Life Science Alliance最新文献_第8页

Synaptobrevin2 monomers and dimers differentially engage to regulate the functional trans-SNARE assembly. Synaptobrevin2单体和二聚体以不同方式参与调节功能性跨SNARE组装。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-18 Print Date: 2024-04-01 DOI: 10.26508/lsa.202402568

Swapnali S Patil, Kinjal Sanghrajka, Malavika Sriram, Aritra Chakraborty, Sougata Majumdar, Bhavya R Bhaskar, Debasis Das

引用次数: 0

Spatiotemporal DNA methylation dynamics shape megabase-scale methylome landscapes. 时空 DNA 甲基化动力学塑造了巨碱基尺度的甲基组景观。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-17 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302403

Hidehiro Toh, Hiroyuki Sasaki

{"title":"Spatiotemporal DNA methylation dynamics shape megabase-scale methylome landscapes.","authors":"Hidehiro Toh, Hiroyuki Sasaki","doi":"10.26508/lsa.202302403","DOIUrl":"10.26508/lsa.202302403","url":null,"abstract":"DNA methylation is an essential epigenetic mechanism that regulates cellular reprogramming and development. Studies using whole-genome bisulfite sequencing have revealed distinct DNA methylome landscapes in human and mouse cells and tissues. However, the factors responsible for the differences in megabase-scale methylome patterns between cell types remain poorly understood. By analyzing publicly available 258 human and 301 mouse whole-genome bisulfite sequencing datasets, we reveal that genomic regions rich in guanine and cytosine, when located near the nuclear center, are highly susceptible to both global DNA demethylation and methylation events during embryonic and germline reprogramming. Furthermore, we found that regions that generate partially methylated domains during global DNA methylation are more likely to resist global DNA demethylation, contain high levels of adenine and thymine, and are adjacent to the nuclear lamina. The spatial properties of genomic regions, influenced by their guanine-cytosine content, are likely to affect the accessibility of molecules involved in DNA (de)methylation. These properties shape megabase-scale DNA methylation patterns and change as cells differentiate, leading to the emergence of different megabase-scale methylome patterns across cell types.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10794778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486013","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

Enhancer mutations modulate the severity of chemotherapy-induced myelosuppression. 增强子突变可调节化疗引起的骨髓抑制的严重程度。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-01-16 Print Date: 2024-03-01 DOI: 10.26508/lsa.202302244

Artemy Zhigulev, Zandra Norberg, Julie Cordier, Rapolas Spalinskas, Hassan Bassereh, Niclas Björn, Sailendra Pradhananga, Henrik Gréen, Pelin Sahlén

{"title":"Enhancer mutations modulate the severity of chemotherapy-induced myelosuppression.","authors":"Artemy Zhigulev, Zandra Norberg, Julie Cordier, Rapolas Spalinskas, Hassan Bassereh, Niclas Björn, Sailendra Pradhananga, Henrik Gréen, Pelin Sahlén","doi":"10.26508/lsa.202302244","DOIUrl":"10.26508/lsa.202302244","url":null,"abstract":"Non-small cell lung cancer is often diagnosed at advanced stages, and many patients are still treated with classical chemotherapy. The unselective nature of chemotherapy often results in severe myelosuppression. Previous studies showed that protein-coding mutations could not fully explain the predisposition to myelosuppression. Here, we investigate the possible role of enhancer mutations in myelosuppression susceptibility. We produced transcriptome and promoter-interaction maps (using HiCap) of three blood stem-like cell lines treated with carboplatin or gemcitabine. Taking advantage of publicly available enhancer datasets, we validated HiCap results in silico and in living cells using epigenetic CRISPR technology. We also developed a network approach for interactome analysis and detection of differentially interacting genes. Differential interaction analysis provided additional information on relevant genes and pathways for myelosuppression compared with differential gene expression analysis at the bulk level. Moreover, we showed that enhancers of differentially interacting genes are highly enriched for variants associated with differing levels of myelosuppression. Altogether, our work represents a prominent example of integrative transcriptome and gene regulatory datasets analysis for the functional annotation of noncoding mutations.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478750","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

