The Early Life Microbiota Mediates Maternal Effects on Offspring Growth in a Nonhuman Primate
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Mammalian mothers influence offspring development by providing nutrients and other bioactive compounds through the placenta or milk. A relatively unexplored mechanism for maternal effects is vertical transmission of bacteria through milk to the infant gut. Infants that receive more glycan-utilizing bacteria from milk might better exploit oligosaccharides, which could improve nutrition and accelerate growth.
Injury-Induced Cooperation of InhibinβA and JunB is Essential for Cell Proliferation in Xenopus Tadpole Tail Regeneration
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Certain animal species (e.g., amphibians) that can regenerate lost tissues and limbs after injury offer potential for applications in regenerative medicine. Cell proliferation is essential for the reconstruction of injured tissue, but the molecular mechanisms that regulate the transition from wound healing to regenerative cell proliferation remain unclear. Using Xenopus tropicalis, investigators examined the effects of injury on the expression of inhibin subunit beta A (inhba) and junB proto-oncogene (junb).
Identification of Constrained Sequence Elements Across 239 Primate Genomes
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Functional genomic elements that have acquired selective constraints specific to the primate order are prime candidates for understanding evolutionary changes in humans, but the selective constraints specific to the phylogenetic branch from which the human species ultimately emerged remain largely unidentified. Researchers constructed a genome-wide multiple sequence alignment of 239 primate species to better characterize constraint at noncoding regulatory sequences in the human genome.
GenomeMUSter Mouse Genetic Variation Service Enables Multitrait, Multipopulation Data Integration and Analysis
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Advances in genetics, including transcriptome-wide and phenome-wide association analysis methods, create compelling new opportunities for using fully reproducible and widely studied inbred mouse strains to characterize the polygenetic basis for individual differences in disease-related traits. Investigators developed an imputation approach and implemented data service to provide a broad and more comprehensive mouse variant resource. They evaluated the strain-specific imputation accuracy on a “held-out” test set that was not used in the imputation process.
Very-Long-Chain Fatty Acids Induce Glial-Derived Sphingosine-1-Phosphate Synthesis, Secretion, and Neuroinflammation
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Very-long-chain fatty acids (VLCFAs) are the most abundant fatty acids in myelin. During age‑associated degeneration of myelin, glia are exposed to increased levels of VLCFAs. Investigators previously described a novel phenotype in patients that harbors a novel variant in the peroxisomal enzyme ACOX1. Here, they report that that glial loss of ACOX1 leads to an increase of VLCFAs, which results in a concomitant increase in sphingosine-1-phosphate (S1P). They found that suppressing S1P function attenuates the pathological phenotypes caused by excess VLCFAs.
Lipid Droplets and Peroxisomes Are Co-Regulated to Drive Lifespan Extension in Response to Mono-Unsaturated Fatty Acids
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Investigators studied the mechanism by which mono-unsaturated fatty acids (MUFAs) extend longevity. They found that MUFAs upregulated the number of lipid droplets in fat storage tissues of Caenorhabditis elegans, and increased lipid droplets are necessary for MUFA-induced longevity and predicted remaining lifespan. Lipidomics data revealed that MUFAs modify the ratio of membrane lipids and ether lipids, which leads to decreased lipid oxidation in middle-aged individuals. MUFAs also upregulate peroxisome number.
Investigation of Monoclonal Antibody CSX-1004 for Fentanyl Overdose
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The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl and has led to more than 70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, the authors present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice, CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil.
Tenth Aquatic Models of Human Disease Conference 2022 Workshop Report: Aquatics Nutrition and Reference Diet Development
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Standard reference diets (SRDs) for aquatic model organisms, vital for supporting scientific rigor and reproducibility, are yet to be adopted. At this workshop, the authors presented findings from a 7-month diet test study conducted across three aquatic research facilities: Zebrafish International Resource Center (University of Oregon), Kent and Sharpton laboratories (Oregon State University), and Xiphophorus Genetic Stock Center (Texas State University).
Age-Associated DNA Methylation Changes in Xenopus Frogs
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Age-associated changes in DNA methylation have not been characterized yet in amphibians, which include widely studied model organisms. Here the authors present clear evidence that the aquatic vertebrate species Xenopus tropicalis displays patterns of age-associated changes in DNA methylation.
CD8+ T Cells Control SIV Infection Using Both Cytolytic Effects and Non-Cytolytic Suppression of Virus Production
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HIV continuously evades and subdues the host immune responses through multiple strategies, and an understanding of these strategies can help inform research efforts. Using a mathematical model, investigators assessed whether CD8+ cells from male rhesus macaques exert a cytolytic response against infected cells prior to viral production. Their goal was to elucidate the possible mode of action of CD8+ cells on simian immunodeficiency virus (SIV)–infected cells.