Biology subjects

Jones, J. W.

Publications and source records attributed to Jones, J. W..

10 recordsLinked to original sources

bioRxiv2026

Isoflurane and surgery aggravate APOE4-dependent lipid dysregulation and neural dysfunction, leading to neurological impairment in male mice

PurposePerioperative exposure to the volatile anesthetic isoflurane (ISO) has been associated with cognitive and olfactory deficits and may increase the risk of Alzheimers disease (AD). Apolipoprotein E4 (APOE4), the strongest genetic risk factor for AD, contributes to disease pathogenesis through disrupted lipid homeostasis. However, whether and how isoflurane interacts with APOE genotype to influence neurological vulnerability remains unclear. MethodsYoung adult, presymptomatic humanized APOE4 and APOE3 knock-in mice underwent laparotomy under 2 h of isoflurane anesthesia. Microglia and astrocytes were isolated from the olfactory bulb (OB) and hippocampus (HI) by magnetic-activated cell sorting. Lipid composition, transcriptional responses, and functional outcomes were assessed using lipidomic, bulk RNA-seq, and longitudinal behavioral testing. In vivo and ex vivo electrophysiological recordings evaluated neuronal excitability and synaptic transmission in both regions. ResultsBy day 7 post-anesthesia, cell type-specific lipidomic profiling of both OB and HI revealed more pronounced lipid perturbations in microglia and astrocytes from APOE4/ISO mice than from APOE3 mice, characterized by elevated free fatty acids, increased lipid peroxidation, triglyceride depletion, and reduced hippocampal hexosylceramides and cardiolipins. Electrophysiological recordings showed greater olfactory circuit dysfunction in APOE4/ISO mice, accompanied by persistent odor memory deficits, transient olfactory sensitivity loss, early motor coordination impairments, and delayed cognitive deficits. RNA sequencing of the OB identified downregulated lipid metabolism and atherosclerosis-related pathways. ConclusionThese findings establish a mechanistic link between APOE4-dependent glial lipid dysregulation, olfactory circuit dysfunction, and delayed cognitive impairment following isoflurane anesthesia and surgery, highlighting lipid homeostasis as a potential therapeutic target.

neuroscience↗

bioRxiv2025

Lysosomal multi-omics reveals altered sphingolipid catabolism as driver of lysosomal dysfunction in the aging brain.

Recent data indicate that lipid composition has profound influence on the brain function and that changes in lipid homeostasis affect brain aging and predisposition to neurodegenerative diseases. Lipids dynamically reside in multiple intracellular locations and their organellar distribution is important for specific interactions and biological function. During brain aging lipid changes have been specifically noted in lysosomes, but the identity of the accumulated lipids, their interactions with other biomolecules such as proteins, and their functional relevance have not been characterized. We used mass spectrometry (MS) to assess longitudinal changes in the lipidome and proteome of lysosomes isolated from the mouse cortex, from the age of 3- to 24-months. Our statistical and machine learning analyses identified two factors demonstrating predictive power for age and differences in both lipids and proteins. Of these, factor 1 was the best predictor of sample age. Factor 1 lipids with the highest feature importance included multiple species of hexosylceramides (HexCer) and their sulfonated derivatives, sulfatides (SHexCer), all of which increased with age. Increased factor 1 proteins included myelin proteins, select sphingolipid catabolism enzymes and proteins associated with lysosomal storage diseases. Our analyses suggested that mechanisms underlying factor 1 encompass the combination of an age-dependent increase in lysosomal delivery of myelin components and alterations in lysosomal sphingolipid catabolism favoring degradation of sphingomyelin over HexCer. The overall age-related lysosomal changes resembled those observed in lysosomal storage diseases, particularly Gaucher disease, where accumulation of HexCer species is associated with lysosomal dysfunction. To corroborate factor 1 predictions, we employed a combination of biochemical, imaging and flow cytometry approaches, which confirmed alterations in sphingolipid catabolism and lysosomal accumulation of myelin components. These changes were associated with age-related alteration in lysosomal morphology, lysosomal dysfunction and inhibition of autophagy in both neurons and microglia. Our findings indicate that factors contributing to lysosomal aging resemble those observed in lysosomal storage diseases and underscore the significance of organelle-specific analyses for dissecting mechanisms contributing to brain aging.

