Integration Of Mutation And Gene Expression Data To Identify Disease Subtypes

Understanding the biological insights hidden in the vast amount of data collected, while investigating a disease, is the main goal for collecting such data in the first place. Changes in the gene expression or the function of proteins are important components in progression of a disease and is a key to understanding the disease mechanism. However, more often than not, the causes of such changes are not easily identified. In many cases, genetic variants may cause some of the observed gene expression changes. In this thesis, we focus on identifying the variants that significantly alter gene expression for an individual by integrating genetic variant data, gene expression data, as well as a priori knowledge about gene-gene interaction networks from multiple databases. Here we show that one can use variants that change gene expression to identify subgroups of patients with significantly different survival profiles. The method is validated on four different cancer types (renal, lung, colorectal cancer and leukemia) from the TCGA database. The results show that this method is able to identify variants that significantly affect the gene expression (and in turn the phenotype), as well as identify disease sub-types that are biologically meaningful as validated by survival and pathway analysis

Network-Based Approaches To Identify The Impacted Genes And Active Interactions

A very important step in system biology is the identification of the networks that are most impacted in the given phenotype. Such networks explain where the target genes are affected by some other genes, and therefore describe the mechanisms involved in a biological process. The identified networks are used to: 1) predict the disease or the responses of the system to a specific impact, 2) find the subset of genes that interact with each other and play an important role in the condition of interest, and 3) understand the mechanisms involved in that condition. In this thesis, we propose an approach that takes advantage of pre-defined pathways obtained from existing databases to identify the impact of a phenotype studied on such pathways. Next, we introduce a method able to build a network that captures the putative mechanisms at play in the given condition, by using datasets from multiple experiments studying the same phenotype. This method takes advantage of known interactions extracted from multiple sources such as protein-protein interactions and curated biological pathways. Based on such prior knowledge, we overcome the drawbacks of snap-shot data by considering the possible effects of each gene on its neighbors

Cytogenetic Evaluation of Couples With Spontaneous Abortion, Still Birth and Recurrent Miscarriage in Qazvin: Report and Review

Background: Chromosomal abnormality plays an important role in different types of miscarriages. Objectives: The present study was designed to investigation chromosomal anomalies in three groups of couples with recurrent abortion (RA), spontaneous abortion (SA) and still birth (SB). PatientsandMethods: In this retrospective study, the frequency of chromosomal aberrations was investigatedamong 260 couples with miscarriage, which had referred to the cytogenetic section of a reference laboratory in Buali hospilal, Qazvin, Iran from 2009 to 2014. Metaphase spreads were analyzed using G-banding. Results: In this study, 7.6% of couples had chromosomal aberrations including, balanced reciprocal translocations, robertsonian translocations, inversions and sex chromosome aneuploidy. Frequency of balanced translocations was higher, specifically in couples with SA. Conclusions: In this investigation we showed that chromosomal abnormalities could be one of the important causes of miscarriages. Cytogenetic evaluation of couples, which experienced different types of miscarriage, may prevent unnecessary treatments. Keywords: Recurrent Abortion, Spontaneous Abortion, Still Birth, Chromosome Abnormalit

Effect of laser-dimpled titanium surfaces on attachment of epithelial-like cells and fibroblasts.

PurposeThe objective of this study was to conduct an in vitro comparative evaluation of polished and laserdimpled titanium (Ti) surfaces to determine whether either surface has an advantage in promoting the attachment of epithelial-like cells and fibroblast to Ti.Materials and methodsForty-eight coin-shaped samples of commercially pure, grade 4 Ti plates were used in this study. These discs were cleaned to a surface roughness (Ra: roughness centerline average) of 180 nm by polishing and were divided into three groups: SM (n=16) had no dimples and served as the control, SM15 (n=16) had 5-µm dimples at 10-µm intervals, and SM30 (n=16) had 5-µm dimples at 25-µm intervals in a 2 × 4 mm(2) area at the center of the disc. Human gingival squamous cell carcinoma cells (YD-38) and human lung fibroblasts (MRC-5) were cultured and used in cell proliferation assays, adhesion assays, immunofluorescent staining of adhesion proteins, and morphological analysis by SEM. The data were analyzed statistically to determine the significance of differences.ResultsThe adhesion strength of epithelial cells was higher on Ti surfaces with 5-µm laser dimples than on polished Ti surfaces, while the adhesion of fibroblasts was not significantly changed by laser treatment of implant surfaces. However, epithelial cells and fibroblasts around the laser dimples appeared larger and showed increased expression of adhesion proteins.ConclusionThese findings demonstrate that laser dimpling may contribute to improving the periimplant soft tissue barrier. This study provided helpful information for developing the transmucosal surface of the abutment

