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Molecular Background (molecular + background)
Selected AbstractsMolecular background of EPM1,Unverricht,Lundborg diseaseEPILEPSIA, Issue 4 2008Tarja Joensuu Summary Unverricht,Lundborg disease (EPM1) is an autosomal recessively inherited neurodegenerative disorder and the most common single cause of progressive myoclonus epilepsy worldwide. Mutations in the gene encoding cystatin B (CSTB), a cysteine protease inhibitor, are responsible for the primary defect underlying EPM1. Here, progress toward understanding the molecular mechanisms in EPM1 is reviewed. We summarize the current knowledge about the CSTB gene and mutations as well as the cellular biology of the CSTB protein with emphasis on data emerging from analysis of EPM1 patients. We shed light on the disease mechanisms of EPM1 based on characterization of the CSTB -deficient mouse model. [source] Skin and heart: une liaison dangereuseEXPERIMENTAL DERMATOLOGY, Issue 8 2009Maria C. Bolling Abstract:, Both skin and heart are subject to shear mechanical stress and need to be stress-resistant in a flexible way. The intercellular connecting structures in skin and heart, the desmosomes, that have to resist these forces show remarkable resemblance in epidermis and myocardium. Mutations in desmosomal proteins lead to inherited desmosomal cardiocutaneous syndromes (DCCS): une liaison dangereuse. This article will critically review the cutaneous and cardiac features as well as the molecular background of DCCS, such as Naxos disease and Carvajal syndrome caused by deficiencies of plakoglobin and desmoplakin respectively. In addition, potential other desmosomal gene candidates for an involvement in cardiocutaneous syndromes are considered. The skin features in these syndromes may be the hallmark for the presence of progressive and ultimately lethal cardiac disease. Knowledge of these skin features and early recognition of such a syndrome may provide opportunities to halt or slow down cardiac disease progression, treat arrhythmias and even prevent sudden death. [source] Mutation spectrum of Meckel syndrome genes: one group of syndromes or several distinct groups?,HUMAN MUTATION, Issue 8 2009Jonna Tallila Abstract Meckel syndrome (MKS) is a lethal malformation syndrome that belongs to the group of disorders that are associated with primary cilia dysfunction. Total of five genes are known to be involved in the molecular background of MKS. Here we have systematically analyzed all these genes in a total of 29 MKS families. Seven of the families were Finnish and the rest originated from elsewhere in Europe. We found 12 novel mutations in 13 families. Mutations in the MKS genes are also found in other syndromes and it seems reasonable to assume that there is a correlation between the syndromes and the mutations. To obtain some supportive information, we collected all the previously published mutations in the genes to see whether the different syndromes are dictated by the nature of the mutations. Based on this study, mutations play a role in the clinical phenotype, given that the same allelic combination of mutations has never been reported in two clinically distinct syndromes. © 2009 Wiley-Liss, Inc. [source] Anatomic site-specific proteomic signatures of gastrointestinal stromal tumorsPROTEOMICS - CLINICAL APPLICATIONS, Issue 5 2009Yoshiyuki Suehara Abstract The gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. Its clinical course ranges widely from a curable disorder to a highly malignant disease. Although its clinical and molecular characteristics depend on the anatomic site of origin, the molecular background of GIST arising in different anatomical site has not been studied yet. To investigate the proteomic background of GIST, we examined the proteomic features corresponding to the anatomic site of tumor origin. Comparison of the proteomic profile of gastric (23 cases) and small intestinal (9 cases) GIST by 2-DE revealed 105 protein spots with significantly different intensity (p <0.01) between the two groups. Mass spectrometric study identified 68 distinct proteins for these 105 protein spots, including cancer-associated ones such as prohibitin, pigment epithelium-derived factor, and alpha-actinin 4. The intensity of 37/105 (35.2%) protein spots was significantly concordant with the corresponding mRNA levels (p <0.01). Although both 2-D DIGE and microarray experiments showed significant up-regulation of vimentin expression in small intestinal GIST, Western blotting did not show a significant difference between the two groups. In conclusion, our study demonstrates the proteins specially expressed in GIST depending on their site of origin, as well as the unique advantage offered by use of proteomics to acquire such data. The identified proteins may provide clues to understanding the different characteristics of GIST depending on their site of origin. [source] Primary male infertility in Kuwait: a cytogenetic and molecular study of 289 infertile Kuwaiti patientsANDROLOGIA, Issue 3 2007F. Mohammed Summary Infertility is one of the major public health problems, affecting 15% of couples who attempt pregnancy; in 50% of these, the male partner is