Physiological genomics最新文献

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Transcriptional dynamics of sleep deprivation and subsequent recovery sleep in the male mouse cortex. 睡眠剥夺和随后恢复睡眠在雄性小鼠皮层的转录动力学。
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-07-01 Epub Date: 2025-05-02 DOI: 10.1152/physiolgenomics.00128.2024
Alexander Popescu, Caitlin Ottaway, Kaitlyn Ford, Elizabeth Medina, Taylor Wintler Patterson, Ashley Ingiosi, Stephanie C Hicks, Kristan Singletary, Lucia Peixoto
{"title":"Transcriptional dynamics of sleep deprivation and subsequent recovery sleep in the male mouse cortex.","authors":"Alexander Popescu, Caitlin Ottaway, Kaitlyn Ford, Elizabeth Medina, Taylor Wintler Patterson, Ashley Ingiosi, Stephanie C Hicks, Kristan Singletary, Lucia Peixoto","doi":"10.1152/physiolgenomics.00128.2024","DOIUrl":"10.1152/physiolgenomics.00128.2024","url":null,"abstract":"<p><p>Sleep is an essential, tightly regulated biological function. Sleep is also a homeostatic process, with the need to sleep increasing as a function of being awake. Acute sleep deprivation (SD) increases sleep need, and subsequent recovery sleep (RS) discharges it. SD is known to alter brain gene expression in rodents, but it remains unclear which changes are linked to sleep homeostasis. To investigate this question, we analyzed RNA-seq data from adult male mice subjected to 3 and 5-6 h of SD and 2 and 6 h of subsequent RS. We hypothesized that molecular changes associated with sleep homeostasis would mirror sleep pressure dynamics as defined by brain electrical activity, peaking at 5-6 h of SD and no longer differentially expressed after 2 h of RS. We report that 5-6 h of SD produces the largest effect on gene expression, and the majority of differentially expressed genes normalize after 2 h of RS. These genes are involved in cellular redox homeostasis, DNA damage/repair, and chromatin regulation and may underlie the molecular basis of sleep homeostasis. Genes associated with cellular stress do not normalize within 6 h of RS and may underlie non-sleep-specific effects of SD. In addition, RS affects gene expression related to energy metabolism and Wnt-signaling, potentially contributing to its restorative effects. Finally, our study also points to the regulation of expression of a subset of circadian transcription factors as a function of sleep need. Overall, our results offer novel insights into the molecular mechanisms underlying sleep homeostasis and the broader effects of SD.<b>NEW & NOTEWORTHY</b> This study investigates different time points of sleep deprivation and recovery sleep to better understand the molecular processes influenced by sleep and lack of sleep. This study highlights redox metabolism, chromatin regulation, and DNA damage/repair as molecular mechanisms linked to sleep homeostasis while showing the effects of stress are probably non-sleep-specific based on transcriptional dynamics.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"431-445"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12140865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alternative splicing of CADM1 in preeclampsia: implications for endothelial dysfunction and offspring cardiovascular risk. 子痫前期CADM1的选择性剪接:内皮功能障碍和后代心血管风险的影响
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-07-01 Epub Date: 2025-04-04 DOI: 10.1152/physiolgenomics.00047.2025
Brandon M Schickling, Mark K Santillan, Donna A Santillan
{"title":"Alternative splicing of CADM1 in preeclampsia: implications for endothelial dysfunction and offspring cardiovascular risk.","authors":"Brandon M Schickling, Mark K Santillan, Donna A Santillan","doi":"10.1152/physiolgenomics.00047.2025","DOIUrl":"10.1152/physiolgenomics.00047.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"403-405"},"PeriodicalIF":2.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780590","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}
引用次数: 0
The acute effects of neuromuscular electrical stimulation on coagulation and cardiovascular factors. 神经肌肉电刺激对凝血和心血管因子的急性影响。
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-06-01 Epub Date: 2025-04-16 DOI: 10.1152/physiolgenomics.00172.2024
Johanna Flodin, Stefan M Reitzner, Nida Mahmoud Hourani Soutari, Aisha S Ahmed, Li Guo, Nils-Krister Persson, Jovan P Antovic, Paul W Ackermann
