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Sample records for human type xvii

  1. Cloning of the human type XVII collagen gene (COL17A1), and detection of novel mutations in generalized atrophic benign epidermolysis bullosa

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    Gatalica, B.; Pulkkinen, L.; Li, K. [Thomas Jefferson Univ., Philadelphia, PA (United States)] [and others

    1997-02-01

    Generalized atrophic benign epidermolysis bullosa (GABEB) is a nonlethal variant of junctional epidermolysis bullosa (JEB). Previous findings have suggested that type XVII collagen is the candidate gene for mutations in this disease. We now have cloned the entire human type XVII collagen gene (COL17A1) and have elucidated its intron-exon organization. The gene comprises 56 distinct exons, which span {approximately}52 kb of the genome, on the long arm of chromosome 10. It encodes a polypeptide, the {alpha}1(XVII) chain, consisting of an intracellular globular domain, a transmembrane segment, and an extracellular domain that contains 15 separate collagenous subdomains, the largest consisting of 242 amino acids. We also have developed a strategy to identify mutations in COL17A1 by use of PCR amplification of genomic DNA, using primers placed on the flanking introns. The PCR products are scanned for sequence variants by heteroduplex analysis using conformation-sensitive gel electrophoresis and then are subjected to direct automated sequencing. We have identified several intragenic polymorphisms in COL17A1, as well as mutations, in both alleles, in two Finnish families with GABEB. The probands in both families showed negative immunofluorescence staining with an anti-type XVII collagen antibody. In one family, the proband was homozygous for a 5-bp deletion, 2944del5, which resulted in frameshift and a premature termination codon of translation. The proband in the other family was a compound heterozygote, with one allele containing the 2944del5 mutation and the other containing a nonsense mutation, Q1023X. These results expand the mutation database in different variants of JEB, and they attest to the functional importance of type XVII collagen as a transmembrane component of the hemidesmosomes at the dermal/epidermal junction. 48 refs., 9 figs., 3 tabs.

  2. Pigmentation and melanocyte supply to the epidermis depend on type XVII collagen : Experimental Dermatology

    NARCIS (Netherlands)

    Gostynski, Antoni; Pasmooij, Anna M. G.; Del Rio, Marcela; Diercks, Gilles F.; Pas, Hendrikus; Jonkman, Marcellinus

    Genetic deficiency of type XVII collagen (C17), laminin-332 or type VII collagen causes epidermolysis bullosa (EB). Spontaneous correction of the deficiency, also known as revertant mosaicism, is caused by a second somatic mutation that restores protein expression resulting in clinically healthy

  3. Distribution of basement membrane anchoring molecules in normal and transformed endometrium: altered expression of laminin gamma2 chain and collagen type XVII in endometrial adenocarcinomas.

    Science.gov (United States)

    Määttä, Marko; Salo, Sirpa; Tasanen, Kaisa; Soini, Ylermi; Liakka, Annikki; Bruckner-Tuderman, Leena; Autio-Harmainen, Helena

    2004-11-01

    Basement membranes (BMs) play an important role in anchoring epithelial cells and separating them from the adjacent stroma. Altered composition and assembly of BMs may influence carcinoma cell growth and invasion. Using immunohistochemistry and in situ hybridization, we investigated the expressions of the BMs components laminin-5 (Ln-5) subunits and collagen types IV, VII and XVII in normal endometrium and compared them to the expression pattern in hyperplastic and neoplastic endometrium. Chains of Ln-5 (alpha3beta3gamma2) and types IV, VII and XVII collagens were observed in normal endometrium. In hyperplastic endometrium, laminin gamma2 chain and type XVII collagen showed intensified expression in foci of dispersed epithelial cells. Individual carcinoma cells in adenocarcinomas of low differentiation grade displayed increased laminin gamma2 chain and type XVII collagen immunoreactivity and mRNA synthesis, whereas type VII collagen usually showed decreased expression. Laminin and type IV collagen showed BM disruptions, especially in tumors with low differentiation. Our results indicate that all the BM anchoring molecules investigated are expressed in normal endometrium, but the expression of laminin gamma2 chain and collagen type XVII is altered in endometrial adenocarcinomas, which support their role in malignant growth.

  4. Macropinocytosis of type XVII collagen induced by bullous pemphigoid IgG is regulated via protein kinase C.

    Science.gov (United States)

    Iwata, Hiroaki; Kamaguchi, Mayumi; Ujiie, Hideyuki; Nishimura, Machiko; Izumi, Kentaro; Natsuga, Ken; Shinkuma, Satoru; Nishie, Wataru; Shimizu, Hiroshi

    2016-12-01

    Macropinocytosis is an endocytic pathway that is involved in the nonselective fluid uptake of extracellular fluid. Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease associated with autoantibodies to type XVII collagen (COL17), which is a component of hemidesmosome. When keratinocytes are treated with BP-IgG, COL17 internalizes into cells by way of the macropinocytosis. We investigated the mechanism of COL17 macropinocytosis using DJM-1 cells, a cutaneous squamous cell carcinoma cell line. First, non-hemidesmosomal COL17 was preferentially depleted by stimulation with the BP-IgG in the DJM-1 cells. To investigate the signaling involved in COL17-macropinocytosis, the inhibition of small GTPase family members Rac1 and Cdc42 was found to strongly repress COL17 internalization; in addition, the Rho inhibitor also partially blocked that internalization, suggesting these small GTPases are involved in signaling to mediate COL17-macropinocytosis. Western blotting using Phostag-SDS-PAGE demonstrated high levels of COL17 phosphorylation in DJM-1 cells under steady-state condition. Treatment with BP-IgG increased the intracellular calcium level within a minute, and induced the overabundant phosphorylation of COL17. The overabundant phosphorylation of COL17 was suppressed by a protein kinase C (PKC) inhibitor. In addition, PKC inhibitor repressed COL17 endocytosis using cell culture and organ culture systems. Finally, the depletion of COL17 was not observed in the HEK293 cells transfected COL17 without intracellular domain. These results suggest that COL17 internalization induced by BP-IgG may be mediated by a PKC pathway. In summary, BP-IgG initially binds to COL17 distributed on the plasma membrane, and COL17 may be internalized by means of a macropinocytic pathway related to the phosphorylation of the intracellular domain by PKC.

