Proceedings of the National Academy of Sciences of the United States of America

最新文章

• Structural basis of the inhibition of TRPV1 by analgesic sesquiterpenes AI翻译
  作者：Sanchez-Hernandez, Raul; Benitez-Angeles, Miguel; Talyzina, Irina A.; Llorente, Itzel; Gonzalez-Avendano, Mariela; Sierra, Felix; Mendez-Resendiz, Angelica; Mercado, Francisco; Vergara-Jaque, Ariela; Sobolevsky, Alexander I.; Islas, Leon D.; Rosenbaum, Tamara
  作者单位：Universidad Nacional Autonoma de Mexico; Columbia University; Universidad de Talca; Universidad Nacional Autonoma de Mexico; Universidad Nacional Autonoma de Mexico; Instituto Nacional de Psiquiatria Ramon de la Fuente Muniz
  摘要：The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in primary nociceptive afferents, which participate in processes such as pain and inflammation. Considerable efforts have been directed toward finding inhibitors of TRPV1 and understanding the molecular details of their interactions with this channel. alpha- humulene (AH) is a sesquiterpene derived from plants such as hops and other members of Cannabaceae family, with a long history of popular use as an analgesic and...
• Systemic delivery of biotherapeutic RNA to the myocardium transiently modulates cardiac contractility in vivo AI翻译
  作者：V. Shuvaev, Vladimir; Tam, Ying K.; Lee, Benjamin W.; Myerson, Jacob W.; Herbst, Alan; Kiseleva, Raisa Yu.; Glassman, Patrick M.; Parhiz, Hamideh; Alameh, Mohamad-Gabriel; Pardi, Norbert; Muramatsu, Hiromi; Shuvaeva, Tea I.; Arguiri, Evguenia; Marcos-Contreras, Oscar A.; Hood, Elizabeth D.; V. Brysgel, Taylor; Nong, Jia; Papp, Tyler E.; Eaton, Deborah M.; Riley, Rachel; Palanki, Rohan; Musunuru, Kiran; Brenner, Jacob S.; Mitchell, Michael J.; Ferrari, Victor A.; Mui, Barbara L.; Semple, Sean C.; Weppler, Sherry A.; Atluri, Pavan; Margulies, Kenneth B.; Weissman, Drew; Muzykantov, Vladimir R.
  作者单位：University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Pennsylvania Commonwealth System of Higher Education (PCSHE); Temple University; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; University of Pennsylvania; Rowan University
  摘要：Lipid nanoparticles (LNP) represent a versatile platform for improving delivery of therapeutic nucleic acids. Yet, delivery to the myocardium remains a formidable challenge due to local barriers in the heart and systemic hindrances. In particular, plasma apolipoprotein E (apoE) directs LNP to the liver, limiting potential extrahepatic delivery. Here, we report a cardiotropic LNP (cLNP), which within 30 min post-intravenous injection accumulates in the heart of ApoE knockout (Apoe-/-) mice. The...
• Characterizing a highly excited and sustained brain response activity during gaming: P300-CE AI翻译
  作者：Pei, Leisi; Green, C. Shawn; Ouyang, Guang
  作者单位：University of Hong Kong; University of Wisconsin System; University of Wisconsin Madison
  摘要：Inspired by the high engagement and sustained behavioral excitement observed in video game players, we hypothesized that distinct brain activity patterns occur during gaming compared to a generic nongame setting. Using electroencephalography (EEG), we characterized the brain's response to critical in- game events, focusing on the response magnitude and adaptation. Data from a large participant cohort (n = 140 for game tasks, n = 200 for nongame tasks) revealed a clear, definite, and consistent...
• Subterranean salamanders lean into mechanical sense following vision loss AI翻译
  作者：Hanken, James
  作者单位：Harvard University; Harvard University
• Cell-to-cell translocation of florigen is inhibited by low ambient temperature through abscisic acid signaling in Arabidopsis thaliana AI翻译
  作者：Murata, Yusuke; Nagata, Kenji; Abe, Mitsutomo
  作者单位：University of Tokyo
  摘要：In Arabidopsis thaliana, the FLOWERING LOCUS T (FT) gene encodes florigen, a floral stimulus that integrates multiple environmental cues to optimize the timing of flowering, which is crucial for reproductive success. The FT protein is synthesized in the phloem companion cells of leaves but exerts its function in the shoot apical meristem (SAM) to initiate floral morphogenesis. While the environment-dependent regulation of FT transcription in leaves is well studied, the mechanisms underlying FT...