neuroscience↗

bioRxiv2025

Inhibition of autophagy-lysosomal function exacerbates microglial and monocyte lipid metabolism reprograming and dysfunction after brain injury

CNS has an overall higher level of lipids than all tissues except adipose and contains up to 25% of total body cholesterol. Recent data demonstrate a complex crosstalk between lipid metabolism and inflammation, suggesting potential contribution of the lipid-rich brain environment to neuroinflammation. While recent data support the importance of brain lipid environment to inflammatory changes observed in age related chronic neurodegenerative diseases, in vivo interactions between lipid environment, lipid metabolism and neuroinflammation in acute brain disease and injury remain poorly understood. Here we utilize a mouse model of traumatic brain injury (TBI) to demonstrate that acute neurotrauma leads to widespread lipid metabolism reprograming in all microglial and brain associated and infiltrating monocyte populations. Additionally, we identify unique microglial and monocyte populations with higher degree of lipid metabolism reprograming and pronounced accumulation of neutral storage lipids, including cholesteryl esters and triglycerides. These lipids accumulate not only in lipid droplets but also in the microglial and monocyte lysosomes and are associated with lysosomal dysfunction and inhibition of autophagy after TBI. Our data indicate that lipid accumulation in these cells is the result of altered lipid handling rather than lipid synthesis and is triggered by phagocytosis of lipid-rich myelin debris generated after TBI. Finally, we use mice with autophagy defects in microglia and monocytes to demonstrate that further inhibition of autophagy leads to more pronounced lipid metabolism reprograming and exacerbated cellular lipid accumulation. Our data suggest a pathological feedback loop, where lipid phagocytosis causes inhibition of autophagy-lysosomal function, which in turn exacerbates cellular lipid retention, reprograming and inflammation.

neuroscience↗

bioRxiv2025

Vacuum and sonication treatment enables efficient transient gene expression in various monocot and eudicot plant seedlings

Transient gene expression in intact plants is essential for rapidly addressing biological questions, where the current toolkit can be improved for higher efficiencies and broader plant species range. Here, we introduce VAST (Vacuum and Sonication-Assisted Transient expression): a transient transformation method that substantially enhances gene expression efficiency, reproducibility, and versatility across diverse monocot and eudicot intact seedlings. By systematically optimizing plant growth conditions and incorporating vacuum infiltration and sonication pre-treatments prior to seedling co-culture with Agrobacterium tumefaciens, we significantly improved transient gene expression efficiency while minimizing tissue damage compared to existing methods in Arabidopsis thaliana. We further demonstrated the broad applicability of VAST by successfully transforming key model and crop species, including tomato, Brassica rapa, Medicago sativa, Setaria italica (foxtail millet), switchgrass, and wheat. We also demonstrated a case study using the VAST-mediated transient transformation, where a cross-species analyses of nitrate-responsive gene expression highlighted both the conserved and diverged biological responses between the two model crops, A. thaliana and S. italica. VASTs simplicity, versatility, and efficiency provide a powerful tool for functional genomics, synthetic biology, and biotechnology research, opening new avenues for the rapid exploration of gene function, regulation, and editing in diverse plant systems.

plant biology↗

bioRxiv2025

A Multi-Model Ensemble Reveals Soil Carbon Gains from Regenerative Practices in the U.S. Midwest Cropland

