1,124 research outputs found
Polycyclic aromatic hydrocarbons influence naive CD4+ T cell differentiation
No full textCD4+ T cells are essential for the effective functioning and appropriate regulation of the immune system. Antigen-naïve T cells require two distinct costimulatory signals to activate and differentiate into effector and memory T cells which can respond to antigen and direct the immune response. The first signal is through cognate antigen presented in major histocompatibility class II on an antigen-presenting cell binding to the T cell receptor. The second signal is the interaction of a costimulatory receptor on the T cell with a counter-receptor expressed on the antigen-presenting cell. This work focuses on the costimulatory receptors CD28, the classic T cell costimulatory molecule, and intercellular adhesion molecule-1 (ICAM-1). ICAM-1 functions in adhesion and extravasation during inflammation, and our lab has previously published that ICAM-1 can function as a T cell second signal for activation. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants which have been shown by many other investigators to have diverse effects on human health including the immune system. In the present work, we examined the consequences of exposure to two PAHs during naïve T cell costimulation. Bisphenol A, a widely used plasticizer and component of epoxy resins, was found to weakly promote naïve T cell proliferation during ICAM-1 costimulation but not in CD28 costimulation and did not perturb effector and memory cell differentiation in either costimulation. Pyrene, a product of incomplete combustion of organic materials, enhanced proliferation of naïve T cells in both ICAM-1 and CD28 costimulations and inhibited effector and memory cell differentiation in both costimulations. We also compared the differentiation of naïve T cells isolated using StemSep and EasySep naïve CD4+ T cell isolation kits upon being informed by StemCell, the manufacturer of the kits, that StemSep was being discontinued in favor of EasySep. In contrast to StemSep naïve T cells, with which we have published previously, EasySep-purified naïve T cells did not differentiate in response to costimulation through ICAM-1 or CD28 without addition of exogenous cytokines and had dramatically increased cell death. We showed that inclusion of CD25 antibody in the EasySep negative selection antibody cocktail was partially responsible for the observed loss of differentiation and viability. Likewise, the EasySep magnetic beads were partially at fault for observed failure to differentiate and loss of viability in EasySep naïve T cells. This result also suggested an important role for the CD25lo population of naïve T cells in the ability of the cells to differentiate, which is in keeping with the published literature
USE OF ANIMAL FREE COMPONENTS IN THE COMMERCIAL MANUFACTURE OF VETERINARY CLOSTRIDIAL ANTIGENS
No full textThe use of animal-origin components and media in the commercial production of clostridial antigens for veterinary vaccine manufacture constitutes an unnecessary and excessive risk to food safety and health. For over 70 years, bacterial strains of the genus Clostridium have been used in the manufacture of veterinary and human vaccines to prevent infection and death. The vast majority of these products are made using animal-based components, including brain, heart and liver infusions, meat peptones and casein digests. Over the last twenty years, the threat of Transmissible Spongiform Encephalopathy (TSE) and adventitious oncogenic viral transmission has generated a significant concern about the safety and reliability of animal-based products. While many animal-free options have been developed in recent years, few manufacturers have adapted vaccine production processes to incorporate such media, primarily due to monetary costs, regulatory restrictions, and corporate inertia. Several manufacturers have made progress on the transition from animal-based to plant-based medias to reduce the TSE risk, but the majority of clostridial vaccines manufactured worldwide are still in animal-based media. While the regulatory agencies responsible for overseeing the human pharmaceutical and vaccine manufacturers have been aggressive in requiring the removal of animal-based components from the products, the animal health regulatory bodies have been slower to follow suit. A rapid and aggressive shift in policy is needed to provide the necessary changes to eliminate the risk of TSE from the livestock vaccine industry
