Life Science Alliance最新文献_第6页

Apical dehydration impairs the cystic fibrosis airway epithelium barrier via a β1-integrin/YAP1 pathway. 顶端脱水通过β1-整合素/YAP1途径损害囊性纤维化气道上皮细胞屏障。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-02-09 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302449

Juliette L Simonin, Caterina Tomba, Vincent Mercier, Marc Bacchetta, Tahir Idris, Mehdi Badaoui, Aurélien Roux, Marc Chanson

{"title":"Apical dehydration impairs the cystic fibrosis airway epithelium barrier via a β1-integrin/YAP1 pathway.","authors":"Juliette L Simonin, Caterina Tomba, Vincent Mercier, Marc Bacchetta, Tahir Idris, Mehdi Badaoui, Aurélien Roux, Marc Chanson","doi":"10.26508/lsa.202302449","DOIUrl":"10.26508/lsa.202302449","url":null,"abstract":"Defective hydration of airway surface mucosa is associated with lung infection in cystic fibrosis (CF), partly caused by disruption of the epithelial barrier integrity. Although rehydration of the CF airway surface liquid (ASL) alleviates epithelium vulnerability to infection by junctional protein expression, the mechanisms linking ASL to barrier integrity are unknown. We show here the strong degradation of YAP1 and TAZ proteins in well-polarized CF human airway epithelial cells (HAECs), a process that was prevented by ASL rehydration. Conditional silencing of YAP1 in rehydrated CF HAECs indicated that YAP1 expression was necessary for the maintenance of junctional complexes. A higher plasma membrane tension in CF HAECs reduced endocytosis, concurrent with the maintenance of active β1-integrin ectopically located at the apical membrane. Pharmacological inhibition of β1-integrin accumulation restored YAP1 expression in CF HAECs. These results indicate that dehydration of the CF ASL affects epithelial plasma membrane tension, resulting in ectopic activation of a β1-integrin/YAP1 signaling pathway associated with degradation of junctional proteins.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10858171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139712532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Inflammatory markers for improved recurrent UTI diagnosis in postmenopausal women. 改善绝经后妇女复发性尿毒症诊断的炎症标记物。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-02-08 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302323

Tahmineh Ebrahimzadeh, Ujjaini Basu, Kevin C Lutz, Jashkaran Gadhvi, Jessica V Komarovsky, Qiwei Li, Philippe E Zimmern, Nicole J De Nisco

{"title":"Inflammatory markers for improved recurrent UTI diagnosis in postmenopausal women.","authors":"Tahmineh Ebrahimzadeh, Ujjaini Basu, Kevin C Lutz, Jashkaran Gadhvi, Jessica V Komarovsky, Qiwei Li, Philippe E Zimmern, Nicole J De Nisco","doi":"10.26508/lsa.202302323","DOIUrl":"10.26508/lsa.202302323","url":null,"abstract":"Recurrent urinary tract infection (rUTI) severely impacts postmenopausal women. The lack of rapid and accurate diagnostic tools is a major obstacle in rUTI management as current gold standard methods have >24-h diagnostic windows. Work in animal models and limited human cohorts have identified robust inflammatory responses activated during UTI. Consequently, urinary inflammatory cytokines secreted during UTI may function as diagnostic biomarkers. This study aimed to identify urinary cytokines that could accurately diagnose UTI in a controlled cohort of postmenopausal women. Women passing study exclusion criteria were classified into no UTI and active rUTI groups, and urinary cytokine levels were measured by immunoassay. Pro-inflammatory cytokines IL-8, IL-18, IL-1β, and monocyte chemoattractant protein-1 were significantly elevated in the active rUTI group, and anti-inflammatory cytokines IL-13 and IL-4 were elevated in women without UTI. We evaluated cytokine diagnostic performance and found that an IL-8, prostaglandin E2, and IL-13 multivariable model had the lowest misclassification rate and highest sensitivity. Our data identify urinary IL-8, prostaglandin E2, and IL-13 as candidate biomarkers that may be useful in the development of immunoassay-based UTI diagnostics.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Oral bacteria induce IgA autoantibodies against a mesangial protein in IgA nephropathy model mice. 口腔细菌诱导 IgA 肾病模型小鼠产生针对间质蛋白的 IgA 自身抗体。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-02-08 Print Date: 2024-04-01 DOI: 10.26508/lsa.202402588

