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最新文章

• Dissecting spatial patterning and signaling with directional diffusion in spatial multi- omics AI翻译
  作者：Wang, Haiyun; Yuan, Zhiyuan; Su, Yansen; Zheng, Chunhou; Sun, Xiaoqiang
  作者单位：Wuhan University of Science & Technology; Wuhan University of Science & Technology; Fudan University; Anhui University; Sun Yat Sen University
  摘要：Spatial multi- omics sequencing enables the simultaneous profiling of transcriptomics, proteomics, and epigenomics at a spatial resolution, offering insights into complex tissue organization and molecular regulation. However, the effective integration of multiple omics modalities in a spatial context remains a major challenge. Here, we present SpaDDM, a spatial multi- omics integration framework based on directional diffusion and inter- and intracellular signaling flow analysis. SpaDDM employs...
• Spike destabilization attenuates Mink Cluster 5 SARS- CoV-2 AI翻译
  作者：Faraone, Julia N.; Li, Pei; Hong, Junping; Zang, Jinkai; Liu, Yajie; Xu, Yan; Qu, Panke; Evans, John P.; Chen, Jie; Zheng, Yi - Min; Chen, Phylip; Peeples, Mark E.; Xu, Kai; Liu, Shan - Lu
  作者单位：University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; Nationwide Childrens Hospital; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University
  摘要：Throughout the COVID-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown the capacity to infect a wide range of nonhuman hosts, including farmed mink. In early 2020, a mink-associated variant, termed mink cluster 5 (MC5V), emerged in Denmark and spread to mink farmers and their household contacts but failed to cause a sustained outbreak and eventually disappeared. Here, we demonstrate that the spike protein (S) of MC5V is intrinsically unstable and impaired in p...
• Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ42 fibrils with cross-seeding activity AI翻译
  作者：Konstantoulea, Katerina; Ramakers, Meine; Borrie, Sarah C.; T'syen, Dries; Moechars, Daan; Sliwinska, Malgorzata A.; Pradhan, Brajabandhu; Albertini, Giulia; Baligacs, Nora; Tsaka, Grigoria; Houben, Bert; Fiers, Mark; Gallardo, Rodrigo; Dewilde, Maarten; Thal, Dietmar Rudolf; Willem, Michael; Neher, Jonas J.; De Strooper, Bart; Rousseau, Frederic; Schymkowitz, Joost
  作者单位：Flanders Institute for Biotechnology (VIB); KU Leuven; KU Leuven; Flanders Institute for Biotechnology (VIB); KU Leuven; KU Leuven; KU Leuven; KU Leuven; KU Leuven; University Hospital Leuven; University of Munich; Helmholtz Association; German Center for Neurodegenerative Diseases (DZNE); University of Munich
  摘要：The prevailing view frames microglia and macrophages as guardians against amyloid demonstrating that human phagocytic cells, including differentiated THP-1 macrophages and hESC-derived microglia, are not merely passive responders but active producers of extracellular, seeding-competent Af342 fibrils, the amyloid species most strongly linked to parenchymal plaque formation and neurodegeneration. These cell-generated aggregates differ structurally and functionally from synthetic fibrils, display...
• Moral stereotyping in large language models AI翻译
  作者：Zewail, Aliah; Figueroa, Alexandra; Graham, Jesse; Atari, Mohammad
  作者单位：University of Massachusetts System; University of Massachusetts Amherst; University of California System; University of California Berkeley; Utah System of Higher Education; University of Utah
  摘要：Can Large Language Models (LLMs) accurately estimate various societies' moral values? Here, we query the perceptions of LLMs regarding the moral norms of the average person from 48 nations and compare them to a large-scale (n = 90,802) survey of six moral values (Care, Equality, Proportionality, Loyalty, Authority, and Purity) from those populations. Our findings indicate that LLMs poorly capture the moral diversity around the globe, systematically overestimating some moral values (particularl...
• HPV16 E6 oncoprotein promotes microhomology-mediated viral integration by increasing PolΘ protein expression AI翻译
  作者：Zhu, Guangli; Asada, Shuhei; Abeykoon, Jithma P.; Sun, Lifang; Mukkavalli, Sirisha; D'andrea, Alan D.
  作者单位：Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Dana-Farber Cancer Institute; Sun Yat Sen University; Mayo Clinic
  摘要：Integration of the high-risk human papillomavirus 16 (HPV16) genome into the host chromosome, frequently driven by microhomology-mediated end joining (MMEJ), is a critical step in the carcinogenesis of HPV-associated tumors. However, the mechanisms by which viral oncoproteins manipulate the error-prone MMEJ pathway remain poorly defined. Here, we demonstrate that the HPV16 E6 oncoprotein upregulates MMEJ to facilitate viral genome integration. This heightened MMEJ activity is driven by a marke...
• Reverse engineering what makes a symbol memorable AI翻译
  作者：Roberts, Brady R. T.; Bainbridge, Wilma A.
