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Search Results: 1 - 10 of 211684 matches for " Ryan L Parr "
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Mitochondrial and nuclear genomics and the emergence of personalized medicine
Ryan L Parr, Luis Martin
Human Genomics , 2012, DOI: 10.1186/1479-7364-6-3
Abstract:
Clinical implications and utility of field cancerization
Gabriel D Dakubo, John P Jakupciak, Mark A Birch-Machin, Ryan L Parr
Cancer Cell International , 2007, DOI: 10.1186/1475-2867-7-2
Abstract: The sequential genetic changes that drive a cell towards malignancy occur over several years. In view of this, the American Association for Cancer Research Task Force on the treatment and prevention of intraepithelial neoplasia (IEN) has recognized the importance of targeting the treatment of early cancerous lesions to prevent or regress carcinogenesis [1]. Considerable research has identified molecular markers of IEN that serve as useful targets or endpoints of chemoprevention [1-3]. This laudable effort by the Task Force can be complemented by identification of biomarkers in normal tissues adjacent to tumors (peri-tumoral cancer fields). Validated biomarkers from cancer fields should be useful for primary chemoprevention studies as well.The idea of field cancerization was conceived by Slaughter almost a decade prior to introducing the term in 1953. In an earlier publication he stated that; "cancer does not arise as an isolated cellular phenomenon, but rather as an anaplastic tendency involving many cells at once" [4]. The term "lateral cancerization" was subsequently used to indicate that the lateral spread of tumors was due to progressive transformation of cells adjacent to a tumor, rather than the spread and destruction of the adjacent epithelium by pre-existing cancer cells [5]. In a more extensive histopathologic review of 783 oral cancer patients, Slaughter and colleagues then used the term field cancerization to describe the existence of generalized carcinogen induced early genetic changes in the epithelium from which multiple independent lesions occur, leading to the development of multifocal tumors [6]. In some cases, multiple contiguous tumor foci coalesce that partly explain the lateral spread of squamous cell cancers. It was also observed that normal looking cells in close proximity to malignant cells were histologically abnormal and therefore were part of the transformed cells in a particular tumor field, and consequently were responsible for the occur
Mitochondrial DNA as a potential tool for early cancer detection
Ryan L Parr, Gabriel D Dakubo, Robert E Thayer, Keith McKenney, Mark A Birch-Machin
Human Genomics , 2006, DOI: 10.1186/1479-7364-2-4-252
Abstract:
The pseudo-mitochondrial genome influences mistakes in heteroplasmy interpretation
Ryan L Parr, Jennifer Maki, Brian Reguly, Gabriel D Dakubo, Andrea Aguirre, Roy Wittock, Kerry Robinson, John P Jakupciak, Robert E Thayer
BMC Genomics , 2006, DOI: 10.1186/1471-2164-7-185
Abstract: Here we report the cloning and sequencing of numts loci, amplified from human tissue and rho-zero (ρ0) cells (control) with primers known to amplify the mitochondrial genome. This paper is the first to fully sequence 46 paralogous nuclear DNA fragments that represent the entire mitochondrial genome. This is a surprisingly small number due primarily to the primer sets used in this study, because prior to this, BLAST searches have suggested that nuclear DNA harbors between 400 to 1,500 paralogous mitochondrial DNA fragments. Our results indicate that multiple numts were amplified simultaneously with the mitochondrial genome and increased the load of pseudogene signal in PCR reactions. Further, the entire mitochondrial genome was represented by multiple copies of paralogous nuclear sequences.These findings suggest that mitochondrial genome disease-associated biomarkers must be rigorously authenticated to preclude any affiliation with paralogous nuclear pseudogenes. Importantly, the common perception that mitochondrial template "swamps" numts loci precluding detectable amplification, depends on the region of the mitochondrial genome targeted by the PCR reaction and the number of pseudogene loci that may co-amplify. Cloning and relevant sequencing data will facilitate the correct interpretation. This is the first complete, wet-lab characterization of numts that represent the entire mitochondrial genome.The unique maternal inheritance pattern of mitochondrial DNA (mtDNA), its small genome size, accelerated mutation rate, lack of recombination, and multiple copy number per cell, in comparison to nuclear DNA, are ideal biological traits for investigating evolution, population genetics and for forensic and medical applications. Thus, the mitochondrial genome has been used as a biosensor for the timing and movement of human populations in antiquity [1,2]. MtDNA analysis is routinely used in forensic biology to type biological material when degradation prevents nuclear STR amp
Facile whole mitochondrial genome resequencing from nipple aspirate fluid using MitoChip v2.0
John P Jakupciak, Andrea Maggrah, Samantha Maragh, Jennifer Maki, Brian Reguly, Katrina Maki, Roy Wittock, Kerry Robinson, Paul D Wagner, Robert E Thayer, Ken Gehman, Teresa Gehman, Sudhir Srivastava, Alioune Ngom, Gabriel D Dakubo, Ryan L Parr
