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Converting sensory information into motor commands is fundamental to most of our actions . In , visuomotor transformations are mediated by Visual Projection Neurons (VPNs) . These neurons encode object location and motion to drive directional behaviors through a synaptic gradient mechanism . However, the molecular origins of such graded connectivity remain unknown. We addressed this question in a VPN cell type called LPLC2 , which integrates looming motion and transforms it into an escape response through two separate dorsoventral synaptic gradients at its inputs and outputs. We identified two corresponding dorsoventral expression gradients of cell recognition molecules within the LPLC2 population that regulate this synaptic connectivity. Dpr13 determines synaptic outputs of LPLC2 axons by interacting with its binding partner, DIP-ε, expressed in the Giant Fiber - a neuron that mediates escape . Similarly, Beat-VI regulates synaptic inputs onto LPLC2 dendrites by interacting with Side-II expressed in upstream motion-detecting neurons. Behavioral, physiological, and molecular experiments demonstrate that these coordinated molecular gradients regulate synaptic connectivity, enabling the accurate transformation of visual features into motor commands. As continuous variation in gene expression within a neuronal type is also observed in the mammalian brain , graded expression of cell recognition molecules may represent a common mechanism underlying synaptic specificity.
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http://dx.doi.org/10.1101/2024.09.04.610846 | DOI Listing |
J Biomed Sci
September 2025
Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Background: PPM1D (protein phosphatase Mg⁺/Mn⁺ dependent 1D) is a Ser/Thr phosphatase that negatively regulates p53 and functions as an oncogenic driver. Its gene amplification and overexpression are frequently observed in various malignancies and disruption of PPM1D degradation has also been reported as a cause of cancer progression. However, the precise mechanisms regulating PPM1D stability remain to be elucidated.
View Article and Find Full Text PDFAAPS J
September 2025
Gene Transfer and Immunogenicity Branch, Division of Gene Therapy 2, Office of Gene Therapy, Office of Therapeutic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration, WO52 RM3124, 10903 New Hampshire Ave, Silver Spring, Maryland, 20993-0002, USA.
As the field of gene therapy advances and as the importance of sex as a biological variable in shaping viral immune responses is recognized, the impact of sex on adeno-associated virus (AAV) vectors mediated gene therapies remain largely unexplored. Here we review current understanding of the immune response against AAV gene therapy as well as the knowledge of sex differences observed in viral responses. We discuss sex differences in innate immune mechanisms such as Toll-like receptor recognition and complement activation, as well as the functional responses of key immune cells such as dendritic cells, macrophages, and T/B cells that are involved in AAV immunogenicity.
View Article and Find Full Text PDFRev Gastroenterol Mex (Engl Ed)
September 2025
Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia; Departamento de Medicina Interna, Servicio de Gastroenterología, Fundación Valle del Lili, Cali, Colombia. Electronic address:
Introduction And Aim: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms originating in neuroendocrine cells from the gastric mucosa and submucosa, small intestine, large intestine, rectum, and pancreas. Our aim was to describe their histopathologic, endoscopic, and clinical characteristics and the experience with these tumors at a tertiary care hospital center in the Colombian Southwest.
Materials And Methods: A retrospective, analytic, observational, and descriptive study included 93 patients diagnosed with GEP-NETs, within the time frame of 2018 and 2022.
J Immunother Cancer
September 2025
Division of Hematology & Oncology, Department of Medicine, School of Medicine, University of California, Irvine, California, USA
Background: γδ T cells possess unique immunological features including tissue tropism, major histocompatibility complex-independent antigen recognition, and hybrid T/natural killer cell properties that make them promising candidates for cancer immunotherapy. However, the therapeutic potential of Vδ1 γδ T cells, particularly when engineered with chimeric antigen receptors (CARs), remains underexplored in solid tumors such as pancreatic cancer (PC), largely due to their low abundance in peripheral blood and challenges in ex vivo expansion. This study aims to directly compare the preclinical safety and efficacy among CAR-engineered Vδ1 γδ T cells, Vδ2 γδ T cells, and conventional αβ T cells.
View Article and Find Full Text PDFInt J Biol Macromol
September 2025
School of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Electronic address:
The development of antiviral nanotherapeutics remains a formidable challenge due to the structural diversity and rapid evolution of viral surface glycoconjugates. Here, we report a rationally engineered multivalent Galectin-1 (Gal-1) nanoplatform based on 13-nm gold nanoparticles (AuNPs) for high-affinity glycan targeting and therapeutic inhibition of influenza virus. By leveraging site-specific conjugation and molecular orientation control, the AuNP/Gal-1 nanocomplex maximizes the exposure of carbohydrate recognition domains (CRDs) while preserving Gal-1's tertiary structure, as confirmed by molecular dynamics simulations and spectroscopic analyses.
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