Life Science Alliance最新文献

4G cloning: rapid gene assembly for expression of multisubunit protein complexes in diverse hosts. 4G克隆：在不同宿主中表达多亚单位蛋白复合物的快速基因组装。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-12-02 Print Date: 2025-01-01 DOI: 10.26508/lsa.202402899

Michael Taschner, Joe Bradley Dickinson, Florian Roisné-Hamelin, Stephan Gruber

引用次数: 0

Correction: Gene expression and chromatin conformation of microglia in virally suppressed people with HIV. 更正：病毒抑制型艾滋病患者小胶质细胞的基因表达和染色质构象。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-10-28 Print Date: 2025-01-01 DOI: 10.26508/lsa.202403085

Johannes Cm Schlachetzki, Sara Gianella, Zhengyu Ouyang, Addison J Lana, Xiaoxu Yang, Sydney O'Brien, Jean F Challacombe, Peter J Gaskill, Kelly L Jordan-Sciutto, Antoine Chaillon, David Moore, Cristian L Achim, Ronald J Ellis, Davey M Smith, Christopher K Glass

引用次数: 0

Mitochondrial apolipoprotein MIC26 is a metabolic rheostat regulating central cellular fuel pathways. 线粒体脂蛋白 MIC26 是调节细胞中心燃料通路的代谢调节器。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-10-11 Print Date: 2024-12-01 DOI: 10.26508/lsa.202403038

Melissa Damiecki, Ritam Naha, Yulia Schaumkessel, Philipp Westhoff, Nika Atanelov, Anja Stefanski, Patrick Petzsch, Kai Stühler, Karl Köhrer, Andreas Pm Weber, Ruchika Anand, Andreas S Reichert, Arun Kumar Kondadi

{"title":"Mitochondrial apolipoprotein MIC26 is a metabolic rheostat regulating central cellular fuel pathways.","authors":"Melissa Damiecki, Ritam Naha, Yulia Schaumkessel, Philipp Westhoff, Nika Atanelov, Anja Stefanski, Patrick Petzsch, Kai Stühler, Karl Köhrer, Andreas Pm Weber, Ruchika Anand, Andreas S Reichert, Arun Kumar Kondadi","doi":"10.26508/lsa.202403038","DOIUrl":"10.26508/lsa.202403038","url":null,"abstract":"Mitochondria play central roles in metabolism and metabolic disorders such as type 2 diabetes. MIC26, a mitochondrial contact site and cristae organising system complex subunit, was linked to diabetes and modulation of lipid metabolism. Yet, the functional role of MIC26 in regulating metabolism under hyperglycemia is not understood. We used a multi-omics approach combined with functional assays using WT and MIC26 KO cells cultured in normoglycemia or hyperglycemia, mimicking altered nutrient availability. We show that MIC26 has an inhibitory role in glycolysis and cholesterol/lipid metabolism under normoglycemic conditions. Under hyperglycemia, this inhibitory role is reversed demonstrating that MIC26 is critical for metabolic adaptations. This is partially mediated by alterations of mitochondrial metabolite transporters. Furthermore, MIC26 deletion led to a major metabolic rewiring of glutamine use and oxidative phosphorylation. We propose that MIC26 acts as a metabolic \"rheostat,\" that modulates mitochondrial metabolite exchange via regulating mitochondrial cristae, allowing cells to cope with nutrient overload.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406584","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

NAD⁺ depletion is central to placental dysfunction in an inflammatory subclass of preeclampsia. NAD+消耗是子痫前期炎症亚型胎盘功能障碍的核心原因。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-10-10 Print Date: 2024-12-01 DOI: 10.26508/lsa.202302505

Fahmida Jahan, Goutham Vasam, Yusmaris Cariaco, Abolfazl Nik-Akhtar, Alex Green, Keir J Menzies, Shannon A Bainbridge

