IF 6.4 1区生物学

eLife Pub Date : 2024-11-04 DOI: 10.7554/eLife.92737

Lianhua Qin, Junfang Xu, Jianxia Chen, Sen Wang, Ruijuan Zheng, Zhenling Cui, Zhonghua Liu, Xiangyang Wu, Jie Wang, Xiaochen Huang, Zhaohui Wang, Mingqiao Wang, Rong Pan, Stefan H E Kaufmann, Xun Meng, Lu Zhang, Wei Sha, Haipeng Liu

{"title":"Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth.","authors":"Lianhua Qin, Junfang Xu, Jianxia Chen, Sen Wang, Ruijuan Zheng, Zhenling Cui, Zhonghua Liu, Xiangyang Wu, Jie Wang, Xiaochen Huang, Zhaohui Wang, Mingqiao Wang, Rong Pan, Stefan H E Kaufmann, Xun Meng, Lu Zhang, Wei Sha, Haipeng Liu","doi":"10.7554/eLife.92737","DOIUrl":"10.7554/eLife.92737","url":null,"abstract":"Deeper understanding of the crosstalk between host cells and Mycobacterium tuberculosis (Mtb) provides crucial guidelines for the rational design of novel intervention strategies against tuberculosis (TB). Mycobacteria possess a unique complex cell wall with arabinogalactan (AG) as a critical component. AG has been identified as a virulence factor of Mtb which is recognized by host galectin-9. Here, we demonstrate that galectin-9 directly inhibited mycobacterial growth through AG-binding property of carbohydrate-recognition domain 2. Furthermore, IgG antibodies with AG specificity were detected in the serum of TB patients. Based on the interaction between galectin-9 and AG, we developed a monoclonal antibody (mAb) screening assay and identified AG-specific mAbs which profoundly inhibit Mtb growth. Mechanistically, proteomic profiling and morphological characterizations revealed that AG-specific mAbs regulate AG biosynthesis, thereby inducing cell wall swelling. Thus, direct AG-binding by galectin-9 or antibodies contributes to protection against TB. Our findings pave the way for the rational design of novel immunotherapeutic strategies for TB control.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Perturbations in eIF3 subunit stoichiometry alter expression of ribosomal proteins and key components of the MAPK signaling pathways. eIF3 亚基化学计量的紊乱会改变核糖体蛋白和 MAPK 信号通路关键成分的表达。

IF 6.4 1区生物学

eLife Pub Date : 2024-11-04 DOI: 10.7554/eLife.95846

Anna Herrmannová, Jan Jelínek, Klára Pospíšilová, Farkas Kerényi, Tomáš Vomastek, Kathleen Watt, Jan Brábek, Mahabub Pasha Mohammad, Susan Wagner, Ivan Topisirovic, Leoš Shivaya Valášek

{"title":"Perturbations in eIF3 subunit stoichiometry alter expression of ribosomal proteins and key components of the MAPK signaling pathways.","authors":"Anna Herrmannová, Jan Jelínek, Klára Pospíšilová, Farkas Kerényi, Tomáš Vomastek, Kathleen Watt, Jan Brábek, Mahabub Pasha Mohammad, Susan Wagner, Ivan Topisirovic, Leoš Shivaya Valášek","doi":"10.7554/eLife.95846","DOIUrl":"10.7554/eLife.95846","url":null,"abstract":"Protein synthesis plays a major role in homeostasis and when dysregulated leads to various pathologies including cancer. To this end, imbalanced expression of eukaryotic translation initiation factors (eIFs) is not only a consequence but also a driver of neoplastic growth. eIF3 is the largest, multi-subunit translation initiation complex with a modular assembly, where aberrant expression of one subunit generates only partially functional subcomplexes. To comprehensively study the effects of eIF3 remodeling, we contrasted the impact of eIF3d, eIF3e or eIF3h depletion on the translatome of HeLa cells using Ribo-seq. Depletion of eIF3d or eIF3e, but not eIF3h reduced the levels of multiple components of the MAPK signaling pathways. Surprisingly, however, depletion of all three eIF3 subunits increased MAPK/ERK pathway activity. Depletion of eIF3e and partially eIF3d also increased translation of TOP mRNAs that encode mainly ribosomal proteins and other components of the translational machinery. Moreover, alterations in eIF3 subunit stoichiometry were often associated with changes in translation of mRNAs containing short uORFs, as in the case of the proto-oncogene MDM2 and the transcription factor ATF4. Collectively, perturbations in eIF3 subunit stoichiometry exert specific effect on the translatome comprising signaling and stress-related transcripts with complex 5' UTRs that are implicated in homeostatic adaptation to stress and cancer.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Coupling of saccade plans to endogenous attention during urgent choices. 紧急选择时，囊跳计划与内源性注意力的耦合。

