Science AdvancesPub Date : 2025-04-09DOI: 10.1126/sciadv.adt9196
Tian Wu, Xinglong Ren, David Cornil, Claudio Quarti, Ian E. Jacobs, Lu Zhang, Naoya Fukui, David Beljonne, Hiroshi Nishihara, Henning Sirringhaus
{"title":"Revealing the charge transport physics in metallic coordination nanosheets by thermoelectric and magnetotransport measurements","authors":"Tian Wu, Xinglong Ren, David Cornil, Claudio Quarti, Ian E. Jacobs, Lu Zhang, Naoya Fukui, David Beljonne, Hiroshi Nishihara, Henning Sirringhaus","doi":"10.1126/sciadv.adt9196","DOIUrl":"10.1126/sciadv.adt9196","url":null,"abstract":"<div >We have studied the charge transport physics of high-quality conducting coordination nanosheets films based on the benchmark material copper benzenehexathiol (CuBHT) by measuring multiple thermoelectric and magnetotransport coefficients on the same film. The films exhibit a metallic temperature dependence of the conductivity over a wide temperature range, but below 15 kelvin charge transport becomes dominated by weak localization and electron-electron interactions. Temperature-dependent Hall, Seebeck, and Nernst measurements consistently indicate the existence of ambipolar transport characteristics in CuBHT. A two-band analysis has been used to extract transport parameters for electron and hole carriers as a function of temperature. The results show that contributions from electron and hole conduction in CuBHT are of comparable magnitude, revealing the complexity of charge transport and allowing one to identify strategies for enhancing the thermoelectric transport coefficients of such conducting coordination nanosheets.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt9196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806333","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}
Science AdvancesPub Date : 2025-04-09DOI: 10.1126/sciadv.adt9693
Zahra S. Navabi, Ryan Peters, Beatrice Gulner, Arun Cherkkil, Eunsong Ko, Farnoosh Dadashi, Jacob O. Brien, Michael Feldkamp, Suhasa B. Kodandaramaiah
{"title":"Computer vision–guided rapid and precise automated cranial microsurgeries in mice","authors":"Zahra S. Navabi, Ryan Peters, Beatrice Gulner, Arun Cherkkil, Eunsong Ko, Farnoosh Dadashi, Jacob O. Brien, Michael Feldkamp, Suhasa B. Kodandaramaiah","doi":"10.1126/sciadv.adt9693","DOIUrl":"10.1126/sciadv.adt9693","url":null,"abstract":"<div >A common procedure that allows interfacing with the brain is cranial microsurgery, wherein small to large craniotomies are performed on the overlying skull for insertion of neural interfaces or implantation of optically clear windows for long-term cranial observation. Performing craniotomies requires skill, time, and precision to avoid damaging the brain and dura. Here, we present a computer vision–guided craniotomy robot (CV-Craniobot) that uses machine learning to accurately estimate the dorsal skull anatomy from optical coherence tomography images. Instantaneous information of skull morphology is used by a robotic mill to rapidly and precisely remove the skull from a desired craniotomy location. We show that the CV-Craniobot can perform small (2- to 4-millimeter diameter) craniotomies with near 100% success rates within 2 minutes and large craniotomies encompassing most of the dorsal cortex in less than 10 minutes. Thus, the CV-Craniobot enables rapid and precise craniotomies, reducing surgery time compared to human practitioners and eliminating the need for long training.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt9693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806346","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}
{"title":"Fully circular shapable transparent paperboard with closed-loop recyclability and marine biodegradability across shallow to deep sea","authors":"Noriyuki Isobe, Keiko Tanaka, Shun’ichi Ishii, Yasuhiro Shimane, Satoshi Okada, Kazuho Daicho, Wataru Sakuma, Kojiro Uetani, Toshihiro Yoshimura, Katsunori Kimoto, Satoshi Kimura, Tsuguyuki Saito, Ryota Nakajima, Masashi Tsuchiya, Tetsuro Ikuta, Shinsuke Kawagucci, Tadahisa Iwata, Hidetaka Nomaki","doi":"10.1126/sciadv.ads2426","DOIUrl":"10.1126/sciadv.ads2426","url":null,"abstract":"<div >To mitigate marine pollution from single-use plastics, it is crucial to transition to next-generation commodity materials that are derived from biomass and are recyclable and marine biodegradable even at abyssal depths in case of the accidental release to the ocean. Here, we develop an optically transparent millimeter-thick paperboard called transparent paperboard (tPB) through dissolution and coagulation of cellulose. The tPB is made entirely of pristine cellulose and compositionally identical to paper. A cup-shaped tPB can hold just-boiled water without an internal film coating because of its high wet tensile properties and anisotropic thermal properties. In addition, the spent tPB is material recyclable in a closed system, where all chemicals and water are also recyclable. Furthermore, the marine biodegradability of tPB across shallow to abyssal depths is confirmed by on-site degradation tests and metagenomic analyses. Hence, tPB is expected to serve as a key fully circular commodity material in sustainable societies of the future.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads2426","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806347","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}
