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Indianapolis, IN, United States

Imamura M.,Baylor College of Medicine | Imamura M.,RIKEN | Chang B.H.-J.,Baylor College of Medicine | Kohjima M.,Baylor College of Medicine | And 6 more authors.
Biochemical Journal

MondoA is a basic helix-loop-helix (bHLH)/leucine zipper (ZIP) transcription factor that is expressed predominantly in skeletal muscle. Studies in vitro suggest that the Max-like protein X (MondoA:Mlx) heterodimer senses the intracellular energy status and directly targets the promoter region of thioredoxin interacting protein (Txnip) and possibly glycolytic enzymes. We generated MondoA-inactivated (MondoA-/-) mice by gene targeting. MondoA-/- mice had normal body weight at birth, exhibited normal growth and appeared to be healthy. However, they exhibited unique metabolic characteristics. MondoA-/- mice built up serum lactate and alanine levels and utilized fatty acids for fuel during exercise. Gene expression and promoter analysis suggested that MondoA functionally represses peroxisomeproliferatoractivated receptor γ co-activator-1α (PGC-1α)-mediated activation of pyruvate dehydrogenase kinase 4 (PDK-4) transcription. PDK4 normally down-regulates the activity of pyruvate dehydrogenase, an enzyme complex that catalyses the decarboxylation of pyruvate to acetyl-CoA for entry into the Krebs cycle; in the absence of MondoA, pyruvate is diverted towards lactate and alanine, both products of glycolysis. Dynamic testing revealed that MondoA-/- mice excel in sprinting as their skeletal muscles display an enhanced glycolytic capacity. Our studies uncover a hitherto unappreciated function of MondoA in fuel selection in vivo. Lack of MondoA results in enhanced exercise capacity with sprinting. © 2014 Biochemical Society. Source

Livorsi D.J.,Richard Roudebush Medical Center | Livorsi D.J.,Indiana University | Arif S.,Indiana University | Garry P.,Richard Roudebush Medical Center | And 7 more authors.
Infection Control and Hospital Epidemiology

Objective. We sought to determine whether the bacterial burden in the nares, as determined by the cycle threshold (CT) value from real-time MRSA PCR, is predictive of environmental contamination with MRSA Methods. Patients identified as MRSA nasal carriers per hospital protocol were enrolled within 72 hours of room admission. Patients were excluded if (1) nasal mupirocin or chlorhexidine body wash was used within the past month or (2) an active MRSA infection was suspected. Four environmental sites, 6 body sites and a wound, if present, were cultured with premoistened swabs. All nasal swabs were submitted for both a quantitative culture and real-time PCR (Roche Lightcycler, Indianapolis, IN) Results. At study enrollment, 82 patients had a positive MRSA-PCR. A negative correlation of moderate strength was observed between the CT value and the number of MRSA colonies in the nares (r= −0.61; P<0.01). Current antibiotic use was associated with lower levels of MRSA nasal colonization (CT value, 30.2 vs 27.7; P < 0.01). Patients with concomitant environmental contamination had a higher median log MRSA nares count (3.9 vs 2.5, P = 0.01) and lower CT values (28.0 vs 30.2; P < 0.01). However, a ROC curve was unable to identify a threshold MRSA nares count that reliably excluded environmental contamination Conclusions. Patients with a higher burden of MRSA in their nares, based on the CT value, were more likely to contaminate their environment with MRSA. However, contamination of the environment cannot be predicted solely by the degree of MRSA nasal colonization. © 2015 by The Society for Healthcare Epidemiology of America. All rights reserved. Source

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