The Influence of Biological Environment on the Silver-Coated Implants

The environment of the human body is very aggressive, containing among others bacteria, which contribute to the degradation of metal implants. Therefore sometimes implants are covered with nanometals to prevent development of aggressive bacteria. This paper deals with implants covered with nanosilver (15nm), which is antibacterial. The tested implants included: PE vein implant, an intramedullary implant made of stainless steel  and  brass implant for tracheotomy. The results showed an appearance of implants covered with silver as dependent on the type of bacteria: although silver significantly protected implants against some bacteria, a presence of some amounts of Staphylococcus aureus and Staphylococcus epidermidis was noticed after long term exposure in the human body. Only single bacteria could be observed on the surface of the tested materials. Such behavior is evidence, that silver coatings are effective for different form of materials in the presence of various bacteria, however, such behavior is related to form of  bacteria

Arabidopsis DXO1 links RNA turnover and chloroplast function independently of its enzymatic activity

The DXO family of proteins participates in eukaryotic mRNA 5'-end quality control, removal of non-canonical NAD+ cap and maturation of fungal rRNA precursors. In this work, we characterize the Arabidopsis thaliana DXO homolog, DXO1. We demonstrate that the plant-specific modification within the active site negatively affects 5'-end capping surveillance properties of DXO1, but has only a minor impact on its strong deNADding activity. Unexpectedly, catalytic activity does not contribute to striking morphological and molecular aberrations observed upon DXO1 knockout in plants, which include growth and pigmentation deficiency, global transcriptomic changes and accumulation of RNA quality control siRNAs. Conversely, these phenotypes depend on the plant-specific N-terminal extension of DXO1. Pale-green coloration of DXO1-deficient plants and our RNA-seq data reveal that DXO1 affects chloroplast-localized processes. We propose that DXO1 mediates the connection between RNA turnover and retrograde chloroplast-to-nucleus signaling independently of its deNADding properties

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Development of an Anthropomorphic Phantom Coronary Artery Network for CT Imaging

In this work, the design of anthropomorphic phantom coronary arteries for optimization of Computed Tomography Coronary Angiography (CTCA) is presented. First, a phantom vascular wall model for minimization of motion artifacts is manufactured. The mechanical properties of porcine coronary arteries and four soft rubber materials were tested and compared to each other, and the wall attenuation of tubular contrast-filled samples was characterized and compared to literature values as well. A coronary artery model was manufactured by segmenting the main coronary arteries from CT images, 3D printing a mold, and coating it in the rubber material with the most appropriate mechanical and CT attenuation properties. In the second part, the feasibility of 3D printing a phantom directly using four flexible commercially available materials is investigated. The CT attenuation properties match ranges for lipid-rich and fibrous plaque; thus the phantom can be used for optimization of non-calcified plaque imaging.M.A.S

In Search for Reliable Markers of Glioma-Induced Polarization of Microglia

Immune cells accumulating in the microenvironment of malignant tumors are tumor educated and contribute to its growth, progression, and evasion of antitumor immune responses. Glioblastoma (GBM), the common and most malignant primary brain tumor in adults, shows considerable accumulation of resident microglia and peripheral macrophages, and their polarization into tumor-supporting cells. There are controversies regarding a functional phenotype of glioma-associated microglia/macrophages (GAMs) due to a lack of consistent markers. Previous categorization of GAM polarization toward the M2 phenotype has been found inaccurate because of oversimplification of highly complex and heterogeneous responses. In this study, we characterized functional responses and gene expression in mouse and human microglial cultures exposed to fresh conditioned media [glioma-conditioned medium (GCM)] from human U87 and LN18 glioma cells. Functional analyses revealed mutual communication reflected by strong stimulation of glioma invasion by microglial cells and increased microglial phagocytosis after GCM treatment. To define transcriptomic markers of GCM-activated microglia, we performed selected and global gene expression analyses of stimulated microglial cells. We found activated pathways associated with immune evasion and TGF signaling. We performed computational comparison of the expression patterns of GAMs from human GBMs and rodent experimental gliomas to select genes consistently changed in different datasets. The analyses of marker genes in GAMs from different experimental models and clinical samples revealed only a small set of common genes, which reflects variegated responses in clinical and experimental settings. Tgm2 and Gpnmb were the only two genes common in the analyzed data sets. We discuss potential sources of the observed differences and stress a great need for definitive elucidation of a functional state of GAMs

Unveiling new interdependencies between significant DNA methylation sites, gene expression profiles and glioma patients survival

In order to find clinically useful prognostic markers for glioma patients' survival, we employed Monte Carlo Feature Selection and Interdependencies Discovery (MCFS-ID) algorithm on DNA methylation (HumanMethylation450 platform) and RNA-seq datasets from The Cancer Genome Atlas (TCGA) for 88 patients observed until death. The input features were ranked according to their importance in predicting patients' longer (400+ days) or shorter (<= 400 days) survival without prior classification of the patients. Interestingly, out of the 65 most important features found, 63 are methylation sites, and only two mRNAs. Moreover, 61 out of the 63 methylation sites are among those detected by the 450 k array technology, while being absent in the HumanMethylation27. The most important methylation feature (cg15072976) overlaps with the RE1 Silencing Transcription Factor (REST) binding site, and was confirmed to intersect with the REST binding motif in human U87 glioma cells. Six additional methylation sites from the top 63 overlap with REST sites. We found that the methylation status of the cg15072976 site affects transcription factor binding in U87 cells in gel shift assay. The cg15072976 methylation status discriminates <= 400 and 400+ patients in an independent dataset from TCGA and shows positive association with survival time as evidenced by Kaplan-Meier plots

