Protons activate acid-sensing ion channel 1a (ASIC1a) in the central nervous system (CNS) although the impact of such activation on brain outputs remains elusive. Progress elucidating the functional roles of ASIC1a in the CNS has been hindered by technical difficulties of achieving acidification with spatial and temporal precision. We have implemented a method to control optically the opening of ASIC1a in brain slices and also in awake animals. The light-driven H(+) pump ArchT was expressed in astrocytes of mouse cortex by injection of adenoviral vectors containing a strong and astrocyte-specific promoter. Illumination with amber light acidified the surrounding interstitium and led to activation of endogenous ASIC1a channels and firing of action potentials in neurons localized in close proximity to ArchT-expressing astrocytes. We conclude that this optogenetic method offers a minimally invasive approach that enables examining the biological consequences of ASIC1a currents in any structure of the CNS and in the modulation of animal behaviors.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140900 | PMC |
http://dx.doi.org/10.1074/jbc.M114.550012 | DOI Listing |
Blood
January 2025
University of Chicago, Chicago, Illinois, United States.
Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores.
View Article and Find Full Text PDFPhysiol Rev
January 2025
Metabolism, Obesity, and Nutrition Lab, School of Health, Concordia University, Montréal, Québec, Canada.
Adult males and females have markedly different body composition, energy expenditure, and have different degrees of risk for metabolic diseases. A major aspect of metabolic regulation involves the appropriate storage and disposal of glucose and fatty acids. The use of sophisticated calorimetry, tracer, and imaging techniques have provided insight into the complex metabolism of these substrates showing that the regulation of these processes varies tremendously throughout the day, from the overnight fasting condition to meal ingestion, to the effects of physical activity.
View Article and Find Full Text PDFJ Med Chem
January 2025
Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province; Engineering Research Center of Natural Medicine Active Molecule Research & Development, Liaoning Province; Key Laboratory of Natural Bioactive Compounds Discovery & Modification, Shenyang; School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for nonsmall cell lung cancer (NSCLC) treatment due to its overexpression in NSCLC cells. In this work, to address the deficiency that sesquiterpene lactone containing α-methylene-γ-lactone moiety was rapidly metabolized by endogenous nucleophiles, series of novel thioether derivatives were designed and synthesized based on a reactive oxygen species (ROS)-triggered prodrug strategy. Among them, prodrug exhibited potent cytotoxicity against NSCLC cells and better release rates in response to ROS.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Medical 3D Printing Center, Orthopedic Institute, Department of Orthopedic Surgery, The First Affiliated Hospital, School of Basic Medical Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, 215000, China.
Stem cell implantation holds promise for enhancing bone repair, but risks of pathogen transmission and malignant cell transformation should not be ignored. Compared to stem cell implantation, recruitment of endogenous stem cells to injured sites is more critical for in situ bone regeneration. In this study, based on the acidic microenvironment of bone injury, an HG-AA-SDF-1α composite hydrogel with a dual-control intelligent switch function is developed by incorporating stromal cell-derived factor (SDF-1α), arginine carbon dots (Arg-CDs), and calcium ions (Ca) into the oxidized hyaluronic acid/gelatin methacryloyl (HG) hydrogel.
View Article and Find Full Text PDFJ Exp Bot
January 2025
College of Grassland Science and Technology, Sichuan Agricultural University, Chengdu, China.
Flowering, a pivotal plant lifecycle event, is intricately regulated by environmental and endogenous signals via genetic and epigenetic mechanisms. Photoperiod is a crucial environmental cue that induces flowering by activating integrators through genetic and epigenetic pathways. However, the specific role of DNA methylation, a conserved epigenetic marker, in photoperiodic flowering remains unclear.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!