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Search Results: 1 - 10 of 227374 matches for " Thomas N. Wight "
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Changes in elastin, elastin binding protein and versican in alveoli in chronic obstructive pulmonary disease
Mervyn J Merrilees, Pamela ST Ching, Brent Beaumont, Aleksander Hinek, Thomas N Wight, Peter N Black
Respiratory Research , 2008, DOI: 10.1186/1465-9921-9-41
Abstract: Lung samples were obtained from 26 control (FEV1 ≥ 80% predicted, FEV1/VC >0.7) and 17 COPD patients (FEV1 ≥ 40% – <80% predicted, FEV1/VC ≤ 0.7) who had undergone a lobectomy for bronchial carcinoma. Samples were processed for histological and immuno-staining. Volume fractions (Vv) of elastin in alveolar walls and alveolar rims were determined by point counting, and versican and EBP assessed by grading of staining intensities.Elastin Vv was positively correlated with FEV1 for both the alveolar walls (r = 0.66, p < 0.001) and rims (r = 0.41, p < 0.01). Versican was negatively correlated with FEV1 in both regions (r = 0.30 and 0.32 respectively, p < 0.05), with the highest staining intensities found in patients with the lowest values for FEV1. Conversely, staining intensities for EBP in alveolar walls and rims and were positively correlated with FEV1 (r = 0.43 and 0.46, p < 0.01).Patients with mild to moderate COPD show progressively increased immuno-staining for versican and correspondingly decreased immuno-staining for EBP, with decreasing values of FEV1. These findings may explain the lack of repair of elastic fibers in the lungs of patients with moderate COPD. Removal of versican may offer a strategy for effective repair.Chronic obstructive pulmonary disease (COPD) is characterised by loss of elastin in the alveolar walls [1-3]. Recently, we reported that in patients with mild to moderate COPD (GOLD stages 1 and 2) the decreased elastic fiber content of alveoli and small airways strongly correlates with decreased FEV1 [4], consistent with a central role for the loss of elastin in the airflow obstruction in COPD.In COPD, elevated levels of the elastin degrading proteinases MMP-2 and MMP-9 have been found in lung tissue [5,6], alveolar macrophages [7], and sputum of subjects with COPD [8,9] and may contribute to the loss of elastic fibers in COPD. There is evidence from animal studies that repair processes are also activated in the parenchyma of lungs affected by e
Cutaneous Chronic Graft-Versus-Host Disease Does Not Have the Abnormal Endothelial Phenotype or Vascular Rarefaction Characteristic of Systemic Sclerosis
Jo Nadine Fleming,Howard M. Shulman,Richard A. Nash,Pamela Y. Johnson,Thomas N. Wight,Allen Gown,Stephen M. Schwartz
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0006203
Abstract: The clinical and histologic appearance of fibrosis in cutaneous lesions in chronic graft-versus -host disease (c-GVHD) resembles the appearance of fibrosis in scleroderma (SSc). Recent studies identified distinctive structural changes in the superficial dermal microvasculature and matrix of SSc skin. We compared the dermal microvasculature in human c-GVHD to SSc to determine if c-GVHD is a suitable model for SSc.
Riot, why wouldn't you?
Colin Wight
Journal of Critical Globalisation Studies (JCGS) , 2012,
Abstract: All systems have their own logics. One logic of capitalism is exploitation. Let us be clear about this: Marx’s labour theory of value might have its problems but the essence of the theory is sound. Capitalism is a system in which small groups of people (the 1%) systematically exploit large groups of people (the 99%). We all know this, and we are all aware of the consequences, yet we seem unable to do anything to change it. Perhaps the Occupy Movement is the beginning of the beginning when the 99% say enough is enough. Of course, it is far too early to say whether we are entering a new stage of political activism, or perhaps a new form of politics itself. But what we do know is that levels of public disenchantment with politics are high. We can see this disenchantment spreading like a virus, engendering open protest and revolt in the Middle East, riots in Greece, looting and disorder in London and major cities in the UK, student protests in Chile, and producing peaceful protest under the banner of the Occupy Movement across the globe. Something is happening, the question is what?...
