2025

最新文章

• Structural basis of disease mutation and substrate recognition by the human SLC2A9 transporter AI翻译
  作者：Khandelwal, Nitesh Kumar; Gupta, Meghna; Kumar, Paras; Balasubramani, Sree Ganesh; Echeverria, Ignacia; Stroud, Robert M.
  作者单位：University of California System; University of California San Francisco; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Oregon Health & Science University
  摘要：Urate provides similar to 50% of the reducing potential in human and primate plasma which is key to detoxifying reactive oxygen by- products of cellular metabolism. Urate is the endpoint of purine metabolism in primates, and its concentration in plasma is a bal-ance between excretion from kidney and intestine, and subsequent reabsorption in and through cells of kidney proximal tubules to maintain a regulated concentration in plasma. SLC2A9 is the primary transporter that returns urate from the...
• The canonical RPA complex interacts with Est3 to regulate yeast telomerase activity AI翻译
  作者：Moeller-McCoy, Corinne A.; Wieser, Thomas A.; Lubin, Johnathan W.; Gillespie, Abigail E.; Ramirez, Jocelyn A.; Paschini, Margherita; Wuttke, Deborah S.; Lundblad, Victoria
  作者单位：Salk Institute; University of California System; University of California San Diego; University of Colorado System; University of Colorado Boulder; University of California System; University of California San Diego; University of Colorado System; University of Colorado Anschutz Medical Campus; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital; Harvard University; Harvard University Medical Affiliates; Boston Children's Hospital
  摘要：In most eukaryotic organisms, cells that rely on continuous cell division employ the enzyme telomerase which replenishes chromosome termini through the addition of telomeric repeats. In budding yeast, the telomerase holoenzyme is composed of a catalytic core associated with two regulatory subunits, Est1 and Est3. The Est1 protein binds a telomere- specific RPA-like complex to recruit telomerase to chromosome ends. However, the regulatory function of the Est3 subunit has remained elusive. We re...
• Astrocytic EphA4 signaling is important for the elimination of excitatory synapses in Alzheimer's disease AI翻译
  作者：Yang, Xin; Wang, Ye; Qiao, Yi; Lin, Jingwen; Lau, Jackie K. Y.; Fu, Wing-Yu; Fu, Amy K. Y.; Ip, Nancy Y.
  作者单位：Hong Kong University of Science & Technology; Hong Kong University of Science & Technology
  摘要：Cell surface receptors, including erythropoietin- producing hepatocellular A4 (EphA4), are important in regulating hippocampal synapse loss, which is the key driver of memory decline in Alzheimer's disease (AD). However, the cell- specific roles and mechanisms of EphA4 are unclear. Here, we show that EphA4 expression is elevated in hippocampal CA1 astrocytes in AD conditions. Specific knockout of astrocytic EphA4 ameliorates excitatory synapse loss in the hippocampus in AD transgenic mouse mod...
• Biochemical and structural bases for talin ABSs-F-actin interactions AI翻译
  作者：Biertumpfel, Christian; Yamada, Yurika; Vasquez-Montes, Victor; Truong, Thien Van; Cada, A. King; Mizuno, Naoko
  作者单位：National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI); National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
  摘要：Focal adhesions (FAs) are large intracellular macromolecular assemblies that play a critical role in cell polarization and migration. Talin serves as a direct connection between integrin receptor and actomyosin cytoskeleton within FAs. Talin contains three actin- binding sites (ABS1-3) that engage discreetly during the development of FAs, thus acting as a critical player in FA initiation and maturation. However, the molecular basis of the ABS-F-actin interactions remains unknown. Here, we expl...
• Variable transduction of thyroid hormone signaling in structures of the mouse brain AI翻译
  作者：Sinko, Richard; Salas-Lucia, Federico; Mohacsik, Petra; Halmos, Emese; Wittmann, Gabor; Egri, Peter; Bocco, Barbara M. L. C.; Batistuzzo, Alice; Fonseca, Tatiana L.; Fekete, Csaba; Bianco, Antonio C.; Gereben, Balazs
  作者单位：HUN-REN; HUN-REN Institute of Experimental Medicine; University of Chicago; Semmelweis University; HUN-REN; HUN-REN Institute of Experimental Medicine
  摘要：L- thyroxine (L- T4) monotherapy is the standard treatment for hypothyroidism, administered daily to normalize TSH levels. Once absorbed, T4 is converted to T3 to alleviate most symptoms. However, this treatment abnormally elevates plasma T4 levels in over 50% of patients. Using L- T4- treated Thyroid Hormone (TH) Action Indicator mice, which express a T3- regulated luciferase (Luc) reporter, we examined whether these T4 elevations disrupt TH signaling. Hypothyroid mice exhibited reduced Luc e...
