Polarized signal transduction from cell surface receptors plays a central role in the development and homeostasis of multicellular organisms, and it also contributes to cellular dysfunction in many disease states. Understanding the molecular and cellular bases of polarized signaling requires experimental methods that provide precise spatiotemporal control of receptor activation. However, we currently lack strategies for inducing both sustained and spatially constrained signal transduction. In the present study, we combined synthetic and cell biological tools to develop a generalizable photoactivation approach for the stimulation of cell surface receptors. Our system, which is based upon the local decaging of a "universal" peptide ligand, is particularly well suited for the live imaging of single cells. We anticipate that it will greatly facilitate future mechanistic analyses of polarized signal transduction in a variety of cell types.
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http://dx.doi.org/10.1021/acschembio.5b00372 | DOI Listing |
Hepatology
January 2025
Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan.
Background Aims: Hepatitis B virus (HBV) leads to severe liver diseases, such as cirrhosis and hepatocellular carcinoma. Identification of host factors that regulate HBV replication can provide new therapeutic targets. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as an HBV entry receptor has enabled the establishment of hepatic cell lines for analyzing HBV infection and propagation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637.
Many proteins form paralogous multimers-molecular complexes in which evolutionarily related proteins are arranged into specific quaternary structures. Little is known about the mechanisms by which they acquired their stoichiometry (the number of total subunits in the complex) and heterospecificity (the preference of subunits for their paralogs rather than other copies of the same protein). Here, we use ancestral protein reconstruction and biochemical experiments to study historical increases in stoichiometry and specificity during the evolution of vertebrate hemoglobin (Hb), an αβ heterotetramer that evolved from a homodimeric ancestor after a gene duplication.
View Article and Find Full Text PDFAnn Surg Oncol
January 2025
Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Background: Three dimensional (3D) cell cultures can be effectively used for drug discovery and development but there are still challenges in their general application to high-throughput screening. In this study, we developed a novel high-throughput chemotherapeutic 3D drug screening system for gastric cancer, named 'Cure-GA', to discover clinically applicable anticancer drugs and predict therapeutic responses.
Methods: Primary cancer cells were isolated from 143 fresh surgical specimens by enzymatic treatment.
Esophagus
January 2025
Department of Medical Oncology, National Taiwan University Cancer Center, 7 Chung-Shan South Road, Taipei, 10002, Taiwan.
Esophageal squamous cell carcinoma (ESCC) is a prevalent and highly lethal malignancy in Asia. Recent advancements in immune checkpoint inhibitors (ICIs) have markedly transformed the systemic therapy landscape for ESCC. Anti-PD-1-based combination with chemotherapy or with ipilimumab, an anti-CTLA-4 antibody, have been established as the new standard first-line treatments for patients with advanced ESCC.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Nanjing University, College of Engineering and Applied Sciences, No. 163 Xianlin Avenue, Qixia District, Nanjing, Nanjing, CHINA.
Electrolyte engineering has emerged as an effective strategy for stabilizing Zn-metal anodes. However, a single solute or solvent additive is far from sufficient to meet the requirements for electrolyte cycling stability. Here, we report a new-type high-entropy electrolyte composed of equal molar amounts of Zn(OTf)2 and LiOTf, along with equal volumes of H2O, triethyl phosphate, and dimethyl sulfoxide, which enhances electrolyte stability by increasing solvation entropy.
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