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Porter, I.

Publications and source records attributed to Porter, I..

4 recordsLinked to original sources

Modeling herpes simplex virus type 2 and Zika virus replication in vaginal organoids and spheroids

Sexually transmitted viral infections disproportionately affect women and have adverse outcomes for maternal and fetal health. Since they are acquired through the vaginal tract, the vaginal epithelium is an important site to study host-viral interactions. An in vitro model of mouse vaginal epithelial organoids that can be infected by herpes simplex virus was recently established. Here, we used multiple vaginal organoid systems and studied their response to infection by herpes simplex virus type 2 (HSV-2) and Zika virus (ZIKV), both of which can be sexually transmitted and result in adverse effects on maternal and fetal health. We showed that mouse vaginal organoids support the replication of HSV-2 and ZIKV and respond to interferon treatment. We also established human vaginal spheroids from VK2/E6E7 cells that contain distinct apical and basal cell layers and are also susceptible to HSV-2 and ZIKV infection. Acyclovir treatment reduced HSV-2 replication in both mouse organoids and VK2 spheroids. However, ZIKV was restricted by remdesivir in VK2 spheroids, but not in mouse organoids, indicating differences in antiviral activity depending on the organoid system. Finally, we established apical-out mouse vaginal organoids that were also susceptible to HSV-2 and ZIKV infection. Altogether, our results show that vaginal organoids are useful in vitro models to study vaginal viral infections and effects of antiviral drugs.

microbiology↗

Utility of a quantitative approach to microbial dysbiosis using machine learning in an African American cohort with self-reported hair loss

ObjectiveHair loss is a common issue that affects a large proportion of the population, leading to lower self-confidence and quality of life. Microbial dysbiosis of the scalp has been shown to be associated with several different disorders leading to hair loss. Though several "microbiome friendly" cosmetic treatments are currently on the market, there is no agreement on the best technique for assessing dysbiosis leading to a lack of scientific rigor for quantifying the effective treatments. To help address this, the association between self-perceived hair loss and the scalp microbiome in an African-American cohort (n=36) was investigated. MethodsUsing a self-controlled design, swabs were collected from both "sparse" and "normal" scalp sites. The scalp microbiome was characterized via 16S rRNA gene sequencing and a dysbiosis score was calculated based on the proportion of all taxa within the samples. Further, we identified the taxa that contributed most to abnormal or dysbiotic hair sites using a machine learning random forest classifier and a negative binomial mixed effects model. ResultsThe dysbiosis index is sensitive to participants self-assessment of hair loss and interindividual variation. We found a core set of operational taxonomic units (OTUs) assigned to 7 genera that significantly contributed to increased scalp dysbiosis. ConclusionThis study demonstrates that self-perceived hair loss is associated with significant and measurable alterations in the scalp microbiome using, making the reported dysbiosis index a practical tool that may be used to assess microbiome changes following cosmetic or medical interventions for hair loss and other microbiome-associated disorders.

microbiology↗

In mouse and gut-on-a-chip models, pre-colonoscopy bowel preparation promotes pathogen colonization of the gut and translocation to other organs

In the United States an estimated 14 million colonoscopies are performed yearly, each requiring patients to undergo bowel preparation, a laxative cleansing of the intestines luminal contents. Despite its widespread use, the effects of bowel preparation on gut physiology and susceptibility to pathogens remains poorly understood, particularly in individuals with compromised gut health. Using mouse and in vitro models, we found that bowel preparation with the laxative polyethylene glycol (PEG) rapidly disrupts, transiently increasing susceptibility to infection by Salmonella Typhimurium, including a non-motile mutant, and by gut pathobionts derived from ulcerative colitis microbiota. Bowel preparation also facilitated bacterial translocation to extraintestinal sites (mesenteric lymph nodes, liver, and spleen) and exacerbated inflammation in a chemically-induced colitis model. Although these findings are preclinical, they suggest that bowel preparation may have underappreciated risks in vulnerable populations, and warrant further clinical investigation.

microbiology↗

Transposon wave remodelled the epigenomic landscape in the rapid evolution of a novel X chromosome dosage compensation mechanism

Sex chromosome dosage compensation is a model to understand the coordinated regulation of transcription, however the advanced age of the sex chromosomes in model systems make it difficult to study how the complex regulatory mechanisms underlying chromosome-wide dosage compensation can evolve. The sex chromosomes of Poecilia picta have undergone recent and rapid divergence, resulting in widespread gene loss on the male Y, coupled with complete X chromosome dosage compensation, the first case reported in a fish. The de novo origin of a novel dosage compensation system presents a unique opportunity to discover new mechanisms of gene regulation and their evolutionary origins. By combining a new chromosome-level assembly of P. picta with whole-genome bisulfite sequencing and RNA-Seq data, we determine that the binding motif of Yin Yang 1 (YY1) is associated with male hypomethylated regions on the X, but not the autosomes. The male-specific hypomethylation of these motifs offers a putative model for male specific upregulation of genes on the X. These YY1 motifs are the result of a recent and rapid repetitive element expansion on the P. picta X chromosome, which is absent in closely related species that lack dosage compensation. Taken together, our results present compelling support that a disruptive wave of repetitive element insertions carrying YY1 motifs resulted in the remodeling of the X chromosome epigenomic landscape and the de novo origin of a new dosage compensation mechanism.

genomics↗