Novel Loci for Non-Syndromic Coarctation of the Aorta in Sporadic and Familial Cases

BackroundCoarctation of the aorta (CoA) accounts for 5-8% of all congenital heart defects. CoA can be detected in up to 20% of patients with Ullrich-Turner syndrome (UTS), in which a part or all of one of the X chromosomes is absent. The etiology of non-syndromic CoA is poorly understood. In the present work, we test the hypothesis that rare copy number variation (CNV) especially on the gonosomes, contribute to the etiology of non-syndromic CoA.MethodsWe performed high-resolution genome-wide CNV analysis using the Affymetrix SNP 6.0 microarray platform for 70 individuals with sporadic CoA, 3 families with inherited CoA (n=13) and 605 controls. Our analysis comprised genome wide association, CNV burden and linkage. CNV was validated by multiplex ligation-dependent probe amplification.ResultsWe identified a significant abundance of large (>100 kb) CNVs on the X chromosome in males with CoA (p=0.005). 11 out of 51 (~ 22%) male cases had these large CNVs. Association analysis in the sporadic cohort revealed 14 novel loci for CoA. The locus on 21q22.3 in the sporadic CoA cohort overlapped with a gene locus identified in all familial cases of CoA (candidate gene TRPM2). We identified one CNV locus within a locus with high multipoint LOD score from a linkage analysis of the familial cases (SEPT9); another locus overlapped with a region implicated in Kabuki syndrome. In the familial cases, we identified a total of 7 CNV loci that were exclusively present in cases but not in unaffected family members.ConclusionOf all candidate loci identified, the TRPM2 locus was the most frequently implicated autosomal locus in sporadic and familial cases. However, the abundance of large CNVs on the X chromosome of affected males suggests that gonosomal aberrations are not only responsible for syndromic CoA but also involved in the development of sporadic and non-syndromic CoA and their male dominance.     

Second-Harmonic Generation from Dendritic Fractal Structures

Plasmonics - Nanostructured conductive surfaces have been exploited for a variety of applications in photonics and optical sensing due to the broad spectral tunability of the localized surface...     

Clinical and molecular studies in two families with Fraser syndrome: a new FRAS1 gene mutation, prenatal ultrasound findings and implications for genetic counselling

Fraser syndrome is a rare autosomal recessive genetic disorder characterized by cryptophthalmus, variable expression of cutaneous syndactyly of fingers and toes, genital ambiguity and renal agenesis/dysgenesis. We present here molecular and clinical findings of four fetuses with FS from two families. Molecular genetic studies in the two families revealed mutations in FRAS1 gene allowing better genetic counselling and subsequent prenatal diagnosis in one of the two families. In family one, a nonsense mutation (c.3730C>T, p.R1244X) previously described in a Polish patient was found. In family two a novel nonsense mutation previously not known was detected (c.370C>T, p.R124X). PGD is planned for family 1.     

Relationships Between Respiratory Function Disorders and Serum Copper Levels in Copper Mineworkers

The aim of this study was to investigate the respiratory function disorders that could be related to dust exposure during the production of copper mine in copper mineworkers (CMWs). The study included 75 male CMWs (mean age, 32.0 ± 7.1 years, 58.6% smokers) and 75 male age- and smoking status-matched healthy control subjects. Serum Cu level was significantly higher in the CMW group (0.80 ± 0.62 μg/ml) than the control group (0.60 ± 0.39 μg/ml) (p = 0.017). Significant negative correlations were found between serum Cu level and forced expiratory volume in first second (r = −0.600; p < 0.001) and between serum Cu level and forced vital capacity (r = −0.593; p = <0.001) in CMWs. Serum Cu level was significantly higher in the restrictive type pulmonary function disorders group (1.36 ± 0.62 μg/ml) than obstructive type (0.90 ± 0.55 μg/ml) and normal pulmonary function pattern group (0.53 ± 0.43 μg/ml) (p < 0.001). Patients with radiological parenchymal abnormalities had significantly higher serum copper levels than those without abnormalities (1.53 ± 0.52 vs. 0.71 ± 0.52 μg/ml, respectively; p = 0.002). In conclusion, result of the study has shown a negative association between pulmonary functions disorders and radiological abnormalities and serum Cu levels in CMWs.     

