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Search Results: 1 - 10 of 404549 matches for " Ronald M Adkins "
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Comparison of the accuracy of methods of computational haplotype inference using a large empirical dataset
Ronald M Adkins
BMC Genetics , 2004, DOI: 10.1186/1471-2156-5-22
Abstract: In contrast to some previous comparisons of haplotype inference methods, there was very little difference in the accuracy of the various methods in terms of either assignment of haplotypes to individuals or estimation of haplotype frequencies. Although none of the methods inferred all of the known haplotypes, the assignment of haplotypes to subjects was about 90% correct for individuals heterozygous for up to three SNPs and was about 80% correct for up to five heterozygous sites. All of the methods identified every haplotype with a frequency above 1%, and none assigned a frequency above 1% to an incorrect haplotype.All of the methods of haplotype inference have high accuracy and one can have confidence in inferences made by any one of the methods. The ability to identify even rare (≥ 1%) haplotypes is reassuring for efforts to identify haplotypes that contribute to disease in a significant proportion of a population. Assignment of haplotypes is relatively accurate among subjects heterozygous for up to 5 sites, and this might be the largest number of SNPs for which one should define haplotype blocks or have confidence in haplotype assignments.Very rapid and inexpensive methods exist for determining the genotype of diploid organisms at single nucleotide polymorphisms (SNPs). Unfortunately, these high-throughput methods do not provide direct information on which SNP alleles at multiple sites coexist on the same chromosome. Instead, computational methods must be employed to infer the set of SNP alleles that are cosegregating on a single chromosome, referred to as haplotypes. However, the inference of haplotypes from phase-unknown data is computationally difficult, partly due to the fact that the number of possible haplotypes roughly increases as a power of 2 with each additional SNP.Interest in the accurate inference of haplotype structure from unphased genotypic data has increased tremendously in recent years for several reasons. Relative to analysis of single polymorp
Association between fetal growth restriction and polymorphisms at sites -1 and +3 of pituitary growth hormone: a case-control study
Ronald M Adkins, Caroline Campese, Rehana Vaidya, Theonia K Boyd
BMC Pregnancy and Childbirth , 2005, DOI: 10.1186/1471-2393-5-2
Abstract: One hundred twenty-five subjects (83 control and 42 case) were selected using stringent inclusion/exclusion criteria. DNA sequencing was used to identify 26 single nucleotide polymorphisms in the pituitary growth hormone gene (GH1) at which all subjects were genotyped. Association with fetal growth restriction was tested by logistic regression for all sites with minor allele frequencies greater than 5%.Logistic regression identified significant association with fetal growth restriction of C alleles at sites -1 and +3 (relative to the start of transcription) that are in complete linkage disequilibrium. These alleles are present at higher frequency (6% vs. 0.4%) in fetal growth restricted subjects and are associated with an average reduction in birth weight of 152 g in normal birth weight and 97 g in low birth weight subjects.There is suggestive association between fetal growth restriction and the presence of C alleles at sites -1 and +3 of the pituitary growth hormone gene.Fetal growth restriction (FGR) is a major risk factor for illness in the perinatal period and throughout life, with the smallest 7.5 percent of infants accounting for two-thirds of infant deaths [1]. Term, low birth weight infants are at least five times more likely to die in the first year [2,3] and are second only to premature infants in their rates of morbidity and mortality [4]. FGR infants have an increased frequency of hypoglycemia, hypothermia, polycythemia, neurodevelopmental deficits, and cerebral palsy [5]. Later in life, individuals born FGR are at elevated risk of hypertension, cardiovascular disease, and non-insulin dependent diabetes [6]. For example, FGR increases the risk for adult onset of non-insulin dependent diabetes two- to three-fold [7,8]. The ability to both diagnose and treat FGR early in gestation has enormous potential to reduce childhood and adult illness.It is difficult to distinguish the genetic and environmental components of human birth weight variation, but recent s
Parental ages and levels of DNA methylation in the newborn are correlated
Ronald M Adkins, Fridtjof Thomas, Frances A Tylavsky, Julia Krushkal
BMC Medical Genetics , 2011, DOI: 10.1186/1471-2350-12-47
