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Search Results: 1 - 10 of 141604 matches for " Joan K. Heath "
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Mediator Subunit 12 Is Required for Neutrophil Development in Zebrafish
Maria-Cristina Keightley, Judith E. Layton, John W. Hayman, Joan K. Heath, Graham J. Lieschke
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023845
Abstract: Hematopoiesis requires the spatiotemporal organization of regulatory factors to successfully orchestrate diverse lineage specificity from stem and progenitor cells. Med12 is a regulatory component of the large Mediator complex that enables contact between the general RNA polymerase II transcriptional machinery and enhancer bound regulatory factors. We have identified a new zebrafish med12 allele, syr, with a single missense mutation causing a valine to aspartic acid change at position 1046. Syr shows defects in hematopoiesis, which predominantly affect the myeloid lineage. Syr has identified a hematopoietic cell-specific requirement for Med12, suggesting a new role for this transcriptional regulator.
Genetic Dissection of Differential Signaling Threshold Requirements for the Wnt/β-Catenin Pathway In Vivo
Michael Buchert equal contributor,Dimitris Athineos equal contributor,Helen E. Abud equal contributor,Zoe D. Burke,Maree C. Faux,Michael S. Samuel,Andrew G. Jarnicki,Catherine E. Winbanks,Ian P. Newton,Valerie S. Meniel,Hiromu Suzuki,Steven A. Stacker,Inke S. N?thke,David Tosh,Joerg Huelsken,Alan R. Clarke,Joan K. Heath,Owen J. Sansom ,Matthias Ernst
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1000816
Abstract: Contributions of null and hypomorphic alleles of Apc in mice produce both developmental and pathophysiological phenotypes. To ascribe the resulting genotype-to-phenotype relationship unambiguously to the Wnt/β-catenin pathway, we challenged the allele combinations by genetically restricting intracellular β-catenin expression in the corresponding compound mutant mice. Subsequent evaluation of the extent of resulting Tcf4-reporter activity in mouse embryo fibroblasts enabled genetic measurement of Wnt/β-catenin signaling in the form of an allelic series of mouse mutants. Different permissive Wnt signaling thresholds appear to be required for the embryonic development of head structures, adult intestinal polyposis, hepatocellular carcinomas, liver zonation, and the development of natural killer cells. Furthermore, we identify a homozygous Apc allele combination with Wnt/β-catenin signaling capacity similar to that in the germline of the Apcmin mice, where somatic Apc loss-of-heterozygosity triggers intestinal polyposis, to distinguish whether co-morbidities in Apcmin mice arise independently of intestinal tumorigenesis. Together, the present genotype–phenotype analysis suggests tissue-specific response levels for the Wnt/β-catenin pathway that regulate both physiological and pathophysiological conditions.
Advances in Swine Biomedical Model Genomics
Joan K. Lunney
International Journal of Biological Sciences , 2007,
Abstract: This review is a short update on the diversity of swine biomedical models and the importance of genomics in their continued development. The swine has been used as a major mammalian model for human studies because of the similarity in size and physiology, and in organ development and disease progression. The pig model allows for deliberately timed studies, imaging of internal vessels and organs using standard human technologies, and collection of repeated peripheral samples and, at kill, detailed mucosal tissues. The ability to use pigs from the same litter, or cloned or transgenic pigs, facilitates comparative analyses and genetic mapping. The availability of numerous well defined cell lines, representing a broad range of tissues, further facilitates testing of gene expression, drug susceptibility, etc. Thus the pig is an excellent biomedical model for humans. For genomic applications it is an asset that the pig genome has high sequence and chromosome structure homology with humans. With the swine genome sequence now well advanced there are improving genetic and proteomic tools for these comparative analyses. The review will discuss some of the genomic approaches used to probe these models. The review will highlight genomic studies of melanoma and of infectious disease resistance, discussing issues to consider in designing such studies. It will end with a short discussion of the potential for genomic approaches to develop new alternatives for control of the most economically important disease of pigs, porcine reproductive and respiratory syndrome (PRRS), and the potential for applying knowledge gained with this virus for human viral infectious disease studies.
