Investigating the molecular basic of AMKL and MDS.

Malignant haematopoiesis is usually associated with various genetic lesions such as chromosomal translocations or mutations in individual genes. This thesis investigates the genetic basis of two such syndromes, acute megakaryoblastic leukaemia (AMKL) and myelodysplastic syndrome (MDS). The most common constitutional aneuploidy with predisposition to leukaemia is trisomy 21, also known as Down Syndrome (DS). DS children have a 500-fold increased risk for AMKL. Somatic mutations acquired during foetal haematopoiesis in the GATA1 transcription factor are detected in megakaryoblasts from all the DS patients with AMKL. Here we show that the Gatal mutation co-operates with the chromosome 21 gene, ERGS, to immortalize foetal megakaryocyte progenitors with the phenotype of AMKL megakaryoblasts. We show that ERG-3 promotes megakaryopoiesis and acts as an oncogene and that progenitor cells harbouring a Gatal mutation plus ERG-3 or ERG-3 alone lead to rapid development of leukaemia in vivo. Our data support a model where trisomy 21 overexpressed genes, that promote foetal megakaryopoiesis, co-operate with mutations that arrest development and lead to DS-AMKL. This is also the first direct demonstration of the leukaemogenic activity of full length ERG protein, possibly explaining the poor prognosis of the acute myeloid leukaemias with high expression of ERG. DS patients are also predisposed to TMD (transient myeloproliferative disorder) and MDS (myelodysplastic syndrome) prior to AMKL development. Myelodysplastic syndromes are a group of clonal haematopoietic disorders, characterised by aberrant proliferation and differentiation of cells of the myeloid lineage resulting in severe cytopenia and dysplasia of myeloid, erythroid and megakaryocytes. The most common chromosomal translocation associated with MDS is the t(3 5)(q25q35) translocation. This rearrangement results in a fusion transcript comprised of nucleophosmin (NPM) gene and myeloid leukaemia factor 1 (MLF1) gene. To determine the importance of the NPM-MLF1 fusion protein in the development and progression of MDS to AML, its role in myelopoiesis and megakaryopoiesis was investigated. Our results show that NPM-MLF1 affects the differentiation of myeloid cells. Our preliminary data predicts that NPM may have a role in megakaryopoiesis and its interaction with NPM-MLF1 may affect the function of the fusion protein

Enzyme activity in terrestrial soil in relation to exploration of the Martian surface

Urease activity in soil is persistent for long periods under low water, low temperature, and sterile regimes, and it was suggested that some form of enzyme-protective mechanism exists in soil. Dublin soil was extracted by sonication in water followed by adding a mixture of salts. Urease activity is associated with the organo-mineral complex thus obtained and is resistant to the activities of proteolytic enzymes. Clay free soil organic matter prepared subsequently by filtration also exhibits urease activity which is resistant to proteolysis. Models consisting of enzymes with bentonite and lignin were found to mimic this resistance to proteolysis. A model system is presented which suggests both the origin and location of soil ureases and a reason for their persistence in nature

Criteria for evidence-based practice in Iranian traditional medicine

The major difference between Iranian traditional medicine and allopathic medicine is in the application of evidence and documents. In this study, criteria for evidence-based practice in Iranian traditional medicine and its rules of practice were studied. The experts� views were investigated through indepth, semi-structured interviews and the results were categorized into four main categories including Designing clinical questions/clinical question-based search, critical appraisal, resource search criteria and clinical prescription appraisal. Although the application of evidence in Iranian traditional medicine follows Evidence Based Medicine (EBM) principles but it benefits from its own rules, regulations, and criteria that are compatible with EBM. © 2015 Tehran University of Medical Sciences. All rights reserved

Alpha/Beta Interferon Receptor Signaling Amplifies Early Proinflammatory Cytokine Production in the Lung during Respiratory Syncytial Virus Infection

Type I interferons (IFNs) are produced early upon virus infection and signal through the alpha/beta interferon (IFN-α/β) receptor (IFNAR) to induce genes that encode proteins important for limiting viral replication and directing immune responses. To investigate the extent to which type I IFNs play a role in the local regulation of inflammation in the airways, we examined their importance in early lung responses to infection with respiratory syncytial virus (RSV). IFNAR1-deficient (IFNAR1−/−) mice displayed increased lung viral load and weight loss during RSV infection. As expected, expression of IFN-inducible genes was markedly reduced in the lungs of IFNAR1−/− mice. Surprisingly, we found that the levels of proinflammatory cytokines and chemokines in the lungs of RSV-infected mice were also greatly reduced in the absence of IFNAR signaling. Furthermore, low levels of proinflammatory cytokines were also detected in the lungs of IFNAR1−/− mice challenged with noninfectious innate immune stimuli such as selected Toll-like receptor (TLR) agonists. Finally, recombinant IFN-α was sufficient to potentiate the production of inflammatory mediators in the lungs of wild-type mice challenged with innate immune stimuli. Thus, in addition to its well-known role in antiviral resistance, type I IFN receptor signaling acts as a central driver of early proinflammatory responses in the lung. Inhibiting the effects of type I IFNs may therefore be useful in dampening inflammation in lung diseases characterized by enhanced inflammatory cytokine production

Space and social distancing in managing and preventing COVID-19 community spread: An overview.

The spread of COVID-19 at a large scale and at a rapid pace indicates the lack of social distancing measures at multiple levels. The individuals are not to be blamed, nor should we assume the early measures were ineffective or not implemented. It is all down to the multiplicity of transmission factors that made the situation more complicated than initially anticipated. Therefore, in facing the COVID-19 pandemic, this overview paper discusses the importance of space in social distancing measures. The methods used to investigate this study are literature review and case study. Many scholarly works have already provided us with evidence-based models that suggest the influential role of social distancing measures in preventing COVID-19 community spread. To further elaborate on this important topic, the aim here is to look at the role of space not only at the individual level but at larger scales of communities, cities, regions, etc. The analysis helps better management of cities during the pandemics such as COVID-19. By reflecting on some of the ongoing research on social distancing, the study concludes with the role of space at multiple scales and how it is central to the practice of social distancing. We need to be more reflective and responsive to achieve earlier control and containment of the disease and the outbreak at the macro level. [Abstract copyright: © 2023 Published by Elsevier Ltd.

Immersed Boundary Method for the Solution of 2D Inviscid Compressible Flow Using Finite Volume Approach on Moving Cartesian Grid

In this study, two-dimensional inviscid compressible flow is solved around a moving solid body using Immersed Boundary Method (IBM) on a Cartesian grid. Translational motion is handled with a Cartesian grid generated around the body which moves with body on a background grid. In IBM, boundaries are immersed within the grid points. In this paper solution domain is discretized using finite volume approach. To implement boundary conditions on immersed boundaries, a set of Ghost finite volumes are defined along the wall boundaries. Boundary conditions are used to assign flow variables on these Ghost finite volumes. Governing equations are solved using dual time step method of Jameson. Finally, numerical results obtained from the present study are compared with the other numerical results to evaluate the correct performance of the present algorithm and its accuracy