BMC Cancer , 2008, DOI: 10.1186/1471-2407-8-95
Abstract: NAF and blood were obtained from women with symptomatic benign breast conditions, and we successfully assessed the mutation load in the entire mitochondrial genome of 19 of these women. DNA extracts from NAF were sequenced using the mitochondrial resequencing array MCv2 and by capillary electrophoresis (CE) methods as a quality comparison. Sequencing was performed independently at two institutions and the results compared. The germline mtDNA sequence determined using DNA isolated from the patient's blood (control) was compared to the mutations present in cellular mtDNA recovered from patient's NAF.From the cohort of 28 women recruited for this study, NAF was successfully recovered from 23 participants (82%). Twenty two (96%) of the women produced fluids from both breasts. Twenty NAF samples and corresponding blood were chosen for this study. Except for one NAF sample, the whole mtgenome was successfully amplified using a single primer pair, or three pairs of overlapping primers. Comparison of MCv2 data from the two institutions demonstrates 99.200% concordance. Moreover, MCv2 data was 99.999% identical to CE sequencing, indicating that MCv2 is a reliable method to rapidly sequence the entire mtgenome. Four NAF samples contained somatic mutations.We have demonstrated that NAF is a suitable material for mtDNA sequence analysis using the rapid and reliable MCv2. Somatic mtDNA mutations present in NAF of women with benign breast diseases could potentially be used as risk factors for progression to breast cancer, but this will require a much larger study with clinical follow up.The increased number of cancer cases around the world is a major concern. Research methods for identifying the presence of cancerous cells by measuring mutations in mtDNA is the subject of intense clinical investigation [1,2]. Frequently, these studies analyze only specific regions of mtDNA and not the entire mitochondrial genome (mtgenome). There are several biological characteristics of mitochon
Does Structural Complexity Determine the Morphology of Assemblages? An Experimental Test on Three Continents
Heloise Gibb, Catherine L. Parr
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064005
Abstract: Understanding how species will respond to global change depends on our ability to distinguish generalities from idiosyncrasies. For diverse, but poorly known taxa, such as insects, species traits may provide a short-cut to predicting species turnover. We tested whether ant traits respond consistently to habitat complexity across geographically independent ant assemblages, using an experimental approach and baits. We repeated our study in six paired simple and complex habitats on three continents with distinct ant faunas. We also compared traits amongst ants with different foraging strategies. We hypothesised that ants would be larger, broader, have longer legs and more dorsally positioned eyes in simpler habitats. In agreement with predictions, ants had longer femurs and dorsally positioned eyes in simple habitats. This pattern was most pronounced for ants that discovered resources. Body size and pronotum width responded as predicted for experimental treatments, but were inconsistent across continents. Monopolising ants were smaller, with shorter femurs than those that occupied or discovered resources. Consistent responses for several traits suggest that many, but not all, aspects of morphology respond predictably to habitat complexity, and that foraging strategy is linked with morphology. Some traits thus have the potential to be used to predict the direction of species turnover, changes in foraging strategy and, potentially, evolution in response to changes in habitat structure.
Comment on "Possible source of ancient carbon in phytolith concentrates from harvested grasses" by G. M. Santos et al. (2012)
L. A. Sullivan ,J. F. Parr
Biogeosciences (BG) & Discussions (BGD) , 2013,
Abstract: Santos et al. (2012) address the important issue that 14C dating of the carbon occluded in silica phytoliths (PhytOC) isolated from contemporary plant materials can produce ages that are incompatible, being often several kyr older, with both their known recent origin and the 14C age of the bulk plant material. In their article, Santos et al. (2012) propose that the anomalously old 14C carbon dates of PhytOC from harvested plant materials are based on plants taking up "old" dissolved soil carbon to the plant by roots during nutrient uptake. They then propose that this old soil-derived carbon is subsequently partitioned from the general plant biomass into either the silica phytoliths they produce or as recalcitrant organic matter elsewhere in the plant. We suggest that the full data available for PhytOC 14C dating do not support this hypothesis. Santos et al. (2012) also address the important issue of contamination of PhytOC by general plant biomass material that can occur with procedures that incompletely extract phytoliths. Whilst we agree that such contamination needs to be avoided when examining the nature of PhytOC, we also point out that the converse problem, i.e. removal of PhytOC by over-vigorous extraction procedures, can also have important adverse consequences.