Pluronic F-127 hydrogel as a promising scaffold for encapsulation of dental-derived mesenchymal stem cells.

Dental-derived mesenchymal stem cells (MSCs) provide an advantageous therapeutic option for tissue engineering due to their high accessibility and bioavailability. However, delivering MSCs to defect sites while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated tissue regeneration. Here, we tested the osteogenic and adipogenic differentiation capacity of dental pulp stem cells (DPSCs) in a thermoreversible Pluronic F127 hydrogel scaffold encapsulation system in vitro. DPSCs were encapsulated in Pluronic (®) F-127 hydrogel and stem cell viability, proliferation and differentiation into adipogenic and osteogenic tissues were evaluated. The degradation profile and swelling kinetics of the hydrogel were also analyzed. Our results confirmed that Pluronic F-127 is a promising and non-toxic scaffold for encapsulation of DPSCs as well as control human bone marrow MSCs (hBMMSCs), yielding high stem cell viability and proliferation. Moreover, after 2 weeks of differentiation in vitro, DPSCs as well as hBMMSCs exhibited high levels of mRNA expression for osteogenic and adipogenic gene markers via PCR analysis. Our histochemical staining further confirmed the ability of Pluronic F-127 to direct the differentiation of these stem cells into osteogenic and adipogenic tissues. Furthermore, our results revealed that Pluronic F-127 has a dense tubular and reticular network morphology, which contributes to its high permeability and solubility, consistent with its high degradability in the tested conditions. Altogether, our findings demonstrate that Pluronic F-127 is a promising scaffold for encapsulation of DPSCs and can be considered for cell delivery purposes in tissue engineering

An Efficient Adaptive Noise Cancellation Scheme Using ALE and NLMS Filters

The basic theme of our paper is to implement a new idea of noise reduction in the real time applications using the concepts of adaptive filters.  Our model which is presented as one of the solutions is based on two stages of operation with the first stage based on the ALE (Adaptive Line Enhancer) filters and the second stage on NLMS (Normalized Least Mean Square) filter. The first stage reduces the sinusoidal noise from the input signal and the second stage reduces the wideband noise. Two input sources of voice are used; one for the normal speech and the other for the noise input, using separate microphones for both signals. The first signal is of the corrupted speech signal and the second signal is of only the noise containing both wideband and narrowband noise. In the first stage the narrowband noise is reduced by using the ALE technique. The second stage gets a signal with ideally only the wideband noise which is reduced using the NLMS technique.  In both the stages the concerned algorithms are used to update the filter coefficients in such a way that the noise is cancelled out from the signal and a clean speech signal is heard at the output.DOI:http://dx.doi.org/10.11591/ijece.v2i3.24

Human Periodontal Ligament- and Gingiva-derived Mesenchymal Stem Cells Promote Nerve Regeneration When Encapsulated in Alginate/hyaluronic Acid 3D Scaffold

