120 results on '"Stevenson DE"'
Search Results
2. Skate egg nursery areas support genetic diversity of Alaska and Aleutian skates in the Bering Sea
- Author
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Spies, I, primary, Orr, JW, additional, Stevenson, DE, additional, Goddard, P, additional, Hoff, G, additional, Guthridge, J, additional, Hollowed, M, additional, and Rooper, C, additional
- Published
- 2021
- Full Text
- View/download PDF
3. Acúmulo de Cargos e o Poder Disciplinar da Controladoria Geral de Disciplina
- Author
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Jacob Stevenson de Santana Carvalho Mendes
- Subjects
lcsh:K1-7720 ,lcsh:Law ,lcsh:Law in general. Comparative and uniform law. Jurisprudence ,General Medicine ,Acúmulo de Cargos. Improbidade Administrativa. Poder Disciplinar ,lcsh:K - Abstract
Neste artigo, realiza-se uma análise crítica da inserção das polícias militares estaduais na Constituição Federal – de forma pioneira, em relação às demais forças policiais brasileiras – e do controle dessas forças militares realizado pela União, mediante o Exército Brasileiro. Faz-se ainda uma reflexão sobre a manutenção de seu status militar como imposição do governo central para um controle mais efetivo desses “exércitos estaduais”. Essa manutenção constitui fator de proteção do Pacto Federativo, principalmente para evitar que estados economicamente mais fortes possam representar uma ameaça à federação.
- Published
- 2016
- Full Text
- View/download PDF
4. Skate egg nursery habitat in the eastern Bering Sea: a predictive model
- Author
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Rooper, CN, primary, Hoff, GR, additional, Stevenson, DE, additional, Orr, JW, additional, and Spies, IB, additional
- Published
- 2019
- Full Text
- View/download PDF
5. Acúmulo de Cargos e o Poder Disciplinar da Controladoria Geral de Disciplina
- Author
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Mendes, Jacob Stevenson de Santana Carvalho, primary
- Published
- 2016
- Full Text
- View/download PDF
6. Federal Constitution of 1988 and the estabeleciment of paradigms new for the prision system: A case study in prison Ceará state. (Inglês)
- Author
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Mendes, Jacob Stevenson de Santana Carvalho, Cunha Filho, Francisco Humberto, Rodrigues, Carlos Roberto Martins, and Santiago, Nestor Eduardo Araruna
- Subjects
Sistema penitenciário ,Direito penal ,Direitos humanos - Abstract
Made available in DSpace on 2022-06-22T23:19:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-10 State and Pen settings are closely linked. The work is presented in a broad sense, with the task of performing a search on the historical development, considering the form of government and socio-economic model that influenced the transformation of the application of penalties and prison regimes, exposing rights violations humans in the form it comes down to enforcement of custodial sentences. The exegesis of the Brazilian prison system, its context, its historical antecedents. The observation of constitutional principles to guarantee a social and democratic state of law in the preamble to the regulation of control over the power to punish the state. In this study we conducted a survey on bibliographic sources for understanding the current situation in prisons. Strictly speaking, we intend to observe the routines of a prison unit in the interaction between mass incarceration, their rules of coexistence, the way it establishes the time, space and labor. The reference work is the knowledge of the reform process of the human being. The relevance of the topic "The Constitution of 1988 and the establishment of new paradigms for the prison system: a case observation of Ceará in prison" is established in the daily violence within prisons, as well as the Public Security established extramural. It studied the characteristics of criminal law enforcement and the need for reformulation. Are set out suggestions for the reorientation of the prison system, since alternative measures to deprivation of liberty, to recommendations of an administrative, judicial, legislative and cultural. We conclude this investigation, the story of deprivation of liberty is not being abolished gradually, but constantly changed; its usefulness in the civil reform, as well as the humane treatment is a right guaranteed. The study methodology was employed using the deductive method, dialectical and systemic, and also the historical auxiliary method, a qualitative approach, through research of documents and references, as well as field research visits to the prison. Keywords: Human rights. Prison. Individual guarantees. Resocialization. Estado e Pena são definições intimamente ligadas entre si. O trabalho se apresenta, em sentido amplo, com a tarefa de realizar uma pesquisa relativa ao desenvolvimento histórico, considerando a forma de Estado e o modelo socioeconômico que influíram na transformação do sistema de aplicação de penas e regimes penitenciários; expor a violação dos direitos humanos na forma que se estabelece a aplicação das penas privativas de liberdade. A exegese do sistema prisional brasileiro, sua contextualização, seus antecedentes históricos e a observação dos princípios constitucionais de garantia de um Estado Social e Democrático de Direito, na fundamentação da regulação do controle sobre o poder de punir do Estado, também são estudadas. Neste estudo foi realizada uma pesquisa bibliográfica para compreender a atual situação carcerária. Em sentido estrito, pretende-se observar as rotinas de uma unidade prisional na interação entre a massa carcerária, suas regras de convivência, a forma como se estabelecem o tempo, o espaço e o trabalho. A referência do trabalho é o conhecimento do processo de reforma do ser humano. A relevância do tema a Constituição Federal de 1988 e o estabelecimento de novos paradigmas para o sistema prisional: observação de caso em presídio do Ceará está no cotidiano de violência estabelecida dentro das unidades prisionais, bem como na Segurança Pública estabelecida extramuros. São estudadas as características da legislação de execução penal e a necessidade de reformulação. São expostas sugestões para a reorientação do sistema carcerário, desde medidas alternativas para a privação da liberdade, até recomendações de caráter administrativo, judicial, legislativo e cultural. Conclui-se, nesta investigação, que a história da pena privativa de liberdade não está sendo progressivamente abolida, mas constantemente reformulada; sua utilidade na função reformadora, bem como ser o tratamento humanitário um direito garantido. A metodologia do estudo empregou utilização do método dedutivo, dialético e sistêmico e, ainda, o método auxiliar histórico, uma abordagem qualitativa, através de pesquisa de documentos e referências bibliográficas, bem como de pesquisa de campo em visitas ao presídio. Palavras-chave: Direitos humanos. Sistema prisional. Garantias individuais. Ressocialização.
- Published
- 2011
7. Acúmulo de Cargos e o Poder Disciplinar da Controladoria Geral de Disciplina
- Author
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Santana Carvalho Mendes, Jacob Stevenson de and Santana Carvalho Mendes, Jacob Stevenson de
- Abstract
Neste artigo, realiza-se uma análise crítica da inserção das polícias militares estaduais na Constituição Federal – de forma pioneira, em relação às demais forças policiais brasileiras – e do controle dessas forças militares realizado pela União, mediante o Exército Brasileiro. Faz-se ainda uma reflexão sobre a manutenção de seu status militar como imposição do governo central para um controle mais efetivo desses “exércitos estaduais”. Essa manutenção constitui fator de proteção do Pacto Federativo, principalmente para evitar que estados economicamente mais fortes possam representar uma ameaça à federação.
- Published
- 2014
8. Role of oxidative stress in the mechanism of dieldrin's hepatotoxicity
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Bachowski S, Kyle Kolaja, Xu Y, Ca, Ketcham, Stevenson DE, Ef, Walborg, and Je, Klaunig
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Male ,Dieldrin ,Liver Neoplasms ,Oxidants ,Antioxidants ,Rats, Inbred F344 ,Rats ,Mice ,Oxidative Stress ,Liver ,Malondialdehyde ,Carcinogens ,Microsomes, Liver ,Animals ,Chemical and Drug Induced Liver Injury ,Reactive Oxygen Species ,Mutagens - Abstract
The production of reactive oxygen species (ROS) by toxic chemicals has been implicated in acute and chronic disease states, including cancer. This increase in cellular ROS can lead to a state of oxidative stress. Many compounds selectively induce hepatic tumors in mice but not rats. The mechanism for the induction of hepatic cancer by these compounds and the observed species selectivity of this effect are not known but may be related to the induction of oxidative stress. Dieldrin is one such compound and is used in the present study to characterize the relationship between oxidative stress and the observed selective hepatotoxicity of dieldrin in mice. It was found that dieldrin induced oxidative stress in the mouse but not the rat, and the observed oxidative stress correlated with the induction of DNA S-phase synthesis. This evidence suggests that the induction of oxidative stress may be a mechanism by which dieldrin and other mouse specific compounds selectively induce their hepatic toxic effects in mice.
- Published
- 1997
9. Current problems in the choice of animals for toxicity testing
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Stevenson De
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Time Factors ,Scope (project management) ,Process (engineering) ,Compromise ,media_common.quotation_subject ,Rodentia ,Toxicology ,Pollution ,Risk analysis (engineering) ,Research Design ,Animals, Laboratory ,Toxicity ,Carcinogens ,Carcinogenicity testing ,Animals ,Psychology ,media_common - Abstract
Animal models for the study of toxicity are chosen more for pragmatic reasons such as life-span, ease of handling, and economics than because of a comprehensive process of validation. There is also a tendency to seek the answers to nonspecific questions and then to use those answers in situations where they cannot lead to proper judgments. In some cases, such as in carcinogenicity testing, an uneasy compromise exists between the sensitivity of the model and the background noise. There is scope, by increased attention to both the control of environmental factors and the genetics of the animal models, to increase the sensitivity and validity of the systems that are used in toxicology.
- Published
- 1979
10. A NEW ARBORESCENT SPECIES OF ZAMIA (CYCADALES, ZAMIACEAE) FROM THE DEPARTMENT OF HUILA, EASTERN CORDILLERA OF COLOMBIA
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Calonje Michael, Esquivel Héctor Eduardo, Morales Gustavo, Mora-Lizcano Yhon Alber, and Stevenson Dennis
- Subjects
Science ,Zoology ,QL1-991 ,Botany ,QK1-989 - Abstract
Zamia huilensis Calonje, Esquivel, & D.W. Stev., a new arborescent species from theEastern Cordillera of Colombia (Department of Huila), is described and illustrated. Itis compared to Z. muricata Willd., which has similar leaflet shape, and to Z. tolimensisCalonje, Esquivel & D.W. Stev., with which it shares some reproductive characters.It differs from Z. muricata in having an arborescent trunk, beige-yellow to beigeovulate strobili supported by short peduncles, and microsporangia aggregated intoa single group on abaxial side of microsporophyll; it differs from Z. muricata in thesubterranean trunk, dark brown to black ovulate strobili supported by long peduncles,and microsporangia separated into two groups on abaxial side of microsporophylls.It differs from Z. tolimensis in having an overall smaller size, leaflets that are notstrongly falcate and with margins toothed below the distal half, compared to Z. tolimensiswhich is a much larger plant, and has strongly falcate leaflets that are nottoothed below the distal half.
