Biology subjects

Rogers, M. B.

Publications and source records attributed to Rogers, M. B..

4 recordsLinked to original sources

bioRxiv2023

Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic

Zoonotic spillovers of viruses have occurred through the animal trade worldwide. The start of the COVID-19 pandemic was traced epidemiologically to the Huanan Wholesale Seafood Market, the site with the most reported wildlife vendors in the city of Wuhan, China. Here, we analyze publicly available qPCR and sequencing data from environmental samples collected in the Huanan market in early 2020. We demonstrate that the SARS-CoV-2 genetic diversity linked to this market is consistent with market emergence, and find increased SARS-CoV-2 positivity near and within a particular wildlife stall. We identify wildlife DNA in all SARS-CoV-2 positive samples from this stall. This includes species such as civets, bamboo rats, porcupines, hedgehogs, and one species, raccoon dogs, known to be capable of SARS-CoV-2 transmission. We also detect other animal viruses that infect raccoon dogs, civets, and bamboo rats. Combining metagenomic and phylogenetic approaches, we recover genotypes of market animals and compare them to those from other markets. This analysis provides the genetic basis for a short list of potential intermediate hosts of SARS-CoV-2 to prioritize for retrospective serological testing and viral sampling.

genomics↗

bioRxiv2019

Post-Transcriptional Bone Morphogenetic Protein 2 (BMP2) Gene Regulation in Aorta

Deletion of an \"ultra-conserved sequence\" (UCS) within the Bone Morphogenetic Protein (Bmp)2 mRNA previously revealed that the sequence represses Bmp2 reporter gene expression in vascular cells. The objective was to determine the impact of the endogenous UCS on Bmp2 mRNA levels, BMP signaling, and calcification in the healthy control aorta and in the calcified aorta of mice with renal disease. We compared the phenotypes of mice bearing a wild type Bmp2 allele or the UCS deletion allele in mice with normal kidney function or in Klotho mutant mice with reduced kidney function. BMP signaling and calcium levels were normally higher in control females relative to males. UCS deletion induced aortic Bmp2 mRNA and BMP signaling in control males, but not in females. UCS deletion significantly increased BMP signaling in both male and female Klotho homozygotes. Inheritance of the Bmp2 UCS deletion and Klotho alleles was skewed from Mendelian expectations suggesting that these alleles influence interacting pathways. Analyses of body and heart weight supported these interactions. The Bmp2 UCS represses BMP signaling in control males and in mice of both sexes with abnormal mineralization associated with kidney disease. Disease and sex-specific differences in Bmp2 gene control may influence the onset and progression of cardiovascular diseases.

molecular biology↗

bioRxiv2019

Post-transcriptional regulation of aortic calcification in KLOTHO deficient mice: impact of miR-145 and miR-378

Our goal was to elucidate microRNAs (miRNAs) that may repress the excess bone morphogenetic protein (BMP) signaling observed during pathological calcification in the Klotho mouse model of kidney disease. We hypothesized that restoring healthy levels of miRNAs that post-transcriptionally repress osteogenic calcific factors may decrease aortic calcification. Our relative abundance profiles of miRNAs in healthy aorta differ greatly from those in calcified mouse aorta. Many of these miRNAs are predicted to regulate proteins involved in BMP signaling and may control osteogenesis. Two differentially regulated miRNAs, miR-145 and miR-378, were selected based on three criteria: reduced levels in calcified aorta, the ability to target more than one protein in the BMP signaling pathway, and conservation of targeted sequences between humans and mice. Forced expression using a lentiviral vector demonstrated that restoring normal levels repressed the synthesis of BMP2 and other pro-osteogenic proteins and inhibited pathological aortic calcification in Klotho mice with renal insufficiency. This study identified miRNAs that may impact BMP signaling in both sexes and demonstrated the efficacy of selected miRNAs in reducing aortic calcification in vivo. Calcification of the aorta and the aortic valve resulting from abnormal osteogenesis is common in those with kidney disease, diabetes, and high cholesterol. Such vascular osteogenesis is a clinically significant feature. The calcification modulating miRNAs described here are candidates for biomarkers and "miRNA replacement therapies" in the context of chronic kidney disease and other pro-calcific conditions.

molecular biology↗

bioRxiv2018

Mitochondrial targeting of glycolysis in a major lineage of eukaryotes

Glycolysis is a major cytosolic catabolic pathway that provides ATP for many organisms1. Mitochondria play an even more important role in the provision of additional cellular ATP for eukaryotes2. Here, we show that in many stramenopiles, the C3 part of glycolysis is localised in mitochondria. We discovered genuine mitochondrial targeting signals on the six last enzymes of glycolysis. These targeting signals are recognised and sufficient to import GFP into mitochondria of a heterologous host. Analysis of eukaryotic genomes identified these targeting signals on many glycolytic C3 enzymes in a large group of eukaryotes found in the SAR supergroup3, in particular the stramenopiles. Stramenopiles, or heterokonts, are a large group of ecologically important eukaryotes that includes multi- and unicellular algae such as kelp and diatoms, but also economically important oomycete pathogens such as Phytophthora infestans. Confocal immunomicroscopy confirmed the mitochondrial location of glycolytic enzymes for the human parasite Blastocystis. Enzyme assays on cellular fractions confirmed the presence of the C3 part of glycolysis in Blastocystis mitochondria. These activities are sensitive to treatment with proteases and Triton X-100 but not proteases alone. Our work clearly shows that core cellular metabolism is more plastic than previously imagined and suggests new strategies to combat stramenopile pathogens such as the causative agent of late potato blight, P. infestans.

evolutionary biology↗