The role of Lrp5/6 in cardiac valve disease: LDL-density-pressure theory

Atherosclerosis and osteoporosis are the leading causes of mortality and morbidity in the World. Recent epidemiologic studies have demonstrated that these disease processes develop in parallel. Evidence indicates that hyperlipidemia plays a paradoxical role in both disease processes. However, the mechanism is not understood. This prospectus hypothesizes the role of lipids activate atherosclerosis within the bone and the heart to initiate the development of diseases in both of these tissues. The Prospectus on the Lrp 5/6 receptors provides a foundation for the mechanisms involved in the Lrp5/6 mediated disease biology. The LDL-Density-Pressure theory: the Role of Lrp5/6 provides a biological and a hemodynamic approach towards understanding the development of valvular heart disease and the implications in the field of bone molecular biology. This prospectus will review the current literature, provide a basis for the development of valve disease and indicate future therapeutic pathways for this disease process in the future.     

Sexual selection on male size drives the evolution of male‐biased sexual size dimorphism via the prolongation of male development

Sexual size dimorphism (SSD) arises when the net effects of natural and sexual selection on body size differ between the sexes. Quantitative SSD variation between taxa is common, but directional intraspecific SSD reversals are rare. We combined micro‐ and macroevolutionary approaches to study geographic SSD variation in closely related black scavenger flies. Common garden experiments revealed stark intra‐ and interspecific variation: Sepsis biflexuosa is monomorphic across the Holarctic, while S. cynipsea (only in Europe) consistently exhibits female‐biased SSD. Interestingly, S. neocynipsea displays contrasting SSD in Europe (females larger) and North America (males larger), a pattern opposite to the geographic reversal in SSD of S. punctum documented in a previous study. In accordance with the differential equilibrium model for the evolution of SSD, the intensity of sexual selection on male size varied between continents (weaker in Europe), whereas fecundity selection on female body size did not. Subsequent comparative analyses of 49 taxa documented at least six independent origins of male‐biased SSD in Sepsidae, which is likely caused by sexual selection on male size and mediated by bimaturism. Therefore, reversals in SSD and the associated changes in larval development might be much more common and rapid and less constrained than currently assumed.     

Purification and Characterization of Extracellular Phytase from a Marine Yeast <Emphasis Type="Italic">Kodamaea ohmeri</Emphasis> BG3

The extracellular phytase in the supernatant of cell culture of the marine yeast Kodamaea ohmeri BG3 was purified to homogeneity with a 7.2-fold increase in specific phytase activity as compared to that in the supernatant by ammonium sulfate fractionation, gel filtration chromatography (Sephadex™ G-75), and anion-exchange chromatography (DEAE Sepharose Fast Flow Anion-Exchange). According to the data from sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the molecular mass of the purified enzyme was estimated to be 98.2 kDa while the molecular mass of the purified enzyme was estimated to be 92.9 kDa and the enzyme was shown to be a monomer according to the results of gel filtration chromatography. The optimal pH and temperature of the purified enzyme were 5.0 and 65°C, respectively. The enzyme was stimulated by Mn²⁺, Ca²⁺, K⁺, Li⁺, Na⁺, Ba²⁺, Mg²⁺ and Co²⁺ (at a concentrations of 5.0 mM), but it was inhibited by Cu²⁺, Hg²⁺, Fe²⁺, Fe³⁺, Ag⁺, and Zn²⁺ (at a concentration of 5.0 mM). The enzyme was also inhibited by phenylmethylsulfonyl fluoride (PMSF), iodoacetic acid (at a concentration of 1.0 mM), and phenylgloxal hydrate (at a concentration of 5.0 mM), and not inhibited by EDTA and 1,10-phenanthroline (at concentrations of 1.0 mM and 5.0 mM). The K _m, V _max, and K _cat values of the purified enzyme for phytate were 1.45 mM, 0.083 μmol/ml · min, and 0.93 s^-1, respectively.     

Investigating the Early Stages of Person Perception: The Asymmetry of Social Categorization by Sex vs. Age

Early perceptual operations are central components of the dynamics of social categorization. The wealth of information provided by facial cues presents challenges to our understanding of these early stages of person perception. The current study aimed to uncover the dynamics of processing multiply categorizable faces, notably as a function of their gender and age. Using a modified four-choice version of a mouse-tracking paradigm (which assesses the relative dominance of two categorical dimensions), the relative influence that sex and age have on each other during categorization of infant, younger adult, and older adult faces was investigated. Results of these experiments demonstrate that when sex and age dimensions are simultaneously categorized, only for infant faces does age influence sex categorization. In contrast, the sex of both young and older adults was shown to influence age categorization. The functional implications of these findings are discussed in light of previous person perception research.     

Oxidative-mechanical stress signals stem cell niche mediated Lrp5 osteogenesis in eNOS(-/-) null mice

Calcific aortic valve disease (CAVD) is the most common indication for valve surgery in the USA. This study hypothesizes that CAVD develops secondary to Wnt3a/Lrp5 activation via oxidative‐mechanical stress in eNOS null mice. eNOS^?/? mice were tested with experimental diets including a control (n = 20), cholesterol (n = 20), cholesterol + Atorvastatin (n = 20). After 23 weeks the mice were tested for the development of aortic stenosis by Echo, Histology, MicroCT, and RTPCR for bone markers. In vitro studies measured Wnt3a secretion from aortic valve endothelial cells and confirmed oxidative stress via eNOS activity. Anion exchange chromatography was performed to isolate the mitogenic protein. Myofibroblast cells were tested to induce bone formation. Cholesterol treated eNOS mice develop severe stenosis with an increase in Wnt3a, Lrp5, Runx2 (threefold increase (P < 0.0001) in the bicuspid versus tricuspid aortic valves. Secretion of Wnt3a from aortic valve endothelium in the presence of abnormal oxidative stress was correlated with diminished eNOS enzymatic activity and tissue nitrite levels. Initial characterization of the architecture for a stem cell nice was determined by protein isolation using anion‐exchange chromatography and cell proliferation via thymidine incorporation. Osteoblastogenesis in the myofibroblast cell occurred via Lrp5 receptor upregulation in the presence of osteogenic media. Targeting the Wnt3a/Lrp5 pathway in valve calcification and activation of osteogenesis is via an oxidative‐mechanical stress in CAVD. These findings provide a foundation for treating this disease process by targeting the cross talk mechanism in a resident stem cell niche. J. Cell. Biochem. 113: 1623–1634, 2012. © 2011 Wiley Periodicals, Inc.     

Polyethylene glycol (PEG)-induced mouse model of choroidal neovascularization

In this study, we describe a new method for inducing choroidal neovascularization (CNV) in C57BL/6 mice, an animal model of wet age-related macular degeneration (AMD). AMD is a disease that causes central blindness in humans. We injected PEG-8 subretinally in different doses (0.125-2 mg) to induce CNV. After PEG-8 injection, we examined CNV at several time points (days 3-42). We also used Western blotting, immunohistochemistry, and ELISA to examine the complement component C3 split products, C9, VEGF, TGF-β2, and basic FGF. As early as day 1 after treatment, we found that a single subretinal injection of 1 mg of PEG-8 increased the C3 split products and the C9, TGF-β2, and basic FGF levels in the retinal pigment epithelium-choroid tissue. By day 3 after PEG-8 injection, the intraocular activation of the complement system caused induction and progression of CNV, including new vessels penetrating the Bruch's membrane. At day 5 after PEG-8 injection, we observed a fully developed CNV and retinal degeneration. Thus, in this study, we present a new, inexpensive, and accelerated mouse model of CNV that may be useful to study AMD.