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作者：Causemann, Marius; Enger, Rune; Rognes, Marie E.
作者单位：University of Oslo; University of Oslo; National Hospital Norway
摘要：Astrocyte endfeet form a near-continuous sheath around the brain's vasculature, defining the perivascular spaces (PVS) that are crucial for brain fluid flow and solute transport. Yet, their precise physiological role remains poorly understood. Using electron microscopy data, we created a high-fidelity poroelastic computational model of an arteriole segment with surrounding endfeet and parenchyma to investigate tissue displacement and fluid flow within the PVS, endfeet, and extracellular space ...
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作者：Crowley, George; Alon, Uri; Quake, Stephen R.
作者单位：Stanford University; Weizmann Institute of Science; Stanford University
摘要：We sought to identify universal organizing principles behind phenotypic variation within cell types. Pareto optimality describes how trade-offs between optimal solutions account for variation, predicting that the boundary points of a data distribution reflect specialized functions. We hypothesized that transcriptomic variation was explained by Pareto optimality across all cell types. We then used the Tabula Sapiens Atlas of single-cell RNA sequencing across cell types and tissues in the human ...
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作者：Minarro, Laura M.; Chakraborty, Saikat; Beck, Christian; Grundel, Anna C.; Mosca, Ilaria; Roosen-Runge, Felix; Morozova, Tatiana I.; Barrat, Jean-Louis; Schreiber, Frank; Seydel, Tilo
作者单位：Institut Laue-Langevin (ILL); Communaute Universite Grenoble Alpes; Centre National de la Recherche Scientifique (CNRS); Universite Grenoble Alpes (UGA); Eberhard Karls University of Tubingen; Ruprecht Karls University Heidelberg; University of Wurzburg; Lund University; Ecole Normale Superieure de Lyon (ENS de LYON); Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; CNRS - Institute of Physics (INP); SciLifeLab; Royal Institute of Technology; University of Perugia
摘要：The molecular mechanisms governing internal fluctuations in intrinsically disordered protein (IDP) assemblies are crucial to the stability and dynamics of both regulated and aberrant toxic cellular aggregates, but remain poorly understood. By comprehensively combining high-resolution quasi-elastic neutron scattering with all-atom molecular dynamics simulations, we probe the motions of D-casein, a model IDP, inside its assemblies. We uncover a previously unresolved slow relaxation process with ...
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作者：Sava-Segal, Clara; Grall, Clare; Finn, Emily S.
作者单位：Dartmouth College
摘要：Given the same input, understanding of that input can differ depending on context. How does the brain represent the latent mental frameworks that support different interpretations of the same sensory information? In this study, participants listened to the same auditory narrative twice; the narrative had a plot twist in the middle that dramatically shifted interpretations of the story. Using a within- subject design that held both the stimulus and the individual constant, we leveraged reinterp...
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作者：Zurawski, Jonathan; Tuncer, Alara; Profant, Martin R.; Wang, Jianuo; Green, Miranda; Park, Yoobhin; Cao, Ke; Paris, Simon; Tauhid, Shahamat; Jalkh, Youmna; Quattrucci, Molly; Chu, Renxin; Cao, Xingshan; Kiss, Alex; Chitnis, Tanuja; Weiner, Howard; Clish, Clary B.; Bakshi, Rohit; Wang, Chao
作者单位：Harvard University; Mass General Brigham; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; University of Toronto; Sunnybrook Health Science Center; Sunnybrook Research Institute; University of Toronto; University of Toronto; Sunnybrook Health Science Center; Sunnybrook Research Institute; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
摘要：Meningeal inflammation, as a clinical feature of multiple sclerosis (MS), is associated with worse clinical disease outcomes. In both relapsing and secondary progressive MS and the experimental autoimmune encephalomyelitis (EAE) MS model, the meninges have been found to contain ectopic lymphoid follicles enriched with B cells. The metabolic requirement of meningeal B cell function in MS or EAE is not well elucidated. Using 7-Tesla MRI brain scans of MS patients and leptomeningeal enhancement a...
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作者：Allaby, Robin G.; Ware, Rosie; Cribdon, Rebecca; Hansford, Teri A.; Kinnaird, Tim; Hamilton, Derek; Kistler, Logan; Murgatroyd, Phil; Bates, Richard; Fitch, Simon; Gaffney, Vincent
作者单位：University of Warwick; University of St Andrews; Smithsonian Institution; Smithsonian National Museum of Natural History; University of Bradford
摘要：Prior to the formation of the present-day North Sea during the mid-Holocene, North-Western Europe was connected through the Doggerland landmass. While it has been known for the past century that Doggerland was forested, it has not been clear when the onset of forestation occurred or whether the environment was more habitable for humans than surrounding European areas. In this study, we reconstruct the paleoecology of a river system, the Southern River, from the late Late Pleistocene to the lat...
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作者：Richards, Miriam H.
作者单位：Brock University
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作者：Yan, Yan; Wang, Xinming; Jeon, Hanna; Kee, Teresa R.; Tran, Khoi D.; Lee, Hyunkyoung; Zhao, Xingyu; Tian, Khoi D.; Liu, Tian; Wing, Simon S.; Woo, Jung-A A.; Kang, David E.
作者单位：University System of Ohio; Case Western Reserve University; McGill University; University System of Ohio; US Department of Veterans Affairs; Case Western Reserve University; Veterans Health Administration (VHA); Louis Stokes Cleveland Veterans Affairs Medical Center
摘要：Aggregation and deposition of TAR DNA-binding protein 43 (TDP-43) is a salient pathological signature of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration-TDP (FTLD-TDP). TDP-43 proteostasis and aggregation are controlled by several posttranslational modifications, including ubiquitination. While multiple E3 ubiquitin ligases are known to facilitate TDP-43 clearance, little is known about the role of deubiquitinases (DUBs) in controlling TDP-43 proteostasis. Through an ...
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作者：An, Joon Soo; Overton, Ellysia N.; Seyedsayamdost, Mohammad R.
作者单位：Princeton University; Princeton University
摘要：Microbial natural products are a foundational source of therapeutic agents, yet a vast majority remain inaccessible due to the limited expression of their biosynthetic gene clusters under standard laboratory conditions. To address this challenge, we developed a simple and broadly applicable screening approach based on the idea of antibiotic hormesis wherein high- dose growth- inhibitory antibiotics serve as low- dose elicitors of secondary metabolites. We generated an in- house library of all ...
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作者：Guptaa, Manish; Waltmanna, Curt; Rennerb, Nadine; Wang, Yihang; James, Leo C.; Jacquesc, David A.; Backing, Till; Votha, Gregory A.
作者单位：University of Chicago; University of Chicago; UK Research & Innovation (UKRI); MRC Laboratory Molecular Biology; Medical Research Council UK (MRC); University of New South Wales Sydney
摘要：The HIV-1 capsid is a fullerene cone composed of hexameric and pentameric capsid proteins (CA) that packages the viral genome and mediates nuclear entry. Lenacapavir (LEN), a potent molecular long-acting inhibitor developed by Gilead, disrupts capsid morphogenesis by binding a phenylalanine-glycine (FG) pocket at the interface between adjacent CA subunits. Interestingly, cellular polyanion inositol hexakisphosphate (IP6) promotes conical capsid assembly by coordinating the central pore, which ...
