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作者：Gomez, Ignacio Lopez; Wan, Zhong Yi; Zepeda-Nunez, Leonardo; Schneider, Tapio; Anderson, John; Sha, Fei
作者单位：Alphabet Inc.; Google Incorporated; California Institute of Technology
摘要：Regional high-resolution climate projections are crucial for many applications, such as agriculture, hydrology, and natural hazard risk assessment. Dynamical downscaling, the state-of-the-art method to produce localized future climate information, involves running a regional climate model (RCM) driven by an Earth System Model (ESM), but it is too computationally expensive to apply to large climate projection ensembles. We propose an approach combining dynamical downscaling with generative AI t...
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作者：Veenbaas, Seth D.; Koehn, Jordan T.; Irving, Patrick S.; Lama, Nicole N.; Weeks, Kevin M.
作者单位：University of North Carolina; University of North Carolina Chapel Hill
摘要：RNAs are critical regulators of gene expression, and their functions are often mediated by complex secondary and tertiary structures. Structured regions in RNA can selectively interact with small molecules-via well-defined ligandbinding pockets-to modulate the regulatory repertoire of an RNA. The broad potential to modulate biological function intentionally via RNA-ligand interactions remains unrealized, however, due to challenges in identifying compact RNA motifs with the ability to bind liga...
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作者：Wang, Jia-nan; Suo, Xiao-guo; Yu, Ju-tao; Luo, Qi-chao; Ji, Ming-lu; Zhang, Meng-meng; Zhu, Qi; Cheng, Xin-ran; Hou, Chao; Chen, Xin; Wang, Fang; Xu, Chuan-hui; Li, Chao; Xie, Shuai-shuai; Wei, Jie; Zhang, Dan-feng; Zhang, Xin-ru; Wang, Zhi-juan; Dong, Yu- hang; Zhu, Sai; Peng, Li-jin; Li, Xiang-yu; Chen, Hai-yong; Xu, Tao; Jin, Juan; Chen, Fei Xavier; Meng, Xiao-ming
作者单位：Anhui Medical University; Anhui Medical University; Anhui Medical University; Anhui Medical University; University of Hong Kong; University of Hong Kong; Fudan University
摘要：Inflammation plays an essential role in eliminating microbial pathogens and repairing tissues, while sustained inflammation accelerates kidney damage and disease progression. Therefore, understanding the mechanisms of the inflammatory response is vital for developing therapies for inflammatory kidney diseases like acute kidney injury (AKI), which currently lacks effective treatment. Here, we identified N-acetyltransferase 10 (NAT10) as an important regulator for acute inflammation. NAT10, the ...
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作者：Kochlamazashvili, Gaga; Swaminathan, Aarti; Stumpf, Alexander; Kumar, Amit; Posor, York; Schmitz, Dietmar; Haucke, Volker; Kuijpers, Marijn
作者单位：Leibniz Association; Leibniz Forschungsinstitut furr Molekulare Pharmakologie (FMP); Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin; Humboldt University of Berlin; Free University of Berlin; Charite Universitatsmedizin Berlin; Berlin Institute of Health; Free University of Berlin; Radboud University Nijmegen; Radboud University Nijmegen
摘要：Glutamate-mediated neuronal hyperexcitation plays a causative role in eliciting seizures and promoting epileptogenesis. Recent data suggest that altered autophagy can contribute to the occurrence of epilepsy. We examined the role of autophagy in neuronal physiology by generating knockout mice conditionally lacking the essential autophagy protein ATG5 in glutamatergic neurons. We demonstrate that conditional genetic blockade of neuronal autophagy results in action potential narrowing, axonal hy...