  5. Type XVII collagen (BP180) and LAD-1 are present as separate trimeric complexes

    NARCIS (Netherlands)

    Pas, HH; Kloosterhuis, GJ; Nijenhuis, Albertine; de Jong, MCJM; van der Meer, JB; Jonkman, MF

    This study characterized the high molecular mass BP180 complex that is observed when unheated sodium dodecyl sulfate extracts of human skin or keratinocytes are subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. In heated extracts BP180 is present as a monomer

  6. The SAURON project - XVII. Stellar population analysis of the absorption line strength maps of 48 early-type galaxies

    NARCIS (Netherlands)

    Kuntschner, Harald; Emsellem, Eric; Bacon, Roland; Cappellari, Michele; Davies, Roger L.; de Zeeuw, P. Tim; Falcón-Barroso, Jesús; Krajnović, Davor; McDermid, Richard M.; Peletier, Reynier F.; Sarzi, Marc; Shapiro, Kristen L.; van den Bosch, Remco C. E.; van de Ven, Glenn

    2010-01-01

    We present a stellar population analysis of the absorption line strength maps for 48 early-type galaxies from the SAURON sample. Using the line strength index maps of Hβ, Fe5015 and Mgb, measured in the Lick/IDS system and spatially binned to a constant signal-to-noise ratio, together with

  7. The SAURON project : XVII. Stellar population analysis of the absorption line strength maps of 48 early-type galaxies

    NARCIS (Netherlands)

    Kuntschner, Harald; Emsellem, Eric; Bacon, Roland; Cappellari, Michele; Davies, Roger L.; de Zeeuw, P. Tim; Falcon-Barroso, Jesus; Krajnovic, Davor; McDermid, Richard M.; Peletier, Reynier F.; Sarzi, Marc; Shapiro, Kristen L.; van den Bosch, Remco C. E.; van de Ven, Glenn; Krajnović, Davor

    2010-01-01

    We present a stellar population analysis of the absorption line strength maps for 48 early-type galaxies from the SAURON sample. Using the line strength index maps of H beta, Fe5015 and Mgb, measured in the Lick/IDS system and spatially binned to a constant signal-to-noise ratio, together with

  8. THE ACS VIRGO CLUSTER SURVEY. XVII. THE SPATIAL ALIGNMENT OF GLOBULAR CLUSTER SYSTEMS WITH EARLY-TYPE HOST GALAXIES

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    Wang Qiushi; Peng, Eric W. [Department of Astronomy, Peking University, Beijing 100871 (China); Blakeslee, John P.; Cote, Patrick; Ferrarese, Laura [Herzberg Institute of Astrophysics, National Research Council of Canada, 5071 West Saanich Road, Victoria, BC V9E 2E7 (Canada); Jordan, Andres [Departamento de Astronomia y Astrofisica, Pontificia Universidad Catolica de Chile, Casilla 306, Santiago 22 (Chile); Mei, Simona [University of Paris 7 Denis Diderot, F-75205 Paris Cedex 13 (France); West, Michael J., E-mail: peng@pku.edu.cn [Maria Mitchell Observatory, 4 Vestal Street, Nantucket, MA 02554 (United States)

    2013-06-01

    We study the azimuthal distribution of globular clusters (GCs) in early-type galaxies and compare them to their host galaxies using data from the ACS Virgo Cluster Survey. We find that in host galaxies with visible elongation ({epsilon} > 0.2) and intermediate to high luminosities (M{sub z} < -19), the GCs are preferentially aligned along the major axis of the stellar light. The red (metal-rich) GC subpopulations show strong alignment with the major axis of the host galaxy, which supports the notion that these GCs are associated with metal-rich field stars. The metal-rich GCs in lenticular galaxies show signs of being more strongly associated with disks rather than bulges. Surprisingly, we also find that the blue (metal-poor) GCs can also show the same correlation. If the metal-poor GCs are part of the early formation of the halo and built up through mergers, then our results support a picture where halo formation and merging occur anisotropically, and that the present-day major axis is an indicator of the preferred merging axis.

  9. Passive transfer of collagen XVII-specific antibodies induces sustained blistering disease in adult mice

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    Chiriac Mircea Teodor

    2013-01-01

    Full Text Available Abstract Background Bullous pemphigoid is a subepidermal blistering disorder associated with tissue-bound and circulating autoantibodies directed mainly to the hemidesmosomal component collagen XVII. While recapitulating the main immunopathological features of the human disease, frank skin blistering does not develop in the absence of skin rubbing in experimental pemphigoid models that have been established in neonatal mice. Moreover, due to their experimental design they only allow for short-term disease observation. In the present study we aimed to establish a model that reproduces the frank skin blistering seen in patients and allows for longer observation times. Methods Rabbit and sheep antibodies specific to several fragments of collagen XVII were generated and the purified antibodies were passively transferred into adult mice. Results Collagen XVII-specific IgG bound to the basal membrane of the skin and mucous membranes activating murine complement in vivo. Mice injected with collagen XVII-specific antibodies, in contrast to mice receiving control antibodies, developed frank skin blistering disease, reproducing human bullous pemphigoid at the clinical, histological and immunopathological levels. Titres of circulating IgG in the serum of mice correlated with the extent of the clinical disease. Mice receiving sheep antibodies specific to murine collagen XVII showed an early onset and a more active disease when compared to litter mates receiving specific rabbit antibodies. Conclusion This novel animal model for bullous pemphigoid should facilitate further investigations of the pathogenesis of bullous pemphigoid and the development of innovative therapies for this disease.

