Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.     

Platelet-Rich Plasma Promotes the Proliferation of Human Keratinocytes via a Progression of the Cell Cycle. A Role of Prolidase

Although the role of platelet-rich plasma (PRP) in tissue regeneration has been confirmed in many studies, the mechanism of this process is still not fully understood. Human keratinocytes (HaCaT) cells were used as an experimental model for studies on the effects of PRP on cell proliferation, migration, collagen biosynthesis, prolidase activity, and its expression and anabolic signaling. The activation of epidermal growth factor receptor (EGFR), β₁-integrin, and insulin-like growth factor-1 receptor (IGF-1R) by PRP were investigated by western blot and immunocytochemistry. It has been found that PRP induced keratinocytes migration and proliferation through activation of cell cycle progression and EGFR downstream signaling. Similar biological effects were achieved by an addition to the culture medium of prolidase (PEPD), a ligand of EGFR (PRP is a rich source of PEPD–2 ng/mL). PRP-dependent stimulation of collagen biosynthesis was accompanied by an increase in the expression of NF-κβ, IGF-1R-downstream signaling proteins, and PEPD activity. The data suggest that PRP activates a complex of growth factors and adhesion receptors that stimulate cell proliferation, migration, and collagen biosynthesis. PRP induces PEPD-dependent human keratinocyte proliferation through activation of the EGFR receptor. Our study provides a novel mechanism of PRP-dependent wound healing.     

Lipofilling in Breast Oncological Surgery: A Safe Opportunity or Risk for Cancer Recurrence?

Lipofilling (LF) is a largely employed technique in reconstructive and esthetic breast surgery. Over the years, it has demonstrated to be extremely useful for treatment of soft tissue defects after demolitive or conservative breast cancer surgery and different procedures have been developed to improve the survival of transplanted fat graft. The regenerative potential of LF is attributed to the multipotent stem cells found in large quantity in adipose tissue. However, a growing body of pre-clinical evidence shows that adipocytes and adipose-derived stromal cells may have pro-tumorigenic potential. Despite no clear indication from clinical studies has demonstrated an increased risk of cancer recurrence upon LF, these observations challenge the oncologic safety of the procedure. This review aims to provide an updated overview of both the clinical and the pre-clinical indications to the suitability and safety of LF in breast oncological surgery. Cellular and molecular players in the crosstalk between adipose tissue and cancer are described, and heterogeneous contradictory results are discussed, highlighting that important issues still remain to be solved to get a clear understanding of LF safety in breast cancer patients.     

Physicochemical properties of calcific deposits isolated from porcine bioprosthetic heart valves removed from patients following 2-13 years function

The purpose of this study was to characterize the physicochemical properties of calcific deposits that cause the failure of tissue-derived heart valve bioprostheses. This was done in an effort to understand the mechanism of pathologic biomineralization in the cardiovascular system and potentially prevent deterioration of bioprostheses. Calcific deposits taken from 10 failed bioprosthetic valves that had been implanted in patients for 2-13 years were characterized by chemical analysis, x-ray diffraction, FTIR spectroscopy, scanning electron microscopy, polarized light microscopy, and solubility measurements. The combined results identified the biomineral as an apatitic calcium phosphate salt with substantial incorporation of sodium, magnesium and carbonate. The average Ca/PO4 ratio for this "young" pathologic biomineral was approximately 1.3, considerably lower than approximately 1.7 found in mature atherosclerotic plaque biomineral and mature skeletal biomineral, both of which approximate hydroxyapatite in composition. Deproteinated calcific deposits from bioprostheses had thermodynamic solubilities comparable to those of both atherosclerotic plaque, typical pathologic biomineral and hydrolyzed octacalcium phosphate (OCP, Ca4H(PO4)3 x 2.5 H2O), a proposed precursor phase to biomineral apatite. This later finding, together with chemical composition and structural details of the bioprosthetic deposits themselves, supports a mechanism of cardiovascular calcification in which OCP plays a crucial role in the formation of the final apatitic phase. This suggests an approach toward prevention of bioprosthetic tissue calcification through control of the formation of the kinetically favored OCP precursor and/or its transformation into bioapatite.     