Process-based cropping systems models (CSMs) are key components of measurement, monitoring, reporting, and verification (MMRV) frameworks of carbon markets, but their application suffers from model-specific differences that keep any one model from working well across all combinations of soils, climates, crops, and agronomic practices at varying scales. Multi-model ensemble (MME), successfully used to quantify soil, management and climate impact on crop productivity, provide an opportunity to better estimate changes in soil organic carbon (SOC) outcomes for agronomic practices that have the potential to mitigate SOC loss at scale. We used an MME across 46 million hectares of US Midwest cropland at a resolution of 4- km2 to assess the aggregate ability of different regenerative practices to sequester SOC at this scale compared to their dynamic baselines. MME was validated with long-term experimental data and compared to its constituent CSMs, showing greater accuracy and lower uncertainty. The results show that adopting no-till combined with cover crops increased SOC stocks by 0.36 {+/-} 0.12 Mg ha-1 yr-1 aggregated across the entire U.S. Midwest cropland. At the regional scale, this corresponds to a net SOC gain of 16.4 Tg C yr-1 compared to business-as-usual baselines. These benefits are approximately halved when each management change is practiced individually, and the modest gains are only fully realized when continued over the long-term in soils with low initial carbon stock. Results demonstrate the power of MMEs run at high resolution for providing robust estimates of environmental outcomes following agricultural practice change, and for pinpointing locations for most effective intervention. This approach can alleviate many producer carbon market participation barriers and help address market issues while ultimately supporting large-scale regenerative agriculture initiatives.

ecology↗

bioRxiv2024

Lipid Nanoparticles from L. meyenii Walp Mitigate Sepsis through Multimodal Protein Corona Formation

BackgroundPlant-derived nanoparticles (PDNP) are nano-sized particles isolated from various edible plants that contain bioactive components involved in regulating cellular immune responses against pathogenic intrusion and inflammation. PurposeThis study describes a novel PDNP derived from Lepidium meyenii Walp (maca) that efficiently captures pro-inflammatory cytokines and acute phase proteins in its protein corona to enhance survival in two representative lethal models of sepsis. MethodsLipid nanoparticles were isolated from maca (MDNP) and triacylglycerols and phytoceramides were identified as major constituents using lipidomics. The physicochemical properties of MDNPs were determined, anti-inflammatory effects of MDNP were evaluated using in vitro models and in vivo using endotoxemia and cecal ligation and puncture (CLP) polymicrobial sepsis models. Proteomic analysis of MDNP in healthy or LPS-induced inflammatory plasma was used to determine the composition and inflammatory pathways modulated due to the MDNP protein corona. ResultsIn vitro studies showed that MDNP were non-toxic, reduced macrophage activation, and effectively sequestered pro-inflammatory cytokines to mitigate NF-{kappa}B activity under lipopolysaccharide (LPS) stimulation. In a pre-established LPS-induced endotoxemia model, MDNP-treated mice showed significantly reduced systemic pro-inflammatory cytokines and enhanced survival. Untargeted proteomics and pathway analysis of the MDNP protein corona identified an enrichment in acute phase proteins in MDNP-LPS plasma coronas. MDNP treatment also significantly improved survival in the CLP sepsis model in the absence of antibiotics. ConclusionThis work identified MDNP as an efficient, plant-derived lipid NP that broadly sequesters and neutralizes a compilation of inflammatory mediators in their coronas, offering multimodal therapeutic potential for treating inflammatory diseases.

bioengineering↗

bioRxiv2021

Dynamic Gene-Based Ecophysiological Models to Predict Phenotype from Genotype and Environment Data

Predicting the phenotype from the genotype is one of the major contemporary challenges in biology. This challenge is greater in plants because their development occurs mostly post-embryonically under diurnal and seasonal environmental fluctuations. Current phenotype prediction models do not adequately capture all of these fluctuations or effectively use genotype information. Instead, we have developed a dynamic modular approach that captures the genotype, environment, and Genotype-by-Environment effects to express the time-to-flowering phenotype in real time in Phaseolus vulgaris. The module we describe can be applied to different plant processes and can gradually replace processes in existing crop models. Our model can enable accelerated progress in diverse breeding programs, particularly with the prospects of climate change. Finally, a gene-based simulation model can assist policy decision makers in matters pertaining to prediction of food supplies.

