Cerebral amyloid load determination in a clinical setting: interpretation of amyloid biomarker discordances aided by tau and neurodegeneration measurements

Neurological Sciences - Alzheimer’s disease (AD) diagnosis can be hindered by amyloid biomarkers discordances. We aim to interpret discordances between amyloid positron emission tomography...     

Fetal phenotypes in otopalatodigital spectrum disorders

Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick–Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra‐skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families.     

Angiotensin converting enzyme insertion/deletion polymorphism in sporadic and familial Alzheimer's disease and longevity

A recent, large meta-analysis has reproposed the role of the angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism as a risk factor for Alzheimer's disease (AD). To further investigate the proposed association and to better clarify the role of ACE as a risk factor for AD, we analyzed the genotype and allele frequency distribution of ACE I/D and apolipoprotein E (APOE) gene polymorphisms in 235 Italian patients with sporadic AD, 153 with familial AD (FAD), 192 healthy controls and 111 centenarians. Patients with AD were consecutively gathered from among the outpatients from the Neurology Department at the University of Florence. All 691 subjects were genotyped for ACE and APOE polymorphisms. There were no significant differences in ACE genotypes or allele frequencies in all the studied groups, even after stratification for APOE epsilon4 carrier status. Centenarians show the highest allele D frequency, although the value is not significant, thus suggesting a possible implication of the D allele as an epistatic allele that has pleiotropic age-dependent effects. In conclusion, our data suggest that the ACE allelic variant is not a susceptibility factor in sporadic and familial AD (FAD), nor does it mitigate the effect of the APOE epsilon4 allele in the risk of developing AD. Moreover, our data do not suggest a possible involvement of the D allele in longevity.     

Genotoxicity of hazardous leachates from solid wastes evaluated for environmental impact with the ames test

Fourteen series of toxic wastes from various origins (metallurgy, chemical industries, incinerators, industrial treatment plants, etc.) have been studied for their genotoxic properties with the Salmonella reversion assay. To consider realism of environmental impact, a strategy is proposed to assess genotoxicity of the water-soluble fraction of the wastes. Water-extractable micropollutants were further concentrated by liquid–liquid extraction or lyophilization prior to genotoxicity testing. None of the 14 crude aqueous fractions was shown to be mutagenic. On the contrary, positive responses were registered on the concentrated phases of two solid wastes derived from one chemical industry and from the treatment of organophosphorus wastewaters. Chemical analysis did not reveal the presence of known mutagens in the positive extracts. Interacting effects between micropollutants is thus hypothesized to explain genotoxicity.     

Delivery devices for exposure of biological cells to nanosecond pulsed electric fields

In this paper, delivery devices for nanosecond pulsed electric field exposure of biological samples in direct contact with electrodes or isolated are presented and characterized. They are based on a modified electroporation cuvette and two transverse electromagnetic cells (TEM cells). The devices were used to apply pulses with high intensity (4.5 kV) and short durations (3 and 13 ns). The delivery devices were electromagnetically characterized in the frequency and time domains. Field intensities of around 5, 0.5, and 12 MV m^?1 were obtained by numerical simulations of the biological sample positioned in the three delivery devices. Two delivery systems had a homogenous electric field spatial distribution, and one was adapted to permit a highly localized exposure in the vicinity of a needle. Experimental biological investigations were carried out at different field intensities for five cancer cell lines. The results using flow cytometry showed that cells kept polarized mitochondrial membrane but lost plasma membrane integrity following a dose–response trend after exposure to different electric field intensities. Certain cell types (U87, MCF7) showed higher sensitivities to nsPEFs than other lines tested.