Pub Date : 2025-11-29DOI: 10.1016/j.isci.2025.114272
Fei Guo , Nannan Liu , Ruiheng Peng , Binyao Wang , Yeqing Chang , Hong Jin , Xinyu Xiong , Dongxu Zhang , Qianlong Zhang , Liqiang Zheng
As one of the prevalent complications during pregnancy, this study discussed the association between gestational diabetes mellitus (GDM) and multi-source built-environment from the perspective of different spatial scales in mega-cities. This study centered on 4,355 women at a Shanghai hospital. Thirteen variables were selected, then multi-scale geographically weighted regression (MGWR) was used to clarity how these variables relate to GDM. The results showed that: MGWR effectively revealed the relationship between the built environment and GDM at different scales. At specific spatial scales, building-density (BD) and sky view factor (SVF) exhibit pronounced spatial heterogeneity. Based on the mean coefficients in MGWR, it can be inferred that for every 0.1 increase in SVF and green view index (GVI), the probability of GDM decreases by 3% and 1%. These findings delve into the association between the built environment and lifestyle-related diseases. They underscore the significance of developing place-specific policies in health interventions and urban planning.
{"title":"How does high-density built-environment affect the incidence of gestational diabetes mellitus","authors":"Fei Guo , Nannan Liu , Ruiheng Peng , Binyao Wang , Yeqing Chang , Hong Jin , Xinyu Xiong , Dongxu Zhang , Qianlong Zhang , Liqiang Zheng","doi":"10.1016/j.isci.2025.114272","DOIUrl":"10.1016/j.isci.2025.114272","url":null,"abstract":"<div><div>As one of the prevalent complications during pregnancy, this study discussed the association between gestational diabetes mellitus (GDM) and multi-source built-environment from the perspective of different spatial scales in mega-cities. This study centered on 4,355 women at a Shanghai hospital. Thirteen variables were selected, then multi-scale geographically weighted regression (MGWR) was used to clarity how these variables relate to GDM. The results showed that: MGWR effectively revealed the relationship between the built environment and GDM at different scales. At specific spatial scales, building-density (BD) and sky view factor (SVF) exhibit pronounced spatial heterogeneity. Based on the mean coefficients in MGWR, it can be inferred that for every 0.1 increase in SVF and green view index (GVI), the probability of GDM decreases by 3% and 1%. These findings delve into the association between the built environment and lifestyle-related diseases. They underscore the significance of developing place-specific policies in health interventions and urban planning.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114272"},"PeriodicalIF":4.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.isci.2025.114271
Ravikumar Thangavel , Kalainathan Sivaperuman , Logu Thirumalaisamy , Christina Josephine Malathi A , Saravanan Pandiaraj , Maha Alruwaili , Nadyah Alanazi , Abdullah N. Alodhayb , R. Ramesh , Chamil Abeykoon , Andrews Nirmala Grace
This study focuses on developing economical and efficient ammonia (NH3) gas sensors capable of detecting low concentrations at room temperature. Cd-doped ZnFe2O4 (CdxZn1-xFe2O4, x = 0, 0.1,0.3, and 0.5) thin films were deposited via spray pyrolysis, showing significantly enhanced sensing performance compared to undoped ZnFe2O4. The Cd0.5Zn0.5Fe2O4 (ZFCD5) film demonstrated the best response (∼8) at 1 ppm NH3, with fast response (105 s) and recovery (54 s) times, a sensitivity of 10.07 ppm-1, repeatability, selectivity, and more stability over 6 weeks. The improved sensing is attributed to the angular-rod-like morphology that increases active sites and enhances charge transfer. Cd incorporation effectively boosts defect density and adsorption-desorption efficiency, resulting in a 10-fold higher response than the undoped film (∼0.8). The findings highlight the potential of Cd-doped ZnFe2O4 thin films as promising, room temperature NH3 sensors for industrial, environmental, and safety applications, also supporting safer environments for individuals with disabilities.