  10. Liberalismo e humanismo: as linguagens da consciência cívica na Inglaterra do século XVII Liberalism and humanism: the languages of the civic conscience in 17th century England

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    2012-12-01

    Full Text Available O surgimento da consciência cívica na Inglaterra do século XVII esteve vinculado à controvérsia constitucional nas décadas que precederam a guerra civil. O conflito político provocou uma intensa exploração intelectual, dando lugar ao surgimento de ideias e conceitos que se transformariam em dominantes no discurso e no pensamento políticos modernos. O texto tem como foco a análise dessas linguagens que contribuíram para o desenvolvimento dessa consciência cívica. Analisaremos, portanto, a linguagem do direito e os elementos nesta linguagem que contribuíram para o desenvolvimento da consciência cívica moderna. Se for verdade que a linguagem do direito foi um dos principais legados políticos do século XVII, o texto sugere que a linguagem da virtude também teve uma importância decisiva e analisa a existência de uma articulação complexa e contraditória entre ambas no surgimento da moderna consciência cívica.The emergence of civic consciousness in 17th century England was linked to constitutional controversy in the decades preceding the civil war. The political conflict sparked an intense intellectual exploration, giving rise to the emergence of ideas and concepts that became dominant in modern political thought. The text focuses on the analysis of these languages that contributed to the development of civic consciousness. We will analyze, therefore, the language of law and the elements that contributed to the development of modern civic consciousness. If it is true that the language of law was one of the main political legacies of the 17th century, the text suggests that the language of virtue also had a crucial importance and we discuss the existence of a complex and contradictory articulation between both in the emergence of modern civic consciousness.

  11. Oratorio in Rome from XVII to XVIII century

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    Dariusz Smolarek

    2012-03-01

    Full Text Available The new vocal-instrumental music type that actively bloomed in the period of baroque came into being partly by the activity of Saint Philip Neri. He organized services associated with singing laudi in a building specially intended for that purpose - named in Italian oratorio. Primarily the term “oratorio”, meant a prayer space, later was related to non-liturgical and musical services that were performed there. Laudi spirituali were gradually replaced with madrigali spirituali and motetti concertati that often had the character of dialog singing. From these forms in the first half of XVII century formed two types of oratorios: folk (oratorio volgare and latin (oratorio latino. The content of compositions was non-liturgical religious text that was inspired by the Bible featured: histories of Old Testament, figures, New Testament events and parables, and also allegoric dialogs between Christ and a Christian soul. The singers in oratorio were accompanied by orchestra (often choir performed particular dramatic roles and did not use means of actor playing. Oratorio as a carrier of religious content served liturgy and became its certain fulfillment.

  12. PREFACE: XVII International Scientific Conference ''RESHETNEV READINGS''

    Science.gov (United States)

    2015-01-01

    The International Scientific Conference ''RESHETNEV READINGS'' is dedicated to the memory of Mikhail Reshetnev, an outstanding scientist, chief-constructor of space-rocket systems and communication satellites. The current volume represents selected proceedings of the main conference materials which were published by XVII International Scientific Conference ''RESHETNEV READINGS'' held on November 12 - 14, 2013. Plenary sessions, round tables and forums will be attended by famous scientists, developers and designers representing the space technology sector, as well as professionals and experts in the IT industry. A number of outstanding academic figures expressed their interest in an event of such a level including Jaures Alferov, Vice-president of the Russian Academy of Sciences (RAS), Academician of RAS, Nobel laureate, Dirk Bochar, General Secretary of the European Federation of National Engineering Associates (FEANI), Prof. Yuri Gulyaev, Academician of RAS, Member of the Presidium of RAS, President of the International Union of Scientific and Engineering Associations, Director of the Institute of Radio Engineering and Electronics of RAS, as well as rectors of the largest universities in Russia, chief executives of well-known research enterprises and representatives of big businesses. We would like to thank our main sponsors such as JSC ''Reshetnev Information Satellite Systems'', JSC ''Krasnoyarsk Engineering Plant'', Central Design Bureau ''Geophysics'', Krasnoyarsk Region Authorities. These enterprises and companies are leading ones in the aerospace branch. It is a great pleasure to cooperate and train specialists for them.

  13. Human Papillomavirus types distribution among women with ...

    African Journals Online (AJOL)

    Introduction: cervical cancer is the leading cause of cancer deaths among females in Angola and human papillomavirus (HPV) is the main risk factor for the development of pre-cancerous squamous intraepithelial lesions. The diversity and frequency of HPV types in Angola has yet to be reported. Aim: to determine the ...

  14. Human papillomavirus type 13 infecting the conjunctiva.

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    Benevides dos Santos, Paulo José; Borborema dos Santos, Cristina Maria; Rufino Mendonça, Rosângela; Vieira do Carmo, Maria Auxiliadora; Astofi-Filho, Spartaco

    2005-09-01

    Focal epithelial hyperplasia (FEH) is a rare infection caused by human papillomavirus (HPV) types 13 or 32 believed to infect exclusively oral mucosa. This report illustrates a case of multiple conjunctival papillomas similar to oral FEH caused by HPV-13, consisting in the first description of its infection outside the oral mucosa in a healthy patient.

  15. Human papillomavirus types and recurrent cervical warts

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    Nuovo, G.J. (Columbia Presbyterian Medical Center, New York, NY (USA)); Pedemonte, B.M. (Harlem Hospital Medical Center, New York, NY (USA))

    1990-03-02

    The authors analyzed cervical intraepithelial neoplasias (CINs) detected after cryotherapy to determine if recurrence is associated with the same human papillomavirus (HPV) type found in the original lesion. Eight women had detectable HPV DNA in CINs that occurred after ablation of another CIN, and for each patient the HPV type in the pretreatment lesion was different from that in the CIN that appeared after cryotherapy. This compares with 12 women who had HPV detected in two or more CINs present at the same time, 11 of whom had the same HPv type noted. they concluded that although multiple, simultaneous CINs in a woman often contain the same HPV type, recurrent CINs that occur after cryotherapy contain an HPV type different from that present in the pretreatment lesion.

  16. XVII sajandi graafika rahvusraamatukogus / Jüri Hain

    Index Scriptorium Estoniae

    Hain, Jüri, 1941-

    2004-01-01

    Kuraator J. Hain VI korruse galeriis avatud näitusest "Euroopa XVII sajandi sügavtrükigraafika Eesti Rahvusraamatukogus". Näitusel on esindatud Jacques Callot, Stefano della Bella, Salvator Rosa, Claude Vignon, Valentin Lefebvre, Jacob Matham, Crispijn (van) de Passe jt.