Abstract: Using a genome-wide survey of 27,578 CpG dinucleotides in a cohort of 168 newborns, we examined the relationship between DNA methylation in newborns and a variety of parental and newborn traits. We found that methylation levels of 144 CpGs belonging to 142 genes were significantly correlated with maternal age. A weaker correlation was observed with paternal age. Among these genes, processes related to cancer were over-represented, as were functions related to neurological regulation, glucose/carbohydrate metabolism, nucleocytoplasmic transport, and transcriptional regulation. CpGs exhibiting gender differences in methylation were overwhelmingly located on the X chromosome, although a small subset of autosomal CpGs were found in genes previously shown to exhibit gender-specific differences in methylation levels.These results indicate that there are differences in CpG methylation levels at birth that are related to parental age and that could influence disease risk in childhood and throughout life.DNA methylation is a normal, heritable epigenetic modification that down-regulates the expression of approximately 1/3 of human genes [1-3] and is key to the allele-specific imprinting of genes [4]. DNA methylation also plays an important role in disease. For example, overall DNA hypomethylation accompanied by gene-specific hypermethylation is a hallmark of cancer [5]. Additionally, shifts in DNA methylation patterns appear to be involved in the normal aging process and increase in disease susceptibility [6]. Indeed, there is ample evidence for characteristic changes in the patterns of DNA methylation with age.The earliest data supporting progressive changes in DNA methylation patterns with age came from global studies of blood that demonstrated lower levels of methylation in older individuals [7] and greater differences in methylation in older monozygotic twins [8]. Christensen et al. [9] examined 217 tissues sampled from a range of non-diseased solid tissues and blood. In
Genome-wide analysis of the RpoN regulon in Geobacter sulfurreducens
Ching Leang, Julia Krushkal, Toshiyuki Ueki, Marko Puljic, Jun Sun, Katy Juárez, Cinthia Nú?ez, Gemma Reguera, Raymond DiDonato, Bradley Postier, Ronald M Adkins, Derek R Lovley
BMC Genomics , 2009, DOI: 10.1186/1471-2164-10-331
Abstract: An rpoN deletion mutant could not be obtained under all conditions tested. In order to investigate the regulon of the G. sulfurreducens RpoN, an RpoN over-expression strain was made in which an extra copy of the rpoN gene was under the control of a taclac promoter. Combining both the microarray transcriptome analysis and the computational prediction revealed that the G. sulfurreducens RpoN controls genes involved in a wide range of cellular functions. Most importantly, RpoN controls the expression of the dcuB gene encoding the fumarate/succinate exchanger, which is essential for cell growth with fumarate as the terminal electron acceptor in G. sulfurreducens. RpoN also controls genes, which encode enzymes for both pathways of ammonia assimilation that is predicted to be essential under all growth conditions in G. sulfurreducens. Other genes that were identified as part of the RpoN regulon using either the computational prediction or the microarray transcriptome analysis included genes involved in flagella biosynthesis, pili biosynthesis and genes involved in central metabolism enzymes and cytochromes involved in extracellular electron transfer to Fe(III), which are known to be important for growth in subsurface environment or electricity production in microbial fuel cells. The consensus sequence for the predicted RpoN-regulated promoter elements is TTGGCACGGTTTTTGCT.The G. sulfurreducens RpoN is an essential sigma factor and a global regulator involved in a complex transcriptional network controlling a variety of cellular processes.RpoN (σ54 or sigma 54) is a subunit of the RNA polymerase and plays a critical role in the regulation of gene expression by recognizing specific promoter elements and initiating transcription. RpoN-dependent promoters do not have conserved -35 and -10 elements typically found in the promoters recognized by sigma factors in the σ70 family. Instead, a GG dinucleotide around position -24 and a GC dinucleotide around position -12 with respect
Breeding Experience, Alternative Reproductive Strategies and Reproductive Success in a Captive Colony of Zebra Finches (Taeniopygia guttata)
Nicole M. Baran, Elizabeth Adkins-Regan
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089808
Abstract: Birds exhibit a remarkable diversity of different reproductive strategies both between and within species. Species such as the zebra finch (Taeniopygia guttata) may evolve the flexible use of alternative reproductive strategies, as well as benefit from prior breeding experience, which allows them to adaptively respond to unpredictable environments. In birds, the flexible use of alternative reproductive strategies, such as extra-pair mating, has been reported to be associated with fast reproduction, high mortality and environmental variability. However, little is known about the role of previous breeding experience in the adaptive use of alternative reproductive strategies. Here we performed an in-depth study of reproductive outcomes in a population of domesticated zebra finches, testing the impact of prior breeding experience on the use of alternative reproductive strategies and reproductive success. We provide evidence that older females with prior breeding experience are quicker to initiate a clutch with a new partner and have increased success in chick rearing, even in a captive colony of zebra finches with minimal foraging demands. We also find evidence that the breeding experience of other females in the same social group influences reproductive investment by female zebra finches. Furthermore, we demonstrate that the use of alternative reproductive strategies in female zebra finches is associated with previous failed breeding attempts with the same pair partner. The results provide evidence that age and breeding experience play important roles in the flexible use of both facultative and adaptive reproductive strategies in female zebra finches.
