Life Science Alliance最新文献

Reframing "disappointing" data at Life Science Alliance. 重构生命科学联盟“令人失望”的数据。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2026-03-02 Print Date: 2026-03-01 DOI: 10.26508/lsa.202603674

Tim Fessenden

引用次数: 0

Targeted recruitment of USP15 enhances CTLA4 surface levels and restricts its degradation. 靶向募集USP15提高CTLA4表面水平，限制其降解。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2026-01-22 Print Date: 2026-04-01 DOI: 10.26508/lsa.202503563

Francesca Querques, Victoria Ciampani, Pei Yee Tey, Victoria D Kutilek, Elma Kadic, Michael J Clague, Sylvie Urbé

{"title":"Targeted recruitment of USP15 enhances CTLA4 surface levels and restricts its degradation.","authors":"Francesca Querques, Victoria Ciampani, Pei Yee Tey, Victoria D Kutilek, Elma Kadic, Michael J Clague, Sylvie Urbé","doi":"10.26508/lsa.202503563","DOIUrl":"10.26508/lsa.202503563","url":null,"abstract":"Induced protein proximity offers powerful new routes to modulate protein fate. Whereas proteolysis-targeting chimeras (PROTACs) promote degradation through E3 ligase recruitment, the converse principle, targeted protein stabilisation or enhancement via deubiquitylase (DUB) recruitment, is only beginning to emerge. The immune checkpoint receptor CTLA4, whose deficiency causes severe autoimmunity, undergoes rapid ubiquitin-dependent lysosomal degradation, making it one of the most short-lived transmembrane proteins. Using an inducible \"RapTag\" system, which brings together tagged proteins through rapalog-mediated FKBP-FRB dimerisation, we show that enforced proximity to the broad-specificity DUB USP15 markedly increases total and cell surface CTLA4 levels. Controlled expression of WT or catalytically inactive USP15 in isogenic cell lines revealed a clear requirement for DUB activity. The elevation of CTLA4 at the plasma membrane exceeded that of the total cellular pool, consistent with a diversion from ubiquitin-driven lysosomal sorting towards recycling. This easily adaptable platform enables systematic testing of DUB-substrate combinations that informs rational Enhancement Targeting Chimera (ENTAC) design for downstream drug discovery efforts and targeted protein rescue in therapeutic contexts.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12827578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030028","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

Brain vascular stability relies on PAK2-cilia-PDGF-BB-HSPGs on basolateral side of endothelium. 脑血管稳定性依赖于内皮基底外侧的pak2 -纤毛- pdgf - bb - hspgs。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2026-01-05 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503460

Shubhangi Prabhudesai, Karthikeyan Thirugnanam, Xuehong Song, Hua Yang, Mariella Errede, Francesco Girolamo, Thomas Neumann, Andrea Marzullo, Sepand Bafti, Kayla Vanderhoef, Kevin R Rarick, Andrew D Spearman, Amy Y Pan, Claudia Alvarez Alvarez, Jiyuan Yang, Fuming Zhang, Jonathan S Dordick, Daniela Virgintino, Lianchun Wang, Ramani Ramchandran

