Physiological genomics最新文献

{"title":"Lost in translation? Evidence for a muted proteomic response to thermal stress in a stenothermal Antarctic fish and possible evolutionary mechanisms.","authors":"W Wesley Dowd, Dietmar Kültz","doi":"10.1152/physiolgenomics.00051.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00051.2024","url":null,"abstract":"<p><p>Stenothermal Antarctic notothenioid fishes are noteworthy for their history of isolation in extreme cold and their corresponding lack of the canonical heat shock response. Despite extensive transcriptomic studies, the mechanistic basis for stenothermy has not been fully elucidated. Given that the proteome better represents an organism's physiology, the possibility exists that some aspects of stenothermy arise post-transcriptionally. Here, Antarctic emerald rockcod (<i>Trematomus bernacchii</i>) were sampled after exposure to chronic and/or acute high temperatures, followed by thorough assessment of proteomic responses in brain, gill, and kidney. Few cellular stress response proteins were induced, and overall responses were modest in terms of numbers of differentially expressed proteins and their fold changes. Inconsistencies in protein induction across treatments and tissues are suggestive of dysregulation, rather than an adaptive response. Changes in regulation of the translational machinery in Antarctic notothenioids could explain these patterns. Some components of translational regulatory pathways are highly conserved (e.g., Ser-52 of eIF2α), but proteins comprising the cellular \"integrative stress response\" - specifically, the eIF2α kinases GCN2 and PERK - may have evolved along different trajectories in Antarctic fishes. Taken together, these observations suggest a novel hypothesis for stenothermy and the absence of a coordinated cellular stress response in Antarctic fishes.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Then and Now in Eukaryotic DNA Methylation","authors":"Richard A. Stein, Faris E. Gomaa, Pranaya Raparla, Leise Riber","doi":"10.1152/physiolgenomics.00091.2024","DOIUrl":"https://doi.org/10.1152/physiolgenomics.00091.2024","url":null,"abstract":"Physiological Genomics, Ahead of Print. <br/>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142200691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide comparative analyses highlight selection signatures underlying saline adaptation in Chilika buffalo.","authors":"Utsav Surati, Saket K Niranjan, Rakesh Kumar Pundir, Ymberzal Koul, Vikas Vohra, Ravi Kumar Gandham, Amod Kumar","doi":"10.1152/physiolgenomics.00028.2024","DOIUrl":"10.1152/physiolgenomics.00028.2024","url":null,"abstract":"<p><p>Chilika, a native buffalo breed of the Eastern coast of India, is mainly distributed around the Chilika brackish water lake connected with the Bay of Bengal Sea. This breed possesses a unique ability to delve deep into the salty water of the lake and stay there to feed on local vegetation of saline nature. Adaptation to salinity is a genetic phenomenon; however, the genetic basis underlying salinity tolerance is still limited in animals, specifically in livestock. The present study explores the genetic evolution that unveils the Chilika buffalo's adaptation to the harsh saline habitat, including both water and food systems. For this study, whole genome resequencing data on 18 Chilika buffalo and for comparison 10 Murrah buffalo of normal habitat were generated. For identification of selection sweeps, intrapopulation and interpopulation statistics were used. A total of 709, 309, 468, and 354 genes were detected to possess selection sweeps in Chilika buffalo using the nucleotide diversity (θπ), Tajima's D, nucleotide diversity ratio (θπ-ratio), and F_ST methods, respectively. Further analysis revealed a total of 23 genes including <i>EXOC6B</i>, <i>VPS8</i>, <i>LYPD1</i>, <i>VPS35</i>, <i>CAMKMT</i>, <i>NCKAP5</i>, <i>COMMD1</i>, myosin light chain kinase 3 (<i>MYLK3</i>), and <i>B3GNT2</i> were found to be common by all the methods. Furthermore, functional annotation study of identified genes provided pathways such as MAPK signaling, renin secretion, endocytosis, oxytocin signaling pathway, etc. Gene network analysis enlists that hub genes provide insights into their interactions with each other. In conclusion, this study has highlighted the genetic basis underlying the local adaptive function of Chilika buffalo under saline environment.