The Escherichia coli RhaS Transcriptional Activator: Transcriptional Activation by the DNA-Binding Domain, The Interdomain Effector Response, and Negative Autoregulation
No full textThe chapters herein are the accepted manuscript versions of articles that were published independently in scholarly research journals. They have been combined and submitted in fulfillment of the thesis requirement for a Master of Arts degree in Microbiology from the University of Kansas Department of Molecular Biosciences. In addition to the work presented here, my graduate work included two additional projects: a high-throughput screen to identify inhibitors of the Escherichia coli RhaS protein, and a site-directed mutagenesis screen to better understand the molecular mechanisms of the L-rhamnose response in RhaS. The high-throughput screen identified a compound that inhibits DNA binding by RhaS, the related E. coli RhaR protein and the virulence activators Rns from enterotoxigenic E. coli and VirF from Shigella flexneri, but by neither E. coli LacI nor CRP. It appears that this compound may have broad, specific inhibitory activity against AraC-family proteins, making it a candidate for development into an antimicrobial drug that functions by blocking the expression of certain bacterial virulence factors that require an AraC-family activator for expression. The compound likely binds in a pocket between the two helix-turn- helix motifs of the conserved AraC-family DNA-binding domain, thereby sterically prohibiting the protein from binding DNA. In order to better understand the molecular mechanism by which the L-rhamnose signal is transmitted through RhaS from the N-terminal effector-binding domain to the C-terminal DNA-binding domain to regulate DNA binding in response to effector, I constructed a library of several dozen site-directed RhaS mutants. The goal of this work was to identify amino acids key to interdomain signaling by identifying point mutants with phenotypes consistent with defects in signaling. I focused my mutagenesis on regions of the protein predicted to be important in signaling, based on molecular modeling and similarities with related proteins. I isolated mutants in the DNA-binding domain with nearly wild-type activity (-)L-rhamnose and reduced activity (+)L-rhamnose, consistent with a decreased ability to stimulate activity (+)L-rhamnose, at positions Asn174 and Leu175. We conclude that these two residues are likely important in the signal transduction pathway; future work will identify the region of the N-terminal domain involved in this interaction
Football -- Team (1919) #2 -- Men
No full textFront row, left to right: George G. Kannapell, John Q, Seipp, Noah Downes, Powell Wilson, Tom G. Matthew, Nathan Lahn, Robert H. Frewing. Second row: Frederick H. Hughes, Fred R. Connor, Edwin G. Benedict, Ernest R. Langenberg, Frank W. Rebal, Samuel Rogalsky, Harry L. Baynes, George H. Davies. Third row: Lewis C. LaFountain, Anton J. Netusil?, Lawrence A. Paxton, Laurence H. Randall, L. Stephen Cherry, Wendell Haley, Joseph W. Bouchard. Fourth row: Robert H. Kannapell, ________?, Nathan Zimble, ________?, ________?, James N. Orman, ________?, ________?, ________? This image is a part of the Gallaudet University Archives\u27 Historical Photographs Collectionhttps://ida.gallaudet.edu/gusports/1349/thumbnail.jp
The interaction of ICAM-1 with LFA-1: intercellular signaling and implication in type I diabetes