{"title":"Asparagine transporter supports macrophage inflammation via histone phosphorylation","authors":"Chuanlong Wang, Yuyi Ye, Muyang Zhao, Qingyi Chen, Bingnan Liu, Wenkai Ren","doi":"10.1126/sciadv.ads3506","DOIUrl":"10.1126/sciadv.ads3506","url":null,"abstract":"<div >Solute carrier (SLC) family is essential for immune responses; nevertheless, whether and how SLCs regulate macrophage inflammation remains unclear. Here, we demonstrate that K636 acetylation mediates high abundance of SLC6A14 in inflammatory macrophages. Notably, the pharmacological inhibition or genetic modulation of SLC6A14 reduces macrophage interleukin-1β (IL-1β) secretion dependently of lower asparagine uptake and subsequently enhanced nuclear LKB1. Mechanistically, nuclear LKB1 lessens MAPK pathway–mediated NLRP3 inflammasome activation by increased histone 3 S10/28 phosphorylation-dependent cyclin O transcription. Moreover, myeloid <i>Slc6a14</i> deficiency alleviates pulmonary inflammation via suppressing inflammatory macrophage responses. Overall, these results uncover a network by which SLC6A14-mediated asparagine uptake orchestrates macrophage inflammation through histone phosphorylation, providing a crucial target for modulation of inflammatory diseases.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads3506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806280","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}
Science AdvancesPub Date : 2025-04-09DOI: 10.1126/sciadv.ads9562
Huachun Deng, Xiong Jiang, Yao Zhang, Yixuan Zeng, Hamdi Barkaoui, Shumin Xiao, Shaohua Yu, Yuri Kivshar, Qinghai Song
{"title":"Chiral lasing enabled by strong coupling","authors":"Huachun Deng, Xiong Jiang, Yao Zhang, Yixuan Zeng, Hamdi Barkaoui, Shumin Xiao, Shaohua Yu, Yuri Kivshar, Qinghai Song","doi":"10.1126/sciadv.ads9562","DOIUrl":"10.1126/sciadv.ads9562","url":null,"abstract":"<div >Chiral quasi-bound states in the continuum are spin-dependent high-<i>Q</i> resonances in meta-photonic structures that are realized by perturbing symmetry-protected optical states by engineering in-plane and out-of-plane asymmetries, and they support chiral lasing in the vertical direction. Here, we explore the coupling between two resonances in a chiral metasurface and introduce a mechanism for high-purity chiral laser emission. We reveal that two resonances with nearly orthogonal polarizations become strongly coupled in an engineered chiral metasurface. The inherent phase difference of the resonances, associated with the coherent destruction on the decay channel, can endow high-<i>Q</i> factor and maximize chirality to one of the hybrid modes. We verify this approach experimentally by measuring transmission spectra, angle-resolved photoluminescence, and laser emission. We believe that this mechanism allows breaking restrictions on conventional chiral quasi-BIC lasing, enabling the realization of chiral emission at any designed direction.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.ads9562","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806334","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}
Science AdvancesPub Date : 2025-04-09DOI: 10.1126/sciadv.adu5091
Michael J. McKenna, Felix Kraus, João P.L. Coelho, Muskaan Vasandani, Jiuchun Zhang, Benjamin M. Adams, Joao A. Paulo, J. Wade Harper, Sichen Shao
