Biology subjects

Vale, G.

Publications and source records attributed to Vale, G..

13 recordsLinked to original sources

bioRxiv2026

Wild rice Oryza rufipogon outperforms cultivated rice in stimulating beneficial bacterial endophytes.

Beneficial interactions between plants and microorganisms strongly influence plant health and productivity, and root exudates play a central role in shaping these associations. This study analyzed the transcriptional responses of the bacterial endophytes Enterobacter asburiae RCA24 and Kosakonia sacchari RCA25 to root exudates from two commercial Italian rice accessions (Oryza sativa Baldo and Vialone Nano) and from an accession of the wild progenitor of tropical rice, Oryza rufipogon. Bacterial transcriptome analyses revealed that RCA24 responds differently to O. sativa varieties and that RCA25 was more stimulated by O. rufipogon. Changes in bacterial gene expression were mainly related to central metabolism, stress response, and signal transduction, highlighting a precise pattern of interaction. On the other hand, transcriptome analysis of inoculated rice revealed that RCA24 triggered broader transcriptional changes in plants than RCA25. Differentially expressed genes were related, especially in shoots, to defense responses, hormone-mediated signaling, and ribosome biogenesis, revealing that plants discriminate bacterial strains in a genotype-specific manner at the transcriptional level. Our findings suggest that traits beneficial to plant-soil microbiota interactions present in O. rufipogon and lost during domestication and diversification could be identified and reintroduced into modern rice varieties to improve sustainable field performance through beneficial microbial associations.

plant biology↗

bioRxiv2026

Salmonella lipopolysaccharide stimulates uptake of long-chain fatty acids in the small intestine

Enteric bacterial pathogens profoundly alter intestinal physiology during infection, yet their effects on host lipid metabolism remain poorly understood. Using mass spectrometry lipidomics, we found that infection of the mouse intestine with the bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) stimulates uptake of long-chain fatty acids by small intestinal epithelial cells. This response coincided with increased expression of epithelial genes involved in lipid uptake and transport and required the long-chain fatty acid transporter CD36. Fatty acid uptake was triggered by S. Typhimurium lipopolysaccharide (LPS) and was impaired by bacterial mutations that alter LPS acyl chains. Mechanistically, S. Typhimurium induced lipid absorption through myeloid cell Toll-like receptor 4, a receptor for LPS. Escherichia coli, a related commensal bacterium, also induced intestinal lipid absorption through LPS, although to a lesser extent than S. Typhimurium. Finally, disruption of long-chain fatty acid absorption impaired host defense during bacterial stimulation, suggesting that bacteria-induced lipid uptake contributes to protection against enteric infection. Together, these findings identify LPS from Gram-negative intestinal bacteria as a key regulator of dietary lipid uptake by the intestinal epithelium. Significance StatementThe intestinal lining absorbs nutrients while also detecting bacteria that enter with food, but how these two functions intersect during infection is poorly understood. Salmonella is a food-borne bacterial pathogen that infects humans. By studying mice, we found that Salmonella infection rapidly enhances absorption of dietary lipids by intestinal epithelial cells. This response was triggered when immune cells beneath the gut lining detected lipopolysaccharide, a molecule in the outer coat of many Gram-negative bacteria. In mice with defective lipid absorption, more Salmonella spread beyond the intestine, suggesting that lipid uptake contributes to host defense. These findings reveal a previously unappreciated link between microbial sensing, nutrient absorption, and defense against intestinal infection.

