Molecular mechanisms underlying thalassemia intermedia in Iran

To improve the differentiation of thalassemia intermedia from other hemoglobinopathies in Iran, four known genetic mechanisms-XmnI (G)gamma polymorphism, inheritance of mild and silent beta-thalassemia alleles, delta beta deletion, and coinheritance of alpha- and beta-thalassemia-were investigated in 52 Iranian individuals suspected to have thalassemia intermedia based on clinical and hematological characteristics. Beta-globin mutations were studied using a reverse-hybridization assay and sequencing of the total beta-globin gene. The XmnI (G)gamma polymorphism, the Sicilian delta beta deletion, and four alpha-globin mutations (-a(3.7), -a(4.2), -(MED), aaa(anti-3.7)) were studied using PCR-based techniques. The inheritance of the XmnI (G)gamma polymorphism with severe beta-thalassemia alleles in the homozygous or compound heterozygous state was the predominant mechanism observed in 27 individuals (55.3%). In five cases, this status overlapped with the -a(3.7)/aa genotype. The second most frequent cause for thalassemia intermedia (14.8%) was the inheritance of mild beta-thalassemia alleles, including IVS-I-6 (T > C), -88 (C > A), and + 113 (A > G). In three subjects (4.3%) the Sicilian delta beta deletion was identified. HbS in association with beta-zero-thalassemia was found in three patients with thalassemia intermedia phenotype. In 11 cases (21.3%) no causative genetic alteration could be identified. Our results reflect the diversity underlying thalassemia intermedia, and the limitations of the applied clinical, hematological, and molecular approaches for correct diagnosis. Some of the unresolved cases will offer an opportunity to discover additional molecular mechanisms leading to thalassemia intermedia.     

Effects of Neurofeedback Training on Performing Bimanual Coordination In-phase and Anti-phase Patterns in Children with ADHD

It is generally accepted that children with attention-deficit/hyperactivity disorder (ADHD) have poor motor control, especially in bimanual coordination tasks. Such children characteristically have impaired fine motor ability, problems with force control, and poor motor coordination. They are at particular risk of loss of motor control and reduced bimanual coordination. We tested whether, compared to a control condition, neurofeedback training (NFT) could improve bimanual coordination among children with ADHD. 20 Children with ADHD (mean age 7.9 years; SD 2.11) were randomly assigned either to NFT or to a control condition. All participants completed a bimanual coordination test at the following time points: baseline, assessment 1, assessment 2, assessment 3, and again 12 session later at posttest. NFT consisted of Sensory Motor Rhythm (SMR) training to achieve increased SMR in C3 and C4, while participants in the control condition were under mock NFT conditions. Bimanual coordination accuracy and consistency improved from baseline to completion of the intervention (significant Time effect), but in the NFT condition (significant time?×?group interaction). Compared to the control condition, the NFT group had fewer errors in both patterns of bimanual coordination (significant Group effect). Among children with ADHD, SMR neurofeedback training (NFT) led to significant improvements in a bimanual coordination task. The SMR NFT thus appears to have the potential to improve and enhance the motor control of ADHD patients.     

Sericin modulates learning and memory behaviors by tuning of antioxidant,inflammatory, and apoptotic markers in the hippocampus of aged mice

Molecular Biology Reports - Sericin is a protein derived from silkworm cocoons and identified as an anti-aging agent. This study aimed to examine the effects of sericin administration on episodic...     

Molecular genetic and biochemical analyses of FGF23 mutations in familial tumoral calcinosis

Fibroblast growth factor 23 (FGF23) is a hormone required for normal renal phosphate reabsorption. FGF23 gain-of-function mutations result in autosomal dominant hypophosphatemic rickets (ADHR), and FGF23 loss-of-function mutations cause familial hyperphosphatemic tumoral calcinosis (TC). In this study, we identified a novel recessive FGF23 TC mutation, a lysine (K) substitution for glutamine (Q) (160 C>A) at residue 54 (Q54K). To understand the molecular consequences of all known FGF23-TC mutants (H41Q, S71G, M96T, S129F, and Q54K), these proteins were stably expressed in vitro. Western analyses revealed minimal amounts of secreted intact protein for all mutants, and ELISA analyses demonstrated high levels of secreted COOH-terminal FGF23 fragments but low amounts of intact protein, consistent with TC patients' FGF23 serum profiles. Mutant protein function was tested and showed residual, yet decreased, bioactivity compared with wild-type protein. In examining the role of the FGF23 COOH-terminal tail (residues 180-251) in protein processing and activity, truncated mutants revealed that the majority of the residues downstream from the known FGF23 SPC protease site ((176)RXXR(179)/S(180)) were not required for protein secretion. However, residues adjacent to the RXXR site (between residues 188 and 202) were required for full bioactivity. In summary, we report a novel TC mutation and demonstrate a common defect of reduced FGF23 stability for all known FGF23-TC mutants. Finally, the majority of the COOH-terminal tail of FGF23 is not required for protein secretion but is required for full bioactivity.