Life Science Alliance最新文献_第6页

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":"7 4","pages":""},"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":"7 4","pages":""},"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":"7 4","pages":""},"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":"7 4","pages":""},"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":"7 4","pages":""},"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":"53 1","pages":""},"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":"4 1","pages":""},"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

Targeting circulating labile heme as a defense strategy against malaria. 将循环中的易变血红素作为抗击疟疾的目标。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-02-02 DOI: 10.26508/lsa.202302276

Susana Ramos, Viktoria Jeney, Ana Figueiredo, Tiago Paixão, Maria Rosário Sambo, Vatúsia Quinhentos, Rui Martins, Zélia Gouveia, Ana Rita Carlos, Ana Ferreira, Teresa F Pais, Hugo Lainé, Pedro Faísca, Sofia Rebelo, Silvia Cardoso, Emanuela Tolosano, Carlos Penha-Gonçalves, Miguel P Soares

{"title":"Targeting circulating labile heme as a defense strategy against malaria.","authors":"Susana Ramos, Viktoria Jeney, Ana Figueiredo, Tiago Paixão, Maria Rosário Sambo, Vatúsia Quinhentos, Rui Martins, Zélia Gouveia, Ana Rita Carlos, Ana Ferreira, Teresa F Pais, Hugo Lainé, Pedro Faísca, Sofia Rebelo, Silvia Cardoso, Emanuela Tolosano, Carlos Penha-Gonçalves, Miguel P Soares","doi":"10.26508/lsa.202302276","DOIUrl":"https://doi.org/10.26508/lsa.202302276","url":null,"abstract":"Severe presentations of malaria emerge as Plasmodium (P.) spp. parasites invade and lyse red blood cells (RBC), producing extracellular hemoglobin (HB), from which labile heme is released. Here, we tested whether scavenging of extracellular HB and/or labile heme, by haptoglobin (HP) and/or hemopexin (HPX), respectively, counter the pathogenesis of severe presentations of malaria. We found that circulating labile heme is an independent risk factor for cerebral and non-cerebral presentations of severe P. falciparum malaria in children. Labile heme was negatively correlated with circulating HP and HPX, which were, however, not risk factors for severe P. falciparum malaria. Genetic Hp and/or Hpx deletion in mice led to labile heme accumulation in plasma and kidneys, upon Plasmodium infection This was associated with higher incidence of mortality and acute kidney injury (AKI) in ageing but not adult Plasmodium-infected mice, and was corroborated by an inverse correlation between heme and HPX with serological markers of AKI in P. falciparum malaria. In conclusion, HP and HPX act in an age-dependent manner to prevent the pathogenesis of severe presentation of malaria in mice and presumably in humans.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"101 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139669048","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

FERM domain-containing proteins are active components of the cell nucleus. 含 FERM 结构域的蛋白质是细胞核的活性成分。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-01-31 DOI: 10.26508/lsa.202302489

Péter Borkúti, Ildikó Kristó, Anikó Szabó, Zoltán Kovács, Péter Vilmos

引用次数: 0

A feedback loop that drives cell death and proliferation and its defect in intestinal stem cells. 驱动细胞死亡和增殖的反馈回路及其在肠干细胞中的缺陷。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-01-31 DOI: 10.26508/lsa.202302238

Shivakshi Sulekh, Yuko Ikegawa, Saki Naito, Asami Oji, Ichiro Hiratani, Sa Kan Yoo

引用次数: 0