{"title":"The acute effects of neuromuscular electrical stimulation on coagulation and cardiovascular factors.","authors":"Johanna Flodin, Stefan M Reitzner, Nida Mahmoud Hourani Soutari, Aisha S Ahmed, Li Guo, Nils-Krister Persson, Jovan P Antovic, Paul W Ackermann","doi":"10.1152/physiolgenomics.00172.2024","DOIUrl":"10.1152/physiolgenomics.00172.2024","url":null,"abstract":"<p><p>Neuromuscular electrical stimulation (NMES) can potentially be used to prevent venous thromboembolism; however, its impact on coagulation-related factors remains poorly understood. We aimed to investigate the acute effects on coagulation- and cardiovascular factors immediately after a 2-h NMES session. Levels of overall hemostatic potential (OHP), fibrinogen, factor VIII, and Olink proteomic cardiovascular factors were assessed before and after the NMES session in 36 healthy participants (20 males and 16 females) with a mean age of 31.9 yr. NMES was administered using integrated textile electrodes in pants (NMES pants). Mean intensities during the quadriceps, hamstrings, and gluteus muscle stimulation were 16.5, 20.5, and 25.4 mA, respectively, corresponding to submaximal intensity levels with acceptable discomfort (just below 4 on the visual analogue scale [VAS], 0-10). The NMES session resulted in a significant increase in mean (SD) OHP [94.4 (28.3) to 103 (31.0)], and overall coagulation potential [292 (50.4) to 307(49.8)], and a decrease in overall fibrinolytic potential [68.2 (5.46) to 67.1 (5.20)]. These changes were highly correlated with the increase in fibrinogen (all <i>R</i> > 0.7, <i>P</i> ≤ 0.001), but not with the increase in factor VIII. In addition, 18 of 92 cardiovascular proteins, specifically those involved in regulating inflammation and extracellular matrix remodeling, were influenced by NMES; however, low correlations were found between the changes in these proteins and OHP analyses. In conclusion, the NMES session resulted in a slight increase in the coagulative state, mirroring that seen after a bout of regular exercise. The changes observed in cardiovascular factors, which are mostly not directly related to coagulation, suggest that NMES may subsequently modulate inflammatory responses, warranting further investigation.<b>NEW & NOTEWORTHY</b> The immediate response to a 2-h neuromuscular electrical stimulation (NMES) session, delivered at an acceptable level of discomfort using NMES-pants, marginally increases the coagulative state, similar to what is observed after regular physical exercise. This change is not expected to significantly increase the risk of blood clotting, as all factors remain within the normal reference range. Interestingly, NMES simultaneously appears to affect proteins that regulate the transition of inflammation into an anti-inflammatory response.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":"57 6","pages":"391-402"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040593","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}
引用次数: 0
Colonic responses to aspirin treatment: transcriptome effects by dose, time, and ancestry. 阿司匹林治疗的结肠应答——剂量、时间和祖先的转录组效应。
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-06-01 Epub Date: 2025-03-25 DOI: 10.1152/physiolgenomics.00043.2025
Victor Guryev
{"title":"Colonic responses to aspirin treatment: transcriptome effects by dose, time, and ancestry.","authors":"Victor Guryev","doi":"10.1152/physiolgenomics.00043.2025","DOIUrl":"10.1152/physiolgenomics.00043.2025","url":null,"abstract":"","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"383-384"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701284","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}
引用次数: 0
A genetic variant associated with aquaporin 3 expression is correlated to in-hospital death in COVID-19 patients with extracellular hyperosmolality. 一种与水通道蛋白3表达相关的基因变异与细胞外高渗COVID-19患者的院内死亡相关。
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-06-01 Epub Date: 2025-04-21 DOI: 10.1152/physiolgenomics.00174.2024
Michael Marks-Hultström, Amanda M Marks, Guillaume Butler-Laporte, Satoshi Yoshiji, Tianyuan Lu, Dave R Morrison, Tomoko Nakanishi, Yiheng Chen, Vincenzo Forgetta, Yossi Farjoun, Robert Frithiof, Miklos Lipcsey, Hugo Zeberg, J Brent Richards