- Published
- 2012
11. Hepatic effects of dieldrin and phenobarbital in male B6C3F1 mice and Fisher 344 rats: species selective induction of DNA synthesis
- Author
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Kyle Kolaja, Stevenson DE, Jt, Johnson, Ef, Walborg, and Je, Klaunig
- Subjects
Male ,Dieldrin ,Mice ,Liver Neoplasms, Experimental ,Liver ,Phenobarbital ,Animals ,Mice, Inbred Strains ,DNA ,Disease Susceptibility ,Rats, Inbred F344 ,Rats
12. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework
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Calabrese, EJ, Clarkson, TW, Cook, RR, Diamond, DM, Doolittle, DJ, Dorato, MA, Duke, SO, Feinendegen, L, Gardner, DE, Hart, RW, Hastings, KL, Bachmann, KA, Hayes, A, Hoffman, GR, Ives, JA, Jaworowski, Z, Johnson, TE, Jonas, WB, Kaminski, NE, Keller, JG, Klaunig, JE, Knudsen, TB, Bailer, AJ, Kozumbo, WJ, Lettieri, T, Liu, S, Maisseu, A, Maynard, KI, Masoro, EJ, McClellan, RO, Mehendale, HM, Mothersill, C, Newlin, DB, Bolger, PM, Nigg, HN, Oehme, FW, Phalen, RF, Philbert, MA, Rattan, SIS, Riviere, JE, Rodricks, J, Sapolsky, RM, Scott, BR, Seymour, C, Borak, J, Sinclair, DA, Smith-Sonneborn, J, Snow, ET, Spear, L, Stevenson, DE, Thomas, Y, Tubiana, M, Williams, GM, Mattson, MP, Cai, L, Cedergreen, N, Cherian, MG, Chiueh, CC, Calabrese, EJ, Clarkson, TW, Cook, RR, Diamond, DM, Doolittle, DJ, Dorato, MA, Duke, SO, Feinendegen, L, Gardner, DE, Hart, RW, Hastings, KL, Bachmann, KA, Hayes, A, Hoffman, GR, Ives, JA, Jaworowski, Z, Johnson, TE, Jonas, WB, Kaminski, NE, Keller, JG, Klaunig, JE, Knudsen, TB, Bailer, AJ, Kozumbo, WJ, Lettieri, T, Liu, S, Maisseu, A, Maynard, KI, Masoro, EJ, McClellan, RO, Mehendale, HM, Mothersill, C, Newlin, DB, Bolger, PM, Nigg, HN, Oehme, FW, Phalen, RF, Philbert, MA, Rattan, SIS, Riviere, JE, Rodricks, J, Sapolsky, RM, Scott, BR, Seymour, C, Borak, J, Sinclair, DA, Smith-Sonneborn, J, Snow, ET, Spear, L, Stevenson, DE, Thomas, Y, Tubiana, M, Williams, GM, Mattson, MP, Cai, L, Cedergreen, N, Cherian, MG, and Chiueh, CC
- Abstract
Many biological subdisciplines that regularly assess dose–response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose–response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose–response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.
13. Are substitution rates and RNA editing correlated?
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Davis Jerrold I, Seberg Ole, Petersen Gitte, Cuenca Argelia, and Stevenson Dennis W
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Evolution ,QH359-425 - Abstract
Abstract Background RNA editing is a post-transcriptional process that, in seed plants, involves a cytosine to uracil change in messenger RNA, causing the translated protein to differ from that predicted by the DNA sequence. RNA editing occurs extensively in plant mitochondria, but large differences in editing frequencies are found in some groups. The underlying processes responsible for the distribution of edited sites are largely unknown, but gene function, substitution rate, and gene conversion have been proposed to influence editing frequencies. Results We studied five mitochondrial genes in the monocot order Alismatales, all showing marked differences in editing frequencies among taxa. A general tendency to lose edited sites was observed in all taxa, but this tendency was particularly strong in two clades, with most of the edited sites lost in parallel in two different areas of the phylogeny. This pattern is observed in at least four of the five genes analyzed. Except in the groups that show an unusually low editing frequency, the rate of C-to-T changes in edited sites was not significantly higher that in non-edited 3rd codon positions. This may indicate that selection is not actively removing edited sites in nine of the 12 families of the core Alismatales. In all genes but ccmB, a significant correlation was found between frequency of change in edited sites and synonymous substitution rate. In general, taxa with higher substitution rates tend to have fewer edited sites, as indicated by the phylogenetically independent correlation analyses. The elimination of edited sites in groups that lack or have reduced levels of editing could be a result of gene conversion involving a cDNA copy (retroprocessing). If so, this phenomenon could be relatively common in the Alismatales, and may have affected some groups recurrently. Indirect evidence of retroprocessing without a necessary correlation with substitution rate was found mostly in families Alismataceae and Hydrocharitaceae (e.g., groups that suffered a rapid elimination of all their edited sites, without a change in substitution rate). Conclusions The effects of substitution rate, selection, and/or gene conversion on the dynamics of edited sites in plant mitochondria remain poorly understood. Although we found an inverse correlation between substitution rate and editing frequency, this correlation is partially obscured by gene retroprocessing in lineages that have lost most of their edited sites. The presence of processed paralogs in plant mitochondria deserves further study, since most evidence of their occurrence is circumstantial.
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- 2010
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14. ESTimating plant phylogeny: lessons from partitioning
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Stevenson Dennis W, Brenner Eric D, Katari Manpreet S, Egan Mary G, de la Torre Jose EB, Coruzzi Gloria M, and DeSalle Rob
- Subjects
Evolution ,QH359-425 - Abstract
Abstract Background While Expressed Sequence Tags (ESTs) have proven a viable and efficient way to sample genomes, particularly those for which whole-genome sequencing is impractical, phylogenetic analysis using ESTs remains difficult. Sequencing errors and orthology determination are the major problems when using ESTs as a source of characters for systematics. Here we develop methods to incorporate EST sequence information in a simultaneous analysis framework to address controversial phylogenetic questions regarding the relationships among the major groups of seed plants. We use an automated, phylogenetically derived approach to orthology determination called OrthologID generate a phylogeny based on 43 process partitions, many of which are derived from ESTs, and examine several measures of support to assess the utility of EST data for phylogenies. Results A maximum parsimony (MP) analysis resulted in a single tree with relatively high support at all nodes in the tree despite rampant conflict among trees generated from the separate analysis of individual partitions. In a comparison of broader-scale groupings based on cellular compartment (ie: chloroplast, mitochondrial or nuclear) or function, only the nuclear partition tree (based largely on EST data) was found to be topologically identical to the tree based on the simultaneous analysis of all data. Despite topological conflict among the broader-scale groupings examined, only the tree based on morphological data showed statistically significant differences. Conclusion Based on the amount of character support contributed by EST data which make up a majority of the nuclear data set, and the lack of conflict of the nuclear data set with the simultaneous analysis tree, we conclude that the inclusion of EST data does provide a viable and efficient approach to address phylogenetic questions within a parsimony framework on a genomic scale, if problems of orthology determination and potential sequencing errors can be overcome. In addition, approaches that examine conflict and support in a simultaneous analysis framework allow for a more precise understanding of the evolutionary history of individual process partitions and may be a novel way to understand functional aspects of different kinds of cellular classes of gene products.
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- 2006
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15. EST analysis in Ginkgo biloba: an assessment of conserved developmental regulators and gymnosperm specific genes
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Runko Suzan J, Twigg Richard W, Moss Walter N, Douglas Andrew W, Rudd Stephen A, Stevenson Dennis W, Katari Manpreet S, Brenner Eric D, Stellari Giulia M, McCombie WR, and Coruzzi Gloria M
- Subjects
Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Ginkgo biloba L. is the only surviving member of one of the oldest living seed plant groups with medicinal, spiritual and horticultural importance worldwide. As an evolutionary relic, it displays many characters found in the early, extinct seed plants and extant cycads. To establish a molecular base to understand the evolution of seeds and pollen, we created a cDNA library and EST dataset from the reproductive structures of male (microsporangiate), female (megasporangiate), and vegetative organs (leaves) of Ginkgo biloba. Results RNA from newly emerged male and female reproductive organs and immature leaves was used to create three distinct cDNA libraries from which 6,434 ESTs were generated. These 6,434 ESTs from Ginkgo biloba were clustered into 3,830 unigenes. A comparison of our Ginkgo unigene set against the fully annotated genomes of rice and Arabidopsis, and all available ESTs in Genbank revealed that 256 Ginkgo unigenes match only genes among the gymnosperms and non-seed plants – many with multiple matches to genes in non-angiosperm plants. Conversely, another group of unigenes in Gingko had highly significant homology to transcription factors in angiosperms involved in development, including MADS box genes as well as post-transcriptional regulators. Several of the conserved developmental genes found in Ginkgo had top BLAST homology to cycad genes. We also note here the presence of ESTs in G. biloba similar to genes that to date have only been found in gymnosperms and an additional 22 Ginkgo genes common only to genes from cycads. Conclusion Our analysis of an EST dataset from G. biloba revealed genes potentially unique to gymnosperms. Many of these genes showed homology to fully sequenced clones from our cycad EST dataset found in common only with gymnosperms. Other Ginkgo ESTs are similar to developmental regulators in higher plants. This work sets the stage for future studies on Ginkgo to better understand seed and pollen evolution, and to resolve the ambiguous phylogenetic relationship of G. biloba among the gymnosperms.
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- 2005
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16. Tips from clinical experts. Allergy testing.
