Pub Date : 2024-10-30eCollection Date: 2024-11-15DOI: 10.1016/j.isci.2024.111206
Yael Gutiérrez, Anna P Ovvyan, Gonzalo Santos, Dilson Juan, Saul A Rosales, Javier Junquera, Pablo García-Fernández, Stefano Dicorato, Maria M Giangregorio, Elena Dilonardo, Fabio Palumbo, Mircea Modreanu, Josef Resl, Olga Ishchenko, Guy Garry, Tigers Jonuzi, Marin Georghe, Cornel Cobianu, Kurt Hingerl, Christoph Cobet, Fernando Moreno, Wolfram H P Pernice, Maria Losurdo
[This corrects the article DOI: 10.1016/j.isci.2022.104377.].
[此处更正文章 DOI：10.1016/j.isci.2022.104377.]。
{"title":"Erratum: Interlaboratory study on Sb<sub>2</sub>S<sub>3</sub> interplay between structure, dielectric function, and amorphous-to-crystalline phase change for photonics.","authors":"Yael Gutiérrez, Anna P Ovvyan, Gonzalo Santos, Dilson Juan, Saul A Rosales, Javier Junquera, Pablo García-Fernández, Stefano Dicorato, Maria M Giangregorio, Elena Dilonardo, Fabio Palumbo, Mircea Modreanu, Josef Resl, Olga Ishchenko, Guy Garry, Tigers Jonuzi, Marin Georghe, Cornel Cobianu, Kurt Hingerl, Christoph Cobet, Fernando Moreno, Wolfram H P Pernice, Maria Losurdo","doi":"10.1016/j.isci.2024.111206","DOIUrl":"https://doi.org/10.1016/j.isci.2024.111206","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1016/j.isci.2022.104377.].</p>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 11","pages":"111206"},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.isci.2024.111289
Lisa A. King , Myrthe Veth , Victoria Iglesias-Guimarais , Iris Blijdorp , Jan Kloosterman , André N. Vis , Rob C. Roovers , David Lutje Hulsik , Thilo Riedl , Anton E.P. Adang , Paul W.H.I. Parren , Pauline M. van Helden , Tanja D. de Gruijl , Hans J. van der Vliet
Vγ9Vδ2 T cells constitute a homogeneous effector T cell population that lyses tumors of different origin, including the prostate. We generated a bispecific T cell engager (bsTCE) to direct Vγ9Vδ2 T cells to PSMA+ prostate cancer (PCa) cells. The PSMA-Vδ2 bsTCE triggered healthy donor and PCa patient-derived Vγ9Vδ2 T cells to lyse PSMA+ PCa cell lines and patient-derived tumor cells while sparing normal prostate cells and enhanced Vγ9Vδ2 T cell antigen cross-presentation to CD8+ T cells. Vγ9Vδ2 T cell expressed NKG2D and DNAM-1 contributed to Vγ9Vδ2 T cell activation and tumor lysis at low PSMA-Vδ2 bsTCE concentrations. In vivo models confirmed the antitumor efficacy of the bsTCE and demonstrated a half-life of 6–7 days. Tissue-cross reactivity analysis was in line with known tissue distribution of PSMA and Vγ9Vδ2 T cells. Together these data show the PSMA-Vδ2 bsTCE to represent a promising anti-tumor strategy and supports its ongoing evaluation in a phase 1/2a clinical trial in therapy refractory metastatic castration-resistant PCa.