Responses of bioenergy sorghum cell wall metabolism to agronomic practices  [PDF]
Jason P. Wight, Frank M. Hons, Godson O. Osuji
Advances in Biological Chemistry (ABC) , 2014, DOI: 10.4236/abc.2014.41010

Maximum lignocellulose yield of biomass sorghum [Sorghum bicolor L. (Moench.)] is hampered by complex biological phenomena related to rotation, nitrogen (N) fertilization, soil tillage, and excessive biomass removal. The biochemical basis of the effects of agronomic practices on sorghum production was studied by the enzymology of the active peroxidase (EC isoenzymes that synthesize lignin. All studied practices altered the peroxidase pI values. Control sorghum without rotation and without N fertilization had the most inhibited peroxidase with very low maximum velocity (Vmax) value (3.10 mmol·min﹣1), and very low lignin (857 kg·ha﹣1) yield, which could decrease soil organic carbon possibly leading to adverse changes in soil chemistry. Corn-sorghum rotations with and without N fertilization increased the Vmax values of peroxidase and lignin and cellulose yields. Rotated sorghum subjected to 50% residue return (the percentage of crop residue was returned to the plot immediately after grinding at harvest) and 280 kg·ha﹣1 N fertilization possessed very active peroxidase (Vmax value 66.4 mmole·min﹣1) and the highest lignin (1387 kg·ha﹣1) yield. The 25% residue return rate without N fertilization induced high lignin (1125 kg·ha﹣1) and cellulose (11,961 kg·ha﹣1) but the 25% residue return rate with 280 kg·ha﹣1 N fertilization induced lower lignin (1046 kg·ha﹣1) yield. Continuously cropped sorghum treated with 336 kg·N·ha﹣1 produced active peroxidase that shared competitive inhibition relationship with the peroxidase of the 84 kg·N·ha﹣1 treatment. Ridge tillage combined with 280 kg·ha﹣1 N fertilization under continuous sorghum resulted in inhibited peroxidase possessing low Vmax value (13.0 μmole·min﹣1). Changing to conventional tillage combined with 280 kg·ha﹣1 N fertilization relieved the inhibition and increased the Vmax value to 23.7 mmol·min﹣1. These biological anomalies of sorghum cell wall related to agronomic practices originated from doubly inhibited sorghum peroxidases. This understanding may guide the choice of sustainable agronomic practices for maximizing lignocellulose yields for the bioenergy industry while protecting the environment.

The N-Terminus of Murine Leukaemia Virus p12 Protein Is Required for Mature Core Stability
Darren J. Wight,Virginie C. Boucherit,Madushi Wanaguru,Efrat Elis,Elizabeth M. A. Hirst,Wilson Li,Marcelo Ehrlich,Eran Bacharach,Kate N. Bishop
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004474
Abstract: The murine leukaemia virus (MLV) gag gene encodes a small protein called p12 that is essential for the early steps of viral replication. The N- and C-terminal regions of p12 are sequentially acting domains, both required for p12 function. Defects in the C-terminal domain can be overcome by introducing a chromatin binding motif into the protein. However, the function of the N-terminal domain remains unknown. Here, we undertook a detailed analysis of the effects of p12 mutation on incoming viral cores. We found that both reverse transcription complexes and isolated mature cores from N-terminal p12 mutants have altered capsid complexes compared to wild type virions. Electron microscopy revealed that mature N-terminal p12 mutant cores have different morphologies, although immature cores appear normal. Moreover, in immunofluorescent studies, both p12 and capsid proteins were lost rapidly from N-terminal p12 mutant viral cores after entry into target cells. Importantly, we determined that p12 binds directly to the MLV capsid lattice. However, we could not detect binding of an N-terminally altered p12 to capsid. Altogether, our data imply that p12 stabilises the mature MLV core, preventing premature loss of capsid, and that this is mediated by direct binding of p12 to the capsid shell. In this manner, p12 is also retained in the pre-integration complex where it facilitates tethering to mitotic chromosomes. These data also explain our previous observations that modifications to the N-terminus of p12 alter the ability of particles to abrogate restriction by TRIM5alpha and Fv1, factors that recognise viral capsid lattices.