• Turbulence enhances wave attenuation of seagrass in combined wave-current flows AI翻译
  作者：Vettori, Davide; Giordana, Francesco; Manes, Costantino
  作者单位：Polytechnic University of Turin
  摘要：these plants are at protecting coasts from erosion and floods. While recent studies have significantly advanced the understanding of seagrass wave attenuation in pure-wave conditions, the presence of a current introduces several complications that have yet to be fully explored. In the present study, we quantify the wave attenuation of seagrass canopies in the presence of a current parallel to the direction of wave propagation via experiments conducted with dynamically scaled mimics of seagrass...
• Extremal structures with embedded prefailure indicators AI翻译
  作者：Christensen, Christoffer Fyllgraf; Engqvist, Jonas; Wang, Fengwen; Sigmund, Ole; Wallin, Mathias
  作者单位：Technical University of Denmark; Lund University
  摘要：Preemptive identification of potential failure under loading of engineering structures is a critical challenge. Our study presents an innovative approach to design built-in prefailure indicators within multiscale structural designs with optimized load carrying capabilities utilizing the design freedom of topology optimization. The indicators are engineered to visibly signal load conditions approaching the global critical buckling load at predefined locations. By showing noncritical local buckl...
• Toxoplasma chitinase- like protein orchestrates cyst wall glycosylation to facilitate effector export and cyst turnover AI翻译
  作者：Fu, Yong; Tomita, Tadakimi; Weiss, Louis M.; West, Christopher M.; Sibley, L. David
  作者单位：Washington University (WUSTL); Montefiore Medical Center; Albert Einstein College of Medicine; Yeshiva University; Yeshiva University; Montefiore Medical Center; Albert Einstein College of Medicine; University System of Georgia; University of Georgia
  摘要：Toxoplasma bradyzoites reside in tissue cysts that undergo cycles of expansion, rupture, and release to foster chronic infection. The glycosylated cyst wall acts as a protective barrier, although the processes responsible for formation, remodeling, and turnover are not understood. Herein, we identify a noncanonical chitinase- like enzyme TgCLP1 that localizes to micronemes and is targeted to the cyst wall after secretion. Genetic deletion of TgCLP1 resulted in a thickened cyst wall that decrea...
• CBX2 suppresses interferon signaling to diminish tumor immunogenicity via a noncanonical corepressor complex AI翻译
  作者：Lin, Yanxun; Jin, Huan; She, Yong; Zhang, Yiqun; Cui, Lei; Xie, Chunyuan; Liu, Yongxiang; Zhang, Huanling; Guo, Hui; Wu, Jiaxin; Li, Lin; Guo, Zixuan; Wang, Xiaojuan; Jiang, Wu; Chen, Xu; He, Shuai; Zhou, Penghui; Tan, Jing; Bei, Jin- Xin; Liu, Jinyun; Chen, Yan- Xing; Zhao, Qi; Xia, Xiaojun; Wang, Zining
  作者单位：State Key Lab Oncology South China; Sun Yat Sen University; Tongji University; Sun Yat Sen University; Sun Yat Sen University; Hainan Medical University
  摘要：Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti- PD1 or adoptive T cell therapies by using murine syngeneic tumor mode...
• Preventing inappropriate signals pre- and post- ligand perception by a toggle switch mechanism of ERECTA AI翻译
  作者：Chen, Liangliang; Maes, Michal; Cochran, Alicia M.; Avila, Julian R.; Derbyshire, Paul; Sklenar, Jan; Haas, Kelsey M.; Villen, Judit; Menke, Frank L. H.; Torii, Keiko U.
  作者单位：Howard Hughes Medical Institute; University of Texas System; University of Texas Austin; University of Texas System; University of Texas Austin; Howard Hughes Medical Institute; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC); John Innes Center; University of East Anglia; University of Washington; University of Washington Seattle; University of Washington; University of Washington Seattle; Harvard University; Massachusetts Institute of Technology (MIT); Broad Institute
  摘要：Dynamic control of signaling events requires swift regulation of receptors at an active state. By focusing on the Arabidopsis ERECTA (ER) receptor kinase, which perceives peptide ligands to control multiple developmental processes, we report a mechanism preventing inappropriate receptor activity. The ER C- terminal tail (ER_CT) functions as an autoinhibitory domain: Its removal confers higher kinase activity and hyperactivity during inflorescence and stomatal development. ER_CT is required for...