Molecular Characterization of Chromosome 7 in AML and MDS Patients

Myelodysplastic syndromes (MDS) share many features with acute myeloid leukemias (AML) and in fact 20 - 40% of the patients eventually develop a picture of full blown AML. Chromosome 7 has been a focus of attention as a site harboring tumor suppressor genes whose loss of function contributes to leukemia transformation or tumor progression. Abnormalities of chromosome 7 are frequently encountered in AML and MDS. The aim of the present study was to detect the molecular abnormalities of chromosome 7 in Egyptian AML and MDS patients using the FISH technique and whether the abnormality has an implication on the prognosis of the disease after a period of one year follow up. Fluorescence in-situ hybridization (FISH) was performed for chromosome 7 using a locus specific probe for 7q31 and a centromeric probe from 7p11.1-q11.1 in a series of 30 patients diagnosed as: AML (20 patients) and MDS (10 patients) according to the FAB criteria. Aberrations of Chromosome 7 were found in 36.6% of AML patients: 3 cases showing monosomy with a mean positivity of 17.3%, 2 cases showing 7q deletion with a mean positivity of 11%. While both monosomy and deletion were detected in 3 cases. However, in MDS patients; monosomy for chromosome 7 was the only abnormality detected and was found in 30% of cases. Genetic abnormality of chromosome 7 showed a significant association with poor prognostic criteria. Patients who had normal FISH results showed a higher percentage (31.6%) of complete remission (CR) versus 0% in patients with monosomy or deletion who showed a higher percentage (100%) of death or poor response to therapy (NR). Although AML patients had a worse prognosis when compared to MDS patients, patients with genetic abnormalities showed the worst outcome

Rapid Screening of \u3b2-Globin Gene Mutations by Real-Time PCR in Egyptian Thalassemic Children

Thalassemia is one of the most common genetic disorders in Egypt. With the total population of 70 million, there are approximately 600,000 affected individuals and more than 20 million thalassemia carriers. Thalassemia is therefore one of the major health problems in Egypt. B-Thalassemias are priority genetic diseases for prevention programs. Rapid genotype characterization is fundamental in the diagnostic laboratory, especially when offering prenatal diagnosis for carrier couples. Introduction of the real time PCR has made a revolution in the time taken for the PCR reactions. We present a method for the diagnosis of the common mutations of the B-thalassemia in Egyptian children & families. The procedure depends on the real-time PCR using specific fluorescently labeled hybridization probes. The melting temperature for each of the specific probes obtained after the PCR reaction permits the identification of the specific mutation. Genotyping of 20 thalassemic children attending the hematology clinic of the children specialized hospital and 10 controls was done using Real-time PCR and the conventional Amplification Refractory Mutation System (ARMS) technique. Analysis revealed identical results to most of the patients and they were further checked by the sequencing results of the DNA samples. The established method is a robust, fast and straight forward assay that allows the detection of the common B-thalassemia mutations in Egypt. The described LightCycler system protocol can rapidly screen for many B-globin gene mutations

Improved thermo-physical properties and energy efficiency of hybrid PCM/graphene-silver nanocomposite in a hybrid CPV/thermal solar system

