Molecular Events Underlying Pregnancy-Induced Cardiomyopathy

The etiology of cardiomyopathy in pregnant women remains unclear. In this issue, Hilfiker-Kleiner et al. (2007) report that a reduction in STAT3 and a concomitant increase in cathepsin D may be a cause of this disease. Cathepsin D generates an antiangiogenic cleavage product of the hormone prolactin. The authors show that an inhibitor of prolactin secretion may be useful in treating this disease

Fighting Fat with Muscle: Bulking Up to Slim Down

Akt1 is a well-characterized mediator of muscle hypertrophy. In this issue of Cell Metabolism, Izumiya et al. (2008) reveal a striking link between Akt1 signaling, fast muscle fiber size, and whole-body metabolism. These results provide new insights into the ability of muscle to combat diet-induced obesity and metabolic dysfunction

Skeletal myosin heavy chain function in cultured lung myofibroblasts

Myofibroblasts are unique contractile cells with both muscle and nonmuscle properties. Typically myofibroblasts are identified by the expression of α smooth muscle actin (ASMA); however some myofibroblasts also express sarcomeric proteins. In this study, we show that pulmonary myofibroblasts express three of the eight known sarcomeric myosin heavy chains (MyHCs) (IIa, IId, and embryonic) and that skeletal muscle myosin enzymatic activity is required for pulmonary myofibroblast contractility. Furthermore, inhibition of skeletal myosin activity and myofibroblast contraction results in a decrease in both ASMA and skeletal MyHC promoter activity and ASMA protein expression, suggesting a potential coupling of skeletal myosin activity and ASMA expression in myofibroblast differentiation. To understand the molecular mechanisms whereby skeletal muscle genes are regulated in myofibroblasts, we have found that members of the myogenic regulatory factor family of transcription factors and Ca2+-regulated pathways are involved in skeletal MyHC promoter activity. Interestingly, the regulation of skeletal myosin expression in myofibroblasts is distinct from that observed in muscle cells and suggests that cell context is important in its control

IIb or not IIb? Regulation of myosin heavy chain gene expression in mice and men

<p>Abstract</p> <p>Background</p> <p>While the myosin heavy chain IIb isoform (MyHC-IIb) is the predominant motor protein in most skeletal muscles of rats and mice, the messenger RNA (mRNA) for this isoform is only expressed in a very small subset of specialized muscles in adult large mammals, including humans.</p> <p>Results</p> <p>We identify the DNA sequences limiting MyHC-IIb expression in humans and explore the activation of this gene in human skeletal muscle. We demonstrate that the transcriptional activity of ~1.0 kb of the human MyHC-IIb promoter is greatly reduced compared to that of the corresponding mouse sequence in both mouse and human myotubes <it>in vitro </it>and show that nucleotide differences that eliminate binding sites for myocyte enhancer factor 2 (MEF2) and serum response factor (SRF) account for this difference. Despite these differences, we show that MyHC-IIb mRNA is expressed in fetal human muscle cells and that MyHC-IIb mRNA is significantly up-regulated in the skeletal muscle of Duchene muscular dystrophy patients.</p> <p>Conclusions</p> <p>These data identify the genetic basis for a key phenotypic difference between the muscles of large and small mammals, and demonstrate that mRNA expression of the MyHC-IIb gene can be re-activated in human limb muscle undergoing profound degeneration/regeneration.</p

A randomized library approach to identifying functional lox site domains for the Cre recombinase

The bacteriophage P1 Cre/loxP site-specific recombination system is a useful tool in a number of genetic engineering processes. The Cre recombinase has been shown to act on DNA sequences that vary considerably from that of its bacteriophage recognition sequence, loxP. However, little is known about the sequence requirements for functional lox-like sequences. In this study, we have implemented a randomized library approach to identify the sequence characteristics of functional lox site domains. We created a randomized spacer library and a randomized arm library, and then tested them for recombination in vivo and in vitro. Results from the spacer library show that, while there is great plasticity, identity between spacer pairs is the most important factor influencing function, especially in in vitro reactions. The presence of one completely randomized arm in a functional loxP recombination reaction revealed that only three wild-type loxP arms are necessary for successful recombination in Cre-expressing bacteria, and that there are nucleotide preferences at the first three and last three positions of the randomized arm for the most efficiently recombined sequences. Finally, we found that in vitro Cre recombination reactions are much more stringent for evaluating which sequences can support efficient recombination compared to the 294-CRE system

Remembering Jeff Robbins: The Father of Cardiac Transgenesis

Jeff graduated from the University of Connecticut with his PhD in 1976 and became an assistant professor in 1978 at the University of Missouri-Columbia. Jeff then moved to Ohio in 1985 to the University of Cincinnati as an associate professor where he stayed until moving his scientific research program across the street to the Cincinnati Children&rsquo;s Hospital in 1993, where he served as a professor in Pediatrics of the University of Cincinnati and as the founding director of the Division of Molecular Cardiovascular Biology. Jeff retired from Cincinnati Children&rsquo;s Hospital and the University of Cincinnati in 2019. &nbsp;</p

Consumer Spending in the Economic Downturn

Consumer Spending in the Economic Downturn -- The Wide Ranging Impact on Consumer Behavio