De Novo Variants Disrupting the HX Repeat Motif of ATN1 Cause a Recognizable Non-Progressive Neurocognitive Syndrome.

Polyglutamine expansions in the transcriptional co-repressor Atrophin-1, encoded by ATN1, cause the neurodegenerative condition dentatorubral-pallidoluysian atrophy (DRPLA) via a proposed novel toxic gain of function. We present detailed phenotypic information on eight unrelated individuals who have de novo missense and insertion variants within a conserved 16-amino-acid "HX repeat" motif of ATN1. Each of the affected individuals has severe cognitive impairment and hypotonia, a recognizable facial gestalt, and variable congenital anomalies. However, they lack the progressive symptoms typical of DRPLA neurodegeneration. To distinguish this subset of affected individuals from the DRPLA diagnosis, we suggest using the term CHEDDA (congenital hypotonia, epilepsy, developmental delay, digit abnormalities) to classify the condition. CHEDDA-related variants alter the particular structural features of the HX repeat motif, suggesting that CHEDDA results from perturbation of the structural and functional integrity of the HX repeat. We found several non-homologous human genes containing similar motifs of eight to 10 HX repeat sequences, including RERE, where disruptive variants in this motif have also been linked to a separate condition that causes neurocognitive and congenital anomalies. These findings suggest that perturbation of the HX motif might explain other Mendelian human conditions.

Hybrid gray wolf optimizer-artificial neural network classification approach for magnetic resonance brain images.

Automated and accurate classification of magnetic resonance images (MRIs) of the brain has great importance for medical analysis and interpretation. This paper presents a hybrid optimized classification method to classify the brain tumor by classifying the given magnetic resonance brain image as normal or abnormal. The proposed system implements a gray wolf optimizer (GWO) combined with a supervised artificial neural network (ANN) classifier to achieve enhanced MRI classification accuracy via selecting the optimal parameters of ANN. The introduced GWO-ANN classification system performance is compared to the traditional neural network (NN) classifier using receiver operating characteristic analysis. Experimental results obviously indicate that the presented system achieves a high classification rate and performs much better than the traditional NN classifier.

Preparation of carbon quantum dots/polyaniline nanocomposite: Towards highly sensitive detection of picric acid.

Carbon quantum dots/polyaniline (CQDs/PANI) nanocomposite was successfully prepared by in-situ polymerization of aniline. CQDs were synthesized hydrothermally from gelatin with a diameter size of 4.2 nm and a 17% quantum yield. FTIR, UV-vis absorption, fluorescence spectrophotometer, XRD, TEM, XPS and lifetime decay were used to characterize the obtained nanocomposite. The formation of PANI revealed a high quenching effect on CQDs where the TEM images showed that the formed CQDs were greatly embedded in PANI matrix. In this study, CQDs/PANI nanocomposite was used for the detection of picric acid (PA) in the range 0.37-1.42 µM with a low detection limit (LOD) of 0.056 µM. The prepared sensor showed good enhancement and sensitivity towards PA in comparison to pristine CQDs and other nanostructured materials. The mechanism of PA detection has been studied where it was observed that PA is electrostatically interacted to the nanocomposite through - OH group of PA and the protonated PANI salt formed in CQDs/PANI nanocomposite by fluorescence resonance energy transfer applications. The proposed CQDs/PANI sensor was then utilized in real water samples and successfully determined the different amounts of PA spiked into tap water.

Association Study of FOXO3a Single-Nucleotide Polymorphism and Bronchial Asthma in Egyptian Children.

Asthma is the most common chronic illness in children and is a leading cause of childhood hospitalization and school absenteeism. Asthma presents with different phenotypes depending on age, gender, genetic background, environmental exposures and epigenetic factors. Forkhead box O3 (FOXO3) is a transcription factor involved in the pathogenesis of a number of inflammatory and respiratory diseases. The study aims to investigate the association between the SNP rs13217795 in FOXO3 gene and pediatric onset asthma in the Egyptian population. Ninety asthmatics and 160 healthy controls were subjected to genotyping of FOXO3 SNP (rs13217795) using the PCR-RFLP method. The proportion of homozygous (CC) and heterozygous (CT) genotypes was lower in the asthmatic group compared to the control group but statistically insignificant; P > 0.05. On the other hand the proportion of the mutant homozygous (TT) genotype in asthmatic group was higher; 30 (33.3%) than the control group; 28(17.5%), the difference was significant in Recessive model of disease penetrance with Odds ratio OR (95% CI) of 2.4(1 - 5.49) and P=0.039. This association was more pronounced in male gender; OR and 95% CI of 5.3 (1.4- 19.3) and P=0.01. In conclusions, Egyptian children carrying the mutant (TT) genotype were at higher risk to develop asthma with a higher risk in male gender.

WITHDRAWN:Randomized controlled trial of effect of N-acetylcysteine as an antioxidant on iron overload in children with thalassemia major.

Ahead of Print article withdrawn by publisher.

Not just a marker: CD34 on human hematopoietic stem/progenitor cells dominates vascular selectin binding along with CD44.

CD34 is routinely used to identify and isolate human hematopoietic stem/progenitor cells (HSPCs) for use clinically in bone marrow transplantation, but its function on these cells remains elusive. Glycoprotein ligands on HSPCs help guide their migration to specialized microvascular beds in the bone marrow that express vascular selectins (E- and P-selectin). Here, we show that HSPC-enriched fractions from human hematopoietic tissue expressing CD34 (CD34pos) bound selectins, whereas those lacking CD34 (CD34neg) did not. An unbiased proteomics screen identified potential glycoprotein ligands on CD34pos cells revealing CD34 itself as a major vascular selectin ligand. Biochemical and CD34 knockdown analyses highlight a key role for CD34 in the first prerequisite step of cell migration, suggesting that it is not just a marker on these cells. Our results also entice future potential strategies to investigate the glycoforms of CD34 that discriminate normal HSPCs from leukemic cells and to manipulate CD34neg HSPC-enriched bone marrow or cord blood populations as a source of stem cells for clinical use.