{"title":"A genetic variant associated with aquaporin 3 expression is correlated to in-hospital death in COVID-19 patients with extracellular hyperosmolality.","authors":"Michael Marks-Hultström, Amanda M Marks, Guillaume Butler-Laporte, Satoshi Yoshiji, Tianyuan Lu, Dave R Morrison, Tomoko Nakanishi, Yiheng Chen, Vincenzo Forgetta, Yossi Farjoun, Robert Frithiof, Miklos Lipcsey, Hugo Zeberg, J Brent Richards","doi":"10.1152/physiolgenomics.00174.2024","DOIUrl":"10.1152/physiolgenomics.00174.2024","url":null,"abstract":"<p><p>Hyperosmolality is increasingly recognized as a factor contributing to severe COVID-19. Recently, a genetic variant near the aquaporin 3 (<i>AQP3</i>) water channel was associated with severe COVID-19 [rs60840586:G; odds ratio (OR): 1.07, <i>P</i> = 2.5 × 10<sup>-9</sup>]. The variant is known to increase gene expression of AQP3 in several organs, including the lung [normalized expression scores (NES) = 0.33, <i>P</i> = 4.1 × 10<sup>-20</sup>] in GTEx. In this study, we investigated 576 patients in the Biobanque Quebecoise de la COVID-19 (BQC-19) with both genetic and clinical data available. We estimated plasma osmolality using the formula: eOSM = 2 × [Na<sup>+</sup>] + 2 × [K<sup>+</sup>] + [Urea] + [Glucose]. Using a logistic regression of mortality against eOSM, genotype at rs60840586, sex, age, and the first 10 genetic principal components, we confirm that hyperosmolality is associated with COVID-19 mortality (OR = 2.06 [95% CI = 1.62-2.65], <i>P</i> = 9.13 × 10<sup>-9</sup>). Interestingly, we found that the risk of death linked to hyperosmolality is influenced by the <i>AQP3</i> variant rs60840586:G genotype (OR = 1.95 [95% CI = 1.22-3.28], <i>P</i> = 0.0075). However, the rs60840586 genotype did not independently affect mortality in this cohort. These findings suggest that the body's ability to regulate and accommodate hyperosmolality may be disrupted by overexpression of <i>AQP3</i>, potentially worsening outcomes in COVID-19. Given the role of AQP3 in water transport and homeostasis, further defining the functionality of its variants may provide key insights into COVID-19 severity and guide clinical management strategies, particularly in critically ill patients with hyperosmolality.<b>NEW & NOTEWORTHY</b> A genetic variant near water channel <i>AQP3</i>, linked to severe COVID-19, amplifies the risk of death in patients with elevated plasma osmolality. In patients hospitalized with COVID-19, we show that although the variant does not affect systemic osmolality directly, it interacts with hyperosmolality to increase mortality risk. These findings highlight a potential mechanism where AQP3 overexpression disrupts cellular water handling during critical illness, offering new insight into the role of water balance in COVID-19 pathophysiology.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":"57 6","pages":"385-390"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009586","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}
引用次数: 0
Molecular insights into human soleus muscle atrophy development: long-term dry immersion effects on the transcriptomic profile and posttranslational signaling. 人类比目鱼肌萎缩发展的分子洞察:长期干浸泡对转录组学特征和翻译后信号传导的影响。
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-06-01 Epub Date: 2025-03-12 DOI: 10.1152/physiolgenomics.00196.2024
Roman O Bokov, Kristina A Sharlo, Natalia A Vilchinskaya, Sergey A Tyganov, Olga V Turtikova, Sergey V Rozhkov, Ruslan M Deviatiiarov, Oleg A Gusev, Elena S Tomilovskaya, Boris S Shenkman, Oleg I Orlov
{"title":"Molecular insights into human soleus muscle atrophy development: long-term dry immersion effects on the transcriptomic profile and posttranslational signaling.","authors":"Roman O Bokov, Kristina A Sharlo, Natalia A Vilchinskaya, Sergey A Tyganov, Olga V Turtikova, Sergey V Rozhkov, Ruslan M Deviatiiarov, Oleg A Gusev, Elena S Tomilovskaya, Boris S Shenkman, Oleg I Orlov","doi":"10.1152/physiolgenomics.00196.2024","DOIUrl":"10.1152/physiolgenomics.00196.2024","url":null,"abstract":"<p><p>Muscle disuse results in complex signaling alterations followed by structural and functional changes, such as atrophy, force decrease, and slow-to-fast fiber-type shift. Little is known about human skeletal muscle signaling alterations under long-term muscle disuse. In this study, we describe the effects of 21-day dry immersion on human postural soleus muscle. We performed both transcriptomic analysis and Western blots to describe the states of the key signaling pathways regulating soleus muscle fiber size, fiber type, and metabolism. Twenty-one-day dry immersion resulted in both slow-type and fast-type myofibers atrophy, downregulation of rRNA content, and mTOR signaling. Twenty-one-day dry immersion also leads to slow-to-fast fiber-type and gene expression shift, upregulation of p-eEF2, p-CaMKII, p-ACC content and downregulation of NFATc1 nuclear content. It also caused massive gene expression alterations associated with calcium signaling, cytoskeletal parameters, and downregulated mitochondrial signaling (including fusion, fission, and marker of mitochondrial density).