Life Science Alliance最新文献_第10页

Single-cell time series analysis reveals the dynamics of HSPC response to inflammation. 单细胞时间序列分析揭示了 HSPC 对炎症反应的动态变化。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2023-12-18 DOI: 10.26508/lsa.202302309

Brigitte J Bouman, Yasmin Demerdash, Shubhankar Sood, Florian Grünschläger, Franziska Pilz, Abdul R Itani, Andrea Kuck, Valérie Marot-Lassauzaie, Simon Haas, Laleh Haghverdi, Marieke Ag Essers

{"title":"Single-cell time series analysis reveals the dynamics of HSPC response to inflammation.","authors":"Brigitte J Bouman, Yasmin Demerdash, Shubhankar Sood, Florian Grünschläger, Franziska Pilz, Abdul R Itani, Andrea Kuck, Valérie Marot-Lassauzaie, Simon Haas, Laleh Haghverdi, Marieke Ag Essers","doi":"10.26508/lsa.202302309","DOIUrl":"https://doi.org/10.26508/lsa.202302309","url":null,"abstract":"Hematopoietic stem and progenitor cells (HSPCs) are known to respond to acute inflammation; however, little is understood about the dynamics and heterogeneity of these stress responses in HSPCs. Here, we performed single-cell sequencing during the sensing, response, and recovery phases of the inflammatory response of HSPCs to treatment (a total of 10,046 cells from four time points spanning the first 72 h of response) with the pro-inflammatory cytokine IFNα to investigate the HSPCs' dynamic changes during acute inflammation. We developed the essential novel computational approaches to process and analyze the resulting single-cell time series dataset. This includes an unbiased cell type annotation and abundance analysis post inflammation, tools for identification of global and cell type-specific responding genes, and a semi-supervised linear regression approach for response pseudotime reconstruction. We discovered a variety of different gene responses of the HSPCs to the treatment. Interestingly, we were able to associate a global reduced myeloid differentiation program and a locally enhanced pyroptosis activity with reduced myeloid progenitor and differentiated cells after IFNα treatment. Altogether, the single-cell time series analyses have allowed us to unbiasedly study the heterogeneous and dynamic impact of IFNα on the HSPCs.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"22 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138741765","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

Changes in searching behaviour of CSL transcription complexes in Notch active conditions. Notch 活跃条件下 CSL 转录复合物搜索行为的变化。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2023-12-14 DOI: 10.26508/lsa.202302336

Sarah Baloul, Charalambos Roussos, Maria Gomez-Lamarca, Leila Muresan, Sarah Bray

{"title":"Changes in searching behaviour of CSL transcription complexes in Notch active conditions.","authors":"Sarah Baloul, Charalambos Roussos, Maria Gomez-Lamarca, Leila Muresan, Sarah Bray","doi":"10.26508/lsa.202302336","DOIUrl":"https://doi.org/10.26508/lsa.202302336","url":null,"abstract":"During development cells receive a variety of signals, which are of crucial importance to their fate determination. One such source of signal is the Notch signalling pathway, where Notch activity regulates expression of target genes through the core transcription factor CSL. To understand changes in transcription factor behaviour that lead to transcriptional changes in Notch active cells, we have probed CSL behaviours in real time, using in vivo Single Molecule Localisation Microscopy. Trajectory analysis reveals that Notch-On conditions increase the fraction of bound CSL molecules, but also the proportion of molecules with exploratory behaviours. These properties are shared by the co-activator Mastermind. Furthermore, both CSL and Mastermind, exhibit characteristics of local exploration near a Notch target locus. A similar behaviour is observed for CSL molecules diffusing in the vicinity of other bound CSL clusters. We suggest therefore that CSL acquires an exploratory behaviour when part of the activation complex, favouring local searching and retention close to its target enhancers. This change explains how CSL can efficiently increase its occupancy at target sites in Notch-On conditions.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"6 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138692888","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

The structural basis for deubiquitination by the fingerless USP-type effector TssM. 无指 USP 型效应物 TssM 去泛素化的结构基础。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2023-12-13 Print Date: 2024-02-01 DOI: 10.26508/lsa.202302422