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作者：Bontorin, Sebastiano; Centellegher, Simone; Gallotti, Riccardo; Pappalardo, Luca; Lepri, Bruno; Luca, Massimiliano
作者单位：Fondazione Bruno Kessler; University of Trento; Fondazione Bruno Kessler; Consiglio Nazionale delle Ricerche (CNR); Istituto di Scienza e Tecnologie dell'Informazione Alessandro Faedo (ISTI-CNR); Scuola Normale Superiore di Pisa
摘要：Predicting human displacements is crucial for addressing various societal challenges, including urban design, traffic congestion, epidemic management, and migration dynamics. While predictive models like deep learning and Markov models offer insights into individual mobility, they often struggle with out-of-routine behaviors. Our study introduces an approach that dynamically integrates individual and collective mobility behaviors, leveraging collective intelligence to enhance prediction accura...
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作者：Danning, Rebecca; Hu, Frank B.; Lin, Xihong
作者单位：Harvard University; Harvard T.H. Chan School of Public Health; Harvard University; Harvard T.H. Chan School of Public Health; Harvard University
摘要：Disease and behavior subtype identification is of significant interest in biomedical research. However, in many settings, subtype discovery is limited by a lack of robust statistical clustering methods appropriate for binary data. Here, we introduce LACE-UP [latent class analysis ensembled with UMAP (uniform manifold approximation and projection) and PCA (principal components analysis)], an ensemble machine-learning method for clustering multidimensional binary data that does not require presp...
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作者：Fisher, Nicole M.; von Zastrow, Mark
作者单位：University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco
摘要：Many GPCRs initiate a second phase of G protein-mediated signaling from endosomes. This inherently requires the GPCR to increase cognate G protein activity on the endosome surface. Gs-coupled GPCRs are thought to achieve this by internalizing and mediating a second round of allosteric coupling to G proteins on the endosome membrane. Here, we provide evidence that the mu- opioid receptor (MOR), a Gi-coupled GPCR, is able to increase endosomal G protein activity in a different way. Leveraging co...
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作者：Pharkjaksu, Sujiraphong; Cai, Hongyi; Walter, Peter J.; Chang, Yun C.; Kwon-Chung, Kyung J.
作者单位：National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
摘要：UDP- glucuronic acid (UDP- GlcUA) is a nucleotide sugar essential for various biological processes in many organisms, and its excess within the cell can disrupt cellular functions. In Cryptococcus, mutations in the UXS1 gene which encodes an enzyme responsible for converting UDP- GlcUA into UDP- xylose, result in excessive accumulation of UDP- GlcUA and confer resistance to the antifungal drug 5- fluorocytosine. Here, we demonstrate that elevation of UDP- GlcUA affects several cellular process...
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作者：Bacheva, Vesna; Rockwell, Fulton E.; Salmon, Jean - Baptiste; Woodson, Jesse D.; Frank, Margaret H.; Stroock, Abraham D.
作者单位：Cornell University; Cornell University; Cornell University; Harvard University; Centre National de la Recherche Scientifique (CNRS); Universite de Bordeaux; CNRS - Institute of Chemistry (INC); University of Arizona; Cornell University
摘要：Local wounding in plants triggers signals that travel locally within the wounded leaf or systemically through the vasculature to distant leaves. Our understanding of the mechanisms of initiation and propagation of this ubiquitous class of signals remains incomplete. Here, we develop a unifying framework based on poroelastic dynamics to study two coupled biophysical processes-propagation of pressure changes and transmission of chemical elicitors via mass flows driven by these pressure changes-a...
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作者：Dickerson, Joshua L.; Naydenova, Katerina; Peet, Mathew J.; Wilson, Hugh; Nandy, Biplob; McMullan, Greg; Morrison, Robert; Russo, Christopher J.
作者单位：MRC Laboratory Molecular Biology
摘要：The physical limit in determining the atomic structure of biological molecules is radiation damage. In electron cryomicroscopy, there have been numerous attempts to reduce the effects of radiation damage by cooling the specimen beyond liquid-nitrogen temperatures, yet all failed to realize the potential improvement for single-particle structure determination. We have identified the physical causes of information loss at liquid-helium temperatures, and overcome them using a combination of nanos...
