Biology subjects

Correa, F.

Publications and source records attributed to Correa, F..

6 recordsLinked to original sources

bioRxiv2024

Systemic metabolic changes in acute and chronic lymphocytic choriomeningitis virus infection

Viral infection of cells leads to metabolic changes, but how viral infection changes whole-body and tissue metabolism in vivo has not been comprehensively studied. In particular, it is unknown how metabolism might be differentially affected by an acute infection that the immune system can successfully clear, compared to a chronic and persistent infection. Here we used metabolomics and isotope tracing to identify metabolic changes in mice infected with acute or chronic forms of lymphocytic choriomeningitis virus (LCMV) for three or eight days. Both types of infection alter metabolite levels in blood and tissues, including itaconate and thymidine. However, we observed more dramatic metabolite changes in the blood and tissues of mice with chronic LCMV infection compared to those with acute infection. Isotope tracing revealed that the contribution of both glucose and glutamine to the tricarboxylic acid (TCA) cycle increase in the spleen, liver, and kidneys of mice infected with chronic LCMV, while acute LCMV only increases the contribution of glutamine to the TCA cycle in the spleen. We found that whole-body turnover of both glutamine and thymidine increase during acute and chronic infection, whereas whole-body glucose turnover was surprisingly unchanged. Activated T cells in vitro produce thymidine and mice with T cell leukemia display elevated serum thymidine, nominating T lymphocytes as the source of thymidine in LCMV infection. In sum, we provide comprehensive measurements of whole-body and tissue metabolism in acute and chronic viral infection, and identify altered thymidine metabolism as a marker of viral infection.

immunology↗

bioRxiv2022

Transcriptomic and DNA methylation modifications during fruit ripening and in response to ABA treatment in sweet cherry

Abscisic acid (ABA) plays a key role in the ripening process of non-climacteric fruits, triggering pigment production, fruit softening, and sugar accumulation. Transcriptomic studies show that ABA modifies the expression of several ripening-related genes, but to date, the epigenetic approach has not been utilized to characterize the role of ABA during this process. Therefore, this work aimed to perform transcriptomic and DNA methylation analyses of fruit samples treated with ABA during the fruit ripening process in the non-climacteric sweet cherry model. RNA-seq analyses revealed an overrepresentation of transcripts annotated in functional categories related to ABA response, secondary metabolism, and sugar synthesis. In contrast, Whole Genome Bisulfite Sequencing (WGBS) revealed DNA hypomethylation in the 5UTR region of genes related to carotene catabolism. Genes encoding xyloglucan enzymes were regulated transcriptionally and epigenetically during ripening. ABA treatment enhanced color development and ripening. GO analysis of DEGs in the RNA-seq of the ABA treatment revealed expression variations in genes encoding members of the Aux/IAA and ARF families. In the WGBS, genes encoding enzymes of the cytokinin biosynthesis had differential DNA methylation after the ABA treatment. Our work shows the genetic factors modulated by ABA at the genetic and epigenetic levels during non-climacteric ripening.

plant biology↗

bioRxiv2022

A Multimodal Atlas of Tumor Metabolism Reveals the Architecture of Gene-Metabolite Co-regulation

Tumor metabolism is controlled by coordinated changes in metabolite abundance and gene expression, but simultaneous quantification of metabolites and transcripts in primary tissue is rare. To overcome this limitation and study gene-metabolite coregulation in cancer, we assembled the Cancer Atlas of Metabolic Profiles (cAMP) of metabolomic and transcriptomic data from 988 tumor/normal specimens spanning 11 cancer types. Meta-analysis of the cAMP revealed two classes of Gene-Metabolite Interactions (GMIs) that transcended cancer types. The first corresponded to a small number of gene-metabolite pairs engaged in direct enzyme-substrate interactions, identifying putative metabolite-pool-size-controlling genes. A second class of GMIs represented a small number of hub metabolites, including quinolinate and NAD+, which correlated to many genes specifically expressed on immune cell populations. These results provide evidence that gene-metabolite coregulation in human tissue arises, in part, from both mechanistic interactions between genes/metabolites, and from metabolic remodeling in specific immune microenvironments.

cancer biology↗

bioRxiv2020

Cognitive deficits found in a pro-inflammatory state are independent of ERK 1/2 signaling in the murine brain hippocampus treated with Shiga toxin 2 from enterohemorrhagic Escherichia Coli

Shiga toxin 2 (Stx2) from enterohemorrhagic Escherichia coli (EHEC) produces hemorrhagic colitis, hemolytic uremic syndrome (HUS) and acute encephalopathy. The mortality rate in HUS increases significantly when the central nervous system (CNS) is involved. Besides, EHEC also releases lipopolysaccharide (LPS). Many reports have described cognitive dysfunctions in HUS patients, the hippocampus being one of the brain areas targeted by EHEC infection. In this context, a translational murine model of encephalopathy was employed to establish the deleterious effects of Stx2 and the contribution of LPS in the hippocampus. Results demonstrate that systemic administration of a sublethal dose of Stx2 reduced memory index and produced depression like behavior, pro-inflammatory cytokine release and NF-kB activation independent of the ERK 1/2 signaling pathway. On the other hand, LPS activated NF-kB dependent on ERK 1/2 signaling pathway. Cotreatment of Stx2 with LPS aggravated the pathologic state, while dexamethasone treatment succeeded in preventing behavioral alterations. Our present work suggests that the use of drugs such as corticosteroids or NF-kB signaling inhibitors may serve as neuroprotectors from EHEC infection.