The origin, evolution, and molecular diversity of the chemokine system. 趋化因子系统的起源、进化和分子多样性。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-01-16 Print Date: 2024-03-01 DOI: 10.26508/lsa.202302471

Alessandra Aleotti, Matthew Goulty, Clifton Lewis, Flaviano Giorgini, Roberto Feuda

{"title":"The origin, evolution, and molecular diversity of the chemokine system.","authors":"Alessandra Aleotti, Matthew Goulty, Clifton Lewis, Flaviano Giorgini, Roberto Feuda","doi":"10.26508/lsa.202302471","DOIUrl":"10.26508/lsa.202302471","url":null,"abstract":"Chemokine signalling performs key functions in cell migration via chemoattraction, such as attracting leukocytes to the site of infection during host defence. The system consists of a ligand, the chemokine, usually secreted outside the cell, and a chemokine receptor on the surface of a target cell that recognises the ligand. Several noncanonical components interact with the system. These include a variety of molecules that usually share some degree of sequence similarity with canonical components and, in some cases, are known to bind to canonical components and/or to modulate cell migration. Whereas canonical components have been described in vertebrate lineages, the distribution of the noncanonical components is less clear. Uncertainty over the relationships between canonical and noncanonical components hampers our understanding of the evolution of the system. We used phylogenetic methods, including gene-tree to species-tree reconciliation, to untangle the relationships between canonical and noncanonical components, identify gene duplication events, and clarify the origin of the system. We found that unrelated ligand groups independently evolved chemokine-like functions. We found noncanonical ligands outside vertebrates, such as TAFA \"chemokines\" found in urochordates. In contrast, all receptor groups are vertebrate-specific and all-except ACKR1-originated from a common ancestor in early vertebrates. Both ligand and receptor copy numbers expanded through gene duplication events at the base of jawed vertebrates, with subsequent waves of innovation occurring in bony fish and mammals.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10792014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478752","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

Accessory genes define species-specific routes to antibiotic resistance. 附属基因决定了抗生素耐药性的物种特异性途径。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-16 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302420

Lucy Dillon, Nicholas J Dimonaco, Christopher J Creevey

{"title":"Accessory genes define species-specific routes to antibiotic resistance.","authors":"Lucy Dillon, Nicholas J Dimonaco, Christopher J Creevey","doi":"10.26508/lsa.202302420","DOIUrl":"10.26508/lsa.202302420","url":null,"abstract":"A deeper understanding of the relationship between the antimicrobial resistance (AMR) gene carriage and phenotype is necessary to develop effective response strategies against this global burden. AMR phenotype is often a result of multi-gene interactions; therefore, we need approaches that go beyond current simple AMR gene identification tools. Machine-learning (ML) methods may meet this challenge and allow the development of rapid computational approaches for AMR phenotype classification. To examine this, we applied multiple ML techniques to 16,950 bacterial genomes across 28 genera, with corresponding MICs for 23 antibiotics with the aim of training models to accurately determine the AMR phenotype from sequenced genomes. This resulted in a >1.5-fold increase in AMR phenotype prediction accuracy over AMR gene identification alone. Furthermore, we revealed 528 unique (often species-specific) genomic routes to antibiotic resistance, including genes not previously linked to the AMR phenotype. Our study demonstrates the utility of ML in predicting AMR phenotypes across diverse clinically relevant organisms and antibiotics. This research proposes a rapid computational method to support laboratory-based identification of the AMR phenotype in pathogens.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10791901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478754","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

The LINC complex ensures accurate centrosome positioning during prophase. LINC 复合物可确保中心体在前期阶段准确定位。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-16 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302404

Joana T Lima, António J Pereira, Jorge G Ferreira

引用次数: 0

Nucleolar protein TAAP1/C22orf46 confers pro-survival signaling in non-small cell lung cancer. 核极蛋白TAAP1/C22orf46在非小细胞肺癌中传递促生存信号

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-16 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302257

Marietta Döring, Melanie Brux, Maciej Paszkowski-Rogacz, Pedro M Guillem-Gloria, Frank Buchholz, M Teresa Pisabarro, Mirko Theis

