Genetic contribution of SCARB1 variants to lipid traits in African Blacks: A candidate gene association study

Background: High-density lipoprotein cholesterol (HDL-C) exerts many anti-atherogenic properties including its role in reverse cholesterol transport (RCT). Scavenger receptor class B member 1 (SCARB1) plays a key role in RCT by selective uptake of HDL cholesteryl esters. We aimed to explore the genetic contribution of SCARB1 to affecting lipid levels in African Blacks from Nigeria. Methods: We resequenced 13 exons and exon-intron boundaries of SCARB1 in 95 individuals with extreme HDL-C levels using Sanger method. Then, we genotyped 147 selected variants (78 sequence variants, 69 HapMap tagSNPs, and 2 previously reported relevant variants) in the entire sample of 788 African Blacks using either the iPLEX Gold or TaqMan methods. A total of 137 successfully genotyped variants were further evaluated for association with major lipid traits. Results: The initial gene-based analysis demonstrated evidence of association with HDL-C and apolipoprotein A-I (ApoA-I). The follow-up single-site analysis revealed nominal evidence of novel associations of nine common variants with HDL-C and/or ApoA-I (P < 0.05). The strongest association was between rs11057851 and HDL-C (P = 0.0043), which remained significant after controlling for multiple testing using false discovery rate. Rare variant association testing revealed a group of 23 rare variants (frequencies ≤1 %) associated with HDL-C (P = 0.0478). Haplotype analysis identified four SCARB1 regions associated with HDL-C (global P < 0.05). Conclusions: To our knowledge, this is the first report of a comprehensive association study of SCARB1 variations with lipid traits in an African Black population. Our results showed the consistent association of SCARB1 variants with HDL-C across various association analyses, supporting the role of SCARB1 in lipoprotein-lipid regulatory mechanism

Comprehensive evaluation of the association of APOE genetic variation with plasma lipoprotein traits in U.S. Whites and African Blacks

Although common APOE genetic variation has a major influence on plasma LDL-cholesterol, its role in affecting HDL-cholesterol and triglycerides is not well established. Recent genome-wide association studies suggest that APOE also affects plasma variation in HDL-cholesterol and triglycerides. It is thus important to resequence the APOE gene to identify both common and uncommon variants that affect plasma lipid profile. Here, we have sequenced the APOE gene in 190 subjects with extreme HDL-cholesterol levels selected from two well-defined epidemiological samples of U.S. non-Hispanic Whites (NHWs) and African Blacks followed by genotyping of identified variants in the entire datasets (623 NHWs, 788 African Blacks) and association analyses with major lipid traits. We identified a total of 40 sequence variants, of which 10 are novel. A total of 32 variants, including common tagSNPs (≥5% frequency) and all uncommon variants (<5% frequency) were successfully genotyped and considered for genotype-phenotype associations. Other than the established associations of APOE∗2 and APOE∗4 with LDL-cholesterol, we have identified additional independent associations with LDL-cholesterol. We have also identified multiple associations of uncommon and common APOE variants with HDL-cholesterol and triglycerides. Our comprehensive sequencing and genotype-phenotype analyses indicate that APOE genetic variation impacts HDL-cholesterol and triglycerides in addition to affecting LDL-cholesterol

Clustering Algorithms: Their Application to Gene Expression Data

Gene expression data hide vital information required to understand the biological process that takes place in a particular organism in relation to its environment. Deciphering the hidden patterns in gene expression data proffers a prodigious preference to strengthen the understanding of functional genomics. The complexity of biological networks and the volume of genes present increase the challenges of comprehending and interpretation of the resulting mass of data, which consists of millions of measurements; these data also inhibit vagueness, imprecision, and noise. Therefore, the use of clustering techniques is a first step toward addressing these challenges, which is essential in the data mining process to reveal natural structures and iden-tify interesting patterns in the underlying data. The clustering of gene expression data has been proven to be useful in making known the natural structure inherent in gene expression data, understanding gene functions, cellular processes, and subtypes of cells, mining useful information from noisy data, and understanding gene regulation. The other benefit of clustering gene expression data is the identification of homology, which is very important in vaccine design. This review examines the various clustering algorithms applicable to the gene expression data in order to discover and provide useful knowledge of the appropriate clustering technique that will guarantee stability and high degree of accuracy in its analysis procedure

Sciatalgia in a patient with a rare peripheral nerve sheath tumor: Differential diagnosis [Nadir gözlenen periferal sinir ki{dotless}li{dotless}f tümörlü hastada siyatalji]

Peripheral schwannomas may mimic lumbar discopathy, and may constitute an important cause of undefined radicular pain. A 64 year-old-woman complained of worsening intermittent, severe pain, and weakness in her feet. We have observed brightness around the sciatic nerve and a tumor was detected in the nerve sheath. Patient had severe neuropathic pain in her right leg in the postoperative period. After the failure of pharmacological treatment for neuropathic pain, nerve blocks were performed to lumbar sympathetic and dorsal root ganglia (DRG). Relief of pain lasted short after the DRG blockade, thus placement of a spinal cord stimulator (SCS) was planned. Eighty percent pain reduction was achieved with the application of SCS test electrode, therefore a SCS was implanted. The management of neuropathic pain was carried out with pain treatment according to the algorithm. In conclucion, interventional pain treatments should be kept in mind in similar cases. © 2011 by Türkiye Klinikleri

Chemical characterization of size-selected nanoparticles emitted by a gasoline direct injection engine: Impact of a catalytic stripper

This work combines laser desorption/ionization mass spectrometry (L2MS) and advanced statistical techniques to reveal the impact of a catalytic stripper (CS) on the chemical composition (at the molecular level) of a gasoline direct injection engine exhaust, and follow the evolution of size-dependent chemical characteristics over the whole particles size range (10–560 nm). The gas phase and polydisperse particles making up the exhaust are separated and sampled on distinct substrates using an original homebuilt two-filter system, while size-selected particles are collected using a cascade impactor and separated into 13 different size bins (smallest diameters 10–18 nm). We demonstrate that a fine molecular-level characterization of the exhaust particulate matter is necessary to assess the effect of the CS, especially for the smallest ultra-fine particles carrying the largest volatile fraction

Structural and chemical characterization of soot particles

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The evolution of the surface of the mineral schreibersite in prebiotic chemistry

We present a study of the reactions of the meteoritic mineral schreibersite (Fe, Ni)(3)P, focusing primarily on surface chemistry and prebiotic phosphorylation. In this work, a synthetic analogue of the mineral was synthesized by mixing stoichiometric proportions of elemental iron, nickel and phosphorus and heating in a tube furnace at 820 degrees C for approximately 235 hours under argon or under vacuum, a modification of the method of Skala and Drabek (2002). Once synthesized, the schreibersite was characterized to confirm the identity of the product as well as to elucidate the oxidation processes affecting the surface. In addition to characterization of the solid product, this schreibersite was reacted with water or with organic solutes in a choline chloride-urea deep eutectic mixture, to constrain potential prebiotic products. Major inorganic solutes produced by reaction of water include orthophosphate, phosphite, pyrophosphate and hypophosphate consistent with prior work on Fe3P corrosion. Additionally, schreibersite corrodes in water and dries down to form a deep eutectic solution, generating phosphorylated products, in this case phosphocholine, using this synthesized schreibersite.FWN – Publicaties zonder aanstelling Universiteit Leide

Structural and chemical characterization of soot particles

International audienceYe

Chemical and structural characterization of airplane soot and surrogates

International audienceYe