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Ectopic expression of Slc1a2 in the prefrontal cortex of sleep-deprived male mice counteracts the glutamate/GABA-glutamine dysfunction.
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-26 DOI: 10.1186/s12915-025-02161-7
Fengying Zhang, Yao Li, Li Jiang, Yingbin Wang, Yonghong Tang, Bo Ouyang, Guojun Song, Xuan Li, Xiajie Quan, Min Li, Hongying Wang, Zhao Pan, Keyan Chen, Ping Zhang
{"title":"Ectopic expression of Slc1a2 in the prefrontal cortex of sleep-deprived male mice counteracts the glutamate/GABA-glutamine dysfunction.","authors":"Fengying Zhang, Yao Li, Li Jiang, Yingbin Wang, Yonghong Tang, Bo Ouyang, Guojun Song, Xuan Li, Xiajie Quan, Min Li, Hongying Wang, Zhao Pan, Keyan Chen, Ping Zhang","doi":"10.1186/s12915-025-02161-7","DOIUrl":"10.1186/s12915-025-02161-7","url":null,"abstract":"<p><strong>Background: </strong>The prefrontal cortex (PFC) plays a pronounced role in cognitive and emotional functions, which may be compromised by dismal sleep quality. This study intended to clarify the impact of Slc1a2 ectopic expression in the PFC on sleep deprivation (SD)-induced disturbances in the glutamate (Glu)/GABA-glutamine cycle and the role of astrocyte (AC)-neuron (Neu) communication.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was adopted to illuminate cell-specific changes in the brainstem, cortex, and hypothalamus of mice under NS, SD, and post-SD conditions. Cell communication analysis was applied to study interactions between ACs and Neus, which altered after the SD. Slc1a2 was ectopically expressed in the PFC and subjected to SD, followed by electrophysiological, immunofluorescence staining, and [<sup>1</sup>H-<sup>13</sup>C]-nuclear magnetic resonance (NMR) assays to examine neural activity and metabolic status. Behavioral tests, including the open field, novel object recognition, and Y-maze, were conducted to examine cognitive functions and emotional states.</p><p><strong>Results: </strong>SD caused notable changes in cellular distribution and downregulation of metabolic and synaptic genes in affected brain regions. Cell communication studies highlighted a reduction in AC-Neu interactions, with corresponding metabolic disruptions in the Glu/GABA-glutamine cycle as depicted by [<sup>1</sup>H-<sup>13</sup>C]-NMR results. Behavior tests confirmed anxiety and cognitive deficits in SD mice, which were substantially alleviated by Slc1a2 ectopic expression in the PFC.</p><p><strong>Conclusions: </strong>Slc1a2 ectopic expression in the PFC negates SD-induced GABA dysfunction through vital AC-Neu communication. This study sheds light on the mechanisms through which SD affects neural function and suggesting potential treatments for sleep-related disorders.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"86"},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Label-free metabolic fingerprinting of motile mammalian spermatozoa with subcellular resolution.
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-24 DOI: 10.1186/s12915-025-02167-1
Fitore Kusari, Lenka Backova, Dalibor Panek, Ales Benda, Zdenek Trachtulec
{"title":"Label-free metabolic fingerprinting of motile mammalian spermatozoa with subcellular resolution.","authors":"Fitore Kusari, Lenka Backova, Dalibor Panek, Ales Benda, Zdenek Trachtulec","doi":"10.1186/s12915-025-02167-1","DOIUrl":"10.1186/s12915-025-02167-1","url":null,"abstract":"<p><strong>Background: </strong>Sperm metabolic pathways that generate energy for motility are compartmentalized within the flagellum. Dysfunctions in metabolic compartments, namely mitochondrial respiration and glycolysis, can compromise motility and male fertility. Studying these compartments is thus required for fertility treatment. However, it is very challenging to capture images of metabolic compartments in motile spermatozoa because the fast beating of the flagellum introduces motion blur. Therefore, most approaches immobilize spermatozoa prior to imaging.</p><p><strong>Results: </strong>Our findings indicate that immobilizing sperm alters their metabolic profile, highlighting the necessity for measuring metabolism in spermatozoa during movement. We achieved this by encapsulating mouse epididymis in a hydrogel followed by two-photon fluorescence lifetime imaging microscopy for imaging motile sperm in situ. The autofluorescence of endogenous metabolites-FAD, NADH, and NADPH-enabled us to visualize sperm metabolic compartments without staining. We trained machine learning for automated image segmentation and generated metabolic fingerprints using object-based phasor analysis. We show that metabolic fingerprints of spermatozoa and the mitochondrial compartment (1) can distinguish individual males by genetic background, age, or fecundity status, (2) correlate with fertility, and (3) change with age likely due to increased oxidative metabolism.</p><p><strong>Conclusions: </strong>Our approach eliminates the need for sperm immobilization and labeling and captures the native state of sperm metabolism. This technique could be adapted for metabolism-based sperm selection for assisted reproduction.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"85"},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