Mizuki Higashiyama, Kei Haniuda, Yoshihito Nihei, Saiko Kazuno, Mika Kikkawa, Yoshiki Miura, Yusuke Suzuki, Daisuke Kitamura

{"title":"Oral bacteria induce IgA autoantibodies against a mesangial protein in IgA nephropathy model mice.","authors":"Mizuki Higashiyama, Kei Haniuda, Yoshihito Nihei, Saiko Kazuno, Mika Kikkawa, Yoshiki Miura, Yusuke Suzuki, Daisuke Kitamura","doi":"10.26508/lsa.202402588","DOIUrl":"10.26508/lsa.202402588","url":null,"abstract":"IgA nephropathy (IgAN) is caused by deposition of IgA in the glomerular mesangium. The mechanism of selective deposition and production of IgA is unclear; however, we recently identified the involvement of IgA autoantibodies. Here, we show that CBX3 is another self-antigen for IgA in gddY mice, a spontaneous IgAN model, and in IgAN patients. A recombinant antibody derived from gddY mice bound to CBX3 expressed on the mesangial cell surface in vitro and to glomeruli in vivo. An elemental diet and antibiotic treatment decreased the levels of autoantibodies and IgAN symptoms in gddY mice. Serum IgA and the recombinant antibody from gddY mice also bound to oral bacteria of the mice and binding was competed with CBX3. One species of oral bacteria was markedly decreased in elemental diet-fed gddY mice and induced anti-CBX3 antibody in normal mice upon immunization. These data suggest that particular oral bacteria generate immune responses to produce IgA that cross-reacts with mesangial cells to initiate IgAN.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

ADAM19 cleaves the PTH receptor and associates with brachydactyly type E. ADAM19 可裂解 PTH 受体并与 E 型手足徐动症相关联。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-02-08 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302400

Atakan Aydin, Christoph Klenk, Katarina Nemec, Ali Işbilir, Lisa M Martin, Henrik Zauber, Trendelina Rrustemi, Hakan R Toka, Herbert Schuster, Maolian Gong, Sigmar Stricker, Andreas Bock, Sylvia Bähring, Matthias Selbach, Martin J Lohse, Friedrich C Luft

{"title":"ADAM19 cleaves the PTH receptor and associates with brachydactyly type E.","authors":"Atakan Aydin, Christoph Klenk, Katarina Nemec, Ali Işbilir, Lisa M Martin, Henrik Zauber, Trendelina Rrustemi, Hakan R Toka, Herbert Schuster, Maolian Gong, Sigmar Stricker, Andreas Bock, Sylvia Bähring, Matthias Selbach, Martin J Lohse, Friedrich C Luft","doi":"10.26508/lsa.202302400","DOIUrl":"10.26508/lsa.202302400","url":null,"abstract":"Brachydactyly type E (BDE), shortened metacarpals, metatarsals, cone-shaped epiphyses, and short stature commonly occurs as a sole phenotype. Parathyroid hormone-like protein (PTHrP) has been shown to be responsible in all forms to date, either directly or indirectly. We used linkage and then whole genome sequencing in a small pedigree, to elucidate BDE and identified a truncated disintegrin-and-metalloproteinase-19 (ADAM19) allele in all affected family members, but not in nonaffected persons. Since we had shown earlier that the extracellular domain of the parathyroid hormone receptor (PTHR1) is subject to an unidentified metalloproteinase cleavage, we tested the hypothesis that ADAM19 is a sheddase for PTHR1. WT ADAM19 cleaved PTHR1, while mutated ADAM-19 did not. We mapped the cleavage site that we verified with mass spectrometry between amino acids 64-65. ADAM-19 cleavage increased Gq and decreased Gs activation. Moreover, perturbed PTHR1 cleavage by ADAM19 increased ß-arrestin2 recruitment, while cAMP accumulation was not altered. We suggest that ADAM19 serves as a regulatory element for PTHR1 and could be responsible for BDE. This sheddase may affect other PTHrP or PTH-related functions.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Knockout of PA200 improves proteasomal degradation and myelination in a proteotoxic neuropathy. 敲除 PA200 可改善蛋白酶体降解和蛋白毒性神经病的髓鞘化。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-02-06 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302349