{"title":"NAD+ depletion is central to placental dysfunction in an inflammatory subclass of preeclampsia.","authors":"Fahmida Jahan, Goutham Vasam, Yusmaris Cariaco, Abolfazl Nik-Akhtar, Alex Green, Keir J Menzies, Shannon A Bainbridge","doi":"10.26508/lsa.202302505","DOIUrl":"10.26508/lsa.202302505","url":null,"abstract":"Preeclampsia (PE) is a hypertensive disorder of pregnancy and a major cause of maternal/perinatal adverse health outcomes with no effective therapeutic strategies. Our group previously identified distinct subclasses of PE, one of which exhibits heightened placental inflammation (inflammation-driven PE). In non-pregnant populations, chronic inflammation is associated with decreased levels of cellular NAD+, a vitamin B3 derivative involved in energy metabolism and mitochondrial function. Interestingly, specifically in placentas from women with inflammation-driven PE, we observed the increased activity of NAD+-consuming enzymes, decreased NAD+ content, decreased expression of mitochondrial proteins, and increased oxidative damage. HTR8 human trophoblasts likewise demonstrated increased NAD+-dependent ADP-ribosyltransferase (ART) activity, coupled with decreased mitochondrial respiration rates and invasive function under inflammatory conditions. Such adverse effects were attenuated by boosting cellular NAD+ levels with nicotinamide riboside (NR). Finally, in an LPS-induced rat model of inflammation-driven PE, NR administration (200 mg/kg/day) from gestational days 1-19 prevented maternal hypertension and fetal/placental growth restriction, improved placental mitochondrial function, and reduced inflammation and oxidative stress. This study demonstrates the critical role of NAD+ in maintaining placental function and identifies NAD+ boosting as a promising preventative strategy for PE.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11467044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400689","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

Naa80 is required for actin N-terminal acetylation and normal hearing in zebrafish. 斑马鱼肌动蛋白 N 端乙酰化和正常听力需要 Naa80。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-10-09 Print Date: 2024-12-01 DOI: 10.26508/lsa.202402795

Rasmus Ree, Sheng-Jia Lin, Lars Ole Sti Dahl, Kevin Huang, Cassidy Petree, Gaurav K Varshney, Thomas Arnesen

{"title":"Naa80 is required for actin N-terminal acetylation and normal hearing in zebrafish.","authors":"Rasmus Ree, Sheng-Jia Lin, Lars Ole Sti Dahl, Kevin Huang, Cassidy Petree, Gaurav K Varshney, Thomas Arnesen","doi":"10.26508/lsa.202402795","DOIUrl":"10.26508/lsa.202402795","url":null,"abstract":"Actin is a critical component of the eukaryotic cytoskeleton. In animals, actins undergo unique N-terminal processing by dedicated enzymes resulting in mature acidic and acetylated forms. The final step, N-terminal acetylation, is catalyzed by NAA80 in humans. N-terminal acetylation of actin is crucial for maintaining normal cytoskeletal dynamics and cell motility in human cell lines. However, the physiological impact of actin N-terminal acetylation remains to be fully understood. We developed a zebrafish naa80 knockout model and demonstrated that Naa80 acetylates both muscle and non-muscle actins in vivo. Assays with purified Naa80 revealed a preference for acetylating actin N-termini. Zebrafish lacking actin N-terminal acetylation exhibited normal development, morphology, and behavior. In contrast, humans with pathogenic actin variants can present with hypotonia and hearing impairment. Whereas zebrafish lacking naa80 showed no obvious muscle defects or abnormalities, we observed abnormal inner ear development, small otoliths, and impaired response to sound. In conclusion, we have established that zebrafish Naa80 N-terminally acetylates actins in vitro and in vivo, and that actin N-terminal acetylation is essential for normal hearing.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391639","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

Laminin-α2 chain deficiency in skeletal muscle causes dysregulation of multiple cellular mechanisms. 骨骼肌中缺乏层粘连蛋白-α2 链会导致多种细胞机制失调。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-10-08 Print Date: 2024-12-01 DOI: 10.26508/lsa.202402829

Susana G Martins, Vanessa Ribeiro, Catarina Melo, Cláudia Paulino-Cavaco, Dario Antonini, Sharadha Dayalan Naidu, Fernanda Murtinheira, Inês Fonseca, Bérénice Saget, Mafalda Pita, Diogo R Fernandes, Pedro Gameiro Dos Santos, Gabriela Rodrigues, Rita Zilhão, Federico Herrera, Albena T Dinkova-Kostova, Ana Rita Carlos, Sólveig Thorsteinsdóttir

