The polymorphic membrane proteins (Pmps) are a family of autotransporters that play an important role in infection, adhesion and immunity in Chlamydia trachomatis. Here we show that the characteristic GGA(I,L,V) and FxxN tetrapeptide repeats fit into a larger repeat sequence, which correspond to the coils of a large beta-helical domain in high quality structure predictions. Analysis of the protein using structure prediction algorithms provided novel insight to the chlamydial Pmp family of proteins.
View Article and Find Full Text PDFThe United States Environmental Protection Agency (US EPA) recently developed a tiered testing strategy to use advances in high-throughput transcriptomics (HTTr) testing to identify molecular targets of thousands of environmental chemicals that can be linked to adverse outcomes. Here, we describe a method that uses a gene expression biomarker to predict chemical activation of heat shock factor 1 (HSF1), a transcription factor critical for proteome maintenance. The HSF1 biomarker was built from transcript profiles derived from A375 cells exposed to a HSF1-activating heat shock protein (HSP) 90 inhibitor in the presence or absence of HSF1 expression.
View Article and Find Full Text PDFinfection activates pattern recognition receptor (PRR) pathways that drive innate inflammatory responses to control infection. Necroptosis is a proinflammatory cell death pathway apart from the innate immune response that has evolved to control pathogenic infection. In this study, we further defined the role of Z-DNA binding protein 1 (ZBP1) as a PRR and assessed its contribution to necroptosis as a host protection mechanism to infection.
View Article and Find Full Text PDFThe long-term host effects caused by the protozoan parasite are poorly understood. High-throughput RNA sequencing analysis previously determined that the host response in the brain was greater and more complex at 28 days than at 10 days postinfection. Here, we analyzed the host transcriptional profile of age- and sex-matched mice during very early (21 days), early (28 days), mid (3 months), and late (6 months) chronic infection.
View Article and Find Full Text PDFThe centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere genomics in biology are laborious. We have identified specific markers in the centromere of 23 of the 24 human chromosomes that allow for rapid PCR assays capable of capturing the genomic landscape of human centromeres at a given time.
View Article and Find Full Text PDFIntrinsic to Toxoplasma gondii infection is the parasite-induced modulation of the host immune response, which ensures establishment of a chronic lifelong infection. This manipulation of the host immune response allows T. gondii to not only dampen the ability of the host to eliminate the parasite but also trigger parasite differentiation to the slow-growing, encysted bradyzoite form.
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