CHARGE syndrome is a disorder characterized by Coloboma, Heart defect, Atresia choanae, Retarded growth and/or development, Genital hypoplasia and Ear anomalies. Heterozygous mutations in the chromodomain helicase DNA-binding protein 7 (CHD7) gene have been identified in about 60% of individuals diagnosed with CHARGE syndrome. We performed a CHD7 mutation screening by direct exon sequencing in 28 index patients (26 sporadic cases, 1 familial case consisting of a brother and sister and 1 case consisting of monozygotic twins) diagnosed with CHARGE syndrome in order to determine the mutations in a cohort of Swedish CHARGE syndrome patients. The patients without a detectable CHD7 mutation, or with a missense mutation, were further investigated by multiplex ligation-dependent probe amplification (MLPA) in order to search for intragenic deletions or duplications. Thirteen novel mutations and five previously reported mutations were detected. The mutations were scattered throughout the gene and included nonsense, frameshift and missense mutations as well as intragenic deletions. In conclusion, CHD7 mutations were detected in a large proportion (64%) of cases diagnosed with CHARGE syndrome. Screening for intragenic deletions with MLPA is recommended in cases where mutations are not found by sequencing. In addition, a CDH7 mutation was found in an individual without temporal bone malformation.

-The objectives of this study were to assess genetic diversity and determine differences between several oriental tobacco genotypes by examining both agro-morphological traits and molecular markers. Simple lattice design with two replications was used to evaluate 100 oriental tobacco genotypes. Analysis of variance manifested that there is high level of genetic diversity in oriental-type tobaccos based on morphological traits including number of leaf, days to 50% flowering, leaf length, leaf width, leaf fresh weight, leaf dry weight, stem height and stem girth. Classification of genotypes using agro-morphological data by means of un-weighted pair-group method using arithmetic average (UPGMA) algorithm based on squared standardized Euclidean distances resulted four distinguishable groups that pursuit own geographical distribution. In the molecular marker investigations, a total of 13 simple sequence repeats (SSR) primer pairs were used to determine polymorphism of the test germplasm. Thirty five alleles were scored at 13 SSR loci. The average number of alleles per locus (na) and the effective allele number (Ae) were 2.69 and 2.34, respectively. By using SSR data, pair wise Jaccard's similarity coefficients were produced. Grouping of genotypes via Jaccard's similarity coefficients and using UPGMA clustering method lead to three groups that had not any accommodated with own origins. Results reveled that there is not completely agreement for classification based on agro-morphological and SSR loci in oriental-type tobaccos. Because of non influence of environmental effects on molecular marker, heterotic groups based on SSR markers could be closer to reality.Key words: Cluster analysis. Euclidean distance. Genetic diversity. Jaccard's similarity. Oriental tobacco.RESUMO -Os objetivos deste estudo foram avaliar a diversidade genética e determinar as diferenças entre diversos genótipos de tabaco oriental através tratos morfológicos e marcadores moleculares. O delineamento utilizado foi o látice simples com duas repetições e foram avaliados 100 genótipos de tabaco simples. As análises de variância mostarram que há pouca alto nível de diversidade genética nos tabacos to tipo oriental baseado nos tratamentos morfológicos incluindo número de folhas, dias para os 50% do florescimento, comprimento da folha, largura da folha, peso fresco da folha, peso seco da folha e maior comprimento e espessura do caule. A classificação dos genótipos usando o método de dados morfológicos por médias de grupos pareados não ponderados usando média aritmética (UPGMA) algoritmo baseado nas distâncias Euclidianas quadradas padronizadas resultou quatro grupos distintos de acordo co a própria distribuição geográfica. Nas investigações dos marcadores moleculares, um total de 13 repetições de sequências simples (RSS) de iniciadores pares foram utilizados para determinar o polimorfismo do germoplasma de teste. Trinta e cinco alelos foram marcados em 13 locos RSS. O numero médio de alelos por loco (na) e o número de alelo efetivo (Ae) forma 2,...