<b>NEW & NOTEWORTHY</b> Indian Chilika buffaloes are being maintained on extensive grazing system and have a unique ability to convert local salty vegetation into valuable human food. However, adaptability to saline habitat of Chilika buffalo has not been explored to date. Here, we identified genes and biological pathways involved, such as MAPK signaling, renin secretion, endocytosis, and oxytocin signaling pathway, underlying adaptability of Chilika buffalo to saline environment. This investigation shed light on the mechanisms underlying the buffalo's resilience in its native surroundings.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic drivers of age-related changes in urinary magnesium excretion.","authors":"Wouter H van Megen, Jeroen H F de Baaij, Gary A Churchill, Olivier Devuyst, Joost G J Hoenderop, Ron Korstanje","doi":"10.1152/physiolgenomics.00119.2023","DOIUrl":"10.1152/physiolgenomics.00119.2023","url":null,"abstract":"<p><p>Although age-dependent alterations in urinary magnesium (Mg²⁺) excretion have been described, the underlying mechanism remains elusive. As heritability significantly contributes to variations in urinary Mg²⁺ excretion, we measured urinary Mg²⁺ excretion at different ages in a cohort of genetically variable Diversity Outbred (DO) mice. Compared with animals aged 6 mo, an increase in Mg²⁺ excretion was observed at 12 and 18 mo. Quantitative trait locus (QTL) analysis revealed an association of a locus on chromosome 10 with Mg²⁺ excretion at 6 mo of age, with <i>Oit3</i> (encoding oncoprotein-induced transcript 3; OIT3) as our primary candidate gene. To study the possible role of OIT3 in renal Mg²⁺ handling, we generated and characterized <i>Oit3</i> knockout (<i>Oit3</i>^-/-) mice. Although a slightly lower serum Mg²⁺ concentration was present in male <i>Oit3</i>^-/- mice, this effect was not observed in female <i>Oit3</i>^-/- mice. In addition, urinary Mg²⁺ excretion and the expression of renal magnesiotropic genes were unaltered in <i>Oit3</i>^-/- mice. For animals aged 12 and 18 mo, QTL analysis revealed an association with a locus on chromosome 19, which contains the gene encoding TRPM6, a known Mg²⁺ channel involved in renal Mg²⁺ reabsorption. Comparison with RNA sequencing (RNA-Seq) data revealed that <i>Trpm6</i> mRNA expression is inversely correlated with the QTL effect, implying that TRPM6 may be involved in age-dependent changes in urinary Mg²⁺ excretion in mice. In conclusion, we show here that variants in <i>Oit3</i> and <i>Trpm6</i> are associated with urinary Mg²⁺ excretion at distinct periods of life, although OIT3 is unlikely to affect renal Mg²⁺ handling.<b>NEW & NOTEWORTHY</b> Aging increased urinary magnesium (Mg²⁺) excretion in mice. We show here that variation in <i>Oit3</i>, a candidate gene for the locus associated with Mg²⁺ excretion in young mice, is unlikely to be involved as knockout of <i>Oit3</i> did not affect Mg²⁺ excretion. Differences in the expression of the renal Mg²⁺ channel TRPM6 may contribute to the variation in urinary Mg²⁺ excretion in older mice.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular signatures of longissimus dorsi differ between dairy cattle based on prepartum muscle reserves and branched-chain volatile fatty acid supplementation.","authors":"Theresa M Casey, Kyrstin M Gouveia, Linda M Beckett, James F Markworth, Jacquelyn P Boerman","doi":"10.1152/physiolgenomics.00060.2024","DOIUrl":"10.1152/physiolgenomics.00060.2024","url":null,"abstract":"<p><p>Dairy cattle with high (HM) versus low muscle (LM) reserves as determined by longissimus dorsi muscle depth (LDD) in late gestation exhibit differential muscle mobilization related to subsequent milk production. Moreover, branched-chain volatile fatty acid (BCVFA) supplementation increased blood glucose levels. We hypothesized that differences in HM and LM reflect distinct muscle metabolism and that BCVFA supplementation altered metabolic pathways. At 42 days before expected calving (BEC), Holstein dairy cows were enrolled in a 2 × 2 factorial study of diet and muscle reserves, by assignment to control (CON)- or BCVFA-supplemented diets and LDD of HM (>4.6 cm) or LM (≤4.6 cm) groups: HM-CON (<i>n</i> = 13), HM-BCVFA (<i>n</i> = 10), LM-CON (<i>n</i> = 9), and LM-BCVFA (<i>n</i> = 9). Longisumus dorsi muscle was biopsied at 21 days BEC, total RNA was isolated, and protein-coding gene expression was measured with RNA sequencing. Between HM and LM, 713 genes were differentially expressed and 481 between BCVFA and CON (<i>P</i> < 0.05). Transcriptional signatures indicated differential distribution of type II fibers between groups, with MYH1 greater in LM cattle and MYH2 greater in HM cattle (<i>P</i> < 0.05). Signatures of LM cattle relative to HM cattle indicated greater activation of autophagy, ubiquitin-proteasome, and Ca²⁺-calpain pathways. HM cattle displayed greater expression of genes that encode extracellular matrix proteins and factors that regulate their proteolysis and turnover. BCVFA modified transcriptomes by increasing expression of genes that regulate fatty acid degradation and flux of carbons into the tricarboxylic acid cycle as acetyl CoA. Molecular signatures support distinct metabolic strategies between LM and HM cattle and that BCVFA supplementation increased substrates for energy generation.