Premature Osteoblast Clustering by Enamel Matrix Proteins Induces Osteoblast Differentiation through Up-Regulation of Connexin 43 and N-Cadherin

In recent years, enamel matrix derivative (EMD) has garnered much interest in the dental field for its apparent bioactivity that stimulates regeneration of periodontal tissues including periodontal ligament, cementum and alveolar bone. Despite its widespread use, the underlying cellular mechanisms remain unclear and an understanding of its biological interactions could identify new strategies for tissue engineering. Previous in vitro research has demonstrated that EMD promotes premature osteoblast clustering at early time points. The aim of the present study was to evaluate the influence of cell clustering on vital osteoblast cell-cell communication and adhesion molecules, connexin 43 (cx43) and N-cadherin (N-cad) as assessed by immunofluorescence imaging, real-time PCR and Western blot analysis. In addition, differentiation markers of osteoblasts were quantified using alkaline phosphatase, osteocalcin and von Kossa staining. EMD significantly increased the expression of connexin 43 and N-cadherin at early time points ranging from 2 to 5 days. Protein expression was localized to cell membranes when compared to control groups. Alkaline phosphatase activity was also significantly increased on EMD-coated samples at 3, 5 and 7 days post seeding. Interestingly, higher activity was localized to cell cluster regions. There was a 3 fold increase in osteocalcin and bone sialoprotein mRNA levels for osteoblasts cultured on EMD-coated culture dishes. Moreover, EMD significantly increased extracellular mineral deposition in cell clusters as assessed through von Kossa staining at 5, 7, 10 and 14 days post seeding. We conclude that EMD up-regulates the expression of vital osteoblast cell-cell communication and adhesion molecules, which enhances the differentiation and mineralization activity of osteoblasts. These findings provide further support for the clinical evidence that EMD increases the speed and quality of new bone formation in vivo

Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances

Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. Reports of deficiencies in disaccharidase enzymatic activity and of beneficial responses to probiotic and dietary therapies led us to survey gene expression and the mucoepithelial microbiota in intestinal biopsies from children with autism and gastrointestinal disease and children with gastrointestinal disease alone. Ileal transcripts encoding disaccharidases and hexose transporters were deficient in children with autism, indicating impairment of the primary pathway for carbohydrate digestion and transport in enterocytes. Deficient expression of these enzymes and transporters was associated with expression of the intestinal transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. Expression levels of disaccharidases and transporters were associated with the abundance of affected bacterial phylotypes. These results indicate a relationship between human intestinal gene expression and bacterial community structure and may provide insights into the pathophysiology of gastrointestinal disturbances in children with autism

BsmI polymorphism in the vitamin D receptor gene is associated with leg extensor muscle strength in elderly men

Background and aims: Sarcopenia is defined as a reduction in skeletal muscle mass, strength, and endurance observed with advancing age. Although Vitamin D receptor (VDR) polymorphism is reported to be associated with muscle mass and strength, evidence for this is limited and conflicting. In this study, we examined the association between the polymorphisms of VDR gene BsmI, TaqI and FokI and muscular mass and strength in elderly men. Methods: This is a cross-sectional study conducted in a university hospital. One hundred and twenty men over 65 years of age participated, all participants were active men living independently in Istanbul, who were followed as outpatients in geriatric polyclinics. Most common diagnoses were hypertension, hyperlipidemia, and mild to moderate osteoarthritis. Morbid obese patients were not included in the study. Genomic DNA was extracted from peripheral blood, and VDR genotypes were determined by the polymerase chain reaction. The peak torque of the knee flexors and extensors was measured on a Cybex 350 dynamometer. Body muscle mass was calculated by using bioelectric impedance analysis. Results: The extensor strength of the knee was higher in BB homozygotic men than in the Bb/bb group. No significant association was found with TaqI and FokI haplotypes. There was no significant association between muscle mass and strength, or between muscle mass and VDR genotype. Conclusion: Our data suggest that VDR gene BsmI polymorphism is associated with muscular strength in elderly men. (Aging Clin Exp Res 2010; 22: 198-205) (C) 2010, Editrice Kurti

Gap Opening of Graphene by Dual FeCl3-Acceptor and K-Donor Doping

The band gap opening of graphene is the most desired property in the device industry because it is vital to the application of graphene as a logical device of semiconductors. Here, we show how to make a reasonably wide band gap in graphene. This is accomplished with bilayer graphene (BLG) dual-doped with FeCl3-acceptor and K-donor. To elucidate this phenomenon, we employed the first-principles method taking into account van der Waals interaction. For the FeCl3 adsorbed BLG, the optimal distance between the adjacent graphene and FeCl3 layers is 4.6-4.8 angstrom, consistent with experiments. Due to the high electronegativity of FeCl3, these graphene layers are hole-doped. The dual-doped BLG gives a band gap of 0.27 eV due to broken symmetry, with a Dirac point shift by -0.09 eV. This increased band gap and proper Dirac point shift could make the dual-doped BLG useful for applications toward future field effect transistor devices.close272