In this research work, novel hybrid graphene-silver (Gr-Ag) nanomaterial has been used for first time with paraffin wax as a phase change material (PCM) to improve its thermo-physical properties. Thermal and electrical energy efficiencies of the novel synthesized nanocomposite (PCM/graphene-silver) has been investigated in solar thermal collector systems (CPV/T). This paper focuses on preparation, characterization, thermo-physical properties and energy efficiency in concentrated photovoltaic/thermal (CPV/T) system of new class of nanocomposites induced with hybrid Gr-Ag nanomaterial in three different concentrations. The specific heat capacity (cp) of hybrid PCM/graphene-silver nanocomposite increased by introducing hybrid Gr-Ag nanomaterial. Electrical and thermal energy performance of the hybrid PCM/graphene-silver is investigated in a CPV/T system using MATLAB 2017b program. The improvement of cp is found to be ~ 40% with 0.3 mass% of hybrid Gr-Ag nanomaterial loaded in PCM. The highest thermal conductivity increment is found to be ~ 11% at 0.3 mass% concentration of hybrid Gr-Ag nanomaterial in PCM. The endothermic enthalpy value of the hybrid PCM/graphene-silver nanocomposite is found to be ~ 75.6 J g−1 at 0.1 mass% loading concentration of hybrid Gr-Ag nanomaterial. Melting point of hybrid PCM/graphene-silver nanocomposite with loading concentration of 0.3 mass% is measured to be 73.2 °C. The highest thermal efficiency using the hybrid graphene-silver nanoparticles reached the value of 39.62% which represents 4.16% increment in comparison with the pure PCM. The equivalent electrical efficiency is improved by 2.8% at the loading concentration of 0.3 mass% of the hybrid Gr-Ag nanomaterial. These new class of nanocomposites represented the capability of enhancement in the performance of the CPV/T system consisting of lower PV temperatures, higher temperature gains across the cooling fluid and higher electrical and thermal efficiencies

Optical, stability and energy performance of water-based MXene nanofluids in hybrid PV/thermal solar systems

Solar thermal collectors have been recognized as promising devices for solar energy harvesting. The absorbing properties of the working fluid are crucial because they can significantly influence the efficiency of the solar thermal collectors. The performance of photovoltaic-thermal (PV/T) systems can be optimized by applying nanofluids as working fluids. MXene is a newly developed 2-D nanomaterial that has proven excellent potential in electrical applications with a lack of research in the thermal and optical applications. The present work extensively studied the optical potential of the water/MXene nanofluids with respect to the variation of MXene concentrations (0.0005–0.05 wt%) and types of surfactant (CTAB or SDBS) used in a hybrid PV/T system. The relationship between the investigated parameters was evaluated through an experimental correlation. The evaluation of the nanofluids in term of the transmittance was conducted through the Rayleigh method. The MXene concentrations and the types of the surfactant play predominant role in the transmittance, absorbance and dispersion stability of the water/MXene nanofluids. The corresponding effects due to these factors become the most noticeable in the wavelengths of 300–1350 nm. Low concentration of the MXene and shorter path lengths lead to higher transmittance. The application of the low concentration of water/MXene nanofluids as the optical filtration in a hybrid PV/T system yields a higher performance compared to a conventional PV/T system. Therefore, this research work provides novelty value in understanding the impacts of using water/MXene nanofluid in the hybrid PV/T solar collectors to harness additional energy

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Numerical methods for the design and description of in vitro expansion processes of human mesenchymal stem cells

Human mesenchymal stem cells (hMSCs) are a valuable source of cells for clinical applications (e.g., treatment of acute myocardial infarction or inflammatory diseases), especially in the field of regenerative medicine. However, for autologous (patient-specific) and allogeneic (off-the-shelf) hMSC-based therapies, in vitro expansion is necessary prior to the clinical application in order to achieve the required cell numbers. Safe, reproducible, and economic in vitro expansion of hMSCs for autologous and allogeneic therapies can be problematic because the cell material is restricted and the cells are sensitive to environmental changes. It is beneficial to collect detailed information on the hydrodynamic conditions and cell growth behavior in a bioreactor system, in order to develop a so called “Digital Twin” of the cultivation system and expansion process. Numerical methods, such as Computational Fluid Dynamics (CFD) which has become widely used in the biotech industry for studying local characteristics within bioreactors or kinetic growth modelling, provide possible solutions for such tasks. In this review, we will present the current state-of-the-art for the in vitro expansion of hMSCs. Different numerical tools, including numerical fluid flow simulations and cell growth modelling approaches for hMSCs, will be presented. In addition, a case study demonstrating the applicability of CFD and kinetic growth modelling for the development of an microcarrier-based hMSC process will be shown

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease