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作者:Biddinger, Jessica E.; Elson, Amanda E. T.; Fathi, Payam A.; Sweet, Serena R.; Nishimori, Katsuhiko; Ayala, Julio E.; Simerly, Richard B.
作者单位:Vanderbilt University; Children's Hospital Los Angeles; Fukushima Medical University
摘要:During postnatal life, leptin specifies neuronal inputs to the paraventricular nucleus of the hypothalamus (PVH) and activates agouti- related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus. Activity- dependent developmental mechanisms impact refinement of sensory circuits, but whether leptin- mediated postnatal neuronal activity specifies hypothalamic neural projections is largely unexplored. Here, we used chemogenetics to manipulate the activity of AgRP neurons during a di...
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作者:Ceribelli, Michele; Tosto, Frances Anne; Zhang, Xiaohu; Melani, Christopher J.; Roschewski, Mark; Beck, Erin; Thomas, Carleen Klumpp -; Peer, Cody J.; Wilson, Kelli M.; Chen, Lu; Mcknight, Crystal; Michael, Sam; Itkin, Zina; Shinn, Paul; Figg Sr, William D.; Wilson, Wyndham H.; Staudt, Louis M.; Thomas, Craig J.
作者单位:National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI); National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
摘要:Clinical trials in cancer are ideally built on a foundation of sound mechanistic rationale and well- validated drug activity in relevant disease models. The screening of approved and investigational drugs in cell- based phenotypic assays can provide evidence of drug activity, but alternative screening paradigms are needed to develop and optimize multidrug combination regimens. Here, we utilize in vitro screening outcomes across a panel of lymphoma cell lines to dissect the activity of four sma...
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作者:Poincloux, Samuel; Takeuchi, Kazumasa A.
作者单位:University of Tokyo; University of Tokyo; Aoyama Gakuin University
摘要:A wide range of disordered materials, from biological to geological assemblies, feature discrete elements undergoing large shape changes. How significant geometrical variations at the microscopic scale affect the response of the assembly, in particular rigidity transitions, is an ongoing challenge in soft matter physics. However, the lack of a model granular-like experimental system featuring large and versatile particle deformability impedes advances. Here, we explore the oscillatory shear re...
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作者:Jaffe, Alexander L.; Harrison, Kaitlin; Wang, Renee Z.; Taylor-Kearney, Leah J.; Jain, Navami; Prywes, Noam; Shih, Patrick M.; Young, Jodi; Rocapb, Gabrielle; Dekas, Anne E.
作者单位:Stanford University; University of Washington; University of Washington Seattle; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Stanford University; University of California System; University of California Berkeley; Howard Hughes Medical Institute; University of California System; University of California Berkeley; United States Department of Energy (DOE); Joint BioEnergy Institute - JBEI; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
摘要:Cyanobacteria are highly abundant in the marine photic zone and primary drivers of the conversion of inorganic carbon into biomass. To date, all studied cyanobacterial lineages encode carbon fixation machinery relying upon form I Rubiscos within a CO2-concentrating carboxysome. Here, we report that the uncultivated anoxic marine zone (AMZ) IB lineage of Prochlorococcus from pelagic oxygen- deficient zones (ODZs) harbors both form I and form II Rubiscos, the latter of which are typically noncar...
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作者:Keszthelyi, Andrea; Mansoubi, Sahar; Whale, Alex; Houseley, Jonathan; Baxter, Jonathan
作者单位:University of Sussex; Islamic Azad University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); Babraham Institute
摘要:The fork protection complex (FPC), composed ofMrc1, Tof1, and Csm3, supports rapid and stable DNA replication. Here, we show that FPC activity also introduces DNA damage by increasing DNA topological stress during replication. Mrc1 action increases DNA topological stress during plasmid replication, while Mrc1 or Tof1 activity causes replication stress and DNA damage within topologically constrained regions. We show that the recruitment of Top1 to the fork by Tof1 suppresses the DNA damage gene...