{"title":"Nucleolar protein TAAP1/C22orf46 confers pro-survival signaling in non-small cell lung cancer.","authors":"Marietta Döring, Melanie Brux, Maciej Paszkowski-Rogacz, Pedro M Guillem-Gloria, Frank Buchholz, M Teresa Pisabarro, Mirko Theis","doi":"10.26508/lsa.202302257","DOIUrl":"10.26508/lsa.202302257","url":null,"abstract":"Tumor cells subvert immune surveillance or lytic stress by harnessing inhibitory signals. Hence, bispecific antibodies have been developed to direct CTLs to the tumor site and foster immune-dependent cytotoxicity. Although applied with success, T cell-based immunotherapies are not universally effective partially because of the expression of pro-survival factors by tumor cells protecting them from apoptosis. Here, we report a CRISPR/Cas9 screen in human non-small cell lung cancer cells designed to identify genes that confer tumors with the ability to evade the cytotoxic effects of CD8+ T lymphocytes engaged by bispecific antibodies. We show that the gene C22orf46 facilitates pro-survival signals and that tumor cells devoid of C22orf46 expression exhibit increased susceptibility to T cell-induced apoptosis and stress by genotoxic agents. Although annotated as a non-coding gene, we demonstrate that C22orf46 encodes a nucleolar protein, hereafter referred to as \"Tumor Apoptosis Associated Protein 1,\" up-regulated in lung cancer, which displays remote homologies to the BH domain containing Bcl-2 family of apoptosis regulators. Collectively, the findings establish TAAP1/C22orf46 as a pro-survival oncogene with implications to therapy.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10791977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139478757","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

Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses. RNF12/RLIM E3 泛素连接酶的染色质靶向控制转录反应。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-01-10 Print Date: 2024-03-01 DOI: 10.26508/lsa.202302282

Carmen Espejo-Serrano, Catriona Aitken, Beatrice F Tan, Danielle G May, Rachel J Chrisopulos, Kyle J Roux, Jeroen Aa Demmers, Samuel G Mackintosh, Joost Gribnau, Francisco Bustos, Cristina Gontan, Greg M Findlay

{"title":"Chromatin targeting of the RNF12/RLIM E3 ubiquitin ligase controls transcriptional responses.","authors":"Carmen Espejo-Serrano, Catriona Aitken, Beatrice F Tan, Danielle G May, Rachel J Chrisopulos, Kyle J Roux, Jeroen Aa Demmers, Samuel G Mackintosh, Joost Gribnau, Francisco Bustos, Cristina Gontan, Greg M Findlay","doi":"10.26508/lsa.202302282","DOIUrl":"10.26508/lsa.202302282","url":null,"abstract":"Protein ubiquitylation regulates key biological processes including transcription. This is exemplified by the E3 ubiquitin ligase RNF12/RLIM, which controls developmental gene expression by ubiquitylating the REX1 transcription factor and is mutated in an X-linked intellectual disability disorder. However, the precise mechanisms by which ubiquitylation drives specific transcriptional responses are not known. Here, we show that RNF12 is recruited to specific genomic locations via a consensus sequence motif, which enables co-localisation with REX1 substrate at gene promoters. Surprisingly, RNF12 chromatin recruitment is achieved via a non-catalytic basic region and comprises a previously unappreciated N-terminal autoinhibitory mechanism. Furthermore, RNF12 chromatin targeting is critical for REX1 ubiquitylation and downstream RNF12-dependent gene regulation. Our results demonstrate a key role for chromatin in regulation of the RNF12-REX1 axis and provide insight into mechanisms by which protein ubiquitylation enables programming of gene expression.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10781586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417453","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

E. hellem Ser/Thr protein phosphatase PP1 targets the DC MAPK pathway and impairs immune functions. E. hellem Ser/Thr 蛋白磷酸酶 PP1 靶向直流 MAPK 通路并损害免疫功能。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-01-10 Print Date: 2024-04-01 DOI: 10.26508/lsa.202302375

Jialing Bao, Yunlin Tang, Yebo Chen, Jiangyan Jin, Xue Wang, Guozhen An, Lu Cao, Huarui Zhang, Gong Cheng, Guoqing Pan, Zeyang Zhou

