Optimisation and Assessment of Three Modern Touch Screen Tablet Computers for Clinical Vision Testing

Technological advances have led to the development of powerful yet portable tablet computers whose touch-screen resolutions now permit the presentation of targets small enough to test the limits of normal visual acuity. Such devices have become ubiquitous in daily life and are moving into the clinical space. However, in order to produce clinically valid tests, it is important to identify the limits imposed by the screen characteristics, such as resolution, brightness uniformity, contrast linearity and the effect of viewing angle. Previously we have conducted such tests on the iPad 3. Here we extend our investigations to 2 other devices and outline a protocol for calibrating such screens, using standardised methods to measure the gamma function, warm up time, screen uniformity and the effects of viewing angle and screen reflections. We demonstrate that all three devices manifest typical gamma functions for voltage and luminance with warm up times of approximately 15 minutes. However, there were differences in homogeneity and reflectance among the displays. We suggest practical means to optimise quality of display for vision testing including screen calibration.     

Temperature Gradient Measurements by Using Thermoelectric Effect in CNTs-Silicone Adhesive Composite

This work presents the fabrication and investigation of thermoelectric cells based on composite of carbon nanotubes (CNT) and silicone adhesive. The composite contains CNT and silicon adhesive 1∶1 by weight. The current-voltage characteristics and dependences of voltage, current and Seebeck coefficient on the temperature gradient of cell were studied. It was observed that with increase in temperature gradient the open circuit voltage, short circuit current and the Seebeck coefficient of the cells increase. Approximately 7 times increase in temperature gradient increases the open circuit voltage and short circuit current up to 40 and 5 times, respectively. The simulation of experimental results is also carried out; the simulated results are well matched with experimental results.     

Molecular mechanism and therapy application of necrosis during myocardial injury

Necrosis is an ancient topic which gains new attraction in the research area these years. There is no doubt that some necrosis can be regulated by genetic manipulation other than an accidental cell death resulting from physical or chemical stimuli. Recent advances in the molecular mechanism underlying the programmed necrosis show a fine regulation network which indicates new therapy targets in human diseases. Heart diseases seriously endanger our health and have high fatality rates in the patients. Cell death of cardiac myocytes is believed to be critical in the pathogenesis of heart diseases. Although necrosis is likely to play a more important role in cardiac cell death than apoptosis, apoptosis has been paid much attention in the past 30 years because it used to be considered as the only form of programmed cell death. However, recent findings of programmed necrosis and the related signalling pathways have broadened our horizon in the field of programmed cell death and promote new pharmacological application in the treatment of heart diseases. In this review, we summarize the advanced progress in these signalling pathways and discuss the pathos‐physiological relevance and therapeutic implication of targeting necrosis in heart diseases treatment.     

Drought stress revealed physiological,biochemical and gene-expressional variations in ‘Yoshihime’ peach (Prunus Persica L) cultivar

It is indispensable to comprehend the mechanism that regulates plant responses to drought conditions to intensify the water use efficiency of stone fruits. The physiological, biochemical and molecular responses of drought-treated peach leaves were investigated. Results revealed that drought-treated plants manifested a significant attenuation in water potential as compared to control plants. Furthermore, sorbitol and proline contents were accumulated contrary to glucose, fructose, and sucrose that were dwindled significantly throughout the drought period. Similarly, the activities of antioxidant enzymes and expression pattern of related genes were hoisted to counter the lipid peroxidation in drought-treated plants. Moreover, reduced stomatal conductance has repressed the photosynthesis process and linked genes during drought stress. The expression level of regulatory genes (dehydration-responsive element-bindings and WRKYs) exhibited up-regulation in the drought-treated group. Overall, this study asserts that ‘Yoshihime’ peach cultivar possesses unique physiological, biochemical, and molecular responses under different spells of drought stress.     

Identification of novel genes and networks governing hematopoietic stem cell development

Hematopoietic stem cells (HSCs) are capable of giving rise to all blood cell lineages throughout adulthood, and the generation of engraftable HSCs from human pluripotent stem cells is a major goal for regenerative medicine. Here, we describe a functional genome‐wide RNAi screen to identify genes required for the differentiation of embryonic stem cell (ESC) into hematopoietic stem/progenitor cells (HSPCs) in vitro. We report the discovery of novel genes important for the endothelial‐to‐hematopoietic transition and subsequently for HSPC specification. High‐throughput sequencing and bioinformatic analyses identified twelve groups of genes, including a set of 351 novel genes required for HSPC specification. As in vivo proof of concept, four of these genes, Ap2a1, Mettl22, Lrsam1, and Hal, are selected for validation, confirmed to be essential for HSPC development in zebrafish and for maintenance of human HSCs. Taken together, our results not only identify a number of novel regulatory genes and pathways essential for HSPC development but also serve as valuable resource for directed differentiation of therapy grade HSPCs using human pluripotent stem cells.     