Repair or regeneration of damaged nerves is still a challenging clinical task in reconstructive surgeries and regenerative medicine. Here, we demonstrate that periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) isolated from adult human periodontal and gingival tissues assume neuronal phenotype in vitro and in vivo via a subcutaneous transplantation model in nude mice. PDLSCs and GMSCs were encapsulated in a three-dimensional scaffold based on alginate and hyaluronic acid hydrogels capable of sustained release of human nerve growth factor (NGF). We demonstrate that, the elasticity of the hydrogels affected the proliferation and differentiation of encapsulated MSCs within scaffolds. Moreover, we observed that PDLSCs and GMSCs were stained positive for βIII-tubulin, while exhibiting high levels of gene expression related to neurogenic differentiation (βIII-tubulin and GFAP) via qPCR. Western blot analysis showed the importance of the elasticity of the matrix and the presence of NGF in the neurogenic differentiation of encapsulated MSCs. In vivo, immunofluorescence staining for neurogenic specific protein markers confirmed islands of dense positively stained structures inside transplanted hydrogels. To our knowledge, this study is the first demonstration of the application of PDLSCs and GMSCs as promising cell therapy candidates for nerve regeneration

Application of Stem Cells Derived From the Periodontal Ligament or Gingival Tissue Sources for Tendon Tissue Regeneration.

Tendon injuries are often associated with significant dysfunction and disability due to tendinous tissue’s very limited self-repair capacity and propensity for scar formation. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material present an alternative therapeutic option for tendon repair/regeneration that may be advantageous compared to other current treatment modalities. The MSC delivery vehicle is the principal determinant for successful implementation of MSC-mediated regenerative therapies. In the current study, a co-delivery system based on TGF-β3-loaded RGD-coupled alginate microspheres was developed for encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs). The capacity of encapsulated dental MSCs to differentiate into tendon tissue was investigated in vitro and in vivo. Encapsulated dental-derived MSCs were transplanted subcutaneously into immunocompromised mice. Our results revealed that after 4 weeks of differentiation in vitro, PDLSCs and GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited high levels of mRNA expression for gene markers related to tendon regeneration (Scx, DCn, Tnmd, and Bgy) via qPCR measurement. In a corresponding in vivo animal model, ectopic neo-tendon regeneration was observed in subcutaneous transplanted MSC-alginate constructs, as confirmed by histological and immunohistochemical staining for protein markers specific for tendons. Interestingly, in our quantitative PCR and in vivo histomorphometric analyses, PDLSCs showed significantly greater capacity for tendon regeneration than GMSCs or hBMMSCs (P\u3c0.05). Altogether, these findings indicate that periodontal ligament and gingival tissues can be considered as suitable stem cell sources for tendon engineering. PDLSCs and GMSCs encapsulated in TGF-β3-loaded RGD-modified alginate microspheres are promising candidates for tendon regeneration

Application of Stem Cells Derived From the Periodontal Ligament or Gingival Tissue Sources for Tendon Tissue Regeneration

Tendon injuries are often associated with significant dysfunction and disability due to tendinous tissue’s very limited self-repair capacity and propensity for scar formation. Dental-derived mesenchymal stem cells (MSCs) in combination with appropriate scaffold material present an alternative therapeutic option for tendon repair/regeneration that may be advantageous compared to other current treatment modalities. The MSC delivery vehicle is the principal determinant for successful implementation of MSC-mediated regenerative therapies. In the current study, a co-delivery system based on TGF-β3-loaded RGD-coupled alginate microspheres was developed for encapsulating periodontal ligament stem cells (PDLSCs) or gingival mesenchymal stem cells (GMSCs). The capacity of encapsulated dental MSCs to differentiate into tendon tissue was investigated in vitro and in vivo. Encapsulated dental-derived MSCs were transplanted subcutaneously into immunocompromised mice. Our results revealed that after 4 weeks of differentiation in vitro, PDLSCs and GMSCs as well as the positive control human bone marrow mesenchymal stem cells (hBMMSCs) exhibited high levels of mRNA expression for gene markers related to tendon regeneration (Scx, DCn, Tnmd, and Bgy) via qPCR measurement. In a corresponding in vivo animal model, ectopic neo-tendon regeneration was observed in subcutaneous transplanted MSC-alginate constructs, as confirmed by histological and immunohistochemical staining for protein markers specific for tendons. Interestingly, in our quantitative PCR and in vivo histomorphometric analyses, PDLSCs showed significantly greater capacity for tendon regeneration than GMSCs or hBMMSCs (