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Stevenson DE and Baer DM
- Published
- 2001
17. Adecuación del SG SST de Stewart & Stevenson de las Américas Colombia Ltda
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Rojas Gómez, Diana Carolina, Forero Clavijo, Fabian Leonardo, Penagos Rojas, Jose Yamid, and Stewart & Stevenson de las Américas Colombia Ltda
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Lista de verificación ,2018 [ISO 45001] ,Sistema de gestión de seguridad y salud en el trabajo ,Checklist ,Security and health management system - Abstract
328 p. The Security and Health Management Systems must be implemented by all public and private employers through the development of processes and policies for the protection of workers in order to improve the work environment, well-being and quality of employees, the decrease in the rates of absenteeism due to occupational disease, the reduction of the accident rate and mortality due to accidents at work and bring with it an increase in the productivity of the organization. At the international level, ISO 45001: 2018 is the one that currently determines the basic requirements to implement a Security and Health Management System in an organization in an integrated manner with the requirements established in ISO 9001 (Quality Management System) and ISO 14001 (Environmental Management System) and was developed in order to help organizations provide safe and healthy workplaces for their employees. Stewart & Stevenson de las Américas Colombia Ltda knows the importance of generating evidence on the Security and Health System and for this reason the objective of this project was to adapt the necessary tools to allow the company to seek a certification for its System of Occupational Health and Safety Management based on the ISO 45001: 2018 standard by applying a checklist. Título del Proyecto - pág. 8 Introducción - pág. 9 Problema de Investigación - pág. 10 Descripción del Problema - pág. 10 Formulación del Problema - pág. 11 Sistematización - pág. 11 Objetivos - pág. 12 Objetivo General - pág.12 Objetivos Específicos - pág. 12 Justificación - pág. 13 Delimitación - pág. 13 Limitaciones - pág. 14 Marcos de Referencia - pág.15 Estado del Arte - pág. 15 Marco Teórico - pág. 19 Sistemas de gestión - pág. 20 Caracterización del sistema de gestión de seguridad y salud en el trabajo - pág. 22 ISO 45001:2018 - pág. 23 Accidente de trabajo - pág. 26 Incidentes de trabajo - pág. 26 Enfermedad laboral - pág. 26 Riesgo químico - pág. 27 Riesgo físico - pág. 27 Riesgo biológico - pág. 28 Guía técnica colombiana GTC 45 - pág. 28 Marco Legal - pág. 28 Marco Metodológico - pág. 31 Paradigma - pág. 31 Tipo y Diseño de Investigación - pág. 31 Población - pág. 32 Muestra - pág. 33 Instrumentos - pág. 33 Técnica de Análisis de Datos - pág. 33 Fases de la Investigación - pág. 35 Cronograma - pág. 36 Presupuesto - pág. 37 Resultados - pág. 40 Análisis de los Resultados - pág. 57 Conclusiones - pág. 61 Recomendaciones - pág. 62 Bibliografía - pág. 63 Anexos - pág. 68 Los Sistemas de Gestión de Seguridad y Salud en el Trabajo deben ser implementados por todos los empleadores públicos y privados mediante el desarrollo de procesos y políticas de protección a los trabajadores con el fin de mejora del ambiente de trabajo, el bienestar y la calidad de los colaboradores, la disminución de las tasas de ausentismo por enfermedad laboral, la reducción de las tasas de accidentalidad y mortalidad por accidentes de trabajo y traer consigo el aumento de la productividad de la organización. A nivel internacional la norma ISO 45001:2018 es aquella que determina actualmente los requisitos básicos para implementar un Sistema de Gestión de Seguridad y Salud en el Trabajo en una organización de manera integrada junto con los requisitos establecidos en la norma ISO 9001 (Sistema de Gestión de Calidad) e ISO 14001 (Sistema de Gestión Ambiental) y se desarrolló con el fin de ayudar a las organizaciones a proporcionar lugares de trabajo seguro y saludable a sus colaboradores. Stewart & Stevenson de las Américas Colombia Ltda conoce la importancia de generar evidencias sobre el Sistema de Seguridad y Salud en el Trabajo y por tal razón se pretendió con este proyecto adecuar las herramientas necesarias para permitir a la empresa buscar una certificación para su Sistema de Gestión de Seguridad y Salud en el Trabajo basado en la norma ISO 45001:2018 mediante la aplicación de una lista de verificación.
- Published
- 2021
18. Interspecific differences in the flow regimes and drag of North Pacific skate egg cases.
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Hall KC, Elcock JN, Hoff GR, Stevenson DE, Summers AP, and Donatelli CM
- Abstract
Skates are a diverse group of dorso-ventrally compressed cartilaginous fishes found primarily in high-latitude seas. These slow-growing oviparous fishes deposit their fertilized eggs into cases, which then rest on the seafloor. Developing skates remain in their cases for 1-4 years after they are deposited, meaning the abiotic characteristics of the deposition sites, such as current and substrate type, must interact with the capsule in a way to promote long residency. Egg cases are morphologically variable and can be identified to species. Both the gross morphology and the microstructures of the egg case interact with substrate to determine how well a case stays in place on a current-swept seafloor. Our study investigated the egg case hydrodynamics of eight North Pacific skate species to understand how their morphology affects their ability to stay in place. We used a flume to measure maximum current velocity, or "break-away velocity," each egg case could withstand before being swept off the substrate and a tilt table to measure the coefficient of static friction between each case and the substrate. We also used the programming software R to calculate theoretical drag on the egg cases of each species. For all flume trials, we found the morphology of egg cases and their orientation to flow to be significantly correlated with break-away velocity. In certain species, the morphology of the egg case was correlated with flow rate required to dislodge a case from the substrate in addition to the drag experienced in both the theoretical and flume experiments. These results effectively measure how well the egg cases of different species remain stationary in a similar habitat. Parsing out attachment biases and discrepancies in flow regimes of egg cases allows us to identify where we are likely to find other elusive species nursery sites. These results will aid predictive models for locating new nursery habitats and protective policies for avoiding the destruction of these nursery sites., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)
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- 2022
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19. Genetic evidence of a northward range expansion in the eastern Bering Sea stock of Pacific cod.
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Spies I, Gruenthal KM, Drinan DP, Hollowed AB, Stevenson DE, Tarpey CM, and Hauser L
- Abstract
Poleward species range shifts have been predicted to result from climate change, and many observations have confirmed such movement. Poleward shifts may represent a homogeneous shift in distribution, seasonal northward movement of specific populations, or colonization processes at the poleward edge of the distribution. The ecosystem of the Bering Sea has been changing along with the climate, moving from an arctic to a subarctic system. Several fish species have been observed farther north than previously reported and in increasing abundances. We examined one of these fish species, Pacific cod, in the northern Bering Sea (NBS) to assess whether they migrated from another stock in the eastern Bering Sea (EBS), Gulf of Alaska, or Aleutian Islands, or whether they represent a separate population. Genetic analyses using 3,599 single nucleotide polymorphism markers indicated that nonspawning cod collected in August 2017 in the NBS were similar to spawning stocks of cod in the EBS. This result suggests escalating northward movement of the large EBS stock during summer months. Whether the cod observed in the NBS migrate south during winter to spawn or remain in the NBS as a sink population is unknown., Competing Interests: None declared., (© 2019 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)
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- 2019
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20. Molecular phylogenetics of snailfishes (Cottoidei: Liparidae) based on MtDNA and RADseq genomic analyses, with comments on selected morphological characters.
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Orr JW, Spies I, Stevenson DE, Longo GC, Kai Y, Ghods S, and Hollowed M
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- Animals, Base Sequence, Phylogeny, Sequence Analysis, DNA, DNA, Mitochondrial, Genomics, Perciformes genetics
- Abstract
Phylogenetic relationships of snailfishes of the family Liparidae were analyzed on the basis of two sets of molecular sequence data: one from the mitochondrial DNA cytochrome c oxidase subunit one gene (COI) and another from restriction-site associated genome-wide sequences (RADseq). The analysis of COI sequence data from at least 122 species of 18 genera from the Pacific, Atlantic, and Southern oceans resulted in a moderately well-resolved phylogeny among the major clades, albeit with significant polytomy among central clades. Nectoliparis was the sister of all other members of the family, followed by Liparis. Liparis, Careproctus, and Paraliparis were paraphyletic. Liparis was recovered in two closely related clades, with L. fucensis sister of all other liparids except Nectoliparis, and both Careproctus and Paraliparis were each recovered among at least three widely separated clades. The RADseq analysis of 26 species of 11 genera from the eastern North Pacific strongly confirmed the overall results of the COI analysis, with the exception of the paraphyly of Liparis due to the absence of L. fucensis. Our results show that the pelvic disc has been independently lost multiple times and the pectoral-fin girdle has been independently reduced in multiple lineages.
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- 2019
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21. Emergency Department Pain Management Following Implementation of a Geriatric Hip Fracture Program.
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Casey SD, Stevenson DE, Mumma BE, Slee C, Wolinsky PR, Hirsch CH, and Tyler K
- Subjects
- Acetaminophen, Aged, Aged, 80 and over, Analgesics, Non-Narcotic, Analgesics, Opioid, Critical Pathways, Fascia innervation, Female, Humans, Male, Musculoskeletal Pain drug therapy, Pain Measurement, Program Evaluation, Retrospective Studies, Time Factors, Analgesics therapeutic use, Emergency Service, Hospital, Hip Fractures therapy, Nerve Block methods, Pain Management
- Abstract
Introduction: Over 300,000 patients in the United States sustain low-trauma fragility hip fractures annually. Multidisciplinary geriatric fracture programs (GFP) including early, multimodal pain management reduce morbidity and mortality. Our overall goal was to determine the effects of a GFP on the emergency department (ED) pain management of geriatric fragility hip fractures., Methods: We performed a retrospective study including patients age ≥65 years with fragility hip fractures two years before and two years after the implementation of the GFP. Outcomes were time to (any) first analgesic, use of acetaminophen and fascia iliaca compartment block (FICB) in the ED, and amount of opioid medication administered in the first 24 hours. We used permutation tests to evaluate differences in ED pain management following GFP implementation., Results: We studied 131 patients in the pre-GFP period and 177 patients in the post-GFP period. In the post-GFP period, more patients received FICB (6% vs. 60%; difference 54%, 95% confidence interval [CI] 45-63%; p<0.001) and acetaminophen (10% vs. 51%; difference 41%, 95% CI 32-51%; p<0.001) in the ED. Patients in the post-GFP period also had a shorter time to first analgesic (103 vs. 93 minutes; p=0.04) and received fewer morphine equivalents in the first 24 hours (15mg vs. 10mg, p<0.001) than patients in the pre-GFP period., Conclusion: Implementation of a GFP was associated with improved ED pain management for geriatric patients with fragility hip fractures. Future studies should evaluate the effects of these changes in pain management on longer-term outcomes., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.
- Published
- 2017
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22. Osteology of the prowfish, Zaprora silenus (Cottiformes: Zoarcoidei: Zaproridae).