{"title":"Trace level detection of NH3 at room temperature using Cd-ZnFe2O4 thin films","authors":"Ravikumar Thangavel , Kalainathan Sivaperuman , Logu Thirumalaisamy , Christina Josephine Malathi A , Saravanan Pandiaraj , Maha Alruwaili , Nadyah Alanazi , Abdullah N. Alodhayb , R. Ramesh , Chamil Abeykoon , Andrews Nirmala Grace","doi":"10.1016/j.isci.2025.114271","DOIUrl":"10.1016/j.isci.2025.114271","url":null,"abstract":"<div><div>This study focuses on developing economical and efficient ammonia (NH<sub>3</sub>) gas sensors capable of detecting low concentrations at room temperature. Cd-doped ZnFe<sub>2</sub>O<sub>4</sub> (Cd<sub>x</sub>Zn<sub>1-x</sub>Fe<sub>2</sub>O<sub>4</sub>, x = 0, 0.1,0.3, and 0.5) thin films were deposited via spray pyrolysis, showing significantly enhanced sensing performance compared to undoped ZnFe<sub>2</sub>O<sub>4</sub>. The Cd<sub>0.5</sub>Zn<sub>0.5</sub>Fe<sub>2</sub>O<sub>4</sub> (ZFCD5) film demonstrated the best response (∼8) at 1 ppm NH<sub>3</sub>, with fast response (105 s) and recovery (54 s) times, a sensitivity of 10.07 ppm<sup>-1</sup>, repeatability, selectivity, and more stability over 6 weeks. The improved sensing is attributed to the angular-rod-like morphology that increases active sites and enhances charge transfer. Cd incorporation effectively boosts defect density and adsorption-desorption efficiency, resulting in a 10-fold higher response than the undoped film (∼0.8). The findings highlight the potential of Cd-doped ZnFe<sub>2</sub>O<sub>4</sub> thin films as promising, room temperature NH<sub>3</sub> sensors for industrial, environmental, and safety applications, also supporting safer environments for individuals with disabilities.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114271"},"PeriodicalIF":4.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-29DOI: 10.1016/j.isci.2025.114281
Reza Mirzaei , Reid McNeil , Charlotte D'Mello , Britney Wong , Susobhan Sarkar , Frank Visser , Candice Poon , Pinaki Bose , V. Wee Yong
Glioblastoma (GBM) contains diverse immune and tumor cell populations whose spatial organization influences disease progression. To better understand how immune cells interact with brain tumor-initiating cells (BTICs), we applied integrated single-cell and spatial transcriptomic approaches to map the immune landscape in a GBM mouse model. This analysis revealed a distinct subset of microglia expressing protein kinase Cδ (PKCδ) that localizes near BTIC-rich regions and displays features associated with anti-tumor activity. We validated the presence of PKCδ+ microglia in human GBM tissues and found that PKCδ enhances inducible nitric oxide synthase (iNOS) expression, supporting microglial cytotoxic and phagocytic functions. Increasing PKCδ levels in microglia, either through adeno-associated viral delivery or niacin treatment, strengthened their ability to engulf and kill BTICs. Analysis of patient datasets further showed that higher PKCδ expression associates with immune activation and cell death pathways. These findings identify PKCδ+ microglia as a therapeutically relevant component of the GBM microenvironment.
{"title":"Spatial single-cell profiling identifies protein kinase Cδ-expressing microglia with anti-tumor function in glioblastoma","authors":"Reza Mirzaei , Reid McNeil , Charlotte D'Mello , Britney Wong , Susobhan Sarkar , Frank Visser , Candice Poon , Pinaki Bose , V. Wee Yong","doi":"10.1016/j.isci.2025.114281","DOIUrl":"10.1016/j.isci.2025.114281","url":null,"abstract":"<div><div>Glioblastoma (GBM) contains diverse immune and tumor cell populations whose spatial organization influences disease progression. To better understand how immune cells interact with brain tumor-initiating cells (BTICs), we applied integrated single-cell and spatial transcriptomic approaches to map the immune landscape in a GBM mouse model. This analysis revealed a distinct subset of microglia expressing protein kinase Cδ (PKCδ) that localizes near BTIC-rich regions and displays features associated with anti-tumor activity. We validated the presence of PKCδ<sup>+</sup> microglia in human GBM tissues and found that PKCδ enhances inducible nitric oxide synthase (iNOS) expression, supporting microglial cytotoxic and phagocytic functions. Increasing PKCδ levels in microglia, either through adeno-associated viral delivery or niacin treatment, strengthened their ability to engulf and kill BTICs. Analysis of patient datasets further showed that higher PKCδ expression associates with immune activation and cell death pathways. These findings identify PKCδ<sup>+</sup> microglia as a therapeutically relevant component of the GBM microenvironment.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114281"},"PeriodicalIF":4.1,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.isci.2025.114288