  作者单位：University of Chicago; University of Chicago; University of Chicago
  摘要：Symbols may represent the first form of human visual communication, yet little is known about the cognitive and neural mechanisms supporting memory for these pervasive graphics. By investigating memory for everyday symbols, we can understand how abstract concepts are concretized with simple referents and later processed in visual memory systems. Recently, symbols have been found to be highly memorable, especially relative to words, but it remains unclear what drives their heightened memorabili...
• D- amino acid aminotransferase1 regulates grain chalkiness in rice by modulating endoplasmic reticulum stress response AI翻译
  作者：Dong, Hui; Lei, Jie; Tian, Yunlu; Liu, Juan; Yang, Hang; Jiang, Xiaokang; Zhang, Rushuang; Zhang, Yu; Chen, Rongbo; Bao, Yiqun; Liu, Feng; Ren, Yulong; Lu, Yaping; Liu, Xi; Liu, Shijia; Yang, Xue; Duan, Erchao; Teng, Xuan; Wang, Yunlong; Gu, Chuanwei; Zhang, Yipeng; Chen, Xiaoli; Zhang, Yunpeng; Xu, Hongyi; Sha, Rui; Xu, Xia; Li, Ruomeng; Li, Gongyu; Wang, Yihua; Wan, Jianmin
  作者单位：Nanjing Agricultural University; Nankai University; Nanjing Agricultural University; Chinese Academy of Agricultural Sciences; Institute of Crop Sciences, CAAS
  摘要：D-amino acids are key components of the bacterial cell wall and play important roles in neural communication and inflammatory responses in animals. However, knowledge about D-amino acid metabolism and physiological functions in plants is limited. Here, we isolated and characterized a rice D-amino acid aminotransferase1, OsDAAT1, which maternally regulates rice grain chalkiness through map-based cloning and a subsequent complementation test. We found that OsDAAT1 is highly expressed in the vasc...
• Direct evidence of acid-driven protein desolvation AI翻译
  作者：Hamdi, Farzad; Skalidis, Ioannis; Schwerin, Inken Kaja; Belapure, Jaydeep; Semchonok, Dmitry A.; Kyrilis, Fotis L.; Tuting, Christian; Muller, Johannes; Kunze, Georg; Kastritis, Panagiotis L.
  作者单位：Martin Luther University Halle Wittenberg; Martin Luther University Halle Wittenberg; Utrecht University; Leipzig University; Universidade Nova de Lisboa; National Hellenic Research Foundation; Martin Luther University Halle Wittenberg; Leipzig University; Leipzig University; Martin Luther University Halle Wittenberg
  摘要：Water and its ability to modulate the protonation states of biomolecules govern the physical chemistry of life, dictating their metabolic functions. However, how amino acid protonation alters protein hydration and solubility is an open question since Kuntz and Kauzmann proposed pH-driven protein desolvation in 1974. Here, in a series of high-resolution cryoelectron microscopy structures of a protein complex at different pH values (from pH 9.0 to 3.5), we examined thousands of observable hydrat...
• Dynamic reprogramming of the tumor immune network via multicycle checkpoint degradation for cancer immunotherapy AI翻译
  作者：Shi, Tao; Wu, Yuanyuan; Cai, Yiran; Luo, Yuting; Ren, Shiji; Cao, Yaning; Tang, Yin; Jiang, Zizheng; Hu, Shiyao; Xie, Wenxue; Chen, Yuanyuan; Shen, Lin; Xing, Hang; Wei, Jia
  作者单位：Nanjing University; Hunan University; Nanjing University; Nanjing Medical University
  摘要：The efficacy of immune checkpoint blockade is often limited by intrinsic immunosuppressive networks within the tumor immune microenvironment (TIME). Despite progress in cancer treatment, current extracellular targeted protein degradation approaches often overlook the multicellular distribution and crosstalk of immune checkpoints. Here we reported a Receptor--mediated Endolysosomal recYcling Chimera (RECYC) platform. RECYC employs a CI-M6PR-targeting aptamer that remains stable across late endo...
• Extended local anesthesia enabled by flavonoid permeation enhancers AI翻译
  作者：Han, Yiyuan; Torre, Matthew; Ma, Xiaojing; Xue, Tianrui; Wang, Yuan; Jo, Sooyeon; Fujita, Akie; Bean, Bruce P.; Kohane, Daniel S.
  作者单位：Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Boston Children's Hospital; Baylor College of Medicine; Harvard University; Harvard Medical School
  摘要：Site 1 sodium channel blockers (S1SCBs), such as tetrodotoxin (TTX) and neosaxitoxin, are ultrapotent local anesthetics with low tissue toxicity. Their duration of action is relatively brief, but increasing the dose can lead to systemic toxicity. Here, we report that selected flavonoids-puerarin (PUE), naringenin, and kaempferol-prolong nerve block from S1SCBs 4-to 25-fold. Using both tympanic membrane (TM) permeation and sciatic nerve fluorescence distribution models, we demonstrate the flavo...