CTCF-anchored chromatin loop dynamics during human meiosis. 人类减数分裂过程中 CTCF 锚定染色质环的动态变化
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-20 DOI: 10.1186/s12915-025-02181-3
Vera B Kaiser, Colin A Semple
{"title":"CTCF-anchored chromatin loop dynamics during human meiosis.","authors":"Vera B Kaiser, Colin A Semple","doi":"10.1186/s12915-025-02181-3","DOIUrl":"10.1186/s12915-025-02181-3","url":null,"abstract":"<p><strong>Background: </strong>During meiosis, the mammalian genome is organised within chromatin loops, which facilitate synapsis, crossing over and chromosome segregation, setting the stage for recombination events and the generation of genetic diversity. Chromatin looping is thought to play a major role in the establishment of cross overs during prophase I of meiosis, in diploid early primary spermatocytes. However, chromatin conformation dynamics during human meiosis are difficult to study experimentally, due to the transience of each cell division and the difficulty of obtaining stage-resolved cell populations. Here, we employed a machine learning framework trained on single cell ATAC-seq and RNA-seq data to predict CTCF-anchored looping during spermatogenesis, including cell types at different stages of meiosis.</p><p><strong>Results: </strong>We find dramatic changes in genome-wide looping patterns throughout meiosis: compared to pre-and-post meiotic germline cell types, loops in meiotic early primary spermatocytes are more abundant, more variable between individual cells, and more evenly spread throughout the genome. In preparation for the first meiotic division, loops also include longer stretches of DNA, encompassing more than half of the total genome. These loop structures then influence the rate of recombination initiation and resolution as cross overs. In contrast, in later mature sperm stages, we find evidence of genome compaction, with loops being confined to the telomeric ends of the chromosomes.</p><p><strong>Conclusion: </strong>Overall, we find that chromatin loops do not orchestrate the gene expression dynamics seen during spermatogenesis, but loops do play important roles in recombination, influencing the positions of DNA breakage and cross over events.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"83"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Sex- and social context-dependent differences in mice fine head movement during social interactions.
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-20 DOI: 10.1186/s12915-025-02191-1
Adèle Phalip, Shai Netser, Shlomo Wagner
{"title":"Sex- and social context-dependent differences in mice fine head movement during social interactions.","authors":"Adèle Phalip, Shai Netser, Shlomo Wagner","doi":"10.1186/s12915-025-02191-1","DOIUrl":"10.1186/s12915-025-02191-1","url":null,"abstract":"<p><strong>Background: </strong>Social decision-making is influenced by multiple factors such as age, sex, emotional state, and the individual's social environment. While various behavioural readouts have been commonly used to study social behaviour in rodents, the role of fine head movements during social interactions remains underexplored despite the presence of accelerometers in many electrophysiological recording systems.</p><p><strong>Results: </strong>Here, we used head acceleration data to analyse head movement kinematics in adult male and female mice across several social discrimination tests in various time scales. Our findings demonstrate the complementary nature of two variables derived from the raw acceleration, namely overall static (OSHA) and dynamic (ODHA) head acceleration, as well as specific head angles (Pitch and Roll). Together, these variables provide a comprehensive, detailed analysis of head movement, which cannot be easily achieved by video analysis systems such as DeepLabCut. Overall, our results suggest that head movement patterns are significantly influenced by sex, stimulus preference, and social context. Specifically, ODHA exhibited strong sex dependence and appeared to be more sensitive to internal states such as arousal and alertness. The static components were primarily influenced by social context, particularly stimulus preference, and seemed to reflect the subject's motivation to engage with the stimulus. The Roll angle also appeared strongly modulated by the broader social context.</p><p><strong>Conclusions: </strong>Our study provides a novel method and analysis pipeline for studying the social behaviour of small rodents in high-time resolution using a head-based accelerometer. Our findings suggest that such measurements may inform the affective and motivational states of the subject during social interactions.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"82"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
The chromosome-scale genomes of two Tinospora species reveal differential regulation of the MEP pathway in terpenoid biosynthesis.
