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Search Results: 1 - 10 of 488564 matches for " Daniel A Pollard "
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Widespread Discordance of Gene Trees with Species Tree in Drosophila: Evidence for Incomplete Lineage Sorting
Daniel A Pollard,Venky N Iyer equal contributor,Alan M Moses equal contributor,Michael B Eisen
PLOS Genetics , 2006, DOI: 10.1371/journal.pgen.0020173
Abstract: The phylogenetic relationship of the now fully sequenced species Drosophila erecta and D. yakuba with respect to the D. melanogaster species complex has been a subject of controversy. All three possible groupings of the species have been reported in the past, though recent multi-gene studies suggest that D. erecta and D. yakuba are sister species. Using the whole genomes of each of these species as well as the four other fully sequenced species in the subgenus Sophophora, we set out to investigate the placement of D. erecta and D. yakuba in the D. melanogaster species group and to understand the cause of the past incongruence. Though we find that the phylogeny grouping D. erecta and D. yakuba together is the best supported, we also find widespread incongruence in nucleotide and amino acid substitutions, insertions and deletions, and gene trees. The time inferred to span the two key speciation events is short enough that under the coalescent model, the incongruence could be the result of incomplete lineage sorting. Consistent with the lineage-sorting hypothesis, substitutions supporting the same tree were spatially clustered. Support for the different trees was found to be linked to recombination such that adjacent genes support the same tree most often in regions of low recombination and substitutions supporting the same tree are most enriched roughly on the same scale as linkage disequilibrium, also consistent with lineage sorting. The incongruence was found to be statistically significant and robust to model and species choice. No systematic biases were found. We conclude that phylogenetic incongruence in the D. melanogaster species complex is the result, at least in part, of incomplete lineage sorting. Incomplete lineage sorting will likely cause phylogenetic incongruence in many comparative genomics datasets. Methods to infer the correct species tree, the history of every base in the genome, and comparative methods that control for and/or utilize this information will be valuable advancements for the field of comparative genomics.
MONKEY: identifying conserved transcription-factor binding sites in multiple alignments using a binding site-specific evolutionary model
Alan M Moses, Derek Y Chiang, Daniel A Pollard, Venky N Iyer, Michael B Eisen
Genome Biology , 2004, DOI: 10.1186/gb-2004-5-12-r98
Abstract: Different types of genomic features have characteristic patterns of evolution that, when sequences from closely related organisms are available, can be exploited to annotate genomes [1]. Methods for comparative sequence analysis that exploit variation in rates and patterns of nucleotide evolution can identify coding exons [1,2], noncoding sequences involved in the regulation of transcription [3,4] and various types of RNAs [5-7]. While most of these methods have been developed for and applied to pairwise comparisons, sequence data are increasingly available for multiple closely related species [8]. It is therefore of considerable importance to develop sequence-analysis methods that optimally exploit evolutionary information, and to explore the dependence of these methods on the evolutionary relationships of the species in comparison.Sequence-specific DNA-binding proteins involved in transcriptional regulation (transcription factors) play a central role in many biological processes. Despite extensive biochemical and molecular analysis, it remains exceedingly difficult to predict where on the genome a given factor will bind. Transcription factors bind to degenerate families of short (6-20 base-pairs (bp)) sequences that occur frequently in the genome, yet only a small fraction of these sequences are actually bona fide targets of the transcription factor [9]. A major challenge in understanding the regulation of transcription is to be able to distinguish real transcription factor binding sites (TFBSs) from sequences that simply match a factor's binding specificity. Because the evolutionary properties of TFBSs are expected to be different from their nonfunctional counterparts, comparative analyses hold great promise in helping to address this challenge.In the past few years, several methods have been introduced to identify conserved (and presumably functional) TFBSs for a factor of known specificity (in contrast to the larger set of methods that use comparative data in m
Detecting the limits of regulatory element conservation and divergence estimation using pairwise and multiple alignments
Daniel A Pollard, Alan M Moses, Venky N Iyer, Michael B Eisen
BMC Bioinformatics , 2006, DOI: 10.1186/1471-2105-7-376