<b>NEW & NOTEWORTHY</b> The main findings of our study are as follows: <i>1</i>) The soleus slow fibers atrophy after 21-day dry immersion (DI) does not exceed that after 7-day DI; <i>2</i>) The soleus ubiquitin ligases expression after 21-day DI returns to its initial level; <i>3</i>) The soleus slow fibers atrophy after 21-day DI is accompanied by a mitochondrial apparatus structural markers decrease; <i>4</i>) The soleus fibers signaling pathways restructuring process during 21-day DI is carried out in a complex manner.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"357-382"},"PeriodicalIF":2.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615994","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}
引用次数: 0
Divergent multiomic acute exercise responses reveal the impact of sex as a biological variable. 不同的多组急性运动反应揭示性别作为一个生物学变量的影响。
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-05-01 Epub Date: 2025-02-27 DOI: 10.1152/physiolgenomics.00055.2024
Kaleen M Lavin, Samia M O'Bryan, Khyatiben V Pathak, Krystine Garcia-Mansfield, Zachary A Graham, Jeremy S McAdam, Devin J Drummer, Margaret B Bell, Christian J Kelley, Manoel E Lixandrão, Brandon Peoples, Regina S Seay, Anakaren R Torres, Rebecca Reiman, Eric Alsop, Elizabeth Hutchins, Anna Bonfitto, Jerry Antone, Joanna Palade, Kendall Van Keuren-Jensen, Matthew J Huentelman, Patrick Pirrotte, Timothy Broderick, Marcas M Bamman
{"title":"Divergent multiomic acute exercise responses reveal the impact of sex as a biological variable.","authors":"Kaleen M Lavin, Samia M O'Bryan, Khyatiben V Pathak, Krystine Garcia-Mansfield, Zachary A Graham, Jeremy S McAdam, Devin J Drummer, Margaret B Bell, Christian J Kelley, Manoel E Lixandrão, Brandon Peoples, Regina S Seay, Anakaren R Torres, Rebecca Reiman, Eric Alsop, Elizabeth Hutchins, Anna Bonfitto, Jerry Antone, Joanna Palade, Kendall Van Keuren-Jensen, Matthew J Huentelman, Patrick Pirrotte, Timothy Broderick, Marcas M Bamman","doi":"10.1152/physiolgenomics.00055.2024","DOIUrl":"10.1152/physiolgenomics.00055.2024","url":null,"abstract":"<p><p>The majority of exercise physiology research has been conducted in males, resulting in a skewed biological representation of how exercise impacts the physiological system. Extrapolating male-centric physiological findings to females is not universally appropriate and may even be detrimental. Thus, addressing this imbalance and taking into consideration sex as a biological variable is mandatory for optimization of precision exercise interventions and/or regimens. Our present analysis focused on establishing multiomic profiles in young, exercise-naïve males (<i>n</i> = 23) and females (<i>n</i> = 17) at rest and following acute exercise. Sex differences were characterized at baseline and following exercise using skeletal muscle and extracellular vesicle transcriptomics, whole blood methylomics, and serum metabolomics. Sex-by-time analysis of the acute exercise response revealed notable overlap, and divergent molecular responses between males and females. An exploratory comparison of two combined exercise regimens [high-intensity tactical training (HITT) and traditional (TRAD)] was then performed using singular value decomposition, revealing latent data structures that suggest a complex dose-by-sex interaction response to exercise. These findings lay the groundwork for an understanding of key differences in responses to acute exercise exposure between sexes. This may be leveraged in designing optimal training strategies, understanding common and divergent molecular interplay guiding exercise responses, and elucidating the role of sex hormones and/or other sex-specific attributes in responses to acute and chronic exercise.<b>NEW & NOTEWORTHY</b> This study examined methylomics, transcriptomics, and metabolomics in circulation and/or skeletal muscle of young, healthy, exercise-naïve males and females before and after exposure to either traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found an overlapping yet considerably sex-divergent response in the molecular mechanisms activated by exercise. These findings may provide insight into optimal training strategies for adaptation when considering sex as a biological variable.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"321-342"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516404","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}
引用次数: 0