<b>NEW & NOTEWORTHY</b> Muscle biopsies of the longissimus dorsi of prepartum dairy cattle indicate that molecular signatures support distinct metabolic strategies between low- and high-muscle cattle and that branched-chain volatile fatty acid supplementation increased substrates for energy generation.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of cholesterol homeostasis is an early signal of β-cell proteotoxicity characteristic of type 2 diabetes.","authors":"Tatyana Gurlo, Ruoshui Liu, Zhongying Wang, Jonathan Hoang, Sergey Ryazantsev, Marie Daval, Alexandra E Butler, Xia Yang, Montgomery Blencowe, Peter C Butler","doi":"10.1152/physiolgenomics.00029.2024","DOIUrl":"10.1152/physiolgenomics.00029.2024","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is a common metabolic disease due to insufficient insulin secretion by pancreatic β-cells in the context of insulin resistance. Islet molecular pathology reveals a role for protein misfolding in β-cell dysfunction and loss with islet amyloid derived from islet amyloid polypeptide (IAPP), a protein coexpressed and cosecreted with insulin. The most toxic form of misfolded IAPP is intracellular membrane disruptive toxic oligomers present in β-cells in T2D and in β-cells of mice transgenic for human IAPP (hIAPP). Prior work revealed a high degree of overlap of transcriptional changes in islets from T2D and prediabetic 9- to 10-wk-old mice transgenic for hIAPP with most changes being pro-survival adaptations and therefore of limited therapeutic guidance. Here, we investigated islets from hIAPP transgenic mice at an earlier age (6 wk) to screen for potential mediators of hIAPP toxicity that precede predominance of pro-survival signaling. We identified early suppression of cholesterol synthesis and trafficking along with aberrant intra-β-cell cholesterol and lipid deposits and impaired cholesterol trafficking to cell membranes. These findings align with comparable lipid deposits present in β-cells in T2D and increased vulnerability to develop T2D in individuals taking medications that suppress cholesterol synthesis.<b>NEW & NOTEWORTHY</b> β-Cell failure in type 2 diabetes (T2D) is characterized by β-cell misfolded protein stress due to the formation of toxic oligomers of islet amyloid polypeptide (IAPP). Most transcriptional changes in islets in T2D are pro-survival adaptations consistent with the slow progression of β-cell loss. In the present study, investigation of the islet transcriptional signatures in a mouse model of T2D expressing human IAPP revealed decreased cholesterol synthesis and trafficking as a plausible early mediator of IAPP toxicity.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial microRNA profiles are altered in thirteen-lined ground squirrels (<i>Ictidomys tridecemlineatus</i>) during hibernation.","authors":"Karyn Robichaud, Brynne Duffy, James F Staples, Paul M Craig","doi":"10.1152/physiolgenomics.00017.2024","DOIUrl":"10.1152/physiolgenomics.00017.2024","url":null,"abstract":"<p><p>Thirteen-lined ground squirrels (TLGSs) are obligate hibernators that cycle between torpor (low metabolic rate and body temperature) and interbout euthermia (IBE; typical euthermic body temperature and metabolism) from late autumn to spring. Many physiological changes occur throughout hibernation, including a reduction in liver mitochondrial metabolism during torpor, which is reversed during arousal to interbout euthermia. Nuclear-encoded microRNA (miRNA, small posttranscriptional regulator molecules) differ in abundance throughout TLGS hibernation and have been shown to regulate mitochondrial gene expression in mammalian cell culture (where they are referred to as mitomiRs). This study characterized differences in mitomiR profiles from TLGS liver mitochondria isolated during summer, torpor, and IBE, and predicted their mitochondrial targets. Using small RNA sequencing, differentially abundant mitomiRs were identified between hibernation states, and using quantitative PCR analysis, we