Science Advances最新文献

dCasMINI-mediated therapy rescues photoreceptors degeneration in a mouse model of retinitis pigmentosa

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adn7540

Qing Wang, Xiaoshu Xu, Siyu Chen, Rui Lu, Liang Li, Chien-Hui Lo, Zhiquan Liu, Ke Ning, Tingting Li, Tia J. Kowal, Biao Wang, Mary E. Hartnett, Sui Wang, Lei S. Qi, Yang Sun

{"title":"dCasMINI-mediated therapy rescues photoreceptors degeneration in a mouse model of retinitis pigmentosa","authors":"Qing Wang, Xiaoshu Xu, Siyu Chen, Rui Lu, Liang Li, Chien-Hui Lo, Zhiquan Liu, Ke Ning, Tingting Li, Tia J. Kowal, Biao Wang, Mary E. Hartnett, Sui Wang, Lei S. Qi, Yang Sun","doi":"10.1126/sciadv.adn7540","DOIUrl":"https://doi.org/10.1126/sciadv.adn7540","url":null,"abstract":"Retinitis pigmentosa (RP) is characterized by degeneration of rod and cone photoreceptors that progresses to irreversible blindness. Now, there are no mutation-agnostic approaches to treat RP. Here, we utilized a single adeno-associated virus (AAV)–based CRISPR activation system to activate phosphodiesterase 6B (Pde6b) to mitigate the severe degeneration in Pde6a nmf363 mice. We demonstrate that transcriptional activation of Pde6b can rescue the loss of Pde6a , with preservation of retinal structure, restoration of electroretinography responses, and improvement of visual function as assessed by optokinetic response and looming-induced escape behaviors. These findings demonstrate the therapeutic potential of a dCasMINI-mediated activation strategy that provides a mutation-independent treatment for retinal degeneration. This study offers a promising therapeutic approach for RP and potentially other forms of genetic diseases.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"30 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841872","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

Hydroalkylation of unactivated olefins with C(sp 3 )─H compounds enabled by NiH-catalyzed radical relay 通过 NiH 催化自由基中继实现未活化烯烃与 C(sp 3 )-H 化合物的氢烷基化反应

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.ads6885

Jiang-Ling Shi, Youcheng Wang, Yufeng Han, Jinqi Chen, Xiaolan Pu, Ying Xia

{"title":"Hydroalkylation of unactivated olefins with C(sp 3 )─H compounds enabled by NiH-catalyzed radical relay","authors":"Jiang-Ling Shi, Youcheng Wang, Yufeng Han, Jinqi Chen, Xiaolan Pu, Ying Xia","doi":"10.1126/sciadv.ads6885","DOIUrl":"https://doi.org/10.1126/sciadv.ads6885","url":null,"abstract":"The hydroalkylation reaction of olefins with alkanes is a highly desirable synthetic transformation toward the construction of C(sp 3 )─C(sp 3 ) bonds. However, such transformation has proven to be challenging for unactivated olefins, particularly when the substrates lack directing groups or acidic C(sp 3 )─H bonds. Here, we address this challenge by merging NiH-catalyzed radical relay strategy with a HAT (hydrogen atom transfer) process. In this catalytic system, a nucleophilic alkyl radical is generated from a C(sp 3 )─H compound in the presence of a HAT promotor, which couples with an alkyl metallic intermediate generated from the olefin substrate with a NiH catalyst to form the C(sp 3 )─C(sp 3 ) bond. Starting from easily available materials, the reaction not only demonstrates wide functional group compatibility but also provides hydroalkylation products with regiodivergence and excellent enantioselectivity through effective catalyst control under mild conditions.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"82 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841870","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

A neurocognitive pathway for engineering artificial touch 人工触摸工程的神经认知途径

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adq6290

Ilana Nisky, Tamar R. Makin

引用次数: 0

Moo19 and B2: Structures of Schitoviridae podophages with T = 9 geometry and tailspikes with esterase activity

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adt0022

Sundharraman Subramanian, Silje M. Bergland Drarvik, Kendal R. Tinney, Sarah M. Doore, Kristin N. Parent

