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The present study aimed to evaluate the effects of type 1 diabetes mellitus on the condylar response during treatment with a functional appliance. Sprague-Dawley rats were divided into 3 groups, normal (NG), diabetes (DG) and diabetes with insulin-treatment (TG). Bite-jumping appliances were fitted to the rats in the experimental groups. At 7, 14, 21 and 28 days following fitting, animals were sacrificed and condyles were excised and processed using routine histological techniques. The expression of matrix metalloproteinase (MMP)-8, MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) was detected using immunohistochemical analysis. Mandibular advancement increased the expression levels of MMP-8 (peaked on day 28), MMP-9 (peaked on day 21), TIMP-1 (peaked on days 21 and 28) and the ratio of MMP-8 to TIMP-1 and MMP-9 to TIMP-1. In the DG, diabetes decreased the expression levels of MMP-8 and MMP-9 induced by mandibular advancement and increased the expression levels of TIMP-1 compared with that of the NG. The ratio of MMP-8 to TIMP-1 and MMP-9 to TIMP-1 also showed a significant decrease in the DG compared with that of the NG. A recovery of these parameters was observed in the TG. Diabetes significantly altered the condylar response, which was triggered by mandibular advancement, and weakened subsequent bone deposition. The results from the TG were not significantly different from that of the NG. [ABSTRACT FROM AUTHOR]

Insulin has been proposed to be a positive regulator of osteoblast proliferation and bone formation. In vivo mechanical loading is essential for maintaining skeletal integrity and bone mass. Since insulin and mechanical force activate similar signaling pathways in osteoblasts, it was hypothesized that insulin may affect mechanical stimulation in osteoblasts. The present study tested the hypothesis that insulin augments mechanical strain-induced signaling and early gene expression in MG63 cells via activation of the extracellular signal-regulated kinase (ERK) pathway and cyclooxygenase-2 (Cox-2) expression. Western blot analysis and quantitative polymerase chain reaction demonstrated respectively that insulin enhanced mechanical strain-induced ERK phosphorylation and Cox-2 expression levels in a dose-dependent manner. The effect of insulin on mechanical strain-induced Cox-2 expression was inhibited by blockade of the ERK pathway. In addition, echistatin, an inhibitor of integrin function, prevented the effects of insulin on mechanical strain-induced ERK phosphorylation and Cox-2 expression. The data obtained from this study suggested that insulin augments mechanical strain-induced Cox-2 expression levels via integrin-dependent activation of the ERK pathway in osteoblasts. [ABSTRACT FROM AUTHOR]

