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‣ Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform

James, Thomas L.; Liu, He; Ulyanov, Nikolai B.; Farr-Jones, Shauna; Zhang, Hong; Donne, David G.; Kaneko, Kiyotoshi; Groth, Darlene; Mehlhorn, Ingrid; Prusiner, Stanley B.; Cohen, Fred E.
Fonte: The National Academy of Sciences of the USA Publicador: The National Academy of Sciences of the USA
Tipo: Artigo de Revista Científica
Publicado em 16/09/1997 Português
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The scrapie prion protein (PrPSc) is the major, and possibly the only, component of the infectious prion; it is generated from the cellular isoform (PrPC) by a conformational change. N-terminal truncation of PrPSc by limited proteolysis produces a protein of ≈142 residues designated PrP 27–30, which retains infectivity. A recombinant protein (rPrP) corresponding to Syrian hamster PrP 27–30 was expressed in Escherichia coli and purified. After refolding rPrP into an α-helical form resembling PrPC, the structure was solved by multidimensional heteronuclear NMR, revealing many structural features of rPrP that were not found in two shorter PrP fragments studied previously. Extensive side-chain interactions for residues 113–125 characterize a hydrophobic cluster, which packs against an irregular β-sheet, whereas residues 90–112 exhibit little defined structure. Although identifiable secondary structure is largely lacking in the N terminus of rPrP, paradoxically this N terminus increases the amount of secondary structure in the remainder of rPrP. The surface of a long helix (residues 200–227) and a structured loop (residues 165–171) form a discontinuous epitope for binding of a protein that facilitates PrPSc formation. Polymorphic residues within this epitope seem to modulate susceptibility of sheep and humans to prion disease. Conformational heterogeneity of rPrP at the N terminus may be key to the transformation of PrPC into PrPSc...

‣ Protection against 3′-to-5′ RNA Decay in Bacillus subtilis

Farr, Glen A.; Oussenko, Irina A.; Bechhofer, David H.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/1999 Português
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A 320-nucleotide RNA with several characteristic features was expressed in Bacillus subtilis to study RNA processing. The RNA consisted of a 5′-proximal sequence from bacteriophage SP82 containing strong secondary structure, a Bs-RNase III cleavage site, and the 3′-proximal end of the ermC transcriptional unit. Comparison of RNA processing in a wild-type strain and a strain in which the pnpA gene, coding for polynucleotide phosphorylase (PNPase), was deleted, as well as in vitro assays of phosphate-dependent degradation, showed that PNPase activity could be stalled in vivo and in vitro. Analysis of mutations in the SP82 moiety mapped the block to PNPase processivity to a particular stem-loop structure. This structure did not provide a block to processivity in the pnpA strain, suggesting that it was specific for PNPase. An abundant RNA with a 3′ end located in the ermC coding sequence was detected in the pnpA strain but not in the wild type, indicating that this block is specific for a different 3′-to-5′ exonuclease. The finding of impediments to 3′-to-5′ degradation, with specificities for different exonucleases, suggests the existence of discrete intermediates in the mRNA decay pathway.

‣ Comparison of Four Antiseptic Preparations for Skin in the Prevention of Contamination of Percutaneously Drawn Blood Cultures: a Randomized Trial

Calfee, David P.; Farr, Barry M.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Publicado em /05/2002 Português
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A number of skin antiseptics have been used to prevent the contamination of blood cultures, but the comparative efficacies of these agents have not been extensively evaluated. We therefore sought to compare the efficacy of four skin antiseptics in preventing blood culture contamination in a randomized, crossover, investigator-blinded study conducted in an emergency department and the inpatient wards of a university hospital. The patient group included all patients from whom blood samples were obtained percutaneously for culture. Skin antisepsis was performed with 10% povidone-iodine, 70% isopropyl alcohol, tincture of iodine, or povidone-iodine with 70% ethyl alcohol (i.e., Persist). The blood culture contamination rate associated with each antiseptic was then determined. A total of 333 (2.62%) of 12,692 blood cultures were contaminated during the study period compared to 413 (3.21%) of 12,859 blood cultures obtained during the previous 12-month period (relative risk = 0.82; 95% confidence interval, 0.71 to 0.94; P = 0.006). During the study, the contamination rates were determined to be 2.93% with povidone-iodine, 2.58% with tincture of iodine, 2.50% with isopropyl alcohol, and 2.46% with Persist (P = 0.62). We detected no significant differences in the blood culture contamination rates among these four antiseptics...