{"title":"Brain vascular stability relies on PAK2-cilia-PDGF-BB-HSPGs on basolateral side of endothelium.","authors":"Shubhangi Prabhudesai, Karthikeyan Thirugnanam, Xuehong Song, Hua Yang, Mariella Errede, Francesco Girolamo, Thomas Neumann, Andrea Marzullo, Sepand Bafti, Kayla Vanderhoef, Kevin R Rarick, Andrew D Spearman, Amy Y Pan, Claudia Alvarez Alvarez, Jiyuan Yang, Fuming Zhang, Jonathan S Dordick, Daniela Virgintino, Lianchun Wang, Ramani Ramchandran","doi":"10.26508/lsa.202503460","DOIUrl":"10.26508/lsa.202503460","url":null,"abstract":"Endothelial cells (ECs) in the brain communicate with mural cells to facilitate vascular stability. Platelet-derived growth factor-BB (PDGF-BB)/platelet-derived growth factor receptor-β (PDGFR-β) signaling mechanism at EC-mural cell interface helps stabilize the vasculature. How this paracrine signaling is mediated is not known. Our laboratory studies endothelial cilia, a microtubule-based organelle, and its role in promoting vascular stability. We discovered that brain endothelial cilia are located primarily on the basolateral side, and PDGF-BB is expressed in EC cilium. Thus, we hypothesized that endothelium cilium in conjunction with PDGF-BB on the basolateral side is responsible for mural cell recruitment. In this study, using a combination of zebrafish, mice, and human brain model systems, we have established a signaling paradigm wherein p21-activated kinase (PAK2) and ADP-ribosylation factor-13b (ARL13b) in ECs induce secretion of PDGF-BB. PDGF-BB associates with heparan sulfate proteoglycans (HSPGs) to form a gradient around ECs. Disrupting PAK2 affects ciliogenesis, HSPGs, and PDGF-BB gradient. We unravel a new mechanism involving endothelial cilia/PAK2-mediated PDGF-BB secretion, and retention by periendothelial HSPGs to promote vascular stability via recruiting mural cells.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12769094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906348","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

Structure and dynamics of 2x(CENP-A/H4)₂ octasome reveal a possible intermediate in centromeric chromatin. 2x(CENP-A/H4)2八体的结构和动力学揭示了着丝粒染色质中可能的中间体。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-15 Print Date: 2026-03-01 DOI: 10.26508/lsa.202503377

Ahmad Ali-Ahmad, Mira Mors, Manuel Carrer, Xinmeng Li, Silvija Bilokapić, Mario Halić, Michele Cascella, Nikolina Sekulić

引用次数: 0

Correction: Transient PU.1 low fetal progenitors generate lymphoid progeny that contribute to adult immunity. 纠正：短暂的PU.1低的胎儿祖细胞产生淋巴样后代，有助于成人免疫。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-02 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503567

Encarnacion Montecino-Rodriguez, Oscar I Estrada, Kenneth Dorshkind

引用次数: 0

GPR88 localization to primary cilia in neurons is cell-type specific. GPR88在神经元原代纤毛上的定位具有细胞类型特异性。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-02 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503366

Yenni H Li Guan, Brigitte L Kieffer, Mark von Zastrow, Aliza T Ehrlich

{"title":"GPR88 localization to primary cilia in neurons is cell-type specific.","authors":"Yenni H Li Guan, Brigitte L Kieffer, Mark von Zastrow, Aliza T Ehrlich","doi":"10.26508/lsa.202503366","DOIUrl":"10.26508/lsa.202503366","url":null,"abstract":"GPR88 is an orphan G protein-coupled receptor that regulates dopamine neurotransmission and is a target for neuropsychiatric disorders. In addition to the somatic membrane, GPR88 can localize to the primary cilium, a membrane microdomain known for dynamically enriching receptors and signaling molecules. However, the distribution of GPR88 in neuronal primary cilia remains uncharacterized. Here, we characterize GPR88 distribution at primary cilia in two brain areas. We show that in the striatum, GPR88 localizes both to somatodendritic and primary cilia compartments on inhibitory GABAergic medium spiny neurons. In contrast, in the somatosensory cortex, GPR88 localizes to somatodendritic and nuclear compartments and not primary cilia of excitatory spiny stellate neurons. In addition, we found that cilia density and length were similar between Gpr88 knockout and wild-type animals. Together, we provide key evidence for neuronal cell-type specific regulation of GPR88 localization to primary cilia, suggesting neuron subtype specific regulatory mechanisms govern receptor ciliary targeting in the brain.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12672383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661513","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

TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation. TRPM7和镁协调人CD4 t细胞的活化和分化。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-12-01 Print Date: 2026-02-01 DOI: 10.26508/lsa.202503357

Anna Madlmayr, Kilian Hoelting, Birgit Karner-Hoeger, Dorothea Lewitz, Marius Weng, Severin Hacker, Julia Eder, Katharina Horner, Christine Schedlberger, Tanja Haider, Max Lechner, Michelle Duggan, Rylee Ross, F David Horgen, Markus Sperandio, Alexander Dietrich, Thomas Gudermann, Susanna Zierler