Joachim Holt , Stephanie K. Holm , Rasmus M. Sandsdal , Simon B.K. Jensen , Christian R. Juhl , Mikkel H. Noer , Yasmin Afshar-Bahadori , Martin B. Blond , Thomas A. Gerds , Bente M. Stallknecht , Sten Madsbad , Jens J. Holst , Birgitte Holst , Bolette Hartmann , Sarah Byberg , Signe S. Torekov
Liver-expressed antimicrobial peptide 2 (LEAP2) is an anorexigenic hormone, but its long-term decrease after diet-induced weight loss may promote weight regain. This study examined whether exercise, glucagon-like peptide-1 receptor agonist (GLP-1RA) (liraglutide), or their combination prevents the post-diet decrease in LEAP2 during 1 year of weight-loss maintenance. LEAP2 plasma levels were measured in the fasting state and during 3-h standard liquid meal tests (600 kcal) in a randomized, double-blinded, placebo-controlled trial. 128 adults with obesity were included (BMI: 36.9 ± 2.9 kg/m2), 79 females and 49 males. Sex differences were evident at data inspection. In males, fasting LEAP2 decreased during the low-calorie diet (LCD) (p < 0.001), while in females, there was a delayed decrease after 1 year in the placebo, liraglutide, and combination groups (p < 0.001 to 0.033). Interestingly, in females in the exercise group, fasting and postprandial LEAP2 levels remained high. These findings raise the possibility that exercise might preserve LEAP2 levels after weight loss in females, supporting weight-loss maintenance.
{"title":"Exercise maintains LEAP2 levels after weight loss in females with obesity","authors":"Joachim Holt , Stephanie K. Holm , Rasmus M. Sandsdal , Simon B.K. Jensen , Christian R. Juhl , Mikkel H. Noer , Yasmin Afshar-Bahadori , Martin B. Blond , Thomas A. Gerds , Bente M. Stallknecht , Sten Madsbad , Jens J. Holst , Birgitte Holst , Bolette Hartmann , Sarah Byberg , Signe S. Torekov","doi":"10.1016/j.isci.2025.114288","DOIUrl":"10.1016/j.isci.2025.114288","url":null,"abstract":"<div><div>Liver-expressed antimicrobial peptide 2 (LEAP2) is an anorexigenic hormone, but its long-term decrease after diet-induced weight loss may promote weight regain. This study examined whether exercise, glucagon-like peptide-1 receptor agonist (GLP-1RA) (liraglutide), or their combination prevents the post-diet decrease in LEAP2 during 1 year of weight-loss maintenance. LEAP2 plasma levels were measured in the fasting state and during 3-h standard liquid meal tests (600 kcal) in a randomized, double-blinded, placebo-controlled trial. 128 adults with obesity were included (BMI: 36.9 ± 2.9 kg/m<sup>2</sup>), 79 females and 49 males. Sex differences were evident at data inspection. In males, fasting LEAP2 decreased during the low-calorie diet (LCD) (<em>p</em> < 0.001), while in females, there was a delayed decrease after 1 year in the placebo, liraglutide, and combination groups (<em>p</em> < 0.001 to 0.033). Interestingly, in females in the exercise group, fasting and postprandial LEAP2 levels remained high. These findings raise the possibility that exercise might preserve LEAP2 levels after weight loss in females, supporting weight-loss maintenance.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114288"},"PeriodicalIF":4.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Indian HIV-1 subtype C, infecting 2.6 million individuals, demonstrates unique geospatial diversity reflecting distinct evolution and host-pathogen interactions that may instruct the development of region-specific therapeutic strategies. An Indian PLHIV cohort was profiled for immune dysfunction, proviral load, broadly neutralizing antibody sensitivity, and drug resistance mutations in putative CD4+ T cell reservoirs. We demonstrate therapy state specific immune dysfunction, including in ART responding individuals, coincident but not correlated with stable proviral load, apparently enriched in CD4+ T memory subsets. Reservoir derived full length envs displayed distinct neutralization profiles against best-in-class broadly neutralizing antibodies, highlighting the need for a combinatorial approach to target potential breakthrough viruses. Surveillance of the archival repertoire demonstrated the occurrence of drug resistance conferring mutations (>10%) across therapy states, including instances of primary and acquired resistance to recently introduced integrase strand transfer inhibitors. Our data, underlines the need for incorporating reservoir diversity in intervention and management strategies.