Jordan Js VerPlank, Joseph M Gawron, Nicholas J Silvestri, Lawrence Wrabetz, Maria Laura Feltri

{"title":"Knockout of PA200 improves proteasomal degradation and myelination in a proteotoxic neuropathy.","authors":"Jordan Js VerPlank, Joseph M Gawron, Nicholas J Silvestri, Lawrence Wrabetz, Maria Laura Feltri","doi":"10.26508/lsa.202302349","DOIUrl":"10.26508/lsa.202302349","url":null,"abstract":"The cellular response to a decrease in protein degradation by 26S proteasomes in chronic diseases is poorly understood. Pharmacological inhibition of proteasomes increases the expression of proteasome subunits and Proteasome Activator 200 (PA200), an alternative proteasome activator. In the S63del mouse model of the peripheral neuropathy Charcot Marie Tooth 1B (CMT1B), proteasomal protein degradation is decreased and proteasome gene expression is increased. Here, we show an increase in PA200 and PA200-bound proteasomes in the peripheral nerves of S63del mice. To test genetically whether the upregulation of PA200 was compensatory, we generated S63del//PA200-/- mice. Unexpectedly, in the sciatic nerves of these mice, there was greater proteasomal protein degradation than in S63del, less polyubiquitinated proteins and markers of the unfolded protein response, and a greater amount of assembled, active 26S proteasomes. These changes were not seen in PA200-/- controls and were therefore specific to the neuropathy. Furthermore, in S63del//PA200-/- mice, myelin thickness and nerve conduction were restored to WT levels. Thus, the upregulation of PA200 is maladaptive in S63del mice and its genetic ablation prevented neuropathy.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139712534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Epigenomic states contribute to coordinated allelic transcriptional bursting in iPSC reprogramming. 表观基因组状态有助于 iPSC 重编程过程中等位基因转录突变的协调。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-02-06 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302337

Parichitran Ayyamperumal, Hemant Chandru Naik, Amlan Jyoti Naskar, Lakshmi Sowjanya Bammidi, Srimonta Gayen

{"title":"Epigenomic states contribute to coordinated allelic transcriptional bursting in iPSC reprogramming.","authors":"Parichitran Ayyamperumal, Hemant Chandru Naik, Amlan Jyoti Naskar, Lakshmi Sowjanya Bammidi, Srimonta Gayen","doi":"10.26508/lsa.202302337","DOIUrl":"10.26508/lsa.202302337","url":null,"abstract":"Two alleles of a gene can be transcribed independently or coordinatedly, which can lead to temporal expression heterogeneity with potentially distinct impacts on cell fate. Here, we profiled genome-wide allelic transcriptional burst kinetics during the reprogramming of MEF to induced pluripotent stem cells. We show that the degree of coordination of allelic bursting differs among genes, and alleles of many reprogramming-related genes burst in a highly coordinated fashion. Notably, we show that the chromatin accessibility of the two alleles of highly coordinated genes is similar, unlike the semi-coordinated or independent genes, suggesting the degree of coordination of allelic bursting is linked to allelic chromatin accessibility. Consistently, we show that many transcription factors have differential binding affinity between alleles of semi-coordinated or independent genes. We show that highly coordinated genes are enriched with chromatin accessibility regulators such as H3K4me3, H3K4me1, H3K36me3, H3K27ac, histone variant H3.3, and BRD4. Finally, we demonstrate that enhancer elements are highly enriched in highly coordinated genes. Our study demonstrates that epigenomic states contribute to coordinated allelic bursting to fine-tune gene expression during induced pluripotent stem cell reprogramming.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10847334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139712533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Stability of gut microbiome after COVID-19 vaccination in healthy and immuno-compromised individuals. 健康和免疫力低下人群接种 COVID-19 疫苗后肠道微生物组的稳定性。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-02-05 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302529

