The Role of Gata3 in Blood Stem Cell Emergence

The first definitive haematopoietic stem cells (HSCs) produced during embryonic development are generated from a specialised subset of endothelial cells known as haemogenic endothelium. Recently, it was reported that Gata3 plays a dual role in the development of sympathetic nervous system and haematopoietic system. In fact, Gata3 has proven to be crucial for the production of HSCs through regulation of catecholamine production from the co-developing sympathetic nervous system. Also, it was recently shown that Gata3 is expressed in the haemogenic endothelium and haematopoietic progenitor cells. Here, I will specifically examine the role of Gata3 in the production of HSCs; if it is expressed and plays a role in the precursors from which HSCs arise. Using a Gata3-GFP reporter mouse line, we found that Gata3 is expressed in various cell types in the HSCs microenvironment, including mesenchymal cells, endothelial cells, haematopoietic cells and sympathetic nervous system, and this expression was stage dependant. In the endothelial cells, we have found that the haemogenic endothelium activity is enriched in Gata3 expressing cells. Within the haematopoietic cells, we have found that Gata3 marks a specific stage along the developmental pathway towards the generation of definitive haematopoietic stem cells, and that Gata3 expressing haematopoietic cells are enriched for the most immature and stem cell like progenitors. Moreover, Gata3 will be specifically knocked out in haemogenic endothelial cells to determine whether it plays an essential role in the production of HSCs from the endothelium using the Vec-Cre system. We found that Gata3 within the haemogenic endothelium plays a major role in haematopoietic progenitors formation, and possibly haematopoietic stem cell formation. Finally, we used molecular assay (RNA seq) to identify the role of Gata3 in the haematopoietic stem cell microenvironment and found that Gata3 plays a major role in the development and differentiation of various cells and systems, and implicated Gata3 as cell cycle regulator. In summary, we found that Gata3 expressing cells is enriched for haemogenic endothelium, crucial for the haematopoietic progenitors formation, plays and important role in endothelial to haematopoietic transition, and plays a key developmental role in both haematopoietic stem cell and its microenvironment.King Abdullah International Medical Research Centre Ministry of National Guards - Health Affairs, Riyadh, Saudi Arabi

The role of clinical decision support systems in preventing stroke in primary care: a systematic review.

Computerized clinical decision support systems (CDSS) are increasingly being used to facilitate the role of clinicians in complex decision-making processes. This systematic review evaluates evidence of the available CDSS developed and tested to support the decision-making process in primary healthcare for stroke prevention and barriers to practical implementations in primary care settings. A systematic search of Web of Science, Medline Ovid, Embase Ovid, and Cinahl was done. A total of five studies, experimental and observational, were synthesised in this review. This review found that CDSS facilitate decision-making processes in primary health care settings in stroke prevention options. However, barriers were identified in designing, implementing, and using the CDSS

Improving the Optical and Structural Properties of the (UHMWPEO/CuNPs/AgNPs) Composite by Silica Nanoparticles

Background: In this work, the optical and structural properties of an composite were studied, the optical properties were studied by the UV-Visible spectrophotometer technique, and the structural properties were studied by the Xray diffraction technique. Materials and Methods: Different amounts of silica nanoparticles (SiO2 NPs) were loaded onto a composite consisting of ultra-high molecular weight polyethylene oxide (UHMWPEO), copper nanoparticles (Cu NPs), and silver nanoparticles (Ag NPs), and silica was added in different amounts (0.05, 0.07 and 0.09 ) wt%.This work was carried out using the traditional casting method.Results: The results showed a good improvement in the optical and structural properties of the composite when it was loaded with silica nanoparticles. .Conclusion: In this study, we have successfully prepared and examined nanocomposite films with outside and inside SiO2 with a thickness of (75–85) μm. The optical properties improve by decreasing the energy gap from (3.95) eV to (3.78) eV. As for the structural properties, where X-ray diffraction tests showed an increase in the crystalline size of the composite films, it was found that the crystalline size increased from (32.1) nm to (33.7) nm. Silica nanoparticles affect the growth of the crystalline structure of the composite

Review of Researches on Techno-Economic Analysis and Environmental Impact of Hybrid Energy Systems

Hybrid energy systems, which are combinations of two or more renewable and non-renewable energy sources, have been identified as a viable mechanism to address the limitations of a single renewable energy source, utilized for electricity generation. In view of this, several research works have been carried out to determine the optimal mix of different renewable and non-renewable energy resources used for electricity generation. This paper presents a comprehensive review of the optimization approaches proposed and adopted by various authors in the literature for optimal sizing of hybrid energy systems. It is observed that the objective functions - considered by a large percentage of researchers to optimize the sizing of hybrid energy systems - are cost minimization of the generated electricity, system reliability enhancement and environmental pollution reduction. Other factors covered in the literature are equally discussed in this article. Similarly, simulation and optimization software used for the same purpose are covered in the paper. In essence, the main aim of this paper is to provide a scope into the works that have been carried out in the field of hybrid energy systems, used for electricity generation with the view to informing researchers and members of the public alike, on trends in methods applied in optimal sizing of hybrid energy systems. It is believed that the information provided in this paper is very crucial in advancing research in the field