No full textT lymphocytes are cells that play an essential role in both the regulation and activation of an immune response. The T cells role is two-fold: they migrate to an inflammatory site by interacting with endothelial cells lining the blood vessels and upon reaching the site of inflammation, interact with antigen presenting cells to facilitate clearance of the invading microorganism. The cell surface molecules ICAM-1 and LFA-1 play a large role in the function of T lymphocytes. These proteins act as counter-receptors that mediate both migration and activation. Proper regulation of T cell activation requires two costimulatory signals, one from the T cell receptor (TCR)-CD3 complex and the second from a surface molecule on an antigen presenting cell (APC). The first signal is characterized by the TCR-CD3 complex binding cognate antigen as it is being presented on a major histocompatibility complex (MHC) molecule. The second signal involves binding of a costimulatory molecule on the surface of a T cell, usually CD28, with a counter receptor present on the surface of an APC. ICAM-1, the focus of the present work, is located on the surface of T cells and functions in adhesion and extravasation of the cell during inflammation. Our lab and others have previously published that ICAM-1 can also act as a costimulatory molecule capable of delivering the second signal for T cell activation independent of the more traditional second signal, CD28. In the present work, we elucidated the components of the signaling complex formed after stimulation through ICAM-1. The proteins identified thus far include mitogen- activated protein kinase (MAPK), CD45, LFA-1, LAT, Gads, the Src tyrosine kinase family proteins Lck and Fyn, and the ZAP-70/CD3ζ complex. Since the ICAM-1/LFA-1 interaction is essential for proper T cell function, blocking the interaction could be a useful means of regulating improper immune response thus treating the diseases associated with its dysfunction. Previous studies in our lab using peptides derived from ICAM-1 and LFA-1 have proven beneficial in treating several autoimmune diseases. Here we sought to test a shorter course of peptide therapy and evaluated the treatment in a model for type I diabetes. The peptides not only delayed the onset of diabetes in the treated animals, but also drastically reduced the amount of infiltration seen within the islets of the pancreas. In addition to the diabetes study using the native peptides, we also used computational approaches to develop an alternative set of peptides with an increased affinity for ICAM-1 and LFA-1 and assessed their effect on T cell activation and function. We found that both peptides were able to inhibit MDHC-induced T cell adhesion in a clumping assay indicating specificity for both ICAM-1 and LFA-1. We also found that stimulating with anti-CD3 in the presence of each peptide caused a marked increase in proliferation of human T cells. This result suggests that the redesigned peptides are capable of acting as a costimulatory signal themselves
Long Primer Extension by a Novel Inverse PCR Method
No full textAn inverse polymerase chain reaction (PCR) was employed to construct an engineered F1-ATPase by means of inserting the repressor of primer (Rop) DNA
sequence into the region of the ATP synthase gamma (γ) subunit DNA sequence encoding a regulatory dithiol-containing domain. A two-step PCR approach was developed to insert two unusually long (>100 base pairs each) primers encoding 189 base pairs of exogenous DNA into a single site within a pACYC multiple cloning
host vector. The construct was verified by means of DNA sequencing. This approach allowed direct insertion of large pieces of DNA into a host DNA molecule
without introducing restriction enzyme sites, thus avoiding common shortcomings
such as inclusion or omission of base pairs that were associated with traditional subcloning
methods. The engineered gamma subunit was designed for assembly with the recombinant alpha (α) and beta (β) subunits into a core F1-ATPase. The rigid twisted
helical structure of the Rop protein extended the regulatory domain of the gamma subunit by approximately 60 Ångstroms, thus creating a rigid, rotating armature within the enzyme. The armature is intended for use as a site for attachment of gold
particles to monitor rotation of the gamma subunit during ATP hydrolysis
Vulnerability: An affliction of the powerless: A Nyoongar Story
