Search results for "Mod"
showing 10 items of 39605 documents
Regulation of long-term repopulating hematopoietic stem cells by EPCR/PAR1 signaling
2016
The common developmental origin of endothelial and hematopoietic cells is manifested by coexpression of several cell surface receptors. Adult murine bone marrow (BM) long-term repopulating hematopoietic stem cells (LT-HSCs), endowed with the highest repopulation and self-renewal potential, express endothelial protein C receptor (EPCR), which is used as a marker to isolate them. EPCR/protease-activated receptor-1 (PAR1) signaling in endothelial cells has anticoagulant and anti-inflammatory roles, while thrombin/PAR1 signaling induces coagulation and inflammation. Recent studies define two new PAR1-mediated signaling cascades that regulate EPCR(+) LT-HSC BM retention and egress. EPCR/PAR1 sig…
Paraoxonase-2 regulates coagulation activation through endothelial tissue factor
2017
Oxidative stress and inflammation of the vessel wall contribute to prothrombotic states. The antioxidative protein paraoxonase-2 (PON2) shows reduced expression in human atherosclerotic plaques and endothelial cells in particular. Supporting a direct role for PON2 in cardiovascular diseases, Pon2 deficiency in mice promotes atherogenesis through incompletely understood mechanisms. Here, we show that deregulated redox regulation in Pon2 deficiency causes vascular inflammation and abnormalities in blood coagulation. In unchallenged Pon2-/- mice, we find increased oxidative stress and endothelial dysfunction. Bone marrow transplantation experiments and studies with endothelial cells provide ev…
Strategies for structuring interdisciplinary education in Systems Biology: an European perspective
2016
Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material and example curricula. As university education at the Bachelor’s level is traditionally built upon…
Generalized Thru-Reflect-Line Calibration Technique for the Measurement of Multimodal Radiating Waveguides
2017
The objective of this letter is to extend the use of the generalized thru-reflect-line measurement technique to the case of a radiating multimodal rectangular waveguide aperture. Although this radiating aperture has been carefully studied from a theoretical point of view, the relevant experimental characterization has been limited to the case where the feeding waveguide is monomodal. In addition to theory, we also present experimental results that agree quite well with full-wave simulations, thereby fully validating the measurement technique.
Integration of animal health and public health surveillance sources to exhaustively inform the risk of zoonosis: An application to echinococcosis in …
2020
The analysis of zoonotic disease risk requires the consideration of both human and animal geo-referenced disease incidence data. Here we show an application of joint Bayesian analyses to the study of echinococcosis granulosus (EG) in the province of Rio Negro, Argentina. We focus on merging passive and active surveillance data sources of animal and human EG cases using joint Bayesian spatial and spatio-temporal models. While similar spatial clustering and temporal trending was apparent, there appears to be limited lagged dependence between animal and human outcomes. Beyond the data quality issues relating to missingness at different times, we were able to identify relations between dog and …
T cells mediate autoantibody-induced cutaneous inflammation and blistering in epidermolysis bullosa acquisita
2016
AbstractT cells are key players in autoimmune diseases by supporting the production of autoantibodies. However, their contribution to the effector phase of antibody-mediated autoimmune dermatoses, i.e., tissue injury and inflammation of the skin, has not been investigated. In this paper, we demonstrate that T cells amplify the development of autoantibody-induced tissue injury in a prototypical, organ-specific autoimmune disease, namely epidermolysis bullosa acquisita (EBA) – characterized and caused by autoantibodies targeting type VII collagen. Specifically, we show that immune complex (IC)-induced inflammation depends on the presence of T cells – a process facilitated by T cell receptor (…
Genome wide DNA methylation profiling identifies specific epigenetic features in high-risk cutaneous squamous cell carcinoma
2019
ABSTRACTCutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer. Although most cSCCs have good prognosis, a subgroup of high-risk cSCC has a higher frequency of recurrence and mortality. Therefore, the identification of molecular risk factors associated with this aggressive subtype is of major interest. In this work we carried out a global-scale approach to investigate the DNA-methylation profile in patients at different stages, from premalignant actinic keratosis to low-risk invasive and high-risk non-metastatic and metastatic cSCC. The results showed massive non-sequential changes in DNA-methylome and identified a minimal methylation signature that discriminates bet…
Monitoring of rheologic variables during postoperative high-dose brachytherapy for uterine cancer.
2004
Oxygenation of tumor tissue has recently been assed an important prerequisite for the effectiveness of radiotherapy in cervical cancer. Hyperviscosity is a common phenomenon in malignancy and a cause of reduced oxygen transport capacity that would favour tissue hypoxia. Hemorheological variables were serially tested preoperatively, during four cycles of fractionated adjuvant IR192 HDR after loading radiation (HDR-AL) of the vaginal vault (weekly intervals), and 6 months postoperatively in patients with cervical (n=12) and endometrial cancer (n=26). Women who were scheduled for benign tumor surgery served as controls (n=29). Preoperatively, in cervical and endometrial cancer patients, mean …
Biosynthesis of heme O in intraerythrocytic stages of Plasmodium falciparum and potential inhibitors of this pathway
2019
A number of antimalarial drugs interfere with the electron transport chain and heme-related reactions; however, the biosynthesis of heme derivatives in Plasmodium parasites has not been fully elucidated. Here, we characterized the steps that lead to the farnesylation of heme. After the identification of a gene encoding heme O synthase, we identified heme O synthesis in blood stage parasites through the incorporation of radioactive precursors. The presence of heme O synthesis in intraerythrocytic stages of Plasmodium falciparum was confirmed by mass spectrometry. Inabenfide and uniconazole–P appeared to interfere in heme synthesis, accordingly, parasite growth was also affected by the additi…
Adaptation of gene loci to heterochromatin in the course of Drosophila evolution is associated with insulator proteins.
2020
AbstractPericentromeric heterochromatin is generally composed of repetitive DNA forming a transcriptionally repressive environment. Dozens of genes were embedded into pericentromeric heterochromatin during evolution of Drosophilidae lineage while retaining activity. However, factors that contribute to insusceptibility of gene loci to transcriptional silencing remain unknown. Here, we find that the promoter region of genes that can be embedded in both euchromatin and heterochromatin exhibits a conserved structure throughout the Drosophila phylogeny and carries motifs for binding of certain chromatin remodeling factors, including insulator proteins. Using ChIP-seq data, we demonstrate that ev…