{"title":"TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.","authors":"Anna Madlmayr, Kilian Hoelting, Birgit Karner-Hoeger, Dorothea Lewitz, Marius Weng, Severin Hacker, Julia Eder, Katharina Horner, Christine Schedlberger, Tanja Haider, Max Lechner, Michelle Duggan, Rylee Ross, F David Horgen, Markus Sperandio, Alexander Dietrich, Thomas Gudermann, Susanna Zierler","doi":"10.26508/lsa.202503357","DOIUrl":"10.26508/lsa.202503357","url":null,"abstract":"T-lymphocyte activation is a crucial process in the regulation of innate and adaptive immune responses. The ion channel-kinase TRPM7, transient receptor potential cation channel subfamily M, member 7, has previously been implicated in cellular Mg2+ homeostasis, proliferation, and immune cell modulation. Here, we show that pharmacological and genetic silencing of TRPM7 leads to diminished activation and influences signaling pathways that guide human TH17 or Treg cell differentiation, following TCR-mediated stimulation. In primary human CD4 T cells and CRISPR-Cas9-engineered Jurkat T cells, inactivation or loss of TRPM7 led to distorted Mg2+ homeostasis and Ca2+ signaling, reduced NFAT translocation, decreased IL-2 secretion and altered TH cell differentiation. While the activation of primary human CD4 T cells, as well as in vitro polarization into pro-inflammatory TH17 cells was critically dependent on TRPM7, the polarization of naïve CD4 T cells into FOXP3+ regulatory T cells was not. Taken together, these results highlight TRPM7 as molecular switch in lymphocyte activation and polarization. Thus, suggesting a therapeutic potential for TRPM7 in numerous T-cell mediated diseases.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"9 2","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12670122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145654851","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 brain slice cultures: translational applications and ethical considerations. 人脑切片培养：翻译应用和伦理考虑。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-10-09 Print Date: 2025-12-01 DOI: 10.26508/lsa.202403160

Kevin Joseph, Ioannis Vasilikos, Juergen Grauvogel, Mukesch Johannes Shah, Peter C Reinacher, Julia M Nakagawa, Ute Häussler, Jakob Straehle, Nicolas N Neidert, Panagiotis Fistouris, Matthias Schneider, Steven A Sloan, Tobias Weiss, Volker A Coenen, Oliver Schnell, Andreas Vlachos, Marco Prinz, Ulrich G Hofmann, Jürgen Beck, Philipp Kellmeyer, Vidhya M Ravi

{"title":"Human brain slice cultures: translational applications and ethical considerations.","authors":"Kevin Joseph, Ioannis Vasilikos, Juergen Grauvogel, Mukesch Johannes Shah, Peter C Reinacher, Julia M Nakagawa, Ute Häussler, Jakob Straehle, Nicolas N Neidert, Panagiotis Fistouris, Matthias Schneider, Steven A Sloan, Tobias Weiss, Volker A Coenen, Oliver Schnell, Andreas Vlachos, Marco Prinz, Ulrich G Hofmann, Jürgen Beck, Philipp Kellmeyer, Vidhya M Ravi","doi":"10.26508/lsa.202403160","DOIUrl":"10.26508/lsa.202403160","url":null,"abstract":"Human organotypic brain slice cultures have emerged as a pivotal tool to study the complexities of the human brain. Human organotypic brain slice cultures preserve the structural integrity, cellular diversity, and vascular networks of living brain tissue, maintaining in vivo characteristics. This advancement enables accurate temporal modeling of neurological diseases and facilitates precise experimental manipulations, accelerating therapeutic development. However, their use raises important ethical and philosophical considerations, including issues of donor consent and the potential for neural activity that prompts questions about consciousness. This study outlines these emerging concerns, emphasizing the need for guidelines that balance scientific innovation with ethical responsibility, particularly in relation to donor consent, transparency, and long-term use of living human tissue.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12511760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258679","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

Predicting nonsense-mediated mRNA decay from splicing events in sepsis using RNA-sequencing data. 利用rna测序数据预测脓毒症剪接事件中无义介导的mRNA衰变。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-09-24 Print Date: 2025-12-01 DOI: 10.26508/lsa.202503380

