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作者：Zhang, Yue; Sigaeva, Alina; Elias-Llumbet, Arturo; Fan, Siyu; Woudstra, Willem; de Boer, Rinse; Escobar, Elkin; Reyes-San-Martin, Claudia; Kisabacak, Robin; Oosterhuis, Dorenda; Gorter, Alan R.; Coenen, Britt; Martinez, Felipe P. Perona; van den Bogaart, Geert; Olinga, Peter; Schirhagl, Romana
作者单位：University of Groningen; Universidad de Chile; University of Groningen; Universidad de Antioquia
摘要：Free radical generation plays a key role in many biological processes including cell communication, maturation, and aging. In addition, free radical generation is usually elevated in cells under stress as is the case for many different pathological conditions. In liver tissue, cells produce radicals when exposed to toxic substances but also, for instance, in cancer, alcoholic liver disease and liver cirrhosis. However, free radicals are small, short- lived, and occur in low abundance making th...
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作者：Calvert, Jacob; Randall, Dana
作者单位：University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology
摘要：The global steady state of a system in thermal equilibrium exponentially favors configurations with lesser energy. This principle is a powerful explanation of selforganization because energy is a local property of configurations. For nonequilibrium systems, there is no such property for which an analogous principle holds, hence no common explanation of the diverse forms of self-organization they exhibit. However, a flurry of recent empirical results has shown that a local property of configura...
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作者：Liu, Jia; Wang, Yang; Tian, Miaomiao; Xia, Mingjie; Zheng, Yi; Hao, Miao; Qian, Yuqiang; Shu, Hengyao; Zhang, Wenxia; Peng, Pinghui; Zhao, Zhexuan; Dong, Kejian; Peng, Wanting; Gao, Tian; Li, Zhanjun; Jin, Xin; Wei, Min; Feng, Yunpeng
作者单位：Northeast Normal University - China; Jilin University; Jilin University; Jilin University
摘要：Elevated lipid synthesis is one of the best-characterized metabolic alterations in cancer and crucial for membrane expansion. As a key rate-limiting enzyme in de novo fatty acid synthesis, ATP-citrate lyase (ACLY) is frequently up-regulated in tumors and regulated by posttranslational modifications (PTMs). Despite emerging evidence showing O-GlcNAcylation on ACLY, its biological function still remains unknown. Here, we observed a significant upregulation of ACLY O-GlcNAcylation in various type...
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作者：Davis, Ester; Avniel-Polak, Shani; Abu-Kamel, Shahd; Antman, Israel; Saadoun, Tsipora; Brim, Chava; Jumaa, Mohammad; Maron, Yariv; Maimon, Ofra; Bel-Ange, Anat; Atlan, Karine; Tzur, Tomer; Abu Akar, Firas; Wald, Ori; Izhar, Uzi; Hecht, Merav; Grozinsky-Glasberg, Simona; Drier, Yotam
作者单位：Hebrew University of Jerusalem; Hebrew University of Jerusalem; Hadassah University Hospital; Hebrew University of Jerusalem; Hadassah University Hospital; Hebrew University of Jerusalem; Hebrew University of Jerusalem; Hadassah University Hospital; Hebrew University of Jerusalem; Hadassah University Hospital; Tel Aviv University; Al-Quds University; Tel Aviv University
摘要：Well- differentiated low- grade lung neuroendocrine tumors (lung carcinoids or LNETs) are histopathologically classified as typical and atypical LNETs, but each subtype is still heterogeneous at both the molecular level and its clinical manifestation. Here, we report genome-wide profiles of primary LNETs' cis- regulatory elements by H3K27ac ChIP-seq with matching RNA-seq profiles. Analysis of these regulatory landscapes revealed three regulatory subtypes, independent of the typical/atypical cl...
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作者：McCoy, R. Thomas; Yao, Shunyu; Friedman, Dan; Hardy, Mathew D.; Griffiths, Thomas L.
作者单位：Princeton University; Princeton University; Yale University; Yale University; OpenAI
摘要：The widespread adoption of large language models (LLMs) makes it important to recognize their strengths and limitations. We argue that to develop a holistic understanding of these systems, we must consider the problem that they were trained to solve: next-word prediction over Internet text. By recognizing the pressures that this task exerts, we can make predictions about the strategies that LLMs will adopt, allowing us to reason about when they will succeed or fail. Using this approach-which w...
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作者：Condezo, Yazmine B.; Sainz-Urruela, Raquel; Gomez-H, Laura; Salas-Lloret, Daniel; Felipe-Medina, Natalia; Bradley, Rachel; Wolff, Ian D.; Tanis, Stephanie; Barbero, Jose Luis; Sanchez-Martin, Manuel; de Rooij, Dirk; Hendriks, Ivo A.; Nielsen, Michael L.; Gonzalez-Prieto, Roman; Cohen, Paula E.; Pendas, Alberto M.; Llano, Elena
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作者：Givnish, Thomas J.
作者单位：University of Wisconsin System; University of Wisconsin Madison
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作者：Villasante, Camila M.; Deng, Xinyue; Cohen, Joel E.; Hudspeth, A. J.
作者单位：Rockefeller University; Rockefeller University; Columbia University; Columbia University; University of Chicago; Howard Hughes Medical Institute; Rockefeller University
摘要：Mechanical force controls the opening and closing of mechanosensitive ion channels atop the hair bundles of the inner ear. The filamentous tip link connecting transduction channels to the tallest neighboring stereocilium modulates the force transmitted to the channels and thus changes their probability of opening. Each tip link comprises four molecules: a dimer of protocadherin 15 (PCDH15) and a dimer of cadherin 23, all of which are stabilized by Ca2+ binding. Using a high- speed optical trap...
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作者：Morimitsu, Yuma; Browne, Christopher A.; Liu, Zhe; Severino, Paul G.; Gopinadhan, Manesh; Sirota, Eric B.; Altintas, Ozcan; Edmond, Kazem V.; Osuji, Chinedum O.
作者单位：University of Pennsylvania; University of Pennsylvania
摘要：Liquid-liquid phase separation, whereby two liquids spontaneously demix, is ubiquitous in industrial, environmental, and biological processes. While isotropic fluids are known to condense into spherical droplets in the binodal region, these dynamics are poorly understood for structured fluids. Here, we report the unique observation of condensate networks, which spontaneously assemble during the demixing of a mesogen from a solvent. Condensing mesogens form rapidly elongating filaments, rather ...
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作者：Oury, Julien; Gamallo-Lana, Begona; Santana, Leah; Steyaert, Christophe; Vergoossen, Dana L. E.; Mar, Adam C.; Vankerckhoven, Bernhardt; Silence, Karen; Vanhauwaert, Roeland; Huijbers, Maartje G.; Burden, Steven J.
作者单位：New York University; New York University; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Leiden University; Leiden University Medical Center (LUMC); Leiden University - Excl LUMC; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital
摘要：Myasthenia gravis (MG) is a chronic and severe disease of the skeletal neuromuscular junction (NMJ) in which the effects of neurotransmitters are attenuated, leading to muscle weakness. In the most common forms of autoimmune MG, antibodies attack components of the postsynaptic membrane, including the acetylcholine receptor (AChR) or with the low- density lipoprotein- related receptor 4 (Lrp4) to form the signaling receptor for neuronal Agrin, a nerve- derived synaptic organizer. Pathogenic ant...