Vγ9Vδ2 T细胞是一种同源效应T细胞群，能溶解不同来源的肿瘤，包括前列腺癌。我们生成了一种双特异性 T 细胞诱导体（bsTCE），将 Vγ9Vδ2 T 细胞导向 PSMA+前列腺癌（PCa）细胞。PSMA-Vδ2 bsTCE 能触发健康供体和 PCa 患者来源的 Vγ9Vδ2 T 细胞裂解 PSMA+ PCa 细胞系和患者来源的肿瘤细胞，同时保护正常前列腺细胞，并增强 Vγ9Vδ2 T 细胞抗原与 CD8+ T 细胞的交叉呈递。在 PSMA-Vδ2 bsTCE 浓度较低时，Vγ9Vδ2 T 细胞表达的 NKG2D 和 DNAM-1 有助于 Vγ9Vδ2 T 细胞的活化和肿瘤溶解。体内模型证实了 bsTCE 的抗肿瘤功效，并证明其半衰期为 6-7 天。组织交叉反应分析与已知的 PSMA 和 Vγ9Vδ2 T 细胞的组织分布一致。这些数据共同表明，PSMA-Vδ2 bsTCE 是一种很有前景的抗肿瘤策略，并支持目前正在进行的针对难治性转移性阉割耐药 PCa 的 1/2a 期临床试验评估。
{"title":"Leveraging Vγ9Vδ2 T cells against prostate cancer through a VHH-based PSMA-Vδ2 bispecific T cell engager","authors":"Lisa A. King , Myrthe Veth , Victoria Iglesias-Guimarais , Iris Blijdorp , Jan Kloosterman , André N. Vis , Rob C. Roovers , David Lutje Hulsik , Thilo Riedl , Anton E.P. Adang , Paul W.H.I. Parren , Pauline M. van Helden , Tanja D. de Gruijl , Hans J. van der Vliet","doi":"10.1016/j.isci.2024.111289","DOIUrl":"10.1016/j.isci.2024.111289","url":null,"abstract":"<div><div>Vγ9Vδ2 T cells constitute a homogeneous effector T cell population that lyses tumors of different origin, including the prostate. We generated a bispecific T cell engager (bsTCE) to direct Vγ9Vδ2 T cells to PSMA<sup>+</sup> prostate cancer (PCa) cells. The PSMA-Vδ2 bsTCE triggered healthy donor and PCa patient-derived Vγ9Vδ2 T cells to lyse PSMA<sup>+</sup> PCa cell lines and patient-derived tumor cells while sparing normal prostate cells and enhanced Vγ9Vδ2 T cell antigen cross-presentation to CD8<sup>+</sup> T cells. Vγ9Vδ2 T cell expressed NKG2D and DNAM-1 contributed to Vγ9Vδ2 T cell activation and tumor lysis at low PSMA-Vδ2 bsTCE concentrations. <em>In vivo</em> models confirmed the antitumor efficacy of the bsTCE and demonstrated a half-life of 6–7 days. Tissue-cross reactivity analysis was in line with known tissue distribution of PSMA and Vγ9Vδ2 T cells. Together these data show the PSMA-Vδ2 bsTCE to represent a promising anti-tumor strategy and supports its ongoing evaluation in a phase 1/2a clinical trial in therapy refractory metastatic castration-resistant PCa.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111289"},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.isci.2024.111288
Molly A. McDonald , Christos T. Maravelias
Global warming concerns have led to emission regulations and various incentives for low-carbon technologies. Energy system models, which are used to examine how investments affect our ability to meet energy demand, are typically based on two assumptions: key parameters are assumed to be known deterministically and a multi-period energy transition plan is determined at one point in time. We argue that for a systematic generation and analysis of energy transition pathways, these assumptions should be relaxed and, accordingly, we propose methods to achieve that. First, we use stochastic programming (SP) to account for uncertainty in key parameters. Second, we pair SP with a sequential decision-making approach that represents how decisions can be updated as uncertainties unfold. Third, we use simulation-based methods to evaluate the quality of energy transitions. Importantly, we find that accounting for uncertainty, proactively and through feedback, yields pathways with diverse technology portfolios that are resilient to uncertainty.