Na/Ca exchanger (NCX) is the main Ca transporter in cardiac myocytes. Its inhibition could be expected to exert positive inotropic action by accumulation of cytosolic Ca ([Ca]). However, we have observed only a marginal positive inotropic effect upon selective inhibition of NCX, which was enhanced when forward activity was facilitated. Here we attempted to clarify the underlying mechanism of the limited inotropic action of selective NCX inhibition by a novel inhibitor ORM-10962 on canine ventricular myocytes. 1µM ORM-10962 reduced the Ca content of sarcoplasmic reticulum (SR) when the reverse NCX was favoured, while SR Ca content was increased by ORM-10962 under conditions favouring the forward activity, like elevation of [Ca]. L-type Ca current (I) was not affected by 1µM ORM-10962 in the absence of SR Ca release, while I was suppressed by ORM-10962 during normal Ca cycling. The apparent degree of forward NCX inhibition was dependent on the elevation of [Ca], suggesting that an increased driving force of forward NCX can also limit the accumulation of [Ca]. We concluded that in healthy myocardium the possible positive inotropic potential of NCX inhibition is considerably weaker than it was expected earlier by theoretical assumptions. The underlying mechanism may involve the autoregulation of Ca handling and/or the preserved inducibility of forward NCX by high [Ca]. This limitation of selective NCX inhibition seen in undiseased myocardium requires further studies in failing heart, which may allow correct evaluation of the potential therapeutic value of selective NCX inhibitors in the treatment of heart failure.

Background In vitro culture of olive, as an economically valuable tree, has fundamentally a genotype-dependant low micropropagation rate which needs to be improved in already established and newly released cultivars. Various plant tissue culture media, planting systems and growth factors were evaluated in two promissing Iranian olive cultivars ˈAminˈ and ˈMeshkatˈ and the commercial Spanish cultivar ˈArbequinaˈ. Results The results showed that cultivars have their specific optimal media, i.e. ˈAminˈ in the MS with 4 mg/L zeatin, ˈArbequinaˈ in the OM with 1 mg/L zeatin, and ˈMeshkatˈ in the OM and MS with 2 mg/L zeatin, which produced significantly a higher number of axillary shoots than other media. The results also indicated a significant improvement in the growth indices of ˈAminˈ (number of axillary shoots) when cultured using periodical mini bioreactor (PMB) in the VS medium. In comparison with VS, OM did not reveal any significant differences when both culturing systems (PMB and semi-solid media (SSM)) were used. Regarding the effect of carbon source and light intensity, mannitol and 2000 cd sr m−2 greatly enhanced ˈArbequinaˈ growth indices (main shoot length and growth quality). The results of genetic stability of callus induced shoots (CIS) and meristem induced shoots (MIS) revealed that 2C DNA value assessed by partec flow cytometery (FCM) had 0.01, 0.03 and 0.08 pg discrepencies in ˈAminˈ, ˈArbequinaˈ and ˈMeshkatˈ, repectively. The Amplified Fragment Length Polymorphism (AFLP) results also indicated that the cultivars were classified regardless of the micropropagation origin (CIS or MIS), except for ˈArbequinaˈ. The AFLP findings showed that ˈArbequinaˈ had the highest dispersal (7–38%) in CIS and MIS, while the Iranian cultivar of ˈMeshkatˈ (5–9%) had the highest stability. Conclusions This study indicated the importance of in vitro growth parameters for improving the micropropagation indices of olive cultivars. It showed that optimized protocols (OM, PMB, zeatin, mannitol and 2000 cd sr m−2) co-produced larger calli resulting in indirect organogenesis. Based on FCM and AFLP analysis, it can be concluded that true-to-typeness of micropropagated olive was cultivar-dependent.

Strongyloides stercoralis and other intestinal parasites among the patients receiving immunosuppressive drugs in northern Iran; a closer look into risk factors ABSTRACT OBJECTIVES:The objective of this study was to evaluate the prevalence of Strongyloides stercoralis and other intestinal parasites among the patients receiving immunosuppressive drugs and related risk factors in northern Iran. METHODS:This cross-sectional study was conducted among 494 patients receiving immunosuppressive drugs including cancer patients undergoing chemotherapy (n=188) and those treated with prolonged corticosteroid administration (n=306). All fresh fecal samples were examined by direct wet-mount, formalin ethyl-acetate concentration, and agar plate culture techniques. RESULTS:In total, 16.8% of patients were positive for at least one intestinal parasite, so among those the helminthic and protozoan infection rates were 5.1% and 12.3%, respectively. The infection rate was significantly higher in corticosteroid treated individuals (19.6%) than cancer patients (12.2%) (P = 0.03). The prevalence rate of S. stercoralis among the patients receiving chemotherapy and those treated with corticosteroids were 4.3% and 5.2%, respectively. The prevalence rate of S. stercoralis infection was significantly higher in older patients (P=0.02). CONCLUSIONS:Strongyloidiasis is one of most common parasites among the patients receiving immunosuppressive drugs in northern Iran. Early diagnosis and proper treatment of these patients are necessary to minimize complications of severe strongyloidiasis.