Background: Bacterial meningitis is more common in the neonatal period than any other time in life; however, it is still a challenge for the evidence based diagnosis. Strategy for identification of neonatal bacterial meningitis pathogens is presented by evaluating three different available methods to establish evidence-based diagnosis for neonatal bacterial meningitis. Methods: The cerebrospinal fluid samples from 56 neonates diagnosed as bacterial meningitis in 2009 in Beijing Children’s Hospital were analyzed in the study. Two PCR based molecular assays, real-time fluorescence quantitative PCR (RT-PCR) and multiplex PCR based-reverse line blot hybridization (mPCR/RLB), were used to assess 7 common neonatal meningitis bacterial pathongens, including Escherichia coli, Staphylococcus aureus, Listerisa monocytogenes, Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, and Streptococcus agalactiae. The findings in examinations of two assays were compared with the results obtained bacterial culture tests. Results: Bacterial meningitis was identified in five cases (9%) by CSF cultures, 25 (45%) by RT-PCR and 16 (29%) by mPCR/RLB. One strain of S. epidermidis and one of E. faecalis were identified using mPCR/RLB but not by RT-PCR. In contrast, cultures identified one strain of S. pneumoniae which was missed by both PCR assays. Overall, the bacterial pathogens in 28 cases were identified with these three methods. Both RT-PCR and mPCR/RLB assays were more sensitive than bacterial culture, (p < 0.05). Conclusion: Our study confirmed that both RT-PCR and mPCR/RLB assays have better sensitivity than bacterial culture. They are capable of detecting the pathogens in CSF samples with negative culture results. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of insulin on receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) expression in human osteosarcoma MG63 cells using real-time polymerase chain reaction. Materials and methods: MG63 cells were exposed to different concentrations of human recombinant insulin (1, 10, and 100 nM) for 24 h, and then the expression of RANKL and OPG mRNA was identified. After that, MG63 cells were exposed to tensile stress combined with 0 or 10 nM insulin respectively for 0, 3, 6, and 12 h, and then the expression of RANKL and OPG mRNA was identified. Human monocytes were cultured with the collected culture media from MG63 cells plates that were exposed to different concentrations of human recombinant insulin (0 and 10 nM) for 7 days, and then were stained with an acid phosphatase kit. Results: After 24 h of treatment with 1, 10, and 100 nM doses of insulin, the expression of RANKL and OPG mRNA was suppressed (P < 0.05), and the ratio of OPG to RANKL also was suppressed (P < 0.05). Application of tensile stress to MG63 cells induced a decrease in RANKL mRNA expression and an increase in OPG mRNA expression at 6 and 12 h (P < 0.05); 10 nM insulin decreased the mechanical stress-induced RANKL and OPG mRNA expression in MG63 cells at 6 and 12 h (P < 0.05). The ratio of OPG to RANKL increased at 6 and 12 h in the 2 groups (P < 0.05), but insulin decreased the mechanical stress-induced OPG/RANKL ratio at 12 h (P < 0.05). For the group of monocytes cultured with DMEM collected from MG63 cells plates that were cultured with 0 nM human recombinant insulin, osteoclast formation was not observed. Osteoclast formation was observed in monocytes cultured with DMEM collected from MG63 cells plates that were cultured with 10 nM human recombinant insulin. Conclusion: These results suggest that insulin can modulate osteoclast differentiation via altering the OPG and RANKL expression in osteoblasts. The deficiency in insulin may decrease the number of osteoclasts and osteoclast-mediated bone resorption in patients with type 1 diabetes mellitus. [ABSTRACT FROM AUTHOR]

In hierarchical classification, class labels are structured, that is each label value corresponds to one non-root node in a tree, where the inter-class relationship for classification is specified by directed paths of the tree. In such a situation, the focus has been on how to leverage the interclass relationship to enhance the performance of flat classification, which ignores such dependency. This is critical when the number of classes becomes large relative to the sample size. This paper considers single-path or partial-path hierarchical classification, where only one path is permitted from the root to a leaf node. A large margin method is introduced based on a new concept of generalized margins with respect to hierarchy. For implementation, we consider support vector machines and ψ-learning. Numerical and theoretical analyses suggest that the proposed method achieves the desired objective and compares favorably against strong competitors in the literature, including its flat counterparts. Finally, an application to gene function prediction is discussed. [ABSTRACT FROM AUTHOR]

Previous studies from our laboratory have indicated that overexpression of the epidermal growth factor receptor pathway substrate 8 (EPS8) enhances cell proliferation, migration and tumorigenicity in vivo, although the mechanisms involved remain unexplored. A microarray screen to search for potential mediators of EPS8 identified upregulation of multiple cell cycle-related targets such as the transcription factor FOXM1 and several of its reported downstream mediators, including cdc20, cyclin B1, cyclin A, aurora-B kinase and cdc25C in cells with elevated EPS8, as well as matrix metalloproteinase-9, which we reported previously to be upregulated by EPS8-dependent mechanisms. Cells engineered to overexpress FOXM1 showed increased proliferation, similar to EPS8-overexpressing cells. Conversely, targeted knockdown of FOXM1 in EPS8-overexpressing cells reduced proliferation. Cotransfection of EPS8 with a FOXM1-luciferase reporter plasmid into 293-T- or SVpgC2a-immortalized buccal keratinocytes demonstrated that EPS8 enhances FOXM1 promoter activity, whereas chromatin immunoprecipitation assays revealed elevated levels of acetylated histone H3 associated with the FOXM1 promoter in cells expressing high levels of EPS8. Treatment of EPS8-overexpressing cells with inhibitors of phosphoinositide 3-OH kinase or AKT reduced expression of FOXM1 and aurora-B kinase, a transcriptional target of FOXM1. Overexpression of EPS8 induced expression of the chemokine ligands CXCL5 and CXCL12 in a FOXM1-dependent manner, which was blocked by LY294002 or a dominant-negative form of AKT. Additionally, overexpression of FOXM1 enhanced cell migration, whereas targeted knockdown of CXCL5 or inhibition of AKT reduced migration of EPS8-expressing cells. These data suggest that EPS8 enhances cell proliferation and migration in part by deregulating FOXM1 activity and inducing CXC-chemokine expression, mediated by PI3K- and AKT-dependent mechanisms. [ABSTRACT FROM PUBLISHER]