Evidence of a novel gene locus ARHGAP44 for longitudinal change in hemoglobin A1c levels among subjects without diabetes from the Long Life Family Study. 新基因位点ARHGAP44与长期家庭研究中非糖尿病受试者血红蛋白A1c水平纵向变化的证据
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-05-01 Epub Date: 2025-02-28 DOI: 10.1152/physiolgenomics.00137.2024
Siyu Wang, Petra Lenzini, Bharat Thyagarajan, Joseph H Lee, Badri N Vardarajan, Anatoli Yashin, Iva Miljkovic, E Warwick Daw, Shiow J Lin, Gary J Patti, Michael R Brent, Joseph M Zmuda, Thomas T Perls, Kaare Christensen, Michael A Province, Ping An
{"title":"Evidence of a novel gene locus <i>ARHGAP44</i> for longitudinal change in hemoglobin A1c levels among subjects without diabetes from the Long Life Family Study.","authors":"Siyu Wang, Petra Lenzini, Bharat Thyagarajan, Joseph H Lee, Badri N Vardarajan, Anatoli Yashin, Iva Miljkovic, E Warwick Daw, Shiow J Lin, Gary J Patti, Michael R Brent, Joseph M Zmuda, Thomas T Perls, Kaare Christensen, Michael A Province, Ping An","doi":"10.1152/physiolgenomics.00137.2024","DOIUrl":"10.1152/physiolgenomics.00137.2024","url":null,"abstract":"<p><p>Glycated hemoglobin A1c (HbA1c) indicates average glucose levels over 3 mo and is associated with insulin resistance and type 2 diabetes (T2D). Longitudinal change in circulating HbA1c (ΔHbA1c) is also associated with aging processes, cognitive performance, and mortality. We analyzed ΔHbA1c in 1,886 nondiabetic Europeans from the Long Life Family Study (LLFS) to uncover gene loci influencing ΔHbA1c. Using growth curve modeling adjusted for multiple covariates, we derived ΔHbA1c and conducted linkage-guided sequence analysis. Our genome-wide linkage scan identified a significant locus on <i>17p12</i>. In-depth analysis revealed a gene locus <i>ARHGAP44</i> (rs56340929, explaining 27% of the linkage peak) that was significantly associated with ΔHbA1c. Interestingly, RNA transcription of <i>ARHGAP44</i> was also significantly associated with ΔHbA1c in the LLFS, and this discovery was replicable on the gene locus level in the Framingham Offspring Study (FOS). Taking together, we successfully identified a novel gene locus <i>ARHGAP44</i> for ΔHbA1c in family members without T2D. Further follow-up studies using longitudinal omics data in large independent cohorts are warranted.<b>NEW & NOTEWORTHY</b> HbA1c is clinically used in T2D diagnosis and monitoring. Its longitudinal change (ΔHbA1c) is associated with T2D-related aging processes and mortality. Targeted association tests under significant linkage peaks in extended families permit identification of unique gene loci. We uncovered a novel gene locus <i>ARHGAP44</i> for ΔHbA1c with gene-level validations from the FOS and RNAseq data in the LLFS. The finding provides genetically informed biological insight into mechanistic inference of glycemia/HbA1c homeostasis and potential T2D pathophysiology.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"293-298"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143528174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel effects of reverse transcriptase inhibitor supplementation in skeletal muscle of old mice. 补充逆转录酶抑制剂对老年小鼠骨骼肌的新作用。
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-05-01 Epub Date: 2025-03-10 DOI: 10.1152/physiolgenomics.00115.2024
Shelby C Osburn, Meghan E Smith, Devin Wahl, Thomas J LaRocca
{"title":"Novel effects of reverse transcriptase inhibitor supplementation in skeletal muscle of old mice.","authors":"Shelby C Osburn, Meghan E Smith, Devin Wahl, Thomas J LaRocca","doi":"10.1152/physiolgenomics.00115.2024","DOIUrl":"10.1152/physiolgenomics.00115.2024","url":null,"abstract":"<p><p>Aging is the primary risk factor for the development of many chronic diseases, including dementias, cardiovascular disease, and diabetes. There is significant interest in identifying novel \"geroprotective\" agents, including by repurposing existing drugs, but such treatments may affect organ systems differently. One current example is the nucleoside reverse transcriptase inhibitor 3TC, which has been increasingly studied as a potential gerotherapeutic. Recent data suggest that 3TC may reduce inflammation and improve cognitive function in older mice; however, the effects of 3TC on other tissues in aged animals are less well characterized. Here, we use transcriptomics (RNA-seq) and targeted metabolomics to investigate the influence of 3TC supplementation on skeletal muscle in older mice. We show that 3TC <i>1</i>) does not overtly affect muscle mass or functional/health markers, <i>2</i>) largely reverses age-related changes in gene expression and metabolite signatures, and <i>3</i>) is potentially beneficial for mitochondrial function in old animals via increases in antioxidant enzymes and decreases in mitochondrial reactive oxygen species. Collectively, our results suggest that, in addition to its protective effects in other tissues, 3TC supplementation does not have adverse effects in aged muscle and may even protect muscle/mitochondrial health in this context.