Autophagy Induction Is a Tor- and Tp53-Independent Cell Survival Response in a Zebrafish Model of Disrupted Ribosome Biogenesis
Yeliz Boglev,Andrew P. Badrock,Andrew J. Trotter,Qian Du,Elsbeth J. Richardson,Adam C. Parslow,Sebastian J. Markmiller,Nathan E. Hall,Tanya A. de Jong-Curtain,Annie Y. Ng,Heather Verkade,Elke A. Ober,Holly A. Field,Donghun Shin,Chong H. Shin,Katherine M. Hannan,Ross D. Hannan,Richard B. Pearson,Seok-Hyung Kim,Kevin C. Ess,Graham J. Lieschke,Didier Y. R. Stainier,Joan K. Heath
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003279
Abstract: Ribosome biogenesis underpins cell growth and division. Disruptions in ribosome biogenesis and translation initiation are deleterious to development and underlie a spectrum of diseases known collectively as ribosomopathies. Here, we describe a novel zebrafish mutant, titania (ttis450), which harbours a recessive lethal mutation in pwp2h, a gene encoding a protein component of the small subunit processome. The biochemical impacts of this lesion are decreased production of mature 18S rRNA molecules, activation of Tp53, and impaired ribosome biogenesis. In ttis450, the growth of the endodermal organs, eyes, brain, and craniofacial structures is severely arrested and autophagy is up-regulated, allowing intestinal epithelial cells to evade cell death. Inhibiting autophagy in ttis450 larvae markedly reduces their lifespan. Somewhat surprisingly, autophagy induction in ttis450 larvae is independent of the state of the Tor pathway and proceeds unabated in Tp53-mutant larvae. These data demonstrate that autophagy is a survival mechanism invoked in response to ribosomal stress. This response may be of relevance to therapeutic strategies aimed at killing cancer cells by targeting ribosome biogenesis. In certain contexts, these treatments may promote autophagy and contribute to cancer cells evading cell death.
Thermal Adaptation and Diversity in Tropical Ecosystems: Evidence from Cicadas (Hemiptera, Cicadidae)
Allen F. Sanborn, James E. Heath, Polly K. Phillips, Maxine S. Heath, Fernando G. Noriega
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0029368
Abstract: The latitudinal gradient in species diversity is a central problem in ecology. Expeditions covering approximately 16°54′ of longitude and 21°4′ of latitude and eight Argentine phytogeographic regions provided thermal adaptation data for 64 species of cicadas. We test whether species diversity relates to the diversity of thermal environments within a habitat. There are general patterns of the thermal response values decreasing in cooler floristic provinces and decreasing maximum potential temperature within a habitat except in tropical forest ecosystems. Vertical stratification of the plant communities leads to stratification in species using specific layers of the habitat. There is a decrease in thermal tolerances in species from the understory communities in comparison to middle level or canopy fauna. The understory Herrera umbraphila Sanborn & Heath is the first diurnally active cicada identified as a thermoconforming species. The body temperature for activity in H. umbraphila is less than and significantly different from active body temperatures of all other studied species regardless of habitat affiliation. These data suggest that variability in thermal niches within the heterogeneous plant community of the tropical forest environments permits species diversification as species adapt their physiology to function more efficiently at temperatures different from their potential competitors.