Biogenesis of cbb(3)-type cytochrome c oxidase in Rhodobacter capsulatus

The cbb(3)-type cytochrome c oxidases (cbb(3)-Cox) constitute the second most abundant cytochrome c oxidase (Cox) group after the mitochondrial-like aa(3)-type Cox. They are present in bacteria only, and are considered to represent a primordial innovation in the domain of Eubacteria due to their phylogenetic distribution and their similarity to nitric oxide (NO) reductases. They are crucial for the onset of many anaerobic biological processes, such as anoxygenic photosynthesis or nitrogen fixation. In addition, they are prevalent in many pathogenic bacteria, and important for colonizing low oxygen tissues. Studies related to cbb(3)-Cox provide a fascinating paradigm for the biogenesis of sophisticated oligomeric membrane proteins. Complex subunit maturation and assembly machineries, producing the c-type cytochromes and the binuclear heme b(3)-Cu(B) center, have to be coordinated precisely both temporally and spatially to yield a functional cbb(3)-Cox enzyme. In this review we summarize our current knowledge on the structure, regulation and assembly of cbb(3)-Cox, and provide a highly tentative model for cbb(3)-Cox assembly and formation of its heme b(3)-Cu(B) binuclear center. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes.     

A single amino acid change (Y318F) in the L-arabitol dehydrogenase (LadA) from Aspergillus niger results in a significant increase in affinity for D-sorbitol

Background  

L-arabitol dehydrogenase (LAD) and xylitol dehydrogenase (XDH) are involved in the degradation of L-arabinose and D-xylose, which are among the most abundant monosaccharides on earth. Previous data demonstrated that LAD and XDH not only differ in the activity on their biological substrate, but also that only XDH has significant activity on D-sorbitol and may therefore be more closely related to D-sorbitol dehydrogenases (SDH). In this study we aimed to identify residues involved in the difference in substrate specificity.     

Ultrastructure of the sodium pump: Comparison of thin sectioning, negative staining, and freeze-fracture of purified, membrane-bound (Na+, K+)-ATPase

Purified (Na+, K+)-ATPase was studied by electron microscopy after thin sectioning, negative staining, and freeze-fracturing, particular emphasis being paid to the dimensions and frequencies of substructures in the membranes. Ultrathin sections show exclusively flat or cup-shaped membrane fragments which are triple-layered along much of their length and have diameters of 0.1-0.6 μm. Negative staining revealed a distinct substructure of particles with diameters between 30 and 50 A and with a frequency of 12,500 +/- 2,400 (SD) per μm(2). Comparisons with sizes of the protein components suggest that each surface particle contains as its major component one large catalytic chain with mol wt close to 100,000 and that two surface particles unite to form the unit of (Na+,K+)-ATPase which binds one molecule of ATP or ouabain. The further observations that the surface particles protrude from the membrane surface and are observed on both membrane surfaces in different patterns and degrees of clustering suggest that protein units span the membrane and are capable of lateral mobility. Freeze-fracturing shows intramembranous particles with diameters of 90-110 A and distributed on both concave and convex fracture faces with a frequency of 3,410 +/- 370 per μm(2) and 390 +/- 170 per μm(2), respectively. The larger diameters and three to fourfold smaller frequency of the intramembranous particles as compared to the surface particles seen after negative staining may reflect technical differences between methods, but it is more likely that the intramembranous particle is an oliogomer composed of two or even more of the protein units which form the surface particles.     

Prospects of partial root zone irrigation for increasing irrigation water use efficiency of major crops in the Mediterranean region

Field experiments were conducted for 3 years from 2000 to 2002 to assess proportional crop yield differences obtained under conventional deficit irrigation (CDI) and partial root zone irrigation (PRI) practices, compared with full irrigation (FULL) where plant water requirements were fully met. The experimental crops included vegetables (tomato and pepper), field crops (maize and cotton) and citrus. The fruit yield of greenhouse‐grown tomato with FULL irrigation was higher than with PRI (7–22% lower) but was not significantly different. The PRI treatments had 7–10% additional tomato yield over CDI receiving the same amount of water. The yield of pepper, however, decreased in proportion to the level of irrigation deficit with no increase of irrigation water use efficiency (IWUE). No seed yield decrease was evident for cotton with the deficit treatments (PRI and CDI) compared with FULL irrigation. Similarly, the PRI treatment did not give any yield benefit for maize compared with CDI. The ranking of fruit yields of mandarin, FULL > PRI > CDI, was the same as that of other crops; however, the differences were not significant. Although the deficit treatments (PRI and CDI) had as high as 39% increase in IWUE, compared with FULL treatment, some adverse effects on fruit quality were evident such as smaller size of fruits under the deficit treatments.