{"title":"Sequential decision-making under uncertainty for long-term energy transition planning","authors":"Molly A. McDonald , Christos T. Maravelias","doi":"10.1016/j.isci.2024.111288","DOIUrl":"10.1016/j.isci.2024.111288","url":null,"abstract":"<div><div>Global warming concerns have led to emission regulations and various incentives for low-carbon technologies. Energy system models, which are used to examine how investments affect our ability to meet energy demand, are typically based on two assumptions: key parameters are assumed to be known deterministically and a multi-period energy transition plan is determined at one point in time. We argue that for a systematic generation and analysis of energy transition pathways, these assumptions should be relaxed and, accordingly, we propose methods to achieve that. First, we use stochastic programming (SP) to account for uncertainty in key parameters. Second, we pair SP with a sequential decision-making approach that represents how decisions can be updated as uncertainties unfold. Third, we use simulation-based methods to evaluate the quality of energy transitions. Importantly, we find that accounting for uncertainty, proactively and through feedback, yields pathways with diverse technology portfolios that are resilient to uncertainty.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111288"},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.isci.2024.111257
Xiao-Ping Wei , Xin Liu , Jiao-Yang Zhang , Ya-Ling Zhang , Xiaoma Tao
Half-metallic materials are widely used as spintronic devices such as electrodes, magnetic tunneling junction, and giant magnetoresistance. In this work, we have systematically investigated the structural stability, Gilbert damping, electronic structure, and magnetism together with exchange interactions and Curie temperatures for Mn2TaAl and Mn2WAl alloys. Initially, we estimate their structural stability and offer possible phase synthesis. Subsequently, the Gilbert damping parameters calculated by the linear response theory are used to assess their response speed as spintronic materials. Furthermore, the Mn2TaAl and Mn2WAl are predicted to be half-metallic and nearly half-metallic ferrimagnets and their total magnetic moments obey the Mt = Zt-18 rule. Accordingly, their Curie temperatures for Mn2TaAl and Mn2WAl are also evaluated by the mean-field approximation. Finally, their thermodynamic parameters within 0∼600 K and thermoelectric properties within 200∼900 K are discussed. Overall, our research for Mn2TaAl and Mn2WAl alloys might provide some valuable clues for their application in spintronic devices.
{"title":"Investigations on full-Heusler alloys Mn2TaAl and Mn2WAl for spintronic and thermoelectric applications","authors":"Xiao-Ping Wei , Xin Liu , Jiao-Yang Zhang , Ya-Ling Zhang , Xiaoma Tao","doi":"10.1016/j.isci.2024.111257","DOIUrl":"10.1016/j.isci.2024.111257","url":null,"abstract":"<div><div>Half-metallic materials are widely used as spintronic devices such as electrodes, magnetic tunneling junction, and giant magnetoresistance. In this work, we have systematically investigated the structural stability, Gilbert damping, electronic structure, and magnetism together with exchange interactions and Curie temperatures for Mn<sub>2</sub>TaAl and Mn<sub>2</sub>WAl alloys. Initially, we estimate their structural stability and offer possible phase synthesis. Subsequently, the Gilbert damping parameters calculated by the linear response theory are used to assess their response speed as spintronic materials. Furthermore, the Mn<sub>2</sub>TaAl and Mn<sub>2</sub>WAl are predicted to be half-metallic and nearly half-metallic ferrimagnets and their total magnetic moments obey the <em>Mt</em> = <em>Zt</em>-18 rule. Accordingly, their Curie temperatures for Mn<sub>2</sub>TaAl and Mn<sub>2</sub>WAl are also evaluated by the mean-field approximation. Finally, their thermodynamic parameters within 0∼600 K and thermoelectric properties within 200<em>∼</em>900 K are discussed. Overall, our research for Mn<sub>2</sub>TaAl and Mn<sub>2</sub>WAl alloys might provide some valuable clues for their application in spintronic devices.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111257"},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.isci.2024.111286
Nisha Singh , Ryan H. Cunnington , Anjali Bhagirath , Ankita Vaishampayan , Mohd Wasif Khan , Tejas Gupte , Kangmin Duan , Abdelilah S. Gounni , Shyamala Dakshisnamurti , John W. Hanrahan , Prashen Chelikani
Cystic fibrosis (CF) is an autosomal recessive disease characterized by microbial infection and progressive decline in lung function, leading to significant morbidity and mortality. The bitter taste receptor T2R14 is a chemosensory receptor that is significantly expressed in airways. Using a combination of cell-based assays and T2R14 knockdown in bronchial epithelial cells from CF and non-CF individuals, we observed that T2R14 plays a crucial role in the detection of bacterial and fungal signals and enhances host innate immune responses. Expression of Gαi protein is enhanced in CF bronchial epithelial cells and T2R14-Gαi specific signaling leads to increased calcium mobilization. Knockdown of T2R14 leads to reduced innate immune activation by bacterial strains deficient in quorum sensing. The results demonstrate that T2R14 helps protect against microbial infection and thus may play an important role in the innate immune defense of the CF airway epithelium.
