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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...
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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...
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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...
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作者:Choi, Han Seul; Park, Hyeyoung; Min, Hyehyun; Kim, Kwan Soo; Kim, Soo Min; Li, Jinan; Liu, Chang; Ko, Hyuk Wan; Lee, Min Goo; Song, Lei; Zhao, Bo; Bok, Jinwoong
作者单位:Yonsei University; Yonsei University Health System; Yonsei University; Yonsei University Health System; Indiana University System; Indiana University Bloomington; Yonsei University; Yonsei University; Yonsei University Health System; Shanghai Jiao Tong University; Yonsei University; Yonsei University Health System; Yonsei University; Yonsei University Health System
摘要:The mammalian auditory system relies on the precise architecture of the hair cell stereociliary bundle for effective sound transduction. Each bundle consists of approximately 100 actin-filled stereocilia arranged in a three-row staircase pattern, forming a linear shape in inner hair cells (IHCs) and a V-shape in outer hair cells (OHCs), the latter geometry being a hallmark of the mammalian cochlea. While the initial development from uniformly distributed microvilli into stereociliary bundles i...
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作者:Ehrlich, Amy M.; MacGregor, Kirstin A.; Ashcroft, Stephen P.; Small, Lewin; Altintas, Ali; Chibalin, Alexander V.; Anagho-Mattanovich, Matthias; Stocks, Ben; Moritz, Thomas; Treebak, Jonas T.; Zierath, Juleen R.
作者单位:University of Copenhagen; Karolinska Institutet; Karolinska Institutet
摘要:The regulation of metabolism in peripheral tissues is intricately linked to circadian rhythms, with hypoxia-inducible factor-1 alpha (HIF1 alpha) implicated in modulating time-of-day-specific exercise responses. To investigate this relationship, we generated a skeletal muscle-specific HIF1 alpha knockout (KO) mouse model and performed extensive metabolic phenotyping and transcriptomic profiling under both basal conditions and following acute exercise during early rest (ZT3) and active (ZT15) p...
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作者:Barnet, Megan B.; L., Katherine J.; Masle, Etienne; Russell, Amanda; Burnett, Deborah L.; Chye, Adrian; Jara, Chris J.; Faulks, Megan; Mawson, Amanda; Peters, Timothy J.; Brink, Robert; Wright, Katherine; Allen, India; Junankar, Simon; Davis, Ian D.; Heller, Gillian; Khan, Zia; Bruce, Jeffrey; Yang, Cindy; Prokopec, Stephenie; Pugh, Trevor; Behren, Andreas; Hold, Georgina L.; Zhang, Fan; Cooper, Wendy A.; Gao, Bo; Nagrial, Adnan; Joshua, Anthony M.; John, Thomas; Peters, Geoffrey; Hui, Rina; Boyer, Michael; Blinman, Prunella L.; Kao, Steven C.; Cebon, Jonathan; Goodnow, Christopher C.
作者单位:Garvan Institute of Medical Research; University of New South Wales Sydney; NSW Health; The Kinghorn Cancer Centre; St Vincents Hospital Sydney; University of Technology Sydney; University of New South Wales Sydney; University of New South Wales Sydney; Monash University; La Trobe University; Olivia Newton-John Cancer Research Institute; Eastern Health; University of Sydney; Roche Holding; Roche Holding USA; Genentech; University of Toronto; University Health Network Toronto; Princess Margaret Cancer Centre; La Trobe University; University of Melbourne; University of New South Wales Sydney; Western Sydney University; University of Sydney; NSW Health; University of Sydney; Royal Prince Alfred Hospital; NSW Health; Blacktown & Mount Druitt Hospital; NSW Health; University of Sydney; Westmead Hospital; Peter Maccallum Cancer Center; Chris O'Brien Lifehouse; Concord Repatriation General Hospital
摘要:Lung cancers and melanomas have many somatically mutated self-proteins that would be expected to trigger an immune rejection response, yet therapeutic responses can only be induced in a subset of patients. Here, we investigated the possibility that inherited differences in immune tolerance checkpoints contribute to variability in outcomes. Whole genome sequencing revealed biallelic germline loss-of-function (LOF) mutations in the immune tolerance checkpoint gene, NOD2, in an exceptional immune...
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作者:Causa, Erika; Das, Debasish; Feriani, Luigi; Kotar, Jurij; Cicuta, Pietro
作者单位:University of Cambridge; University of Strathclyde
摘要:The ciliated epithelium of the human respiratory tract is covered by the airway surface liquid, a protective fluid consisting of two layers: the periciliary layer (PCL), where motile cilia reside and generate fluid flow, and an overlying mucus layer. The complex structure and stratified nature of the PCL complicate both the prediction and quantification of fluid flow at the scale of individual or small groups of cilia, making it difficult to connect microscopic flows to macroscopic clearance. ...
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作者:Ramos, Kevin E.; Nandigrami, Prithviraj; Najafian, Ahmad; Lai, Jonathan R.; Fiser, Andras
作者单位:Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine
摘要:Single-domain antibodies, such as variable heavy domain of heavy chain (VHH) domains from camelids, are an attractive platform for therapeutic purposes. VHHs have a smaller size than traditional antibodies, which harbors certain advantages such as tissue penetration or accessing epitopes that may be shielded by protein domains. However, the smaller size of VHHs typically involves a smaller binding site, which can limit the scope of related antigens they are able to bind and, in the specific ca...
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作者:Singh, Milind; Wolfe, Aaron D.; Vishwanath, Anjali A.; Tsives, Anastasia; Gonzalez, Ian J.; Emerson, Sarah E.; Goodman, Richard; Colon-Ramos, Daniel
作者单位:Yale University; Yale University; Yale University; Marine Biological Laboratory - Woods Hole; University of Puerto Rico; University of Puerto Rico Medical Sciences Campus
摘要:Glycogen is the largest energy reserve in the brain, but the specific role of glycogen in supporting neuronal energy metabolism in vivo is not well understood. We established a system in Caenorhabditis elegans to dynamically probe glycolytic states in single cells of living animals via the use of the glycolytic sensor HYlight and determined that neurons can dynamically regulate glycolysis in response to activity or transient hypoxia. We performed an RNAi screen and identified that PYGL-1, an o...
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作者:Zhang, Rui; Wu, Xiaokang; Kim, Seho; Kim, Brian; Xie, Catherine; Gonzalez, Devina; Norris, Raven; Chin, Nicholas; Li, Liang; John, Scott; Philipson, Kenneth D.; Ottolia, Michela; Goldhaber, Joshua I.
作者单位:Cedars Sinai Medical Center; University of California System; University of California Los Angeles; David Geffen School of Medicine at UCLA; University of California Los Angeles Medical Center; University of California System; University of California Los Angeles; David Geffen School of Medicine at UCLA; University of California Los Angeles Medical Center; University of California System; University of California Los Angeles; University of California Los Angeles Medical Center; David Geffen School of Medicine at UCLA; Cedars Sinai Medical Center
摘要:The cardiac sodium-calcium exchanger (NCX1) is a critical regulator of intracellular calcium (Ca) in cardiomyocytes. Although strongly regulated by pH, the role of NCX1 pH sensitivity in cardiac function and intracellular Ca regulation is not understood. We used CRISPR/Cas9 to produce a pH-resistant NCX1 mouse by replacing histidine 165 with alanine (H165A). H165A mice live into adulthood and are fertile. Comparative studies in isolated ventricular myocytes demonstrated that NCX1 current (I-NC...