- Author
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Hilton EJ and Stevenson DE
- Subjects
- Animals, Perciformes classification, Phylogeny, Bone and Bones anatomy & histology, Perciformes anatomy & histology
- Abstract
The prowfish, Zaprora silenus, is the sole member of the family Zaproridae. It is a large, relatively elongate species with a robust head and body, and it feeds primarily on jellyfishes. Although the larvae and juveniles are pelagic, the adults are demersal, and the species is widely distributed from Southern California around the Pacific Rim to Hokkaido, Japan. The stichaeid affinities of this species have long been recognized, and the family is currently placed, along with the Stichaeidae, in the Zoarcoidei. Previous anatomical studies of Zaprora have been based on relatively few specimens from a limited geographic range and have not included cleared and stained (c&s) specimens. Here, we provide a complete description of the osteology of the prowfish, based on a large series of specimens representing a broad ontogenetic range, including a series of c&s specimens. Our results contradict the findings of previous authors in the structure of the pharyngeal teeth, presence of the pelvic girdle, and the placement of the first dorsal pterygiophore. However, we concur with the findings of previous morphological and molecular phylogenetic studies, which indicate that the prowfish is probably most closely related to at least some members of the Stichaeidae., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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23. Fecal microbial metabolism of polyphenols and its effects on human gut microbiota.
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Parkar SG, Trower TM, and Stevenson DE
- Subjects
- Bacteria classification, Bacteria genetics, Bacteria growth & development, Biotransformation, Culture Media chemistry, Feces microbiology, Healthy Volunteers, Humans, Male, Models, Theoretical, Real-Time Polymerase Chain Reaction, Bacteria drug effects, Biota, Gastrointestinal Tract microbiology, Polyphenols metabolism
- Abstract
We investigated the biotransformation of four common dietary polyphenols, rutin, quercetin, chlorogenic acid and caffeic acid, in an in vitro mixed culture model of human intestinal microbiota, to determine effects on human gut bacteria. All four compounds were biotransformed rapidly, disappearing from the medium within 0.5 h and later replaced by known phenolic acid breakdown products, at concentrations up to hundreds of micromolar, much higher than in no-polyphenol control experiments. Quantitative PCR was used to measure effects of the polyphenols on the balance between the major groups of intestinal bacteria that are known to influence gut health, i.e., Bifidobacterium spp., Bacteroidetes, and Firmicutes. Fermentation of polyphenols stimulated proliferation of bifidobacteria and decreased the ratio of Firmicutes to Bacteroidetes, relative to controls. Polyphenols also stimulated short chain fatty acid production by the bacteria. Pure bifidobacterial cultures were treated separately with either fermented media isolated from the incubations, the pure test polyphenols, or the biotransformation products detected in the fermentations. Growth stimulation was observed only with fermented polyphenol media and the pure biotransformation products. It appears that dietary polyphenols may have the ability to modify the gut microbial balance, but this effect is indirect, i.e., it is mediated by biotransformation products, rather than the original plant compounds., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Published
- 2013
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24. Phenotypic changes associated with RNA interference silencing of chalcone synthase in apple (Malus × domestica).
- Author
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Dare AP, Tomes S, Jones M, McGhie TK, Stevenson DE, Johnson RA, Greenwood DR, and Hellens RP
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- Acyltransferases genetics, Biological Transport, Cell Shape, Chalcones metabolism, Enzyme Activation, Flavanones, Fruit anatomy & histology, Fruit enzymology, Fruit genetics, Genes, Plant, Genetic Complementation Test, Indoleacetic Acids metabolism, Malus anatomy & histology, Malus genetics, Phlorhizin, Plant Cells enzymology, Plant Proteins genetics, Plant Proteins metabolism, Plants, Genetically Modified enzymology, Plants, Genetically Modified genetics, Acyltransferases metabolism, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Plant, Malus enzymology, Phenotype, RNA Interference
- Abstract
We have identified in apple (Malus × domestica) three chalcone synthase (CHS) genes. In order to understand the functional redundancy of this gene family RNA interference knockout lines were generated where all three of these genes were down-regulated. These lines had no detectable anthocyanins and radically reduced concentrations of dihydrochalcones and flavonoids. Surprisingly, down-regulation of CHS also led to major changes in plant development, resulting in plants with shortened internode lengths, smaller leaves and a greatly reduced growth rate. Microscopic analysis revealed that these phenotypic changes extended down to the cellular level, with CHS-silenced lines showing aberrant cellular organisation in the leaves. Fruit collected from one CHS-silenced line was smaller than the 'Royal Gala' controls, lacked flavonoids in the skin and flesh and also had changes in cell morphology. Auxin transport experiments showed increased rates of auxin transport in a CHS-silenced line compared with the 'Royal Gala' control. As flavonoids are well known to be key modulators of auxin transport, we hypothesise that the removal of almost all flavonoids from the plant by CHS silencing creates a vastly altered environment for auxin transport to occur and results in the observed changes in growth and development., (© 2013 The Authors The Plant Journal © 2013 Blackwell Publishing Ltd.)
- Published
- 2013
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25. Apple skin patterning is associated with differential expression of MYB10.
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Telias A, Lin-Wang K, Stevenson DE, Cooney JM, Hellens RP, Allan AC, Hoover EE, and Bradeen JM
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- Alleles, Anthocyanins analysis, Cytosine metabolism, DNA Methylation, Fruit metabolism, Galactosides analysis, Gene Expression Regulation, Plant, Malus metabolism, Malus physiology, Phenotype, Pigmentation, Plant Proteins genetics, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Transcription Factors genetics, Transcription, Genetic, Up-Regulation, Anthocyanins biosynthesis, Fruit physiology, Malus genetics, Plant Proteins metabolism, Transcription Factors metabolism
- Abstract
Background: Some apple (Malus × domestica Borkh.) varieties have attractive striping patterns, a quality attribute that is important for determining apple fruit market acceptance. Most apple cultivars (e.g. 'Royal Gala') produce fruit with a defined fruit pigment pattern, but in the case of 'Honeycrisp' apple, trees can produce fruits of two different kinds: striped and blushed. The causes of this phenomenon are unknown., Results: Here we show that striped areas of 'Honeycrisp' and 'Royal Gala' are due to sectorial increases in anthocyanin concentration. Transcript levels of the major biosynthetic genes and MYB10, a transcription factor that upregulates apple anthocyanin production, correlated with increased anthocyanin concentration in stripes. However, nucleotide changes in the promoter and coding sequence of MYB10 do not correlate with skin pattern in 'Honeycrisp' and other cultivars differing in peel pigmentation patterns. A survey of methylation levels throughout the coding region of MYB10 and a 2.5 Kb region 5' of the ATG translation start site indicated that an area 900 bp long, starting 1400 bp upstream of the translation start site, is highly methylated. Cytosine methylation was present in all three contexts, with higher methylation levels observed for CHH and CHG (where H is A, C or T) than for CG. Comparisons of methylation levels of the MYB10 promoter in 'Honeycrisp' red and green stripes indicated that they correlate with peel phenotypes, with an enrichment of methylation observed in green stripes., Conclusions: Differences in anthocyanin levels between red and green stripes can be explained by differential transcript accumulation of MYB10. Different levels of MYB10 transcript in red versus green stripes are inversely associated with methylation levels in the promoter region. Although observed methylation differences are modest, trends are consistent across years and differences are statistically significant. Methylation may be associated with the presence of a TRIM retrotransposon within the promoter region, but the presence of the TRIM element alone cannot explain the phenotypic variability observed in 'Honeycrisp'. We suggest that methylation in the MYB10 promoter is more variable in 'Honeycrisp' than in 'Royal Gala', leading to more variable color patterns in the peel of this cultivar.
- Published
- 2011
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26. Changing challenges and paradigms.
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Stevenson DE
- Subjects
- Animals, Diffusion of Innovation, History, 20th Century, History, 21st Century, Humans, Models, Biological, Public Health, Risk Assessment, Toxicology history, United States, United States Environmental Protection Agency, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Toxicology methods
- Abstract
Change comes as a surprise because things do not happen in a straight line. Concepts often evolve haphazardly, reacting to specific events. Assumptions are made but are not challenged, sometimes for political or social expedience. It has long been recognized that the dose makes the poison. Concepts of the relationship evolved from both events and the availability of exploratory tools. There are consequences to risk aversion. The general concept of hormesis is perhaps not unexpected. The acceptance of multiphasic dose-responses has the potential to unleash additional and productive insights into this relationship. The activities of BELLE and its Newsletter provide an excellent example of what can be achieved when dogmas are challenged by the accrual of information that has not been previously examined to see whether additional insights are possible. A forthcoming challenge will be the critical examination of all the inputs and assumptions that will be used in the increasing sophistication of biological modeling.
- Published
- 2010
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27. Determining circadian response of adult male Acrobasis nuxvorella (Lepidoptera: Pyralidae) to synthetic sex attractant pheromone through time-segregated trapping with a new clockwork timing trap.
- Author
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Stevenson DE and Harris MK
- Subjects
- Animals, Carya parasitology, Female, Flight, Animal, Insect Control instrumentation, Male, Circadian Rhythm, Moths physiology, Sex Attractants physiology, Sexual Behavior, Animal
- Abstract
Mate finding is a key lifecycle event for the pecan nut casebearer, Acrobasis nuxvorella Neunzig, as it is for virtually all Lepidoptera, many of which rely on long-range, species-specific sex pheromones, regulated largely by circadian clocks. Adult male moths were trapped at discrete time intervals during the first two seasonal flights for 6 yr to determine times of peak activity associated with male response to pheromones. From 1997 to 2002, the Harris-Coble automated clockwork timing trap was used for hourly time-segregated sampling. Analysis of variance with linear contrasts determined that circadian response of A. nuxvorella males to pecan nut casebearer pheromone began at approximately 2100 hours, the first hour of total darkness, lasting for 6-7 h. It peaked from midnight to 0400 hours and ended at the onset of morning twilight, approximately 0500 hours. The hours of peak activity are hours of minimal bat predation. The study shows that pecan nut casebearer males become responsive to pheromone several hours before females start calling and remain responsive for at least 1 h after they stop. The extended response period conforms to studies of other polygamous Lepidoptera in which a selective advantage is conferred on early responding males in scramble competition for available females.
- Published
- 2009
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28. Physiological time model for predicting adult emergence of western corn rootworm (Coleoptera: Chrysomelidae) in the Texas High Plains.