‣ The Newcastle exercise project: a randomised controlled trial of methods to promote physical activity in primary care

Harland, Jane; White, Martin; Drinkwater, Chris; Chinn, David; Farr, Lorna; Howel, Denise
Fonte: British Medical Journal Publicador: British Medical Journal
Tipo: Artigo de Revista Científica
Publicado em 25/09/1999 Português
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‣ ESTIMATION OF BLOOD VOLUME FROM CHANGE IN BLOOD SPECIFIC GRAVITY FOLLOWING A PLASMA INFUSION 12

Phillips, R. A.; Yeomans, A.; Dole, V. P.; Farr, L. E.; Van Slyke, D. D.; Hogan, David
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1946 Português
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‣ STUDIES ON THE METABOLISM OF PLASMA PROTEINS IN THE NEPHROTIC SYNDROME. I. ALBUMIN, γ-GLOBULIN AND IRON-BINDING GLOBULIN 1

Gitlin, David; Janeway, Charles A.; Farr, Lee E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1956 Português
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‣ Expression of a β-Defensin mRNA, Lingual Antimicrobial Peptide, in Bovine Mammary Epithelial Tissue Is Induced by Mastitis

Swanson, Kara; Gorodetsky, Stas; Good, Laura; Davis, Stephen; Musgrave, David; Stelwagen, Kerst; Farr, Vicki; Molenaar, Adrian
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/2004 Português
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The expression of a β-defensin, the lingual antimicrobial peptide (LAP), in response to mastitis was investigated by real-time PCR of RNA from mastitic and control udder quarters. There was a positive relationship between somatic cell count in milk and LAP expression. In situ hybridization showed that LAP mRNA was expressed in epithelial cells of mastitic tissue. These results suggest that LAP plays a role in the innate immune response to mastitis.

‣ Structural changes in human serum albumin induced by ingestion of acetylsalicylic acid

Hawkins, David; Pinckard, R. Neal; Crawford, Irving P.; Farr, Richard S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1969 Português
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Acetylsalicylic acid (aspirin) acetylates human serum albumin under physiologic conditions in vitro. These investigations were done to determine whether this phenomenon occurs in vivo and to delineate the site(s) of acetylation on the albumin molecule.

‣ Interaction among Gsk-3, Gbp, Axin, and APC in Xenopus Axis Specification

Farr, Gist H.; Ferkey, Denise M.; Yost, Cynthia; Pierce, Sarah B.; Weaver, Carole; Kimelman, David
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 21/02/2000 Português
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Glycogen synthase kinase 3 (GSK-3) is a constitutively active kinase that negatively regulates its substrates, one of which is β-catenin, a downstream effector of the Wnt signaling pathway that is required for dorsal–ventral axis specification in the Xenopus embryo. GSK-3 activity is regulated through the opposing activities of multiple proteins. Axin, GSK-3, and β-catenin form a complex that promotes the GSK-3–mediated phosphorylation and subsequent degradation of β-catenin. Adenomatous polyposis coli (APC) joins the complex and downregulates β-catenin in mammalian cells, but its role in Xenopus is less clear. In contrast, GBP, which is required for axis formation in Xenopus, binds and inhibits GSK-3. We show here that GSK-3 binding protein (GBP) inhibits GSK-3, in part, by preventing Axin from binding GSK-3. Similarly, we present evidence that a dominant-negative GSK-3 mutant, which causes the same effects as GBP, keeps endogenous GSK-3 from binding to Axin. We show that GBP also functions by preventing the GSK-3–mediated phosphorylation of a protein substrate without eliminating its catalytic activity. Finally, we show that the previously demonstrated axis-inducing property of overexpressed APC is attributable to its ability to stabilize cytoplasmic β-catenin levels...