microbiology↗

bioRxiv2026

Epithelial sensing of vitamin A shapes intestinal antimicrobial defense

Vitamin A is a central regulator of intestinal adaptive immunity, but its role in innate immunity is less defined. Antimicrobial proteins form a chemical barrier that protects the intestinal epithelium from microbial invasion. Among these, REG3 family lectins are induced by the microbiota, yet how nutritional cues intersect with microbial signals to control their expression remains unclear. Here, we show that dietary vitamin A promotes expression of REG3 antimicrobial lectins, including REG3G, in intestinal epithelial cells from both mice and humans. This induction is mediated by retinoic acid and requires retinoic acid receptor (RAR) signaling. Mechanistically, RARs bind directly to the Reg3g promoter adjacent to a STAT3 binding site. As STAT3 mediates microbiota-induced IL-22 signaling in epithelial cells, this arrangement provides a molecular framework for integrating nutritional and microbial inputs at the level of REG3G transcription. Extending these findings, we demonstrate that vitamin A-retinoic acid signaling similarly promotes expression of -defensin antimicrobial proteins. Together, these findings define a transcriptional mechanism by which vitamin A enhances epithelial antimicrobial defenses and strengthens mucosal innate immunity. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/710399v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@18dd8aforg.highwire.dtl.DTLVardef@18cf2fdorg.highwire.dtl.DTLVardef@a4dc89org.highwire.dtl.DTLVardef@18aa9c7_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIVitamin A promotes epithelial expression of REG3 antimicrobial proteins in the intestine C_LIO_LIRetinoic acid receptors (RARs) directly activate mouse Reg3g and human REG3G transcription C_LIO_LIRARs bind the Reg3g promoter adjacent to STAT3, integrating nutritional and microbial signals C_LIO_LIVitamin A-RAR signaling broadly regulates epithelial antimicrobial programs, including -defensins C_LI

immunology↗

bioRxiv2026

Unrestrained fatty acid oxidation triggers heart failure in mice via cardiolipin loss and mitochondrial dysfunction

Cardiomyocytes primarily rely on fatty acid oxidation (FAO), which provides more than 70% of their energy. However, excessive FAO can disrupt cardiac metabolism by increasing oxygen demand and suppressing glucose utilization through the Randle cycle. Although inhibition of FAO has been investigated in heart failure, its overall therapeutic impact remains uncertain. To determine the consequences of enhanced FAO, we generated cardiomyocyte-specific ACC1 and ACC2 double-knockout (ACC dHKO) mice, which exhibit constitutively elevated FAO. ACC dHKO mice developed dilated cardiomyopathy and heart failure. Lipidomic analysis revealed marked depletion of cardiolipin caused by reduced linoleic acid, a direct consequence of excessive FAO. This cardiolipin deficiency impaired mitochondrial electron transport chain (ETC) activity, leading to mitochondrial dysfunction. Pharmacologic inhibition of FAO with etomoxir or oxfenicine restored cardiolipin levels, normalized ETC activity, and prevented cardiac dysfunction in ACC dHKO mice. These findings demonstrate that unrestrained FAO disrupts both lipid and energy homeostasis, culminating in heart failure in this model. Collectively, these results indicate that although FAO is essential for cardiac energy production, therapeutic strategies aimed at stimulating cardiac FAO may be detrimental rather than beneficial in heart failure.

cell biology↗

bioRxiv2025

The gut microbiota directs vitamin A flux to regulate intestinal T cell development

The intestinal microbiota shapes adaptive immunity, but the mechanisms remain incompletely defined. Here, we show that the microbiota initiates the movement of retinoids--dietary vitamin A derivatives including retinol and retinoic acid--through a sequential pathway from epithelial cells to myeloid cells and ultimately to T cells in the mesenteric lymph nodes (mLNs). This cellular axis is traversed over three days. Microbe-associated molecular patterns (MAMPs) initiate retinoid flux by inducing expression of serum amyloid A (SAA) proteins. These epithelial retinol-binding proteins are necessary and sufficient for epithelial-to-myeloid cell retinoid transfer and for myeloid cell migration to the mLNs. In the mLNs, microbial antigen drives retinoid transfer from myeloid cells to developing T cells, culminating in T cell retinoid uptake and transcriptional programming. This pathway is activated during postnatal development, when gut adaptive immunity is first established. These findings reveal that the microbiota programs intestinal adaptive immunity by regulating immune cell access to a nutrient-derived developmental signal. HighlightsO_LIThe gut microbiota enables vitamin A flux to developing intestinal CD4 T cells. C_LIO_LIMicrobiota-induced SAA initiates vitamin A flux along a gut myeloid-T cell axis. C_LIO_LIMicrobial molecular patterns and antigen drive distinct steps of vitamin A flux. C_LIO_LIMicrobiota-driven vitamin A flux programs intestinal T cell homing and maturation. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=192 HEIGHT=200 SRC="FIGDIR/small/674524v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@13b3906org.highwire.dtl.DTLVardef@11ceee3org.highwire.dtl.DTLVardef@87913forg.highwire.dtl.DTLVardef@50c9a0_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

Insulin-mTOR hyperfunction drives C. elegans aging opposed by the megaprotein LPD-3