Data_Sheet_1_In Search for Reliable Markers of Glioma-Induced Polarization of Microglia.docx

<p>Immune cells accumulating in the microenvironment of malignant tumors are tumor educated and contribute to its growth, progression, and evasion of antitumor immune responses. Glioblastoma (GBM), the common and most malignant primary brain tumor in adults, shows considerable accumulation of resident microglia and peripheral macrophages, and their polarization into tumor-supporting cells. There are controversies regarding a functional phenotype of glioma-associated microglia/macrophages (GAMs) due to a lack of consistent markers. Previous categorization of GAM polarization toward the M2 phenotype has been found inaccurate because of oversimplification of highly complex and heterogeneous responses. In this study, we characterized functional responses and gene expression in mouse and human microglial cultures exposed to fresh conditioned media [glioma-conditioned medium (GCM)] from human U87 and LN18 glioma cells. Functional analyses revealed mutual communication reflected by strong stimulation of glioma invasion by microglial cells and increased microglial phagocytosis after GCM treatment. To define transcriptomic markers of GCM-activated microglia, we performed selected and global gene expression analyses of stimulated microglial cells. We found activated pathways associated with immune evasion and TGF signaling. We performed computational comparison of the expression patterns of GAMs from human GBMs and rodent experimental gliomas to select genes consistently changed in different datasets. The analyses of marker genes in GAMs from different experimental models and clinical samples revealed only a small set of common genes, which reflects variegated responses in clinical and experimental settings. Tgm2 and Gpnmb were the only two genes common in the analyzed data sets. We discuss potential sources of the observed differences and stress a great need for definitive elucidation of a functional state of GAMs.</p

Image_4_In Search for Reliable Markers of Glioma-Induced Polarization of Microglia.tif

<p>Immune cells accumulating in the microenvironment of malignant tumors are tumor educated and contribute to its growth, progression, and evasion of antitumor immune responses. Glioblastoma (GBM), the common and most malignant primary brain tumor in adults, shows considerable accumulation of resident microglia and peripheral macrophages, and their polarization into tumor-supporting cells. There are controversies regarding a functional phenotype of glioma-associated microglia/macrophages (GAMs) due to a lack of consistent markers. Previous categorization of GAM polarization toward the M2 phenotype has been found inaccurate because of oversimplification of highly complex and heterogeneous responses. In this study, we characterized functional responses and gene expression in mouse and human microglial cultures exposed to fresh conditioned media [glioma-conditioned medium (GCM)] from human U87 and LN18 glioma cells. Functional analyses revealed mutual communication reflected by strong stimulation of glioma invasion by microglial cells and increased microglial phagocytosis after GCM treatment. To define transcriptomic markers of GCM-activated microglia, we performed selected and global gene expression analyses of stimulated microglial cells. We found activated pathways associated with immune evasion and TGF signaling. We performed computational comparison of the expression patterns of GAMs from human GBMs and rodent experimental gliomas to select genes consistently changed in different datasets. The analyses of marker genes in GAMs from different experimental models and clinical samples revealed only a small set of common genes, which reflects variegated responses in clinical and experimental settings. Tgm2 and Gpnmb were the only two genes common in the analyzed data sets. We discuss potential sources of the observed differences and stress a great need for definitive elucidation of a functional state of GAMs.</p

Image_3_In Search for Reliable Markers of Glioma-Induced Polarization of Microglia.tif

<p>Immune cells accumulating in the microenvironment of malignant tumors are tumor educated and contribute to its growth, progression, and evasion of antitumor immune responses. Glioblastoma (GBM), the common and most malignant primary brain tumor in adults, shows considerable accumulation of resident microglia and peripheral macrophages, and their polarization into tumor-supporting cells. There are controversies regarding a functional phenotype of glioma-associated microglia/macrophages (GAMs) due to a lack of consistent markers. Previous categorization of GAM polarization toward the M2 phenotype has been found inaccurate because of oversimplification of highly complex and heterogeneous responses. In this study, we characterized functional responses and gene expression in mouse and human microglial cultures exposed to fresh conditioned media [glioma-conditioned medium (GCM)] from human U87 and LN18 glioma cells. Functional analyses revealed mutual communication reflected by strong stimulation of glioma invasion by microglial cells and increased microglial phagocytosis after GCM treatment. To define transcriptomic markers of GCM-activated microglia, we performed selected and global gene expression analyses of stimulated microglial cells. We found activated pathways associated with immune evasion and TGF signaling. We performed computational comparison of the expression patterns of GAMs from human GBMs and rodent experimental gliomas to select genes consistently changed in different datasets. The analyses of marker genes in GAMs from different experimental models and clinical samples revealed only a small set of common genes, which reflects variegated responses in clinical and experimental settings. Tgm2 and Gpnmb were the only two genes common in the analyzed data sets. We discuss potential sources of the observed differences and stress a great need for definitive elucidation of a functional state of GAMs.</p