Science Advances最新文献_第10页

Nucleo-cytoplasmic environment modulates spatiotemporal p53 phase separation.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.ads0427

Debalina Datta, Ambuja Navalkar, Arunima Sakunthala, Ajoy Paul, Komal Patel, Shalaka Masurkar, Laxmikant Gadhe, Shouvik Manna, Arpita Bhattacharyya, Shinjinee Sengupta, Manisha Poudyal, Jyoti Devi, Ajay Singh Sawner, Pradeep Kadu, Ranjit Shaw, Satyaprakash Pandey, Semanti Mukherjee, Nitisha Gahlot, Kundan Sengupta, Samir K Maji

{"title":"Nucleo-cytoplasmic environment modulates spatiotemporal p53 phase separation.","authors":"Debalina Datta, Ambuja Navalkar, Arunima Sakunthala, Ajoy Paul, Komal Patel, Shalaka Masurkar, Laxmikant Gadhe, Shouvik Manna, Arpita Bhattacharyya, Shinjinee Sengupta, Manisha Poudyal, Jyoti Devi, Ajay Singh Sawner, Pradeep Kadu, Ranjit Shaw, Satyaprakash Pandey, Semanti Mukherjee, Nitisha Gahlot, Kundan Sengupta, Samir K Maji","doi":"10.1126/sciadv.ads0427","DOIUrl":"10.1126/sciadv.ads0427","url":null,"abstract":"Liquid-liquid phase separation of various transcription factors into biomolecular condensates plays an essential role in gene regulation. Here, using cellular models and in vitro studies, we show the spatiotemporal formation and material properties of p53 condensates that might dictate its function. In particular, p53 forms liquid-like condensates in the nucleus of cells, which can bind to DNA and perform transcriptional activity. However, cancer-associated mutations promote misfolding and partially rigidify the p53 condensates with impaired DNA binding ability. Irrespective of wild-type and mutant forms, the partitioning of p53 into cytoplasm leads to the condensate formation, which subsequently undergoes rapid solidification. In vitro studies show that abundant nuclear components such as RNA and nonspecific DNA promote multicomponent phase separation of the p53 core domain and maintain their liquid-like property, whereas specific DNA promotes its dissolution into tetrameric functional p53. This work provides mechanistic insights into how the life cycle and DNA binding properties of p53 might be regulated by phase separation.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 50","pages":"eads0427"},"PeriodicalIF":11.7,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

3D seismic evidence for a single Early Pleistocene glaciation of the central North Sea

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adq6089

Dag Ottesen, Christine L. Batchelor, Helge Løseth, Harald Brunstad

引用次数: 0

An alternate route for cellulose microfibril biosynthesis in plants

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-13 DOI: 10.1126/sciadv.adr5188

Eric M. Roberts, Kai Yuan, Arielle M. Chaves, Ethan T. Pierce, Rosalie Cresswell, Ray Dupree, Xiaolan Yu, Richard L. Blanton, Shu-Zon Wu, Magdalena Bezanilla, Paul Dupree, Candace H. Haigler, Alison W. Roberts

{"title":"An alternate route for cellulose microfibril biosynthesis in plants","authors":"Eric M. Roberts, Kai Yuan, Arielle M. Chaves, Ethan T. Pierce, Rosalie Cresswell, Ray Dupree, Xiaolan Yu, Richard L. Blanton, Shu-Zon Wu, Magdalena Bezanilla, Paul Dupree, Candace H. Haigler, Alison W. Roberts","doi":"10.1126/sciadv.adr5188","DOIUrl":"https://doi.org/10.1126/sciadv.adr5188","url":null,"abstract":"Similar to cellulose synthases (CESAs), cellulose synthase–like D (CSLD) proteins synthesize β-1,4-glucan in plants. CSLDs are important for tip growth and cytokinesis, but it was unknown whether they form membrane complexes in vivo or produce microfibrillar cellulose. We produced viable CESA-deficient mutants of the moss Physcomitrium patens to investigate CSLD function without interfering CESA activity. Microscopy and spectroscopy showed that CESA-deficient mutants synthesize cellulose microfibrils that are indistinguishable from those in vascular plants. Correspondingly, freeze-fracture electron microscopy revealed rosette-shaped particle assemblies in the plasma membrane that are indistinguishable from CESA-containing rosette cellulose synthesis complexes (CSCs). Our data show that proteins other than CESAs, most likely CSLDs, produce cellulose microfibrils in P. patens protonemal filaments. The data suggest that the specialized roles of CSLDs in cytokinesis and tip growth are based on differential expression and different interactions with microtubules and possibly Ca 2+ , rather than structural differences in the microfibrils they produce.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"82 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of dosing schedules on performance of rotavirus vaccines in Ghana.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-13 Epub Date: 2024-12-11 DOI: 10.1126/sciadv.adn4176

Ernest O Asare, Mohammad A Al-Mamun, George E Armah, Benjamin A Lopman, Virginia E Pitzer

引用次数: 0

Landscape changes caused by the 2024 Noto Peninsula earthquake in Japan.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-06 Epub Date: 2024-12-04 DOI: 10.1126/sciadv.adp9193