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作者:Michalczyk, Elizabeth; Pakosz-Stepen, Zuzanna; Liston, Jonathon D.; Gittins, Olivia; Pabis, Marta; G. Heddle, Jonathan; Ghilarov, Dmitry
作者单位:Jagiellonian University; Jagiellonian University; Durham University; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Center
摘要:Type II topoisomerase DNA gyrase transduces the energy of ATP hydrolysis into the negative supercoiling of DNA. The postulated catalytic mechanism involves stabilization of a chiral DNA loop followed by the passage of the T- segment through the temporarily cleaved G- segment resulting in sign inversion. The molecular basis for this is poorly understood as the chiral loop has never been directly observed. We have obtained high- resolution cryoEM structures of Escherichia coli gyrase with chiral...
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作者:Borges, Beatriz; Foroutan, Negar; Bayazit, Deniz; Sotnikova, Anna; Montariol, Syrielle; Nazaretzky, Tanya; Banaei, Mohammadreza; Sakhaeirad, Alireza; Servant, Philippe; Neshaei, Seyed Parsa; Frey, Jibril; Romanou, Angelika; Weiss, Gail; Mamooler, Sepideh; Chen, Zeming; Fan, Simin; Gao, Silin; Ismayilzada, Mete; Paul, Debyit; Schwaller, Philippe; Friedli, Sacha; Jermann, Patrick; Kaser, Tanya; Bosselut, Antoine; EPFL Grader Consortium, E. P. F. L. Grader; EPFL Data Consortium, E. P. F. L. Data
作者单位:Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne
摘要:AI assistants, such as ChatGPT, are being increasingly used by students in higher education institutions. While these tools provide opportunities for improved teaching and education, they also pose significant challenges for assessment and learning outcomes. We conceptualize these challenges through the lens of vulnerability, the potential for university assessments and learning outcomes to be impacted by student use of generative AI. We investigate the potential scale of this vulnerability by...
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作者:Patel, Aara; Pauzuolyte, Valda; Ingham, Neil J.; Leong, Yeh Chwan; Berger, Wolfgang; Steel, Karen P.; Sowden, Jane C.
作者单位:University of London; University College London; University of London; King's College London; University of Zurich; University of Zurich; Zurich Center Integrative Human Physiology (ZIHP); University of Zurich; University of Zurich; Swiss Federal Institutes of Technology Domain; ETH Zurich
摘要:Variants in the gene NDP cause Norrie disease, a severe dual- sensory disorder characterized by congenital blindness due to disrupted retinal vascular development and progressive hearing loss accompanied by sensory hair cell death. NDP encodes the secreted signaling molecule norrin. The role of norrin in the cochlea is incompletely understood. We investigated whether the Norrie disease cochlear pathology can be ameliorated in an Ndp- knockout (Ndp- KO) mouse model by conditional activation of ...
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作者:Porwal, Anupreet; Raftery, Adrian E.
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作者:Sutter, Markus; Utschig, Lisa M.; Niklas, Jens; Paul, Sathi; Kahan, Darren N.; Gupta, Sayan; Poluektov, Oleg G.; Ferlez, Bryan H.; Tefft, Nicholas M.; Teravest, Michaela A.; Hickey, David P.; Vermaas, Josh V.; Ralston, Corie Y.; Kerfeld, Cheryl A.
作者单位:Michigan State University; United States Department of Energy (DOE); United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; United States Department of Energy (DOE); Argonne National Laboratory; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley; Michigan State University; Michigan State University
摘要:Bacterial microcompartments (BMCs) are prokaryotic organelles that consist of a protein shell which sequesters metabolic reactions in its interior. While most of the substrates and products are relatively small and can permeate the shell, many of the encapsulated enzymes require cofactors that must be regenerated inside. We have analyzed the occurrence of an enzyme previously assigned as a cobalamin (vitamin B12) reductase and, curiously, found it in many unrelated BMC types that do not employ...