  17. [SANTORIO AND THE FIRST SCIENTIFIC REVOLUTION OF XVII CENTURY].

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    Jmurkin, V P; Chalova, V V

    2015-01-01

    The national publications about Santorio and his works factually provide no information to medical society of Russia. The article presents discussion about significance of his works for the first scientific revolution in XVII century. The conception of this significance is expanded. The personal position is substantiated concerning evaluation of ratio of inputs by Santorio and Galileo into initiation of scientific revolution.

  18. Ice XVII as a Novel Material for Hydrogen Storage

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    Leonardo del Rosso

    2017-02-01

    Full Text Available Hydrogen storage is one of the most addressed issues in the green-economy field. The latest-discovered form of ice (XVII, obtained by application of an annealing treatment to a H 2 -filled ice sample in the C 0 -phase, could be inserted in the energy-storage context due to its surprising capacity of hydrogen physisorption, when exposed to even modest pressure (few mbars at temperature below 40 K, and desorption, when a thermal treatment is applied. In this work, we investigate quantitatively the adsorption properties of this simple material by means of spectroscopic and volumetric data, deriving its gravimetric and volumetric capacities as a function of the thermodynamic parameters, and calculating the usable capacity in isothermal conditions. The comparison of ice XVII with materials with a similar mechanism of hydrogen adsorption like metal-organic frameworks shows interesting performances of ice XVII in terms of hydrogen content, operating temperature and kinetics of adsorption-desorption. Any application of this material to realistic hydrogen tanks should take into account the thermodynamic limit of metastability of ice XVII, i.e., temperatures below about 130 K.

  19. XVII Congress of Portuguese Association of Operational Research (APDIO)

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    Miranda, Joao

    2015-01-01

    The development of Operations Research (OR) requires constant improvements, such as the integration of research results with business applications and innovative educational practice. The full deployment and commercial exploitation of goods and services generally need the construction of strong synergies between educational institutions and businesses. The IO2015 -XVII Congress of APDIO aims at strengthening the knowledge triangle in education, research and innovation, in order to maximize the contribution of OR for sustainable growth, the promoting of a knowledge-based economy, and the smart use of finite resources. The IO2015-XVII Congress of APDIO is a privileged meeting point for the promotion and dissemination of OR and related disciplines, through the exchange of ideas among teachers, researchers, students , and professionals with different background, but all sharing a common desire that is the development of OR.

  20. Hacienda real y sociedad en la Francia del siglo XVII

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    Badosa Coll, Elisa

    1994-01-01

    Los estudios sobre las rentas fiscales en Francia se remontan al siglo XVIII. El estudio más utilizado y riguroso es el de Jean Roland Mallet, un alto funcionario dependiente del controleur general Dezmarets a comienzos del siglo XVIII. Sus Comptes rendus de l'administration des ¡inances du royaume de France es el único que proporciona series continuas de cifras de las rentas de la corona en el siglo XVII.

  1. PREFACE: XVII Congress of Bioengineering and VI Clinical Engineering Conference

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    Rocha, Darío

    2011-09-01

    SABI 2009 was the XVII Biennial Congress of the Argentinean Bioengineering Society (SABI - www.sabi.org.ar), celebrated along with the VI Clinical Engineering Conference. It took place in Rosario, the second city of Argentina, located on the west bank of the Paraná, one of the world's most important rivers. This city, with its 150 year history and one million inhabitants, is characterized by a strong enterprising spirit. It is the agroindustrial leader of Argentina, with cereal ports recognized to be among the most active in the world, and its cereal stock exchange competes with Chicago's in international cereal pricing. Demographically Rosario presents a European profile, and there are seven national and private higher level universities in the area. SABI 2009 was the first time the Congress was celebrated in Rosario. Usually the Congress is organized by the Bioengineering Society in cooperation with a university with an undergraduate program, which Rosario lacks. To meet the needs of this exceptional case, a young local institution was asked to coordinate the Congress, the Rosario Technological Center (www.polotecnologico.net). This organization gathers together around 100 companies that produce technology, with a large number focused on IT, but those focused on biotechnology also stand out. The Center is also integrated with relevant public and government bodies. Traditionally, bioengineering has been related to human health applications, with less emphasis on applications significant to agrotechnology, an area in which Rosario is growing as an economic force. In order to address this oversight, the Congress formulated its main goals for integrating and synergizing bioengineering and biotechnology, particularly bioengineering and agrotechnology. This initiative has produced promising results. The importance of the Congress was reflected in the high number of participants - including researchers, professionals and students - from abroad, with participants from

  2. Hacienda universitaria salmantina del siglo XVII: gastos y alcances

    OpenAIRE

    Luis Enrique RODRÍGUEZ-SAN PEDRO BEZARES; Juan Luis POLO RODRÍGUEZ; Carmen CARO; José Antonio SANTOS; María Auxiliadora BARRIOS RODRÍGUEZ; Miguel Ángel MARTÍN

    2009-01-01

    Este trabajo constituye el complemento necesario de otro anterior que llevó por título «Hacienda Universitaria Salmantina del siglo XVII: Ingresos y tercias». Ambos dos fueron resultado de una labor de equipo efectuada el curso académico de 1986-1987 en el Área de Historia Moderna de la Universidad de Salamanca, como investigación aplicada a la asignatura optativa de especialidad titulada Sociedad, Universidad y Cultura de élites, ss. XVIIy XVIII. Se buscaba airear los condicionantes económic...

  3. Fiesta y urbanismo. Valencia en los siglos XVI y XVII

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    Juliana Colomer, Desirée

    2017-01-01

    El objetivo principal de la presente tesis doctoral se centra en el análisis de la influencia que ejerció la fiesta como elemento transformador de la ciudad de Valencia durante los siglos XVI y XVII. Nuestra investigación se configuró a través de un estudio bicéfalo en el que por un lado tratamos de profundizar en el urbanismo valenciano y por otro, en el mundo festivo. Basándonos en algunas investigaciones que abarcaban el periodo medieval valenciano, como las regestas de María Milagros Cárc...

  4. Una mentalidad demoníaca del siglo XVII.

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    Mario Elkin Ramírez.

