Biology subjects

Di, J.

Publications and source records attributed to Di, J..

5 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2025

A multi-tissue atlas of genetic regulatory effects in sheep

Characterizing the impact of genomic variants on genome function and ultimately complex traits in livestock is essential for the development of sustainable precision agriculture and comparative genomics. Here, as part of the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we present the pilot phase of the SheepGTEx resource through analyzing 6,761 RNA-sequencing samples of 51 primary tissues in a multi-breed population of sheep. We identify millions of regulatory variants associated with seven types of molecular phenotypes, and fine-map 322,468 primary and 114,017 non-primary effects, revealing a high degree of regulatory allelic heterogeneity. We systematically characterize the pleiotropic effects of these variants on molecular phenotypes, assess their context-specific regulatory patterns across tissues, breeds, sexes, and developmental stages, as well as explore their evolutionary constraints across mammals. Finally, we demonstrate the substantial potential of the SheepGTEx resource (https://sheepgtex.farmgtex.org), by providing examples of regulatory mechanisms underpinning 34 complex traits, population divergence between European and Asian breeds, and adaptive evolution in sheep over the past ten millennia.

genomics↗

bioRxiv2021

Exophers are components of mammalian cell neurobiology in health and disease

Maintenance of cellular homeostasis is critically important for the survival of cells and organisms. Degradation and recycling of biomolecules and whole organelles is an essential mechanism for maintaining cellular homeostasis. The main systems responsible for these processes are the ubiquitin-proteasome system and autophagy-lysosome pathway. Another mechanism was reported in c. elegans--formation of large, membrane-enclosed projections called "exophers," into which cells direct debris and toxic protein aggregates1. Exophers were shown to act as large, temporary disposal compartments that disconnected from the cells within several hours. Here, we report the discovery of exophers in the mammalian brain, including the brains of humans and mice. Similar to those described in nematodes, the mammalian exophers appear to emanate from the cell body, initially connected by a nanotube, and eventually disconnect. Rare, innate exophers were found in healthy human brain and primary neurons from wild-type mice, presumably mediating transfer of large cargo between cells. The number of exophers increased as an adaptive response under proteostatic stress, e.g., in Alzheimers disease brain or in primary neurons from two tauopathy mouse models, where the exophers likely facilitated expulsion of proteotoxic material. Our findings suggest that exopherogenesis is a rare, innate house-keeping process that is elevated adaptively in response to proteostatic pressure and is a conserved mechanism from nematodes to humans.

cell biology↗

bioRxiv2020

Identifying Neural Signatures Mediating Behavioral Symptoms and Psychosis Onset: High-Dimensional Whole Brain Functional Mediation Analysis

Along the pathway from behavioral symptoms to the development of psychotic disorders sits the multivariate mediating brain. The functional organization and structural topography of large-scale neural mediators among patients with brain disorders, however, are not well understood. Here, we design a high-dimensional brain-wide functional mediation framework to investigate brain regions that intermediate between baseline behavioral symptoms and future conversion to full psychosis among individuals at clinical high risk (CHR). Using resting-state functional magnetic resonance imaging (fMRI) data from 263 CHR subjects, we extract an brain atlas and a {beta} brain atlas: the former underlines brain areas associated with prodromal symptoms and the latter highlights brain areas associated with disease onset. In parallel, we identify the P mediators and the N mediators that respectively facilitate or protect against developing brain disorders among subjects with more severe behavioral symptoms and quantify the effect of each neural mediator on disease development. Taken together, the -{beta} atlases and the P-N mediators paint a brain-wide picture of neural markers that are potentially regulating behavioral symptoms and the development of psychotic disorders and highlight a statistical framework that is useful to uncover large-scale intermediating variables in a regulatory biological organization.

bioinformatics↗

bioRxiv2017

Patterns of sedentary and active time accumulation are associated with mortality in US adults: The NHANES study

PurposeSedentary behavior has become a public health pandemic and has been associated with a variety of comorbidities including cardiovascular disease, type 2 diabetes, and some cancers. Previous studies have also shown that excessive amount of sedentary behavior is associated with all-cause mortality. However, no studies investigated whether patterns of sedentary and active time accumulation are associated with mortality independently of total sedentary and total active times. This study addresses this question by i) comparing several analytical ways to quantify patterns of both sedentary and active time accumulation through metrics of fragmentation of objectively-measured physical activity and ii) exploring the association of these metrics with all-cause mortality in a nationally representative US sample of elderly adults.\n\nMethodsThe accelerometry data of 3400 participants aged 50 to 84 in the National Health and Nutrition Examination Survey 2003-2006 cohorts were analyzed. Ten fragmentation metrics were calculated to quantify the duration of sedentary and active bouts: average bout duration, Gini index, average hazard, between-state transition probability, and the parameter of power law distribution. The association of these fragmentation metrics with all-cause mortality followed through December 31, 2011 was assessed with survey-weighted Cox proportional hazard models.\n\nResultsIn models adjusted for age, sex, race/ethnicity, education, body mass index, common comorbidities, and total sedentary/active time, four fragmentation metrics were associated with lower mortality risk: average active bout duration (HR=0.72 for 1SD increase, 95% CI = 0.590.88), Gini index for active bouts (HR = 0.75, 95% CI = 0.64-0.86), the parameter of power law distribution for sedentary bouts (HR = 0.75, 95% CI = 0.63-0.90), and sedentary-to-active transition probability (HR = 0.77, 95% CI = 0.61-0.96), and four fragmentation metrics were associated with higher mortality risk: the active-to-sedentary transition probability (HR = 1.40, 95% CI=1.23-1.58), the parameter of power law distribution for active bouts (HR = 1.33, 95% CI = 1.16-1.52), average hazard for durations of active bouts (HR = 1.32, 95% CI = 1.18-1.48), and average sedentary bout duration (HR =1.07, 95% CI = 1.01-1.13). After sensitivity analysis, average sedentary bout duration and sedentary-to-active transition probability became insignificant.\n\nConclusionLonger average duration of active bouts, a lower probability of transitioning from active to sedentary behavior, and a higher normalized variability of active bout durations were strongly negatively associated with all-cause mortality independently of total active time. A larger proportion of longer sedentary bouts were positively associated with all-cause mortality independently of total sedentary time. The results also suggested a nonlinear association of average active bout duration with mortality that corresponded to the largest risk increase in subjects with average active bout duration less than 3 minutes.

epidemiology↗