{"title":"Laminin-α2 chain deficiency in skeletal muscle causes dysregulation of multiple cellular mechanisms.","authors":"Susana G Martins, Vanessa Ribeiro, Catarina Melo, Cláudia Paulino-Cavaco, Dario Antonini, Sharadha Dayalan Naidu, Fernanda Murtinheira, Inês Fonseca, Bérénice Saget, Mafalda Pita, Diogo R Fernandes, Pedro Gameiro Dos Santos, Gabriela Rodrigues, Rita Zilhão, Federico Herrera, Albena T Dinkova-Kostova, Ana Rita Carlos, Sólveig Thorsteinsdóttir","doi":"10.26508/lsa.202402829","DOIUrl":"10.26508/lsa.202402829","url":null,"abstract":"LAMA2, coding for the laminin-α2 chain, is a crucial ECM component, particularly abundant in skeletal muscle. Mutations in LAMA2 trigger the often-lethal LAMA2-congenital muscular dystrophy (LAMA2-CMD). Various phenotypes have been linked to LAMA2-CMD; nevertheless, the precise mechanisms that malfunction during disease onset in utero remain unknown. We generated Lama2-deficient C2C12 cells and found that Lama2-deficient myoblasts display proliferation, differentiation, and fusion defects, DNA damage, oxidative stress, and mitochondrial dysfunction. Moreover, fetal myoblasts isolated from the dy W mouse model of LAMA2-CMD display impaired differentiation and fusion in vitro. We also showed that disease onset during fetal development is characterized by a significant down-regulation of gene expression in muscle fibers, causing pronounced effects on cytoskeletal organization, muscle differentiation, and altered DNA repair and oxidative stress responses. Together, our findings provide unique insights into the critical importance of the laminin-α2 chain for muscle differentiation and muscle cell homeostasis.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391638","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

Cholesterol promotes IFNG mRNA expression in CD4⁺ effector/memory cells by SGK1 activation. 胆固醇通过激活 SGK1 促进 CD4+ 效应细胞/记忆细胞中 IFNG mRNA 的表达。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-10-04 Print Date: 2024-12-01 DOI: 10.26508/lsa.202402890

Aurélie Hanin, Michela Comi, Tomokazu S Sumida, David A Hafler

{"title":"Cholesterol promotes IFNG mRNA expression in CD4+ effector/memory cells by SGK1 activation.","authors":"Aurélie Hanin, Michela Comi, Tomokazu S Sumida, David A Hafler","doi":"10.26508/lsa.202402890","DOIUrl":"10.26508/lsa.202402890","url":null,"abstract":"IFNγ-secreting T cells are central for the maintenance of immune surveillance within the central nervous system (CNS). It was previously reported in healthy donors that the T-cell environment in the CNS induces distinct signatures related to cytotoxic capacity, CNS trafficking, tissue adaptation, and lipid homeostasis. These findings suggested that the CNS milieu consisting predominantly of lipids mediated the metabolic conditions leading to IFNγ-secreting brain CD4 T cells. Here, we demonstrate that the supplementation of CD4+CD45RO+CXCR3+ cells with cholesterol modulates their function and increases IFNG expression. The heightened IFNG expression was mediated by the activation of the serum/glucocorticoid-regulated kinase (SGK1). Inhibition of SGK1 by a specific enzymatic inhibitor significantly reduces the expression of IFNG Our results confirm the crucial role of lipids in maintaining T-cell homeostasis and demonstrate a putative role of environmental factors to induce effector responses in CD4+ effector/memory cells. These findings offer potential avenues for further research targeting lipid pathways to modulate inflammatory conditions.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375665","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

Epithelial-specific loss of Smad4 alleviates the fibrotic response in an acute colitis mouse model. 上皮特异性缺失 Smad4 可减轻急性结肠炎小鼠模型的纤维化反应。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-10-04 Print Date: 2024-12-01 DOI: 10.26508/lsa.202402935

Zahra Hashemi, Thompson Hui, Alex Wu, Dahlia Matouba, Steven Zukowski, Shima Nejati, Crystal Lim, Julianna Bruzzese, Cindy Lin, Kyle Seabold, Connor Mills, Kylee Wrath, Haoyu Wang, Hongjun Wang, Michael P Verzi, Ansu Perekatt

