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Search Results: 1 - 10 of 299726 matches for " Graham J. Lieschke "
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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.
Nerve Growth Factor Stimulates Cardiac Regeneration via Cardiomyocyte Proliferation in Experimental Heart Failure
Nicholas T. Lam, Peter D. Currie, Graham J. Lieschke, Nadia A. Rosenthal, David M. Kaye
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0053210
Abstract: Although the adult heart likely retains some regenerative capacity, heart failure (HF) typically remains a progressive disorder. We hypothesise that alterations in the local environment contribute to the failure of regeneration in HF. Previously we showed that nerve growth factor (NGF) is deficient in the failing heart and here we hypothesise that diminished NGF limits the cardiac regenerative response in HF. The capacity of NGF to augment cardiac regeneration was tested in a zebrafish model of HF. Cardiac injury with a HF phenotype was induced in zebrafish larvae at 72 hours post fertilization (hpf) by exposure to aristolochic acid (AA, 2.5 μM, 72–75 hpf). By 168 hpf, AA induced HF and death in 37.5% and 20.8% of larvae respectively (p<0.001). NGF mRNA expression was reduced by 42% (p<0.05). The addition of NGF (50 ng/ml) after exposure to AA reduced the incidence of HF by 50% (p<0.01) and death by 65% (p<0.01). Mechanistically, AA mediated HF was characterised by reduced cardiomyocyte proliferation as reflected by a 6.4 fold decrease in BrdU+ cardiomyocytes (p<0.01) together with features of apoptosis and loss of cardiomyocytes. Following AA exposure, NGF increased the abundance of BrdU+ cardiomyocytes in the heart by 4.8 fold (p<0.05), and this was accompanied by a concomitant significant increase in cardiomyocyte numbers. The proliferative effect of NGF on cardiomyocytes was not associated with an anti-apoptotic effect. Taken together the study suggests that NGF stimulates a regenerative response in the failing zebrafish heart, mediated by stimulation of cardiomyocyte proliferation.
PhagoSight: An Open-Source MATLAB? Package for the Analysis of Fluorescent Neutrophil and Macrophage Migration in a Zebrafish Model
Katherine M. Henry, Luke Pase, Carlos Fernando Ramos-Lopez, Graham J. Lieschke, Stephen A. Renshaw, Constantino Carlos Reyes-Aldasoro
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072636
Abstract: Neutrophil migration in zebrafish larvae is increasingly used as a model to study the response of these leukocytes to different determinants of the cellular inflammatory response. However, it remains challenging to extract comprehensive information describing the behaviour of neutrophils from the multi-dimensional data sets acquired with widefield or confocal microscopes. Here, we describe PhagoSight, an open-source software package for the segmentation, tracking and visualisation of migrating phagocytes in three dimensions. The algorithms in PhagoSight extract a large number of measurements that summarise the behaviour of neutrophils, but that could potentially be applied to any moving fluorescent cells. To derive a useful panel of variables quantifying aspects of neutrophil migratory behaviour, and to demonstrate the utility of PhagoSight, we evaluated changes in the volume of migrating neutrophils. Cell volume increased as neutrophils migrated towards the wound region of injured zebrafish. PhagoSight is openly available as MATLAB? m-files under the GNU General Public License. Synthetic data sets and a comprehensive user manual are available from http://www.phagosight.org.
Real-Time Whole-Body Visualization of Chikungunya Virus Infection and Host Interferon Response in Zebrafish
Nuno Palha,Florence Guivel-Benhassine,Valérie Briolat,Georges Lutfalla,Marion Sourisseau,Felix Ellett,Chieh-Huei Wang,Graham J. Lieschke,Philippe Herbomel,Olivier Schwartz,Jean-Pierre Levraud
PLOS Pathogens , 2013, DOI: 10.1371/journal.ppat.1003619
Abstract: Chikungunya Virus (CHIKV), a re-emerging arbovirus that may cause severe disease, constitutes an important public health problem. Herein we describe a novel CHIKV infection model in zebrafish, where viral spread was live-imaged in the whole body up to cellular resolution. Infected cells emerged in various organs in one principal wave with a median appearance time of ~14 hours post infection. Timing of infected cell death was organ dependent, leading to a shift of CHIKV localization towards the brain. As in mammals, CHIKV infection triggered a strong type-I interferon (IFN) response, critical for survival. IFN was mainly expressed by neutrophils and hepatocytes. Cell type specific ablation experiments further demonstrated that neutrophils play a crucial, unexpected role in CHIKV containment. Altogether, our results show that the zebrafish represents a novel valuable model to dynamically visualize replication, pathogenesis and host responses to a human virus.