{"title":"ARMC1 partitions between distinct complexes and assembles MIRO with MTFR to control mitochondrial distribution","authors":"Michael J. McKenna, Felix Kraus, João P.L. Coelho, Muskaan Vasandani, Jiuchun Zhang, Benjamin M. Adams, Joao A. Paulo, J. Wade Harper, Sichen Shao","doi":"10.1126/sciadv.adu5091","DOIUrl":"10.1126/sciadv.adu5091","url":null,"abstract":"<div >Maintaining an optimal mitochondrial distribution is critical to ensure an adequate supply of energy and metabolites to support important cellular functions. How cells balance dynamic mitochondrial processes to achieve homeostasis is incompletely understood. Here, we show that ARMC1 partitioning between distinct mitochondrial protein complexes is a key determinant of mitochondrial distribution. In one complex, the mitochondrial trafficking adaptor MIRO recruits ARMC1, which mediates the assembly of a mitochondrial fission regulator (MTFR). MTFR stability depends on ARMC1, and MIRO-MTFR complexes specifically antagonize retrograde mitochondrial movement. In another complex, DNAJC11 facilitates ARMC1 release from mitochondria. Disrupting MIRO-MTFR assembly fails to rescue aberrant mitochondrial distributions clustered in the perinuclear area observed with ARMC1 deletion, while disrupting ARMC1 interaction with DNAJC11 leads to excessive mitochondrially localized ARMC1 and distinct mitochondrial defects. Thus, the abundance and trafficking impact of MIRO-MTFR complexes require ARMC1, whose mito-cytoplasmic shuttling balanced by DNAJC11 tunes steady-state mitochondrial distributions.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu5091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806351","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}
{"title":"Invention of an oral medication for cardiac Fabry disease caused by RNA mis-splicing","authors":"Tomonari Awaya, Masahiko Ajiro, Hiroko Kobayashi, Teruo Sawada, Kentoku Gotanda, Toshiharu Noji, Naohiro Takemoto, Kei Iida, Megumu K. Saito, Dau-Ming Niu, Masatoshi Hagiwara","doi":"10.1126/sciadv.adt9695","DOIUrl":"10.1126/sciadv.adt9695","url":null,"abstract":"<div >Pathogenic RNA splicing variants have emerged as promising therapeutic targets due to their role in disease while preserving coding sequences. In this study, we developed RECTAS-2.0, a small molecule designed to correct RNA mis-splicing caused by the <i>GLA</i> c.639+919G>A mutation, which leads to the inclusion of a 57-nucleotide poison exon, resulting in later-onset Fabry disease, particularly prevalent in East Asia. RECTAS-2.0 restored normal <i>GLA</i> mRNA splicing and α-galactosidase activity in patient-derived B-lymphoblastoid cell lines and induced pluripotent stem cell–derived cardiomyocytes. Furthermore, oral administration of RECTAS-2.0 effectively corrected splicing in a transgenic mouse model, demonstrating its substantial splice-switching activity and safety for clinical application. RECTAS-2.0 demonstrated potential applicability to other genetic disorders that involve similar exon competition. These findings underscore the therapeutic potential of RECTAS-2.0 for Fabry disease and highlight its broader implications for RNA splicing–targeted therapies in genetic disorders.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt9695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806093","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}
Science AdvancesPub Date : 2025-04-09DOI: 10.1126/sciadv.adu2318
Jianjun Wang, Xuemei Yang, Zirong Huang, Yong Su, Xinxin Zhang, Ni Song, Peng Wang, Chen Yang, Hongzhi Cao, Xue-Wei Liu, Xuechen Li, Sheng Chen, Ming Li
{"title":"Synthesis of Campylobacter jejuni capsular oligosaccharides and identification of a potential O-antigen against campylobacteriosis","authors":"Jianjun Wang, Xuemei Yang, Zirong Huang, Yong Su, Xinxin Zhang, Ni Song, Peng Wang, Chen Yang, Hongzhi Cao, Xue-Wei Liu, Xuechen Li, Sheng Chen, Ming Li","doi":"10.1126/sciadv.adu2318","DOIUrl":"10.1126/sciadv.adu2318","url":null,"abstract":"<div >The vaccines against campylobacteriosis are urgently needed because of the rising multidrug resistance of pathogenic <i>Campylobacter jejuni</i>. The capsular polysaccharides of these bacteria, containing unique 6-deoxy-β-<span>d</span>-<i>ido</i>-heptopyranosyl or <span>l</span>-<i>glycero</i>-β-<span>d</span>-<i>ido</i>-heptopyranosyl residues, have emerged as attractive antigens. Expeditious assembly of the oligosaccharides derived from these glycans is challenging because β-<span>d</span>-idopyranosidic linkages are formidable to directly construct. Furthermore, whether the synthetic <i>C. jejuni</i> oligosaccharides could induce sufficient immunogenicity as the potential antigens remains unexplored. Here, we report a protocol for directly forming β-<span>d</span>-idopyranosidic bonds using α-<span>d</span>-6-deoxy-<i>ido</i>-heptopyranosyl, α-<span>d</span>-idopyranosyl, and <span>d</span>-/<span>l</span>-<i>glycero</i>-α-<span>d</span>-<i>ido</i>-heptopyranosyl <i>ortho</i>-hexynylbenzoates as glycosylating agents under gold(I) catalysis. To demonstrate the versatility of these methods, concise synthesis of conjugatable <i>C. jejuni</i> capsular di-/tetra-/hexa-/octasaccharides, having a backbone of [→3)-6-deoxy-β-<span>d</span>-<i>ido</i>-heptopyranosyl-(1→4)-2-acetamido-2-deoxy-β-<span>d</span>-glucopyranosyl-(1→], has been achieved. The immunogenicity assessment of the glycoconjugates, prepared by conjugating the synthesized oligosaccharides to cross-reactive material 197, reveals the disaccharide as a potential <i>O</i>-antigen for developing vaccines against campylobacteriosis. This work should facilitate development of synthetic vaccines against <i>Campylobacter</i> infections.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adu2318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806094","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}
