Hexosamine-Induced TGF-β Signaling and Osteogenic Differentiation of Dental Pulp Stem Cells Are Dependent on N-Acetylglucosaminyltransferase V

Glycans of cell surface glycoproteins are involved in the regulation of cell migration, growth, and differentiation. N-acetyl-glucosaminyltransferase V (GnT-V) transfers N-acetyl-d-glucosamine to form β1,6-branched N-glycans, thus playing a crucial role in the biosynthesis of glycoproteins. This study reveals the distinct expression of GnT-V in STRO-1 and CD-146 double-positive dental pulp stem cells (DPSCs). Furthermore, we investigated three types of hexosamines and their N-acetyl derivatives for possible effects on the osteogenic differentiation potential of DPSCs. Our results showed that exogenous d-glucosamine (GlcN), N-acetyl-d-glucosamine (GlcNAc), d-mannosamine (ManN), and acetyl-d-mannosamine (ManNAc) promoted DPSCs' early osteogenic differentiation in the absence of osteogenic supplements, but d-galactosamine (GalN) or N-acetyl-galactosamine (GalNAc) did not. Effects include the increased level of TGF-β receptor type I, activation of TGF-β signaling, and increased mRNA expression of osteogenic differentiation marker genes. The hexosamine-treated DPSCs showed an increased mineralized matrix deposition in the presence of osteogenic supplements. Moreover, the level of TGF-β receptor type I and early osteogenic differentiation were abolished in the DPSCs transfected with siRNA for GnT-V knockdown. These results suggest that GnT-V plays a critical role in the hexosamine-induced activation of TGF-β signaling and subsequent osteogenic differentiation of DPSCs.

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Tinnitus and Headache

Background. Tinnitus and headache are frequent disorders. Here, we aimed to investigate whether the occurrence of headache among tinnitus patients is purely coincidental or whether tinnitus and headache are pathophysiologically linked. We investigated a large sample of patients with tinnitus and headache to estimate prevalence rates of different headache forms, to determine the relationship between tinnitus laterality and headache laterality, and to explore the relationship between tinnitus and headache over time. Method. Patients who presented at a tertiary referral center because of tinnitus and reported comorbid headache were asked to complete validated questionnaires to determine the prevalence of migraine and tension-type headache and to assess tinnitus severity. In addition, several questions about the relationship between headache and tinnitus were asked. Results. Datasets of 193 patients with tinnitus and headache were analysed. 44.6% suffered from migraine, 13% from tension-type headache, and 5.7% from both. Headache laterality was significantly related to tinnitus laterality and in the majority of patients fluctuations in symptom severity of tinnitus and headache were interrelated. Conclusion. These findings suggest a significant relationship between tinnitus and headache laterality and symptom interaction over time and argue against a purely coincidental cooccurrence of tinnitus and headache. Both disorders may be linked by common pathophysiological mechanisms.

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The Effect of Risk Factors on the Levels of Chemical Elements in the Tibial Plateau of Patients with Osteoarthritis following Knee Surgery

The aim of this study was to evaluate the aforementioned chemical elements in tibial plateau samples obtained during knee arthroplasty. The gender-specific analysis of chemical element levels in the bone samples revealed that there were statistically significant differences in the concentration of Pb and Se/Pb ratio. The contents of elements in the tibial plateau in the patients with osteoarthritis (OA) can be arranged in the following descending order: F− > K > Zn > Fe > Sr > Pb > Mn > Se > Cd > THg. We observed statistical significant effects of environmental factors including smoking, seafood diet, and geographical distribution on the levels of the elements in tibial bone. Significant positive correlation coefficients were found for the relationships K-Cd, Zn-Sr, Zn-F−, THg-Pb, Pb-Cd, Se-Se/Pb, Se-Se/Cd, Se/Pb-Se/Cd, Pb-Cd/Ca, Cd-Cd/Ca, and F−-F−/Ca1000. Significant negative correlations were found for the relationships THg-Se/Pb, Pb-Se/Pb, Cd-Se/Pb, K-Se/Cd, Pb-Se/Cd, Cd-Se/Cd, THg-Se/THg, Pb-Se/THg, Se-Pb/Cd, Zn-Cd/Ca, and Se/Cd-Cd/Ca. The results reported here may provide a basis for establishing reference values for the tibial plateau in patients with OA who had undergone knee replacement surgery. The concentrations of elements in the bone with OA were determined by age, presence of implants, smoking, fish and seafood diet, and sport activity.

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Image-Based Structural Modeling of the Cardiac Purkinje Network

The Purkinje network is a specialized conduction system within the heart that ensures the proper activation of the ventricles to produce effective contraction. Its role during ventricular arrhythmias is less clear, but some experimental studies have suggested that the Purkinje network may significantly affect the genesis and maintenance of ventricular arrhythmias. Despite its importance, few structural models of the Purkinje network have been developed, primarily because current physical limitations prevent examination of the intact Purkinje network. In previous modeling efforts Purkinje-like structures have been developed through either automated or hand-drawn procedures, but these networks have been created according to general principles rather than based on real networks. To allow for greater realism in Purkinje structural models, we present a method for creating three-dimensional Purkinje networks based directly on imaging data. Our approach uses Purkinje network structures extracted from photographs of dissected ventricles and projects these flat networks onto realistic endocardial surfaces. Using this method, we create models for the combined ventricle-Purkinje system that can fully activate the ventricles through a stimulus delivered to the Purkinje network and can produce simulated activation sequences that match experimental observations. The combined models have the potential to help elucidate Purkinje network contributions during ventricular arrhythmias.