‣ Cloning of the Murine Thymic Stromal Lymphopoietin (Tslp) Receptor: Formation of a Functional Heteromeric Complex Requires Interleukin 7 Receptor

Park, Linda S.; Martin, Unja; Garka, Kirsten; Gliniak, Brian; Di Santo, James P.; Muller, Werner; Largaespada, David A.; Copeland, Neal G.; Jenkins, Nancy A.; Farr, Andrew G.; Ziegler, Steven F.; Morrissey, Philip J.; Paxton, Raymond; Sims, John E.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 05/09/2000 Português
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The cellular receptor for murine thymic stromal lymphopoietin (TSLP) was detected in a variety of murine, but not human myelomonocytic cell lines by radioligand binding. cDNA clones encoding the receptor were isolated from a murine T helper cell cDNA library. TSLP receptor (TSLPR) is a member of the hematopoietin receptor family. Transfection of TSLPR cDNA resulted in only low affinity binding. Cotransfection of the interleukin 7 (IL-7)Rα chain cDNA resulted in conversion to high affinity binding. TSLP did not activate cells from IL-7Rα−/− mice, but did activate cells from γc−/− mice. Thus, the functional TSLPR requires the IL-7Rα chain, but not the γc chain for signaling.

‣ An ALS-Linked Mutant SOD1 Produces a Locomotor Defect Associated with Aggregation and Synaptic Dysfunction When Expressed in Neurons of Caenorhabditis elegans

Wang, Jiou; Farr, George W.; Hall, David H.; Li, Fei; Furtak, Krystyna; Dreier, Lars; Horwich, Arthur L.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Português
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The nature of toxic effects exerted on neurons by misfolded proteins, occurring in a number of neurodegenerative diseases, is poorly understood. One approach to this problem is to measure effects when such proteins are expressed in heterologous neurons. We report on effects of an ALS-associated, misfolding-prone mutant human SOD1, G85R, when expressed in the neurons of Caenorhabditis elegans. Stable mutant transgenic animals, but not wild-type human SOD1 transgenics, exhibited a strong locomotor defect associated with the presence, specifically in mutant animals, of both soluble oligomers and insoluble aggregates of G85R protein. A whole-genome RNAi screen identified chaperones and other components whose deficiency increased aggregation and further diminished locomotion. The nature of the locomotor defect was investigated. Mutant animals were resistant to paralysis by the cholinesterase inhibitor aldicarb, while exhibiting normal sensitivity to the cholinergic agonist levamisole and normal muscle morphology. When fluorescently labeled presynaptic components were examined in the dorsal nerve cord, decreased numbers of puncta corresponding to neuromuscular junctions were observed in mutant animals and brightness was also diminished. At the EM level...

‣ A Comparison of Two Spirituality Instruments and Their Relationship to Depression and Quality of Life in Chronic Heart Failure

Bekelman, David B.; Parry, Carla; Curlin, Farr A.; Yamashita, Traci E.; Fairclough, Diane L.; Wamboldt, Frederick S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/2010 Português
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Spirituality is a multifaceted construct related to health outcomes that remains ill-defined and difficult to measure. Spirituality in patients with advanced chronic illnesses such as chronic heart failure has received limited attention. We compared two widely-used spirituality instruments, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) and the Ironson-Woods Spirituality/Religiousness Index (IW), to better understand what they measure in 60 outpatients with chronic heart failure. We examined how these instruments related to each other and to measures of depression and quality of life using correlations and principal components analyses. The FACIT-Sp measured aspects of spirituality related to feelings of peace and coping whereas the IW measured beliefs, coping, and relational aspects of spirituality. Only the FACIT-Sp Meaning/Peace subscale consistently correlated with depression (r = −0.50, P<.0001) and quality of life (r = 0.41, P=0.001). Three items from the depression measure loaded onto the same factor as the FACIT-Sp Meaning/Peace subscale (r= 0.43, −0.43, and 0.71), while the remaining 12 items formed a separate factor (Cronbach’s alpha=0.82) when combined with the spirituality instruments in a principal components analysis. The results demonstrate several clinically-useful constructs of spirituality in patients with heart failure and suggest that psychological well-being and spiritual well-being...