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.
Hydrogen Peroxide in Inflammation: Messenger, Guide, and Assassin
C. Wittmann,P. Chockley,S. K. Singh,L. Pase,G. J. Lieschke,C. Grabher
Advances in Hematology , 2012, DOI: 10.1155/2012/541471
Abstract: Starting as a model for developmental genetics, embryology, and organogenesis, the zebrafish has become increasingly popular as a model organism for numerous areas of biology and biomedicine over the last decades. Within haematology, this includes studies on blood cell development and function and the intricate regulatory mechanisms within vertebrate immunity. Here, we review recent studies on the immediate mechanisms mounting an inflammatory response by in vivo analyses using the zebrafish. These recently revealed novel roles of the reactive oxygen species hydrogen peroxide that have changed our view on the initiation of a granulocytic inflammatory response. 1. Introduction The innate immune system comprises the cells and mechanisms that defend the host from infection by other organisms or damage to tissue integrity, in a nonspecific manner. This means that the cells of the innate system recognise and respond to pathogens and trauma in a generic way, but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host. The innate immune system provides an immediate defence. A typical vertebrate immune response depends on the orchestrated motility and activity of various haematopoietic compartments and their interactions that ultimately control the magnitude of the response [1–3]. Inflammation is one of the first responses of the immune system to infection or irritation. Stimulated by factors released from injured cells, it serves to establish a physical barrier against the spread of infection. This further promotes healing of any damaged tissue following the clearance of pathogens or cell debris. Molecules produced during inflammation sensitise pain receptors, cause localised vasodilatation of blood vessels, and attract phagocytes, especially neutrophils and macrophages, which then trigger other parts of the immune system. Failure to initiate a response allows uncontrolled proliferation of invading microorganisms and severe tissue damage that may become fatal. Failure to resolve an immune response can also cause severe tissue damage, due to persistent degranulation, and may lead to chronic inflammation, which ceases to be beneficial to the host. Overall, inflammation is now recognised as a central feature of prevalent pathologies, such as atherosclerosis, cancer, asthma, thyroiditis, inflammatory bowel disease, autoimmune disease, as well as Alzheimer’s and Parkinson’s disease [4–6]. Hence, the regulation of an inflammatory response is an active field of research. New players or novel functions of old players
The Effects of Stabilized Urea and Split-Applied Nitrogen on Sunflower Yield and Oil Content  [PDF]
Christopher J. Graham, Jac J. Varco
American Journal of Plant Sciences (AJPS) , 2017, DOI: 10.4236/ajps.2017.88125
Abstract: Sunflower is an efficient nitrogen (N) accumulator due to its aggressive taproot and extensive root system. While N rate studies in sunflower have shown a yield response, the response is often highly variable and difficult to predict in many instances. Additionally, since most sunflower production is intended for the oil market, surplus nitrogen tends to decrease oil content. Therefore, it is critical to hone nitrogen rates to maximize both yield and oil production and to incorporate alternative approaches to fertilizer application, which includes timing and method of application. The objective of the present study was to assess the efficacy of a split-application of N at either the V4 or R1 growth stage to increase yield and/or oil content in sunflower. A second objective was to examine whether a urease inhibitor could be used to retain soil N longer and achieve a similar effect as a split-application. Studies were conducted at two locations over two growing seasons in South Dakota, USA. A target rate of 90 kg·ha-1 was applied as urea-ammonium nitrate (UAN) either as an at-planting application or split-applied. Overall, N additions did significantly increase yield over a control. On average, the urease inhibitor tended to increase grain yields over split-applying N at either growth stage, however, there was no statistical effect on either grain yield or oil content. Based on 15N analysis, approximately 27% of the N in the grain was derived from the UAN fertilizer, which indicates a relatively large reliance upon soil N for grain N content. The addition of a urease inhibitor significantly increased average fertilizer uptake by nearly 6% to 32.7%.
