MicroRNAs (miRNAs) are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. We used microarrays and RT-PCR to profile miRNA expression changes in the brains of mice infected with mouse-adapted scrapie. We determined 15 miRNAs were de-regulated during the disease processes; miR-342-3p, miR-320, let-7b, miR-328, miR-128, miR-139-5p and miR-146a were over 2.5 fold up-regulated and miR-338-3p and miR-337-3p over 2.5 fold down-regulated. Only one of these miRNAs, miR-128, has previously been shown to be de-regulated in neurodegenerative disease. De-regulation of a unique subset of miRNAs suggests a conserved, disease-specific pattern of differentially expressed miRNAs is associated with prion–induced neurodegeneration. Computational analysis predicted numerous potential gene targets of these miRNAs, including 119 genes previously determined to be also de-regulated in mouse scrapie. We used a co-ordinated approach to integrate miRNA and mRNA profiling, bioinformatic predictions and biochemical validation to determine miRNA regulated processes and genes potentially involved in disease progression. In particular, a correlation between miRNA expression and putative gene targets involved in intracellular protein-degradation pathways and signaling pathways related to cell death, synapse function and neurogenesis was identified.
Shiga toxin-producing Escherichia coli (STEC) are zoonotic foodborne and waterborne pathogens that are a serious public health concern because they cause outbreaks and the potentially fatal hemolytic uremic syndrome (HUS). The most common STEC serotype associated with human disease is O157:H7, but there is a growing recognition of over 100 non-O157 serotypes that also may result in human illness. Some of these non-O157 STEC strains cause outbreaks and severe disease such as HUS and hemorrhagic colitis, whereas others are associated with only mild diarrhea or with no human disease at all. The relative scarceness of whole genome sequence data for non-O157 STEC has limited the scientific discovery into the genetic basis of these differences in virulence. Uncovering the scope of genetic diversity and phylogeny of the non-O157 STEC through targeting sequencing of clinically relevant isolates will offer new biological insight to the pathogenic behavior of these emerging pathogens. These approaches would also enable molecular risk assessment strategies to rapidly identify and respond to emerging non-O157 STEC that pose a serious public health risk to humans.
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