responsible. Chromosomal abnormalities and Y microdeletions in the azoospermia factor (AZF) region are known to be associated with spermatogenetic failure. In the present study, 289 patients with primary male infertility because of spermatogenetic failure were studied in order to highlight the molecular background of male infertility in Kuwait, and to avoid the possibility of transmission of any microdeletions/chromosomal aberrations to offspring via intracytoplasmic sperm injection (ICSI). Of the 289 infertile men, 23 patients (8%) had chromosomal aberration in the form of Klinefelter syndrome/variant (16/23; 69.6%), XYY syndrome (3/23; 13%), XX male syndrome (2/23; 8.7%), 45,X/46X, i(Yp)(1/23; 4.4%) and 45,XY, t(9;22) (1/23;4.4%). Y-chromosome microdeletion in the AZFb and AZFc regions were detected in 7/266 cases (2.6%). Testicular biopsy was carried out in 31 azoospermic patients, of whom five men had Sertoli-cell only syndrome, while 26 patients had spermatogenic arrest. In conclusion, this study showed that the frequency of both chromosomal anomalies and Y microdeletions were found in 10.4% of the infertile men. The potential risk of transmitting these genetic disorders to offspring provides a rationale for screening infertile men prior to ICSI. [source] Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of 2-keto-3-deoxy-6-phosphogluconate aldolase from Zymomonas mobilis ZM4ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2010Ho-Chang Ryu Zymomonas mobilis ZM4 is an organism optimized for ethanol production which uses the Entner,Doudoroff (ED) pathway for the breakdown of glucose. The key enzyme in this process is 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, which produces glyceraldehyde 3-phosphate and pyruvate. In order to provide a molecular background for the KDPG aldolase from this ethanologenic organism (zmKDPG aldolase), the ZMO0997 gene of Z. mobilis ZM4 coding for zmKDPG aldolase was cloned and expressed and the purified protein was crystallized from 25%(w/v) polyethylene glycol 3350 and 0.1,M bis-tris pH 5.5. Diffraction data were collected to 1.8,Å resolution using synchrotron radiation. The crystal belonged to the orthorhombic space group P212121, with unit-cell parameters a = 63.7, b = 83.0, c = 117.2,Å. A trimeric zmKDPG aldolase molecule was present in the asymmetric unit, resulting in a crystal volume per unit protein weight of 2.40,Å3,Da,1 and a solvent content of 48%. [source] Expression, crystallization and preliminary X-ray diffraction analysis of a modification subunit of a putative type I restriction enzyme from Vibrio vulnificus YJ016ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 12 2009Hyun-Ju Lee Modification (HsdM) and specificity (HsdS) subunits are constituents of an active methyltransferase (MTase) of multifunctional type I restriction enzymes. To provide a molecular background on HsdM, a putative hsdM gene from Vibrio vulnificus YJ016 (HsdM_Vv) was cloned and the expressed protein was purified and crystallized from 22%(w/v) polyethylene glycol 8000, 0.02,M imidazole pH 7.5 and 5,mM,-mercaptoethanol. Diffraction data were collected to 1.86,Å resolution using synchrotron radiation. The crystal belonged to the tetragonal space group P41212 or P43212, with unit-cell parameters a = b = 78.9, c = 165.8,Å. With one molecule in the asymmetric unit, the crystal volume per unit protein weight was 2.12,Å3,Da,1, with a solvent content of 42%. [source] Antibody-based proteomics for esophageal cancer: Identification of proteins in the nuclear factor-,B pathway and mitotic checkpointCANCER SCIENCE, Issue 9 2009Norihisa Uemura To identify the molecular background of esophageal cancer, we conducted a proteomics study using an antibody microarray consisting of 725 antibodies and surgical specimens from three cases. The microarray analysis identified 24 proteins with aberrant expression in esophageal cancer compared with the corresponding normal mucosa. The overexpression of 14 of the 24 proteins was validated by western blotting analysis of the same samples. These 14 proteins were examined by immunohistochemistry, in which nine proteins showed consistent results with those obtained by western blotting. Among the nine proteins, seven were localized in tumor cells, and two in infiltrating cells. The former included proteins associated with mitotic checkpoint control and the nuclear factor (NF)-,B pathway. Although mitotic checkpoint gene products (budding uninhibited by benzidazoles 1 homolog beta (BubR1) and mitotic arrest deficient-like 1 (Mad2)) have previously been reported to be involved in esophageal cancer, the association of NF-,B-activating kinase, caspase 10, and activator protein-1 with esophageal cancer has not been previously reported. These proteins play a key role in the NF-,B pathway, and NF-,B is a signal transduction factor that has emerged as an important modulator of altered gene programs and malignant phenotype in the development of cancer. The association of these proteins with esophageal cancer may indicate that mitotic checkpoint gene products and NF-,B play an important part in the carcinogenesis of esophageal cancer. (Cancer Sci 2009; 100: 1612,1622) [source] | |||||||||||||