Comment on: "Possible source of ancient carbon in phytolith concentrates from harvested grasses" by G. M. Santos et al. (2012)
L. A. Sullivan,J. F. Parr
Biogeosciences Discussions , 2012, DOI: 10.5194/bgd-9-13773-2012
Abstract: Santos et al. (2012) address the important issue that 14C dating of the carbon occluded in silica phytoliths (PhytOC) isolated from contemporary plant materials can produce ages that are incompatible, being often several kyr older, with both their known recent origin and the 14C age of the bulk plant material. In their article, Santos et al. (2012) propose that the anomalously old 14C carbon dates of PhytOC from harvested plant materials are based on plants taking up "old" dissolved soil carbon to the plant by roots during nutrient uptake. They then propose that this old soil-derived carbon is subsequently partitioned from the general plant biomass into either the silica phytoliths they produce, or as recalcitrant organic matter elsewhere in the plant. We suggest that the full data available for PhytOC 14C dating does not support this hypothesis. Santos et al. (2012) also address the important issue of contamination of PhytOC by general plant biomass material that can occur with procedures that incompletely extract phytoliths. Whilst we agree that such contamination needs to be avoided when examining the nature of PhytOC, we also point out that the converse problem, i.e. removal of PhytOC by over-vigorous extraction procedures, can also have important adverse consequences.
Using Story as Sites of Dialogue, Disillusionment, and Development of Dispositions to Support Inclusive Education  [PDF]
Michelann Parr, Terry Campbell
Creative Education (CE) , 2012, DOI: 10.4236/ce.2012.33054
Abstract: This article reports on an ongoing action research project regarding stories and dialogue that can be used as experiences of difference and diversity, and their impact on the classroom environment/community and the teacher. Over a period of ten years, the researchers have engaged a total of 2400 teacher candidates, through their language and literacy course, in a discussion of what it means to be different and how these values and attitudes impact what happens in the classroom. Using children’s literature as a starting point, teacher candidates are encouraged to make connections between read alouds, reader response, critical literacy, and how this ultimately transforms their knowledge, values, and zones of comfort in both the teacher education classroom and the regular classroom.
Comparative Biomechanical Modeling of Metatherian and Placental Saber-Tooths: A Different Kind of Bite for an Extreme Pouched Predator
Stephen Wroe, Uphar Chamoli, William C. H. Parr, Philip Clausen, Ryan Ridgely, Lawrence Witmer
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066888
Abstract: Questions surrounding the dramatic morphology of saber-tooths, and the presumably deadly purpose to which it was put, have long excited scholarly and popular attention. Among saber-toothed species, the iconic North American placental, Smilodon fatalis, and the bizarre South American sparassodont, Thylacosmilus atrox, represent extreme forms commonly forwarded as examples of convergent evolution. For S. fatalis, some consensus has been reached on the question of killing behaviour, with most researchers accepting the canine-shear bite hypothesis, wherein both head-depressing and jaw closing musculatures played a role in delivery of the fatal bite. However, whether, or to what degree, T. atrox may have applied a similar approach remains an open question. Here we apply a three-dimensional computational approach to examine convergence in mechanical performance between the two species. We find that, in many respects, the placental S. fatalis (a true felid) was more similar to the metatherian T. atrox than to a conical-toothed cat. In modeling of both saber-tooths we found that jaw-adductor-driven bite forces were low, but that simulations invoking neck musculature revealed less cranio-mandibular stress than in a conical-toothed cat. However, our study also revealed differences between the two saber-tooths likely reflected in the modus operandi of the kill. Jaw-adductor-driven bite forces were extremely weak in T. atrox, and its skull was even better-adapted to resist stress induced by head-depressors. Considered together with the fact that the center of the arc described by the canines was closer to the jaw-joint in Smilodon, our results are consistent with both jaw-closing and neck musculature playing a role in prey dispatch for the placental, as has been previously suggested. However, for T. atrox, we conclude that the jaw-adductors probably played no major part in the killing bite. We propose that the metatherian presents a more complete commitment to the already extreme saber-tooth ‘lifestyle’.
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