Insulin-mTOR signaling drives anabolic growth during organismal development, while its late-life dysregulation may detrimentally contribute to aging and limit lifespans. Age-related regulatory mechanisms and functional consequences of insulin-mTOR remain incompletely understood. Here we identify LPD-3 as a megaprotein that orchestrates the tempo of insulin-mTOR signaling during C. elegans aging. We find that an agonist insulin INS-7 is drastically over-produced in early life and shortens lifespan in lpd-3 mutants, a C. elegans model of human Alkuraya-Ku[c]inskas syndrome. LPD-3 forms a bridge-like tunnel megaprotein to facilitate phospholipid trafficking to plasma membranes. Lipidomic profiling reveals increased abundance of hexaceramide species in lpd-3 mutants, accompanied by up-regulation of hexaceramide biosynthetic enzymes, including HYL-1 (Homolog of Yeast Longevity). Reducing HYL-1 activity decreases INS-7 levels and rescues the lifespan of lpd-3 mutants through insulin receptor/DAF-2 and mTOR/LET-363. LPD-3 antagonizes SINH-1, a key mTORC2 component, and decreases expression with age in wild type animals. We propose that LPD-3 acts as a megaprotein brake for aging and its age-dependent decline restricts lifespan through the sphingolipid-hexaceramide and insulin-mTOR pathways.

physiology↗

bioRxiv2022

A megaprotein-based molecular bridge critical for lipid trafficking and cold resilience

Cells adapt to cold by increasing levels of unsaturated phospholipids and membrane fluidity through homeostatic mechanisms conserved in nearly all forms of life. As most eukaryotic enzymes for lipid synthesis and desaturation localize on endoplasmic reticulum (ER) membranes, it remains unknown how ER-resident lipids rapidly distribute to plasma membranes (PM). Here we report an exceptionally large and evolutionarily conserved protein LPD-3 in C. elegans that plays critical roles in lipid trafficking and cold resilience. We identified lpd-3 mutants in a mutagenesis screen for genetic suppressors of the lipid desaturase FAT-7, and found that the 452 kDa megaprotein LPD-3 bridges ER and PM, consisting of a structurally predicted hydrophobic tunnel for lipid trafficking. Loss of LPD-3 caused abnormal cellular distribution of phospholipids, diminished FAT-7 abundance, and organismic vulnerability to cold. These phenotypic defects of lpd-3 mutants were rescued by Lecithin comprising unsaturated phospholipids. Importantly, we found that deficient lpd-3 homologues in Zebrafish and mammalian cells led to defects similar to those observed in C. elegans. As mutations in KIAA1109/BLTP1, the human orthologue of lpd-3, cause Alkuraya-Kucinskas syndrome, we propose that the LPD-3 family proteins may serve as evolutionarily conserved "highway bridges" critical for ER-associated non-vesicular trafficking of lipids and resilience to cold stress in eukaryotic cells.

cell biology↗

bioRxiv2021

Transcriptional integration of distinct microbial and nutritional signals by the small intestinal epithelium

To preserve its physiologic functions, the intestine must interpret and adapt to complex combinations of stimuli from dietary and microbial sources. However, the transcriptional strategies by which the intestinal epithelium integrates and adapts to dietary and microbial information remains unresolved. We compared adult mice reared germ free (GF) or conventionalized with a microbiota (CV) either fed normally or after a single high-fat meal (HFM). Jejunal epithelium preparations were queried using genomewide assays for RNA-seq, the activating histone mark H3K27ac ChIP-seq, and ChIP-seq of the microbially-responsive transcription factor HNF4A. We identified distinct nutritional and microbial responses at certain genes, but also apparent simultaneous influence of both stimuli at many other loci and regulatory regions. Increased expression levels and H3K27ac enrichment following HFM at a subset of these sites was dependent on microbial status. H3K27ac sites that were preferentially increased by HFM in the presence of microbes neighbor lipid anabolism and proliferation genes as well as intestinal stem cell (ISC) markers, were usually active only in ISCs, and were not HNF4A targets. In contrast, H3K27ac sites that were preferentially increased by HFM in the absence of microbes neighbored targets of the nuclear receptor and energy homeostasis regulator PPARA, were frequently accessible only in enterocytes, and were HNF4A bound. These results reveal that HNF4A supports a differentiated enterocyte and FAO program in GF, and that suppression of HNF4A by the combination of microbes and HFM may result in preferential activation of IEC proliferation programs. Microbial and nutritional responses are therefore integrated with some of the same transcriptional programs that regulate intestinal proliferation and differentiation.