plant biology↗

bioRxiv2021

INCORPORATING A DYNAMIC GENE-BASED PROCESS MODULE INTO A CROP SIMULATION MODEL

Dynamic crop simulation models are tools that predict plant phenotype grown in specific environments for genotypes using genotype-specific parameters (GSPs), often referred to as "genetic coefficients." These GSPs are estimated using phenotypic observations and may not represent "true" genetic information. Instead, estimating GSPs requires experiments to measure phenotypic responses when new cultivars are released. The goal of this study was to evaluate a new approach that incorporates a dynamic gene-based module for simulating time-to-flowering for common bean (Phaseolus vulgaris L.) into an existing dynamic crop model. A multi-environment study conducted in 2011 and 2012 included 187 recombinant inbred lines (RILs) from a bi-parental bean family to measure the effects of quantitative trait loci (QTL), environment (E), and QTLxE interactions across five sites. The dynamic mixed linear model from Vallejos et al. (2020) was modified in this study to create a dynamic module that was then integrated into the CSM-CROPGRO-Drybean model. This new hybrid crop model, with the gene-based flowering module replacing the original flowering component, requires allelic makeup of each genotype being simulated and daily E data. The hybrid model was compared to the original CSM model using the same E data and previously estimated GSPs to simulate time-to-flower. The integrated gene-based module simulated days of first flower agreed closely with observed values (root mean square error of 2.73 days and model efficiency of 0.90) across the five locations and 187 genotypes. The hybrid model with its gene-based module also described most of the G, E and GxE effects on time-to-flower and was able to predict final yield and other outputs simulated by the original CSM. These results provide the first evidence that dynamic crop simulation models can be transformed into gene-based models by replacing an existing process module with a gene-based module for simulating the same process.

genomics↗

bioRxiv2018

The genome of the water strider Gerris buenoi reveals expansions of gene repertoires associated with adaptations to life on the water

The semi-aquatic bugs conquered water surfaces worldwide and occupy ponds, streams, lakes, mangroves, and even open oceans. As such, they inspired a range of scientific studies from ecology and evolution to developmental genetics and hydrodynamics of fluid locomotion. However, the lack of a representative water strider genome hinders thorough investigations of the mechanisms underlying the processes of adaptation and diversification in this group. Here we report the sequencing and manual annotation of the Gerris buenoi (G. buenoi) genome, the first water strider genome to be sequenced so far. G. buenoi genome is about 1 000Mb and the sequencing effort recovered 20 949 predicted protein-coding genes. Manual annotation uncovered a number of local (tandem and proximal) gene duplications and expansions of gene families known for their importance in a variety of processes associated with morphological and physiological adaptations to water surface lifestyle. These expansions affect key processes such as growth, vision, desiccation resistance, detoxification, olfaction and epigenetic components. Strikingly, the G. buenoi genome contains three Insulin Receptors, a unique case among metazoans, suggesting key changes in the rewiring and function of the insulin pathway. Other genomic changes include wavelength sensitivity shifts in opsin proteins likely in association with the requirements of vision in water habitats. Our findings suggest that local gene duplications might have had an important role during the evolution of water striders. These findings along with the G. buenoi genome open exciting research opportunities to understand adaptation and genome evolution of this unique hemimetabolous insect.

genomics↗

bioRxiv2017

A model species for agricultural pest genomics: the genome of the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae)

The Colorado potato beetle is one of the most challenging agricultural pests to manage. It has shown a spectacular ability to adapt to a variety of solanaceaeous plants and variable climates during its global invasion, and, notably, to rapidly evolve insecticide resistance. To examine evidence of rapid evolutionary change, and to understand the genetic basis of herbivory and insecticide resistance, we tested for structural and functional genomic changes relative to other arthropod species using genome sequencing, transcriptomics, and community annotation. Two factors that might facilitate rapid evolutionary change include transposable elements, which comprise at least 17% of the genome and are rapidly evolving compared to other Coleoptera, and high levels of nucleotide diversity in rapidly growing pest populations. Adaptations to plant feeding are evident in gene expansions and differential expression of digestive enzymes in gut tissues, as well as expansions of gustatory receptors for bitter tasting. Surprisingly, the suite of genes involved in insecticide resistance is similar to other beetles. Finally, duplications in the RNAi pathway might explain why Leptinotarsa decemlineata has high sensitivity to dsRNA. The L. decemlineata genome provides opportunities to investigate a broad range of phenotypes and to develop sustainable methods to control this widely successful pest.

genomics↗