• WT1 directs normal progesterone receptor-chromatin binding essential for uterine receptivity at peri- implantation AI翻译
  作者：Ni, Zhangli; Guo, Chuanhui; Liu, Xiaojing; Li, Gaizhen; Tang, Yedong; Cai, Han; Huang, Weiyu; Gao, Fei; Tu, Zhaowei; Wang, Chao; Wang, Haibin; Kong, Shuangbo; Bao, Haili
  作者单位：Xiamen University; China Agricultural University; Chinese Academy of Sciences; Institute of Zoology, CAS; Guangzhou Medical University; Xiamen University
  摘要：Progesterone receptor (PR)- mediated progesterone (P4) signaling plays a crucial role in the establishment of uterine receptivity which is the prerequisite for successful embryo implantation in mammals. However, detailed molecular mechanisms underlying PR-chromatin binding and transcriptional activity in the uterus remain largely elusive. Here, combining the P4- administrated ovariectomized mouse model and PR-chromatin immunoprecipitation sequencing, we identified transcription factor WT1 as a...
• The pathogenic factor of ZC4H2-associated rare disorder is a postsynaptic regulator for synaptic activity and cognitive function AI翻译
  作者：Wan, Li Pear; Li, Yuwei; Zhao, Shuhua; Zhao, Shiping; Song, Ning - Ning- Ning; Yang, Cuiping; Ding, Yu- Qiang; Yuan, Kai-Ming; Mao, Bingyu; Sheng, Nengyin; Tao, Wucheng; Ma, Pengcheng
  作者单位：Fujian Medical University; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Kunming Medical University; Fudan University; Wenzhou Medical University; Wenzhou Medical University; Shanghai Jiao Tong University; Fudan University; Fudan University; Chinese Academy of Sciences; Chinese Academy of Sciences; Kunming Institute of Zoology, CAS; Chinese Academy of Sciences
  摘要：The maintenance of excitatory synaptic activity is crucial for cognitive function and genetic mutations are responsible for the pathogenesis of related brain disorders. However, the roles of these pathogenic factors in synaptic dysregulation and cognitive malfunction are still poorly understood. In this study, a conditional knockout mouse model lacking ZC4H2-an X-linked gene implicated in ZC4H2-associated rare disorder (ZARD) -in forebrain excitatory neurons is generated and these mice exhibit...
• TEAD-targeting small molecules induce a cofactor switch to regulate the Hippo pathway AI翻译
  作者：Guarnaccia, Alissa D.; Hagenbeek, Thijs J.; Lee, Wendy; Kljavin, Noelyn; Choi, Meena; Tombling, Benjamin; Peukert, Carsten; Ulas, Gozde; Kameswaran, Vasumathi; Le, Daniel; Paul, Sayantanee; Vaidya, Samir; Zbieg, Jason R.; Crawford, James J.; Daniel, Bence; Dey, Anwesha; Lill, Jennie R.
  作者单位：Roche Holding; Roche Holding USA; Genentech; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Genentech; Roche Holding USA; Roche Holding; Roche Holding USA; Genentech; Roche Holding; Genentech; Roche Holding USA
  摘要：TEAD proteins are the main transcriptional effectors of the Hippo signaling pathway and a clinical-stage pharmacological target in oncology. Most TEAD-targeting small molecules are designed to disrupt interaction between TEAD and the oncogenic transcriptional activators YAP and TAZ. Here, we uncover an alternative mechanism for a subset of TEAD lipid pocket-binding molecules. We report that select sulfonamide-containing TEAD-targeting compounds enhance the interaction between TEAD and the tran...
• The epigenetic impacts of pubertal acceleration following early caregiver disruptions AI翻译
  作者：Jopling, Ellen; Drury, Stacy S.; Fox, Nathan A.; Zeanah, Charles H.; Nelson, Charles A.
  作者单位：Tulane University
  摘要：A stable caregiving environment early in life is essential for children's development, and disruptions have the potential to impact biological processes. Using data from the Bucharest Early Intervention Project, we examined a developmental cascade model in which shifts in pubertal tempo following early caregiving disruptions come at an epigenetic cost. Among 115 individuals, all of whom experienced severe deprivation early in life, we tracked caregiving disruptions across childhood; assessed p...
• Molecular basis for substrate recognition and transport of mammalian taurine transporters AI翻译
  作者：Wang, Mingxing; He, Jin; Cai, Qianwen; Zhang, Shen-ao; She, Ji
  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
  摘要：The taurine transporter (TAUT) mediates cellular taurine uptake, playing a critical role in human health and longevity. In this study, we present cryogenic electron microscopy structures of both mouse and human TAUT in various conformational states. The taurine-bound, occluded forms of mouse and human TAUT reveal the substrate binding pocket and the ion binding sites. The amino group of taurine interacts with Glu406 at the binding site, constituting a key structural feature determining substra...