{"title":"Epithelial-specific loss of Smad4 alleviates the fibrotic response in an acute colitis mouse model.","authors":"Zahra Hashemi, Thompson Hui, Alex Wu, Dahlia Matouba, Steven Zukowski, Shima Nejati, Crystal Lim, Julianna Bruzzese, Cindy Lin, Kyle Seabold, Connor Mills, Kylee Wrath, Haoyu Wang, Hongjun Wang, Michael P Verzi, Ansu Perekatt","doi":"10.26508/lsa.202402935","DOIUrl":"10.26508/lsa.202402935","url":null,"abstract":"Mucosal healing is associated with better clinical outcomes in patients with inflammatory bowel disease. But the epithelial-specific contribution to mucosal healing in vivo is poorly understood. We evaluated mucosal healing in an acute dextran sulfate sodium mouse model that shows an alleviated colitis response after epithelial-specific loss of Smad4. We find that enhanced epithelial wound healing alleviates the fibrotic response. Dextran sulfate sodium caused increased mesenchymal collagen deposition-indicative of fibrosis-within a week in the WT but not in the Smad4 KO colon. The fibrotic response correlated with decreased epithelial proliferation in the WT, whereas uninterrupted proliferation and an expanded zone of proliferation were observed in the Smad4 KO colon epithelium. Furthermore, the Smad4 KO colon showed epithelial extracellular matrix alterations that promote epithelial regeneration. Our data suggest that epithelium is a key determinant of the mucosal healing response in vivo, implicating mucosal healing as a strategy against fibrosis in inflammatory bowel disease patients.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375666","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

Mitochondria remodeling during endometrial stromal cell decidualization. 子宫内膜基质细胞蜕膜化过程中的线粒体重塑

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-10-04 Print Date: 2024-12-01 DOI: 10.26508/lsa.202402627

Marco Dalla Torre, Daniele Pittari, Alessandra Boletta, Laura Cassina, Roberto Sitia, Tiziana Anelli

引用次数: 0

SLMAP3 is essential for neurulation through mechanisms involving cytoskeletal elements, ABP, and PCP. SLMAP3 通过涉及细胞骨架元素、ABP 和 PCP 的机制对神经形成至关重要。

IF 3.3 2区生物学

Life Science Alliance Pub Date : 2024-10-04 Print Date: 2024-12-01 DOI: 10.26508/lsa.202302545

Taha Rehmani, Ana Paula Dias, Billi Dawn Applin, Maysoon Salih, Balwant S Tuana

{"title":"SLMAP3 is essential for neurulation through mechanisms involving cytoskeletal elements, ABP, and PCP.","authors":"Taha Rehmani, Ana Paula Dias, Billi Dawn Applin, Maysoon Salih, Balwant S Tuana","doi":"10.26508/lsa.202302545","DOIUrl":"10.26508/lsa.202302545","url":null,"abstract":"SLMAP3 is a tail-anchored membrane protein that targets subcellular organelles and is believed to regulate Hippo signaling. The global loss of SLMAP3 causes late embryonic lethality in mice, with some embryos exhibiting neural tube defects such as craniorachischisis. We show here that SLMAP3 -/- embryos display reduced length and increased width of neural plates, signifying arrested convergent extension. The expression of planar cell polarity (PCP) components Dvl2/3 and the activity of the downstream targets ROCK2, cofilin, and JNK1/2 were dysregulated in SLMAP3 -/- E12.5 brains. Furthermore, the cytoskeletal proteins (γ-tubulin, actin, and nestin) and apical components (PKCζ and ZO-1) were mislocalized in neural tubes of SLMAP3 -/- embryos, with a subsequent decrease in colocalization of PCP proteins (Fzd6 and pDvl2). However, no changes in PCP or cytoskeleton proteins were found in cultured neuroepithelial cells depleted of SLMAP3, suggesting an essential requirement for SLMAP3 for these processes in vivo for neurulation. The loss of SLMAP3 had no impact on Hippo signaling in SLMAP3 -/- embryos, brains, and neural tubes. Proteomic analysis revealed SLMAP3 in an interactome with cytoskeletal components, including nestin, tropomyosin 4, intermediate filaments, plectin, the PCP protein SCRIB, and STRIPAK members in embryonic brains. These results reveal a crucial role of SLMAP3 in neural tube development by regulating the cytoskeleton organization and PCP pathway.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":"7 12","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11452652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375668","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