genomics↗

bioRxiv2020

Proximity labeling of Snx14 reveals a functional interaction with delta-9 desaturase SCD1 to maintain ER homeostasis

Fatty acids (FAs) are central cellular metabolites that contribute to lipid synthesis, and can be stored or harvested for metabolic energy. Dysregulation in FA processing and storage causes toxic FA accumulation or altered membrane compositions and contributes to metabolic and neurological disorders. Saturated lipids are particularly detrimental to cells, but how lipid saturation levels are maintained remains poorly understood. Here, we identify the cerebellar ataxia SCAR20-associated protein Snx14, an endoplasmic reticulum (ER)-lipid droplet (LD) tethering protein, as a novel factor required to maintain the lipid saturation balance of cell membranes. We show that SNX14KO cells and SCAR20 disease patient-derived cells are hypersensitive to saturated FA (SFA)-mediated lipotoxic cell death that compromises ER integrity. Using APEX2-based proximity labeling, we reveal the protein composition of Snx14-associated ER-LD contacts and define a functional interaction between Snx14 and {Delta}-9 FA desaturase SCD1. Lipidomic profiling reveals that SNX14KO cells increase membrane lipid saturation following exposure to palmitate, phenocopying cells with reduced SCD1 activity. In line with this, SNX14KO cells manifest delayed FA processing and lipotoxicity, which can be rescued by SCD1 over-expression. Altogether these mechanistic insights reveal a role for Snx14 in FA and ER homeostasis, defects in which may underlie the neuropathology of SCAR20. Significance StatementSCAR20 disease is an autosomal recessive spinocerebellar ataxia primarily affecting children, and results from loss-of-function mutations in the SNX14 gene. Snx14 is an endoplasmic reticulum (ER)-localized protein that localizes to ER-lipid droplet (LD) contacts and promotes LD biogenesis following exogenous FA treatment, but why Snx14 loss causes SCAR20 is unclear. Here, we demonstrate that following exposure to saturated fatty acids, Snx14-deficient cells have defective ER homeostasis and altered lipid saturation profiles. We reveal a functional interaction between Snx14 and fatty acid (FA) desaturase SCD1. Lipidomics shows Snx14-deficient cells contain elevated saturated lipids, closely mirroring SCD1-defective cells. Furthermore, SCD1 over-expression can rescue Snx14 loss. We propose that Snx14 maintains cellular lipid homeostasis, the loss of which underlies the cellular basis for SCAR20 disease.

cell biology↗

bioRxiv2020

Assessing the effect of insecticide-treated cattle on tsetse abundance and trypanosome transmission at the wildlife-livestock interface in Serengeti, Tanzania

In the absence of national control programmes against Rhodesian human African trypanosomiasis, farmer-led treatment of cattle with pyrethroid-based insecticides may be an effective strategy for foci at the edges of wildlife areas, but there is limited evidence to support this. We combined data on insecticide use by farmers, tsetse abundance and trypanosome prevalence with mathematical models to quantify the likely impact of insecticide-treated cattle. Sixteen percent of farmers reported treating cattle with a pyrethroid, and chemical analysis indicated 18% of individual cattle had been treated, in the previous week. Treatment of cattle was estimated to increase daily mortality of tsetse by 5 - 14%. Trypanosome prevalence in tsetse, predominantly from wildlife areas, was 1.25% for T. brucei s.l. and 0.03% for T. b. rhodesiense. For 750 cattle sampled from 48 herds, 2.3% were PCR positive for T. brucei s.l. and none for T. b. rhodesiense. Using mathematical models, we estimated there was 8 - 29% increase in mortality of tsetse in farming areas and this increase can explain the relatively low prevalence of T. brucei s.l. in cattle. Farmer-led treatment of cattle with pyrethroids is likely, in part, to be limiting the spill-over of human-infective trypanosomes from wildlife areas. Author summaryThe acute form of sleeping sickness in Africa is caused by the parasite Trypanosoma brucei rhodesiense. It is transmitted by tsetse flies and can be maintained in cycles involving both livestock and wildlife as hosts. Humans are incidentally infected and are particularly at risk of infection near protected areas where there are both wildlife and suitable habitat for tsetse. In these regions, the tsetse vector cannot be eradicated, nor can infection be prevented in wildlife. Here we use field studies of tsetse and livestock in combination with mathematical models of tsetse population change and trypanosome transmission to show that use of pyrethroid-based insecticides on cattle by farmers at the edge of protected areas could be contributing to lowering the risk of sleeping sickness in Serengeti District, Tanzania. To our knowledge, our study is the first to report farmer-led tsetse control, co-incident with tsetse decline and relatively low prevalence of T. brucei s.l. in cattle.

