We analyzed 12 families with autosomal dominant early-onset Alzheimer' s disease (EOAD)for mutations in the coding region of the presenilin I (PSNLI) gene corresponding to the AD3 locus on chromosome 14q24.3. A total of eight missense mutations at codons 82, 115, 139, 163, 231, 264, 392, and 410 including six novel mutations, were identified in eight families. Cosegregation of the mutations with EOAD was confirmed in three families, one including 36 affected individuals. This study underlines the great allelic heterogeneity and the large distribution of the mutations within the PSNLI coding region. Our results support the notion that PSNLI is the major gene involved in autosomal dominant EOAD.

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We report eight cases of airway colonization by Geosmithia argillacea in patients with cystic fibrosis. This filamentous fungus, resembling members of the genera Penicillium and Paecilomyces, was identified by molecular analysis. All patients carried a mutation on each CFTR (cystic fibrosis transmembrane conductance regulator) allele, with at least one copy of the F508del mutation. The first isolation of this fungus occurred from F508del-homozygous patients at a younger age than in F508del-heterozygous patients. Before recovery of G. argillacea, all patients were treated with itraconazole; two of them had also received voriconazole for an Aspergillus fumigatus infection. However, antifungal susceptibility patterns showed high MICs of voriconazole for all isolates, and high MICs of amphotericin B and itraconazole for the majority of them, but mostly low minimum effective concentrations (MECs) of caspofungin. The appearance and persistence of G. argillacea in the airways were not associated with exacerbation of the disease. However, the clinical implications of G. argillacea, particularly in immunocompromised patients, remain a concern, particularly given recent observations suggesting that this fungus may also cause disseminated infections.

The Xlr (X‐chromosome linked, lymphocyte regulated) multigene family was previously found to determine, in the lymphoid cell lineage, the stage‐specific expression of a nuclear protein with a primary sequence suggestive of a transcriptional activator function. We report here the characterization of a second functional member of the Xlr gene family that is abundantly transcribed in testis in a tissue‐specific and developmentally regulated manner. The protein product of this newly identified gene, called Xmr (Xlr‐related, meiosis regulated), is located in the nuclei of spermatocytes, early in the prophase of the first meiotic division, and later becomes concentrated in the XY nuclear subregion where it is in particular associated with the axes of sex chromosomes. The Xmr protein provides a new tool for the investigation of sex chromosome behaviour during meiosis in mammals.

The potential benefits to health of antioxidant enzymes supplied either through dietary intake or supplementation is still a matter of controversy. The development of dietary delivery systems using wheat gliadin biopolymers as a natural carrier represents a new alternative. Combination of antioxidant enzymes with this natural carrier not only delayed their degradation (i.e. the superoxide dismutase, SOD) during the gastrointestinal digestive process, but also promoted, in vivo, the cellular defences by strengthening the antioxidant status. The effects of supplementation for 28 days with a standardized melon SOD extract either combined (Glisodin) or not with gliadin, were evaluated on various oxidative-stress biomarkers. As already described there was no change either in superoxide dismutase, catalase or glutathione peroxidase activities in blood circulation or in the liver following non-protected SOD supplementation. However, animals supplemented with Glisodin showed a significant elevation in circulated antioxidant enzymes activities, correlated with an increased resistance of red blood cells to oxidative stress-induced hemolysis. In the presence of Sin-1, a chemical donor of peroxynitrites, mitochondria from hepatocytes regularly underwent membrane depolarization as the primary biological event of the apoptosis cascade. Hepatocytes isolated from animals supplemented with Glisodin presented a delayed depolarization response and an enhanced resistance to oxidative stress-induced apoptosis. It is concluded that supplementation with gliadin-combined standardized melon SOD extract (Glisodin) promoted the cellular antioxidant status and protected against oxidative stress-induced cell death.

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