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-20 DOI: 10.1186/s12915-025-02185-z
Zhiyu Chen, Lan Xun, Yunyan Lu, Xingyu Yang, Minghui Chen, Tianyu Yang, Zhinan Mei, Yunqiang Yang, Xuefei Yang, Yongping Yang
{"title":"The chromosome-scale genomes of two Tinospora species reveal differential regulation of the MEP pathway in terpenoid biosynthesis.","authors":"Zhiyu Chen, Lan Xun, Yunyan Lu, Xingyu Yang, Minghui Chen, Tianyu Yang, Zhinan Mei, Yunqiang Yang, Xuefei Yang, Yongping Yang","doi":"10.1186/s12915-025-02185-z","DOIUrl":"10.1186/s12915-025-02185-z","url":null,"abstract":"<p><strong>Background: </strong>The relationship between gene family expansion and the resulting changes in plant phenotypes has shown remarkable complexity during the evolution. The gene family expansion has contributed to the diversity in plant phenotypes, specifically metabolites through neo-functionalization and sub-functionalization. However, the negative regulatory effects associated with the gene family expansion remain poorly understood.</p><p><strong>Results: </strong>Here, we present the chromosome-scale genomes of Tinospora crispa and Tinospora sinensis. Comparative genomic analyses demonstrated conserved chromosomal evolution within the Menispermaceae family. KEGG analysis revealed a significant enrichment of genes related to terpenoid biosynthesis in T. sinensis. However, T. crispa exhibited a higher abundance of terpenoids compared to T. sinensis. Detailed analysis revealed the expansion of genes encoding 1-hydroxy-2-methyl 2-(E)-butenyl 4-diphosphate synthase (HDS), a key enzyme in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway of terpenoid biosynthesis in T. sinensis. TsiHDS4 retained the ancestral function of converting methylerythritol cyclic diphosphate (MEcPP) to (E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP). However, the noncanonical CDS-derived small peptide TsiHDS5 was shown to interact with TsiHDS4, inhibiting its catalytic activity. This interaction reduced the levels of HMBPP and isopentenyl pyrophosphate (IPP), which represent key substrates for downstream terpenoid biosynthesis.</p><p><strong>Conclusions: </strong>These findings offer clues to decipher the variations in the MEP pathway of terpenoid biosynthesis between T. crispa and T. sinensis and form a basis for further detailed research on the negative regulation of expanded genes.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"84"},"PeriodicalIF":4.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling.
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-13 DOI: 10.1186/s12915-025-02183-1
Jerome Jatzlau, Sophie-Nhi Do, Rebeca A Mees, Paul-Lennard Mendez, Rameez Jabeer Khan, Lukas Maas, Lidia Ruiz, Pau Martin-Malpartida, Maria J Macias, Petra Knaus
{"title":"Rare but specific: 5-bp composite motifs define SMAD binding in BMP signaling.","authors":"Jerome Jatzlau, Sophie-Nhi Do, Rebeca A Mees, Paul-Lennard Mendez, Rameez Jabeer Khan, Lukas Maas, Lidia Ruiz, Pau Martin-Malpartida, Maria J Macias, Petra Knaus","doi":"10.1186/s12915-025-02183-1","DOIUrl":"10.1186/s12915-025-02183-1","url":null,"abstract":"<p><strong>Background: </strong>Receptor-activated SMADs trimerize with SMAD4 to regulate context-dependent target gene expression. However, the presence of a single SMAD1/5/8 binding motif in cis-regulatory elements alone does not trigger transcription in native contexts. We hypothesize that binding to composite motifs in which at least two SMAD binding sites are in close proximity would be enough to induce transcription as this scenario allows the simultaneous interaction of at least two SMAD proteins, thereby increasing specificity and affinity.</p><p><strong>Results: </strong>Using more than 65 distinct firefly luciferase constructs, we delineated the minimal requirements for BMP-induced gene activation. We propose a model in which two SMAD-MH1 domains bind a SMAD-composite motif in a back-to-back fashion with a 5-bp distance between the SMAD-motifs on opposing DNA strands. However screening of SMAD1-bound regions across a variety of cell types highlights that these composite motifs are extremely uncommon, explaining below 1% of SMAD1 binding events.</p><p><strong>Conclusions: </strong>Deviations from these minimal requirements prevent transcription and underline the need for co-transcription factors to achieve gene activation.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"79"},"PeriodicalIF":4.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Gfa1 (glutamine fructose-6-phosphate aminotransferase) is essential for Aspergillus fumigatus growth and virulence.