{"title":"Bitter taste receptor T2R14-Gαi coupling mediates innate immune responses to microbial quorum sensing molecules in cystic fibrosis","authors":"Nisha Singh , Ryan H. Cunnington , Anjali Bhagirath , Ankita Vaishampayan , Mohd Wasif Khan , Tejas Gupte , Kangmin Duan , Abdelilah S. Gounni , Shyamala Dakshisnamurti , John W. Hanrahan , Prashen Chelikani","doi":"10.1016/j.isci.2024.111286","DOIUrl":"10.1016/j.isci.2024.111286","url":null,"abstract":"<div><div>Cystic fibrosis (CF) is an autosomal recessive disease characterized by microbial infection and progressive decline in lung function, leading to significant morbidity and mortality. The bitter taste receptor T2R14 is a chemosensory receptor that is significantly expressed in airways. Using a combination of cell-based assays and T2R14 knockdown in bronchial epithelial cells from CF and non-CF individuals, we observed that T2R14 plays a crucial role in the detection of bacterial and fungal signals and enhances host innate immune responses. Expression of Gαi protein is enhanced in CF bronchial epithelial cells and T2R14-Gαi specific signaling leads to increased calcium mobilization. Knockdown of T2R14 leads to reduced innate immune activation by bacterial strains deficient in quorum sensing. The results demonstrate that T2R14 helps protect against microbial infection and thus may play an important role in the innate immune defense of the CF airway epithelium.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111286"},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142655255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.isci.2024.111290
Daoquan Liu , Jianmin Liu , Yan Li , Lu Du , Qingqiong Cao , Liang Yang , Yongying Zhou , Ping Chen , Yuming Guo , Guang Zeng , Michael E. DiSanto , Weidong Hu , Xinhua Zhang
Benign prostatic hyperplasia (BPH) is a common condition in aging males, but its underlying pathogenesis remains unclear. Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) play important roles in various diseases, while less studied in prostate. Current study attempts to clarify the expression and functional activities of S1P/S1PRs in the prostate. We discovered that S1P/S1PRs were richly expressed in the prostate, with S1PR1/2/3 localized in the epithelial/stromal compartments, while S1PR4/5 were less expressed. In vitro, S1P/S1PR1/S1PR3 promoted cell proliferation via AKT and ERK1/2 pathways, S1P/S1PR2/S1PR3 enhanced contraction of WPMY-1 cells and human prostate via RhoA/ROCK pathway, while S1P/S1PR1/S1PR2/S1PR3 alleviated the inflammation response via STAT3 pathway. In vivo, S1P and S1PR1/3 agonists (SEW2871, CYM5541) led to prostate enlargement in rats, while S1PR1/3 antagonists (W-146, TY-52156) suppressed testosterone-induced BPH. Overall, this study suggests that S1P/S1PRs play a critical role in the development of BPH and may be a promising therapeutic target for BPH treatment.