Yo Fukushima, Daisuke Ishimura, Naoya Takahashi, Yoshiya Iwasa, Luca C Malatesta, Takayuki Takahashi, Chi-Hsien Tang, Keisuke Yoshida, Shinji Toda

引用次数: 0

A trafficking regulatory subnetwork governs α_Vβ₆ integrin-HER2 cross-talk to control breast cancer invasion and drug resistance.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-06 Epub Date: 2024-12-04 DOI: 10.1126/sciadv.adk9944

Horacio Maldonado, Marcel Dreger, Lara D Bedgood, Theano Kyriakou, Katarzyna I Wolanska, Megan E Rigby, Valeria E Marotta, Justine M Webster, Jun Wang, Emma V Rusilowicz-Jones, John F Marshall, Judy M Coulson, Iain R Macpherson, Adam Hurlstone, Mark R Morgan

{"title":"A trafficking regulatory subnetwork governs αVβ6 integrin-HER2 cross-talk to control breast cancer invasion and drug resistance.","authors":"Horacio Maldonado, Marcel Dreger, Lara D Bedgood, Theano Kyriakou, Katarzyna I Wolanska, Megan E Rigby, Valeria E Marotta, Justine M Webster, Jun Wang, Emma V Rusilowicz-Jones, John F Marshall, Judy M Coulson, Iain R Macpherson, Adam Hurlstone, Mark R Morgan","doi":"10.1126/sciadv.adk9944","DOIUrl":"10.1126/sciadv.adk9944","url":null,"abstract":"HER2 and αVβ6 integrin are independent predictors of breast cancer survival and metastasis. We identify an αVβ6/HER2 cross-talk mechanism driving invasion, which is dysregulated in drug-resistant HER2+ breast cancer cells. Proteomic analyses reveal ligand-bound αVβ6 recruits HER2 and a trafficking subnetwork, comprising guanosine triphosphatases RAB5 and RAB7A and the Rab regulator guanine nucleotide dissociation inhibitor 2 (GDI2). The RAB5/RAB7A/GDI2 functional module mediates direct cross-talk between αVβ6 and HER2, affecting receptor trafficking and signaling. Acute exposure to trastuzumab increases recruitment of the subnetwork to αVβ6, but trastuzumab resistance decouples GDI2 recruitment. GDI2, RAB5, and RAB7A cooperate to regulate migration and transforming growth factor-β activation to promote invasion. However, these mechanisms are dysregulated in trastuzumab-resistant cells. In patients, RAB5A, RAB7A, and GDI2 expression correlates with patient survival and αVβ6 expression predicts relapse following trastuzumab treatment. Thus, the RAB5/RAB7A/GDI2 subnetwork regulates αVβ6-HER2 cross-talk to drive breast cancer invasion but is subverted in trastuzumab-resistant cells to drive αVβ6-independent and HER2-independent tumor progression.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 49","pages":"eadk9944"},"PeriodicalIF":11.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Arabidopsis histone acetyltransferase complex coordinates cytoplasmic histone acetylation and nuclear chromatin accessibility.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-06 Epub Date: 2024-12-04 DOI: 10.1126/sciadv.adp1840

Chan-Juan Wu, Xin Xu, Dan-Yang Yuan, Zhen-Zhen Liu, Lian-Mei Tan, Yin-Na Su, Lin Li, She Chen, Xin-Jian He

{"title":"Arabidopsis histone acetyltransferase complex coordinates cytoplasmic histone acetylation and nuclear chromatin accessibility.","authors":"Chan-Juan Wu, Xin Xu, Dan-Yang Yuan, Zhen-Zhen Liu, Lian-Mei Tan, Yin-Na Su, Lin Li, She Chen, Xin-Jian He","doi":"10.1126/sciadv.adp1840","DOIUrl":"10.1126/sciadv.adp1840","url":null,"abstract":"Conserved type B histone acetyltransferases are recognized for their role in acetylating newly synthesized histones in the cytoplasm of eukaryotes. However, their involvement in regulating chromatin within the nucleus remains unclear. Our study shows that the Arabidopsis thaliana type B histone acetyltransferase HAG2 interacts with the histone chaperones MSI2, MSI3, and NASP, as well as the histones H3 and H4, forming a complex in both the cytoplasm and the nucleus. Within this complex, HAG2 and MSI2/3 constitute a histone acetylation module essential for acetylating histone H4 in the cytoplasm. Furthermore, this module works together with NASP to regulate histone acetylation, chromatin accessibility, and gene transcription in the nucleus. This complex enhances chromatin accessibility near transcription start sites while reducing accessibility near transcription termination sites. Our findings reveal a distinct role for the Arabidopsis type B histone acetyltransferase in the nucleus, shedding light on the coordination between cytoplasmic histone acetylation and nuclear chromatin regulation in plants.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 49","pages":"eadp1840"},"PeriodicalIF":11.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Atroposelective synthesis of axially chiral imidazo[1,2-a]pyridines via asymmetric multicomponent reaction.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-06 Epub Date: 2024-12-04 DOI: 10.1126/sciadv.adr6135