Rebecca H Boston, Rui Guan, Lajos Kalmar, Sina Beier, Emily C Horner, Nonantzin Beristain-Covarrubias, Juan Carlos Yam-Puc, Pehuén Pereyra Gerber, Luisa Faria, Anna Kuroshchenkova, Anna E Lindell, Sonja Blasche, Andrea Correa-Noguera, Anne Elmer, Caroline Saunders, Areti Bermperi, Sherly Jose, Nathalie Kingston, Sofia Grigoriadou, Emily Staples, Matthew S Buckland, Sara Lear, Nicholas J Matheson, Vladimir Benes, Christine Parkinson, James Ed Thaventhiran, Kiran R Patil

{"title":"Stability of gut microbiome after COVID-19 vaccination in healthy and immuno-compromised individuals.","authors":"Rebecca H Boston, Rui Guan, Lajos Kalmar, Sina Beier, Emily C Horner, Nonantzin Beristain-Covarrubias, Juan Carlos Yam-Puc, Pehuén Pereyra Gerber, Luisa Faria, Anna Kuroshchenkova, Anna E Lindell, Sonja Blasche, Andrea Correa-Noguera, Anne Elmer, Caroline Saunders, Areti Bermperi, Sherly Jose, Nathalie Kingston, Sofia Grigoriadou, Emily Staples, Matthew S Buckland, Sara Lear, Nicholas J Matheson, Vladimir Benes, Christine Parkinson, James Ed Thaventhiran, Kiran R Patil","doi":"10.26508/lsa.202302529","DOIUrl":"10.26508/lsa.202302529","url":null,"abstract":"Bidirectional interactions between the immune system and the gut microbiota are key contributors to various physiological functions. Immune-associated diseases such as cancer and autoimmunity, and efficacy of immunomodulatory therapies, have been linked to microbiome variation. Although COVID-19 infection has been shown to cause microbial dysbiosis, it remains understudied whether the inflammatory response associated with vaccination also impacts the microbiota. Here, we investigate the temporal impact of COVID-19 vaccination on the gut microbiome in healthy and immuno-compromised individuals; the latter included patients with primary immunodeficiency and cancer patients on immunomodulating therapies. We find that the gut microbiome remained remarkably stable post-vaccination irrespective of diverse immune status, vaccine response, and microbial composition spanned by the cohort. The stability is evident at all evaluated levels including diversity, phylum, species, and functional capacity. Our results indicate the resilience of the gut microbiome to host immune changes triggered by COVID-19 vaccination and suggest minimal, if any, impact on microbiome-mediated processes. These findings encourage vaccine acceptance, particularly when contrasted with the significant microbiome shifts observed during COVID-19 infection.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10844540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Genome-wide CRISPR screen reveals the synthetic lethality between BCL2L1 inhibition and radiotherapy. 全基因组 CRISPR 筛选揭示了 BCL2L1 抑制与放疗之间的合成致死率。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-02-05 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302353

Ling Yin, Xiaoding Hu, Guangsheng Pei, Mengfan Tang, You Zhou, Huimin Zhang, Min Huang, Siting Li, Jie Zhang, Citu Citu, Zhongming Zhao, Bisrat G Debeb, Xu Feng, Junjie Chen