A method for sensorless on-line vibration monitoring of inductionmachines

This paper proposes a method for the sensorless online vibration monitoring of induction machines based on the relationship between the current harmonics in the machine and their related vibration harmonics. Initially, the vibration monitoring system records two baseline measurements of current and vibration with the machine operating under normal conditions. The baseline data is then evaluated to determine the critical frequencies to monitor online. Once these frequencies are determined, the baseline vibration measurement is simply used to scale the current harmonic signal to an estimated vibration level. Based on theoretical analysis, simulation results and the experimental results shown here, a linear relationship between the current harmonics and vibration level can be assumed. The results of two experiments on a three-phase 230 V 10 hp induction motor operating under no load are discussed and show the feasibility of this method for sensorless online vibration monitoring     

A lumped-parameter model to investigate the effect of plantar pressure on arterial blood flow in a diabetic foot

This paper presents a lumped-parameter model for the big-toe region that investigates the effect of plantar pressure on the diameter of the blood vessels, specifically the arteries, in the presence of arterial and/or tissue changes. The model developed in this paper uses a multi-domain energy system approach to develop the lumped-parameter differential equations. Blood flow is modelled as fluidic flow through compliant pipes that have inertia, stiffness, and damping. The tissue material is treated as a soft compliant material that transmits the external force to the blood vessels. Conclusions have been drawn to show the effect of plantar pressure, tissue damage, and their combination on the diameter of the blood vessels. The principles used here can be used to model the entire foot and the model used to investigate the effect of plantar pressure, tissue damage, and arterial changes on different parts of the foot. The work presented here may also have applications in other vascular diseases.     

Energy Spectra Of Dislocations In Silicon And Germanium

The properties of edge-type dislocations are strongly dependent on the temperature at which they have been introduced into the crystal. Dislocations produced at T < 0·6 T_m (T_m melting point) exhibit a richer variety of properties than those introduced at T > 0·6 T_m: in germanium a strong increase of the hole density, in silicon an electron para-magnetic resource (EPR)-signal, showing many fine details, and several peaks in the deep level transient spectroscopy (DLTS)-signal, are only found after low-temperature deformation. The increase in the hole density has been ascribed to point defect clouds, which surround the dislocation, and seem to control their mobility. The clouds are not stable at the deformation temperature. The electrical and optical properties of edge-type dislocations, introduced at T > 0·6 T_m into germanium, can be interpreted in terms of a half-filled one-dimensional band (for T ≥ 50 K), which might be due to dangling bonds in the dislocation core. In silicon the experimental data indicate a similar form of the local energy spectrum at dislocations.     

Relative contributions of nearshore and wetland habitats to coastal food webs in the Great Lakes

Hydrologic linkages among coastal wetland and nearshore areas allow coastal fish to move among the habitats, which has led to a variety of habitat use patterns. We determined nutritional support of coastal fishes from 12 wetland-nearshore habitat pairs using stable isotope analyses, which revealed differences among species and systems in multi-habitat use. Substantial (proportions?>?0.30) nutrition often came from the habitat other than that in which fish were captured. Nearshore subsidies to coastal wetlands indicate wetlands are not exclusively exporters of energy and materials; rather, there is reciprocity in the mutual energetic support of nearshore and wetland food webs. Coastal wetland hydrogeomorphology influenced the amount of multi-habitat use by coastal fishes. Fishes from systems with relatively open interfaces between wetland and nearshore habitats exhibited less nutritional reliance on the habitat in which they were captured, and higher use of resources from the adjacent habitat. Comparisons of stable isotope analyses of nutrition with otolith analyses of occupancy indicated nutritional sources often corresponded with habitat occupancy; however, disparities among place of capture, otolith analyses, and nutritional analyses indicated differences in the types of support those analyses inform. Disparities between occupancy information and nutritional information can stem from movements for support functions other than foraging. Together, occupancy information from otolith microchemistry and nutritional information from stable isotope analyses provide complementary measures of the use of multiple habitats by mobile consumers. This work underscores the importance of protecting or restoring a diversity of coastal habitats and the hydrologic linkages among them.