Haplotype analysis of APOE intragenic SNPs

BACKGROUND: APOE epsilon4 allele is most common genetic risk factor for Alzheimer\u27s disease (AD) and cognitive decline. However, it remains poorly understood why only some carriers of APOE epsilon4 develop AD and how ethnic variabilities in APOE locus contribute to AD risk. Here, to address the role of APOE haplotypes, we reassessed the diversity of APOE locus in major ethnic groups and in Alzheimer\u27s Disease Neuroimaging Initiative (ADNI) dataset on patients with AD, and subjects with mild cognitive impairment (MCI), and control non-demented individuals. RESULTS: We performed APOE gene haplotype analysis for a short block of five SNPs across the gene using the ADNI whole genome sequencing dataset. The compilation of ADNI data with 1000 Genomes identified the APOE epsilon4 linked haplotypes, which appeared to be distant for the Asian, African and European populations. The common European epsilon4-bearing haplotype is associated with AD but not with MCI, and the Africans lack this haplotype. Haplotypic inference revealed alleles that may confer protection against AD. By assessing the DNA methylation profile of the APOE haplotypes, we found that the AD-associated haplotype features elevated APOE CpG content, implying that this locus can also be regulated by genetic-epigenetic interactions. CONCLUSIONS: We showed that SNP frequency profiles within APOE locus are highly skewed to population-specific haplotypes, suggesting that the ancestral background within different sites at APOE gene may shape the disease phenotype. We propose that our results can be utilized for more specific risk assessment based on population descent of the individuals and on higher specificity of five site haplotypes associated with AD

Liver damage in children and adolescents with newly diagnosed celiac disease: clinical and anamnestic, serological and morphological patterns

Hypertransaminasemia is a common extra-intestinal manifestation of celiac disease. Aim. To analyze the frequency of hypertransaminasemia, clinical and anamnestic, serological and morphological picture in children in the active period of celiac disease. Materials and methods. The study included 272 children with celiac disease aged from 8 months to 17 years. The patients were divided into two groups: the first children with hypertransaminasemia, the second without hypertransaminasemia. Results. Hypertransaminasemia was detected in 55.9% of children with celiac disease. The age of manifestation of the disease in the first group was 1.0 [0.5; 2.0] years, in the second group 1.9 [0.5; 4.0] years (p=0.0004). Children of the first group were diagnosed at 2.5 [1.7; 4.9] years, the second group at 4.9 [3.0; 10.8] years (p0.001). The duration of the latency period in children of the first and second groups was 1.4 [0.6; 3.1] years and 2.4 [0.9; 4.3] years, respectively (p=0.002). The average values of IgA anti-tTG antibodies in children of the analyzed groups did not differ, and the indicators of IgG anti-tTG antibodies in the first group were 1.6 (p=0.04) times higher. The level of EMA in children with hypertransaminasemia was 2 times higher than in children without hypertransaminasemia. Conclusion. Hypertransaminasemia is more often detected in young children with early manifestation of the disease, increases with the deepening of atrophy in the mucous membrane of the small intestine. Higher titers of celiac-specific antibodies were detected in children with hypertransaminasemia

The ALICE experiment at the CERN LHC

ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries. Its overall dimensions are 161626 m3 with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008

Pump-Intensity- and Shell-Thickness-Dependent Evolution of Photoluminescence Blinking in Individual Core/Shell CdSe/CdS Nanocrystals

We report a systematic study of photoluminescence (PL) intensity and lifetime fluctuations in individual CdSe/CdS core/shell nanocrystal quantum dots (NQDs) as a function of shell thickness. We show that while at low pump intensities PL blinking in thin-shell (4–7 monolayers, MLs) NQDs can be described by random switching between two states of high (ON) and low (OFF) emissivities, it changes to the regime with a continuous distribution of ON intensity levels at high pump powers. A similar behavior is observed in samples with a medium shell thickness (10–12 MLs) without, however, the PL intensity ever switching to a complete “OFF” state and maintaining ca. 30% emissivity (“gray” state). Further, our data indicate that highly stable, blinking-free PL of thick-shell (15–19 MLs) NQDs (“giant” or g-NQDs) is characterized by nearly perfect Poisson statistics, corresponding to a narrow, shot-noise limited PL intensity distribution. Interestingly, in this case the PL lifetime shortens with increasing pump power and the PL decay may deviate from monoexponential. However, the PL intensity distribution remains shot-noise limited, indicating the absence of significant quantum yield fluctuations at a given pump power intensity during the experimental time window

Nanocrystal quantum dots: building blocks for tunable optical amplifiers and lasers

We study optical processes relevant to optical amplification and lasing in CdSe nanocrystal quantum dots (NQD). NQDs are freestanding nanoparticles prepared using solution-based organometallic reactions originally developed for the Cd chalcogenides, CdS, CdSe and CdTe [J. Am. Chem. Soc. 115, 8706 (1993)]. We investigate NQDs with diameters ranging from 2 to 8 nm. Due to strong quantum confinement, they exhibit size-dependent spectral tunability over an energy range as wide as several hundred meV. We observe a strong effect of the matrix/solvent on optical gain properties of CdSe NQDs. In most of the commonly used solvents (such as hexane and toluene), gain is suppressed due to strong photoinduced absorption associated with carriers trapped at solvent-related interface states. In contrast, matrix-free close packed NQD films (NQD solids) exhibit large optical gain with a magnitude that is sufficiently high for the optical gain to successfully compete with multiparticle Auger recombination [Science 287, 10117 (2000)]. These films exhibit narrowband stimulated emission at both cryogenic and room temperature, and the emission color is tunable with dot size [Science 290, 314 (2000)]. Moreover, the NQD films can be incorporated into microcavities of different geometries (micro-spheres, wires, tubes) that produce lasing in whispering gallery modes. The facile preparation, chemical flexibility and wide-range spectral tunability due to strong quantum confinement are the key advantages that should motivate research into NQD applications in optical amplifiers and lasers