{"title":"Broad and diverse roles of sphingosine-1-phosphate/sphingosine-1-phosphate receptors in the prostate","authors":"Daoquan Liu , Jianmin Liu , Yan Li , Lu Du , Qingqiong Cao , Liang Yang , Yongying Zhou , Ping Chen , Yuming Guo , Guang Zeng , Michael E. DiSanto , Weidong Hu , Xinhua Zhang","doi":"10.1016/j.isci.2024.111290","DOIUrl":"10.1016/j.isci.2024.111290","url":null,"abstract":"<div><div>Benign prostatic hyperplasia (BPH) is a common condition in aging males, but its underlying pathogenesis remains unclear. Sphingosine-1-phosphate (S1P) and its receptors (S1PRs) play important roles in various diseases, while less studied in prostate. Current study attempts to clarify the expression and functional activities of S1P/S1PRs in the prostate. We discovered that S1P/S1PRs were richly expressed in the prostate, with S1PR1/2/3 localized in the epithelial/stromal compartments, while S1PR4/5 were less expressed. <em>In vitro</em>, S1P/S1PR1/S1PR3 promoted cell proliferation via AKT and ERK1/2 pathways, S1P/S1PR2/S1PR3 enhanced contraction of WPMY-1 cells and human prostate via RhoA/ROCK pathway, while S1P/S1PR1/S1PR2/S1PR3 alleviated the inflammation response via STAT3 pathway. <em>In vivo</em>, S1P and S1PR1/3 agonists (SEW2871, CYM5541) led to prostate enlargement in rats, while S1PR1/3 antagonists (W-146, TY-52156) suppressed testosterone-induced BPH. Overall, this study suggests that S1P/S1PRs play a critical role in the development of BPH and may be a promising therapeutic target for BPH treatment.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111290"},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.isci.2024.111291
Simon Hirschberger , David Effinger , Polina Yoncheva , Annika Schmid , Mara-Noel Weis , Lesca-Miriam Holdt , Daniel Teupser , Simone Kreth
A ketogenic diet (KD) is increasingly debated as a countermeasure against nutrition-related modern diseases. While being immunologically beneficial, KD is still suspected of having severe metabolic side effects and negatively impacting general well-being, which prevents its widespread clinical use. We conducted a prospective pre-post interventional study investigating the effects of an eucaloric KD on metabolism, weight loss, body composition, diet adherence, and quality of life. The study had two stages: first, feasibility was tested in healthy, normal-weight participants over three weeks. After positive results, the KD period was expanded to three months, enrolling adults with overweight. Significant weight loss was observed in both groups, reducing body fat without affecting muscle or bone mass and without adverse metabolic changes. Quality of life improved, and fatigue symptoms in subjects with overweight decreased. These findings may help to overcome reservations about KD, encouraging its use as a medical tool for treating nutrition-related disorders.
{"title":"The impact of a ketogenic diet on weight loss, metabolism, body composition and quality of life","authors":"Simon Hirschberger , David Effinger , Polina Yoncheva , Annika Schmid , Mara-Noel Weis , Lesca-Miriam Holdt , Daniel Teupser , Simone Kreth","doi":"10.1016/j.isci.2024.111291","DOIUrl":"10.1016/j.isci.2024.111291","url":null,"abstract":"<div><div>A ketogenic diet (KD) is increasingly debated as a countermeasure against nutrition-related modern diseases. While being immunologically beneficial, KD is still suspected of having severe metabolic side effects and negatively impacting general well-being, which prevents its widespread clinical use. We conducted a prospective pre-post interventional study investigating the effects of an eucaloric KD on metabolism, weight loss, body composition, diet adherence, and quality of life. The study had two stages: first, feasibility was tested in healthy, normal-weight participants over three weeks. After positive results, the KD period was expanded to three months, enrolling adults with overweight. Significant weight loss was observed in both groups, reducing body fat without affecting muscle or bone mass and without adverse metabolic changes. Quality of life improved, and fatigue symptoms in subjects with overweight decreased. These findings may help to overcome reservations about KD, encouraging its use as a medical tool for treating nutrition-related disorders.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111291"},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-30DOI: 10.1016/j.isci.2024.111293
Matthew Turner , Landen Van Hulzen , Kylene Guse , Diing Agany , Jose E. Pietri
Cockroaches exhibit unexplained intra- and interpopulation variation in susceptibility to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection. Here, we show that the gut microbiota has a protective effect against colonization by ingested S. Typhimurium in cockroaches. We further examine two potential mechanisms for this effect, showing that commensal bacteria present in the gut do not compete with S. Typhimurium during growth in cockroach feces, but rather prime expression of host antimicrobial peptide genes that suppress S. Typhimurium infection. Lastly, we determine that neither absolute abundance of the microbiota nor its overall diversity is linked to infection susceptibility. Instead, we identify several minority bacterial taxa that exhibit interindividual variation in abundance as key indicators of infection susceptibility among genetically similar individuals. These findings illuminate the potential of cockroaches as an invertebrate model for interspecies microbial interactions and provide insight into vector-borne Salmonella transmission, suggesting that the microbiota of cockroaches could be targeted to reduce pathogen transmission.