Methylene blue alleviates nuclear and mitochondrial abnormalities in progeria

Hutchinson–Gilford progeria syndrome (HGPS), a fatal premature aging disease, is caused by a single‐nucleotide mutation in the LMNA gene. Previous reports have focused on nuclear phenotypes in HGPS cells, yet the potential contribution of the mitochondria, a key player in normal aging, remains unclear. Using high‐resolution microscopy analysis, we demonstrated a significantly increased fraction of swollen and fragmented mitochondria and a marked reduction in mitochondrial mobility in HGPS fibroblast cells. Notably, the expression of PGC‐1α, a central regulator of mitochondrial biogenesis, was inhibited by progerin. To rescue mitochondrial defects, we treated HGPS cells with a mitochondrial‐targeting antioxidant methylene blue (MB). Our analysis indicated that MB treatment not only alleviated the mitochondrial defects but also rescued the hallmark nuclear abnormalities in HGPS cells. Additional analysis suggested that MB treatment released progerin from the nuclear membrane, rescued perinuclear heterochromatin loss and corrected misregulated gene expression in HGPS cells. Together, these results demonstrate a role of mitochondrial dysfunction in developing the premature aging phenotypes in HGPS cells and suggest MB as a promising therapeutic approach for HGPS.     

Lipid lowering activity of novel N-(benzoylphenyl)pyridine-3-carboxamide derivatives in Triton WR-1339-induced hyperlipidemic rats

Abstract

Context: Dyslipidemia is a major risk factor for the development of cardiovascular diseases. Many dyslipidemic patients do not achieve their target lipid levels with the currently available medications, and most of them may experience many side effects.

Objective: The present work aimed toward identifying a new class of novel nicotinic acid-carboxamide derivatives as promising antihyperlipidemic compounds.

Materials and methods: Six novel N-(benzoylphenyl)pyridine-3-carboxamide derivatives were synthesized using acid chloride pathways. All structures were confirmed using ¹H-NMR, ¹³C-NMR, IR, and HRMS. The evaluation of biological activity was conducted using Triton WR-1339-induced hyperlipidemic rats model.

Results: This study revealed that some of the newly synthesized novel N-(benzoylphenyl)pyridine-3-carboxamide derivatives mainly C4 and C6 possessed significant antihyperlipidemic activities on lipid components TG and TC (p value?<0.05).

Discussion and conclusion: This research opens the door for new potential antihyperlipidemic compounds derived from nicotinic acid that need further optimization of their biological activities.     

A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies

Background

Fifty random genetically unstudied families (limb-girdle muscular dystrophy (LGMD)/myopathy) were screened with a gene panel incorporating 759 OMIM genes associated with neurological disorders. Average coverage of the CDS and 10 bp flanking regions of genes was 99 %. All families were referred to the Neurosciences Clinic of King Faisal Specialist Hospital and Research Centre, Saudi Arabia. Patients presented with muscle weakness affecting the pelvic and shoulder girdle. Muscle biopsy in all cases showed dystrophic or myopathic changes. Our main objective was to evaluate a neurological gene panel as a first-line diagnostic test for LGMD/myopathies.

Results

Our panel identified the mutation in 76 % of families (38/50; 11 novel). Thirty-four families had mutations in LGMD-related genes with four others having variants not typically associated with LGMD. The majority of cases had recessive inheritance with homoallelic pathogenic variants (97.4 %, 37/38), as expected considering the high rate of consanguinity in the study population. In one case, we detected a heterozygous mutation in DNAJB responsible for LGMD-1E. Our cohort included seven different subtypes of LGMD2. Mutations of DYSF were the most commonly identified cause of disease followed by that in CAPN3 and FKRP. Non-LGMD myopathies were due to mutations in genes associated with congenital disorder of glycosylation (ALG2), rigid spine muscular dystrophy 1 (SEPN1), inclusion body myopathy2/Nonaka myopathy (GNE), and neuropathy (WNK1). Whole exome sequencing (WES) of patients who remained undiagnosed with the neurological panel did not improve our diagnostic yield.

Conclusions

Our neurological panel achieved a high clinical sensitivity (76 %) and is an effective first-line laboratory test in patients with LGMD and other myopathies. This sensitive, cost-effective, and rapid assay significantly assists clinical practice especially in these phenotypically and genetically heterogeneous disorders. Moreover, the application of the American College of Medical Genetics (ACMG) and Association for Molecular Pathology (AMP) guidelines applied in the classification of variant pathogenecity provides a clear interpretation for physicians on the relevance of such findings.