Physicians’ Use of Patients’ Daily Reports of Quality of Life to Evaluate Treatment Response in Phase I Cancer Trials  [PDF]
Felicity W. K. Harper, Elisabeth I. Heath, Marci E. J. Gleason, Louis Penner, Patricia LoRusso, Ding Wang, Terrance L. Albrecht
Journal of Cancer Therapy (JCT) , 2012, DOI: 10.4236/jct.2012.35074
Abstract: For cancer patients on Phase I trials, one of the most important physician decisions is whether or not patients are deriving benefit from therapy. With an increasing number of cytostatic treatment agents, the criteria to determine patient response to Phase I treatment has become harder to define. Physicians are increasingly looking to patient-reported outcomes (PROs) such as quality of life (QOL) to help evaluate treatment response. Electronic daily diary (EDD) devices can be used by patients to report their QOL over extended periods of time, thereby providing a more accurate picture of how patients are affected by treatment on a daily basis. However, questions remain about how to integrate this patient-reported information into decisions about Phase I treatment. This study investigated how physicians use patients’ daily QOL reports to evaluate patient response to Phase I treatment. Data were collected over a 4-month period from Phase I patients (N = 30) and physicians (N = 3) in an NCI-designated comprehensive cancer center. Patients completed daily QOL reports using EDD devices and physicians were provided with a summary of patients’ QOL before each visit. After the visit, doctors recorded their treatment decision and also rated the importance of four biomedical factors (Toxicity, Imaging, Labs, and Performance Status) and QOL in their treatment decision for that visit. Although physicians rated QOL as being very important in evaluating treatment response, in practice, when predictors of their decisions were analyzed, results showed they relied exclusively on biomedical data (Toxicity, Imaging) to make Phase I treatment decisions. Questions remain about the utility and effective integration of QOL and biomedical data in clinical decision-making processes in Phase I clinical trials.
Field Assessment and Specification Review for Roller-Integrated Compaction Monitoring Technologies
David J. White,Pavana K. R. Vennapusa,Heath H. Gieselman
Advances in Civil Engineering , 2011, DOI: 10.1155/2011/783836
Abstract: Roller-integrated compaction monitoring (RICM) technologies provide virtually 100-percent coverage of compacted areas with real-time display of the compaction measurement values. Although a few countries have developed quality control (QC) and quality assurance (QA) specifications, broader implementation of these technologies into earthwork construction operations still requires a thorough understanding of relationships between RICM values and traditional in situ point test measurements. The purpose of this paper is to provide: (a) an overview of two technologies, namely, compaction meter value (CMV) and machine drive power (MDP); (b) a comprehensive review of field assessment studies, (c) an overview of factors influencing statistical correlations, (d) modeling for visualization and characterization of spatial nonuniformity; and (e) a brief review of the current specifications. 1. Introduction Roller-integrated compaction monitoring (RICM) technologies refer to sensor measurements integrated into compaction machines. Work in this area was initiated over 30 years ago in Europe for smooth drum rollers compacting granular soils and involved instrumenting the roller with an accelerometer and calculating the ratio of the fundamental frequency to the first harmonic [1, 2]. Modern sensor technologies, computers, and global positioning system (GPS) technologies now make it possible to collect, transmit, and visualize a variety of RICM measurements in real time. As a quality assessment tool for compaction of earth materials, these technologies offer tremendous potential for field controlling the construction process to meet performance quality standards. Recent efforts in the United States (US) have focused attention on how RICM technologies can be used in road building [3–5] and relating selected RICM parameters to mechanistic pavement design values. Several manufactures currently offer RICM technologies on smooth drum vibratory roller configurations for compaction of granular materials and asphalt, and nonvibratory roller configurations for compaction of cohesive materials. The current technologies calculate: (1) an index value based on a ratio of selected frequency harmonics for a set time interval for vibratory compaction [1, 2], (2) ground stiffness or dynamic elastic modulus based on a drum-ground interaction model for vibratory compaction [6–8], or (3) a measurement of rolling resistance calculated from machine drive power (MDP) for vibratory and nonvibratory compaction [9]. When the accelerometer-based measurement system provides automatic feedback
Simulation suggests that rapid activation of social distancing can arrest epidemic development due to a novel strain of influenza
Joel K Kelso, George J Milne, Heath Kelly
BMC Public Health , 2009, DOI: 10.1186/1471-2458-9-117
