Life Science Alliance最新文献_第4页

Subdomains of the Helicobacter pylori Cag T4SS outer membrane core complex exhibit structural independence 幽门螺旋杆菌 Cag T4SS 外膜核心复合体的子域在结构上具有独立性

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-17 DOI: 10.26508/lsa.202302560

Jacquelyn R. Roberts, Sirena C Tran, A. Frick-Cheng, Kaeli N. Bryant, Chiamaka D Okoye, W. H. McDonald, T. Cover, M. Ohi

引用次数: 0

Frataxin deficiency shifts metabolism to promote reactive microglia via glucose catabolism 缺乏 Frataxin 会改变新陈代谢，通过葡萄糖分解促进反应性小胶质细胞的生长

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-17 DOI: 10.26508/lsa.202402609

Francesca Sciarretta, Fabio Zaccaria, Andrea Ninni, Veronica Ceci, Riccardo Turchi, S. Apolloni, M. Milani, Ilaria Della Valle, Marta Tiberi, V. Chiurchiù, N. D’Ambrosi, S. Pedretti, N. Mitro, C. Volonté, S. Amadio, Katia Aquilano, Daniele Lettieri-Barbato

引用次数: 0

Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson's. Nr1h4 和 Thrb 可改善 ER 压力，并为 MPTP 帕金森病小鼠模型提供保护。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-12 DOI: 10.26508/lsa.202302416

Nancy Ahuja, Shalini Gupta, Rashmi Arora, Ella Bhagyaraj, Drishti Tiwari, Sumit Kumar, Pawan Gupta

{"title":"Nr1h4 and Thrb ameliorate ER stress and provide protection in the MPTP mouse model of Parkinson's.","authors":"Nancy Ahuja, Shalini Gupta, Rashmi Arora, Ella Bhagyaraj, Drishti Tiwari, Sumit Kumar, Pawan Gupta","doi":"10.26508/lsa.202302416","DOIUrl":"https://doi.org/10.26508/lsa.202302416","url":null,"abstract":"Elevated ER stress has been linked to the pathogenesis of several disease conditions including neurodegeneration. In this study, we have holistically determined the differential expression of all the nuclear receptors (NRs) in the presence of classical ER stress inducers. Activation of Nr1h4 and Thrb by their cognate ligands (GW4064 and T3) ameliorates the tunicamycin (TM)-induced expression of ER stress genes. A combination of both ligands is effective in mitigating cell death induced by TM. Further exploration of their protective effects in the Parkinson's disease (PD) model shows that they reduce MPP+-induced dissipation of mitochondrial membrane potential and ROS generation in an in vitro PD model in neuronal cells. Furthermore, the generation of an experimental murine PD model reveals that simultaneous treatment of GW4064 and T3 protects mice from ER stress, dopaminergic cell death, and functional deficits in the MPTP mouse model of PD. Thus, activation of Nr1h4 and Thrb by their respective ligands plays an indispensable role in ER stress amelioration and mounts protective effects in the MPTP mouse model of PD.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563403","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

Structural basis of translation inhibition by a valine tRNA-derived fragment. 缬氨酸 tRNA 衍生片段抑制翻译的结构基础

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-10 DOI: 10.26508/lsa.202302488