Abstract: Here we develop a molecular evolution simulation platform, CisEvolver, with models of background noncoding and transcription factor binding site evolution, and use simulated alignments to systematically examine multiple alignment accuracy and its impact on two key molecular evolutionary inferences: transcription factor binding site conservation and divergence estimation. We find that the accuracy of multiple alignments is determined almost exclusively by the pairwise divergence distance of the two most diverged species and that additional species have a negligible influence on alignment accuracy. Conserved transcription factor binding sites align better than surrounding noncoding DNA yet are often found to be misaligned at relatively short divergence distances, such that studies of binding site gain and loss could easily be confounded by alignment error. Divergence estimates from multiple alignments tend to be overestimated at short divergence distances but reach a tool specific divergence at which they cease to increase, leading to underestimation at long divergences. Our most striking finding was that overall alignment accuracy, binding site alignment accuracy and divergence estimation accuracy vary greatly across branches in a tree and are most accurate for terminal branches connecting sister taxa and least accurate for internal branches connecting sub-alignments.Our results suggest that variation in alignment accuracy can lead to errors in molecular evolutionary inferences that could be construed as biological variation. These findings have implications for which species to choose for analyses, what kind of errors would be expected for a given set of species and how multiple alignment tools and phylogenetic inference methods might be improved to minimize or control for alignment errors.Annotation of cis-regulatory sequences, non-coding RNAs and other functional noncoding sequences is a major challenge in molecular genetics today. Whole genome sequences of closel
Benchmarking tools for the alignment of functional noncoding DNA
Daniel A Pollard, Casey M Bergman, Jens Stoye, Susan E Celniker, Michael B Eisen
BMC Bioinformatics , 2004, DOI: 10.1186/1471-2105-5-6
Abstract: Using rates of noncoding sequence evolution estimated from the genus Drosophila, we simulated alignments over a range of divergence times under varying models incorporating point substitution, insertion/deletion events, and short blocks of constrained sequences such as those found in cis-regulatory regions. We then compared "correct" alignments generated by a modified version of the ROSE simulation platform to alignments of the simulated derived sequences produced by eight pairwise alignment tools (Avid, BlastZ, Chaos, ClustalW, DiAlign, Lagan, Needle, and WABA) to determine the off-the-shelf performance of each tool. As expected, the ability to align noncoding sequences accurately decreases with increasing divergence for all tools, and declines faster in the presence of insertion/deletion evolution. Global alignment tools (Avid, ClustalW, Lagan, and Needle) typically have higher sensitivity over entire noncoding sequences as well as in constrained sequences. Local tools (BlastZ, Chaos, and WABA) have lower overall sensitivity as a consequence of incomplete coverage, but have high specificity to detect constrained sequences as well as high sensitivity within the subset of sequences they align. Tools such as DiAlign, which generate both local and global outputs, produce alignments of constrained sequences with both high sensitivity and specificity for divergence distances in the range of 1.25–3.0 substitutions per site.For species with genomic properties similar to Drosophila, we conclude that a single pair of optimally diverged species analyzed with a high performance alignment tool can yield accurate and specific alignments of functionally constrained noncoding sequences. Further algorithm development, optimization of alignment parameters, and benchmarking studies will be necessary to extract the maximal biological information from alignments of functional noncoding DNA.The increasing availability of genome sequences of related organisms offers myriad opportunities
Benchmarking tools for the alignment of functional noncoding DNA
Pollard Daniel A,Bergman Casey M,Stoye Jens,Celniker Susan E
BMC Bioinformatics , 2004,
Abstract: Background Numerous tools have been developed to align genomic sequences. However, their relative performance in specific applications remains poorly characterized. Alignments of protein-coding sequences typically have been benchmarked against "correct" alignments inferred from structural data. For noncoding sequences, where such independent validation is lacking, simulation provides an effective means to generate "correct" alignments with which to benchmark alignment tools. Results Using rates of noncoding sequence evolution estimated from the genus Drosophila, we simulated alignments over a range of divergence times under varying models incorporating point substitution, insertion/deletion events, and short blocks of constrained sequences such as those found in cis-regulatory regions. We then compared "correct" alignments generated by a modified version of the ROSE simulation platform to alignments of the simulated derived sequences produced by eight pairwise alignment tools (Avid, BlastZ, Chaos, ClustalW, DiAlign, Lagan, Needle, and WABA) to determine the off-the-shelf performance of each tool. As expected, the ability to align noncoding sequences accurately decreases with increasing divergence for all tools, and declines faster in the presence of insertion/deletion evolution. Global alignment tools (Avid, ClustalW, Lagan, and Needle) typically have higher sensitivity over entire noncoding sequences as well as in constrained sequences. Local tools (BlastZ, Chaos, and WABA) have lower overall sensitivity as a consequence of incomplete coverage, but have high specificity to detect constrained sequences as well as high sensitivity within the subset of sequences they align. Tools such as DiAlign, which generate both local and global outputs, produce alignments of constrained sequences with both high sensitivity and specificity for divergence distances in the range of 1.25–3.0 substitutions per site. Conclusion For species with genomic properties similar to Drosophila, we conclude that a single pair of optimally diverged species analyzed with a high performance alignment tool can yield accurate and specific alignments of functionally constrained noncoding sequences. Further algorithm development, optimization of alignment parameters, and benchmarking studies will be necessary to extract the maximal biological information from alignments of functional noncoding DNA.