Use of the Internal Transcribed Spacer (ITS) Regions to Examine Symbiont Divergence and as a Diagnostic Tool for Sodalis-Related Bacteria
Anna K. Snyder,Kenneth Z. Adkins,Rita V. M. Rio
Insects , 2011, DOI: 10.3390/insects2040515
Abstract: Bacteria excel in most ecological niches, including insect symbioses. A cluster of bacterial symbionts, established within a broad range of insects, share high 16S rRNA similarities with the secondary symbiont of the tsetse fly (Diptera: Glossinidae), Sodalis glossinidius. Although 16S rRNA has proven informative towards characterization of this clade, the gene is insufficient for examining recent divergence due to selective constraints. Here, we assess the application of the internal transcribed spacer (ITS) regions, specifically the ITS glu and ITS ala,ile, used in conjunction with 16S rRNA to enhance the phylogenetic resolution of Sodalis-allied bacteria. The 16S rRNA + ITS regions of Sodalis and allied bacteria demonstrated significant divergence and were robust towards phylogenetic resolution. A monophyletic clade of Sodalis isolates from tsetse species, distinct from other Enterobacteriaceae, was consistently observed suggesting diversification due to host adaptation. In contrast, the phylogenetic distribution of symbionts isolated from hippoboscid flies and various Hemiptera and Coleoptera were intertwined suggesting either horizontal transfer or a recent establishment from an environmental source. Lineage splitting of Sodalis-allied bacteria into symbiotic and free-living sister groups was also observed. Additionally, we propose an ITS region as a diagnostic marker for the identification of additional Sodalis-allied symbionts in the field. These results expand our knowledge of informative genome regions to assess genetic divergence since splitting from the last common ancestor, of this versatile insect symbiont clade that have become increasingly recognized as valuable towards our understanding of the evolution of symbiosis. These facultative and recently associated symbionts may provide a novel source of traits adaptable to the dynamic ecologies encountered by diverse host backgrounds.
Computation of haplotypes on SNPs subsets: advantage of the "global method"
Cédric Coulonges, Olivier Delaneau, Manon Girard, Hervé Do, Ronald Adkins, Jean-Louis Spadoni, Jean-Fran?ois Zagury
BMC Genetics , 2006, DOI: 10.1186/1471-2156-7-50
Abstract: We used empirical haplotypes data sets from the GH1 promoter and the APOE gene, and 10 simulated datasets, and randomly introduced in them missing information (from 0% up to 20%) to compare the 2 methods. For each method, we used the PHASE haplotyping software since it was described to be the best. We showed that the use of the "global method" for subhaplotyping leads always to a better error rate than the classical direct haplotyping. The advantage provided by this alternative method increases with the percentage of missing genotyping data (diminution of the average error rate from 25% to less than 10%). We applied the global method software on the GRIV cohort for AIDS genetic associations and some associations previously identified through direct subhaplotyping were found to be erroneous.The global method for subhaplotyping can reduce, sometimes dramatically, the error rate on patient resolutions and haplotypes frequencies. One should thus use this method in order to minimise the risk of a false interpretation in genetic studies involving subhaplotypes. In practice the global method is always more efficient than the direct method, but a combination method taking into account the level of missing information in each subject appears to be even more interesting when the level of missing information becomes larger (>10%).Large-scale genomic studies are becoming a standard nowadays. The exploitation of this huge body of data leads to multiple biological applications and in particular, to the unraveling of new molecular mechanisms for diseases through the identification of genetic associations. Genetic association studies are based on the comparison of genetic markers, the most frequent ones being Single Nucleotide Polymorphisms (or SNPs), between a diseased group versus a healthy group (case-control study). If a statistically significant difference is observed in the frequency of a SNP allele between a group of patients and a group of control subjects, it could mean th
3-D Modeling of Axial Fans  [PDF]
Ali Sahili, Bashar Zogheib, Ronald M. Barron