ecology↗

bioRxiv2019

Vibrio deploys Type 2 secreted lipase to esterify cholesterol with host fatty acids and mediate cell egress

Pathogens find diverse niches for survival inside host cells where replication occurs in a relatively protected environment. Vibrio parahaemolyticus, a facultative intracellular pathogen, uses its type 3 secretion system 2 (T3SS2) to invade and replicate inside host cells. However, after extensive analysis, the T3SS2 pathogenicity island appeared to lack a mechanism for egress of this bacterium from the invaded host cell. Using a combination of cell biology, microbial genetics and lipid biochemistry, we found that VPA0226, a constitutively secreted lipase, is required for escape of Vibrio parahaemolyticus from host cells. Remarkably, this lipase must be delivered into the host cytoplasm where it preferentially uses fatty acids associated with innate immune response (i.e. arachidonic acid, 20:4) to esterify cholesterol, weakening the plasma membrane and allowing egress of the bacteria. This study reveals the resourcefulness of microbes and the interplay between virulence systems to evolve an ingenious scheme for survival and escape. Impact StatementConsidering the course of a pathogens evolution, there appears to be interplay between secretion systems, providing unique, synergistic mechanisms to support a successful lifestyle for possibly pathogenesis, symbiosis and/or parasitosis.

microbiology↗

bioRxiv2019

Drosophila Snazarus regulates a lipid droplet population at plasma membrane-droplet contacts in adipocytes

Adipocytes store nutrients as lipid droplets (LDs), but how they organize their LD stores to balance lipid uptake, storage, and mobilization remains poorly understood. Here, using Drosophila fat body (FB) adipocytes we characterize spatially distinct LD populations that are maintained by different lipid pools. We identify peripheral LDs (pLDs) that make close contact with the plasma membrane (PM) and are maintained by lipophorin-dependent lipid trafficking. pLDs are distinct from larger cytoplasmic medial LDs (mLDs) which are maintained by FASN1-dependent de novo lipogenesis. We find that sorting nexin CG1514/Snazarus (Snz) associates with pLDs and regulates LD homeostasis at ER-PM contact sites. Loss of SNZ perturbs pLD organization whereas Snz over-expression drives LD expansion, triacylglyceride production, starvation resistance, and lifespan extension through a DESAT1-dependent pathway. We propose that Drosophila adipocytes maintain spatially distinct LD populations and identify Snz as a novel regulator of LD organization and inter-organelle crosstalk.

cell biology↗

bioRxiv2018

Genomic prediction accounting for genotype by environment interaction offers an effective framework for breeding simultaneously for adaptation to an abiotic stress and performance under normal cropping conditions in rice

Developing rice varieties adapted to alternate wetting and drying water management is crucial for the sustainability of irrigated rice cropping systems. Here we report the first study exploring the feasibility of breeding rice for adaptation to alternate wetting and drying using genomic prediction methods that account for genotype by environment interactions. Two breeding populations (a reference panel of 284 accessions and a progeny population of 97 advanced lines) were evaluated under alternate wetting and drying and continuous flooding management systems. The accuracy of genomic prediction for response variables (index of relative performance and the slope of the joint regression) and for multi-environment genomic prediction models were compared. For the three traits considered (days to flowering, panicle weight and nitrogen-balance index), significant genotype by environment interactions were observed in both populations. In cross validation, prediction accuracy for the index was on average lower (0.31) than that of the slope of the joint regression (0.64) whatever the trait considered. Similar results were found for across population validation (progeny validation). Both cross-validation and progeny validation experiments showed that the performance of multi-environment models predicting unobserved phenotypes of untested entrees was similar to the performance of single environment models with differences in accuracy ranging from - 6% to 4% depending on the trait and on the statistical model concerned. The accuracy of multi-environment models predicting unobserved phenotypes of entrees evaluated under both water management systems outperformed single environment models by an average of 30%. Practical implications for breeding rice for adaptation to AWD are discussed.

genetics↗