No full textThis thesis analyses and investigates the issue of vulnerability among Australian Aboriginal people, as exemplified through the Nyoongar Shaw family and in particular myself. The Shaw family is from southwest Western Australia, more specifically the area belonging to the Yued nation. This thesis examines events in the lives of ancestors and descendants of the Nyoongar Shaw family. It specifically reconstructs the personal stories of our Aboriginal great-grandmother, Mary Ann Chuberan, our Aboriginal great-grandfather (in law), Frederick John Blurton, our Aboriginal grandfather George Shaw, Charles Fitzgerald (our Aboriginal grandfather in law), our Aboriginal aunties, Lilly, Jane and Margaret Shaw, and our Aboriginal mother, Ruby Shaw. By examining these lives, this thesis offers a way of understanding past Indigenous and non-Indigenous relationships in a West Australian context. It does this by drawing on government records, personal interviews, and the telling of my story as a member of the ‘Stolen Generations’. Using the post-modern concept of auto-ethnography as a literary tool, it combines the genres of biography and autobiography. Through the telling of my story, I explicate my experience of being raised to be vulnerable, manifesting itself through inadequate emotional care in childhood, thereby setting me up for failure in dealing appropriately with relationships in adult life. This provides a personal account of the effects of removal. Through recording the stories of both ancestors and descendants, I demonstrate the vulnerability of Aboriginal people, the result of living under government legislation during the years 1920-1959. These stories will show how, over time, this legislation disempowered and dispossessed them, and are intended to facilitate further discussion on what the effects of vulnerability mean for the lives of Aboriginal people and the community more broadly
Grupos sanguíneos y metabolismo basal.- Dos nuevos métodos antropológicos.. Anales del Museo Nacional de Arqueología, Historia y Etnografía. Num. 26 Tomo I (1934) Quinta Época (1934-1938)
No full textAub, J. C. and Du Bois, E. F. Arch. lnt. Med., 1917, 19, 823-831.Benedict, F. G. Boston Med. Surg. J. 1927, 197, 1161-1175; Bull.Soc. Sci. d'Hygiene Alimen., 1927, 15, 216.Chinese J. Physiol Report Ser., 1928, N° 1.Carpenter, T. M. Carn. lnst. Wash. Pub. 1924, N° 303 A, 108-122, Tables 19-20.De Almedia, A. O. J. de Physiol et de Path. gén., 1921. 19, 713-730; 958-964; 1924, 22, 12-18.Deryer, G. Lancet, 1920, Part 2, 289-291.Earle, H. G. The Caducens, 1922, 1, 85.Eijkman, C. (Pflüger's) Arch. f. d. Ges. Physiol., 1896, 64, 47-78; J. de Physiol et de Path. gén., 1921, 19, 33-35.Harris, J. A. and Benedict, Carn. Inst. Pub. 1919, N° 279. F. G.Knipping, H. W. Arch f. Schiffs u. Tropen-Hyg., 1923, 27, 169-178.McLeod, G., Crofts, E. E. Am. J. Physiol 1925, 73, 449-462; Poc. Nat. and Benedict, F. G. Acda. Sci., 1925, 11, 342-343.A Comparison of Methods for Determining the Respiratory Exchange of Man. By Thorne M. Carpenter, Washington, D. C. 1915. Carnegie Institution.A Comparative Study of Temperature Fluctuations in Different Parts of the Human Body. By Francis G. Benedict and Edgar P. Slack. Washington, 1911. Carnegie Institution.A Respiration Calorimeter. With Appliances for the Direct Determination of Oxygen. By W. O. Atwater and F. G. Benedict. Washington, D. C., 1905. Institution Carnegie.Energy Transformations During Horizontal Walking. By Francis G. Benedict and Hans Murschhauser. Washington, D. C. 1915. Carnegie Institution.Food Ingestion and Energy Transforrnations with special reference to the stimulating effect of Nutrients. By Francis G. Benedict and Thorne M. Carpenter. Washington, D. C. 1918. Carnegie Institution.Respiration Caloramienters for Studying the Respiratory Exchange and Energy Transformations of Man. By Francis G. Benedict and Thorne M. Carpenter. Washington, D. C. 1910. Carnegie Institution.Tables Factors and Formulas for Computing Respiratory Exchange and Biological Transformations of Energy. By Thorne M. Carpenter. Washington, D. C. 1924. Carnegie Institution.The Influence of Inanition on Metabolism. By Francis Gano Benedict. Washington, D. C. 1907. Carnegie Institution.The Metabolism and Energy Transformations of Healthy Man during Rest. By Francis G. Benedict and Thorne M. Carpenter. Washington, D. C. 1910. Carnegie Institution.The Physiology of the New-Born Infant. Character and Amount of the Katabolism. By Francis G. Benedict and Fritz B. Talbot. Washington, D. C. 1915. Carnegie Institution.Undernutrition in Steers: its Relation to Metabolism, Digestion, and Subsequent Realimentation. By Francis G. Benedict and Ernest G. Ritzman. Washington, D. C. Carnegie