537 research outputs found
Runnin\u27 Wild / music by Harrington Harris; words by Joe Grey and Leo Wood
An Ebony Jazz Tune (Cover). Key of Bb. Cover: a caricature of a man running; [Back page missing]; Publisher: Leo Feist Inc. (New York); Also includes Dusting the Keys (J. Edward Killalea and Edward B. Claypoole) and River Shannon Moon (Walter Wallace Smith)https://egrove.olemiss.edu/sharris_d/1043/thumbnail.jp
Physicochemical properties of oat beta-glucan influence its LDL cholesterol lowering effect in human subjects
Clinical, Endoscopic, and Histologic Findings Distinguish Eosinophilic Esophagitis From Gastroesophageal Reflux Disease
Features of eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) overlap; because they cannot be differentiated based on eosinophil counts alone, it can be a challenge to distinguish between these disorders. We aimed to characterize the clinical, endoscopic, and histologic features of EoE and GERD and identify factors that might be used to differentiate them
Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association
The identification of multiple signals at individual loci could explain additional phenotypic variance (‘missing heritability’) of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work
Imputation of variants from the 1000 Genomes Project modestly improves known associations and can identify low-frequency variant-phenotype associations undetected by HapMap based imputation
notes: PMCID: PMC3655956This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Genome-wide association (GWA) studies have been limited by the reliance on common variants present on microarrays or imputable from the HapMap Project data. More recently, the completion of the 1000 Genomes Project has provided variant and haplotype information for several million variants derived from sequencing over 1,000 individuals. To help understand the extent to which more variants (including low frequency (1% ≤ MAF <5%) and rare variants (<1%)) can enhance previously identified associations and identify novel loci, we selected 93 quantitative circulating factors where data was available from the InCHIANTI population study. These phenotypes included cytokines, binding proteins, hormones, vitamins and ions. We selected these phenotypes because many have known strong genetic associations and are potentially important to help understand disease processes. We performed a genome-wide scan for these 93 phenotypes in InCHIANTI. We identified 21 signals and 33 signals that reached P<5×10(-8) based on HapMap and 1000 Genomes imputation, respectively, and 9 and 11 that reached a stricter, likely conservative, threshold of P<5×10(-11) respectively. Imputation of 1000 Genomes genotype data modestly improved the strength of known associations. Of 20 associations detected at P<5×10(-8) in both analyses (17 of which represent well replicated signals in the NHGRI catalogue), six were captured by the same index SNP, five were nominally more strongly associated in 1000 Genomes imputed data and one was nominally more strongly associated in HapMap imputed data. We also detected an association between a low frequency variant and phenotype that was previously missed by HapMap based imputation approaches. An association between rs112635299 and alpha-1 globulin near the SERPINA gene represented the known association between rs28929474 (MAF = 0.007) and alpha1-antitrypsin that predisposes to emphysema (P = 2.5×10(-12)). Our data provide important proof of principle that 1000 Genomes imputation will detect novel, low frequency-large effect associations
VERITAS Observations of the gamma-Ray Binary LS I +61 303
LS I +61 303 is one of only a few high-mass X-ray binaries currently detected
at high significance in very high energy gamma-rays. The system was observed
over several orbital cycles (between September 2006 and February 2007) with the
VERITAS array of imaging air-Cherenkov telescopes. A signal of gamma-rays with
energies above 300 GeV is found with a statistical significance of 8.4 standard
deviations. The detected flux is measured to be strongly variable; the maximum
flux is found during most orbital cycles at apastron. The energy spectrum for
the period of maximum emission can be characterized by a power law with a
photon index of Gamma=2.40+-0.16_stat+-0.2_sys and a flux above 300 GeV
corresponding to 15-20% of the flux from the Crab Nebula.Comment: accepted for publication in The Astrophysical Journa
Heritability and Phenotypic Variation of Canine Hip Dysplasia Radiographic Traits in a Cohort of Australian German Shepherd Dogs
Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14–0.24 (ordinal models), 0.14–0.25 (linear models) and 0.12–0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30±0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals
Resonant nonlinear magneto-optical effects in atoms
In this article, we review the history, current status, physical mechanisms,
experimental methods, and applications of nonlinear magneto-optical effects in
atomic vapors. We begin by describing the pioneering work of Macaluso and
Corbino over a century ago on linear magneto-optical effects (in which the
properties of the medium do not depend on the light power) in the vicinity of
atomic resonances, and contrast these effects with various nonlinear
magneto-optical phenomena that have been studied both theoretically and
experimentally since the late 1960s. In recent years, the field of nonlinear
magneto-optics has experienced a revival of interest that has led to a number
of developments, including the observation of ultra-narrow (1-Hz)
magneto-optical resonances, applications in sensitive magnetometry, nonlinear
magneto-optical tomography, and the possibility of a search for parity- and
time-reversal-invariance violation in atoms.Comment: 51 pages, 23 figures, to appear in Rev. Mod. Phys. in Oct. 2002,
Figure added, typos corrected, text edited for clarit
Integration of GWAS SNPs and tissue specific expression profiling reveal discrete eQTLs for human traits in blood and brain
Our knowledge of the transcriptome has become much more complex since the days of
the central dogma of molecular biology. We now know that splicing takes place to
create potentially thousands of isoforms from a single gene, and we know that RNA
does not always faithfully recapitulate DNA if RNA editing occurs. Collectively, these
observations show that the transcriptome is amazingly rich with intricate regulatory
mechanisms for overall gene expression, splicing, and RNA editing.