IF 6.4 1区生物学

eLife Pub Date : 2024-11-04 DOI: 10.7554/eLife.97883

Allison T Goldstein, Terrence R Stanford, Emilio Salinas

{"title":"Coupling of saccade plans to endogenous attention during urgent choices.","authors":"Allison T Goldstein, Terrence R Stanford, Emilio Salinas","doi":"10.7554/eLife.97883","DOIUrl":"10.7554/eLife.97883","url":null,"abstract":"The neural mechanisms that willfully direct attention to specific locations in space are closely related to those for generating targeting eye movements (saccades). However, the degree to which the voluntary deployment of attention to a location necessarily activates a corresponding saccade plan remains unclear. One problem is that attention and saccades are both automatically driven by salient sensory events; another is that the underlying processes unfold within tens of milliseconds only. Here, we use an urgent task design to resolve the evolution of a visuomotor choice on a moment-by-moment basis while independently controlling the endogenous (goal-driven) and exogenous (salience-driven) contributions to performance. Human participants saw a peripheral cue and, depending on its color, either looked at it (prosaccade) or looked at a diametrically opposite, uninformative non-cue (antisaccade). By varying the luminance of the stimuli, the exogenous contributions could be cleanly dissociated from the endogenous process guiding the choice over time. According to the measured time courses, generating a correct antisaccade requires about 30 ms more processing time than generating a correct prosaccade based on the same perceptual signal. The results indicate that saccade plans elaborated during fixation are biased toward the location where attention is endogenously deployed, but the coupling is weak and can be willfully overridden very rapidly.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Caspases promote cell proliferation after necrosis. Caspases 在细胞坏死后促进细胞增殖。

IF 6.4 1区生物学

eLife Pub Date : 2024-11-04 DOI: 10.7554/eLife.103786

Prathibha Yarikipati, Andreas Bergmann

引用次数: 0

Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM. 重新评估金黄色葡萄球菌主要肽聚糖水解酶 lysostaphin 和 LytM 的底物特异性。

IF 6.4 1区生物学

eLife Pub Date : 2024-11-04 DOI: 10.7554/eLife.93673

Lina Antenucci, Salla Virtanen, Chandan Thapa, Minne Jartti, Ilona Pitkänen, Helena Tossavainen, Perttu Permi

{"title":"Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM.","authors":"Lina Antenucci, Salla Virtanen, Chandan Thapa, Minne Jartti, Ilona Pitkänen, Helena Tossavainen, Perttu Permi","doi":"10.7554/eLife.93673","DOIUrl":"10.7554/eLife.93673","url":null,"abstract":"Orchestrated action of peptidoglycan (PG) synthetases and hydrolases is vital for bacterial growth and viability. Although the function of several PG synthetases and hydrolases is well understood, the function, regulation, and mechanism of action of PG hydrolases characterised as lysostaphin-like endopeptidases have remained elusive. Many of these M23 family members can hydrolyse glycyl-glycine peptide bonds and show lytic activity against Staphylococcus aureus whose PG contains a pentaglycine bridge, but their exact substrate specificity and hydrolysed bonds are still vaguely determined. In this work, we have employed NMR spectroscopy to study both the substrate specificity and the bond cleavage of the bactericide lysostaphin and the S. aureus PG hydrolase LytM. Yet, we provide substrate-level evidence for the functional role of these enzymes. Indeed, our results show that the substrate specificities of these structurally highly homologous enzymes are similar, but unlike observed earlier both LytM and lysostaphin prefer the D-Ala-Gly cross-linked part of mature peptidoglycan. However, we show that while lysostaphin is genuinely a glycyl-glycine hydrolase, LytM can also act as a D-alanyl-glycine endopeptidase.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Difficulty in artificial word learning impacts targeted memory reactivation and its underlying neural signatures. 人工单词学习的困难会影响目标记忆的重新激活及其潜在的神经特征。