Thomas Hermanns, Matthias Uthoff, Ulrich Baumann, Kay Hofmann

{"title":"The structural basis for deubiquitination by the fingerless USP-type effector TssM.","authors":"Thomas Hermanns, Matthias Uthoff, Ulrich Baumann, Kay Hofmann","doi":"10.26508/lsa.202302422","DOIUrl":"10.26508/lsa.202302422","url":null,"abstract":"Intracellular bacteria are threatened by ubiquitin-mediated autophagy, whenever the bacterial surface or enclosing membrane structures become targets of host ubiquitin ligases. As a countermeasure, many intracellular pathogens encode deubiquitinase (DUB) effectors to keep their surfaces free of ubiquitin. Most bacterial DUBs belong to the OTU or CE-clan families. The betaproteobacteria Burkholderia pseudomallei and Burkholderia mallei, causative agents of melioidosis and glanders, respectively, encode the TssM effector, the only known bacterial DUB belonging to the USP class. TssM is much shorter than typical eukaryotic USP enzymes and lacks the canonical ubiquitin-recognition region. By solving the crystal structures of isolated TssM and its complex with ubiquitin, we found that TssM lacks the entire \"Fingers\" subdomain of the USP fold. Instead, the TssM family has evolved the functionally analog \"Littlefinger\" loop, which is located towards the end of the USP domain and recognizes different ubiquitin interfaces than those used by USPs. The structures revealed the presence of an N-terminal immunoglobulin-fold domain, which is able to form a strand-exchange dimer and might mediate TssM localization to the bacterial surface.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10719079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087435","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 AP-2 complex interacts with γ-TuRC and regulates the proliferative capacity of neural progenitors. AP-2 复合物与 γ-TuRC 相互作用，调节神经祖细胞的增殖能力。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2023-12-12 Print Date: 2024-02-01 DOI: 10.26508/lsa.202302029

Santiago Camblor-Perujo, Ebru Ozer Yildiz, Hanna Küpper, Melina Overhoff, Saumya Rastogi, Hisham Bazzi, Natalia L Kononenko

{"title":"The AP-2 complex interacts with γ-TuRC and regulates the proliferative capacity of neural progenitors.","authors":"Santiago Camblor-Perujo, Ebru Ozer Yildiz, Hanna Küpper, Melina Overhoff, Saumya Rastogi, Hisham Bazzi, Natalia L Kononenko","doi":"10.26508/lsa.202302029","DOIUrl":"10.26508/lsa.202302029","url":null,"abstract":"Centrosomes are organelles that nucleate microtubules via the activity of gamma-tubulin ring complexes (γ-TuRC). In the developing brain, centrosome integrity is central to the progression of the neural progenitor cell cycle, and its loss leads to microcephaly. We show that NPCs maintain centrosome integrity via the endocytic adaptor protein complex-2 (AP-2). NPCs lacking AP-2 exhibit defects in centrosome formation and mitotic progression, accompanied by DNA damage and accumulation of p53. This function of AP-2 in regulating the proliferative capacity of NPCs is independent of its role in clathrin-mediated endocytosis and is coupled to its association with the GCP2, GCP3, and GCP4 components of γ-TuRC. We find that AP-2 maintains γ-TuRC organization and regulates centrosome function at the level of MT nucleation. Taken together, our data reveal a novel, noncanonical function of AP-2 in regulating the proliferative capacity of NPCs and open new avenues for the identification of novel therapeutic strategies for the treatment of neurodevelopmental and neurodegenerative disorders with AP-2 complex dysfunction.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798202","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

Human RAD52 stimulates the RAD51-mediated homology search. 人类 RAD52 可刺激 RAD51 介导的同源搜索。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2023-12-11 Print Date: 2024-03-01 DOI: 10.26508/lsa.202201751

Ali Akbar Muhammad, Clara Basto, Thibaut Peterlini, Josée Guirouilh-Barbat, Melissa Thomas, Xavier Veaute, Didier Busso, Bernard Lopez, Gerard Mazon, Eric Le Cam, Jean-Yves Masson, Pauline Dupaigne

{"title":"Human RAD52 stimulates the RAD51-mediated homology search.","authors":"Ali Akbar Muhammad, Clara Basto, Thibaut Peterlini, Josée Guirouilh-Barbat, Melissa Thomas, Xavier Veaute, Didier Busso, Bernard Lopez, Gerard Mazon, Eric Le Cam, Jean-Yves Masson, Pauline Dupaigne","doi":"10.26508/lsa.202201751","DOIUrl":"10.26508/lsa.202201751","url":null,"abstract":"Homologous recombination (HR) is a DNA repair mechanism of double-strand breaks and blocked replication forks, involving a process of homology search leading to the formation of synaptic intermediates that are regulated to ensure genome integrity. RAD51 recombinase plays a central role in this mechanism, supported by its RAD52 and BRCA2 partners. If the mediator function of BRCA2 to load RAD51 on RPA-ssDNA is well established, the role of RAD52 in HR is still far from understood. We used transmission electron microscopy combined with biochemistry to characterize the sequential participation of RPA, RAD52, and BRCA2 in the assembly of the RAD51 filament and its activity. Although our results confirm that RAD52 lacks a mediator activity, RAD52 can tightly bind to RPA-coated ssDNA, inhibit the mediator activity of BRCA2, and form shorter RAD51-RAD52 mixed filaments that are more efficient in the formation of synaptic complexes and D-loops, resulting in more frequent multi-invasions as well. We confirm the in situ interaction between RAD51 and RAD52 after double-strand break induction in vivo. This study provides new molecular insights into the formation and regulation of presynaptic and synaptic intermediates by BRCA2 and RAD52 during human HR.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 3","pages":""},"PeriodicalIF":3.3,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10713436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138798276","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

tRF-1:30-Gly-CCC-3 inhibits thyroid cancer via binding to PC and modulating metabolic reprogramming tRF-1:30-Gly-CCC-3通过与PC结合和调节代谢重编程抑制甲状腺癌