Genetic variability can play a role in controlling gene expression, which can be
identified by examining expression quantitative trait loci (eQTLs). eQTLs are genomic
regions where genetic variants, including single nucleotide polymorphisms (SNPs)
show a statistical association with expression of mRNA transcripts. In humans, many
SNPs are also associated with disease, and have been identified using genome wide
association studies (GWAS) but the biological effects of those SNPs are usually not
known. If SNPs found in GWAS are also found in eQTLs, then one could hypothesize
that expression levels may contribute to disease risk. Performing eQTL analysis with
GWAS SNPs in both blood and brain, specifically the frontal cortex and the
cerebellum, we found both shared and tissue unique eQTLS. The identification of
tissue-unique eQTLs supports the argument that choice of tissue type is important in
eQTL studies (Paper I).
Aging is a complex process with the mechanisms underlying aging still being poorly
defined. There is evidence that the transcriptome changes with age, and hence we used
the brain dataset from our first paper as a discovery set, with an additional replication
dataset, to investigate any aging-gene expression associations. We found evidence that
many genes were associated with aging. We further found that there were more
statically significant expression changes in the frontal cortex versus the cerebellum,
indicating that brain regions may age at different rates. As the brain is a heterogeneous
tissue including both neurons and non-neuronal cells, we used LCM to capture Purkinje
cells as a representative neuronal type and repeated the age analysis. Looking at the
discovery, replication and Purkinje cell datasets we found five genes with strong,
replicated evidence of age-expression associations (Paper II).
Being able to capture and quantify the depth of the transcriptome has been a lengthy
process starting with methods that could only measure a single gene to genome-wide
techniques such as microarray. A recently developed technology, RNA-Seq, shows
promise in its ability to capture expression, splicing, and editing and with its broad
dynamic range quantification is accurate and reliable. RNA-Seq is, however, data
intensive and a great deal of computational expertise is required to fully utilize the
strengths of this method. We aimed to create a small, well-controlled, experiment in
order to test the performance of this relatively new technology in the brain. We chose
embryonic versus adult cerebral cortex, as mice are genetically homogenous and there
are many known differences in gene expression related to brain development that we
could use as benchmarks for analysis testing. We found a large number of differences
in total gene expression between embryonic and adult brain. Rigorous technical and
biological validation illustrated the accuracy and dynamic range of RNA-Seq. We were also able to interrogate differences in exon usage in the same dataset. Finally we
were able to identify and quantify both well-known and novel A-to-I edit sites. Overall
this project helped us develop the tools needed to build usable pipelines for RNA-Seq
data processing (Paper III).
Our studies in the developing brain (Paper III) illustrated that RNA-Seq was a useful
unbiased method for investigating RNA editing. To extend this further, we utilized a
genetically modified mouse model to study the transcriptomic role of the RNA editing
enzyme ADAR2. We found that ADAR2 was important for editing of the coding
region of mRNA as a large proportion of RNA editing sites in coding regions had a
statistically significant decrease in editing percentages in Adar2
-/-Gria2
R/R
mice versus
controls. However, despite indications in the literature that ADAR2 may also be
involved in splicing and expression regulatory machinery we found no changes in gene
expression or exon utilization in Adar2
-/-Gria2
R/R
mice as compared to their littermate
controls (Paper IV).
In our final study, based on the methods developed in Papers III and IV, we revisited
the idea of age related gene expression associations from Paper II. We used a subset of
human frontal cortices for RNA sequencing. Interestingly we found more gene
expression changes with aging compared to the previous data using microarrays in
Paper II. When the significant gene lists were analysed for gene ontology enrichment,
we found that there was a large number of downregulated genes involved in synaptic
function while those that were upregulated had enrichment in immune function. This
dataset illustrates that the aging brain may be predisposed to the processes found in
neurodegenerative diseases (Paper V)
VERITAS Upper Limit on the VHE Emission from the Radio Galaxy NGC 1275
The recent detection by the Fermi gamma-ray space telescope of high-energy
gamma-rays from the radio galaxy NGC 1275 makes the observation of the very
high energy (VHE: E > 100 GeV) part of its broadband spectrum particularly
interesting, especially for the understanding of active galactic nuclei (AGN)
with misaligned multi-structured jets. The radio galaxy NGC 1275 was recently
observed by VERITAS at energies above 100 GeV for about 8 hours. No VHE
gamma-ray emission was detected by VERITAS from NGC 1275. A 99% confidence
level upper limit of 2.1% of the Crab Nebula flux level is obtained at the
decorrelation energy of approximately 340 GeV, corresponding to 19% of the
power-law extrapolation of the Fermi Large Area Telescope (LAT) result.Comment: Accepted for publication in ApJ Letter
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