Yun Wu, Meng-Ting Ni, Ying-Hui Wang, Chen Wang, Hai Hou, Xing Zhang, Jie Zhou

{"title":"Structural basis of translation inhibition by a valine tRNA-derived fragment.","authors":"Yun Wu, Meng-Ting Ni, Ying-Hui Wang, Chen Wang, Hai Hou, Xing Zhang, Jie Zhou","doi":"10.26508/lsa.202302488","DOIUrl":"https://doi.org/10.26508/lsa.202302488","url":null,"abstract":"Translational regulation by non-coding RNAs is a mechanism commonly used by cells to fine-tune gene expression. A fragment derived from an archaeal valine tRNA (Val-tRF) has been previously identified to bind the small subunit of the ribosome and inhibit translation in Haloferax volcanii Here, we present three cryo-electron microscopy structures of Val-tRF bound to the small subunit of Sulfolobus acidocaldarius ribosomes at resolutions between 4.02 and 4.53 Å. Within these complexes, Val-tRF was observed to bind to conserved RNA-interacting sites, including the ribosomal decoding center. The binding of Val-tRF destabilizes helices h24, h44, and h45 and the anti-Shine-Dalgarno sequence of 16S rRNA. The binding position of this molecule partially overlaps with the translation initiation factor aIF1A and occludes the mRNA P-site codon. Moreover, we found that the binding of Val-tRF is associated with steric hindrance of the H69 base of 23S rRNA in the large ribosome subunit, thereby preventing 70S assembly. Our data exemplify how tRNA-derived fragments bind to ribosomes and provide new insights into the mechanisms underlying translation inhibition by Val-tRFs.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563199","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

Sensitive circulating tumor DNA-based residual disease detection in epithelial ovarian cancer. 基于循环肿瘤 DNA 的上皮性卵巢癌残留疾病灵敏检测。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-05 DOI: 10.26508/lsa.202402658

Heini Ml Kallio, Kalle Savolainen, Tuomo Virtanen, Lauri Ryyppö, Hanna Selin, Päivi Martikainen, Synnöve Staff, Kati Kivinummi, Joonatan Sipola, Juuso Vuorinen, Jussi Nikkola, Matti Nykter, Annika Auranen, Matti Annala

{"title":"Sensitive circulating tumor DNA-based residual disease detection in epithelial ovarian cancer.","authors":"Heini Ml Kallio, Kalle Savolainen, Tuomo Virtanen, Lauri Ryyppö, Hanna Selin, Päivi Martikainen, Synnöve Staff, Kati Kivinummi, Joonatan Sipola, Juuso Vuorinen, Jussi Nikkola, Matti Nykter, Annika Auranen, Matti Annala","doi":"10.26508/lsa.202402658","DOIUrl":"https://doi.org/10.26508/lsa.202402658","url":null,"abstract":"Epithelial ovarian cancer (EOC) is one of the leading causes of cancer-related death in women worldwide, and is characterized by a high rate of recurrence after surgery and chemotherapy. We sought to implement a circulating tumor DNA (ctDNA)-based blood test for more accurate post-operative surveillance of this disease. We analyzed 264 plasma samples collected between June 2016 and September 2021 from 63 EOC patients using tumor-guided plasma cell-free DNA analysis to detect residual disease after treatment. Assay specificity was verified using cross-patient analysis of 1,195 control samples. ctDNA was detected in 51 of 55 (93%) samples at diagnosis, and 18 of 18 (100%) samples at progression. Positive ctDNA in the last on-treatment sample was associated with rapid progression (median 1.02 versus 3.38 yr, HR = 5.63, P < 0.001) and reduced overall survival (median 2.31 versus NR yr, HR = 8.22, P < 0.001) in patients with high-grade serous cancer. In the case of 12 patients, ctDNA assays detected progression earlier than standard surveillance, with a median lead time of 5.9 mo. To approach the physical limits of ctDNA detection, five patients were analyzed using ultra-sensitive assays interrogating 479-1,856 tumor mutations, capable of tracking ctDNA fractions down to 0.0004%. Our results demonstrate that ctDNA assays achieve high sensitivity and specificity in detecting post-operative residual disease in EOC.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563198","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

DEFA1A3 DNA gene-dosage regulates the kidney innate immune response during upper urinary tract infection. DEFA1A3 DNA 基因剂量调节上尿路感染时肾脏的先天性免疫反应

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-05 DOI: 10.26508/lsa.202302462

Jorge J Canas, Samuel W Arregui, Shaobo Zhang, Taylor Knox, Christi Calvert, Vijay Saxena, Andrew L Schwaderer, David S Hains