Eigenvalues of Jacobian Matrices Report on Steps of Metabolic Reprogramming in a Complex Plant-Environment Interaction  [PDF]
Thomas N?gele, Wolfram Weckwerth
Applied Mathematics (AM) , 2013, DOI: 10.4236/am.2013.48A007

Mathematical modeling of biochemical systems aims at improving the knowledge about complex regulatory networks. The experimental high-throughput measurement of levels of biochemical components, like metabolites and proteins, has become an integral part for characterization of biological systems. Yet, strategies of mathematical modeling to functionally integrate resulting data sets is still challenging. In plant biology, regulatory strategies that determine the metabolic output of metabolism as a response to changes in environmental conditions are hardly traceable by intuition. Mathematical modeling has been shown to be a promising approach to address such problems of plant-environment interaction promoting the comprehensive understanding of plant biochemistry and physiology. In this context, we recently published an inversely calculated solution for first-order partial derivatives, i.e. the Jacobian matrix, from experimental high-throughput data of a plant biochemical model system. Here, we present a biomathematical strategy, comprising 1) the inverse calculation of a biochemical Jacobian; 2) the characterization of the associated eigenvalues and 3) the interpretation of the results with respect to biochemical regulation. Deriving the real parts of eigenvalues provides information about the stability of solutions of inverse calculations. We found that shifts of the eigenvalue real part distributions occur together with metabolic shifts induced by short-term and long-term exposure to low temperature. This indicates the suitability of mathematical Jacobian characterization for recognizing perturbations in the metabolic homeostasis of plant metabolism. Together with our previously published results on inverse Jacobian calculation this represents a comprehensive strategy of mathematical modeling for the analysis of complex biochemical systems and plant-environment interactions from the molecular to the ecosystems level.

Purification of Active Peroxidase Isoenzymes and Their Responses to Nitrogen Fertilization and Rotation of Biomass Sorghum  [PDF]
Jason P. Wight, Frank M. Hons, Sanique M. South, Godson O. Osuji
American Journal of Plant Sciences (AJPS) , 2012, DOI: 10.4236/ajps.2012.310172
Abstract: Peroxidases (EC participate in lignin biosynthesis. But peroxidation is not a tool for assaying lignocellulose metabolism because the active cannot yet be separated from the inactive peroxidases. A biochemical tool for assaying plant cell wall responses to agronomic practices is needed in the lignocellulosic feedstock renewable energy industry. Peroxidase of biomass sorghum was purified to 9 - 13 charge isomers by free solution IEF (Rotofor) technique. Free solution IEF was more effective than chromatographic purification of active peroxidase isoenzymes. Native PAGE separated each charge isomer to three anionic and three cationic isoenzymes. Hydrogen peroxide and o-dianisidine assays showed that only 20% - 30% of the isoenzymes displayed normal Michaelis-Menten kinetics. Sorghum planted without nitrogen fertilization induced the hydrogen peroxide noncompetitive inhibition of peroxidase, but 280 kg·ha–1 nitrogen fertilization and 100% sorghum mineral residue return to the soil tripled the concentration of active peroxidase and relieved the inhibition with concomitant increases of 350 kg lignin and 3532 kg·cellulose·ha–1. Nitrogen fertilization without crop rotation induced hydrogen peroxide inhibition of the peroxidase, but nitrogen fertilization and 25% sorghum rotation changed the PI of the active peroxidase from neutral to mildly acidic and relieved the inhibition with concomitant enormous increases of 690 kg lignin and 7151 kg·cellulose·ha–1. Hydrogen peroxide inhibition kinetics is consistent with the known peroxidase-substrate intermediate dead-end complex formation. Lignocellulosic yield was greatest under the agronomic management that combined 280 kg·ha–1 nitrogen fertilizer with 25% sorghum residue, which resulted in a shift of pI value of the active peroxidase due to a reduction in the Km value of the peroxidase. Therefore, up to 75% of sorghum biomass rather than only 50% can be harvested for conversion to bioenergy products.