{"title":"Genome-wide CRISPR screen reveals the synthetic lethality between BCL2L1 inhibition and radiotherapy.","authors":"Ling Yin, Xiaoding Hu, Guangsheng Pei, Mengfan Tang, You Zhou, Huimin Zhang, Min Huang, Siting Li, Jie Zhang, Citu Citu, Zhongming Zhao, Bisrat G Debeb, Xu Feng, Junjie Chen","doi":"10.26508/lsa.202302353","DOIUrl":"10.26508/lsa.202302353","url":null,"abstract":"Radiation therapy (RT) is one of the most commonly used anticancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part because of the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival after radiation. BCL2L1 inhibition combined with RT dramatically impeded tumor growth in several breast cancer cell lines and syngeneic models. Taken together, our results suggest that the combination of an apoptosis inhibitor such as a BCL2L1 inhibitor with RT may represent a promising anticancer strategy for solid cancers including breast cancer.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10844523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Micronucleus is not a potent inducer of the cGAS/STING pathway. 微核不是 cGAS/STING 通路的强效诱导剂。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-02-02 DOI: 10.26508/lsa.202302424

Yuki Sato, Makoto T Hayashi

{"title":"Micronucleus is not a potent inducer of the cGAS/STING pathway.","authors":"Yuki Sato, Makoto T Hayashi","doi":"10.26508/lsa.202302424","DOIUrl":"https://doi.org/10.26508/lsa.202302424","url":null,"abstract":"Micronuclei (MN) have been associated with the innate immune response. The abrupt rupture of MN membranes results in the accumulation of cGAS, potentially activating STING and downstream interferon-responsive genes. However, direct evidence connecting MN and cGAS activation has been lacking. We have developed the FuVis2 reporter system, which enables the visualization of the cell nucleus carrying a single sister chromatid fusion and, consequently, MN. Using this FuVis2 reporter equipped with cGAS and STING reporters, we rigorously assessed the potency of cGAS activation by MN in individual living cells. Our findings reveal that cGAS localization to membrane-ruptured MN during interphase is infrequent, with cGAS primarily capturing MN during mitosis and remaining bound to cytosolic chromatin. We found that cGAS accumulation during mitosis neither activates STING in the subsequent interphase nor triggers the interferon response. Gamma-ray irradiation activates STING independently of MN formation and cGAS localization to MN. These results suggest that cGAS accumulation in cytosolic MN is not a robust indicator of its activation and that MN are not the primary trigger of the cGAS/STING pathway.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection. 斑马鱼tsc1和cxcl12a增加了对霉菌感染的易感性。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-02-02 DOI: 10.26508/lsa.202302523

Kathryn Wright, Darryl Jy Han, Renhua Song, Kumudika de Silva, Karren M Plain, Auriol C Purdie, Ava Shepherd, Maegan Chin, Elinor Hortle, Justin J-L Wong, Warwick J Britton, Stefan H Oehlers

{"title":"Zebrafish tsc1 and cxcl12a increase susceptibility to mycobacterial infection.","authors":"Kathryn Wright, Darryl Jy Han, Renhua Song, Kumudika de Silva, Karren M Plain, Auriol C Purdie, Ava Shepherd, Maegan Chin, Elinor Hortle, Justin J-L Wong, Warwick J Britton, Stefan H Oehlers","doi":"10.26508/lsa.202302523","DOIUrl":"https://doi.org/10.26508/lsa.202302523","url":null,"abstract":"Regulation of host miRNA expression is a contested node that controls the host immune response to mycobacterial infection. The host must counter subversive efforts of pathogenic mycobacteria to launch a protective immune response. Here, we examine the role of miR-126 in the zebrafish-Mycobacterium marinum infection model and identify a protective role for infection-induced miR-126 through multiple effector pathways. We identified a putative link between miR-126 and the tsc1a and cxcl12a/ccl2/ccr2 signalling axes resulting in the suppression of non-tnfa expressing macrophage accumulation at early M. marinum granulomas. Mechanistically, we found a detrimental effect of tsc1a expression that renders zebrafish embryos susceptible to higher bacterial burden and increased cell death via mTOR inhibition. We found that macrophage recruitment driven by the cxcl12a/ccl2/ccr2 signalling axis was at the expense of the recruitment of classically activated tnfa-expressing macrophages and increased cell death around granulomas. Together, our results delineate putative pathways by which infection-induced miR-126 may shape an effective immune response to M. marinum infection in zebrafish embryos.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0