We prepared ordered sub-100nm pseudo-spin-valve (PSV) element arrays byelectrodeposition of NiFe/Cu/Co into the pores of self-organized nanoporous anodizedaluminium templates. Field-emission scanning electron microscopy reveals thatthe sub-100nm PSV arrays, of uniform size, are well separated and exhibit aperfect two-dimensional array with a hexagonal pattern. The easy-axis hysteresisloops show two distinct steps related to the separate reversal of soft (NiFe) andhard (Co) layers. The switching fields of the PSV arrays are approximately−50Oe for the NiFe and 570Oe for the Co. The dependence of the magnetoresistance on the Cuspacer layer thickness indicates the presence of an oscillatory interlayer exchange couplingthrough the Cu layers. [ABSTRACT FROM AUTHOR]

We have prepared by electrodeposition nanoscale spin valves into the pores of anodic alumina membranes. Aligned nanometric spin valve arrays, well characterized by field emission scanning electron microscopy, are vertical with respect to the plane of the template and exhibit a perfect two-dimensional array with a hexagonal pattern. The largest value of room temperature giant magnetoresistance (GMR) we achieved is 6.8% at 75 Oe. The relatively low saturation fields together with relatively large GMR should make such structures attractive for sensor applications. [ABSTRACT FROM AUTHOR]

We have investigated the role of the signaling intermediate, EPS8, in tumor progression using a model system and in vivo. HN4 primary tumor cells express low levels of EPS8, similar to normal keratinocytes, and show minimal invasion in vitro in response to epidermal growth factor, whereas HN12 cells express high levels of EPS8 and are highly motile in vitro and tumorigenic in vivo. Additional independent tumor cell lines also showed elevated EPS8 expression compared with normal keratinocytes. Using retroviral transduction, we generated HN4 cell lines expressing EPS8 (HN4/EPS8) at levels equivalent to those present in HN12 cells. HN4/EPS8 cells showed increased proliferation and migration compared with controls, together with elevated expression and activity of matrix metalloprotease (MMP)-9, which was dependent on protein kinase B (AKT) activity. Introduction of plasmids that direct synthesis of EPS8 short hairpin RNA (shRNA) into HN12 cells resulted in decreased EPS8 expression in these cells, which correlated with a decrease in their capacity to migrate and invade in vitro. In addition, shRNA-mediated knockdown of EPS8 reduced expression and activity of MMP-9 produced by these cells and reduced MMP-9 promoter activity. EPS8 knockdown cells showed decreased tumorigenicity in vivo compared with controls and lower MMP-9 expression. Conversely, overexpression of EPS8 in HN4 cells was sufficient to induce growth of these non-tumorigenic cells in orthotopic transplantation assays. Furthermore, EPS8 expression in clinical samples of squamous cell carcinoma showed variable expression levels and broadly paralleled expression of MMP-9. The data support a role for EPS8 in squamous carcinogenesis. [ABSTRACT FROM AUTHOR]

We report the synthesis of transition-metal (Co2+)-doped ZnO nanowire arrays embedded in anodic alumina membrane (AAM) by a sol precipitation method. The direct synthetic method ensures the successful doping of cobalt in the ZnO nanocrystals and exhibiting bivalent state. [ABSTRACT FROM AUTHOR]