Absence of mutations in GJB2 (Connexin-26) gene in an ethnic group of southwest Iran

BACKGROUND:

The common GJB2 gene mutation (35delG) has been previously reported from Iranian patients that were affected with nonsyndromic autosomal recessive deafness. We, therefore, for the first time, investigated the prevalence and frequency of the GJB2 gene mutation in the Iranian deaf population with Arabian origins.

MATERIALS AND METHODs:

We amplified and sequenced the entire coding sequence of the GJB2 gene from 61 deaf patients and 26 control subjects.

RESULT:

None of the analyzed samples revealed deafness-associated mutation.

CONCLUSION:

This finding differs from several reports from Iran as we have focused on the GJB2 gene that possesses various mutations as the cause of congenital recessive deafness.     

The influence of Sc doping on structural,electronic and optical properties of Be<Subscript>12</Subscript>O<Subscript>12</Subscript>, Mg<Subscript>12</Subscript>O<Subscript>12</Subscript> and Ca<Subscript>12</Subscript>O<Subscript>12</Subscript> nanocages: a DFT study

Density functional theory (DFT) calculations were used to study the effect of scandium doping on the structural, energetic, electronic, linear and nonlinear optical (NLO) properties of Be₁₂O₁₂, Mg₁₂O₁₂ and Ca₁₂O₁₂ nanoclusters. Scandium (Sc) doping on nanoclusters leads to narrowing of their E _g, which enhances their conductance greatly. Also, the polarizability (α) and first hyperpolarizability (β₀) of nanoclusters were dramatically increased as Be, Mg or Ca atoms are substituted with a Sc atom. Among all clusters, α and β₀ values for Sc-doped Ca₁₂O₁₂ were the largest. Consequently, the effect of the doping atom, as well as of cluster size, on electronic and optical properties was explored. Time dependent (TD)-DFT calculations were also carried out to confirm the β₀ values; the results show that the higher value of first hyperpolarizability belongs to Sc-doped Ca₁₂O₁₂, which has the smallest transition energy (ΔEgn). The results obtained show that these clusters can be candidates for using in electronic devices and NLO materials in industry.     

Synthesis and carbonic anhydrase I,II, VII,and IX inhibition studies with a series of benzo[d]thiazole-5- and 6-sulfonamides

A series of benzo[d]thiazole-5- and 6-sulfonamides has been synthesized and investigated for the inhibition of several human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, using ethoxzolamide (EZA) as lead molecule. 2-Amino-substituted, 2-acylamino- and halogenated (bromo-and iodo-derivatives at the heterocyclic ring) compounds led to several interesting inhibitors against the cytosolic hCA I, II and VII, as well as the transmembrane, tumor-associated hCA IX isoforms. Several subnanomolar/low nanomolar, isoform-selective sulfonamide inhibitors targeting hCA II, VII and IX were detected. The sharp structure–activity relationship for CA inhibition with this small series of derivatives, with important changes of activity observed even after minor changes in the scaffold or at the 2-amino moiety, make this class of scarcely investigated sulfonamides of particular interest for further investigations.     

Optimization of recombinant β-NGF expression in Escherichia coli using response surface methodology

Human nerve growth factor a member of the neurotrophin family can be used to treat neurodegenerative diseases. As it has disulfide bonds in its structure, periplasmic expression of it using appropriate signal sequence is beneficial. Therefore, in this work β-nerve growth factor (β-NGF) was expressed in Escherichia coli using pET39b expression vector containing DsbA signal sequence. In an initial step, the effect of isopropyl β-D-1-thiogalactopyranoside (IPTG) and lactose concentration as inducer on protein production was investigated using response surface methodology. Then the effect of different postinduction time and temperature on protein production was studied. Our results indicated that the highest β-NGF production was achieved with 1?mM IPTG and low concentrations of lactose (0–2% w/v), low cultivation temperature of 25°C and postinduction time of 2?hr. Also following β-NGF purification, bioassay test using PC12 cell line was done. The biological activity of the purified β-NGF showed a similar cell proliferation activity with the standard recombinant human β-NGF. In conclusion, the results indicated an optimized upstream process to obtain high yields of biologically active β-NGF.     

SAR comparative studies on pyrimido[4,5-b][1,4] benzothiazine derivatives as 15-lipoxygenase inhibitors, using ab initio calculations

The enzyme inhibitory activity of a new group of 2-substituted pyrimido[4,5-b][1,4]benzothiazines on soybean 15-lipoxygenase (15-LO) was evaluated and compared with those of their 4-methyl analogs using ab initio calculations. The results of these studies showed that the lack of 4-methyl substituent in the pyrimido[4,5-b][1,4] benzothiazine molecules greatly reduces their 15-LO inhibitory activities.     

Characterization of estrogen receptor beta2 and expression of the estrogen receptor subtypes alpha, beta1, and beta2 in the protandrous black porgy (Acanthopagrus schlegeli) during the sex change process

Estrogens play an important role in many physiological processes in both female and male vertebrates, mediated by specific nuclear receptor, estrogen receptors (ERs). We have isolated a third ER (ERbeta2), which was found to contain 2004 nucleotides including an open reading frame that encodes 667 amino acids. We have also cloned ERalpha and ERbeta1 from the published information (GenBank accession nos. AY074780 and AY074779) and investigated the expression pattern of these ER subtypes in the gonads during gonad sex change of black porgy by quantitative polymerase chain reaction. Maturity stages can be divided into five stages during the sex change process from immature male to female (immature male, mature male, male of mostly testis, male of mostly ovary and mature female). The expression of ERalpha mRNA was highest in the ovary of mature female, followed by the testis of mature male and testicular portion of mostly testis. ERbeta1 expression was higher in the mature testis and ovary than in the gonads of other maturity stages. In contrast to that, ERbeta2 was highest in the ovary of mature female, and significantly lower levels of ERbeta2 expression were observed in the gonads of the other maturity stages. The present study describes the molecular characterization of ERbeta2, and documents the expression changes of three ER subtypes during sex change process of the protandrous black porgy.     

Innovative serum-free medium for in vitro cultivation of promastigote forms of Leishmania species

We described a comparatively simple medium formula (CML) using common, available and reasonably priced ingredients that could be used in place of medium that requires calf serum enhancement for cultivation of Leishmania promastigote forms. This medium equivalently supported the growth of parasites at rates comparable with those obtained with serum supplemented RPMI-1640 medium. Leishmania promastigotes reproduced in CML exhibited moderate to high infectivity capacities when tested against J774 macrophage cell line. No significant difference was noted between Leishmania strains cultivated in the newly modified medium and those grown in RPMI-1640 medium in their cells infectivity and replication potentials. The use of new CML can easily take the place of other biphasic or liquid media because of its easy preparation and instantaneous use, reasonable price, availability of ingredients, and its long shelf life, which is 30–45 days. The fact that this medium is similar to other culture media as far as durability and quantity of produced parasites might give it an advantage over the other currently used media.     

Computational Challenges of Personal Genomics

It is widely predicted that cost and efficiency gains in sequencing will usher in an era of personal genomics and personalized, predictive, preventive, and participatory medicine within a decade. I review the computational challenges ahead and propose general and specific directions for research and development. There is an urgent need to develop semantic ontologies that span genomics, molecular systems biology, and medical data. Although the development of such ontologies would be costly and difficult, the benefits will far outweigh the costs. I argue that availability of such ontologies would allow a revolution in web-services for personal genomics and medicine.