Abstract: We used a detailed, individual-based model of a real community with a population of approximately 30,000. We simulated the effect of four social distancing interventions: school closure, increased isolation of symptomatic individuals in their household, workplace nonattendance, and reduction of contact in the wider community. We simulated each of the intervention measures in isolation and in several combinations; and examined the effect of delays in the activation of interventions on the final and daily attack rates.For an epidemic with an R0 value of 1.5, a combination of all four social distancing measures could reduce the final attack rate from 33% to below 10% if introduced within 6 weeks from the introduction of the first case. In contrast, for an R0 of 2.5 these measures must be introduced within 2 weeks of the first case to achieve a similar reduction; delays of 2, 3 and 4 weeks resulted in final attack rates of 7%, 21% and 45% respectively. For an R0 of 3.5 the combination of all four measures could reduce the final attack rate from 73% to 16%, but only if introduced without delay; delays of 1, 2 or 3 weeks resulted in final attack rates of 19%, 35% or 63% respectively. For the higher R0 values no single measure has a significant impact on attack rates.Our results suggest a critical role of social distancing in the potential control of a future pandemic and indicate that such interventions are capable of arresting influenza epidemic development, but only if they are used in combination, activated without delay and maintained for a relatively long period.Concern exists that the avian H5N1 influenza virus may become readily transmissible between humans, leading to a pandemic with significant mortality [1].Social distancing interventions, such as school closure, reducing workplace numbers, reducing social and community contacts, and increasing home isolation are embedded within the pandemic influenza preparedness plans of most countries [2-4] and appear in curr
The plant communities of the Andover Game Reserve, South Africa
Heath P. Cronje,Mike D. Panagos,Brian K. Reilly
Koedoe : African Protected Area Conservation and Science , 2008, DOI: 10.4102/koedoe.v50i1.137
Abstract: Floristic characteristics of the Andover Game Reserve (AGR) were surveyed using an area-based survey technique and classified according to the data recorded from 88 relevés, using the PHYTOTAB-PC software package. Three plant communities, of which two each contain two variants, were described and mapped. The plant communities and their causative environmental factors were validated through detrended- and canonical correspondence multivariate analyses. The plant communities of the AGR were found to typify the floristics associated with the catenal sequences located in undulating areas on granite. Broad-leaved savanna is located at the crest and upper mid-slopes while fine-leaved savanna occurs along the footslopes of the AGR. Seeplines, a characteristic occurrence along catenas, are found at the transitional zone between the upper broad- and lower fine-leaved savanna plant communities. This study forms the basis for the compilation of a revised ecological management plan for the Andover Game Reserve.
Does High Altitude Protect Against Irreversible Pulmonary Hypertension?
Heath Alexandra,Stewart K,Mendes J,Ramirez M
PVRI Review , 2010,
Abstract: Aim: To present observations regarding the pulmonary pressure characteristics of children and young adults with congenital heart defects who were born and living in high altitude, before and after correction of the defect. Materials and Method: We analyzed 2 groups of patients. Group 1: 21 patients were diagnosed with clinically significant ventricle septum defects (VSD), measuring an average of 17 mm in its larger diameter (7-35 mm), aged 6.2 years on average (range: 1-23 years), with preoperative New York Heart Association (NYHA) class being an average of 2.1. Their arterial oxygen saturation was 92% on average (82%-99%) and systolic pulmonary pressure (SPP) was 64 mmHg, (range: 22-94 mmHg). Group 2: 60 patients were diagnosed with hemodynamically significant patent ductus arteriosus (PDA), 4.85 mm in its minimum diameter (range: 1.8-13 mm), aged 9.2 years on average (range: 9 months-30 years), in whom the SPP measured preoperatively reached 50.6 mmHg (range: 21-94 mmHg). The intervention involved VSD surgical repair or interventional closure of the PDA. Results: Postinterventional results: Group 1 improved its NYHA functional class to an average of 1.2; the mean oxygen saturation rose to 93% (88%-96%) and the SPP dropped to 36 mmHg (range: 20-61 mmHg). In Group 2, the SPP dropped to an average of 39.8 mmHg (range: 16-79 mmHg). The preoperative SPP to systolic aortic pressure ratio was on average 53.15% (range: 22.58%-96.84%); postoperative, the ratio dropped to 38.39% (16.7%-82%). Conclusions: After intervention, the average SPP invariably dropped in both the groups, although its levels could not be considered normal in all the patients. In addition, the intervention led to clinical improvement. High altitude seems to give this group of patients a protection against irreversible changes in the pulmonary circulation. More prospective, controlled studies and a longer follow-up are needed to confirm this observation.
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