{"title":"DEFA1A3 DNA gene-dosage regulates the kidney innate immune response during upper urinary tract infection.","authors":"Jorge J Canas, Samuel W Arregui, Shaobo Zhang, Taylor Knox, Christi Calvert, Vijay Saxena, Andrew L Schwaderer, David S Hains","doi":"10.26508/lsa.202302462","DOIUrl":"https://doi.org/10.26508/lsa.202302462","url":null,"abstract":"Antimicrobial peptides (AMPs) are host defense effectors with potent neutralizing and immunomodulatory functions against invasive pathogens. The AMPs α-Defensin 1-3/DEFA1A3 participate in innate immune responses and influence patient outcomes in various diseases. DNA copy-number variations in DEFA1A3 have been associated with severity and outcomes in infectious diseases including urinary tract infections (UTIs). Specifically, children with lower DNA copy numbers were more susceptible to UTIs. The mechanism of action by which α-Defensin 1-3/DEFA1A3 copy-number variations lead to UTI susceptibility remains to be explored. In this study, we use a previously characterized transgenic knock-in of the human DEFA1A3 gene mouse to dissect α-Defensin 1-3 gene dose-dependent antimicrobial and immunomodulatory roles during uropathogenic Escherichia coli (UPEC) UTI. We elucidate the relationship between kidney neutrophil- and collecting duct intercalated cell-derived α-Defensin 1-3/DEFA1A3 expression and UTI. We further describe cooperative effects between α-Defensin 1-3 and other AMPs that potentiate the neutralizing activity against UPEC. Cumulatively, we demonstrate that DEFA1A3 directly protects against UPEC meanwhile impacting pro-inflammatory innate immune responses in a gene dosage-dependent manner.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563100","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

Differential effects of translation inhibitors on Plasmodium berghei liver stage parasites. 翻译抑制剂对疟原虫肝阶段寄生虫的不同影响

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-04 DOI: 10.26508/lsa.202302540

James L McLellan, Kirsten K Hanson

{"title":"Differential effects of translation inhibitors on Plasmodium berghei liver stage parasites.","authors":"James L McLellan, Kirsten K Hanson","doi":"10.26508/lsa.202302540","DOIUrl":"https://doi.org/10.26508/lsa.202302540","url":null,"abstract":"Increasing numbers of antimalarial compounds are being identified that converge mechanistically at inhibition of cytoplasmic translation, regardless of the molecular target or mechanism. A deeper understanding of how their effectiveness as liver stage translation inhibitors relates to their chemoprotective potential could prove useful. Here, we probed that relationship using the Plasmodium berghei-HepG2 liver stage infection model. After determining translation inhibition EC50s for five compounds, we tested them at equivalent effective concentrations to compare the parasite response to, and recovery from, a brief period of translation inhibition in early schizogony, followed by parasites to 120 h post-infection to assess antiplasmodial effects of the treatment. We show compound-specific heterogeneity in single parasite and population responses to translation inhibitor treatment, with no single metric strongly correlated to the release of hepatic merozoites for all compounds. We also demonstrate that DDD107498 is capable of exerting antiplasmodial effects on translationally arrested liver stage parasites and uncover unexpected growth dynamics during the liver stage. Our results demonstrate that translation inhibition efficacy does not determine antiplasmodial efficacy for these compounds.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563196","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

Acetylation of Rec8 cohesin complexes regulates reductional chromosome segregation in meiosis. Rec8凝聚素复合物的乙酰化调节减数分裂过程中的还原染色体分离。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-04 DOI: 10.26508/lsa.202402606

Ziqiang Li, Yu Liu, Andrew W Jones, Yoshinori Watanabe

引用次数: 0

Genetic mutation of Cep76 results in male infertility due to abnormal sperm tail composition. Cep76 基因突变会导致精子尾部成分异常，从而导致男性不育。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-03 DOI: 10.26508/lsa.202302452

