53 research outputs found
Identification of novel high-impact recessively inherited type 2 diabetes risk variants in the Greenlandic population
Static charged perfect fluid spheres in general relativity
Interior perfect fluid solutions for the Reissner-Nordstrom metric are
studied on the basis of a new classification scheme. General formulas are found
in many cases. Explicit new global solutions are given as illustrations. Known
solutions are briefly reviewed.Comment: 23 pages, Revtex (galley), journal version, to appear in Phys.Rev.
Investigation of the genetic interaction between BDNF and DRD3 genes in suicidical behaviour in psychiatric disorders
Suicide is a serious public health concern, and it is partly genetic. The brain-derived neurotrophic factor (BDNF) gene has been a strong candidate in genetic studies of suicide (Zai et al, 2012; Dwivedi et al, 2010) and BDNF regulates the expression of the dopamine D3 receptor
The genetic determinants of recurrent somatic mutations in 43,693 blood genomes
Nononcogenic somatic mutations are thought to be uncommon and inconsequential. To test this, we analyzed 43,693 National Heart, Lung and Blood Institute Trans-Omics for Precision Medicine blood whole genomes from 37 cohorts and identified 7131 non-missense somatic mutations that are recurrently mutated in at least 50 individuals. These recurrent non-missense somatic mutations (RNMSMs) are not clearly explained by other clonal phenomena such as clonal hematopoiesis. RNMSM prevalence increased with age, with an average 50-year-old having 27 RNMSMs. Inherited germline variation associated with RNMSM acquisition. These variants were found in genes involved in adaptive immune function, proinflammatory cytokine production, and lymphoid lineage commitment. In addition, the presence of eight specific RNMSMs associated with blood cell traits at effect sizes comparable to Mendelian genetic mutations. Overall, we found that somatic mutations in blood are an unexpectedly common phenomenon with ancestry-specific determinants and human health consequences
Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed
Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes
Genetic diversity fuels gene discovery for tobacco and alcohol use
Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe
Hierarchical cystine flower based electrochemical genosensor for detection of Escherichia coli O157:H7
This work reports on a facile and reproducible approach to synthesize novel organic flowers of cystine (CysFls) with high uniformity. These 3D flower-like structures have a purely hierarchical arrangement, wherein each petal is composed of several cystine molecules with an average size of 50 mu M, as determined by transmission electron microscopy. The CysFls were self-assembled onto a gold electrode and were utilized as matrices for the covalent immobilization of an Escherichia coli O157:H7 (E. coli) specific probe oligonucleotide that was identified from the 16s rRNA coding region of the E. coli genome. This fabricated CysFl platform sought to provide improved fundamental characteristics to electrode interface in terms of electro-active surface area and diffusion coefficient. Electrochemical impedance spectroscopy revealed that this genosensor exhibits a linear response to complementary DNA in the concentration range of 10(-6) to 10(-15) M with a detection limit of 1 x 10(-15) M. Under optimal conditions, this genosensor was found to retain about 88% of its initial activity after being used for 6 times
Electrochemical detection of a pathogenic Escherichia coli specific DNA sequence based on a graphene oxide-chitosan composite decorated with nickel ferrite nanoparticles
In this report, an electrochemical genosensor has been fabricated for Escherichia coli O157:H7 (E. coli) detection using a graphene oxide-nickel ferrite-chitosan (GO/NiF/ch) nanocomposite film as the sensing platform. The prepared GO/NiF/ch nanocomposite was characterized by scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, Fourier transform infrared spectroscopy and thermo-gravimetric analysis. Nucleic acid hybridization technique was employed for the detection of a specific sequence of E. coli. The hybridization between the complementary DNA and probe DNA was investigated by differential pulse voltammetry (DPV) using methylene blue as redox indicator. The fabricated biosensor exhibits a linear response to complementary DNA in the concentration range of 10(-6) to 10(-16) M with a detection limit of 1 x 10(-16) M
Copper oxide assisted cysteine hierarchical structures for immunosensor application
The present work describes the promising electrochemical immunosensing strategy based on copper (II) assisted hierarchical cysteine structures (CuCys) varying from star to flower like morphology. The CuCys having average size of 10 mu m have been synthesised using L-Cysteine as initial precursor in presence of copper oxide under environmentally friendly conditions in aqueous medium. To delineate the synthesis mechanism, detailed structural investigations have been carried out using characterization techniques such as X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy. The electrochemical behaviour of self-assembled CuCys on gold electrode shows surface controlled electrode reaction with an apparent electron transfer rate constant of 3.38 x 10(-4) cm s(-1). This innovative platform has been utilized to fabricate an immunosensor by covalently immobilizing monoclonal antibodies specific for Escherichia coli O157:H7 (E. coli). Under the optimal conditions, the fabricated immunosensor is found to be sensitive and specific for the detection of E. coli with a detection limit of 10 cfu/ml. (C) 2014 AIP Publishing LL
Nanostructuring of hierarchical 3D cystine flowers for high-performance electrochemical immunosensor
Here, we report a simple and reproducible method for large scale fabrication of novel flower and palm-leaf like 3D cystine microstructures (CMs) with high uniformity having a size of 50 gm and 10 gm respectively, through a facile aqueous solution route as a function of pH and concentration. In a proof-of-concept study, the 3D CMs have been further explored to fabricate a label-free high-performance electrochemical immunosensor by immobilizing monoclonal antibodies. Electrochemical methods were employed to study the stepwise modification of the system and the electronic transduction for the detection. The fabricated immunosensor design demonstrates high performance with enhanced sensitivity (4.70 cfu ml(-1)) and linear sensing range from 10 to 3 x 10(9) cfu ml(-1) a long shelf-life (35 days) and high selectivity over other bacterial pathogens. The enhanced performance originates from a novel nanostructuring in which the CMs provide higher surface coverage for the immobilization of antibodies providing excellent electronic/ionic conductivity which result in the enhanced sensitivity
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