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Biology subjects

Diaz, I. A.

Publications and source records attributed to Diaz, I. A..

3 recordsLinked to original sources

Host response during unresolved urinary tract infection alters mammary tissue homeostasis through collagen deposition and TIMP1

Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explored how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell RNA sequencing and flow cytometry, we identified that mammary tissue from UTI-bearing mice display collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition. Bacterial cells were absent in the mammary tissue and blood of UTI-bearing mice, therefore, alterations to the distal mammary tissue were mediated by the systemic host response to local infection. Furthermore, broad spectrum antibiotic treatment resolved the infection and restored mammary cellular and tissue homeostasis. Systemically, unresolved UTI correlated with increased plasma levels of the metalloproteinase inhibitor, TIMP1, which controls extracellular matrix (ECM) remodeling and neutrophil function. Treatment of nulliparous and post-lactation UTI-bearing female mice with a TIMP1 neutralizing antibody, or broad-spectrum antibiotic, prevented mammary collagen deposition, thus providing evidence for an unexpected link between the systemic host response during UTI and mammary alterations. SummaryThe systemic response during urinary tract infection induces TIMP1-driven collagen deposition specifically into the mammary gland.

developmental biology↗

Haplotype phased genome of 'Fairchild' mandarin highlights influence of local chromatin state on gene expression

BackgroundCis-regulatory sequences control gene expression through the coordinated action of transcription factors and their associated partners. Both genetic and epigenetic perturbation of cis-regulatory sequences can lead to novel patterns of gene expression. Phased genome assemblies now enable the local dissection of linkages between cis-regulatory sequences, including their epigenetic state, and gene expression to further characterize gene regulation in heterozygous genomes. ResultsWe assembled a locally phased genome for a mandarin hybrid named Fairchild to explore the molecular signatures of allele-specific gene expression. With genome phasing, genes with allele-specific expression were paired with haplotype-specific chromatin states, including levels of chromatin accessibility, histone modifications, and DNA methylation. We found that 30% of variation in allele-specific expression could be attributed to haplotype associated factors, with allelic levels of chromatin accessibility and three histone modifications in gene bodies having the most influence. Structural variants in promoter regions were also associated with allele-specific expression, including specific enrichments of hAT and MULE-MuDR DNA transposon sequences. Mining of cis-regulatory sequences underlying regions with allelic variation in chromatin accessibility revealed a paternally-associated sequence motif bound by ERF48, a target of the Polycomb repressive complex 2 (PRC2), and sequence similarity of this motif corresponded to local levels of H3K27me3, a signature of PRC2 activity. ConclusionsUsing a locally phased assembly of a heterozygous citrus cultivar, we dissected the interplay between genetic variants and molecular phenotypes with the goal of revealing functional cis-regulatory sequences and exploring the evolution of gene regulation.

genomics↗

Early vegetation recovery after the 2008-2009 explosive eruption of the Chaiten Volcano

In May 2008, Chaiten volcano entered in eruptive process, one of the world largest eruptions in the last decades. The catastrophic event left different type of disturbance and caused diverse environmental damage distributed heterogeneously in the surrounding areas of the volcano. We went to the field to assess the early vegetation responses a year after the eruption, in September 2009. Particularly, we evaluated the lateral-blast disturbance zone. We distributed a set of plots in three disturbed sites, and one in an undisturbed site. In each of these sites, in a plot of 1000m2 we marked all stand tree, recording whether they were alive, resprouting or dead. Additionally, in each site 80 small-plots (~4m2) we tallied the plants regeneration, its coverage, and the log-volume. We described whether the plant regeneration was growing on mineral or organic substrate. In the blast-zone the eruption created a gradient of disturbance. Close to the crater we found high devastation marked by no surviving species, scarce standing-dead trees and logs, as well as no tree regeneration. On the other extreme of the disturbance gradient, the trees with damaged crown were resprouting, small-plants were regrowing and seedlings were more dispersed. The main regeneration strategy was the resprouting of trunks or buried roots, while few seedlings were observed in the small plots and elsewhere in disturbed areas. However, the assessment was too soon after the eruption and updated monitoring is required to confirm observed patterns. The main findings of this study are: i) a mosaic of pioneering-wind dispersed species, scattered survivors regrowing and spreading from biological legacies, and plant species dispersed by frugivorous birds, likely favored by the biological legacies; (ii) the early succession is influenced by the interaction of the species-specific life history, altitudinal gradient and the different intensity of disturbance.

ecology↗