Large-Scale Turnover of Functional Transcription Factor Binding Sites in Drosophila
Alan M Moses,Daniel A Pollard,David A Nix,Venky N Iyer,Xiao-Yong Li,Mark D Biggin,Michael B Eisen
PLOS Computational Biology , 2006, DOI: 10.1371/journal.pcbi.0020130
Abstract: The gain and loss of functional transcription factor binding sites has been proposed as a major source of evolutionary change in cis-regulatory DNA and gene expression. We have developed an evolutionary model to study binding-site turnover that uses multiple sequence alignments to assess the evolutionary constraint on individual binding sites, and to map gain and loss events along a phylogenetic tree. We apply this model to study the evolutionary dynamics of binding sites of the Drosophila melanogaster transcription factor Zeste, using genome-wide in vivo (ChIP–chip) binding data to identify functional Zeste binding sites, and the genome sequences of D. melanogaster, D. simulans, D. erecta, and D. yakuba to study their evolution. We estimate that more than 5% of functional Zeste binding sites in D. melanogaster were gained along the D. melanogaster lineage or lost along one of the other lineages. We find that Zeste-bound regions have a reduced rate of binding-site loss and an increased rate of binding-site gain relative to flanking sequences. Finally, we show that binding-site gains and losses are asymmetrically distributed with respect to D. melanogaster, consistent with lineage-specific acquisition and loss of Zeste-responsive regulatory elements.
The epidemiology of golfrelated injuries in Australian amateur golfers - a multivariate analysis
A McHardy, H Pollard, K Lou
South African Journal of Sports Medicine , 2007,
Abstract: Objective. To perform an epidemiological study in order to determine the golf-related injury locations, injury rates and possible risk factors for golf injury in amateur golfers across Australia. Method. A retrospective cross-sectional survey of Australian golf club members was used to collect data for the study. Chi-square testing was used to evaluate the association between golf injury and each possible risk factor at univariate level. All the possible risk factors were further examined in multivariate analysis using logistical regression. Results. There were 1 634 golfers included in the present study. Of these, 288 reported having had one or more golfrelated injuries in the previous year. The most common injury location was the lower back (25.3%), followed by the elbow (15.3%) and shoulder (9.4%). The most common injury mechanism was poor technique in execution of the golf swing (44.8%). Age, warm-up status, conditioning habits, wearing a golf glove/s and injury acquired in other sports / activities were significantly associated with risk of golf injury (p < 0.05). Equipment use such as type of golf club shaft used, type of shoes used and other factors studied were not statistically significant. Conclusion. The most injured sites identified in this study were the lower back, elbow and shoulder respectively. Risk of injury during golfing varied according to age group, warm-up status, conditioning habits, whether the player wore a golf glove/s, and whether the golfer had been injured in other activities. South African Journal of Sports Medicine Vol. 19 (1) 2007: pp. 12-19
A comparison of the modern and classic golf swing: a clinician\'s perspective
A McHardy, H Pollard, G Bayley
South African Journal of Sports Medicine , 2006,
Abstract: Objective. There is little descriptive research on the motion the body displays during the golf swing. The purpose of this research is to review the modern golf swing and compare its motion to the classic golf swing. Discussion. The comparison revealed subtle but significant differences in the backswing and the follow-through positions. The potential implications for power and injury, particularly of the lower back, are discussed. The discussion describes a third swing, the hybrid swing, which is a combination of the classic and modern swing. The hybrid swing may potentially reduce the chances of sustaining a low back injury while still retaining the power of the modern swing. Conclusion. The golf swing has evolved over time as a result of a combination of advanced equipment, course design and human experimentation. The hybrid swing is being taught by some golf professionals as a balance between the power-potential of the modern swing and the ‘back-friendly\' nature of the classic swing, though no studies have so far been conducted on its efficacy. Further investigation into the three golf swings, classic, modern and hybrid, is required to determine which swing is the most effective while also being friendly to the body. Such research will make possible the development programmes aimed at reducing golf injury rates, particularly to the lower back. South African Journal of Sports Medicine Vol. 18 (3) 2006: pp. 80-91
