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Biology subjects

shen, y.

Publications and source records attributed to shen, y..

3 recordsLinked to original sources

Ancient admixture catalyzes homoploid hybrid speciation and intense genomic erosion in Asian langurs

Ancient admixture catalyzes evolutionary innovation, yet its long-term genomic consequences for newly formed lineages remain poorly understood. Here, based on 53 genomes covering 19 species of the Asian langur genus Trachypithecus, we explore admixtures role in shaping a reticulated radiation. Genome-wide analyses of phylogenomic triplet topologies demonstrate that phylogenetic discordance across this radiation is primarily driven by widespread introgression rather than incomplete lineage sorting. To mitigate historical noise and resolve the ancestral species tree, we anchored our phylogenetic analysis on the X-linked recombination desert (XLRD), which exhibits an 84.5% introgression reduction compared to autosomes. We identify Delacours langur as a clear case of homoploid hybrid speciation, arising from ancient admixture with [~]70:30 genomic contributions from ancestral northern and southern limestone langur lineages. This hybrid species fixed key reproductive isolation loci; notably, alternate inheritance of pigmentation genes (SLC45A4, HPS5, ADCY10) systematically coupled with a fixed RNF175 chimeric allele to drive its diagnostic pelage phenotype. This illustrates how introgressed multi-gene networks rapidly establish prezygotic visual barriers and profound phenotypic divergence. However, subsequent spatial isolation within fragmented karst landscapes forced a major conversion of genetic burden into realized load. Genome-wide, over 82% of loss-of-function variants occur in a homozygous state, reflecting the expression of lethal recessive mutations within long runs of homozygosity. Together, our findings demonstrate that ancient admixture can trigger homoploid hybrid speciation, yet subsequent ecological restriction locks derived lineages into severe, long-term genomic erosion, revealing a fundamental trade-off in reticulate evolutionary radiations.

evolutionary biology↗

Microglia-derived IL-18 remodels hippocampal plasticity to constrain traumatic fear memory

Post-traumatic stress disorder (PTSD) involves complex neuroimmune-synaptic crosstalk in the hippocampus. Here we show that interleukin-18 (IL-18), an extensively studied pro-inflammatory cytokine, serves a protective role against traumatic fear memory through a microglia-to-neuron signaling axis. Traumatic stress induces sustained upregulation of IL-18 in the hippocampus. Exogenous IL-18 administration attenuates fear memory, whereas blockade of IL-18 signaling exacerbates it. Mechanistically, microglial-derived IL-18 acts on neuronal IL-18R1 to restore stress-impaired synaptic plasticity and reduce perineuronal net density, thereby facilitating structural synaptic remodeling. In addition, IL-18 modulates the synaptic organization of fear memory-encoding engram cells within hippocampal ensembles. Together, these findings redefine IL-18 as a homeostatic regulator of post-trauma hippocampal synaptic function and identify the hippocampal IL-18 pathway as a potential therapeutic target for PTSD.

neuroscience↗

Adipocyte microRNA-802 promotes adipose tissue inflammation and insulin resistance by modulating macrophages in obesity

Adipose tissue inflammation is now considered to be a key process underlying metabolic diseases in obese individuals. However, it remains unclear how adipose inflammation is initiated and maintained or the mechanism by which inflammation develops. We found that microRNA-802 (miR-802) expression in adipose tissue is progressively increased with the development of dietary obesity in obese mice and humans. The increasing trend of miR-802 preceded the accumulation of macrophages. Adipose tissue-specific knockout of miR-802 lowered macrophage infiltration and ameliorated systemic insulin resistance. Conversely, the specific overexpression of miR-802 in adipose tissue aggravated adipose inflammation in mice fed a high-fat diet. Mechanistically, miR-802 activates noncanonical and canonical NF-{kappa}B pathways by targeting its negative regulator, TRAF3. Next, NF-{kappa}B orchestrated the expression of chemokine and SREBP1, which translated into strong recruitment and M1-like polarization of macrophages. Our findings indicate that miR-802 endows adipose tissue with the ability to recruit and polarize macrophages, which underscores miR-802 as an innovative and attractive candidate for miRNA-based immune therapy for adipose inflammation.

immunology↗