{"title":"The gut microbiota confers resistance against Salmonella Typhimurium in cockroaches by modulating innate immunity","authors":"Matthew Turner , Landen Van Hulzen , Kylene Guse , Diing Agany , Jose E. Pietri","doi":"10.1016/j.isci.2024.111293","DOIUrl":"10.1016/j.isci.2024.111293","url":null,"abstract":"<div><div>Cockroaches exhibit unexplained intra- and interpopulation variation in susceptibility to <em>Salmonella enterica</em> serovar Typhimurium (<em>S.</em> Typhimurium) infection. Here, we show that the gut microbiota has a protective effect against colonization by ingested <em>S.</em> Typhimurium in cockroaches. We further examine two potential mechanisms for this effect, showing that commensal bacteria present in the gut do not compete with <em>S.</em> Typhimurium during growth in cockroach feces, but rather prime expression of host antimicrobial peptide genes that suppress <em>S.</em> Typhimurium infection. Lastly, we determine that neither absolute abundance of the microbiota nor its overall diversity is linked to infection susceptibility. Instead, we identify several minority bacterial taxa that exhibit interindividual variation in abundance as key indicators of infection susceptibility among genetically similar individuals. These findings illuminate the potential of cockroaches as an invertebrate model for interspecies microbial interactions and provide insight into vector-borne <em>Salmonella</em> transmission, suggesting that the microbiota of cockroaches could be targeted to reduce pathogen transmission.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111293"},"PeriodicalIF":4.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.isci.2024.111284
Simon R. Carlile , Seán C. Cahill , Eóin C. O’Brien , Nuno G.B. Neto , Michael G. Monaghan , Rachel M. McLoughlin
Staphylococcus aureus can induce trained immunity in murine macrophages offering protection against repeat exposure during S. aureus skin infection. Here we demonstrate that S. aureus exposure can result in non-specific trained immunity in humans and mice, enhancing macrophage responsiveness and bacterial clearance in a heterologous challenge. In humans, the enhanced macrophage responsiveness was accompanied by metabolic changes and histone modification. In mice, the enhanced responsiveness of macrophages occurred in conjunction with enhanced myelopoiesis. This report provides further insights on the host’s response to the bacterium S. aureus, indicating that exposure to this organism induces heterologous protection against subsequent gram-negative infection that is provided by macrophages. These findings support the hypothesis that S. aureus has evolved to develop a mutualistic relationship with the host, imbuing the host with enhanced capacity to protect itself from attack by alternative pathogens, while potentially allowing S. aureus to exert its dominance within its niche.
