In silico analysis of single nucleotide polymorphism (SNPs) in human β-globin gene

Single amino acid substitutions in the globin chain are the most common forms of genetic variations that produce hemoglobinopathies--the most widespread inherited disorders worldwide. Several hemoglobinopathies result from homozygosity or compound heterozygosity to beta-globin (HBB) gene mutations, such as that producing sickle cell hemoglobin (HbS), HbC, HbD and HbE. Several of these mutations are deleterious and result in moderate to severe hemolytic anemia, with associated complications, requiring lifelong care and management. Even though many hemoglobinopathies result from single amino acid changes producing similar structural abnormalities, there are functional differences in the generated variants. Using in silico methods, we examined the genetic variations that can alter the expression and function of the HBB gene. Using a sequence homology-based Sorting Intolerant from Tolerant (SIFT) server we have searched for the SNPs, which showed that 200 (80%) non-synonymous polymorphism were found to be deleterious. The structure-based method via PolyPhen server indicated that 135 (40%) non-synonymous polymorphism may modify protein function and structure. The Pupa Suite software showed that the SNPs will have a phenotypic consequence on the structure and function of the altered protein. Structure analysis was performed on the key mutations that occur in the native protein coded by the HBB gene that causes hemoglobinopathies such as: HbC (E→K), HbD (E→Q), HbE (E→K) and HbS (E→V). Atomic Non-Local Environment Assessment (ANOLEA), Yet Another Scientific Artificial Reality Application (YASARA), CHARMM-GUI webserver for macromolecular dynamics and mechanics, and Normal Mode Analysis, Deformation and Refinement (NOMAD-Ref) of Gromacs server were used to perform molecular dynamics simulations and energy minimization calculations on β-Chain residue of the HBB gene before and after mutation. Furthermore, in the native and altered protein models, amino acid residues were determined and secondary structures were observed for solvent accessibility to confirm the protein stability. The functional study in this investigation may be a good model for additional future studies.     

Association of Obesity and Hypertension With Left Ventricular Geometry and Function in Children and Adolescents

Obesity, especially when complicated with hypertension, is associated with structural and functional cardiac changes. Recent studies have focused on the prognostic impact of the type of left ventricular (LV) geometric remodeling. This study looked at the prevalence and clinical correlates of LV geometric patterns and their relation to cardiac function in a sample of predominantly African‐American (AA) youth. Echocardiographic data was collected on 213 obese (BMI of 36.53 ± 0.53 kg/m²) and 130 normal‐weight subjects (BMI of 19.73 ± 0.21 kg/m²). The obese subjects had significantly higher LV mass index (LVMI; 49.6 ± 0.9 vs. 46.0 ± 1.0 g/m^2.7, P = 0.01), relative wall thickness (RWT; 0.45 ± 0.00 vs. 0.40 ± 0.00, P < 0.001), left atrial (LA) index (33.2 ± 0.7 vs. 23.5 ± 0.6 ml/m, P < 0.001), more abnormal diastolic function by tissue Doppler E/Ea septal (7.5 ± 0.14 vs. 6.5 ± 0.12 ms, P < 0.001), E/Ea lateral (5.7 ± 0.12 vs. 4.8 ± 0.1 ms, P < 0.001), myocardial performance index (MPI; 0.43 ± 0.00 vs. 0.38 ± 0.00, P < 0.001), and Doppler mitral EA ratio (2.0 ± 0.04 vs. 2.4 ± 0.07, P < 0.001) but similar systolic function. Concentric remodeling (CR) was the most prevalent pattern noted in the obese group and concentric hypertrophy (CH) in the obese and hypertensive group. Obesity, hypertension, and CH were independent predictor of diastolic dysfunction. Systolic (SBP) and diastolic blood pressures (DBP) were the prime mediators for CH whereas obesity and diastolic blood pressure were predictors of CR. No significant association was observed between the geometric patterns and systolic function. Tracking LV hypertrophy (LVH) status and geometric adaptations in obesity may be prognostic tools for assessing cardiac risk and therapeutic end points with weight loss.     

Centaurea bruguierana inhibits cell proliferation,causes cell cycle arrest,and induces apoptosis in human MCF-7 breast carcinoma cells

Molecular Biology Reports - Centaurea bruguierana, of the Asteraceae family, has a long history of use in traditional medicines for the treatment of various ailments. However, the anticancer...     

Optimization of caulogenesis in Populus nigra under lead (Pb) stress via response surface methodology (RSM) and desirability function analysis

Plant Cell, Tissue and Organ Culture (PCTOC) - Polyethylene glycol (PEG)-mediated transient expression system in plant protoplasts has been widely used in a variety of plants for gene function...     