- Author
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Stevenson DE, Michels GJ, Bible JB, Jackman JA, and Harris MK
- Subjects
- Animals, Climate, Temperature, Texas, Time Factors, Zea mays growth & development, Zea mays parasitology, Coleoptera growth & development, Models, Biological
- Abstract
Field observations at three locations in the Texas High Plains were used to develop and validate a degree-day phenology model to predict the onset and proportional emergence of adult Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae) adults. Climatic data from the Texas High Plains Potential Evapotranspiration network were used with records of cumulative proportional adult emergence to determine the functional lower developmental temperature, optimum starting date, and the sum of degree-days for phenological events from onset to 99% adult emergence. The model base temperature, 10 degrees C (50 degrees F), corresponds closely to known physiological lower limits for development. The model uses a modified Gompertz equation, y = 96.5 x exp (-(exp(6.0 - 0.00404 x (x - 4.0), where x is cumulative heat (degree-days), to predict y, cumulative proportional emergence expressed as a percentage. The model starts degree-day accumulation on the date of corn, Zea mays L., emergence, and predictions correspond closely to corn phenological stages from tasseling to black layer development. Validation shows the model predicts cumulative proportional adult emergence within a satisfactory interval of 4.5 d. The model is flexible enough to accommodate early planting, late emergence, and the effects of drought and heat stress. The model provides corn producers ample lead time to anticipate and implement adult control practices.
- Published
- 2008
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29. Preparative enzymatic synthesis of glucuronides of zearalenone and five of its metabolites.
- Author
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Stevenson DE, Hansen RP, Loader JI, Jensen DJ, Cooney JM, Wilkins AL, and Miles CO
- Subjects
- Animals, Cattle, Glucuronides chemistry, Magnetic Resonance Spectroscopy, Models, Molecular, Zearalenone chemistry, Zearalenone metabolism, Glucuronides biosynthesis, Glucuronosyltransferase metabolism, Zearalenone biosynthesis
- Abstract
The resorcylic acid lactones zearalenone ( 1), alpha-zearalenol ( 2), beta-zearalenol ( 3), alpha-zearalanol (zeranol) ( 4), beta-zearalanol (taleranol) ( 5), and zearalanone ( 6) were converted to their glucuronides on a preparative scale in good yields. Reactions were conducted with bovine uridine 5'-diphosphoglucuronyl transferase (UDPGT) as catalyst and uridine 5'-diphosphoglucuronic acid (UDPGA) as cofactor. The glucuronides were isolated by column chromatography and characterized by NMR spectroscopy and mass spectrometry. Although the principal products were 4- O-glucuronides (i.e., linkage through a phenolic hydroxyl), significant quantities of the 6'- O-glucuronides (i.e., linkage through the aliphatic hydroxyl) of alcohols 2, 4, and 5 were also isolated. In the case of 3, the 2- O-glucuronide was isolated as the minor product. Overall isolated yields of glucuronides, performed on a 20-50 mg scale, were typically ca. 80% based on the resorcylic acid lactone starting material. LC-UV-MS (2) analysis of purified specimens revealed MS (2) fragmentations useful for defining the point of attachment of the glucuronide moiety to the zearalenone nucleus.
- Published
- 2008
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30. The potential influence of fruit polyphenols on colonic microflora and human gut health.
- Author
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Parkar SG, Stevenson DE, and Skinner MA
- Subjects
- Caco-2 Cells, Colony Count, Microbial, Dose-Response Relationship, Drug, Escherichia coli drug effects, Escherichia coli growth & development, Escherichia coli physiology, Humans, Lacticaseibacillus rhamnosus drug effects, Lacticaseibacillus rhamnosus growth & development, Lacticaseibacillus rhamnosus physiology, Microbial Sensitivity Tests, Polyphenols, Probiotics, Salmonella typhimurium drug effects, Salmonella typhimurium growth & development, Salmonella typhimurium physiology, Staphylococcus aureus drug effects, Staphylococcus aureus growth & development, Staphylococcus aureus physiology, Bacterial Adhesion drug effects, Bacterial Adhesion physiology, Colon microbiology, Enterocytes microbiology, Flavonoids pharmacology, Phenols pharmacology
- Abstract
The effect of common dietary polyphenols on growth of human gut bacteria and their adhesion to enterocytes was investigated. The influence on the growth of a probiotic (Lactobacillus rhamnosus), a commensal (Escherichia coli) and two pathogenic bacteria (Staphylococcus aureus, Salmonella typhimurium) was determined, together with effects on adhesion of pathogenic and probiotic bacteria to cultured Caco-2 cells. All polyphenols, except rutin, were found to affect the viability of representative gut flora in vitro, at doses likely to be present in the gastrointestinal tract, but to differing degrees. Naringenin and quercetin were the most active with the lowest minimum inhibitory concentrations for all the four bacteria tested. The remaining polyphenols had the most marked effect on the Gram positive enteropathogen S. aureus. Naringenin and phloridzin were the most effective inhibitors of S. typhimurium adherence to Caco-2 enterocytes while phloridzin and rutin enhanced the adherence of the probiotic L. rhamnosus. Polyphenols appear to have potential to alter gut microecology and, by affecting the total number of beneficial microflora in the gut, may confer positive gut health benefits.
- Published
- 2008
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31. Comparison of enzymically glucuronidated flavonoids with flavonoid aglycones in an in vitro cellular model of oxidative stress protection.
- Author
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Stevenson DE, Cooney JM, Jensen DJ, Wibisono R, Adaim A, Skinner MA, and Zhang J
- Subjects
- Cell Line, Tumor, Cell Survival drug effects, Humans, Antioxidants pharmacology, Flavonoids pharmacology, Glucuronides pharmacology, Hydrogen Peroxide pharmacology, Oxidative Stress drug effects
- Abstract
This study modeled, in vitro, the potential effect of conjugative (phase II) metabolism on the cytoprotective capacity of fruit flavonoids against oxidative stress. Flavonoid aglycones were compared with their corresponding isomeric mixtures of glucuronides for their ability to enhance the survival of cultured human Jurkat T and neuroblastoma cells stressed with hydrogen peroxide. Various polyphenolic compounds were tested as substrates in vitro for an ovine liver glucuronyl transferase preparation. Flavonoids and their glycoside derivatives were found to be good substrates, whereas phenolic acids were either poor or nonsubstrates. Five common flavonoids were glucuronidated to prepare mixtures for bioassay testing. Glucuronidation generally weakened the cytoprotective capacities of flavonoids (in the presence of H(2)O(2)), but some compounds were weakened much more than others. The concentration that halved cell death was well below 0.5 microM for most flavonoids tested, but glucuronidation increased median effective concentration values to a range of 1-16 microM. This compares with the generally accepted physiological range (0.1-10 microM) for circulating dietary polyphenolics detected in the body. Therefore, some flavonoids may retain a reduced cytoprotective capacity in vitro, after glucuronidation, whereas others may be effectively inactivated.
- Published
- 2008
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32. Polyphenolic phytochemicals--just antioxidants or much more?
- Author
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Stevenson DE and Hurst RD
- Subjects
- Antioxidants metabolism, Diet, Energy Metabolism drug effects, Flavonoids metabolism, Humans, In Vitro Techniques, Inflammation drug therapy, Intestinal Absorption, Neoplasms drug therapy, Neuroprotective Agents pharmacology, Phenols metabolism, Phytotherapy, Plant Extracts metabolism, Plants metabolism, Polyphenols, Signal Transduction, Antioxidants pharmacology, Flavonoids pharmacology, Phenols pharmacology, Plant Extracts pharmacology
- Abstract
Polyphenolic phytochemicals are ubiquitous in plants, in which they function in various protective roles. A 'recommended' human diet contains significant quantities of polyphenolics, as they have long been assumed to be 'antioxidants' that scavenge excessive, damaging, free radicals arising from normal metabolic processes. There is recent evidence that polyphenolics also have 'indirect' antioxidant effects through induction of endogenous protective enzymes. There is also increasing evidence for many potential benefits through polyphenolic-mediated regulation of cellular processes such as inflammation. Inductive or signalling effects may occur at concentrations much lower than required for effective radical scavenging. Over the last 2-3 years, there have been many exciting new developments in the elucidation of the in vivo mechanisms of the health benefits of polyphenolics. We summarise the current knowledge of the intake, bio-availability and metabolism of polyphenolics, their antioxidant effects, regulatory effects on signalling pathways, neuro-protective effects and regulatory effects on energy metabolism and gut health.
- Published
- 2007
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33. Stochastic modeling of aphid population growth with nonlinear, power-law dynamics.
- Author
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Matis JH, Kiffe TR, Matis TI, and Stevenson DE
- Subjects
- Animals, Aphids pathogenicity, Carya parasitology, Female, Male, Mathematics, Nonlinear Dynamics, Population Growth, Reproduction, Stochastic Processes, Aphids physiology, Models, Biological
- Abstract
This paper develops a deterministic and a stochastic population size model based on power-law kinetics for the black-margined pecan aphid. The deterministic model in current use incorporates cumulative-size dependency, but its solution is symmetric. The analogous stochastic model incorporates the prolific reproductive capacity of the aphid. These models are generalized in this paper to include a delayed feedback mechanism for aphid death. Whereas the per capita aphid death rate in the current model is proportional to cumulative size, delayed feedback is implemented by assuming that the per capita rate is proportional to some power of cumulative size, leading to so-called power-law dynamics. The solution to the resulting differential equations model is a left-skewed abundance curve. Such skewness is characteristic of observed aphid data, and the generalized model fits data well. The assumed stochastic model is solved using Kolmogrov equations, and differential equations are given for low order cumulants. Moment closure approximations, which are simple to apply, are shown to give accurate predictions of the two endpoints of practical interest, namely (1) a point estimate of peak aphid count and (2) an interval estimate of final cumulative aphid count. The new models should be widely applicable to other aphid species, as they are based on three fundamental properties of aphid population biology.
- Published
- 2007
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34. Comparison of the relative recovery of polyphenolics in two fruit extracts from a model of degradation during digestion and metabolism.