{"title":"Moo19 and B2: Structures of Schitoviridae podophages with T = 9 geometry and tailspikes with esterase activity","authors":"Sundharraman Subramanian, Silje M. Bergland Drarvik, Kendal R. Tinney, Sarah M. Doore, Kristin N. Parent","doi":"10.1126/sciadv.adt0022","DOIUrl":"https://doi.org/10.1126/sciadv.adt0022","url":null,"abstract":"Podophages are, by far, the least well studied of all the bacteriophages. Despite being classified together due to their short, noncontractile tails, there is a huge amount of diversity among members of this group. Of the podophages, the N4-like Schitoviridae family is the least well studied structurally and is quite divergent from well-characterized podophages such as T7 and P22. In this work, we isolate and fully characterize two members of the Schitoviridae family by cryo–electron microscopy, genetics, and biochemistry. We describe the capsid features of Moo19 and B2, including a decoration protein. In addition, we have fully modeled the tail machinery for both phages and identify proteins with esterase activity. Genetic knockouts of the host reveal factors specific for host attachment including key modifications to the O-antigen on the lipopolysaccharide. Moo19 and B2 are both Schitoviridae members, yet some distinct differences in the genome and structure place them into distinct clades.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"55 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841864","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

Terrestrial evidence for volcanogenic sulfate-driven cooling event ~30 kyr before the Cretaceous–Paleogene mass extinction 白垩纪-古近纪大灭绝前 30 千年火山硫酸盐驱动冷却事件的陆地证据

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.ado5478

Lauren K. O’Connor, Rhodri M. Jerrett, Gregory D. Price, Tyler R. Lyson, Sabine K. Lengger, Francien Peterse, Bart E. van Dongen

{"title":"Terrestrial evidence for volcanogenic sulfate-driven cooling event ~30 kyr before the Cretaceous–Paleogene mass extinction","authors":"Lauren K. O’Connor, Rhodri M. Jerrett, Gregory D. Price, Tyler R. Lyson, Sabine K. Lengger, Francien Peterse, Bart E. van Dongen","doi":"10.1126/sciadv.ado5478","DOIUrl":"https://doi.org/10.1126/sciadv.ado5478","url":null,"abstract":"Alongside the Chicxulub meteorite impact, Deccan volcanism is considered a primary trigger for the Cretaceous–Paleogene (K–Pg) mass extinction. Models suggest that volcanic outgassing of carbon and sulfur—potent environmental stressors—drove global temperature change, but the relative timing, duration, and magnitude of such change remains uncertain. Here, we use the organic paleothermometer MBT′ 5me and the carbon-isotope composition of two K–Pg-spanning lignites from the western Unites States, to test models of volcanogenic air temperature change in the ~100 kyr before the mass extinction. Our records show long-term warming of ~3°C, probably driven by Deccan CO 2 emissions, and reveal a transient (<10 kyr) ~5°C cooling event, coinciding with the peak of the Poladpur “pulse” of Deccan eruption ~30 kyr before the K–Pg boundary. This cooling was likely caused by the aerosolization of volcanogenic sulfur. Temperatures returned to pre-event values before the mass extinction, suggesting that, from the terrestrial perspective, volcanogenic climate change was not the primary cause of K–Pg extinction.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"30 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841830","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

Distinct impact modes of polygenic disposition to dyslexia in the adult brain

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adq2754

Sourena Soheili-Nezhad, Dick Schijven, Rogier B. Mars, Simon E. Fisher, Clyde Francks

{"title":"Distinct impact modes of polygenic disposition to dyslexia in the adult brain","authors":"Sourena Soheili-Nezhad, Dick Schijven, Rogier B. Mars, Simon E. Fisher, Clyde Francks","doi":"10.1126/sciadv.adq2754","DOIUrl":"https://doi.org/10.1126/sciadv.adq2754","url":null,"abstract":"Dyslexia is a common and partially heritable condition that affects reading ability. In a study of up to 35,231 adults, we explored the structural brain correlates of genetic disposition to dyslexia. Individual dyslexia-disposing genetic variants showed distinct patterns of association with brain structure. Independent component analysis revealed various brain networks that each had their own genomic profiles related to dyslexia susceptibility. Circuits involved in motor coordination, vision, and language were implicated. Polygenic scores for eight traits genetically correlated with dyslexia, including cognitive, behavioral, and reading-related psychometric measures, showed partial similarities to dyslexia in terms of brain-wide associations. Notably, microstructure of the internal capsule was consistently implicated across all of these genetic dispositions, while lower volume of the motor cortex was more specifically associated with dyslexia genetic disposition alone. These findings reveal genetic and neurobiological features that may contribute to dyslexia and its associations with other traits at the population level.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"1 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841833","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

