Modifications in serotonin (5-HT) neurotransmission have been associated with the physiopathology of anxiety and depression. Among the numerous 5-HT receptor subtypes, several (5-HT1A, 5-HT1B, 5-HT2 and 5-HT3) could be involved in these etiologies. By using a murine genetic model, we attempted to correlate variations in the density of receptor subtypes with modifications of anxiety-related behaviors. From a classic inbred strain (C57BL/6ByJ) and a linkage-testing inbred strain (ABP/Le), segregated F(2) populations for 3 loci located in the 4th, 7th and 9th chromosomes have been selected for their different responses in anxiety-related behavioral tests. The regional density of 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2B receptors has been measured in the brains of parental strains, F(1) and F(2) populations by quantitative autoradiography. The results suggest that chromosomal fragments containing the brown, pink-eyed dilution and the short-ear loci, previously shown to be involved in anxiogenic processes, are mainly associated with a variation in the density of the 5-HT1B receptors.
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http://dx.doi.org/10.1016/0006-8993(95)01297-4 | DOI Listing |
Proc Natl Acad Sci U S A
February 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China.
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 models.
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February 2025
Department of Biological Sciences, College of Liberal Arts and Sciences, Wayne State University, Detroit, MI 48202.
The mammalian Hippo kinases, MST1 and MST2, regulate organ development and suppress tumor formation by balancing cell proliferation and death. In macrophages, inflammasomes detect molecular patterns from invading pathogens or damaged host cells and trigger programmed cell death. In addition to lytic pyroptosis, the signatures associated with apoptosis are induced by inflammasome activation, but how the inflammasomes coordinate different cell death processes remains unclear.
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February 2025
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.
The ionizable lipid component of lipid nanoparticle (LNP) formulations is essential for mRNA delivery by facilitating endosomal escape. Conventionally, these lipids are synthesized through complex, multistep chemical processes that are both time-consuming and require significant engineering. Furthermore, the development of new ionizable lipids is hindered by a limited understanding of the structure-activity relationships essential for effective mRNA delivery.
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January 2025
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Cochlear inner hair cells (IHCs) and outer hair cells (OHCs) require different transcription factors for their cell fate stabilization and survival, suggesting separate mechanisms are involved. Here, we found that the transcription factor Casz1 was crucial for early IHC fate consolidation and for OHC survival during mouse development. Loss of Casz1 resulted in transdifferentiation of IHCs into OHCs, without affecting OHC production.
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January 2025
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
Studying the functional consequences of structural variants (SVs) in mammalian genomes is challenging because (i) SVs arise much less commonly than single-nucleotide variants or small indels and (ii) methods to generate, map, and characterize SVs in model systems are underdeveloped. To address these challenges, we developed Genome-Shuffle-seq, a method that enables the multiplex generation and mapping of thousands of SVs (deletions, inversions, translocations, and extrachromosomal circles) throughout mammalian genomes. We also demonstrate the co-capture of SV identity with single-cell transcriptomes, facilitating the measurement of SV impact on gene expression.
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