pathology↗

bioRxiv2019

Identifying and validating housekeeping hybrid Prunus sp. genes for root gene-expression studies

Prunus rootstock belonging to subgenera Amygdalus (peach), Prunus (plum) and Cerasus (cherry) are either from the same species as the scion or another one. The number of inter-species (including inter-subgenera) hybrids have increased as a result of efforts to broaden the genetic basis for biotic and abiotic resistance/tolerance. Identifying genes associated with important traits and responses requires expression analysis. Relative quantification is the simplest and most popular alternative, which requires reference genes (housekeeping) to normalize RT-qPCR data. However, there is a scarcity of validated housekeeping genes for hybrid Prunus rootstock species. This research aims to increase the number of housekeeping genes suitable for Prunus rootstock expression analysis.\n\nTwenty-one candidate housekeeping genes were pre-selected from previous RNAseq data that compared the response of root transcriptomes of two rootstocks subgenera to hypoxia treatment, Mariana 2624 (P. cerasifera Ehrh.x P. munsoniana W. Wight & Hedrick), and Mazzard F12/1 (P. avium L.). Representing groups of low, intermediate or high levels of expression, the genes were assayed by RT-qPCR at 72 hours of hypoxia treatment and analyzed with NormFinder software. A sub-set of seven housekeeping genes that presented the highest level of stability were selected, two with low levels of expression (Unknown 3, Unknown 7) and five with medium levels (GTB 1, TUA 3, ATPase P, PRT 6, RP II). The stability of these genes was evaluated under different stress conditions, cold and heat with the hybrid Mariana 2624 and N nutrition with the hybrids Colt (P. avium x P. pseudocerasus Lindl.) and Garnem [P. dulcis Mill.x (P. persica L.x P. davidiana Carr.)]. The algorithms of geNorm and BestKeeper software also were used to analyze the performance of these genes as housekeepers.\n\nStability rankings varied according to treatments, genotypes and the software for evaluation, but the gene GBT 1 often had the highest ranking. However, most of the genes are suitable depending on the stressor and/or genotype to be evaluated. No optimal number of reference genes could be determined with geNorm software when all conditions and genotypes were considered. These results strongly suggest that relative RT-qPCR should be analyzed separately with their respective best housekeeper according to the treatment and/or genotypes in Prunus spp rootstocks.

plant biology↗

bioRxiv2018

New insights of the local immune response against both fertile and infertile hydatid cysts

BackgroundCystic echinococcosis is caused by the metacestode of the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, the metacestode grows as a unilocular cyst known as hydatid cyst. This cyst is comprised of two layers of parasite origin: germinal and laminated layers, and one of host origin: the adventitial layer, that encapsulates the parasite. This adventitial layer is composed of collagen fibers, epithelioid cells, eosinophils and lymphocytes. To establish itself inside the host, the germinal layer produces the laminated layer, and to continue its life cycle, generates protoscoleces. Some cysts are unable to produce protoscoleces, and are defined as infertile cysts. The molecular mechanisms involved in cyst fertility are not clear, however, the host immune response could play a crucial role.\n\nMethodology/Principal fidingsWe collected hydatid cysts from both liver and lungs of slaughtered cattle, and histological sections of fertile, infertile and small hydatid cysts were stained with haematoxylin-eosin. A common feature observed in infertile cysts was the disorganization of the laminated layer by the infiltration of host immune cells. These infiltrating cells eventually destroy parts of laminated layer. Immunohistochemical analysis of both parasite and host antigens, identify these cells as cattle macrophages and are present inside the cysts associated to germinal layer.\n\nConclusions/SignificanceThis is the first report that indicates to cell from immune system present in adventitial layer of infertile bovine hydatid cysts could disrupt the laminated layer, infiltrating and probably causing the infertility of cyst.\n\nAuthor SummaryCystic echinococcosis is caused by the zoonotic flatworm Echinococcus granulosus. Within the viscera of the intermediate host, mainly liver and lungs of herbivores such as cows and sheep as well as human beings, the parasite grows as a unilocular cyst known as hydatid cyst. These cysts develop in their inner chamber a structure known as protoscolex, when consumed by the definitive host (e.g. dogs), it grows into a worm that resides in the small intestine and produces eggs that contaminate the environment. In cattle, most hydatid cysts are unable to produce protoscoleces, and thus are termed infertile hydatid cysts. The molecular mechanisms that explain the causes of hydatid cyst infertility remain unknown. We routinely collected cattle hydatid cysts from both liver and lugs and processed them for histological analysis. We found that there is a subset of fertile hydatid cysts that have low protoscolex viability and high immune infiltration surrounding the cyst. All infertile cysts have high immune infiltration, and many of them show disruption of the laminated layer and immune cells of host origin inside the cyst. This is the first report that shows that the cyst can be infiltrated by the host immune system.

immunology↗