neurons have limited capacity for axon regeneration. We have previously demonstrated that neuronal axon growth both in the central and the peripheral nervous systems is markedly enhanced when non-muscle myosin II (NMII) is inhibited with blebbistatin. The activity of NMII is primarily regulated by MLCK and MLCP via the phosphorylation and dephosphorylation of its light chain, respectively; however, the functional roles of MLCK and MLCP in mammalian axonal regeneration remain unknown. In the present study, we provide strong evidence that the inhibition of MLCK activity significantly blocks axon regeneration in the mouse. Conversely, inhibition of MLCP promotes axon regrowth of both peripheral and central nervous system. Our findings further indicate that the MLCK/MLCP regulates axon regeneration via the reorganization of F-actin distribution in the growth cone, and this result suggests that direct regulation of the growth cone machinery is a potential strategy to promote axon regeneration.","PeriodicalId":501557,"journal":{"name":"bioRxiv - Physiology","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141868621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}