Reactive vapor-phase dealloying-alloying turns oxides into sustainable bulk nano-structured porous alloys 反应气相脱合金将氧化物转化为可持续的大块纳米结构多孔合金

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.ads2140

Shaolou Wei, Yan Ma, Dierk Raabe

引用次数: 0

Deep representation learning of protein-protein interaction networks for enhanced pattern discovery

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adq4324

Rui Yan, Md Tauhidul Islam, Lei Xing

{"title":"Deep representation learning of protein-protein interaction networks for enhanced pattern discovery","authors":"Rui Yan, Md Tauhidul Islam, Lei Xing","doi":"10.1126/sciadv.adq4324","DOIUrl":"https://doi.org/10.1126/sciadv.adq4324","url":null,"abstract":"Protein-protein interaction (PPI) networks, where nodes represent proteins and edges depict myriad interactions among them, are fundamental to understanding the dynamics within biological systems. Despite their pivotal role in modern biology, reliably discerning patterns from these intertwined networks remains a substantial challenge. The essence of the challenge lies in holistically characterizing the relationships of each node with others in the network and effectively using this information for accurate pattern discovery. In this work, we introduce a self-supervised network embedding framework termed discriminative network embedding (DNE). Unlike conventional methods that primarily focus on direct or limited-order node proximity, DNE characterizes a node both locally and globally by harnessing the contrast between representations from neighboring and distant nodes. Our experimental results demonstrate DNE’s superior performance over existing techniques across various critical network analyses, including PPI inference and the identification of protein functional modules. DNE emerges as a robust strategy for node representation in PPI networks, offering promising avenues for diverse biomedical applications.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"145 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841866","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

Solvent-responsive covalent organic framework membranes for precise and tunable molecular sieving 用于精确和可调分子筛分的溶剂响应型共价有机框架膜

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.ads0260

Hao Yang, Haoyuan Zhang, Chengjun Kang, Chunqing Ji, Dongchen Shi, Dan Zhao

引用次数: 0

Future spinal reflex is embedded in primary motor cortex output

IF 13.6 1区综合性期刊

Science Advances Pub Date : 2024-12-18 DOI: 10.1126/sciadv.adq4194

Tatsuya Umeda, Osamu Yokoyama, Michiaki Suzuki, Miki Kaneshige, Tadashi Isa, Yukio Nishimura

{"title":"Future spinal reflex is embedded in primary motor cortex output","authors":"Tatsuya Umeda, Osamu Yokoyama, Michiaki Suzuki, Miki Kaneshige, Tadashi Isa, Yukio Nishimura","doi":"10.1126/sciadv.adq4194","DOIUrl":"https://doi.org/10.1126/sciadv.adq4194","url":null,"abstract":"Mammals can execute intended limb movements despite the fact that spinal reflexes involuntarily modulate muscle activity. To generate appropriate muscle activity, the cortical descending motor output must coordinate with spinal reflexes, yet the underlying neural mechanism remains unclear. We simultaneously recorded activities in motor-related cortical areas, afferent neurons, and forelimb muscles of monkeys performing reaching movements. Motor-related cortical areas, predominantly primary motor cortex (M1), encode subsequent afferent activities attributed to forelimb movement. M1 also encodes a subcomponent of muscle activity evoked by these afferent activities, corresponding to spinal reflexes. Furthermore, selective disruption of the afferent pathway specifically reduced this subcomponent of muscle activity, suggesting that M1 output drives muscle activity not only through direct descending pathways but also through the “transafferent” pathway composed of descending plus subsequent spinal reflex pathways. Thus, M1 provides optimal motor output based on an internal forward model that prospectively computes future spinal reflexes.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"79 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841860","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