Shibin Hong, Wei Liu, Chongyi Zhang, Xiaoyu Yang

{"title":"Atroposelective synthesis of axially chiral imidazo[1,2-a]pyridines via asymmetric multicomponent reaction.","authors":"Shibin Hong, Wei Liu, Chongyi Zhang, Xiaoyu Yang","doi":"10.1126/sciadv.adr6135","DOIUrl":"10.1126/sciadv.adr6135","url":null,"abstract":"Imidazo[1,2-a]pyridines are privileged heterocycles with diverse applications in medicinal chemistry; however, the catalytic asymmetric synthesis of these heterocyclic structures remains underexplored. Herein, we present an efficient and modular approach for the atroposelective synthesis of axially chiral imidazo[1,2-a]pyridines via an asymmetric multicomponent reaction. By utilizing a chiral phosphoric acid catalyst, the Groebke-Blackburn-Bienaymé reaction involving various 6-aryl-2-aminopyridines, aldehydes, and isocyanides gave access to a wide range of imidazo[1,2-a]pyridine atropoisomers with high to excellent yields and enantioselectivities. Extensive control experiments underscored the pivotal role of the remote hydrogen bonding donor on the substrates in achieving high stereoselectivity for these reactions. The versatile derivatizations of these atropisomeric products, especially their role as an analog of NOBINs and their facile conversion into unique 6,6-spirocyclic products, further emphasize the merits of this methodology.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 49","pages":"eadr6135"},"PeriodicalIF":11.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comediation of voltage gating and ion charge in MXene membrane for controllable and selective monovalent cation separation.

IF 11.7 1区综合性期刊

Science Advances Pub Date : 2024-12-06 Epub Date: 2024-12-04 DOI: 10.1126/sciadv.ado3998

Xu Wang, Haiguang Zhang, Gaoliang Wei, Jiajian Xing, Shuo Chen, Xie Quan

{"title":"Comediation of voltage gating and ion charge in MXene membrane for controllable and selective monovalent cation separation.","authors":"Xu Wang, Haiguang Zhang, Gaoliang Wei, Jiajian Xing, Shuo Chen, Xie Quan","doi":"10.1126/sciadv.ado3998","DOIUrl":"10.1126/sciadv.ado3998","url":null,"abstract":"Artificial ion channels with controllable mono/monovalent cation separation fulfill important roles in biomedicine, ion separation, and energy conversion. However, it remains a daunting challenge to develop an artificial ion channel similar to biological ion channels due to ion-ion competitive transport and lack of ion-gating ability of channels. Here, we report a conductive MXene membrane with polydopamine-confined angstrom-scale channels and propose a voltage gating and ion charge comediation strategy to concurrently achieve gated and selective mono/monovalent cation separation. The membrane shows a highly switchable \"on-off\" ratio of ∼9.9 for K+ transport and an excellent K+/Li+ selectivity of 40.9, outperforming the ion selectivity of reported membranes with electrical gating (typically 1.5 to 6). Theoretical simulations reveal that the introduced high-charge cations such as Mg2+ enable the preferential distribution of target K+ over competing Li+ at the channel entrance, and the surface potential reduces the ionic transport energy barrier for allowing K+ to pass quickly through the channel.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"10 49","pages":"eado3998"},"PeriodicalIF":11.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Heat disproportionately kills young people: Evidence from wet-bulb temperature in Mexico

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-06 DOI: 10.1126/sciadv.adq3367

Andrew J. Wilson, R. Daniel Bressler, Catherine Ivanovich, Cascade Tuholske, Colin Raymond, Radley M. Horton, Adam Sobel, Patrick Kinney, Tereza Cavazos, Jeffrey G. Shrader

{"title":"Heat disproportionately kills young people: Evidence from wet-bulb temperature in Mexico","authors":"Andrew J. Wilson, R. Daniel Bressler, Catherine Ivanovich, Cascade Tuholske, Colin Raymond, Radley M. Horton, Adam Sobel, Patrick Kinney, Tereza Cavazos, Jeffrey G. Shrader","doi":"10.1126/sciadv.adq3367","DOIUrl":"https://doi.org/10.1126/sciadv.adq3367","url":null,"abstract":"Recent studies project that temperature-related mortality will be the largest source of damage from climate change, with particular concern for the elderly whom it is believed bear the largest heat-related mortality risk. We study heat and mortality in Mexico, a country that exhibits a unique combination of universal mortality microdata and among the most extreme levels of humid heat. Combining detailed measurements of wet-bulb temperature with age-specific mortality data, we find that younger people who are particularly vulnerable to heat: People under 35 years old account for 75% of recent heat-related deaths and 87% of heat-related lost life years, while those 50 and older account for 96% of cold-related deaths and 80% of cold-related lost life years. We develop high-resolution projections of humid heat and associated mortality and find that under the end-of-century SSP 3–7.0 emissions scenario, temperature-related deaths shift from older to younger people. Deaths among under-35-year-olds increase 32% while decreasing by 33% among other age groups.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"5 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0