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作者：El-Sobky, Mohanad H.; Rijal, Ramesh; Gomer, Richard H.
作者单位：Texas A&M University System; Texas A&M University College Station; University of Southern Mississippi
摘要：The directed movement of eukaryotic cells is critical for processes such as development and immune responses. While much is known about chemoattraction, much less is known about chemorepulsion. The eukaryotic amoeba Dictyostelium discoideum secretes a 60 kDa chemorepellent protein called AprA to cause cells at the edge of a colony to move away from the colony. In addition to AprA, cells secrete a <10 kDa chemorepellent. Here, we show that the <10 kDa chemorepellent is a polymer of phosphates (...
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作者：Greener, Joe G.
作者单位：MRC Laboratory Molecular Biology
摘要：The next generation of force fields for molecular dynamics will be developed using a wealth of data. Training systematically with experimental data remains a challenge, however, especially for machine-learning potentials. Differentiable molecular simulation calculates gradients of observables with respect to parameters through molecular dynamics trajectories. Here, we improve this approach by explicitly calculating gradients using a reverse-time simulation with effectively constant memory cost...
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作者：Lai, Alvina Grace; Doherty, Colleen J.; Mueller-Roeber, Bernd; Kay, Steve A.; Schippers, Jos H. M.; Dijkwel, Paul P.
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作者：Vafa, Keyon; Athey, Susan; Blei, David M.
作者单位：Harvard University; Stanford University; Stanford University; Columbia University; Columbia University
摘要：The rise of foundation models marks a paradigm shift in machine learning: instead of training specialized models from scratch, foundation models are trained on massive datasets before being adjusted or fine-tuned to make predictions on smaller datasets. Initially developed for text, foundation models have also excelled at making predictions about social science data. However, while many estimation problems in the social sciences use prediction as an intermediate step, they ultimately require d...
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作者：Yoshimura, Shin-ichiro; Sobajima, Tomoaki; Kunii, Masataka; Harada, Akihiro
作者单位：University of Osaka
摘要：Maintenance of pH within membranous organelles is crucial for cellular processes such as posttranslational modifications, ligand-receptor interactions, and proteostasis. The precise mechanisms that determine the luminal pH of each organelle are not fully understood. This study investigated the mechanisms that regulate luminal pH to ensure optimal enzymatic activity. We identified Oxr1 and its paralog Ncoa7, which regulate the vacuolar-type proton pump ATPase (V-ATPase) at the Golgi apparatus a...
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作者：Sella, Yehonatan; Bergman, Aviv
作者单位：Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; The Santa Fe Institute
摘要：This study investigates the intricate interplay among neutral landscape structure, mutation rate, recombination rate, and population dynamics in shaping evolutionary robustness. We provide a comprehensive framework that elucidates how different evolutionary forces interact to influence genotypic robustness and localization within haploid and diploid populations. We demonstrate that in haploid populations, high mutation rates relative to recombination typically drive the population toward regio...
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作者：He, Zhangping; Zuo, Peiyao; Xu, Peiliu; Yuan, Haozhi; Bhave, Madhura; Wei, Xiangying; Yang, Ziyan; Han, Lu; Schmid, Sandra L.; Chen, Zhiming
作者单位：University of South China; University of South China; University of Texas System; University of Texas Southwestern Medical Center; Chan Zuckerberg Initiative (CZI); Minjiang University
摘要：Clathrin-mediated endocytosis (CME) begins with the assembly of clathrin onto the plasma membrane. These structures grow and stabilize to form clathrin-coated pits (CCPs), which invaginate and accumulate cargo. Finally, through membrane fission, CCPs detach to form clathrin-coated vesicles (CCVs). Mechanisms governing the transition of CCPs from flat-to-curved structures have been a matter of debate. GAK and its chaperone protein, Hsc70, are well known to mediate clathrin release from CCVs, an...
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作者：Tian, Limin; Long, Guangyu; Zhu, Siqi; Wang, Yuelong; Xu, Pengcheng; Liu, Lifeng; Yao, Hong; Fang, Shentong; Chen, Shuqing; Li, Suxin
作者单位：China Pharmaceutical University; Inner Mongolia Medical University; China Pharmaceutical University; China Pharmaceutical University; Huazhong University of Science & Technology
摘要：Imbalanced production and clearance of amyloid-n (An) is a hallmark pathological feature of Alzheimer's disease (AD). While several monoclonal antibodies targeting An have shown reductions in amyloid burden, their impact on cognitive function remains controversial, with the added risk of inflammatory side effects. Dysregulated stimulator of interferon genes (STING) signaling is implicated in neurodegenerative disorders, yet the biological interaction between this pathway and An, as well as the...
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作者：Broka, Derrick; Klein, Shoshana; Shir, Alexei; Schade, Babette; Saxena, Meera; Dasargyri, Athanasia; Jarzebinska, Anita; De Feyter, Caroline; Bajic, Davor; Colecchia, David; Amico, Lucia D.; Kitas, Eric; Hikri, Elad; Skowicki, Michal Jerzy; Okoniewski, Michal Jerzy; Baldino, Laura; Qeriqi, Besnik; de Stanchina, Elisa; Schreiber, Joerg; Buchi, Melanie; Palivan, Cornelia G.; Benenson, Yaakov; Zippelius, Alfred; Fabbro, Doriano; Scaltriti, Maurizio; Mizrachi, Aviram; Levitzki, Alexander; Pombo-Villar, Esteban; Zigler, Maya
作者单位：Hebrew University of Jerusalem; Tel Aviv University; Rabin Medical Center; Sackler Faculty of Medicine; Tel Aviv University; Rabin Medical Center; Sackler Faculty of Medicine; University of Basel; Swiss Federal Institutes of Technology Domain; ETH Zurich; Memorial Sloan Kettering Cancer Center; Memorial Sloan Kettering Cancer Center; Swiss Federal Institutes of Technology Domain; ETH Zurich; University of Basel
摘要：Aberrant activation and overexpression of the epidermal growth factor receptor (EGFR) occurs in various solid cancers and often correlates with poor outcome. The clinical benefit from EGFR-targeted therapies is usually short-lived, with resistance being driven by tumor heterogeneity and an immunosuppressive tumor microenvironment (TME). To address these limitations, we developed Targeted Apoptotic Immune Modulators (TAIM), a nonviral nanoparticle platform for the targeted delivery of polyinosi...
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作者：Scheidegger, Alan; Golubev, Nikolay V.; Vanicek, Jiri J. L.
作者单位：Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; University of Arizona
摘要：Coherent superposition of electronic states, created by ionizing a molecule, can initiate ultrafast dynamics of the electron density. Correlation between nuclear and electron motions, however, typically dissipates the electronic coherence in only a few femtoseconds, especially in larger and more flexible molecules. We, therefore, use ab initio semiclassical dynamics to study decoherence in a sequence of analogous organic molecules of increasing size and find, surprisingly, that extending the c...