Use of Flame Atomic Absorption Spectroscopy and Multivariate Analysis for the Determination of Trace Elements in Human Scalp  [PDF]
Sayo O. Fakayode, Sri Lanka Owen, David A. Pollard, Mamudu Yakubu
American Journal of Analytical Chemistry (AJAC) , 2013, DOI: 10.4236/ajac.2013.47044
Abstract:

The analysis of trace elements in human hair for use as biomarkers continues to generate considerable interest in environmental and bioanalytical studies, medical diagnostics, and forensic science. This study investigated the concentrations of essential and toxic elements (Fe, Mg, Ca, Cu, Zn, Cr, Cd, and Pb) using flame atomic absorption spectroscopy (FAAS) in human scalp hair obtained from subjects living in Forsyth County, North Carolina, USA. The influence of age, sex, race, and smoking habits on the levels of trace elements in the hair samples were also investigated. Additionally, analyses were subjected to a statistical, regression, and principal component analysis to evaluate inter-elemental association and possible pattern recognition in hair samples. Furthermore, Ca/Mg and Zn/Cu ratios, which are often used to evaluate the degree of Ca and Cu utilization in humans and as markers for various health related issues including, atherosclerosis, hypertension, insulin sensitivity, and pancreatic cancer, were calculated. The overall mean concentrations of Fe (25 μg/g), Ca (710 μg/g), Mg (120 μg/g), Zn (190 μg/g), Cu (12 μg/g), and Cr (0.20 μg/g) were found in hair samples. The trace element concentrations varied widely in hair samples as demonstrated by large range of concentrations obtained for each element. However, levels of Cd and Pb elements of <0.030 μg/g were detected in hair sample. In general, the levels of the trace elements in hair samples were poorly correlated. However, significant correlations were found between Ca and Mg (r = 0.840, p = 0.05). The levels of Fe, Ca, Mg, Zn, Cu, and Cr in hair samples and the calculated Ca/Mg and Zn/Cu ratios were found to be

Stachybotrys chartarum (atra) spore extract alters surfactant protein expression and surfactant function in isolated fetal rat lung epithelial cells, fibroblasts and human A549 cells  [PDF]
Gail F. Pollard, Anthony Shaw, Michael Sowa, Thomas Rand, James A. Thliveris, James E. Scott
Open Journal of Pediatrics (OJPed) , 2013, DOI: 10.4236/ojped.2013.33043
Abstract:

Moulds, notably Stachybotrys chartarum (atra), are constant contributors to air pollution particularly to air quality in buildings. The spores themselves or their volatile organic products are present in variable amounts in almost all environments, particularly in buildings affected by flooding. These moulds and products can account for the sick building syndrome and have been tied to such occurrences as the outbreak of pulmonary hemosiderosis and hemorrhage in infants in Cleveland, Ohio. The present study was designed to investigate the effects of S. chartarum extracts on surfactant protein expression, surfactant quality and cell survival in the developing lung. S. chartarum extracts were incubated with cultures of several cell types; isolated fetal lung type II cells and fetal lung fibroblasts, and human lung A549 cells, a continuously growing cell line derived from surfactant producing type II alveolar cells. MTT formazan assays were employed to test cell viability. The synthesis and release of the predominant surfactant protein A (SP-A), which is involved in the regulation of surfactant turnover and metabolism, and surfactant protein B (SP-B) involved in shuttling phospholipids between surfactant subcompartments was also assessed. Antibodies to these proteins and western blotting results were used to assess the quantity of protein produced by the various cell types. A novel approach utilizing captive bubble surfactometry was employed to investigate the quality of surfactant in terms of surface tension and bubble volume measurements. Electron microscopy was used to examine changes in cellular structure of control and S. chartarum-treated cells. Results of the study showed that exposure to the S. chartarum extracts had deleterious effects on fetal lung epithelial cell viability

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