{"title":"Immune and viral surveillance of HIV-1C reservoirs in an Indian cohort","authors":"Snehal Kaginkar , Shilpa Bhowmick , Nandini Kasarpalkar , Sharad Bhagat , Jyoti Sutar , Sapna Yadav , Sameen Khan , Pranay Gurav , Nandan Mohite , Namrata Neman , Nidhi Sehgal , Satyajit Musale , Varsha Padwal , Pratik Devadiga , Ranajoy Mullick , Priyanka Jayal , Tejaswini Pandey , Amit Kumar Singh , Shilpa Velhal , Sayantani Ghosh , Vainav Patel","doi":"10.1016/j.isci.2025.114278","DOIUrl":"10.1016/j.isci.2025.114278","url":null,"abstract":"<div><div>Indian HIV-1 subtype C, infecting 2.6 million individuals, demonstrates unique geospatial diversity reflecting distinct evolution and host-pathogen interactions that may instruct the development of region-specific therapeutic strategies. An Indian PLHIV cohort was profiled for immune dysfunction, proviral load, broadly neutralizing antibody sensitivity, and drug resistance mutations in putative CD4<sup>+</sup> T cell reservoirs. We demonstrate therapy state specific immune dysfunction, including in ART responding individuals, coincident but not correlated with stable proviral load, apparently enriched in CD4<sup>+</sup> T memory subsets. Reservoir derived full length <em>envs</em> displayed distinct neutralization profiles against best-in-class broadly neutralizing antibodies, highlighting the need for a combinatorial approach to target potential breakthrough viruses. Surveillance of the archival repertoire demonstrated the occurrence of drug resistance conferring mutations (>10%) across therapy states, including instances of primary and acquired resistance to recently introduced integrase strand transfer inhibitors. Our data, underlines the need for incorporating reservoir diversity in intervention and management strategies.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114278"},"PeriodicalIF":4.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145788753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spatial patterning in multicellular organisms is commonly explained by Turing-type reaction-diffusion systems, but the maturation of diffusible inhibitors remains poorly understood. In the cyanobacterium Nostoc PCC 7120, nitrogen deprivation triggers a pattern of nitrogen-fixing heterocysts regulated by HetR and inhibitory peptides, including PatX. We uncover the post-translational mechanism controlling PatX maturation, demonstrating its export and subsequent processing by the peptidase PatP. We identify HRGTGR, a PatX-derived hexapeptide, as the direct inhibitor of HetR, linking maturation to suppressed differentiation. Genomic analyses reveal that patP is ancient and conserved across all cyanobacteria, predating the patX-hetR module found only in filamentous clades. We therefore propose that this ancient peptidase was co-opted to process a new ligand, transforming a proteolytic event into a spatial patterning mechanism. This repurposing parallels eukaryotic signaling, underscoring a universal principle in the emergence of multicellular organization and providing a model for how complex patterns evolve from “simple” components.
{"title":"Co-option of an ancestral peptidase controls developmental patterning in multicellular cyanobacteria","authors":"Xiaomei Xu , Anaïs Scholivet , Stéphanie Champ , Matthieu Bergé , Zulihumaer Yeerkenjiang , Jonas Desjardins , Yann Denis , Badreddine Douzi , Deborah Byrne , Emmanuel Talla , Amel Latifi","doi":"10.1016/j.isci.2025.114265","DOIUrl":"10.1016/j.isci.2025.114265","url":null,"abstract":"<div><div>Spatial patterning in multicellular organisms is commonly explained by Turing-type reaction-diffusion systems, but the maturation of diffusible inhibitors remains poorly understood. In the cyanobacterium <em>Nostoc</em> PCC 7120, nitrogen deprivation triggers a pattern of nitrogen-fixing heterocysts regulated by HetR and inhibitory peptides, including PatX. We uncover the post-translational mechanism controlling PatX maturation, demonstrating its export and subsequent processing by the peptidase PatP. We identify HRGTGR, a PatX-derived hexapeptide, as the direct inhibitor of HetR, linking maturation to suppressed differentiation. Genomic analyses reveal that <em>patP</em> is ancient and conserved across all cyanobacteria, predating the <em>patX-hetR</em> module found only in filamentous clades. We therefore propose that this ancient peptidase was co-opted to process a new ligand, transforming a proteolytic event into a spatial patterning mechanism. This repurposing parallels eukaryotic signaling, underscoring a universal principle in the emergence of multicellular organization and providing a model for how complex patterns evolve from “simple” components.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114265"},"PeriodicalIF":4.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145712199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.isci.2025.114273
Chiara De Gregorio , Adriano R. Lameira
Rhythmic pulse, the division of a beat into subordinate patterns, is the backbone of music. Across the world’s musical traditions, the division of the primary beat into two equal parts – “double meter” – represents a prototypical pulse, also found in singing nonhuman primates. The last great ape common ancestor was, however, a non-singing species. How rhythmic pulse evolved in human song and music is, thus, enigmatic. Here, we analyze wild male orangutan long calls, which are structurally isochronous (i.e., with a steady of 1:1 rhythm). Males divided the primary rhythm into 1:2 and 2:1 subordinate patterns and did so by two distinct mechanisms: tempo changes as used by other primates and voiced in-exhale alternations as still used today by some human song traditions. Findings confirm double-meter in a non-singing great ape and suggest the two-phase cycle of the phonatory-respiratory system may have been leveraged for the evolution of human song and music.