    1998-01-01

    En el presente artículo el autor hace un ejercicio de reconstrucción histórica de algunos de los elementos que constituyen la mentalidad Europea en el siglo XVI y XVII, en lo que concierne la demonología, la creencia en el padre y las luchas religiosas ; para contextualizar el escrito de Freud sobre “una neurosis demoniaca del siglo XVII”. Muestra que el pintor Haizmann disponía en la utilería de su época, de las concepciones del demonio, de la virgen y de los santos que anudados a su complej...

  5. Human intestinal microbiota and type 1 diabetes.

    Science.gov (United States)

    Vaarala, Outi

    2013-10-01

    The role of intestinal microbiota in immune-mediated diseases, such as type 1 diabetes, has deservedly received a lot of attention. Evidently, changes in the intestinal microbiota are associated with type 1 diabetes as demonstrated by recent studies. Children with beta-cell autoimmunity have shown low abundance of butyrate-producing bacteria and increase in the abundance of members of the Bacteroidetes phylum in fecal microbiota. These alterations could explain increased gut permeability, subclinical small intestinal inflammation, and dysregulation of oral tolerance in type 1 diabetes. However, these studies do not provide evidence of the causative role of the gut microbiota in the development of beta-cell autoimmunity, yet. In animal models, the composition of gut microbiota modulates the function of both innate and adaptive immunity, and intestinal bacteria are regulators of autoimmune diabetes. Thus, prevention of type 1 diabetes could, in the future, be based on the interventions targeted to the gut microbiota.

  6. Human immunodeficiency virus type 2: pathogenesis and antiretroviral therapy

    NARCIS (Netherlands)

    M.E. van der Ende (Marchina)

    2000-01-01

    textabstractHuman immunodeficiency virus type1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), and simian immunodeficiency virus (SIV) have been identified as hither unknown primate members of the Lentivirinae subfamily of the family Retroviridae in 1983, 1986 and 1985 respectively, HIV-1

  7. Seroprevalence of human parainfluenza virus type 2 infection ...

    African Journals Online (AJOL)

    Serological survey was carried out to determine the level of Human Parainfluenza virus type 2 (HPIV-2) IgG antibodies in children aged 1-5 years. Blood samples were collected from 379 children who met the selection criteria in selected hospitals in Zaria. Serum IgG antibody level for. Human Parainfluenza virus type 2 was ...

  8. Human Herpes Simplex Virus Type 1 in Confiscated Gorilla

    Science.gov (United States)

    Oxford, Kristie L.; Gardner-Roberts, David; Kinani, Jean-Felix; Spelman, Lucy; Barry, Peter A.; Cranfield, Michael R.; Lowenstine, Linda J.

    2014-01-01

    In 2007, we detected human herpes simplex virus type 1, which caused stomatitis, in a juvenile confiscated eastern lowland gorilla (Gorilla beringei graueri) that had a high degree of direct contact with human caretakers. Our findings confirm that pathogens can transfer between nonhuman primate hosts and humans. PMID:25341185

  9. Los vidrios esmaltados catalanes (siglos XVI y XVII

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    Justina Rodríguez García

    2000-01-01

    Full Text Available Dentro de la producción vidriera catalana de los siglos xv al xvii, los vidrios esmaltados ocupan el lugar más destacado, por su peculiaridad y calidad artística. Sabemos que Barcelona y Matará fueron los centros más prestigiosos en donde se manufacturó esta calidad de vidrio. No son muy numerosas las piezas conservadas, y aunque el mayor número está concentrado en Barcelona, el resto se encuentra disperso por otras ciudades españolas y extranjeras. Esta serie de objetos nos ha permitido hacer un estudio pormenorizado de la técnica del vidrio esmaltado catalán, siguiendo sus tipologías, y sobre todo, su decoración.Among the Catalonian glass 'production during the xv to xvii centuries, the enamelled glasses are the most significant ones because of tfieir peculiarity and artistic quality. We know that the Barcelona and Mataró were the most prestigious centers where this quality of glass was manifactured. Only a few pieces are preserved and although most of them are concentrated in Barcelona, the rest are dispersed among other spanish and foreign cities.

  10. Icon Painters of the Nizhniy Novgorod Volga Region of the XVII Century

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    Veronicka N. Belyaeva

    2012-09-01

    Full Text Available The author considers specificity and basic difficulties of biographies of the icon painters of the Nizhniy Novgorod Volga region of the XVII-th century restore. The data on the masters are cites.

  11. RUSSIAN STATE AND MISSIONARY ORTHODOX СHURCH IN SIBERIA IN XVII CENTURY

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    V. D. Puzanov

    2016-01-01

    In 1620 Siberian diocese was founded in eastern Russia. In the scientific literature, it was noted that in Siberia XVII century representatives of the Orthodox Church were not deployed missionary activity among the peoples of the region. Historian Alexander Y. Konev, studying the state policy towards the peoples of Siberia, noted that the nature of religious policy in Siberia in the XVII century was defined "world outlook figures most of the Russian Orthodox Church." The head of the Siberian ...

  12. La violencia en el siglo XVII: los pijao

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    Manuel Lucena Salmoral

    1963-05-01

    Full Text Available A principios del siglo XVII sufrían los habitantes de las poblaciones fundadas en los hoy departamentos de Huila, Tolima y parte de Valle, Cauca y Caldas, uno de los mayores azotes de toda su historia colonial: los Pijao. Estos indios belicosos, antropófagos y valientes, habían decidido no permitir que los españoles colonizasen en sus tierras y luchar encarnizadamente para exterminar todo aquel, español o indio, que intentara establecerse en su medio geográfico, que comprendía desde cerca de !bagué al Río Páez, y desde el Magdalena y Saldaña hasta las estribaciones de la cordillera, hacia Cartago, Buga y Caloto.