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2023-12-11 DOI: 10.26508/lsa.202302285

Bifei Fu, Yuming Lou, Xiaofeng Lu, Zhaolin Wu, Junjie Ni, Cong Jin, Pu Wu, Chaoyang Xu

引用次数: 0

RedRibbon: A new rank–rank hypergeometric overlap for gene and transcript expression signatures 红丝带基因和转录本表达特征的新等级超几何重叠

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2023-12-08 DOI: 10.26508/lsa.202302203

Anthony Piron, F. Szymczak, Theodora Papadopoulou, M. I. Alvelos, Matthieu Defrance, Tom Lenaerts, D. Eizirik, M. Cnop

引用次数: 0

A high-throughput two-cell assay for interrogating inhibitory signaling pathways in T cells 用于检测 T 细胞抑制信号通路的高通量双细胞检测法

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2023-12-07 DOI: 10.26508/lsa.202302359

Sumana Sharma, Toby Whitehead, M. Kotowski, Emily Zhi Qing Ng, Joseph Clarke, Judith Leitner, Yi-Ling Chen, Ana Mafalda Santos, Peter Steinberger, Simon J Davis

引用次数: 0

Structural maintenance of chromosomes (SMC) proteins are required for DNA elimination in Paramecium. 在草履虫中，染色体的结构维持(SMC)蛋白是DNA消除所必需的。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2023-12-06 Print Date: 2024-02-01 DOI: 10.26508/lsa.202302281

Fukai Zhang, Sebastian Bechara, Mariusz Nowacki

{"title":"Structural maintenance of chromosomes (SMC) proteins are required for DNA elimination in Paramecium.","authors":"Fukai Zhang, Sebastian Bechara, Mariusz Nowacki","doi":"10.26508/lsa.202302281","DOIUrl":"10.26508/lsa.202302281","url":null,"abstract":"Chromosome (SMC) proteins are a large family of ATPases that play important roles in the organization and dynamics of chromatin. They are central regulators of chromosome dynamics and the core component of condensin. DNA elimination during zygotic somatic genome development is a characteristic feature of ciliated protozoa such as Paramecium This process occurs after meiosis, mitosis, karyogamy, and another mitosis, which result in the formation of a new germline and somatic nuclei. The series of nuclear divisions implies an important role of SMC proteins in Paramecium sexual development. The relationship between DNA elimination and SMC has not yet been described. Here, we applied RNA interference, genome sequencing, mRNA sequencing, immunofluorescence, and mass spectrometry to investigate the roles of SMC components in DNA elimination. Our results show that SMC4-2 is required for genome rearrangement, whereas SMC4-1 is not. Functional diversification of SMC4 in Paramecium led to a formation of two paralogues where SMC4-2 acquired a novel, development-specific function and differs from SMC4-1. Moreover, our study suggests a competitive relationship between these two proteins.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10700549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498803","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

IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signalling by lithium. 锂离子对磷脂酰肌醇4,5-二磷酸和钙信号的IMPA1依赖性调节。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2023-12-06 Print Date: 2024-02-01 DOI: 10.26508/lsa.202302425

Sankhanil Saha, Harini Krishnan, Padinjat Raghu

{"title":"IMPA1 dependent regulation of phosphatidylinositol 4,5-bisphosphate and calcium signalling by lithium.","authors":"Sankhanil Saha, Harini Krishnan, Padinjat Raghu","doi":"10.26508/lsa.202302425","DOIUrl":"10.26508/lsa.202302425","url":null,"abstract":"Lithium (Li) is widely used as a mood stabilizer to treat bipolar affective disorder. However, the molecular targets of Li that underpin its therapeutic effect remain unresolved. Inositol monophosphatase (IMPA1) is an enzyme involved in phosphatidylinositol 4,5-bisphosphate (PIP2) resynthesis after PLC signaling. In vitro, Li inhibits IMPA1, but the relevance of this inhibition within neural cells remains unknown. Here, we report that treatment with therapeutic concentrations of Li reduces receptor-activated calcium release from intracellular stores and delays PIP2 resynthesis. These effects of Li are abrogated in IMPA1 deleted cells. We also observed that in human forebrain cortical neurons, treatment with Li reduced neuronal excitability and calcium signals. After Li treatment of human cortical neurons, transcriptome analyses revealed down-regulation of signaling by glutamate, a key excitatory neurotransmitter in the human brain. Collectively, our findings suggest that inhibition of IMPA1 by Li reduces receptor-activated PLC signaling and neuronal excitability.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10700560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498801","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