{"title":"Staphylococcus aureus induced trained immunity in macrophages confers heterologous protection against gram-negative bacterial infection","authors":"Simon R. Carlile , Seán C. Cahill , Eóin C. O’Brien , Nuno G.B. Neto , Michael G. Monaghan , Rachel M. McLoughlin","doi":"10.1016/j.isci.2024.111284","DOIUrl":"10.1016/j.isci.2024.111284","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> can induce trained immunity in murine macrophages offering protection against repeat exposure during <em>S. aureus</em> skin infection. Here we demonstrate that <em>S. aureus</em> exposure can result in non-specific trained immunity in humans and mice, enhancing macrophage responsiveness and bacterial clearance in a heterologous challenge. In humans, the enhanced macrophage responsiveness was accompanied by metabolic changes and histone modification. In mice, the enhanced responsiveness of macrophages occurred in conjunction with enhanced myelopoiesis. This report provides further insights on the host’s response to the bacterium <em>S. aureus</em>, indicating that exposure to this organism induces heterologous protection against subsequent gram-negative infection that is provided by macrophages. These findings support the hypothesis that <em>S. aureus</em> has evolved to develop a mutualistic relationship with the host, imbuing the host with enhanced capacity to protect itself from attack by alternative pathogens, while potentially allowing <em>S. aureus</em> to exert its dominance within its niche.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111284"},"PeriodicalIF":4.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.isci.2024.111283
Jayakumar R. Nair , Tzu-Ting Huang , Anu Sunkara , Margaret R. Pruitt , Kristen R. Ibanez , Chih-Yuan Chiang , Ken Chih-Chien Cheng , Kelli Wilson , Thomas M. Cardillo , Scott Hofsess , Jung-Min Lee
Antibody–drug conjugates (ADCs) have become an important class of anticancer drugs in solid tumors including drug-resistant gynecologic malignancies. TROP2 is a cell surface antigen that is highly expressed in ovarian carcinoma (OC) but minimally expressed in normal ovarian tissues. In this study, we aimed to identify how TROP2-specific ADC, sacituzumab govitecan (SG), modulates DNA damage response pathways in drug-resistant OC. We found that SG induces G2/M arrest, increases RPA1 foci, and decreases replication fork speed, resulting in replication stress in TROP2-positive cells while these were less evident in TROP2-negative cells. In OC in vitro and in vivo models, SN-38 sensitivity and TROP2 expression play key roles in response to either ATR inhibitor or SG alone, or in combination. Additionally, inhibition of translesion DNA synthesis enhances SG and PARP inhibitor (PARPi) sensitivity in PARPi-resistant OC cells. These findings provide mechanistic insights for clinical development of SG in drug-resistant OC.
{"title":"Distinct effects of sacituzumab govitecan and berzosertib on DNA damage response in ovarian cancer","authors":"Jayakumar R. Nair , Tzu-Ting Huang , Anu Sunkara , Margaret R. Pruitt , Kristen R. Ibanez , Chih-Yuan Chiang , Ken Chih-Chien Cheng , Kelli Wilson , Thomas M. Cardillo , Scott Hofsess , Jung-Min Lee","doi":"10.1016/j.isci.2024.111283","DOIUrl":"10.1016/j.isci.2024.111283","url":null,"abstract":"<div><div>Antibody–drug conjugates (ADCs) have become an important class of anticancer drugs in solid tumors including drug-resistant gynecologic malignancies. TROP2 is a cell surface antigen that is highly expressed in ovarian carcinoma (OC) but minimally expressed in normal ovarian tissues. In this study, we aimed to identify how TROP2-specific ADC, sacituzumab govitecan (SG), modulates DNA damage response pathways in drug-resistant OC. We found that SG induces G2/M arrest, increases RPA1 foci, and decreases replication fork speed, resulting in replication stress in TROP2-positive cells while these were less evident in TROP2-negative cells. In OC <em>in vitro</em> and <em>in vivo</em> models, SN-38 sensitivity and TROP2 expression play key roles in response to either ATR inhibitor or SG alone, or in combination<em>.</em> Additionally, inhibition of translesion DNA synthesis enhances SG and PARP inhibitor (PARPi) sensitivity in PARPi-resistant OC cells. These findings provide mechanistic insights for clinical development of SG in drug-resistant OC.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"27 12","pages":"Article 111283"},"PeriodicalIF":4.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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