Brendan J Houston, D Jo Merriner, G Gemma Stathatos, Joseph H Nguyen, Anne E O'Connor, Alexandra M Lopes, Donald F Conrad, Mark Baker, Jessica Em Dunleavy, Moira K O'Bryan

{"title":"Genetic mutation of Cep76 results in male infertility due to abnormal sperm tail composition.","authors":"Brendan J Houston, D Jo Merriner, G Gemma Stathatos, Joseph H Nguyen, Anne E O'Connor, Alexandra M Lopes, Donald F Conrad, Mark Baker, Jessica Em Dunleavy, Moira K O'Bryan","doi":"10.26508/lsa.202302452","DOIUrl":"https://doi.org/10.26508/lsa.202302452","url":null,"abstract":"The transition zone is a specialised gate at the base of cilia/flagella, which separates the ciliary compartment from the cytoplasm and strictly regulates protein entry. We identified a potential new regulator of the male germ cell transition zone, CEP76. We demonstrated that CEP76 was involved in the selective entry and incorporation of key proteins required for sperm function and fertility into the ciliary compartment and ultimately the sperm tail. In the mutant, sperm tails were shorter and immotile as a consequence of deficits in essential sperm motility proteins including DNAH2 and AKAP4, which accumulated at the sperm neck in the mutant. Severe annulus, fibrous sheath, and outer dense fibre abnormalities were also detected in sperm lacking CEP76. Finally, we identified that CEP76 dictates annulus positioning and structure. This study suggests CEP76 as a male germ cell transition zone protein and adds further evidence to the hypothesis that the spermatid transition zone and annulus are part of the same functional structure.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563193","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

VCP/p97 mediates nuclear targeting of non-ER-imported prion protein to maintain proteostasis. VCP/p97 介导非 ER 导入的朊病毒蛋白的核靶向，以维持蛋白稳态。

IF 4.4 2区生物学

Life Science Alliance Pub Date : 2024-04-03 DOI: 10.26508/lsa.202302456

Papiya Banik, Koustav Ray, Janine Kamps, Qi-Yin Chen, Hendrik Luesch, Konstanze F Winklhofer, Jörg Tatzelt

{"title":"VCP/p97 mediates nuclear targeting of non-ER-imported prion protein to maintain proteostasis.","authors":"Papiya Banik, Koustav Ray, Janine Kamps, Qi-Yin Chen, Hendrik Luesch, Konstanze F Winklhofer, Jörg Tatzelt","doi":"10.26508/lsa.202302456","DOIUrl":"https://doi.org/10.26508/lsa.202302456","url":null,"abstract":"Mistargeting of secretory proteins in the cytosol can trigger their aggregation and subsequent proteostasis decline. We have identified a VCP/p97-dependent pathway that directs non-ER-imported prion protein (PrP) into the nucleus to prevent the formation of toxic aggregates in the cytosol. Upon impaired translocation into the ER, PrP interacts with VCP/p97, which facilitates nuclear import mediated by importin-ß. Notably, the cytosolic interaction of PrP with VCP/p97 and its nuclear import are independent of ubiquitination. In vitro experiments revealed that VCP/p97 binds non-ubiquitinated PrP and prevents its aggregation. Inhibiting binding of PrP to VCP/p97, or transient proteotoxic stress, promotes the formation of self-perpetuating and partially proteinase resistant PrP aggregates in the cytosol, which compromised cellular proteostasis and disrupted further nuclear targeting of PrP. In the nucleus, RNAs keep PrP in a soluble and non-toxic conformation. Our study revealed a novel ubiquitin-independent role of VCP/p97 in the nuclear targeting of non-imported secretory proteins and highlights the impact of the chemical milieu in triggering protein misfolding.","PeriodicalId":18081,"journal":{"name":"Life Science Alliance","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563202","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