{"title":"E. hellem Ser/Thr protein phosphatase PP1 targets the DC MAPK pathway and impairs immune functions.","authors":"Jialing Bao, Yunlin Tang, Yebo Chen, Jiangyan Jin, Xue Wang, Guozhen An, Lu Cao, Huarui Zhang, Gong Cheng, Guoqing Pan, Zeyang Zhou","doi":"10.26508/lsa.202302375","DOIUrl":"10.26508/lsa.202302375","url":null,"abstract":"Microsporidia are difficult to be completely eliminated once infected, and the persistence disrupts host cell functions. Here in this study, we aimed to elucidate the impairing effects and consequences of microsporidia on host DCs. Enterocytozoon hellem, one of the most commonly diagnosed zoonotic microsporidia species, was applied. In vivo models demonstrated that E. hellem-infected mice were more susceptible to further pathogenic challenges, and DCs were identified as the most affected groups of cells. In vitro assays revealed that E. hellem infection impaired DCs' immune functions, reflected by down-regulated cytokine expressions, lower extent of maturation, phagocytosis ability, and antigen presentations. E. hellem infection also detained DCs' potencies to prime and stimulate T cells; therefore, host immunities were disrupted. We found that E. hellem Ser/Thr protein phosphatase PP1 directly interacts with host p38α (MAPK14) to manipulate the p38α(MAPK14)/NFAT5 axis of the MAPK pathway. Our study is the first to elucidate the molecular mechanisms of the impairing effects of microsporidia on host DCs' immune functions. The emergence of microsporidiosis may be of great threat to public health.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10781585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139417454","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

CLN3 deficiency leads to neurological and metabolic perturbations during early development. CLN3 缺乏症会导致早期发育过程中的神经和代谢紊乱。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-01-09 Print Date: 2024-03-01 DOI: 10.26508/lsa.202302057

Ursula Heins-Marroquin, Randolph R Singh, Simon Perathoner, Floriane Gavotto, Carla Merino Ruiz, Myrto Patraskaki, Gemma Gomez-Giro, Felix Kleine Borgmann, Melanie Meyer, Anaïs Carpentier, Marc O Warmoes, Christian Jäger, Michel Mittelbronn, Jens C Schwamborn, Maria Lorena Cordero-Maldonado, Alexander D Crawford, Emma L Schymanski, Carole L Linster

{"title":"CLN3 deficiency leads to neurological and metabolic perturbations during early development.","authors":"Ursula Heins-Marroquin, Randolph R Singh, Simon Perathoner, Floriane Gavotto, Carla Merino Ruiz, Myrto Patraskaki, Gemma Gomez-Giro, Felix Kleine Borgmann, Melanie Meyer, Anaïs Carpentier, Marc O Warmoes, Christian Jäger, Michel Mittelbronn, Jens C Schwamborn, Maria Lorena Cordero-Maldonado, Alexander D Crawford, Emma L Schymanski, Carole L Linster","doi":"10.26508/lsa.202302057","DOIUrl":"10.26508/lsa.202302057","url":null,"abstract":"Juvenile neuronal ceroid lipofuscinosis (or Batten disease) is an autosomal recessive, rare neurodegenerative disorder that affects mainly children above the age of 5 yr and is most commonly caused by mutations in the highly conserved CLN3 gene. Here, we generated cln3 morphants and stable mutant lines in zebrafish. Although neither morphant nor mutant cln3 larvae showed any obvious developmental or morphological defects, behavioral phenotyping of the mutant larvae revealed hyposensitivity to abrupt light changes and hypersensitivity to pro-convulsive drugs. Importantly, in-depth metabolomics and lipidomics analyses revealed significant accumulation of several glycerophosphodiesters (GPDs) and cholesteryl esters, and a global decrease in bis(monoacylglycero)phosphate species, two of which (GPDs and bis(monoacylglycero)phosphates) were previously proposed as potential biomarkers for CLN3 disease based on independent studies in other organisms. We could also demonstrate GPD accumulation in human-induced pluripotent stem cell-derived cerebral organoids carrying a pathogenic variant for CLN3 Our models revealed that GPDs accumulate at very early stages of life in the absence of functional CLN3 and highlight glycerophosphoinositol and BMP as promising biomarker candidates for pre-symptomatic CLN3 disease.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10776888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403553","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