{"title":"Twice times two: Dual mechanism for double rhythmic meter in orangutans and the evolution of human song","authors":"Chiara De Gregorio , Adriano R. Lameira","doi":"10.1016/j.isci.2025.114273","DOIUrl":"10.1016/j.isci.2025.114273","url":null,"abstract":"<div><div>Rhythmic pulse, the division of a beat into subordinate patterns, is the backbone of music. Across the world’s musical traditions, the division of the primary beat into two equal parts – “double meter” – represents a prototypical pulse, also found in singing nonhuman primates. The last great ape common ancestor was, however, a non-singing species. How rhythmic pulse evolved in human song and music is, thus, enigmatic. Here, we analyze wild male orangutan long calls, which are structurally isochronous (i.e., with a steady of 1:1 rhythm). Males divided the primary rhythm into 1:2 and 2:1 subordinate patterns and did so by two distinct mechanisms: tempo changes as used by other primates and voiced in-exhale alternations as still used today by some human song traditions. Findings confirm double-meter in a non-singing great ape and suggest the two-phase cycle of the phonatory-respiratory system may have been leveraged for the evolution of human song and music.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114273"},"PeriodicalIF":4.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145736038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.isci.2025.114261
Sally W. Yousief , Nader Abdelmalek , Martin S. Bojer , Yibing Ma , Priscila R. Guerra , Sajid Nisar , John E. Olsen , Bianca Paglietti
Staphylococcus aureus must dynamically rewire its metabolism to persist within distinct host tissues during infection. We applied in vivo transposon-directed insertion site sequencing (TraDIS) in murine models of skin, kidney, and spleen infections to define tissue-specific fitness landscapes for the epidemic USA300 lineage. We identified 46, 76, and 69 fitness genes in the skin, kidney, and spleen, respectively. The core gluconeogenesis gene fbp was essential across all tissues, whereas pckA and gapB showed organ-specific essentiality in the kidney and spleen. Skin infection required oxidative stress and DNA repair genes (ahpC, ahpF, dps, uvrC, and xseA), consistent with elevated genotoxic pressure. In contrast, kidney and spleen relied on branched-chain amino acid catabolism (bkdAB), lipid metabolism (SAUSA300_0355), and putative polyamine biosynthesis (SAUSA300_0458). Competition assays in vivo and under oxidative (H2O2) and gluconeogenic (M9) conditions validated these tissue-specific dependencies. These results reveal how S. aureus remodels metabolic networks and identifies context-specific vulnerabilities for therapeutic targeting.