Institution.The Basal Metabolism of Mayas in Yucatan. G. D. Williams and F. G. Benedict.Age and Basal Metabolism of Adults. Francis G. Benedict.The Basal Metabolism of some Browns and Blacks in Jamaica. M. Steggerda.Respiration Apparatus for a Metabolic Study of the various Subdivisions of the Human Race. By Francis G. Benedict.Basal Metabolism data on Normal Men and Women (Serie II). With some considerations on the use of Predication Standards. Francis G. Benedict.Basal Metabolism in Anthropology. Francis G. Benedict.Basal Metabolism. The modern Measure of Vital Activity. Dr. F. Benedict.Field Respiration Apparatus for a medical and physiological survey of Racial Metabolism. By Francis Benedict. P. h. 1.A method for the determination of the Energy Values of foods and excreta. By Francis Benedict and Edward L. Fox.Royal Institution of Great Britain by France M. Carpenter.Skin Temperature and Heat Loss. Francis Benedict.The Measurement and standards of Basal Metabolism. Francis Benedict. Ph. D.The Pursuitmeter and Apparatus for measuring the adequacy of Neuro-Musculus Coordination. Descibed to Getheer, with illustration, W. R. Miles. Notes on the use the portable respiration apparatus. Francis Benedict.The Temperature of the human skin. F. G. Benedict, W. R. Miles and A. John.Portable respiration apparatus for clinical use. F. B. Benedict.Leopoldina amerikaband Sonderdruck.Large-number. Division by calculating machine. Harry H. Laughlin.The Motivation of Child bearing. R. H. Johnson.Intelligence as a Mendelian character. Harrison H. Hutt.The inheritance of dialects mellitus a study in polyfactorial Genetics and apparatus for Studying the respiration Exchange, Francis Benedict.Control Tests of a respiration Calorimeters. Francis G. Benedict, J. A. Riche and D. E. Emmes
Borrowed silence: A history of the practice of retreat in the Church of England
No full textThis thesis, which is the first attempt to write about the growth of retreats, deals with a rather sidelined but important development in the history of spirituality. It states when, how and why the practice of retreat was adopted and adapted in the Church of England after having been a devotion in the Church of Rome since the time of the Catholic Reformation and how it has developed since. It is divided chronologically into three major sections. The first tells the story of its adoption in 1858 by a group of Anglo Catholics in the form of the preached retreat and its subsequent spread to a small number of adherents, despite meeting opposition from Evangelical Christians. The second tells of the influence of a Jesuit brother, Charles Plater, and how after the First World War a number of Diocesan retreat houses were opened, the use of which continued to rise until after the Second World War. The third takes the story up to our present day with its adaptation to the needs of the present search for faith, its decline accompanying the present loss in membership in the churches whilst at the same time its adoption in various forms by non-Anglican groups. In particular it contains a history of the Society of Retreat Conductors. All the time comparison is made with what was happening in the Church of Rome. There are resonances with the history of the Victorian church, the attitude of the established church to the working classes, evangelism, the changing fortunes of Anglo Catholicism, the ecumenical movement and New Age Christianity. It is of interest to all who are concerned about spread of religious faith today.University of Chester ; Society of Retreat Conductor
Postoperative concurrent chemoradiotherapy versus postoperative radiotherapy in high-risk cutaneous Squamous cell carcinoma of the head and neck: the randomized phase III TROG 05.01 trial
No full textPublished at jco.org on March 14, 2018.Abstract not availableSandro Virgilio Porceddu, Mathias Bressel, Michael Geoffrey Poulsen, Adam Stoneley, Michael John Veness, Lizbeth Moira Kenny, Chris Wratten, June Corry, Stephen Cooper, Gerald Blaise Fogarty, Marnie Collins, Michael Kevin Collins, Andrew Martin John Macann, Christopher Gerard Milross, Michael Gordon Penniment, Howard Yu-hao Liu, Madeleine Trudy King, Benedict James Panizza, and Danny Rischi
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