Heat output from spreading and rifting models of the Taupo Volcanic Zone, New Zealand
Graham J. Weir
Advances in Decision Sciences , 2001, DOI: 10.1155/s1173912601000098
Abstract: A conceptual model of the Taupo Volcanic Zone (TVZ) is developed, to a depth of 25 km, formed from three constant density layers. The upper layer is formed from eruption products. A constant rate of eruption is assumed, which eventually implies a constant rate of extension, and a constant rate of volumetric creation in the middle and bottom layers. Tectonic extension creates volume which can accomodate magmatic intrusions. Spreading models assume this volume is distributed throughout the whole region, perhaps in vertical dykes, whereas rifting models assume the upper crust is thinned and the volume created lies under this upper crust. Bounds on the heat flow from such magmatic intrusions are calculated. Heat flow calculations are performed and some examples are provided which match the present total heat output from the TVZ of about 4200 MW, but these either have extension rates greater than the low values of about 8 ± 4 mm/a being reported from GPS measurements, or else consider extension rates in the TVZ to have varied over time.
On the Spectral Entropy of Thermodynamic Paths for Elementary Systems
Daniel J. Graham
Entropy , 2009, DOI: 10.3390/e11041025
Abstract: Systems do not elect thermodynamic pathways on their own. They operate in tandem with their surroundings. Pathway selection and traversal require coordinated work and heat exchanges along with parallel tuning of the system variables. Previous research by the author (Reference [1]) focused on the information expressed in thermodynamic pathways. Examined here is how spectral entropy is a by-product of information that depends intricately on the pathway structure. The spectral entropy has proven to be a valuable tool in diverse fields. This paper illustrates the contact between spectral entropy and the properties which distinguish ideal from non-ideal gases. The role of spectral entropy in the first and second laws of thermodynamics and heat → work conversions is also discussed.
A note on the use of sensitivity analysis to explore the potential impact of declining institutional care utilisation on disability prevalence
Patrick J Graham
Population Health Metrics , 2004, DOI: 10.1186/1478-7954-2-3
Abstract: Prevalence measures of disability, functional limitation and other health states are important descriptive statistics for assessing population health and are integral to the construction of summary measures such as health expectancy [1]. Commonly used health and disability survey sampling frames exclude individuals living in institutions such as hospitals or retirement homes. For example, reports based on the United States National Health Interview Survey [2], the French Health and Medical Care Survey [3], the Finnish and Norwegian Surveys of Living Conditions [4] and the New-Zealand Household Health Survey [5] all note that the survey data refer to the non-institutionalised population. Because the prevalence of limiting and disabling conditions is likely to be higher among the population in institutional care, prevalence estimates based solely on the non-institutionalised population are likely to underestimate prevalence for the full population, particularly at older ages. In the context of health expectancy calculations, one response to this situation has been to define institutional care as a distinct health state and to produce estimates of the expectation of life in institutional care, not in institutional care but with functional limitations or disability and not in institutional care and free of limitations or disabilities [2,6]. Surveys of the non-institutionalised population produce estimates of the conditional prevalence, Pr(limitation|non-institutionalised), which is exactly what is required to compute the expectation of life with non-institutionalised disability in a health expectancy calculation, partitioned as just discussed.The strategy of defining institutional care as a distinct health state yields a coherent set of point-in-time health state prevalences and health expectancy estimates, covering the entire population. However changes in the prevalence of institutionalisation complicate the interpretation of changes in non-institutionalised health st
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