Project description:Studying properties of non-cancerous high-risk human breast epithelial cells is challenged by limitations in acquiring primary epithelial cells for investigation. Here we used conditional reprogramming cell (CRC) technology to isolate n=27 serial samples of non-cancer derived mammary epithelial cells ipsilateral to breast cancer, considered at risk cells for future breast cancer development. Comparative samples included cancer (n=8) and contralateral (n=3) and prophylactic mastectomy (n=1) non-cancer derived breast epithelial cells. Significant in vitro behavioral differences between samples were connected to baseline transcriptome characteristics. An exploratory analysis identified patterns of aberrantly expressed pregnancy development genes in both at risk and cancer samples. In conclusion, it is possible to approach the investigation of breast cancer risk utilizing human primary breast epithelial cells for targeted in vitro and genetic studies.
Project description:Dermabacter vaginalis AD1-86T was isolated from the vaginal fluid of a Korean woman. Whole genome sequencing analysis was conducted using a PacBio RS II platform and annotated on RAST. The nucleotide sequence of this genome was deposited into DDBJ/EMBL/GenBank under the accession NZ_CP012117.
Project description:We conducted a preliminary investigation to determine whether ethanol-induced alterations in placental gene expression may have some utility as a diagnostic indicator of maternal drinking during pregnancy as well as a prognostic indicator of risk for adverse neurobehavioral outcomes in affected offspring.
Project description:Trichomonas vaginalis is a sexually transmitted infection that causes vaginitis and increases the risk of HIV transmission. We are interested in the secreted and membrane glycoproteins of Trichomonas because they are likely involved in pathogenesis and may include novel vaccine targets. Four mass spectrometric methods (identification of all parasite proteins, glycoprotein enrichment with the plant lectin Concanavalin A, peptide:N-glycanase treatment to identify occupied N-glycans sites, and analysis of N-terminal peptides) were used to identify >300 Trichomonas secreted and membrane proteins. The first group of these proteins, which were present in multiple genome copies and had homologs in diverse eukaryotes, included 1) those involved in the N-glycan-dependent quality control protein folding in the ER lumen, 2) metalloproteases, serine proteases, cysteine proteases, and other lysosomal enzymes, and 3) transporters and membrane-associated cyclases. The second group of secreted and membrane proteins were, for the most part, encoded by single copy genes, unique to Trichomonas, and missing N-terminal signal peptides. The latter observation is despite evidence that the signal peptide peptidase functions normally in Trichomonas. As the unique secreted and membrane proteins of Trichomonas were often large and lacked features that make it easy to choose vaccine candidates, alternative strategies for vaccination and/or therapy are discussed.
Project description:Pregnant women appear to be at increased risk for severe outcomes associated with COVID-19, but the pathophysiology underlying this increased morbidity and its potential impact on the developing fetus is not well understood. In this study of pregnant women with and without COVID-19, we assessed viral and immune dynamics at the placenta during maternal SARS-CoV-2 infection. Viral RNA was only rarely detected in the placentas from SARS-CoV-2-positive women in our cohort, with only 1/11 positive for infection at the maternal-fetal interface. Through bulk RNA transcriptomic analyses, we found that placentas from SARS-CoV-2-positive pregnancies exhibited inflammatory markers of immune activation, even in the majority of samples which did not show local invasion of the virus. These markers are associated with pregnancy complications such as preeclampsia and poor fetal outcomes. Overall, this study suggests that SARS-CoV-2 is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion. While this likely represents a protective mechanism shielding the placenta from infection, inflammatory changes in the placenta may also contribute to poor pregnancy outcomes and thus warrant further investigation.
Project description:Patients who are diagnosed with thrombotic thrombocytopenic purpura (TTP) during pregnancy are at increased risk of maternal and fetal complications including fetal demise. We present a case of a 32-year-old G3P0 (gravida 3, para 0) who presented at 20 weeks’ gestation with a new diagnosis of congenital TTP (cTTP) and fetal demise. Methods: We describe the pathophysiology of pregnancy complications in a patient with cTTP using platelet procoagulant membrane dynamics analysis and quantitative proteomic studies, compared to 4 pregnant patients with gestational hypertension, 4 pregnant patients with preeclampsia and 4 healthy pregnant controls. Results: The cTTP patient had increased P-selectin, tissue factor expression, annexin-V binding on platelets and neutrophils, and localized thrombin generation, suggestive of hypercoagulability. Among 15 proteins that were upregulated, S100A8 and S100A9 were distinctly overexpressed.Conclusions: There is platelet-neutrophil activation and interaction, platelet hypercoagulability and proinflammation in our case of cTTP with fetal demise.
Project description:Dermabacter hominis was the cause of a peritoneal dialysis-associated peritonitis. D. hominis was identified by phenotypic criteria and by sequencing the 16S rRNA gene. Clinical cure was achieved with cefuroxime treatment despite the isolate's reduced susceptibility to this drug (MIC, 12 mg/liter) on in vitro testing. The successful treatment was probably due to the high concentrations attained by intraperitoneal administration of the drug.