Duchenne Muscular Dystrophy (DMD) Diagnosis: Past and Present Perspectives

Duchenne muscular dystrophy (DMD) is a fatal X-linked disorder, characterized by progressive skeletal muscle wasting. The disease is caused by various types of mutations in the dystrophin gene (DMD). The disease occurs at a frequency of about 1 in 5000 male births, making it the most common severe neuro-muscular disease. In addition to clinical examinations of muscle strength and function, diagnosis of DMD usually involves a combination of immunological assays using muscle biopsies, typically immunohistochemistry and western blotting, and molecular techniques such as DMD gene sequencing or Multiplex Ligation Dependent Probe Amplification (MLPA) using blood samples. In fact, precise molecular diagnosis is a prerequisite for determining the appropriate personalized therapeutic approach such as exon-skipping, gene therapy or stem cell-based therapies in conjunction with gene editing techniques like CRISPR-Cas9. However, the quest for reliable biomarkers with high sensitivity and specificity for DMD from liquid biopsy is still a hotspot of research, as such non-invasive biomarker(s) would not only facilitate disease diagnosis but would also help in carrier detection, which will eventually result in better disease management. In this chapter, we will illustrate the detailed current and prospect strategies for disease

Site-1 protease inhibits mitochondrial respiration by controlling the TGF-β target gene Mss51

The mitochondrial response to changes in cellular energy demand is necessary for cellular adaptation and organ function. Many genes are essential in orchestrating this response, including the transforming growth factor (TGF)-β1 target gene Mss51, an inhibitor of skeletal muscle mitochondrial respiration. Although Mss51 is implicated in the pathophysiology of obesity and musculoskeletal disease, how Mss51 is regulated is not entirely understood. Site-1 protease (S1P) is a key activator of several transcription factors required for cellular adaptation. However, the role of S1P in muscle is unknown. Here, we identify S1P as a negative regulator of muscle mass and mitochondrial respiration. S1P disruption in mouse skeletal muscle reduces Mss51 expression and increases muscle mass and mitochondrial respiration. The effects of S1P deficiency on mitochondrial activity are counteracted by overexpressing Mss51, suggesting that one way S1P inhibits respiration is by regulating Mss51. These discoveries expand our understanding of TGF-β signaling and S1P function

Correlation of Prehypertension with Left Ventricular Mass Assessed by Cardiac Magnetic Resonance Imaging

Introduction. The purpose of this observational cross-sectional study was to assess left ventricular mass (LVM) in prehypertensive individuals in comparison to normotensives and to determine if central blood pressure (BP) correlates better with LVM index (LVMI) than brachial BP. Methods and Result. Brachial and central BP measurements were completed at first visit and at 4 weeks in 65 healthy volunteers who were at least 40 years old and not on medication. Subjects were divided into two groups of normotensives and prehypertensives based on JNC-7 criteria and LVM was obtained using cardiac magnetic resonance imaging. Prehypertensives had significantly higher LVMI compared to normotensives (P<0.01). Brachial and central BP also both positively correlate with LVMI (r=0.460, P<0.01; r=0.318, P=0.012, resp.) in both groups and neither method was superior to the other. After multivariate regression analysis and adjusting for cardiovascular risk factors, prehypertension remained an independent determinant of LVM. Conclusion. Prehypertension is associated with cardiovascular target organ damage, and central BP was not superior to brachial BP or vice versa for association with LVMI

A new flat shell finite element for the linear analysis of thin shell structures

In this paper, a new rectangular flat shell element denoted ‘ACM_RSBE5’ is presented. The new element is obtained by superposition of the new strain-based membrane element ‘RSBE5’ and the well-known plate bending element ‘ACM’. The element can be used for the analysis of any type of thin shell structures, even if the geometry is irregular. Comparison with other types of shell elements is performed using a series of standard test problems. A correlation study with an experimentally tested aluminium shell is also conducted. The new shell element proved to have a fast rate of convergence and to provide accurate results

Duchenne Muscular Dystrophy (DMD) Treatment: Past and Present Perspectives

Duchenne muscular dystrophy (DMD) is one of the fatal X-linked disorders that are characterized by progressive muscle weakness and occur due to mutation in the largest human gene known as the DMD gene which encodes dystrophin protein that is mandatory for keeping the muscles structurally and functionally intact. The disease always affects boys (1 from every ~5000), and in some cases the female carriers are symptomatic. The disease usually leads to impairment in cardiac and pulmonary functions leading to the death of the patients in very young ages. Understanding DMD through precise molecular diagnosis will aid in determining the suitable therapeutic approach for the cases like designing exon-skipping antisense oligonucleotides (AOs) or stem cell-based therapies in conjunction with gene editing techniques (CRISPR/Cas9). Such therapies can correct the genetic defect in the DMD gene and ameliorate the symptoms. In this chapter, we will illustrate the past and current strategies for DMD disease treatment