‣ An HIV epidemic is ready to emerge in the Philippines

Farr, Anna C; Wilson, David P
Fonte: The International AIDS Society Publicador: The International AIDS Society
Tipo: Artigo de Revista Científica
Publicado em 22/04/2010 Português
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‣ Allosteric signalling of ATP hydrolysis in GroEL-GroES complexes

Ranson, Neil A.; Clare, Daniel K.; Farr, George W.; Houldershaw, David; Horwich, Arthur L.; Saibil, Helen R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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The double ring chaperonin GroEL and its lid-like co-chaperonin GroES form asymmetric complexes that in the ATP-bound state mediate productive folding in a hydrophilic, GroES-encapsulated chamber, the so-called cis cavity. Upon ATP hydrolysis within the cis ring, the asymmetric complex becomes able to accept non-native polypeptide and ATP in the open, trans ring. Here we have examined the structural basis for this allosteric switch in activity by electron cryo-microscopy and single particle image processing. ATP hydrolysis does not change the conformation of the cis ring, but its effects are transmitted through an inter-ring contact and cause domain rotations in the mobile trans ring. These rigid-body movements in the trans ring lead to disruption of its intra-ring contacts, expansion of the entire ring and opening of both the nucleotide pocket and of the substrate-binding domains, admitting ATP and new substrate protein.

‣ Dolabra nepheliae on rambutan and lychee represents a novel lineage of phytopathogenic Eurotiomycetes

Rossman, Amy Y.; Schoch, Conrad L.; Farr, David F.; Nishijima, Kate; Keith, Lisa; Goenaga, Ricardo
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/07/2010 Português
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Rambutan (Nephelium lappaceum) and lychee (Litchi chinensis) are tropical trees in the Sapindaceae that produce delicious edible fruits and are increasingly cultivated in tropical regions. These trees are afflicted with a stem canker disease associated with the ascomycete Dolabra nepheliae. Previously known from Asia and Australia, this fungus was recently reported from Hawaii and Puerto Rico. The sexual and asexual states of Dolabra nepheliae are redescribed and illustrated. In addition, the ITS and large subunit of the nuclear ribosomal DNA plus fragments from the genes RPB2, TEF1, and the mitochondrial small ribosomal subunit were sequenced for three isolates of D. nepheliae and compared with other sequences of ascomycetes. It was determined that D. nepheliae represents a new lineage within the Eurotiomycetes allied with Phaeomoniella chlamydospora, the causal agent of Petri grapevine decline.

‣ Gemcitabine and Doxetaxel for Hepatocellular Carcinoma: A Phase II North Central Cancer Treatment Group (NCCTG) Clinical Trial1

Alberts, Steven R.; Reid, Joel M.; Morlan, Bruce W.; Farr, Gist H.; Camoriano, John K.; Johnson, David B.; Egner, James R.; Seay, Thomas E.; Kim, George P.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/2012 Português
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‣ Keratinocyte Apoptosis in Epidermal Remodeling and Clearance of Psoriasis Induced by UV Radiation

Weatherhead, Sophie C; Farr, Peter M; Jamieson, David; Hallinan, Jennifer S; Lloyd, James J; Wipat, Anil; Reynolds, Nick J
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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Psoriasis is a common chronic skin disorder, but the mechanisms involved in the resolution and clearance of plaques remain poorly defined. We investigated the mechanism of action of UVB, which is highly effective in clearing psoriasis and inducing remission, and tested the hypothesis that apoptosis is a key mechanism. To distinguish bystander effects, equal erythemal doses of two UVB wavelengths were compared following in vivo irradiation of psoriatic plaques; one is clinically effective (311 nm) and one has no therapeutic effect on psoriasis (290 nm). Only 311 nm UVB induced significant apoptosis in lesional epidermis, and most apoptotic cells were keratinocytes. To determine clinical relevance, we created a computational model of psoriatic epidermis. Modeling predicted apoptosis would occur in both stem and transit-amplifying cells to account for plaque clearance; this was confirmed and quantified experimentally. The median rate of keratinocyte apoptosis from onset to cell death was 20 minutes. These data were fed back into the model and demonstrated that the observed level of keratinocyte apoptosis was sufficient to explain UVB-induced plaque resolution. Our human studies combined with a systems biology approach demonstrate that keratinocyte apoptosis is a key mechanism in psoriatic plaques clearance...