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-13 DOI: 10.1186/s12915-025-02184-0
Qijian Qin, Pingzhen Wei, Sayed Usman, Chukwuemeka Samson Ahamefule, Cheng Jin, Bin Wang, Kaizhou Yan, Daan M F van Aalten, Wenxia Fang
{"title":"Gfa1 (glutamine fructose-6-phosphate aminotransferase) is essential for Aspergillus fumigatus growth and virulence.","authors":"Qijian Qin, Pingzhen Wei, Sayed Usman, Chukwuemeka Samson Ahamefule, Cheng Jin, Bin Wang, Kaizhou Yan, Daan M F van Aalten, Wenxia Fang","doi":"10.1186/s12915-025-02184-0","DOIUrl":"10.1186/s12915-025-02184-0","url":null,"abstract":"<p><strong>Background: </strong>Aspergillus fumigatus, the primary etiological agent of invasive aspergillosis, causes over 1.8 million deaths annually. Targeting cell wall biosynthetic pathways offers a promising antifungal strategy. Gfa1, a rate-limiting enzyme in UDP-GlcNAc synthesis, plays a pivotal role in the hexosamine biosynthetic pathway (HBP).</p><p><strong>Results: </strong>Deletion of gfa1 (Δgfa1) results in auxotrophy for glucosamine (GlcN) or N-acetylglucosamine (GlcNAc). Under full recovery (FR) conditions, where minimal medium is supplemented with 5 mM GlcN as the sole carbon source, the Δgfa1 mutant shows growth comparable to the wild-type (WT). However, when supplemented with 5 mM GlcN and 55 mM glucose, growth is partially repressed, likely due to carbon catabolite repression, a condition termed partial repression (PR). Under PR conditions, Δgfa1 exhibits compromised growth, reduced conidiation, defective germination, impaired cell wall integrity, and increased sensitivity to endoplasmic reticulum (ER) stress and high temperatures. Additionally, Δgfa1 demonstrates disruptions in protein homeostasis and iron metabolism. Transcriptomic analysis of the mutant under PR conditions reveals significant alterations in carbohydrate and amino acid metabolism, unfolded protein response (UPR) processes, and iron assimilation. Importantly, Gfa1 is essential for A. fumigatus virulence, as demonstrated in Caenorhabditis elegans and Galleria mellonella infection models.</p><p><strong>Conclusions: </strong>These findings underscore the critical role of Gfa1 in fungal pathogenicity and suggest its potential as a therapeutic target for combating A. fumigatus infections.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"80"},"PeriodicalIF":4.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11907850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Correction: Phylogenomics of angiosperms based on mitochondrial genes: insights into deep node relationships.
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-12 DOI: 10.1186/s12915-025-02189-9
Dongliang Lin, Bingyi Shao, Zhiyuan Gao, Jianwu Li, Zhanghai Li, Tingyu Li, Weichang Huang, Xin Zhong, Chao Xu, Mark W Chase, Xiaohua Jin
{"title":"Correction: Phylogenomics of angiosperms based on mitochondrial genes: insights into deep node relationships.","authors":"Dongliang Lin, Bingyi Shao, Zhiyuan Gao, Jianwu Li, Zhanghai Li, Tingyu Li, Weichang Huang, Xin Zhong, Chao Xu, Mark W Chase, Xiaohua Jin","doi":"10.1186/s12915-025-02189-9","DOIUrl":"10.1186/s12915-025-02189-9","url":null,"abstract":"","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"77"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Bradykinin's carbamylation as a mechanistic link to impaired wound healing in patients with kidney dysfunction.