IF 6.4 1区生物学

eLife Pub Date : 2024-11-04 DOI: 10.7554/eLife.90930

Arndt-Lukas Klaassen, Björn Rasch

{"title":"Difficulty in artificial word learning impacts targeted memory reactivation and its underlying neural signatures.","authors":"Arndt-Lukas Klaassen, Björn Rasch","doi":"10.7554/eLife.90930","DOIUrl":"10.7554/eLife.90930","url":null,"abstract":"Sleep associated memory consolidation and reactivation play an important role in language acquisition and learning of new words. However, it is unclear to what extent properties of word learning difficulty impact sleep associated memory reactivation. To address this gap, we investigated in 22 young healthy adults the effectiveness of auditory targeted memory reactivation (TMR) during non-rapid eye movement sleep of artificial words with easy and difficult to learn phonotactical properties. Here, we found that TMR of the easy words improved their overnight memory performance, whereas TMR of the difficult words had no effect. By comparing EEG activities after TMR presentations, we found an increase in slow wave density independent of word difficulty, whereas the spindle-band power nested during the slow wave up-states - as an assumed underlying activity of memory reactivation - was significantly higher in the easy/effective compared to the difficult/ineffective condition. Our findings indicate that word learning difficulty by phonotactics impacts the effectiveness of TMR and further emphasize the critical role of prior encoding depth in sleep associated memory reactivation.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"12 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

IF 6.4 1区生物学

eLife Pub Date : 2024-11-04 DOI: 10.7554/eLife.96155

Xingfeng Shao, Qinyang Shou, Kimberly Felix, Brandon Ojogho, Xuejuan Jiang, Brian T Gold, Megan M Herting, Eric L Goldwaser, Peter Kochunov, Elliot Hong, Ioannis Pappas, Meredith Braskie, Hosung Kim, Steven Cen, Kay Jann, Danny J J Wang

{"title":"Age-related decline in blood-brain barrier function is more pronounced in males than females in parietal and temporal regions.","authors":"Xingfeng Shao, Qinyang Shou, Kimberly Felix, Brandon Ojogho, Xuejuan Jiang, Brian T Gold, Megan M Herting, Eric L Goldwaser, Peter Kochunov, Elliot Hong, Ioannis Pappas, Meredith Braskie, Hosung Kim, Steven Cen, Kay Jann, Danny J J Wang","doi":"10.7554/eLife.96155","DOIUrl":"10.7554/eLife.96155","url":null,"abstract":"The blood-brain barrier (BBB) plays a pivotal role in protecting the central nervous system (CNS), and shielding it from potential harmful entities. A natural decline of BBB function with aging has been reported in both animal and human studies, which may contribute to cognitive decline and neurodegenerative disorders. Limited data also suggest that being female may be associated with protective effects on BBB function. Here, we investigated age and sex-dependent trajectories of perfusion and BBB water exchange rate (kw) across the lifespan in 186 cognitively normal participants spanning the ages of 8-92 years old, using a non-invasive diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL) MRI technique. We found that the pattern of BBB kw decline with aging varies across brain regions. Moreover, results from our DP-pCASL technique revealed a remarkable decline in BBB kw beginning in the early 60 s, which was more pronounced in males. In addition, we observed sex differences in parietal and temporal regions. Our findings provide in vivo results demonstrating sex differences in the decline of BBB function with aging, which may serve as a foundation for future investigations into perfusion and BBB function in neurodegenerative and other brain disorders.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Nuclear translocation of SIRT4 mediates deacetylation of U2AF2 to modulate renal fibrosis through alternative splicing-mediated upregulation of CCN2. SIRT4的核转位通过替代剪接介导的CCN2上调，介导U2AF2的去乙酰化，从而调节肾脏纤维化。

IF 6.4 1区生物学

eLife Pub Date : 2024-11-04 DOI: 10.7554/eLife.98524

Guangyan Yang, Jiaqing Xiang, Xiaoxiao Yang, Xiaomai Liu, Yanchun Li, Lixing Li, Lin Kang, Zhen Liang, Shu Yang

