-
作者:Li, Shanlong; Chen, Jianhan
作者单位:University of Massachusetts System; University of Massachusetts Amherst
摘要:RNAs are major drivers of phase separation in the formation of biomolecular condensates and can undergo protein-free phase separation in the presence of divalent ions or crowding agents. Much remains to be understood regarding how the complex interplay of base stacking, base pairing, electrostatics, ion interactions, and particularly structural propensities governs RNA phase behavior. Here, we develop an intermediate resolution model for condensates of RNAs (iConRNA) that can capture key local...
-
作者:Bayer, Alexandra C.; Sanmarco, Liliana M.; Pellerin, Alex; Masi, Gianvito; Plasencia, Agustin; Anderson, Jordan M.; Nowak, Richard J.; Damato, Valentina; Massacesi, Luca; Pham, Minh C.; Khani-Habibabadi, Fatemeh; Vital, Heather; Higginson-Scott, Nathan; Otipoby, Kevin L.; Xing, Yi; Mascanfroni, Ivan D.; O'connor, Kevin C.
作者单位:Yale University; Yale University; University of Florence
摘要:Myasthenia gravis (MG) is an autoimmune disorder caused mainly by autoantibodies against the acetylcholine receptor (AChR), leading to muscle weakness. While treatments targeting AChR autoantibodies benefit many, some patients remain refractory, highlighting the need for personalized therapies. This study evaluates the therapeutic potential of S-1117, a pan-IgG-specific protease, in AChR autoantibody-mediated pathology. Using live cell-based assays, we examined AChR-specific monoclonal IgG aut...
-
作者:Karatepe, Kutay; Faria, Bruna Mafra De; Zhang, Jian; Chen, Xinyue; Pinto, Hugo; Fyodorov, Dmitry; Sefik, Esen; Willcockson, Michael A.; Flavell, Richard A.; Skoultchi, Arthur I.; Guo, Shangqin
作者单位:Yale University; Yale University; Montefiore Medical Center; Yeshiva University; Albert Einstein College of Medicine; Yale University
摘要:Myeloid-biased differentiation of multipotent hematopoietic stem and progenitor cells (HSPCs) occurs with aging or exhaustion. The molecular mechanism(s) responsible for this fate bias remain unclear. Here, we report that linker histone regulates HSPC fate choice at the lymphoid versus myeloid bifurcation. Linker histones package nucleosomes and compact chromatin. HSPCs expressing a doxycycline (dox)-inducible H1.0 transgene favor the lymphoid fate, display strengthened nucleosome organization...
-
作者:Lillard, Angeline S.; Loeb, David; Berg, Juliette; Escueta, Maya; Manship, Karen; Hauser, Alison; Daggett, Emily D.
作者单位:University of Virginia; University of Pennsylvania; American Institutes for Research
摘要:Although seminal studies from the early 1960s suggested quality preschool can have lasting positive effects, agreement is lacking on the efficacy of different preschool models. The Montessori model is longstanding but lacks rigorous impact studies; prior random lottery studies included just one or two schools, among other compromises. Here, we report on end-of-kindergarten (age 5 to 6) impacts from a national study of public Montessori preschool. We compared children offered a Montessori seat ...
-
作者:Schramma, Nico; Weeks, Eric R.; Jalaal, Maziyar
作者单位:University of Amsterdam; Emory University
摘要:Photosynthesis is essential for ecosystem survival, but while plants require light, via self-organized motion within cells to optimize light absorption. These disk-shaped organelles must balance two competing needs: dense packing to enhance absorption under dim light and rapid spatial rearrangement to avoid damage from excess light. Using microscopy, we show that plant cell shape and chloroplast size achieve both goals: dense monolayer packing for optimal absorption in low light and sidewall p...