Applied Mathematics (AM) , 2013, DOI: 10.4236/am.2013.44088
Abstract:

In this paper we present a full-geometry Computational Fluid Dynamics (CFD) modeling of air flow distribution from an automotive engine cooling fan. To simplify geometric modeling and mesh generation, different solution domains have been considered, the Core model, the Extended-Hub model, and the Multiple Reference Frame (MRF) model. We also consider the effect of blockage on the flow and pressure fields. The Extended-Hub model simplifies meshing without compromising accuracy. Optimal locations of the computational boundary conditions have been determined for the MRF model. The blockage results in significant difference in pressure rise, and the difference increases with increasing flow rates. Results are in good agreement with data obtained from an experimental test facility. Finally, we consider Simplified Fan Models which simplifies geometric modeling and mesh generation and significantly reduce the amount of computer memory used and time needed to carry out the calculations. Different models are compared in regards to efficiency and accuracy. The effect of using data from different planes is considered to optimize performance. The effect of blockage on simplified models is also considered.

The World Health Organization Surgical Safety Checklist Improves Post-Operative Outcomes: A Meta-Analysis and Systematic Review  [PDF]
Christine S. M. Lau, Ronald S. Chamberlain
Surgical Science (SS) , 2016, DOI: 10.4236/ss.2016.74029
Abstract: Background: The incidence of in-hospital adverse events is about 10%, with a majority of these related to surgery, and nearly half considered preventable events. In attempts to improve patient safety, the World Health Organization (WHO) developed a checklist to be used at critical perioperative moments. This meta-analysis examines the impact of the WHO surgical safety checklist (SSC) on various patient outcomes. Methods: A comprehensive search of all published studies assessing the use of the WHO SSC in patients undergoing surgery was conducted. Studies using the WHO SSC in any surgical setting, with pre-implementation and post-implementation outcome data were included. The incidence of patient outcomes (total complications, surgical site infections, unplanned return to the operating room (OR) within 30 days, and overall mortality) and adherence to safety measures were analyzed. Results: 10 studies involving 51,125 patients (27,490 prior to implementation and 23,635 after implementation of the WHO SSC) were analyzed. The implementation of the WHO SSC significantly reduced the risk of total complications by 37.9%, surgical site infections by 45.5%, unplanned return to OR by 32.1%, and mortality by 15.3%. Increased adherence to safety measures including airway evaluation, use of pulse oximetry, prophylactic antibiotics when necessary, confirmation of patient name and surgical site, and sponge count was also observed. Conclusions: The use of the WHO SSC is associated with a significant reduction in post-operative complication rates and mortality. The WHO SSC is a valuable tool that should be universally implemented in all surgical centers and utilized in all surgical patients.
Maize Development: Cell Wall Changes in Leaves and Sheaths  [PDF]
Ronald D. Hatfield, Jane M. Marita
American Journal of Plant Sciences (AJPS) , 2017, DOI: 10.4236/ajps.2017.86083
Abstract: Developmental changes occur in maize (Zea mays L.) as it transitions from juvenile stages to the mature plant. Changes also occur as newly formed cells mature into adult cells. Maize leaf blades including the midribs and sheaths undergo cell wall changes as cells transition to fully mature cell types. As is common in grasses during cell wall maturation, the lignin in the plant tissue is acylated with p-coumarates (pCA). This work characterizes cell walls in maize that make up leaf blade, leaf midrib, and sheath tissues corresponding to tissue development. Maize plants grown in the greenhouse were harvested; leaf, leaf midrib, and sheath tissues from nodes 9 through 14 tissues were analyzed for cell wall composition. Cell wall carbohydrates varied with the type of maize tissue, but there was little change within a tissue type among the different nodes. Lignin concentrations were lowest in the leaf blade (70 - 88 g·kg-1 CW) followed by the sheath (123 - 140 g·kg-1 CW) and highest in the midrib (140 -
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