- Author
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Stevenson DE, Cooney JM, Jensen DJ, Zhang J, and Wibisono R
- Subjects
- Anthocyanins analysis, Blueberry Plants chemistry, Chlorogenic Acid analysis, Chlorogenic Acid metabolism, Digestion, Glucuronides metabolism, Hydrogen-Ion Concentration, Hydrolysis, Malus chemistry, Models, Biological, Phloretin analysis, Phloretin metabolism, Polyphenols, Quercetin analysis, Quercetin metabolism, Species Specificity, Flavonoids analysis, Flavonoids metabolism, Fruit chemistry, Phenols analysis, Phenols metabolism, Plant Extracts chemistry
- Abstract
To simulate the effects of digestion and metabolism on the survival of different polyphenolic compounds, extracts of blueberry and apple were deglycosylated by acid hydrolysis, followed by enzymic glucuronidation under neutral conditions, yielding approximately 5% overall recovery of polyphenolics. The major polyphenolics before and after the treatment were compared, to estimate which species are likely to be present in the intestinal lumen, undegraded and available for absorption, after consumption of the fruit. Whereas blueberry extract consisted predominantly of anthocyanins, epicatechin and caffeoyl quinate esters, the major components of the treated extract were quercetin glucuronides and (unglucuronidated) caffeoyl quinates, with only traces of anthocyanidin derivatives. In apple extract, compositional changes were less marked, but caffeoyl quinates, procyanidins and quercetin were enriched at the expense of caffeic acid, epicatechin and catechin. Hydrophobic compounds like phloretin and quercetin were extensively glucuronidated, whereas caffeic acid and caffeoyl quinate were not. These results suggest that the major polyphenolic components of a fruit are not necessarily the most important contributors to any health benefits because the polyphenolic composition in the intestinal lumen and consequently, in the circulation, may be considerably different.
- Published
- 2007
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35. Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework.
- Author
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Calabrese EJ, Bachmann KA, Bailer AJ, Bolger PM, Borak J, Cai L, Cedergreen N, Cherian MG, Chiueh CC, Clarkson TW, Cook RR, Diamond DM, Doolittle DJ, Dorato MA, Duke SO, Feinendegen L, Gardner DE, Hart RW, Hastings KL, Hayes AW, Hoffmann GR, Ives JA, Jaworowski Z, Johnson TE, Jonas WB, Kaminski NE, Keller JG, Klaunig JE, Knudsen TB, Kozumbo WJ, Lettieri T, Liu SZ, Maisseu A, Maynard KI, Masoro EJ, McClellan RO, Mehendale HM, Mothersill C, Newlin DB, Nigg HN, Oehme FW, Phalen RF, Philbert MA, Rattan SI, Riviere JE, Rodricks J, Sapolsky RM, Scott BR, Seymour C, Sinclair DA, Smith-Sonneborn J, Snow ET, Spear L, Stevenson DE, Thomas Y, Tubiana M, Williams GM, and Mattson MP
- Subjects
- Animals, Humans, Adaptation, Physiological, Biology, Dose-Response Relationship, Drug, Stress, Physiological, Terminology as Topic
- Abstract
Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.
- Published
- 2007
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36. Red colouration in apple fruit is due to the activity of the MYB transcription factor, MdMYB10.
- Author
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Espley RV, Hellens RP, Putterill J, Stevenson DE, Kutty-Amma S, and Allan AC
- Subjects
- Amino Acid Sequence, Anthocyanins chemistry, Chromatography, High Pressure Liquid, Fruit enzymology, Gene Expression Profiling, Gene Expression Regulation, Plant, Luciferases metabolism, Malus enzymology, Malus genetics, Molecular Sequence Data, Plant Leaves metabolism, Plants, Genetically Modified, Reverse Transcriptase Polymerase Chain Reaction, Sequence Alignment, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Nicotiana genetics, Transcription Factors genetics, Transformation, Genetic, Anthocyanins biosynthesis, Fruit metabolism, Malus metabolism, Pigmentation physiology, Transcription Factors metabolism
- Abstract
Anthocyanin concentration is an important determinant of the colour of many fruits. In apple (Malus x domestica), centuries of breeding have produced numerous varieties in which levels of anthocyanin pigment vary widely and change in response to environmental and developmental stimuli. The apple fruit cortex is usually colourless, although germplasm does exist where the cortex is highly pigmented due to the accumulation of either anthocyanins or carotenoids. From studies in a diverse array of plant species, it is apparent that anthocyanin biosynthesis is controlled at the level of transcription. Here we report the transcript levels of the anthocyanin biosynthetic genes in a red-fleshed apple compared with a white-fleshed cultivar. We also describe an apple MYB transcription factor, MdMYB10, that is similar in sequence to known anthocyanin regulators in other species. We further show that this transcription factor can induce anthocyanin accumulation in both heterologous and homologous systems, generating pigmented patches in transient assays in tobacco leaves and highly pigmented apple plants following stable transformation with constitutively expressed MdMYB10. Efficient induction of anthocyanin biosynthesis in transient assays by MdMYB10 was dependent on the co-expression of two distinct bHLH proteins from apple, MdbHLH3 and MdbHLH33. The strong correlation between the expression of MdMYB10 and apple anthocyanin levels during fruit development suggests that this transcription factor is responsible for controlling anthocyanin biosynthesis in apple fruit; in the red-fleshed cultivar and in the skin of other varieties, there is an induction of MdMYB10 expression concurrent with colour formation during development. Characterization of MdMYB10 has implications for the development of new varieties through classical breeding or a biotechnological approach.
- Published
- 2007
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37. Methylated polyphenols are poor "chemical" antioxidants but can still effectively protect cells from hydrogen peroxide-induced cytotoxicity.
- Author
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Deng D, Zhang J, Cooney JM, Skinner MA, Adaim A, Jensen DJ, and Stevenson DE
- Subjects
- Dose-Response Relationship, Drug, Humans, Hydrogen Peroxide pharmacology, Hydroxybenzoates pharmacology, Jurkat Cells, Methylation, Oxidants pharmacology, Polyphenols, Reactive Oxygen Species antagonists & inhibitors, Reactive Oxygen Species metabolism, Antioxidants pharmacology, Cytoprotection, Flavonoids pharmacology, Hydrogen Peroxide toxicity, Oxidants toxicity, Phenols pharmacology
- Abstract
Several polyphenolic compounds, including flavonoids and phenolic acids, were compared with their per-methylated forms in both chemical and cell-based assays for antioxidant capacity. Methylation largely eliminated "chemical" antioxidant capacity, according to ferric reducing antioxidant power and oxygen radical absorbance capacity assays. Methylation, however, only moderately reduced protection of human Jurkat cells in culture, from hydrogen peroxide-mediated cytotoxicity, at physiologically relevant concentrations. Neither methylated nor un-methylated compounds were detectably metabolized by the cells. It appears that the protective mechanism of polyphenolic antioxidants against high concentrations of hydrogen peroxide in human cells may be largely unrelated to chemical antioxidant capacity.
- Published
- 2006
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38. Modelling the impact of geometric parameters on the redox potential of blue copper proteins.
- Author
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Taylor MK, Stevenson DE, Berlouis LE, Kennedy AR, and Reglinski J
- Subjects
- Crystallography, X-Ray, Electrochemistry, Models, Molecular, Molecular Structure, Oxidation-Reduction, Azurin chemistry, Copper chemistry, Models, Chemical, Plastocyanin chemistry, Schiff Bases chemistry
- Abstract
The synthesis and structure of a homologous series of cationic N(2)S(2) copper(I) Schiff base complexes constructed using o-tert-butylthiobenzaldehyde and a series of terminal diamines (ethane, propane, butane) are reported. The complexes differ only in the length of the methylene chain between the imine groups. This simple modification forces the copper centre to shift geometry from a planar (1,2-diaminoethane) to a more distorted tetrahedral motif (1,4-diaminobutane). The redox potentials of the three cations were measured using cyclic voltammetry in donor (acetonitrile) and non-donor solvents (dichloromethane). The S-Cu-N angles for each complex are correlated against the respective redox potential allowing an analysis of the geometric impact on the redox potential in soft copper centres. The redox potential is observed to increase as the metal centre moves from a planar towards a tetrahedral motif. Comparing this data with the reported structures of the blue copper proteins (rusticyanin and plastocyanin) allows an assessment of the contribution of the geometry of the metal binding site to the operating potential of these proteins to be made.
- Published
- 2006
- Full Text
- View/download PDF
39. Nonlinear stochastic modeling of aphid population growth.
- Author
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Matis JH, Kiffe TR, Matis TI, and Stevenson DE
- Subjects
- Animals, Mathematics, Models, Biological, Models, Statistical, Nonlinear Dynamics, Population Growth, Stochastic Processes, Aphids growth & development
- Abstract
This paper develops a stochastic population size model for the black-margined pecan aphid. Prajneshu [Prajneshu, A nonlinear statistical model for aphid population growth. J. Indian Soc. Agric. Statist. 51 (1998), p. 73] proposes a novel nonlinear deterministic model for aphid abundance. The per capita death rate in his model is proportional to the cumulative population size, and the solution is a symmetric analytical function. This paper fits Prajneshu's deterministic model to data. An analogous stochastic model, in which both the current and the cumulative aphid counts are state variables, is then proposed. The bivariate solution of the model, with parameter values suggested by the data, is obtained by solving a large system of Kolmogorov equations. Differential equations are derived for the first and second order cumulants, and moment closure approximations are obtained for the means and variances by solving the set of only five equations. These approximations, which are simple for ecologists to calculate, are shown to give accurate predictions of the two endpoints of applied interest, namely (1) the peak aphid count and (2) the final cumulative aphid count.
- Published
- 2005
- Full Text
- View/download PDF
40. Physiological time model of Scirpophaga incertulas (Lepidoptera: Pyralidae) in rice in Guandong Province, People's Republic of China.
- Author
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Stevenson DE, Feng G, Zhang R, and Harris MK
- Subjects
- Animals, China, Models, Biological, Population Dynamics, Temperature, Time Factors, Moths physiology, Oryza parasitology
- Abstract
Scirpophaga incertulas (Walker) (Lepidoptera: Pyralidae) is autochthonous and monophagous on rice, Oryza spp., which favors the development of a physiological time model using degree-days (degrees C) to establish a well defined window during which adults will be present in fields. Model development of S. incertulas adult flight phenology used climatic data and historical field observations of S. incertulas from 1962 through 1988. Analysis of variance was used to evaluate 5,203 prospective models with starting dates ranging from 1 January (day 1) to 30 April (day 121) and base temperatures ranging from -3 through 18.5 degrees C. From six candidate models, which shared the lowest standard deviation of prediction error, a model with a base temperature of 10 degrees C starting on 19 January was selected for validation. Validation with linear regression evaluated the differences between predicted and observed events and showed the model consistently predicted phenological events of 10 to 90% cumulative flight activity within a 3.5-d prediction interval regarded as acceptable for pest management decision making. The degree-day phenology model developed here is expected to find field application in Guandong Province. Expansion to other areas of rice production will require field validation. We expect the degree-day characterization of the activity period will remain essentially intact, but the start day may vary based on climate and geographic location. The development and validation of the phenology model of the S. incertulas by using procedures originally developed for pecan nut casebearer, Acrobasis nuxvorella Neunzig, shows the fungibility of this approach to developing prediction models for other insects.