-
作者:Li, Zhuowen; Bharambe, Nikhil; Lande, Kashmiri Manishrao; Feddersen, Bjarne; Balakrishna, Asha Manikkoth; Biggin, Philip C.; Sahu, Giriraj; Basak, Sandip
作者单位:Nanyang Technological University; Indian Institute of Science (IISC) - Bangalore; University of Oxford; Nanyang Technological University
摘要:Pentameric ligand- gated ion channels (pLGICs) are vital neurotransmitter receptors that are key therapeutic targets for neurological disorders. Although the high- resolution structures of these channels have been elucidated, capturing their dynamic conformational transitions remains challenging due to the transient nature of intermediate states. In this study, we investigated a prokaryotic proton- gated pLGIC, GLIC. In our cryo- EM data at pH 4.0, we identified and segregated asymmetric parti...
-
作者:Milkman, Katherine L.; Patel, Mitesh S.; Gandhi, Linnea; Graci, Heather N.; Gromet, Dena M.; Ho, Hung; Kay, Joseph S.; Lee, Timothy W.; Akinola, Modupe; Beshears, John; Bogard, Jonathan E.; Buttenheim, Alison; Chabris, Christopher F.; Chapman, Gretchen B.; Choi, James J.; Dai, Hengchen; Fox, Craig R.; Goren, Amir; Hilchey, Matthew D.; Hmurovic, Jillian; John, Leslie K.; Karlan, Dean; Kim, Melanie; Laibson, David; Lamberton, Cait; Madrian, Brigitte C.; Meyer, Michelle N.; Modanu, Maria; Nam, Jimin; Rogers, Todd; Rondina, Renante; Saccardo, Silvia; Shermohammed, Maheen; Soman, Dilip; Sparks, Jehan; Warren, Caleb; Weber, Megan; Berman, Ron; Evans, Chalanda N.; Snider, Christopher K.; Tsukayama, Eli; Van den Bulte, Christophe; Volpp, Kevin G.; Duckworth, Angela L.
-
作者:Tesniere, Chloe; Boudghene-Stambouli, Fadia; Severin, Marc; Poet, Mallorie; Voisin, Laure; Ponniah, Muthulakshmi; Pascariu, Mirela; Bonneil, Eric; Trempef, Jean-Francois; Thibault, Pierre; Counillon, Laurent; Pedersen, Stine Falsig; Meloche, Sylvain
作者单位:Universite de Montreal; Universite de Montreal; Universite de Montreal; University of Copenhagen; Centre National de la Recherche Scientifique (CNRS); Universite Cote d'Azur; McGill University; McGill University; Universite de Montreal
摘要:Intracellular pH (pHi) influences diverse cellular processes, including cell proliferation, metabolism, and migration, and is linked to metabolic diseases and cancer. Protonation alters protein charge and conformation, modulating different aspects of protein function. How pHi fluctuations are sensed by signaling proteins and translated into cellular responses remains incompletely understood. Here, we reveal that pHi plays a key role in regulating the stability of the mitogen-activated protein ...
-
作者:Xu, Xiangcong; Zhang, Renlong; Luo, Chenggui; Zhang, Chi; Li, Yanping; Lin, Danying; Yu, Bin; Liu, Liwei; Weng, Xiaoyu; Wang, Yiping; Kong, Lingjie; Li, Jia; Qu, Junle
作者单位:Shenzhen University; Tsinghua University
摘要:Imaging biological structures deep inside tissues is crucial but challenging due to common light scattering. This study proposes a multiattention network that directly maps degraded scattering two-photon excitation fluorescence (TPEF) images to high-quality scattering-free images, thereby computationally extending the imaging depth for TPEF without requiring complex optical additions. The model relies solely on simulated data rather than well-registered real data pairs, and is trained to desca...
-
作者:Ma, Shouwen; Frankl-Vilches, Carolina; Gahr, Manfred
摘要:Testosterone administration to nonsinging adult female canaries induces song, making this a model for behavioral plasticity and its underlying neural mechanisms in vertebrates. The song control nucleus HVC is traditionally believed to undergo a substantial size change when transitioning from a nonfunctional to a functional (song-producing) state. Using 2-photon in vivo imaging, we tracked the spatial distribution and anatomical properties of HVC neurons over several weeks of testosterone-induc...