Science AdvancesPub Date : 2025-04-09DOI: 10.1126/sciadv.adt9694
Taihua Yang, Jiahao Ge, Lei Huang, Xinye Zhu, Dexin Zhang, Siyuan Tang, Jie Zhao, Yinhe Ma, Mei Long, Xiaochen Bo, Jie Li, Yiqing Zhang, Qinggong Yuan, Amar Deep Sharma, Michael Ott, Hongquan Geng, Yicheng Zhao, Liang Zhang, Haifa Shen, Hangwen Li, Dali Li, Ping Wan, Qiang Xia
{"title":"Preclinical evaluation of AGT mRNA replacement therapy for primary hyperoxaluria type I disease","authors":"Taihua Yang, Jiahao Ge, Lei Huang, Xinye Zhu, Dexin Zhang, Siyuan Tang, Jie Zhao, Yinhe Ma, Mei Long, Xiaochen Bo, Jie Li, Yiqing Zhang, Qinggong Yuan, Amar Deep Sharma, Michael Ott, Hongquan Geng, Yicheng Zhao, Liang Zhang, Haifa Shen, Hangwen Li, Dali Li, Ping Wan, Qiang Xia","doi":"10.1126/sciadv.adt9694","DOIUrl":"10.1126/sciadv.adt9694","url":null,"abstract":"<div >Primary hyperoxaluria type 1 (PH1) is a rare inherited liver disorder caused by alanine glyoxylate aminotransferase (AGT) dysfunction, leading to accumulation of glyoxylate which is then converted into oxalate. Excessive oxalate results in kidney damage due to deposition of oxalate crystals. We have developed an mRNA-based protein replacement therapy for PH1 to restore normal glyoxylate to glycine metabolism. Sequence optimized human <i>AGT</i> mRNA (<i>hAGT</i> mRNA) was encapsulated in lipopolyplex (LPP) and produced functional AGT enzyme in peroxisomes. Pharmacokinetics and pharmacodynamics (PK/PD) were evaluated in vitro and in vivo. PK demonstrated that <i>AGT</i> mRNA and AGT protein maintained high expression levels for up to 48 hours. A single 2 mg/kg dose in <i>Agxt</i>Q84<sup>−/−</sup> rats achieved a 70% reduction in urinary oxalate. Toxicological assessment identified the highest nonserious toxic dose (HNSTD) as 2 mg/kg. These findings affirm the efficacy and safety of <i>hAGT</i> mRNA/LPP and support its clinical application in PH1 treatment.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adt9694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806342","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}
Science AdvancesPub Date : 2025-04-09DOI: 10.1126/sciadv.adq2519
Moriah R. Arnold, Gabriel M. Cohn, Kezia Catharina Oxe, Somarr N. Elliott, Cynthia Moore, Allison May Zhou, Peter V. Laraia, Sahar Shekoohi, Dillon Brownell, Rosalie C. Sears, Randall L. Woltjer, Charles K. Meshul, Stephan N. Witt, Dorthe H. Larsen, Vivek K. Unni
{"title":"Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma","authors":"Moriah R. Arnold, Gabriel M. Cohn, Kezia Catharina Oxe, Somarr N. Elliott, Cynthia Moore, Allison May Zhou, Peter V. Laraia, Sahar Shekoohi, Dillon Brownell, Rosalie C. Sears, Randall L. Woltjer, Charles K. Meshul, Stephan N. Witt, Dorthe H. Larsen, Vivek K. Unni","doi":"10.1126/sciadv.adq2519","DOIUrl":"10.1126/sciadv.adq2519","url":null,"abstract":"<div >Although an increased risk of the skin cancer melanoma in people with Parkinson’s disease (PD) has been shown in multiple studies, the mechanisms involved are poorly understood, but increased expression of the PD-associated protein alpha-synuclein (αSyn) in melanoma cells may be important. Our previous work suggests that αSyn can facilitate DNA double-strand break (DSB) repair, promoting genomic stability. We now show that αSyn is preferentially enriched within the nucleolus in melanoma, where it colocalizes with DNA damage markers and DSBs. Inducing DSBs specifically within nucleolar ribosomal DNA (rDNA) increases αSyn levels near sites of damage. αSyn knockout increases DNA damage within the nucleolus at baseline, after specific rDNA DSB induction, and prolongs the rate of recovery from this induced damage. αSyn is important downstream of ataxia-telangiectasia–mutated signaling to facilitate MDC1-mediated 53BP1 recruitment to DSBs, reducing micronuclei formation and promoting cellular proliferation, migration, and invasion.</div>","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"11 15","pages":""},"PeriodicalIF":11.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.science.org/doi/reader/10.1126/sciadv.adq2519","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143806345","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}
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