  13. Hacienda universitaria salmantina del siglo XVII: gastos y alcances

    Directory of Open Access Journals (Sweden)

    Luis Enrique RODRÍGUEZ-SAN PEDRO BEZARES

    2009-12-01

    Full Text Available Este trabajo constituye el complemento necesario de otro anterior que llevó por título «Hacienda Universitaria Salmantina del siglo XVII: Ingresos y tercias». Ambos dos fueron resultado de una labor de equipo efectuada el curso académico de 1986-1987 en el Área de Historia Moderna de la Universidad de Salamanca, como investigación aplicada a la asignatura optativa de especialidad titulada Sociedad, Universidad y Cultura de élites, ss. XVIIy XVIII. Se buscaba airear los condicionantes económicos de la institución universitaria salmantina, durante una época comúnmente etiquetada de «crisis» y postración tradicionalista, cuando no de verdadera desintegración institucional.

  14. XVII 'Jacques-Louis Lions' Spanish-French School

    CERN Document Server

    Alonso, Pedro

    2017-01-01

    The first part of this volume gathers the lecture notes of the courses of the “XVII Escuela Hispano-Francesa”, held in Gijón, Spain, in June 2016. Each chapter is devoted to an advanced topic and presents state-of-the-art research in a didactic and self-contained way. Young researchers will find a complete guide to beginning advanced work in fields such as High Performance Computing, Numerical Linear Algebra, Optimal Control of Partial Differential Equations and Quantum Mechanics Simulation, while experts in these areas will find a comprehensive reference guide, including some previously unpublished results, and teachers may find these chapters useful as textbooks in graduate courses. The second part features the extended abstracts of selected research work presented by the students during the School. It highlights new results and applications in Computational Algebra, Fluid Mechanics, Chemical Kinetics and Biomedicine, among others, offering interested researchers a convenient reference guide to these l...

  15. Enzymatic Breakdown of Type II Collagen in the Human Vitreous

    NARCIS (Netherlands)

    van Deemter, Marielle; Pas, Hendri H.; Kuijer, Roel; van der Worp, Roelofje J.; Hooymans, Johanna M. M.; Los, Leonoor I.

    2009-01-01

    PURPOSE. To investigate whether enzymatic collagen breakdown is an active process in the human vitreous. METHODS. Human donor eyes were used for immunohistochemistry to detect the possible presence of the matrix metalloproteinase (MMP)-induced type II collagen breakdown product col2-3/4C-short in

  16. Human leukocyte antigen (HLA) polymorphism and type 1 diabetes ...

    African Journals Online (AJOL)

    Insulin-dependent diabetes mellitus or type 1 diabetes is an autoimmune multifactorial disease which has a great socio-economic impact. In Morocco, less is known about the contribution of Human leukocyte antigen (HLA) alleles to type 1 diabetes susceptibility. Our study focused on evaluating the distribution of class II ...

  17. Herpes Simplex Virus Type-2 and Human Immunodeficiency Virus ...

    African Journals Online (AJOL)

    Objectives: To estimate the seroprevalence of Herpes Simplex Type 2 (HSV-2) and its association with Human Immunodeficiency Virus type 1 (HIV-1) infections in rural Kilimanjaro Tanzania. Methods: A cross-sectional survey was conducted in Oria village from March to June 2005 involving all individuals aged 15-44 years ...

  18. Modelling and verification of melanin concentration on human skin type

    CSIR Research Space (South Africa)

    Karsten, AE

    2012-03-01

    Full Text Available /or in vitro and elucidated the melanosomal differences between 5 the different skin types. Meinhardt et al (9) measured the absorption spectra of in vivo human 6 skin from the lighter skin types before and after exposure to natural UV radiation, while Wan 7... et al (10) measured the epidermal (including the Stratum corneum) transmittance of in vitro 8 light and dark coloured human skin over the UVA, UVB and visible wavelength ranges. 9 None of these studies however specifically determined epidermal...

  19. Contractors and Manufacturers: Supplying Arms and Ammunition to the Spanish State in XVII and XVIII Centuries

    Directory of Open Access Journals (Sweden)

    Agustín GONZÁLEZ ENCISO

    2014-02-01

    Full Text Available This paper deals with the problem of provisioning arms and ammunition by the Spanish state during the XVII and XVIII centuries according to the types of entrepreneur (the asentista or contractor involved and the characteristics of the organization developed. First, there is a formal description of the arms industrial sector (cannons, ammunition, muskets, touching such aspects as industrial organization and the technology implied. The body of the paper goes on the figure of the asentista in each subsector: who were them, if they had other business, what were the characteristics of the contracts and the real relation with the Administration, if they developed family links in their business, and so on. Up to 1760, contracting by the state was dominant, but afterwards the policy was changed in several sectors so the state became a manufacturer state, owner of his factories. The last part of the paper focuses on this period, looking at the circumstances and consequences of that change of policy on provisioning and on the entrepreneurs.

  20. Transmembrane collagen XVII modulates integrin dependent keratinocyte migration via PI3K/Rac1 signaling.

    Directory of Open Access Journals (Sweden)

    Stefanie Löffek

    Full Text Available The hemidesmosomal transmembrane component collagen XVII (ColXVII plays an important role in the anchorage of the epidermis to the underlying basement membrane. However, this adhesion protein seems to be also involved in the regulation of keratinocyte migration, since its expression in these cells is strongly elevated during reepithelialization of acute wounds and in the invasive front of squamous cell carcinoma, while its absence in ColXVII-deficient keratinocytes leads to altered cell motility. Using a genetic model of murine Col17a1⁻/⁻ keratinocytes we elucidated ColXVII mediated signaling pathways in cell adhesion and migration. Col17a1⁻/⁻ keratinocytes exhibited increased spreading on laminin 332 and accelerated, but less directed cell motility. These effects were accompanied by increased expression of the integrin subunits β4 and β1. The migratory phenotype, as evidenced by formation of multiple unstable lamellipodia, was associated with enhanced phosphoinositide 3-kinase (PI3K activity. Dissection of the signaling pathway uncovered enhanced phosphorylation of the β4 integrin subunit and the focal adhesion kinase (FAK as activators of PI3K. This resulted in elevated Rac1 activity as a downstream consequence. These results provide mechanistic evidence that ColXVII coordinates keratinocyte adhesion and directed motility by interfering integrin dependent PI3K activation and by stabilizing lamellipodia at the leading edge of reepithelializing wounds and in invasive squamous cell carcinoma.