‣ Office of the University President Sous fonds: Dr. James A. Gibson; Dr. James A. Gibson fonds

Williams, Edie
Fonte: Brock University Publicador: Brock University
Tipo: Outros
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Dr. James A. Gibson was born in Ottawa on January 29, 1912 to John W. and Belle Gibson. At an early age the family moved to Victoria, B.C. where John W. Gibson was a director of the Elementary Agricultural Education Branch, Department of Education. Gibson received his early education in Victoria, receiving a B.A. (honours) at UBC in 1931. In 1931 he was awarded the Rhodes scholarship and received his B.A., M.A., B.Litt and D. Phil at New College, Oxford. This was to be the beginning of a long and dedicated relationship with the Rhodes Scholar Association. Upon his return to Canada, Dr. Gibson lectured in Economics and Government at the University of British Columbia. In 1938 he was married to Caroline Stein in Philadelphia, and the same year joined the staff of the Department of External Affairs as a Foreign Service officer. Within twenty minutes of his arrival he was seconded to the Office of the Prime Minister and Secretary of State for External Affairs, W. L. Mackenzie King in charge of War Records and Liaison Officer. This was a critical time in the history of Canada, and Dr. Gibson experienced firsthand several milestones, including the Royal Visit of King George VI and Queen Elizabeth in 1939. Dr. Gibson was present at the formation of the United Nations in San Francisco in 1945...

‣ Slope-matched dispersion-compensating photonic crystal fibre

Mangan, Brian J.; Couny, Francois; Farr, Lance; Langford, Alan; Roberts, P. John.; Williams, David P.; Banham, Matthew; Mason, Matt W.; Murphy, Dominic F.; Brown, Elsa A. M.; Sabert, Hendrik; Birks, Tim A.; Knight, Jonathan C.; Russell, Philip St. J.
Fonte: Universidade de Adelaide Publicador: Universidade de Adelaide
Tipo: Conference paper
Publicado em //2004 Português
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Brian J. Mangan, Francois Couny, Lance Farr, Alan Langford, P John. Roberts, David P. Williams, Matthew Banham, Matt W. Mason, Dominic F. Murphy, Elsa A. M. Brown, Hendrik Sabert, Tim A. Birks, Jonathan C. Knight, and Philip St. J. Russell

‣ Análise da tradução/adaptação de textos dramáticos sob a perspectiva da Linguística de Corpus

Perroti-Garcia, Ana Julia
Fonte: Universidade de São Paulo. Faculdade de Filosofia, Letras e Ciências Humanas Publicador: Universidade de São Paulo. Faculdade de Filosofia, Letras e Ciências Humanas
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; Formato: application/pdf
Publicado em 04/12/2011 Português
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Computer tools may help the analysis of written texts. The aim of the present study was to determine if such tools would also be useful for the analysis of drama texts. The following computer tools were used in the present study: a worl-list generator, an aligner and a parallel concordancer. The tapescript of the English dramatist David Farrs’ play Ruckus in the Garden, and its Brazilian Portuguese translated version were part of the study corpus. The pilot study has shoen that the computer tools can help systematize and treat linguistic data to be analysed, speeding analysis and making it more consistent.; As ferramentas computadorizadas podem ajudar na análise de textos em geral. O objetivo do presente estudo foi testar se tais ferramentas também poderiam ser úteis ao analisar textos dramáticos. As ferramentas computacionais incluídas no presente estudo são: um gerador de listas de palavras, um alinhador e um concordanciador paralelo. Para a análise, utilizamos a peça Ruckus in the Garden, escrita por David Farr, dramaturgo britânico e sua tradução ao português. A partir da pesquisa aqui realizada, pudemos concluir que as ferramentas computacionais ajudam na sistematização e no tratamento dos dados a serem analisados...