- Published
- 2005
- Full Text
- View/download PDF
41. Structural analysis of carrageenans from the red alga, Callophyllis hombroniana Mont. Kütz (Kallymeniaceae, Rhodophyta).
- Author
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Falshaw R, Furneaux RH, and Stevenson DE
- Subjects
- Acetates chemistry, Acetylation, Magnetic Resonance Spectroscopy, Methylation, Molecular Structure, New Zealand, Spectrophotometry, Infrared, Sulfur chemistry, Carrageenan chemistry, Rhodophyta chemistry
- Abstract
The use of a range of modern analytical techniques has facilitated the structural characterisation of the polysaccharide from the New Zealand endemic red alga, Callophyllis hombroniana. The native polysaccharide contains a number of structural units with the largest proportion consisting of 3-linked beta-D-galactopyranosyl 2-sulfate units, alternating with 4-linked 3,6-anhydro-alpha-D-galactopyranosyl 2-sulfate units, that is, theta-carrageenan (36 mol%). C. hombroniana is the first red seaweed reported to naturally contain such a large proportion of theta-carrageenan.
- Published
- 2005
- Full Text
- View/download PDF
42. Effect of transport stress on respiratory disease, serum antioxidant status, and serum concentrations of lipid peroxidation biomarkers in beef cattle.
- Author
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Chirase NK, Greene LW, Purdy CW, Loan RW, Auvermann BW, Parker DB, Walborg EF Jr, Stevenson DE, Xu Y, and Klaunig JE
- Subjects
- Animals, Body Weight, Cattle, Lipid Peroxidation, Stress, Physiological physiopathology, Transportation, Antioxidants analysis, Cattle Diseases physiopathology, Malondialdehyde blood, Respiratory Tract Diseases veterinary, Stress, Physiological veterinary
- Abstract
Objective: To determine the effect of transportation stress on serum concentrations of oxidative stress biomarkers of calves., Animals: 105 crossbred beef steer calves (mean [+/-SD] body weight, 207 +/- 21.2 kg)., Procedure: Calves were assembled at 1 location in Tennessee, and pretransit (day -3) blood samples were collected. Calves were allotted randomly by body weight into 2 groups. Calves were transported 1,930 miles to a feedlot in Texas, and 1 group received tilmicosin phosphate (33 microg/kg, s.c.) upon arrival. Calves were weighed and blood samples collected on the day of arrival (day 1) and on days 15, 22, and 28. Calves were scored daily for signs of bovine respiratory disease (BRD). Serum total antioxidant capacity (TACA) and serum malondialdehyde (MDA) concentrations were determined., Results: Transportation stress significantly decreased mean serum TACA concentrations (from 147 +/- 31.2 U/mL to 133 +/- 20.1 U/mL) and significantly increased serum MDA concentrations (from 10.9 +/- 18.3 microg/mL to 30.2 +/- 50.5 microg/mL). Calves that died had a 43% increase in serum MDA concentration on day 1, compared with calves that lived (42.2 +/- 67.0 microg/mL vs 29.4 +/- 49.4 microg/mL, respectively). Calves that had > or =3 episodes of BRD had 2-fold higher serum MDA concentrations on day 1 than healthy calves. Tilmicosin-treated calves had a 20.8% significantly greater average daily gain and significantly greater serum TACA concentration than nontreated calves on day 28., Conclusions and Clinical Relevance: Transportation stress increases serum concentrations of oxidative stress biomarkers that are related to episodes of BRD and mortality in calves.
- Published
- 2004
- Full Text
- View/download PDF
43. Comparative effects of dieldrin on hepatic ploidy, cell proliferation, and apoptosis in rodent liver.
- Author
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Kamendulis LM, Kolaja KL, Stevenson DE, Walborg EF Jr, and Klaunig JE
- Subjects
- Animals, DNA biosynthesis, DNA drug effects, Male, Mice, Mice, Inbred Strains, Mitotic Index, Rats, Rats, Inbred F344, Apoptosis drug effects, Cell Division drug effects, Dieldrin adverse effects, Disease Models, Animal, Environmental Exposure adverse effects, Hepatocytes drug effects, Insecticides adverse effects, Liver Neoplasms chemically induced, Liver Neoplasms pathology, Ploidies
- Abstract
Dieldrin-induced hepatocarcinogenesis, which is seen only in the mouse, apparently occurs through a nongenotoxic mechanism. Previous studies have demonstrated that dieldrin induces hepatic DNA synthesis in mouse, but not rat liver. A number of nongenotoxic hepatocarcinogens have been shown to increase hepatocyte nuclear ploidy following acute and subchronic treatment in rodents, suggesting that an induction of hepatocyte DNA synthesis may occur without a concomitant increase in cell division. The current study examined the effects of dieldrin on changes in hepatocyte DNA synthesis, mitosis, apoptosis, and ploidy in mouse liver (the sensitive strain and target tissue for dieldrin-induced carcinogenicity) and the rat liver (an insensitive species). Male F344 rats and B6C3F1 mice were treated with 0, 1, 3, or 10 mg dieldrin/kg diet and were sampled after 7, 14, 28, or 90 d on diet. Liver from mice fed 10 mg dieldrin/kg diet exhibited significantly increased DNA synthesis and mitosis at 14, 28, or 90 d on diet. In rats, no increase in DNA synthesis or mitotic index was observed. The apoptotic index in liver of mice and rats did not change over the 90-d study period. Exposure of mice to only the highest dose of dieldrin produced a significant increase in octaploid (8N) hepatocytes and a decrease in diploid (2N) hepatocytes, which were restricted primarily to centrilobular hepatocytes, with the periportal region showing little or no change from control. No changes in hepatocyte nuclear ploidy were observed in the rat. This study demonstrates that exposure to high concentrations of dieldrin is accompanied by increased nuclear ploidy and mitosis in mouse, but not rat, liver. It is proposed that the observed increase in nuclear ploidy in the mouse may reflect an adaptive response to dieldrin exposure.
- Published
- 2001
- Full Text
- View/download PDF
44. Production of high-oleic acid tallow fractions using lipase-catalyzed directed interesterification, using both batch and continuous processing.
- Author
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MacKenzie AD and Stevenson DE
- Abstract
Immobilized lipases were used to catalyze batch-directed interesterification of tallow, resulting in oleins containing significantly higher levels of unsaturated fatty acids than obtained by fractionation without lipase. After 14 days, a reaction catalyzed by 2% Novozym 435 yielded 57% olein unsaturation, compared with 45% in a no-enzyme control. Free fatty acid levels increased to 2-3% during reactions. Incubation of the enzyme in multiple batches of melted fat caused a gradual loss of interesterification activity, apparently due to progressive dehydration. The activity could be restored by addition of water to the reaction medium. Immobilized lipase was also used to catalyze directed interesterification in a continuous flow reactor. Melted tallow was circulated through a packed bed enzyme reactor and a separate crystallization vessel. The temperatures of the two parts of the apparatus were controlled separately to allow crystallization to occur separately from interesterification. Operation of the reactor with conventionally dry, prefractionated tallow allowed the formation of an olein consisting of up to 60% unsaturated fatty acids. The greatest changes in olein fatty acid composition were achieved when the fractionation temperature was kept constant at a value that promoted selective crystallization of trisaturated triglycerides that were continuously produced by enzymic interesterification. The enzyme could be reused without apparent loss of activity, and its activity was apparently enhanced by preincubation in melted tallow for up to several days. Control of both the water activity of the enzyme and tallow feedstock and of the absorption of atmospheric water vapor were required to maintain enzyme activity, during multiple reuse and minimize free fatty acid formation. This method may form the basis for a process to produce highly mono-unsaturated tallow fractions for use in food applications (e.g. frying) where a "healthy" low saturated fat product is required.
- Published
- 2000
- Full Text
- View/download PDF
45. Are calories responsible for a decline in longevity?
- Author
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Stevenson DE and Sielken RL Jr
- Subjects
- Animals, Animals, Laboratory physiology, Dose-Response Relationship, Drug, Humans, Models, Biological, Mortality, Risk Assessment, Energy Intake physiology, Longevity physiology
- Published
- 2000
- Full Text
- View/download PDF
46. Cancer dose-response modeling of epidemiological data on worker exposures to aldrin and dieldrin.
- Author
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Sielken RL Jr, Bretzlaff RS, Valdez-Flores C, Stevenson DE, and de Jong G
- Subjects
- Aldrin administration & dosage, Animals, Dieldrin administration & dosage, Dose-Response Relationship, Drug, Humans, Insecticides administration & dosage, Likelihood Functions, Liver Neoplasms, Experimental chemically induced, Male, Mice, Models, Biological, Netherlands epidemiology, Occupational Diseases chemically induced, Occupational Diseases mortality, Occupational Exposure, Proportional Hazards Models, Risk Assessment, Aldrin adverse effects, Dieldrin adverse effects, Insecticides adverse effects, Neoplasms chemically induced, Neoplasms mortality
- Abstract
The paper applies classical statistical principles to yield new tools for risk assessment and makes new use of epidemiological data for human risk assessment. An extensive clinical and epidemiological study of workers engaged in the manufacturing and formulation of aldrin and dieldrin provides occupational hygiene and biological monitoring data on individual exposures over the years of employment and provides unusually accurate measures of individual lifetime average daily doses. In the cancer dose-response modeling, each worker is treated as a separate experimental unit with his own unique dose. Maximum likelihood estimates of added cancer risk are calculated for multistage, multistage-Weibull, and proportional hazards models. Distributional characterizations of added cancer risk are based on bootstrap and relative likelihood techniques. The cancer mortality data on these male workers suggest that low-dose exposures to aldrin and dieldrin do not significantly increase human cancer risk and may even decrease the human hazard rate for all types of cancer combined at low doses (e.g., 1 microgram/kg/day). The apparent hormetic effect in the best fitting dose-response models for this data set is statistically significant. The decrease in cancer risk at low doses of aldrin and dieldrin is in sharp contrast to the U.S. Environmental Protection Agency's upper bound on cancer potency based on mouse liver tumors. The EPA's upper bound implies that lifetime average daily doses of 0.0000625 and 0.00625 microgram/kg body weight/day would correspond to increased cancer risks of 0.000001 and 0.0001, respectively. However, the best estimate from the Pernis epidemiological data is that there is no increase in cancer risk in these workers at these doses or even at doses as large as 2 micrograms/kg/day.
