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作者：Liu, Kaien; Tao, Youqi; Zhao, Qinyue; Xia, Wencheng; Li, Xiang; Zhang, Shenqing; Yao, Yuxuan; Xiang, Huaijiang; Han, Chao; Tan, Li; Sun, Bo; Li, Dan; Li, Ang; Liu, Cong
作者单位：Chinese Academy of Sciences; Shanghai Institute of Organic Chemistry, CAS; Shanghai Jiao Tong University; Shanghai Jiao Tong University; ShanghaiTech University; Chinese Academy of Sciences; Shanghai Institute of Organic Chemistry, CAS
摘要：alpha- synuclein (alpha- syn) assembles into structurally distinct fibril polymorphs seen in different synucleinopathies, such as Parkinson's disease and multiple system atrophy. Targeting these unique fibril structures using chemical ligands holds diagnostic significance for different disease subtypes. However, the molecular mechanisms governing small molecules interacting with different fibril polymorphs remain unclear. Here, we investigated the interactions of small molecules belonging to f...
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作者：Abbate, Maria Francesca; Dupic, Thomas; Vigne, Emmanuelle; Shahsavarian, Melody A.; Walczak, Aleksandra M.; Mora, Thierry
作者单位：Universite PSL; Ecole Normale Superieure (ENS); Sorbonne Universite; Universite Paris Cite; Centre National de la Recherche Scientifique (CNRS); Universite Paris Cite; Sanofi-Aventis; Sanofi France; Harvard University
摘要：B cell receptors (BCRs) play a crucial role in recognizing and fighting foreign antigens. High-throughput sequencing enables in-depth sampling of the BCRs repertoire after immunization. However, only a minor fraction of BCRs actively participate in any given infection. To what extent can we accurately identify antigen-specific sequences directly from BCRs repertoires? We present a computational method grounded on sequence similarity, aimed at identifying statistically significant responsive BC...
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作者：Tang, Huangqi; Lu, Ya-Fei; Zeng, Rongsheng; Liu, Chaohua; Shu, Yuxin; Wu, Yupei; Su, Jiajie; Di, Longjiang; Qian, Jinqin; Zhang, Jun; Tian, Yuan; Lu, Xiaopeng; Pei, Xin-Hai; Zhu, Qian; Zhu, Wei-Guo
作者单位：Shenzhen University; Shenzhen University; Fudan University; Shenzhen University
摘要：Breast Cancer Type 1 Susceptibility Protein (BRCA1) is a tumor- suppressor protein that regulates various cellular pathways, including those that are essential for preserving genome stability. One essential mechanism involves a BRCA1-A complex that is recruited to double- strand breaks (DSBs) by RAP80 before initiating DNA damage repair (DDR). How RAP80 itself is recruited to DNA damage sites, however, is unclear. Here, we demonstrate an intrinsic correlation between a methyltransferase DOT1L-...
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作者：Tang, Ruocong; Busby, Rachel; Laursen, Willem J.; Keane, Geoffrey T.; Garrity, Paul A.
作者单位：Brandeis University; Brandeis University
摘要：Aeries aegypti mosquitoes are major vectors of dengue, chikungunya, and other arboviral diseases. Ae. aegypti's capacity to reproduce and to spread disease depends on the female mosquitoes' ability to obtain blood meals and find water- filled containers in which to lay eggs (oviposit). While humidity sensation (hygrosensation) has been implicated in these behaviors, the specific hygrosensory pathways involved have been unclear. Here, we establish the distinct molecular requirements and anatomi...
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作者：Valenstein, Max L.; V. Lalgudi, Pranav; Gu, Xin; Kedir, Jibril F.; Taylor, Martin S.; Chivukula, Raghu R.; Sabatini, David M.
作者单位：Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Massachusetts Institute of Technology (MIT); Whitehead Institute; Massachusetts Institute of Technology (MIT); Harvard University; Harvard Medical School; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Brown University; Brown University; Brown University; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute; Czech Academy of Sciences; Institute of Organic Chemistry & Biochemistry of the Czech Academy of Sciences
摘要：The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth and metabolism in response to many environmental cues, including nutrients. Amino acids signal to mTORC1 by modulating the guanine nucleotide loading states of the heterodimeric Rag GTPases, which bind and recruit mTORC1 to the lysosomal surface, its site of activation. The Rag GTPases are tethered to the lysosome by the Ragulator complex and regulated by the GATOR1, GATOR2, and KICSTOR multiprotein complexes ...
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作者：Zhang, Yu; Wang, Wenzhong; Li, Yunguo; Wu, Zhongqing
作者单位：Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Chinese Academy of Sciences; University of Science & Technology of China, CAS
摘要：Seismological studies have exposed numerous ultralow velocity zones (ULVZs) exhibiting extraordinary physical attributes at Earth's core-mantle boundary, yet their compositions and origins remain controversial. Water-iron reaction can generate unique phases under lowermost- mantle conditions and likely plays a crucial role in forming ULVZs. Through first- principles molecular dynamic simulations with machine learning techniques, we determine that iron hydride, the product of water-iron reactio...
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作者：Deneen, Benjamin
作者单位：Baylor College of Medicine; Baylor College Medical Hospital; Baylor College of Medicine; Baylor College of Medicine
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作者：Jackman, William R.; Portillo, Lyn S. Miranda; Cox, Carol K.; Ambrosio, Alison; Gibert, Yann
作者单位：Bowdoin College; University of Mississippi; University of Mississippi Medical Center; University of Mississippi Medical Center; University of Mississippi
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作者：Ji, Jie; Du, Shengli; Wang, Kun; Qi, Ziyan; Zhang, Chunyang; Wang, Rui; Bruening, George; Wang, Pengwei; Duanmu, Deqiang; Fan, Qiuling
作者单位：Huazhong Agricultural University; Huazhong Agricultural University; Huazhong Agricultural University; University of California System; University of California Davis
摘要：Many virus genomes encode proteases that facilitate infection. The molecular mechanism of plant recognition of viral proteases is largely unexplored. Using the system of Vigna unguiculata and cowpea mosaic virus (CPMV), we identified a cowpea lipid transfer protein (LTP1) which interacts with CPMV- encoded 24KPro, a cysteine protease, but not with the enzymatically inactive mutant 24KPro(C166A). Biochemical assays showed that LTP1 inhibited 24KPro proteolytic cleavage of the coat protein precu...
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作者：Pironon, Nathalie; Bourrat, Emmanuelle; Prost, Catherine; Chen, Mei; Woodley, David T.; Titeux, Matthias; Hovnanian, Alain
作者单位：Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Saint-Louis - APHP; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Avicenne - APHP; Universite Paris 13; University of Southern California; Assistance Publique Hopitaux Paris (APHP); Universite Paris Cite; Hopital Universitaire Necker-Enfants Malades - APHP
摘要：Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and most often severe genetic disease characterized by recurrent blistering and erosions of the skin and mucous membranes after minor trauma, leading to major local and systemic complications. The disease is caused by loss-of-function variants in COL7A1 encoding type VII collagen (C7), the main component of anchoring fibrils, which form attachment structures stabilizing the cutaneous basement membrane zone. Alterations in C7 protein s...