{"title":"Genome-wide identification of tissue-specific fitness genes in murine models of Staphylococcus aureus infection","authors":"Sally W. Yousief , Nader Abdelmalek , Martin S. Bojer , Yibing Ma , Priscila R. Guerra , Sajid Nisar , John E. Olsen , Bianca Paglietti","doi":"10.1016/j.isci.2025.114261","DOIUrl":"10.1016/j.isci.2025.114261","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> must dynamically rewire its metabolism to persist within distinct host tissues during infection. We applied <em>in vivo</em> transposon-directed insertion site sequencing (TraDIS) in murine models of skin, kidney, and spleen infections to define tissue-specific fitness landscapes for the epidemic USA300 lineage. We identified 46, 76, and 69 fitness genes in the skin, kidney, and spleen, respectively. The core gluconeogenesis gene <em>fbp</em> was essential across all tissues, whereas <em>pckA</em> and <em>gapB</em> showed organ-specific essentiality in the kidney and spleen. Skin infection required oxidative stress and DNA repair genes (<em>ahpC</em>, <em>ahpF</em>, <em>dps</em>, <em>uvrC</em>, and <em>xseA</em>), consistent with elevated genotoxic pressure. In contrast, kidney and spleen relied on branched-chain amino acid catabolism (<em>bkdAB</em>), lipid metabolism (<em>SAUSA300_0355</em>), and putative polyamine biosynthesis (<em>SAUSA300_0458</em>). Competition assays <em>in vivo</em> and under oxidative (H<sub>2</sub>O<sub>2</sub>) and gluconeogenic (M9) conditions validated these tissue-specific dependencies. These results reveal how <em>S. aureus</em> remodels metabolic networks and identifies context-specific vulnerabilities for therapeutic targeting.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114261"},"PeriodicalIF":4.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.isci.2025.114286
Enhui Shen , Yifan Yu , Xiaoya Ma , Zhicheng Shen , Yuxuan Ye
Tracking parental genome contributions in segregating populations is crucial for accelerating genetic gain in plant breeding. We introduce GCCVision (Genome Contribution Calculator and Visualizer), an integrated bioinformatics toolkit to simplify this process. GCCVision uses an efficient Python-based backend and a user-friendly web-based frontend to analyze Variant Call Format (VCF) files from biparental crosses. The software identifies informative single-nucleotide polymorphisms (SNPs), calculates parental contribution rates, and generates clear, customizable graphical genotype maps where chromosome segments are color-coded by parental origin. By providing clear visualizations of genomic composition, GCCVision assists breeders in selection decisions for backcrossing, F2 analysis, quality control of hybrid seeds, and other breeding programs. This streamlined workflow shortens breeding cycles and accelerates the development of improved crop varieties.
{"title":"GCCVision: An integrated toolkit for calculating and visualizing parental genome contribution in breeding populations","authors":"Enhui Shen , Yifan Yu , Xiaoya Ma , Zhicheng Shen , Yuxuan Ye","doi":"10.1016/j.isci.2025.114286","DOIUrl":"10.1016/j.isci.2025.114286","url":null,"abstract":"<div><div>Tracking parental genome contributions in segregating populations is crucial for accelerating genetic gain in plant breeding. We introduce GCCVision (Genome Contribution Calculator and Visualizer), an integrated bioinformatics toolkit to simplify this process. GCCVision uses an efficient Python-based backend and a user-friendly web-based frontend to analyze Variant Call Format (VCF) files from biparental crosses. The software identifies informative single-nucleotide polymorphisms (SNPs), calculates parental contribution rates, and generates clear, customizable graphical genotype maps where chromosome segments are color-coded by parental origin. By providing clear visualizations of genomic composition, GCCVision assists breeders in selection decisions for backcrossing, F<sub>2</sub> analysis, quality control of hybrid seeds, and other breeding programs. This streamlined workflow shortens breeding cycles and accelerates the development of improved crop varieties.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"29 1","pages":"Article 114286"},"PeriodicalIF":4.1,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145735582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1016/j.isci.2025.114293
Ian Mersich , Brian S.J. Blagg , Aktar Ali
Broad drug resistance arises from diverse transcriptional, metabolic, and genetic adaptations, yet the unifying features that sustain cross-resistant phenotypes remain unclear. We developed an integrative framework combining PRISM drug-response data with transcriptomic, metabolomic, and mutational profiles to define the molecular programs associated with broad resistance and to nominate compounds capable of reversing them. Resistant cell lines exhibited coordinated activation of extracellular matrix remodeling, stress-adaptation pathways, and survival signaling, with NFE2L2 emerging as a central regulatory hub linking upstream mutations to oxidative-stress transcriptional programs. Multi-omic analyses revealed metabolic reprogramming as a conserved feature of resistance, and patient cohort analyses showed that resistance-associated alterations correlated with shorter progression-free survival. Computational perturbagen screening identified compounds predicted to counteract these transcriptional signatures, converging on regulators of NFE2L2 activity. Experimental testing confirmed that rosiglitazone reduced NFE2L2-associated gene expression and re-sensitized resistant cells to chemotherapy, demonstrating a scalable strategy for rational phenotypic reprogramming.
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