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Vascular calcification is common in people with diabetes and its presence predicts premature mortality. To clarify the underlying mechanisms, we used low density lipoprotein receptor-deficient (LDLR -/-) mice to study vascular calcification in the ascending aorta. LDLR -/- mice on a chow diet did not develop obesity, diabetes, atheroma, or vascular(More)
Osteocalcin (OC) is a small calcium binding protein expressed in bones and teeth undergoing mineralization. OC expression in calvarial osteoblasts and odontoblasts is regulated in part via protein-protein interactions between the homeodomain repressor, Msx2, and components of the cell type-specific basal OC promoter. Recent work suggests that homeodomain(More)
Msx2 is a homeodomain transcription factor that regulates craniofacial development in vivo and osteocalcin (Osc) promoter activity in vitro. Msx2 is expressed in many craniofacial structures prior to embryonic day (E) E14 but is expressed at later stages in a restricted pattern, primarily in developing teeth and the calvarium. We examine Osc expression by(More)
Inducible membrane remodeling is an adaptive mechanism that enables Gram-negative bacteria to resist killing by cationic antimicrobial peptides and to avoid eliciting an immune response. Addition of 4-amino-4-deoxy-l -arabinose (4-aminoarabinose) moieties to the phosphate residues of the lipid A portion of the lipopolysaccharide decreases the net negative(More)
Osteocalcin (OC) is a calcium binding protein expressed in mature osteoblasts undergoing mineralization. The OC gene has been identified as a target for transcriptional suppression by Msx2, a homeodomain transcription factor that controls ossification in calvarial bone of the developing skull. We have initiated systematic structure-function analyses of(More)
A fundamental question in biology is how an organism integrates multiple signals to mediate an appropriate cellular response. The PmrAPmrB two-component system of Salmonella enterica can be activated independently by Fe(3+), which is sensed by the PmrB protein, and in low Mg(2+), which is sensed by the PhoQ protein. The low-Mg(2+) activation requires pmrD,(More)
Drug efflux systems play a major role in resistance to a wide range of noxious compounds in several Gram negative species. Here, we report the drug resistance and virulence phenotypes of Salmonella mutants defective in either resistance-nodulation-division (RND)-type systems and/or in drug efflux systems belonging to the major facilitator (MFS), multidrug(More)
Genetic and genomic approaches have been successfully used to assign genes to distinct regulatory networks. However, the present challenge of distinguishing differentially regulated genes within a network is particularly hard because members of a given network tend to have similar regulatory features. We have addressed this challenge by developing a method,(More)
Most RNA molecules require Mg(2+) for their structure and enzymatic properties. Here we report the first example of an RNA serving as sensor for cytoplasmic Mg(2+). We establish that expression of the Mg(2+) transporter MgtA of Salmonella enterica serovar Typhimurium is controlled by its 5' untranslated region (5'UTR). We show that the 5'UTR of the mgtA(More)
The sigma factor RpoS regulates the expression of many stress response genes and is required for virulence in several bacterial species. We now report that RpoS accumulates when Salmonella enterica serovar Typhimurium is growing logarithmically in media with low Mg(2+) concentrations. This process requires the two-component regulatory system PhoP/PhoQ,(More)