  1. Selecting Human Error Types for Cognitive Modelling and Simulation

    NARCIS (Netherlands)

    Mioch, T.; Osterloh, J.P.; Javaux, D.

    2010-01-01

    This paper presents a method that has enabled us to make a selection of error types and error production mechanisms relevant to the HUMAN European project, and discusses the reasons underlying those choices. We claim that this method has the advantage that it is very exhaustive in determining the

  2. Prevalence of Human Papillomavirus Type 58 in Women With or ...

    African Journals Online (AJOL)

    High prevalence of human papillomavirus 58 in Northeast Brazil. Annals of Medical and Health Sciences Research | Oct-Dec 2013 | Vol 3 | Issue 4 |. 505 of the cervical lesions of low‑grade to high‑grade and invasive cancer.[9] Studies on the prevalence of genotypes indicate that. HPV 16 is the most prevalent type in the ...

  3. Epidemiologic Evaluation of Human Papillomavirus Type Competition and the Potential for Type Replacement Post-Vaccination.

    Science.gov (United States)

    Tota, Joseph E; Jiang, Mengzhu; Ramanakumar, Agnihotram V; Walter, Stephen D; Kaufman, Jay S; Coutlée, François; Richardson, Harriet; Burchell, Ann N; Koushik, Anita; Mayrand, Marie Hélène; Villa, Luisa L; Franco, Eduardo L

    2016-01-01

    Millions of women have been vaccinated with one of two first-generation human papillomavirus (HPV) vaccines. Both vaccines remain in use and target two oncogenic types (HPVs 16 and 18); however, if these types naturally compete with others that are not targeted, type replacement may occur following reductions in the circulating prevalence of targeted types. To explore the potential for type replacement, we evaluated natural HPV type competition in unvaccinated females. Valid HPV DNA typing information was available from five epidemiological studies conducted in Canada and Brazil (n = 14,685; enrollment across studies took place between1993 and 2010), which used similar consensus-primer PCR assays, capable of detecting up to 40 HPV types. A total of 38,088 cervicovaginal specimens were available for inclusion in our analyses evaluating HPV type-type interactions involving vaccine-targeted types (6, 11, 16, and 18), and infection with each of the other HPV types. Across the studies, the average age of participants ranged from 21.0 to 43.7 years. HPV16 was the most common type (prevalence range: 1.0% to 13.8%), and in general HPV types were more likely to be detected as part of a multiple infection than as single infections. In our analyses focusing on each of the vaccine-targeted HPV types separately, many significant positive associations were observed (particularly involving HPV16); however, we did not observe any statistically significant negative associations. Our findings suggest that natural HPV type competition does not exist, and that type replacement is unlikely to occur in vaccinated populations.

  4. Pensando en el sur. El Llano en el siglo XVII

    Directory of Open Access Journals (Sweden)

    lzard, Miquel

    1994-06-01

    Full Text Available Not available.

    La agresión occidental a la futura Venezuela supuso, entre otras muchas cosas, que quienes la rechazaron, africanos que no querían ser esclavos, nativos huyendo del acoso o blancos refractarios, organizaran una sociedad cimarrona en el Llano. Cuadrúpedos huidos también del norte incrementaron la oferta de herbívoros cazables e implicaron, con los equinos, mayor autonomía y capacidad defensiva. También pensaron en el sur, por motivos antagónicos, quienes descendieron a capturar indígenas para venderlos como esclavos y quienes vieron en los orejanos la posibilidad de organizar una ganadería excedentaria. Estos últimos, miembros de la oligarquía, resolvieron que debían ocupar las sabanas por tres razones: aumentar su control sobre los pastos, liquidar competidores y extirpar un muy mal ejemplo, el de las personas libres de la cimarronera. El conflicto que a finales del siglo XVIII devendría fatal, en las dos acepciones de la palabra, se fraguó ya a mediados del siglo XVII.

  5. Una mentalidad demoníaca del siglo XVII.

    Directory of Open Access Journals (Sweden)

    Mario Elkin Ramírez.

    1998-06-01

    Full Text Available En el presente artículo el autor hace un ejercicio de reconstrucción histórica de algunos de los elementos que constituyen la mentalidad Europea en el siglo XVI y XVII, en lo que concierne la demonología, la creencia en el padre y las luchas religiosas ; para contextualizar el escrito de Freud sobre “una neurosis demoniaca del siglo XVII”. Muestra que el pintor Haizmann disponía en la utilería de su época, de las concepciones del demonio, de la virgen y de los santos que anudados a su complejo paterno personal, explican su neurosis, pero permiten además la hipótesis de que el resquebrajamiento de la figura del padre, a partir del politeísmo cristiano, y la pérdida de la hegemonía religiosa de la Iglesia católica sobrevenida por la reforma, el creciente escepticismo, -que no del ateísmo- colocan a la época entera en un instante de transición de mentalidad de un mundo cerrado de dioses y demonios a un universo positivo, científico y angustiante, por la muerte del Dios-padre protector.

  6. Human Immunodeficiency Virus Type 1 Infection of Neural Xenografts

    Science.gov (United States)

    Cvetkovich, Therese A.; Lazar, Eliot; Blumberg, Benjamin M.; Saito, Yoshihiro; Eskin, Thomas A.; Reichman, Richard; Baram, David A.; del Cerro, Coca; Gendelman, Howard E.; del Cerro, Manuel; Epstein, Leon G.

    1992-06-01

    Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain.

