Neoplastic Transformation Induced by the gep Oncogenes Involves the Scaffold Protein JNK-Interacting Leucine Zipper Protein

The activated mutants of the α-subunits of G proteins G₁₂ and G₁₃ have been designated as the gep oncogenes owing to their ability to stimulate diverse oncogenic signaling pathways that lead to neoplastic transformation of fibroblast cell lines and tumorigenesis in nude mice models. Studies from our laboratory as well as others have shown that the growth-promoting activities of Gα₁₂ and Gα₁₃ involve potent activation of c-Jun N-terminal kinases (JNKs). Our previous studies have indicated that the JNK-interacting leucine zipper protein (JLP), a scaffold protein involved in the structural and functional organization of the JNK/p38 mitogen-activated protein kinase module, tethers Gα₁₂ and Gα₁₃ to the JNK signaling module. In the present study, in addition to demonstrating the physical association between JLP and Gα₁₂, we show that this interaction is enhanced by the receptor- or mutation-mediated activation of Gα₁₂. We also establish that JLP interacts with Gα₁₂ through the C-terminal domain that has been previously identified to be involved in binding to Gα₁₃. Furthermore, using this C-terminal domain as a competitively inhibitor of JLP that can disrupt Gα₁₂-JLP interaction, we demonstrate that JLP is required for the stimulation of JNK by Gα₁₂. Our results also indicate that such JLP interaction is required for Gα₁₂ as well as Gα₁₃-mediated neoplastic transformation of JLP. These studies demonstrate for the first time a functional role for JLP in the gep oncogene-regulated neoplastic signaling pathway.     

Electrodeposition and characterization of polypyrrole films on copper

In the present study, citric acid (CA), sodium acetate (SA) and sodium benzoate (SB) are used as electrolytes and compared in terms of easiness for polypyrrole deposition and film characteristics. Electrochemical measurements in the solution having these electrolytes with and without pyrrole demonstrate that copper can be efficiently passivated before PPy electrodeposition. This layer was sufficiently protective to inhibit further dissolution of the copper electrode and adequately conductive to enable the electropolymerization of pyrrole at the interface leading to the generation of an adherent polypyrrole film. The characterization of these coatings is carried out by cyclic voltammetry, UV–visible absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) studies. The performance of polypyrrole as protective coating against corrosion of Cu in both acidic and basic solutions is assessed by the potentiodynamic polarization technique and electrochemical impedance spectroscopy (EIS).     

Genetic male infertility and mutation of CATSPER ion channels

A clinically significant proportion of couples experience difficulty in conceiving a child. In about half of these cases male infertility is the cause and often genetic factors are involved. Despite advances in clinical diagnostics ∼50% of male infertility cases remain idiopathic. Based on this, further analysis of infertile males is required to identify new genetic factors involved in male infertility. This review focuses on cation channel of sperm (CATSPER)-related male infertility. It is based on PubMed literature searches using the keywords ‘CATSPER'', ‘male infertility'', ‘male contraception'', ‘immunocontraception'' and ‘pharmacologic contraception'' (publication dates from January 1979 to December 2009). Previously, contiguous gene deletions including the CATSPER2 gene implicated the sperm-specific CATSPER channel in syndromic male infertility (SMI). Recently, we identified insertion mutations of the CATSPER1 gene in families with recessively inherited nonsyndromic male infertility (NSMI). The CATSPER channel therefore represents a novel human male fertility factor. In this review we summarize the genetic and clinical data showing the role of CATSPER mutation in human forms of NSMI and SMI. In addition, we discuss clinical management and therapeutic options for these patients. Finally, we describe how the CATSPER channel could be used as a target for development of a male contraceptive.     

E-shaver: an improved DullRazor(®) for digitally removing dark and light-colored hairs in dermoscopic images

We present an efficient and improved method for hair removal from dermoscopic images, which is faster and can remove hairs more effectively as compared to the existing and widely used DullRazor^®. To do so, we first detect the predominant orientation of hairs in the image by using Radon transform, followed by filtering the image by Prewitt filters using the orientation of existing hairs. Undesirable effects, such as non-hair structures and noise are removed from the image by thresholding–averaging–thresholding, followed by smoothing. The proposed scheme has the advantage of removing bubbles, as well. Implementation of our proposed scheme on different dermoscopic images validates its improved performance.     

Chromosome abnormality rate among Iranian patients with idiopathic mental retardation from consanguineous marriages

Introduction

Mental retardation (MR) has heterogeneous aetiology mostly with genetic causes. Chromosomal aberrations are one of the most common causes of MR. Reports on chromosome abnormality rate among consanguineous families are sparse. In order to identify the chromosome abnormality rate in idiopathic mental retardation from consanguineous marriages, a total of 322 Iranian families with positive family history for MR were investigated in the Genetics Research Center.

Material and methods

In the majority of families (92%) at least two sibs were affected with MR and none had specific chromosomal syndromes such as Down syndrome. Standard cytogenetic techniques using high resolution GTG banding were carried out on all the patients.

Results

The overall chromosome abnormality rate contributing to mental retardation was 1.24% (4 cases), which comprised 46,XY,der(18)t(4;18)(q31.1;q23)mat; 45,XY,-21,-22,+der(22)t(21;22)(q21.1;q13.33)mat; 46,XY,rec(2)dup(2p)inv(2)(p25.1q37.3)pat, and 46,XY,der(11)t(10;11)(q25.2;q25)pat.

Conclusions

Although the most likely genetic cause of mental retardation in patients with consanguineous parents is autosomal recessive, the fact that 1.24% of our patients had chromosomal abnormalities emphasizes the importance of cytogenetic investigation as the first laboratory genetic tests for all MR patients. To our knowledge, this is the first report on the rate of chromosome abnormality among patients with idiopathic mental retardation from consanguineous marriages.     

Screening for MYO15A gene mutations in autosomal recessive nonsyndromic, GJB2 negative Iranian deaf population

MYO15A is located at the DFNB3 locus on chromosome 17p11.2, and encodes myosin-XV, an unconventional myosin critical for the formation of stereocilia in hair cells of cochlea. Recessive mutations in this gene lead to profound autosomal recessive nonsyndromic hearing loss (ARNSHL) in humans and the shaker2 (sh2) phenotype in mice. Here, we performed a study on 140 Iranian families in order to determine mutations causing ARNSHL. The families, who were negative for mutations in GJB2, were subjected to linkage analysis. Eight of these families showed linkage to the DFNB3 locus, suggesting a MYO15A mutation frequency of 5.71% in our cohort of Iranian population. Subsequent sequencing of the MYO15A gene led to identification of 7 previously unreported mutations, including 4 missense mutations, 1 nonsense mutation, and 2 deletions in different regions of the myosin-XV protein.