Jaewook Shin, Alger M Fredericks, Brandon E Armstead, Alfred Ayala, Maya Cohen, William G Fairbrother, Mitchell M Levy, Kwesi K Lillard, Emanuele Raggi, Gerard J Nau, Sean F Monaghan

{"title":"Predicting nonsense-mediated mRNA decay from splicing events in sepsis using RNA-sequencing data.","authors":"Jaewook Shin, Alger M Fredericks, Brandon E Armstead, Alfred Ayala, Maya Cohen, William G Fairbrother, Mitchell M Levy, Kwesi K Lillard, Emanuele Raggi, Gerard J Nau, Sean F Monaghan","doi":"10.26508/lsa.202503380","DOIUrl":"10.26508/lsa.202503380","url":null,"abstract":"Alternative splicing (AS) and nonsense-mediated mRNA decay (NMD) are highly conserved cellular mechanisms that modulate gene expression. Here, we introduce the NMD pipeline that computes how splicing events introduce premature termination codons to mRNA transcripts via frameshift, then predicts the rate of premature termination codon-dependent NMD. We use whole-blood, deep RNA-sequencing data from critically ill patients to study gene expression in sepsis. Statistical significance was determined as adjusted P < 0.05 and |log2 fold change| > 2 for differential gene expression and probability ≥0.9 and |DeltaPsi| > 0.1 for AS. The NMD pipeline was developed based on the AS data from Whippet. We demonstrate that the rate of NMD is higher in the sepsis and deceased groups compared with the control and survived groups, which may signify aberrant splicing because of altered physiology in critical illness. Predominance of non-exon skipping events was associated with disease and mortality states. The NMD pipeline also revealed proteins with potential association with sepsis. Together, these results emphasize the utility of the NMD pipeline in studying AS-NMD along with differential gene expression analysis and uncovering proteins associated with sepsis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 12","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138069","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

Elucidating the role of human skeletal muscles in the pathogenesis of enterovirus D68 infection. 阐明人类骨骼肌在肠病毒D68感染发病机制中的作用。

IF 2.9 2区生物学

Life Science Alliance Pub Date : 2025-09-05 Print Date: 2025-11-01 DOI: 10.26508/lsa.202503372

Brigitta M Laksono, Atze J Bergsma, Alessandro Iuliano, Dominique Y Veldhoen, Stefan van Nieuwkoop, Marjan Boter, Lonneke Leijten, Lisa Bauer, Bas B Oude Munnink, Wwm Pim Pijnappel, Debby van Riel

{"title":"Elucidating the role of human skeletal muscles in the pathogenesis of enterovirus D68 infection.","authors":"Brigitta M Laksono, Atze J Bergsma, Alessandro Iuliano, Dominique Y Veldhoen, Stefan van Nieuwkoop, Marjan Boter, Lonneke Leijten, Lisa Bauer, Bas B Oude Munnink, Wwm Pim Pijnappel, Debby van Riel","doi":"10.26508/lsa.202503372","DOIUrl":"10.26508/lsa.202503372","url":null,"abstract":"Enterovirus D68 (EV-D68) is an emerging respiratory virus associated with extra-respiratory complications, especially acute flaccid myelitis. However, the pathogenesis of acute flaccid myelitis is not fully understood. It is hypothesised that through infection of skeletal muscles, the virus further infects motor neurons via the neuromuscular junction. We hypothesise that EV-D68 infection of human skeletal muscles can impair muscle function directly, thereby contributing to the development of EV-D68-associated muscle weakness. Here, we inoculated human induced pluripotent stem cell-derived skeletal muscle myotubes grown in 2D and 3D with different EV-D68 isolates, which resulted in a productive infection and cell death. We showed through neuraminidase treatment that sialic acids facilitate infection of these cells. EV-D68 infection of the 3D model led to tissue damage, reduction of contractile force, and hampered muscle regeneration. Altogether, we showed that human skeletal muscle can act as an extra-respiratory replication site and infection of skeletal muscles may contribute to EV-D68-associated muscle weakness.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"8 11","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12413549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006312","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