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The Association between Cerebral White Matter Lesions and Plasma Omega-3 to Omega-6 Polyunsaturated Fatty Acids Ratio to Cognitive Impairment Development

Objective. Cerebral white matter hyperintensity (WMH) with magnetic resonance imaging (MRI) has a potential for predicting cognitive impairment. Serum polyunsaturated fatty acid (PUFA) levels are important for evaluating the extent of atherosclerosis. We investigated whether abnormal PUFA levels affected WMH grading and cognitive function in patients without significant cognitive impairment. Methods. Atherosclerotic risk factors, the internal carotid artery (ICA) plaque, and serum ratios of eicosapentaenoic to arachidonic acids (EPA/AA) and docosahexaenoic to arachidonic acids (DHA/AA) were assessed in 286 patients. The relationship among these risk factors, WMH, and cognitive function was evaluated using WMH grading and the Mini-Mental State Examination (MMSE). Results. The development of WMH was associated with aging, hypertension, ICA plaques, and a low serum EPA/AA ratio (

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Epidemiology of rubella and congenital rubella syndrome in Japan before 1989

Publication date: Available online 21 October 2015
Source:Vaccine
Author(s): Kohji Ueda
Epidemiological studies of rubella and congenital rubella syndrome (CRS) in Japan have been conducted since the first nationwide rubella epidemic of 1965–1969 and subsequent epidemics of 1975–1977, 1982, 1987–1988, and 1992–1993. Rubella was non-endemic in Japan before the 1975–1977 epidemic, and endemic thereafter. Japan started a selective rubella vaccination program for junior high school girls in 1977, and universal rubella vaccination of children of both sexes in 1989. No nationwide rubella epidemics have occurred since 1994.Only three children with CRS were reported in Japan before 1964; however, many children with CRS were identified in 1965 when a rubella epidemic struck Okinawa, which has many the United States military bases. After the 1965–1969 and 1975–1977 rubella epidemics on the Japanese mainland, small numbers of children with CRS were identified (hospital survey). These findings led to the hypothesis that, compared to U.S. rubella virus strains, Japanese strains of rubella virus are less teratogenic. This hypothesis strongly affected the development of rubella vaccines in Japan. However, retrospective seroepidemiological studies attributed the CRS in many children in Okinawa to the high rate of rubella infection in pregnant women. According to the survey conducted at special schools for the deaf, 83, 232, 77, and 167 children were born with CRS on the Japanese mainland respectively after the 1965–1969, 1975–1977, 1982, and 1987–1988 nationwide rubella epidemics, suggesting that the incidence of CRS in Japan is in fact comparable to that in the U.S. and Europe.Rubella epidemics in children have been effectively prevented since 1994. However, a rubella outbreak among adult males and CRS occurred between 2012 and 2014.



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A cytomegalovirus DNA vaccine induces antibodies that block viral entry into fibroblasts and epithelial cells

Publication date: Available online 24 October 2015
Source:Vaccine
Author(s): Michael A. McVoy, Ronzo Lee, Frances M. Saccoccio, Jukka Hartikka, Larry R. Smith, Rohit Mahajan, Jian Ben Wang, Xiaohong Cui, Stuart P. Adler
A vaccine to prevent congenital cytomegalovirus (CMV) infections is a national priority. Investigational vaccines have targeted the viral glycoprotein B (gB) as an inducer of neutralizing antibodies and phosphoprotein 65 (pp65) as an inducer of cytotoxic T cells. Antibodies to gB neutralize CMV entry into all cell types but their potency is low compared to antibodies that block epithelial cell entry through targeting the pentameric complex (gH/gL/UL128/UL130/UL131). Hence, more potent overall neutralizing responses may result from a vaccine that combines gB with pentameric complex-derived antigens. To assess the ability of pentameric complex subunits to generate epithelial entry neutralizing antibodies, DNA vaccines encoding UL128, UL130, and/or UL131 were formulated with Vaxfectin^®, an adjuvant that enhances antibody responses to DNA vaccines. Mice were immunized with individual DNA vaccines or with pair-wise or trivalent combinations. Only the UL130 vaccine induced epithelial entry neutralizing antibodies and no synergy was observed from bi- or trivalent combinations. In rabbits the UL130 vaccine again induced epithelial entry neutralizing antibodies while UL128 or UL131 vaccines did not. To evaluate compatibility of the UL130 vaccine with DNA vaccines encoding gB or pp65, mono-, bi-, or trivalent combinations were evaluated. Fibroblast and epithelial entry neutralizing titers did not differ between rabbits immunized with gB alone vs. gB/UL130, gB/pp65, or gB/UL130/pp65 combinations, indicating a lack of antagonism from coadministration of DNA vaccines. Importantly, gB-induced epithelial entry neutralizing titers were substantially higher than activities induced by UL130, and both fibroblast and epithelial entry neutralizing titers induced by gB alone as well as gB/pp65 or gB/UL130/pp65 combinations were comparable to those observed in sera from humans with naturally-acquired CMV infections. These findings support further development of Vaxfectin^®-formulated gB-expressing DNA vaccine for prevention of congenital CMV infections.



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