Abstract

The exposure of the developing foetal heart to hyperglycaemia in mothers with diabetes mellitus is a major risk factor for foetal cardiac complications that lead to heart failure. We studied the effects of hyperglycaemia on the layout of cardiac myofilament proteins in stem cell-derived cardiomyocytes and their possible underlying mechanisms. Mouse embryonic stem cells (mESCs) were differentiated into cardiac-like cells and cultured in media containing baseline- or high glucose concentrations. Cellular biomarkers were detected using Western blot analysis, immunocytochemistry, 5–ethynyl–2-deoxyuridine (EdU) cell proliferation assay, and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay. High glucose decreased the proportion of cardiac troponin T and α-actinin 2 positive mESCs as well as disrupted the α-actinin 2 striated pattern and the distribution of the cardiac myosin heavy chain α- and β isoforms. However, there was no alteration of the cellular EdU uptake nor the expression of the receptor of advanced glycation end-product (RAGE). High glucose also increased the presence of the oxidative stress marker nitrotyrosine as well as the number of TUNEL-stained nuclei in cardiaclike cells. Treatment with the antioxidant N-acetyl cysteine decreased the number of TUNEL-stained cells in high glucose and improved the α-actinin 2 striated pattern. Hyperglycaemia negatively impacted the expression and cellular organisation of cardiac myofilament proteins in mESC-derived cardiomyocytes through oxidative stress. The results add further insights into the pathophysiological mechanisms of cardiac contractile dysfunction in diabetic cardiac developmental disease.

This article indicates that Arab Libyan EFL learners are incompetent in oral communication. Despite spending years in learning English, they fail to employ that knowledge in real communicative situations. This might be the outcome of inadequate teaching approaches that are employed by Arab EFL teachers. Diaaba (2016) pointed out that, their overreliance on traditional approaches which emphasize extensive linguistic input rather than communicative output result in what Wolff (2010 cited in ibed, 2016 p. 338) calls 'mute English learners', who can read and write but cannot speak. The purpose of this study was to uncover challenges facing Arabic-speaking ESL students as well as teachers .13 participations are included in this article. Research questions focused on the needs of the Arab Libyan-speaking ESL students, the factors that influence their learning, and the problems the teachers face in supporting these students. Data sources included teacher and student interviews, classroom observations the results revealed that Arab Libyan learners face challenges in speaking skills due to linguistic and psychological barriers. The study concluded that several important challenges for teachers and students exist, including time, language support, and knowledge insufficient exposure to the target language and frequent use of Arabic were the main factors contributing to the Libyan EFL learners' speaking difficulties. Lack of speaking activities and overemphasis on accuracy at the expense of fluency by the teachers were other contributing factors.

Keywords: Speaking skills; speaking difficulties; instructional approaches; linguistic and psychological barriers

Abstract

Hyperglycaemia, a key metabolic abnormality in diabetes mellitus, is implicated in pathological cardiogenesis during embryological development. However, the underlying mechanisms and potential therapeutic targets remain unknown. We, therefore, studied the effect of hyperglycaemia on mouse embryonic stem cell (mESC) cardiac differentiation. The mESCs were differentiated via embryoid body (EB) formation and cultured under conditions with baseline (25 mM) or high (50 mM) glucose. Time-lapse microscopy images of pulsatile mESCs and Ca2+ntransients were recorded. Biomarkers of cellular changes were detected using immunocytochemistry, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay, and Western blot analyses. Differentiated, spontaneously beating mESCs stained positive for cardiac troponin T, α-actinin 2,nmyosin heavy chain, and connexin 43. Hyperglycaemia decreased the EB diameter and number of beating EBs as well asnthe cellular amplitude of contraction, the Ca2+ transient, and the contractile response to caffeine (1 mM), but had no effect. on the expression of the sarco-endoplasmic reticulum calcium transport ATPase 2 (SERCA 2). Furthermore, hyperglycaemia decreased the expression of B cell lymphoma 2 (Bcl-2) and increased the expression of cytoplasmic cytochrome c and the number of TUNEL-positive cells, but had no effect on the expression of one of the mitochondrial fusion regulatory proteins, optic atrophy protein 1 (OPA1). Overall, hyperglycaemia suppressed the mESC cardiomyocyte-like differentiation and induced contractile dysfunction. The results are consistent with mechanisms involving abnormal Ca2+ handling and mitochondrial-dependent apoptosis, factors which represent potential therapeutic targets in developmental diabetic cardiac disease.

Small molecule, (2-(2-(2-nitrophenyl)diazenyl)malononitrile) (NPDAM), is synthesized and its chemical structure is characterized by different analyses. NPDAM powder is identified as polycrystalline monoclinic structure, whereas the thermally deposited films have nanostructure character with average particle size of 39 nm. NPDAM films are utilized for manufacturing hybrid solar cells in the structure of Au/NPDAM/p-Si/Al. The dark current-voltage (I-V) curves of the diode are measured in the temperature range 303-383 K and the thermionic emission theory is employed to extract the ideality factor, n, and potential barrier height, ∅ at forward applied voltages of V≤0.20 volt. The n value increases, whereas the ∅ value decreases with decreasing temperature. This behavior is analyzed in terms of the lateral inhomogeneous barrier following Gaussian distribution at the NPDAM/p-Si interface. Cheung and Cheung functions are used for extracting the values of series resistance, Rs, n and ∅. The behavior of these parameters as a function of temperature is discussed. At forward applied voltages 0.20<V≤2, the I-V relation reveals crossover from thermionic emission to square power law. This behavior is discussed by means of the space charge limited current. Under illumination, the device exhibits a response to light exposure with a photoelectrical conversion efficiency of 2.91 %.