{"title":"Nuclear translocation of SIRT4 mediates deacetylation of U2AF2 to modulate renal fibrosis through alternative splicing-mediated upregulation of CCN2.","authors":"Guangyan Yang, Jiaqing Xiang, Xiaoxiao Yang, Xiaomai Liu, Yanchun Li, Lixing Li, Lin Kang, Zhen Liang, Shu Yang","doi":"10.7554/eLife.98524","DOIUrl":"10.7554/eLife.98524","url":null,"abstract":"TGF-β stimulates CCN2 expression which in turn amplifies TGF-β signaling. This process promotes extracellular matrix production and accelerates the pathological progression of fibrotic diseases. Alternative splicing plays an important role in multiple disease development, while U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential factor in the early steps of pre-mRNA splicing. However, the molecular mechanism underlying abnormal CCN2 expression upon TGF-β stimulation remains unclear. This study elucidates that SIRT4 acts as a master regulator for CCN2 expression in response to TGF-β by modulating U2AF2-mediated alternative splicing. Analyses of renal biopsy specimens from patients with CKD and mouse fibrotic kidney tissues revealed marked nuclear accumulation of SIRT4. The tubulointerstitial fibrosis was alleviated by global deletion or tubular epithelial cell (TEC)-specific knockout of Sirt4, and aggravated by adeno-associated virus-mediated SIRT4 overexpression in TECs. Furthermore, SIRT4 was found to translocate from the mitochondria to the cytoplasm through the BAX/BAK pore under TGF-β stimulation. In the cytoplasm, TGF-β activated the ERK pathway and induced the phosphorylation of SIRT4 at Ser36, which further promoted its interaction with importin α1 and subsequent nuclear translocation. In the nucleus, SIRT4 was found to deacetylate U2AF2 at K413, facilitating the splicing of CCN2 pre-mRNA to promote CCN2 protein expression. Importantly, exosomes containing anti-SIRT4 antibodies were found to effectively mitigate the UUO-induced kidney fibrosis in mice. Collectively, these findings indicated that SIRT4 plays a role in kidney fibrosis by regulating CCN2 expression via the pre-mRNA splicing.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Cryo-electron tomographic investigation of native hippocampal glutamatergic synapses. 原生海马谷氨酸能突触的低温电子断层扫描研究

IF 6.4 1区生物学

eLife Pub Date : 2024-11-04 DOI: 10.7554/eLife.98458

Aya Matsui, Cathy Spangler, Johannes Elferich, Momoko Shiozaki, Nikki Jean, Xiaowei Zhao, Maozhen Qin, Haining Zhong, Zhiheng Yu, Eric Gouaux

引用次数: 0

Human DCP1 is crucial for mRNA decapping and possesses paralog-specific gene regulating functions. 人类 DCP1 对 mRNA 脱帽至关重要，并具有旁系特异性基因调控功能。

IF 6.4 1区生物学

eLife Pub Date : 2024-11-01 DOI: 10.7554/eLife.94811

Ting-Wen Chen, Hsiao-Wei Liao, Michelle Noble, Jing-Yi Siao, Yu-Hsuan Cheng, Wei-Chung Chiang, Yi-Tzu Lo, Chung-Te Chang

{"title":"Human DCP1 is crucial for mRNA decapping and possesses paralog-specific gene regulating functions.","authors":"Ting-Wen Chen, Hsiao-Wei Liao, Michelle Noble, Jing-Yi Siao, Yu-Hsuan Cheng, Wei-Chung Chiang, Yi-Tzu Lo, Chung-Te Chang","doi":"10.7554/eLife.94811","DOIUrl":"10.7554/eLife.94811","url":null,"abstract":"The mRNA 5'-cap structure removal by the decapping enzyme DCP2 is a critical step in gene regulation. While DCP2 is the catalytic subunit in the decapping complex, its activity is strongly enhanced by multiple factors, particularly DCP1, which is the major activator in yeast. However, the precise role of DCP1 in metazoans has yet to be fully elucidated. Moreover, in humans, the specific biological functions of the two DCP1 paralogs, DCP1a and DCP1b, remain largely unknown. To investigate the role of human DCP1, we generated cell lines that were deficient in DCP1a, DCP1b, or both to evaluate the importance of DCP1 in the decapping machinery. Our results highlight the importance of human DCP1 in decapping process and show that the EVH1 domain of DCP1 enhances the mRNA-binding affinity of DCP2. Transcriptome and metabolome analyses outline the distinct functions of DCP1a and DCP1b in human cells, regulating specific endogenous mRNA targets and biological processes. Overall, our findings provide insights into the molecular mechanism of human DCP1 in mRNA decapping and shed light on the distinct functions of its paralogs.","PeriodicalId":11640,"journal":{"name":"eLife","volume":"13 ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

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