quantified the expression of predicted mitochondrial mRNA targets. Most differences in mitomiR abundances were seasonal (i.e., between summer and winter) with only one mitomiR differentially abundant between IBE and torpor. Multiple factor analysis (MFA) revealed three clusters divided by hibernation states, where clustering was predominantly driven by mitomiR abundances. Nine of these differentially abundant mitomiRs had predicted mitochondrial RNA targets, including subunits of electron transfer system complexes I and IV, 12S rRNA, and two tRNAs. Overall, mitomiRs were predicted to suppress the expression of their mitochondrial targets and may have some involvement in regulating protein translation in mitochondria. This study found differences in mitomiR abundances between seasons and hibernation states of TLGS and suggests potential mechanisms for regulating the mitochondrial electron transfer system.<b>NEW & NOTEWORTHY</b> During the hibernation season, thirteen-lined ground squirrels periodically increase metabolism remarkably between torpor and interbout euthermia (IBE). This process involves rapid reactivation of mitochondrial respiration. We predicted that mitochondrial microRNA (mitomiRs) might be altered during this response. We found that the abundance of 38 liver mitomiRs differs based on hibernation state (summer, IBE, and torpor). Small RNA sequencing identified mitomiR profiles, including some mitomiRs that are predicted to bind to mitochondrial RNAs.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational modeling of the synergistic role of GCN2 and the HPA axis in regulating the integrated stress response in the central circadian timing system.","authors":"Yannuo Li, Lingjun Lu, Jordan L Levy, Tracy G Anthony, Ioannis P Androulakis","doi":"10.1152/physiolgenomics.00030.2024","DOIUrl":"10.1152/physiolgenomics.00030.2024","url":null,"abstract":"<p><p>The circadian timing system and integrated stress response (ISR) systems are fundamental regulatory mechanisms that maintain body homeostasis. The central circadian pacemaker in the suprachiasmatic nucleus (SCN) governs daily rhythms through interactions with peripheral oscillators via the hypothalamus-pituitary-adrenal (HPA) axis. On the other hand, ISR signaling is pivotal for preserving cellular homeostasis in response to physiological changes. Notably, disrupted circadian rhythms are observed in cases of impaired ISR signaling. In this work, we examine the potential interplay between the central circadian system and the ISR, mainly through the SCN and HPA axis. We introduce a semimechanistic mathematical model to delineate SCN's capacity for indirectly perceiving physiological stress through glucocorticoid-mediated feedback from the HPA axis and orchestrating a cellular response via the ISR mechanism. Key components of our investigation include evaluating general control nonderepressible 2 (GCN2) expression in the SCN, the effect of physiological stress stimuli on the HPA axis, and the interconnected feedback between the HPA and SCN. Simulation revealed a critical role for GCN2 in linking ISR with circadian rhythms. Experimental findings have demonstrated that a <i>Gcn2</i> deletion in mice leads to rapid re-entrainment of the circadian clock following jetlag as well as to an elongation of the circadian period. These phenomena are well replicated by our model, which suggests that both the swift re-entrainment and prolonged period can be ascribed to a reduced robustness in neuronal oscillators. Our model also offers insights into phase shifts induced by acute physiological stress and the alignment/misalignment of physiological stress with external light-dark cues. Such understanding aids in strategizing responses to stressful events, such as nutritional status changes and jetlag.<b>NEW & NOTEWORTHY</b> This study is the first theoretical work to investigate the complex interaction between integrated stress response (ISR) sensing and central circadian rhythm regulation, encompassing the suprachiasmatic nucleus (SCN) and hypothalamus-pituitary-adrenal (HPA) axis. The findings carry implications for the development of dietary or pharmacological interventions aimed at facilitating recovery from stressful events, such as jetlag. Moreover, they provide promising prospects for potential therapeutic interventions that target circadian rhythm disruption and various stress-related disorders.