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-12 DOI: 10.1186/s12915-025-02187-x
Marta Kaminska, Urszula Kałucka, Janka Babickova, Małgorzata Benedyk-Machaczka, Eleni Skandalou, Melissa M Grant, Hans-Peter Marti, Piotr Mydel
{"title":"Bradykinin's carbamylation as a mechanistic link to impaired wound healing in patients with kidney dysfunction.","authors":"Marta Kaminska, Urszula Kałucka, Janka Babickova, Małgorzata Benedyk-Machaczka, Eleni Skandalou, Melissa M Grant, Hans-Peter Marti, Piotr Mydel","doi":"10.1186/s12915-025-02187-x","DOIUrl":"10.1186/s12915-025-02187-x","url":null,"abstract":"<p><strong>Background: </strong>Uremic impairment of wound healing is a well-established phenomenon, however the etiology of this condition continues to be a medical enigma. Carbamylation, posttranslational modification (PTM) occurring with high frequency in uremic milieu, is known to have impact on structural and functional properties of proteins and peptides. Herein we show that carbamylation of the members of kinin-kallikrein system, that play an essential role in wound healing process, results in its aberrant functionality and impedes the complex process of tissue regeneration in uremic patients.</p><p><strong>Results: </strong>Through enzymatic assays we demonstrate that carbamylation of kininogen results in aberrant bradykinin generation. We confirmed that bradykinin is efficiently carbamylated in uremic conditions and, alternatively, by activated neutrophiles. Moreover, this modification affects proteolytic cleavage of the peptide, potentially leading to the accumulation of the carbamylated form. Modified peptide demonstrated lower affinity toward its receptors. Carbamylation diminished bradykinin's ability to stimulate expression of the B<sub>1</sub> receptor and cytokines essential in wound healing process. Carbamylated bradykinin was significantly less potent in promoting angiogenesis and keratinocyte motility as compared to the native form. In the in vivo murine model of wound healing, we observed impaired collagen fiber production and delayed re-epithelialisation in the presence of carbamylated form.</p><p><strong>Conclusions: </strong>Carbamylation-driven impairment of wound healing is a mechanistic link to wound persistence in uremia. Importantly, production of carbamylated bradykinin in localized inflammatory milieus could be a significant contributor to delayed wound healing and formation of chronic wounds in diabetes or psoriasis.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"76"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
A dynamic transcriptional cell atlas of testes development after birth in Hu sheep.
IF 4.4 1区 生物学
BMC Biology Pub Date : 2025-03-12 DOI: 10.1186/s12915-025-02186-y
Jie Su, Yanyan Yang, Daqing Wang, Hong Su, Feifei Zhao, Chuanqiang Zhang, Min Zhang, Xiunan Li, Tingyi He, Xihe Li, Ying Tian, Biao Song, Chao Chen, Yongli Song, Guifang Cao
{"title":"A dynamic transcriptional cell atlas of testes development after birth in Hu sheep.","authors":"Jie Su, Yanyan Yang, Daqing Wang, Hong Su, Feifei Zhao, Chuanqiang Zhang, Min Zhang, Xiunan Li, Tingyi He, Xihe Li, Ying Tian, Biao Song, Chao Chen, Yongli Song, Guifang Cao","doi":"10.1186/s12915-025-02186-y","DOIUrl":"10.1186/s12915-025-02186-y","url":null,"abstract":"<p><strong>Background: </strong>Testes development is a fundamental process in sexual development and reproduction. The testes undergo dramatic structural changes during development, including the proliferation and differentiation of somatic cells such as Sertoli cells, Leydig cells, and myoid cells, as well as the maturation of spermatogonia. However, little is known about the onset of spermatogenesis and cell proliferation and maturation in the spermatogonial niche in large animals.</p><p><strong>Results: </strong>We used single-cell RNA sequencing (scRNA-seq) to profile nearly 100,000 cells from Hu sheep testes across seven developmental stages (birth, prepuberty, puberty, and adulthood). We constructed single-cell transcriptomic atlases and identified distinct spermatogonial subtypes, revealing dynamic gene expression patterns during spermatogenesis. Notably, we observed that two distinct Sertoli cell states converge into a mature population during puberty. Additionally, we identified a common prepubertal progenitor for Leydig and myoid cells, with Leydig cells transitioning through progenitor and immature stages before reaching maturity.</p><p><strong>Conclusions: </strong>Our study provides a comprehensive atlas of Hu sheep testes development, revealing key insights into the dynamic changes and regulatory mechanisms of spermatogenesis and somatic cell maturation from birth to adulthood. These findings offer new perspectives on testicular development in large mammals and support future research on reproductive biology and breeding strategies.</p>","PeriodicalId":9339,"journal":{"name":"BMC Biology","volume":"23 1","pages":"78"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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