<b>NEW & NOTEWORTHY</b> Recent studies suggest that the nucleoside reverse transcriptase inhibitor 3TC may improve brain health and cognitive function in old mice, but its effects on other aging tissues have not been comprehensively studied. This is the first study to use a multiomics approach to investigate the effects of 3TC treatment on skeletal muscle of old mice. The results suggest that 3TC reverses age-related transcriptomic and metabolite signatures and is potentially beneficial for mitochondrial function in aged muscle.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"308-320"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12139428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differences in the bacterial communities along the intestinal tract of juvenile channel (Ictalurus punctatus) and hybrid (I. punctatus× I. furcatus) catfish. 幼鱼和杂交鲶鱼肠道细菌群落的差异。
IF 2.5 4区 生物学
Physiological genomics Pub Date : 2025-05-01 Epub Date: 2025-02-28 DOI: 10.1152/physiolgenomics.00008.2025
Caitlin E Older, Penelope M Goodman, J Grant Reifers, Fernando Y Yamamoto
{"title":"Differences in the bacterial communities along the intestinal tract of juvenile channel (<i>Ictalurus punctatus</i>) and hybrid (<i>I. punctatus</i>× <i>I. furcatus</i>) catfish.","authors":"Caitlin E Older, Penelope M Goodman, J Grant Reifers, Fernando Y Yamamoto","doi":"10.1152/physiolgenomics.00008.2025","DOIUrl":"10.1152/physiolgenomics.00008.2025","url":null,"abstract":"<p><p>Hybrid catfish (<i>Ictalurus punctatus</i> × <i>I. furcatus</i>) is the preferred catfish for US aquaculture due to the heterosis exhibited in many production traits. Improvements in fry production protocols have enabled widespread adoption of these hybrids, with producers using management practices optimized for channel catfish. Research to consider differences, outside of production traits, which may exist between hybrids and their parent species is lacking. Utilizing management practices specifically designed for hybrids may improve production efficiency. The gut microbiome plays critical roles in host development and health and, thus, is relevant to production. In the present study, the microbiota in the anterior, middle, and posterior segments of the intestinal tract were compared between channel and hybrid catfish using high-throughput 16S rRNA gene sequencing. Bacterial community structure was different between channels and hybrids across all intestinal segments (<i>P</i> < 0.05) despite a lack of difference in community diversity. <i>Cetobacterium</i> spp. were found in higher abundances in the middle intestinal segment of hybrids compared with channels (<i>q</i> = 0.02) and found to have a trend of increasing abundance with increasingly distal segments in both channels and hybrids (<i>q</i> < 0.05). <i>Vibrio</i> spp., a low-abundance taxon, was similarly found in higher abundances in the anterior segment of hybrids. These results provide evidence of differences in the gut microbiomes of channels and hybrids and insight into the bacterial communities along the catfish intestinal tract. Additional research will be valuable in understanding why do differences between channel and hybrid catfish exist and how they may contribute to variation in gut microbiome-related production traits.<b>NEW & NOTEWORTHY</b> Hybrid and channel catfish are inhabited by gut bacterial communities of similar overall diversity but of significantly different structure and composition. <i>Cetobacterium</i> spp., a genus previously shown to confer benefits in other hosts, was found in higher abundances in the middle intestinal segment of hybrids and was found to have increasing abundance along the intestinal tract of both channels and hybrids.</p>","PeriodicalId":20129,"journal":{"name":"Physiological genomics","volume":" ","pages":"299-307"},"PeriodicalIF":2.5,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524134","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}
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