Beyond the Levant: First Evidence of a Pre-Pottery Neolithic Incursion into the Nefud Desert,Saudi Arabia

Pre-Pottery Neolithic assemblages are best known from the fertile areas of the Mediterranean Levant. The archaeological site of Jebel Qattar 101 (JQ-101), at Jubbah in the southern part of the Nefud Desert of northern Saudi Arabia, contains a large collection of stone tools, adjacent to an Early Holocene palaeolake. The stone tool assemblage contains lithic types, including El-Khiam and Helwan projectile points, which are similar to those recorded in Pre-Pottery Neolithic A and Pre-Pottery Neolithic B assemblages in the Fertile Crescent. Jebel Qattar lies ∼500 kilometres outside the previously identified geographic range of Pre-Pottery Neolithic cultures. Technological analysis of the typologically diagnostic Jebel Qattar 101 projectile points indicates a unique strategy to manufacture the final forms, thereby raising the possibility of either direct migration of Levantine groups or the acculturation of mobile communities in Arabia. The discovery of the Early Holocene site of Jebel Qattar suggests that our view of the geographic distribution and character of Pre-Pottery Neolithic cultures may be in need of revision.     

Nucleosides,IV1 Synthesis and Properties of 2-Metylthio-Naphthimidazole-Ribonucleoside

Abstract

The synthesis of 2-Methylthio-1-(β-D-ribofuranosyl) naphthimidazole has been accomplished by condensation of 2-methylthio-1-trimethylsilylnaphthimidazole(3) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose(4) in the presence of trimethylsilyl triflate in 1,2-dichloroethane, followed by subsequent debenzoylation. Structural proofs are based on elementary analysis, UV- and ¹H-NMR-spectra.     

Role of patient chronotype on circadian pattern of myocardial infarction: a pilot study

Population-based studies indicate the risk of acute myocardial infarction (AMI) is greatest in the morning, during the initial hours of diurnal activity. The aim of this pilot study was to determine whether chronotype, i.e., morningness and eveningness, impacts AMI onset time. The sample comprised 63 morning- and 40 evening-type patients who were classified by the Horne-?stberg Morningness-Eveningness Questionnaire (MEQ) in the hospital after experiencing the AMI. The average wake-up and bed times of morning types were ~2?h earlier than evening types. Although the lag in time between waking up from nighttime sleep and AMI onset during the day did not differ between the two chronotypes, the actual clock-hour time of the peak in the 24-h AMI pattern did. The peak in AMI of morning types occurred between 06:01 and 12:00?h and that of the evening types between 12:01 and 18:00?h. Although the results of this small sample pilot study suggest one's chronotype influences the clock time of AMI onset, larger scale studies, which also include assessment of 24-h patterning of events in neither types, must be conducted before concluding the potential influence of chronotype on the timing of AMI onset.     

An improved hybrid of SVM and SCAD for pathway analysis

Pathway analysis has lead to a new era in genomic research by providing further biological process information compared to traditional single gene analysis. Beside the advantage, pathway analysis provides some challenges to the researchers, one of which is the quality of pathway data itself. The pathway data usually defined from biological context free, when it comes to a specific biological context (e.g. lung cancer disease), typically only several genes within pathways are responsible for the corresponding cellular process. It also can be that some pathways may be included with uninformative genes or perhaps informative genes were excluded. Moreover, many algorithms in pathway analysis neglect these limitations by treating all the genes within pathways as significant. In previous study, a hybrid of support vector machines and smoothly clipped absolute deviation with groups-specific tuning parameters (gSVM-SCAD) was proposed in order to identify and select the informative genes before the pathway evaluation process. However, gSVM-SCAD had showed a limitation in terms of the performance of classification accuracy. In order to deal with this limitation, we made an enhancement to the tuning parameter method for gSVM-SCAD by applying the B-Type generalized approximate cross validation (BGACV). Experimental analyses using one simulated data and two gene expression data have shown that the proposed method obtains significant results in identifying biologically significant genes and pathways, and in classification accuracy.     

A comparative study of hematological parameters of α and β thalassemias in a high prevalence zone: Saudi Arabia

BACKGROUND AND AIMS:

Saudi Arabia falls in the high prevalent zone of αα and β thalassemias. Early screening for the type of thalassemia is essential for further investigations and management. The study was carried out to differentiate the type of thalassemia based on red cell indices and other hematological parameters.

MATERIALS AND METHODS:

The study was carried out on 991 clinically suspected cases of thalassemias in Riyadh, Saudi Arabia. The hematological parameters were studied on Coulter STKS. Cellulose acetate hemoglobin electrophoresis and high-performance liquid chromatography (HPLC) were performed on all the blood samples. Gene deletion studies were carried out by restriction fragment length polymorphism (RFLP) technique using the restriction endonucleases Bam HI.

STATISTICAL ANALYSIS:

Statistical analysis was performed on SPSS 11.5 version.

RESULTS:

The hemoglobin electrophoresis and gene studies revealed that there were 406 (40.96%) and 59 (5.95 %) cases of β thalassemia trait and β thalassemia major respectively including adults and children. 426 cases of various deletion forms of α thalassemias were seen. Microcytosis was a common feature in β thalassemias trait and (-α/-α) and (--/αα) types of α thalassemias. MCH was a more significant distinguishing feature among thalassemias. β thalassemia major and α thalassemia (-α/αα) had almost normal hematological parameters.

CONCLUSION:

MCV and RBC counts are not statistically significant features for discriminating between α and β thalassemias. There is need for development of a discrimination index to differentiate between α and β thalassemias traits on the lines of discriminatory Indices available for distinguishing β thalassemias trait from iron deficiency anemia.