YY1 negatively regulates mouse myelin proteolipid protein (Plp1) gene expression in oligodendroglial cells
Olga E Zolova,Patricia A Wight
ASN Neuro , 2011, DOI: 10.1042/an20110021
Abstract: YY1 (Yin and Yang 1) is a multifunctional, ubiquitously expressed, zinc finger protein that can act as a transcriptional activator, repressor, or initiator element binding protein. Previous studies have shown that YY1 modulates the activity of reporter genes driven by the myelin PLP (proteolipid protein) (PLP1/Plp1) promoter. However, it is known that Plp1 intron 1 DNA contains regulatory elements that are required for the dramatic increase in gene activity, coincident with the active myelination period of CNS (central nervous system) development. The intron in mouse contains multiple prospective YY1 target sites including one within a positive regulatory module called the ASE (anti-silencer/enhancer) element. Results presented here demonstrate that YY1 has a negative effect on the activity of a Plp1-lacZ fusion gene [PLP(+)Z] in an immature oligodendroglial cell line (Oli-neu) that is mediated through sequences present in Plp1 intron 1 DNA. Yet YY1 does not bind to its alleged site in the ASE (even though the protein is capable of recognizing a target site in the promoter), indicating that the down-regulation of PLP(+)Z activity by YY1 in Oli-neu cells does not occur through a direct interaction of YY1 with the ASE sequence. Previous studies with Yy1 conditional knockout mice have demonstrated that YY1 is essential for the differentiation of oligodendrocyte progenitors. Nevertheless, the current study suggests that YY1 functions as a repressor (not an activator) of Plp1 gene expression in immature oligodendrocytes. Perhaps YY1 functions to keep the levels of PLP in check in immature cells before vast quantities of the protein are needed in mature myelinating oligodendrocytes.
Augmenting Locomotion in an Anthropomorphic System
Derek Wight,Eric Kubica,David Wang
Journal of Systemics, Cybernetics and Informatics , 2005,
Abstract: A powered orthosis has applications ranging from assisting the elderly to augmenting astronauts. An assistive control scheme is developed that uses the force from a slave actuator to augment the force of a master actuator. This can be used to augment a closed-loop control scheme applied to the master actuator. Initially, actuator augmentation is explored both theoretically and experimentally using a simple mechanical system. The control scheme is then applied to a scale model of human lower limbs on a stationary bicycle to investigate the feasibility of a powered orthosis using pneumatic muscle actuators.
How a masculine work ethic and economic circumstances affect uptake of HIV treatment: experiences of men from an artisanal gold mining community in rural eastern Uganda
Godfrey E Siu,Daniel Wight,Janet Seeley
Journal of the International AIDS Society , 2012, DOI: 10.7448/ias.15.3.17368
Abstract: Background: Current data from Uganda indicate that, compared to women, men are under-represented in HIV treatment, seek treatment later and have a higher mortality while on antiretroviral therapy (ART). By focusing on a masculine work ethic as one of the most predominant expressions of masculinity, this study explores why for some men HIV treatment enhances their masculinity while for others it undermines masculine work identity, leading them to discontinue the treatment. Methods: Participant observation and 26 in-depth interviews with men were conducted in a gold mining village in Eastern Uganda between August 2009 and August 2010. Interviewees included men who were taking HIV treatment, who had discontinued treatment, who suspected HIV infection but had not sought testing, or who had other symptoms unrelated to HIV infection. Results: Many participants reported spending large proportions of their income, alleviating symptoms prior to confirming their HIV infection. This seriously undermined their sense of masculinity gained from providing for their families. Disclosing HIV diagnosis and treatment to employers and work colleagues could reduce job offers and/or collaborative work, as colleagues feared working with “ill” people. Drug side-effects affected work, leading some men to discontinue the treatment. Despite being on ART, some men believed their health remained fragile, leading them to opt out of hard work, contradicting their reputation as hard workers. However, some men on treatment talked about “resurrecting” due to ART and linked their current abilities to work again to good adherence. For some men, it was work colleagues who suggested testing and treatment-seeking following symptoms. Conclusions: The central role of a work ethic in expressing masculinity can both encourage and discourage men's treatment-seeking for AIDS. HIV testing and treatment may be sought in order to improve health and get back to work, thereby in the process regaining one's masculine reputation as a hard worker and provider for one's family. However, disclosure can affect opportunities for work and drug side-effects disrupt one's ability to labour, undermining the sense of masculinity gained from work. HIV support organizations need to recognize how economic and gender concerns impact on treatment decisions and help men deal with work-related fears.
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