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study of exercise-induced skeletal muscle hypertrophy and the construction of predictive model.","authors":"Xiaolin Yang, Yanchun Li, Tao Mei, Jiayan Duan, Xu Yan, Lars Robert McNaughton, Zihong He","doi":"10.1152/physiolgenomics.00019.2024","DOIUrl":"10.1152/physiolgenomics.00019.2024","url":null,"abstract":"<p><p>The aim of the current study was to investigate interindividual differences in muscle thickness of the rectus femoris (MTRF) following 12 wk of resistance training (RT) or high-intensity interval training (HIIT) to explore the genetic architecture underlying skeletal muscle hypertrophy and to construct predictive models. We conducted musculoskeletal ultrasound assessments of the MTRF response in 440 physically inactive adults after the 12-wk exercise period. A genome-wide association study was used to identify variants associated with the MTRF response, separately for RT and HIIT. Using the polygenic predictor score (PPS), we estimated the genetic contribution to exercise-induced hypertrophy. Predictive models for the MTRF response were constructed using random forest (RF), support vector mac (SVM), and generalized linear model (GLM) in 10 cross-validated approaches. MTRF increased significantly after both RT (8.8%, <i>P</i> < 0.05) and HIIT (5.3%, <i>P</i> < 0.05), but with considerable interindividual differences (RT: -13.5 to 38.4%, HIIT: -14.2 to 30.7%). Eleven lead single-nucleotide polymorphisms in RT and eight lead single-nucleotide polymorphisms in HIIT were identified at a significance level of <i>P</i> < 1 × 10^-5. The PPS was associated with the MTRF response, explaining 47.2% of the variation in response to RT and 38.3% of the variation in response to HIIT. Notably, the GLM and SVM predictive models exhibited superior performance compared with RF models (<i>P</i> < 0.05), and the GLM demonstrated optimal performance with an area under curve of 0.809 (95% confidence interval: 0.669-0.949). Factors such as PPS, baseline MTRF, and exercise protocol exerted influence on the MTRF response to exercise, with PPS being the primary contributor. The GLM and SVM predictive model, incorporating both genetic and phenotypic factors, emerged as promising tools for predicting exercise-induced skeletal muscle hypertrophy.<b>NEW & NOTEWORTHY</b> The interindividual variability induced muscle hypertrophy by resistance training (RT) or high-intensity interval training (HIIT) and the associated genetic architecture remain uncertain. We identified genetic variants that underlie RT- or HIIT-induced muscle hypertrophy and established them as pivotal factors influencing the response regardless of the training type. The genetic-phenotype predictive model developed has the potential to identify nonresponders or individuals with low responsiveness before engaging in exercise training.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbiota-induced inflammatory responses in bladder tumors promote epithelial-mesenchymal transition and enhanced immune infiltration.","authors":"Qiang Li, Yichao Sun, Kun Zhai, Bingzhi Geng, Zhenkun Dong, Lei Ji, Hui Chen, Yan Cui","doi":"10.1152/physiolgenomics.00032.2024","DOIUrl":"10.1152/physiolgenomics.00032.2024","url":null,"abstract":"<p><p>The intratumoral microbiota can modulate the tumor immune microenvironment (TIME); however, the underlying mechanism by which intratumoral microbiota influences the TIME in urothelial carcinoma of the bladder (UCB) remains unclear. To address this, we collected samples from 402 patients with UCB, including paired host transcriptome and tumor microbiome data, from The Cancer Genome Atlas (TCGA). We found that the intratumoral microbiome profiles were significantly correlated with the expression pattern of epithelial-mesenchymal transition (EMT)-related genes. Furthermore, we detected that the genera <i>Lachnoclostridium</i> and <i>Sutterella</i> in tumors could indirectly promote the EMT program by inducing an inflammatory response. Moreover, the inflammatory response induced by these two intratumoral bacteria further enhanced intratumoral immune infiltration, affecting patient survival and response to immunotherapy. In addition, an independent immunotherapy cohort of 348 patients with bladder cancer was used to validate our results. Collectively, our study elucidates the potential mechanism by which the intratumoral microbiota influences the TIME of UCB and provides a new guiding strategy for the targeted therapy of UCB.<b>NEW & NOTEWORTHY</b> The intratumoral microbiota may mediate the bladder tumor inflammatory response, thereby promoting the epithelial-mesenchymal transition program and influencing tumor immune infiltration.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}