- Published
- 1999
- Full Text
- View/download PDF
47. Monograph: reassessment of human cancer risk of aldrin/dieldrin.
- Author
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Stevenson DE, Walborg EF Jr, North DW, Sielken RL Jr, Ross CE, Wright AS, Xu Y, Kamendulis LM, and Klaunig JE
- Subjects
- Aldrin pharmacokinetics, Animals, Carcinogens pharmacokinetics, Cell Transformation, Neoplastic, DNA, Neoplasm metabolism, Dieldrin pharmacokinetics, Humans, Insecticides pharmacokinetics, Neoplasms epidemiology, Neoplasms metabolism, Risk Factors, Aldrin toxicity, Carcinogens toxicity, Dieldrin toxicity, Insecticides toxicity, Neoplasms chemically induced
- Abstract
In 1987, the US Environmental Protection Agency (EPA) classified aldrin and dieldrin as category B2 carcinogens, i.e. probable human carcinogens, based largely on the increase in liver tumors in mice fed either organochlorine insecticide. At that date, the relevant epidemiology was deemed inadequate to influence the cancer risk assessment. More time has now elapsed since early exposures of manufacturing workers to aldrin/dieldrin; therefore, updated epidemiological data possess more power to detect exposure-related differences in cancer risk and mortality. Also, recent experimental studies provide a plausible mode of action to explain the mouse specificity of dieldrin-induced hepatocarcinogenesis and call into question the relevance of this activity to human cancer risk. This monograph places this new information within the historic and current perspectives of human cancer risk assessment, including EPA's 1996 Proposed Guidelines for Carcinogen Risk Assessment. Updated epidemiological studies of manufacturing workers in which lifetime exposures to aldrin/dieldrin have been quantified do not indicate increased mortality or cancer risk. In fact, at the middle range of exposures, there is evidence of a decrease in both mortality from all causes and cancer. Recent experimental studies indicate that dieldrin-induced hepatocarcinogenesis in mice occurs through a nongenotoxic mode of action, in which the slow oxidative metabolism of dieldrin is accompanied by an increased production of reactive oxygen species, depletion of hepatic antioxidant defenses (particularly alpha-tocopherol), and peroxidation of liver lipids. Dieldrin-induced oxidative stress or its sequelae apparently result in modulation of gene expression that favors expansion of initiated mouse, but not rat, liver cells; thus, dieldrin acts as a nongenotoxic promoter/accelerator of background liver tumorigenesis in the mouse. Within the framework of EPA's Proposed Guidelines for Carcinogen Risk Assessment, it is proposed that the most appropriate cancer risk descriptor for aldrin/dieldrin, relating to the mouse liver tumor response, is 'not likely a human carcinogen', a descriptor consistent with the example of phenobarbital cited by EPA.
- Published
- 1999
- Full Text
- View/download PDF
48. Role of oxidative stress in the selective toxicity of dieldrin in the mouse liver.
- Author
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Bachowski S, Xu Y, Stevenson DE, Walborg EF Jr, and Klaunig JE
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine, Administration, Oral, Animals, Ascorbic Acid analysis, Deoxyguanosine analogs & derivatives, Deoxyguanosine metabolism, Deoxyguanosine urine, Dieldrin administration & dosage, Dose-Response Relationship, Drug, Glutathione analysis, Insecticides administration & dosage, Liver pathology, Male, Malondialdehyde metabolism, Malondialdehyde urine, Mice, Rats, Rats, Inbred F344, Species Specificity, Vitamin E analysis, Carcinogens toxicity, Dieldrin toxicity, Insecticides toxicity, Liver drug effects, Oxidative Stress
- Abstract
Dieldrin, an organochlorine insecticide, induces hepatic tumors in mice but not in rats. Although the mechanism(s) responsible for this species specificity is not fully understood, accumulating evidence indicates that oxidative stress may be involved. This study examined the association of dieldrin-induced hepatic DNA synthesis with the modulation of biomarkers of oxidative damage to lipids (malondialdehyde [MDA]) and DNA (8-hydroxy-2-deoxyguanosine [oh8dG]), in male B6C3F1 mice and F344 rats fed dieldrin (0.1, 1.0, or 10 mg/kg diet) for 7, 14, 28, and 90 days. The nonenzymatic components of the antioxidant defense system (ascorbic acid, glutathione, and alpha-tocopherol) were also examined. Increased urinary MDA was observed in mice fed 0.1, 1.0, or 10 mg dieldrin/kg diet for 7, 14, 28, and 90 days; while increased hepatic MDA was seen only after 7 days in mice fed 0.1, 1.0, or 10 mg dieldrin/kg diet and after 14 days in mice fed 10 mg/kg diet. In rats, dieldrin had no effect on either hepatic MDA or urine MDA levels after 7, 14, and 28 days of treatment. A dose-dependent increase in urinary MDA was observed in rats at the 90-day sampling time. The only significant elevation in urinary or hepatic oh8dG content was limited to urinary oh8dG in mice fed 10 mg/kg dieldrin diet for 14 days. Dietary dieldrin produced sustained decreases in hepatic and serum alpha-tocopherol and sustained elevations in hepatic ascorbic acid in both mice and rats. Rats, however, possessed a three- to four-fold higher content of endogenous or basal (control) hepatic alpha-tocopherol; and, even when fed 10 mg dieldrin/kg diet, the levels of hepatic alpha-tocopherol were maintained at higher levels than those of mice fed control diet. In both rats and mice fed dieldrin, transient (14 and 28 days on diet) elevations in hepatic glutathione were observed. These data support the hypothesis that the species specificity of dieldrin-induced hepatotoxicity may be related to dieldrin's ability to induce oxidative stress in the liver of mice, but not in rats. Only in mice fed dieldrin was a temporal association of increases in hepatic MDA content and hepatic DNA synthesis seen, suggesting that oxidative damage (shown by increased lipid peroxidation) may be involved in early events in dieldrin-induced hepatocarcinogenesis. Rats may be protected from dieldrin-induced oxidative stress by a more effective antioxidant defense system, characterized by higher basal levels of hepatic alpha-tocopherol and ascorbic acid than that seen in the mouse.
- Published
- 1998
- Full Text
- View/download PDF
49. Some implications for quantitative risk assessment if hormesis exists.
- Author
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Sielken RL Jr and Stevenson DE
- Subjects
- Animals, Dose-Response Relationship, Drug, Humans, Research Design, Toxicology statistics & numerical data, Risk Assessment, Toxicology methods
- Abstract
The existence of hormesis should impact quantitative risk assessment in at least seven fundamental ways. (1) The dose-response models for bioassay and epidemiological data should have greater flexibility to fit the observed shape of the dose-response data and no longer be forced to always be linearly increasing at low doses. (2) Experimental designs should be altered to provide greater opportunity to identify the hormetic component of a dose-response relationship. (3) Rather than a lifetime average daily dose or its analog for shorter time periods, dose scales or metrics should be used that reflect the age or time dependence of the dose level. (4) Low-dose risk characterization should include the likelihood of beneficial effects and the likelihood that a dose level has reasonable certainty of no appreciable adverse health effects. (5) Exposure assessments should make greater efforts to characterize the distribution of actual doses from exposure rather than just upper bounds. (6) Uncertainty characterizations should be expanded to include both upper and lower bounds, and there should be an increased explicit use of expert judgement and weight-of-evidence based distributional analyses reflecting more of the available relevant dose-response information and alternative risk characterizations. (7) Risk should be characterized in terms of the net effect of a dose on health rather than a dose's effect on a single factor affecting health - for example, risk would be better expressed in terms of mortality from all causes combined rather than a specific type of fatal disease.
- Published
- 1998
- Full Text
- View/download PDF
50. Vitamin E modulation of dieldrin-induced hepatic focal lesion growth in mice.
- Author
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Kolaja KL, Xu Y, Walborg EF Jr, Stevenson DE, and Klaunig JE
- Subjects
- Animals, Apoptosis, Chemical and Drug Induced Liver Injury, Liver pathology, Liver Diseases pathology, Male, Mice, Precancerous Conditions chemically induced, Precancerous Conditions pathology, Carcinogens toxicity, Dieldrin toxicity, Insecticides toxicity, Liver drug effects, Liver Diseases drug therapy, Precancerous Conditions drug therapy, Vitamin E therapeutic use
- Abstract
The effect of vitamin E on dieldrin-induced hepatic focal lesion growth in male B6C3F1 mice previously treated with diethylnitrosamine (DEN) was investigated. After hepatic focal lesions were formed, mice were placed into one of the following treatment groups: Group 1, 50 mg vitamin E/kg diet (control NIH-07 diet); Group 2, 10 mg dieldrin/kg NIH-07 diet; Group 3, 10 mg dieldrin and 450 mg vitamin E/kg NIH-07 diet; and Group 4, 450 mg vitamin E/kg NIH-07 diet. Mice were killed and necropsied after 30 and 60 d of dietary treatment. The effect of treatment on lesion growth was examined by measuring the number of focal lesions per liver and the relative hepatic focal lesion volume. In addition, the possible cellular mechanism of focal hepatocyte growth was investigated by examining both focal DNA synthesis and apoptosis. Dieldrin treatment alone (Group 2) increased the focal lesion volume, focal lesion number, and focal lesion labeling index. Supplementation with vitamin E (Group 3) blocked this effect. Vitamin E supplementation to the diet alone (Group 4) also enhanced focal lesion growth and increased the number of lesions per liver, the relative focal volume, and the labeling index in hepatic focal lesions. Interestingly, vitamin E supplementation inhibited apoptosis in normal liver but did not produce an observable decrease in apoptosis in hepatic focal lesions. The present study showed that dieldrin (Group 2) or vitamin E supplementation alone (Group 4) promoted the growth of hepatic focal lesions in mice. However, when vitamin E is supplemented to dieldrin-fed mice (Group 3), there is an inhibition of hepatic focal lesion growth.
- Published
- 1998
- Full Text
- View/download PDF
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