  7. A four-fold humanity: Margaret Mead and psychological types.

    Science.gov (United States)

    Sullivan, Gerald

    2004-01-01

    Beginning in 1933, while working in New Guinea, Margaret Mead developed her so-called squares hypothesis. Mead never published its terms, though she made a brief comment on it in her autobiography, Blackberry Winter (1972), and the arguments found in Sex and Temperament in Three Primitive Societies (1935) and the research leading to Balinese Character (Bateson & Mead, 1942) bore its imprint. Beginning with William McDougall's distinction between temperament (innate predispositions) and character (learned organization of habit), Mead articulated a morphological approach to the interplay between biology and culture that yielded four primary and four intermediary personality types. Under specified but not inevitable circumstances, the conscious choices of a given people could render one or another of these types characteristic or predominantly stable within their population, giving each of the other types a definite relation to the dominant type and thereby the cultural ethos of its society. Persons of each type followed a developmental path specific to their type different both from that of other types and in its manifestations given the various relations of the individual's type to the dominant type. Mead's hypothesis was, therefore, a vision of the unity and diversity of a single human species as well as an approach to the differing psychological positioning of individuals in cultures. In examining Mead's hypothesis, this essay also takes up Mead's debts to several leading psychologists (McDougall, C. G. Jung, and Erik Erikson), and (provisionally) how her vision differed from that of Ruth Benedict. Copyright 2004 Wiley Periodicals, Inc.

  8. Identification and typing of human enterovirus: a genomic barcode approach.

    Directory of Open Access Journals (Sweden)

    Chengguo Wei

    Full Text Available Identification and typing of human enterovirus (HEVs are important to pathogen detection and therapy. Previous phylogeny-based typing methods are mainly based on multiple sequence alignments of specific genes in the HEVs, but the results are not stable with respect to different choices of genes. Here we report a novel method for identification and typing of HEVs based on information derived from their whole genomes. Specifically, we calculate the k-mer based barcode image for each genome, HEV or other human viruses, for a fixed k, 1human viruses and 395 HEV sequences. The tree shows a clear separation of the HEV viruses from all the non-HEV viruses with 100% accuracy and a separation of the HEVs into four distinct clads with 93.4% consistency with a multiple sequence alignment-based phylogeny. Our detailed analyses of the HEVs having different typing results by the two methods indicate that our results are in better agreement with known information about the HEVs.

  9. Human muscle fiber type-specific insulin signaling: Impact of obesity and type 2 diabetes

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth; Pedersen, Andreas J T; Birk, Jesper Bratz

    2015-01-01

    /or metabolic enzymes. Pools of type I and II fibers were prepared from biopsies of the vastus lateralis muscles from lean, obese and type 2 diabetic subjects before and after a hyperinsulinemic-euglycemic clamp. Type I fibers compared to type II fibers have higher protein levels of the insulin receptor, GLUT4......-responses to insulin adjusted for protein level were not different between fiber types. Independently of fiber type, insulin signaling was similar (TBC1D1, GS and PDH-E1α) or decreased (Akt and TBC1D4) in muscle from patients with type 2 diabetes compared to lean and obese subjects. We conclude that human type I......, hexokinase II, glycogen synthase (GS), pyruvate dehydrogenase (PDH-E1α) and a lower protein content of Akt2, TBC1D4 and TBC1D1. In type I fibers compared to type II fibers, the phosphorylation-response to insulin was similar (TBC1D4, TBC1D1 and GS) or decreased (Akt and PDH-E1α). Phosphorylation...

  10. Are 20 human papillomavirus types causing cervical cancer?

    OpenAIRE

    Arbyn, Marc; Tommasino, Massimo; Depuydt, Christophe; Dillner, Joakim

    2014-01-01

    Abstract: In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the -Papillomaviridae, in particular to the species 5 (HPV51), 6 (HPV56), 7 (H...

  11. Jacques Lacan and the Other Side of Psychoanalysis: Reflections on Seminar XVII (Book Review

    Directory of Open Access Journals (Sweden)

    Lizzy Newman

    2006-01-01

    Full Text Available A review of Justin Clemens and Russell Grigg (eds., Jacques Lacan and the Other Side of Psychoanalysis: Reflections on Seminar XVII, Duke University Press, 2006. ISBN: 0-8223-3719-3.A new book that brings together 16 essays, mostly all commentaries upon Lacan''s Seminar XVII, known as 'The other Side of Psychoanalysis'. Topics include the four discourses, the relation between psychoanalysis and contemporary social discourses, the question of social change, the relationship between psychoanalysis and politics, and the structuring function of the Oedipus complex.

  12. Genetic heterogeneity and recombination in type-3 human astroviruses.

    Science.gov (United States)

    Medici, Maria Cristina; Tummolo, Fabio; Martella, Vito; Banyai, Krisztián; Bonerba, Elisabetta; Chezzi, Carlo; Arcangeletti, Maria Cristina; De Conto, Flora; Calderaro, Adriana

    2015-06-01

    Human astroviruses (HAstVs) are important enteric pathogens and can be classified genetically and antigenically into eight types. During molecular surveillance for HAstVs in Italy, sequence analysis of the diagnostic region C (about 400 nucleotide in length), located on the capsid (ORF2) gene, identified a novel type-3 strain. Upon sequencing of the full-length ORF2, the type-3 HAstV strain was characterized as a novel ORF2 genetic lineage, designated as 3c. By converse, in the ORF1b the virus was more similar to type-1 HAstVs, rather than to type-3 strains, suggesting a recombination nature, with the crossover site being mapped to the ORF1b/ORF2 junction region. Region C sequences of similar type-3 HAstV identified from European and extra-European countries were retrieved in the databases, suggesting the global distribution of this novel type-3 lineage. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Human immunodeficiency virus type-1 (HIV-1) genetic diversity and ...

    African Journals Online (AJOL)

    PROGMANAGER

    2013-04-24

    Apr 24, 2013 ... Human immunodeficiency virus type-1 (HIV-1) genetic diversity and prevalence of antiretroviral drug resistance mutations in treatment-naïve adults in Jos,. North Central Nigeria. Anejo-Okopi J. A.1*, Agbaji O. O.1,2, Agaba P. A.1,3, Ugoagwu P. O.1, Were K.4, Onywera H.4,. Owiti P.4, Isa S. E1,2, Otecko N.4 ...

  14. Citation Type Analysis on Humanity Literature of Taiwan

    Directory of Open Access Journals (Sweden)

    Ming-Yueh Tsay

    2014-04-01

    Full Text Available Using informetrics and citation analysis, the present study explores and compares characteristics and types of citations in the humanity journal articles that published in Taiwan. Research articles published in 2011, from top humanity journals, assessed by the Institute of Humanities and Social Sciences, National Science Council in Taiwan, were collected and analyzed. The analysis was done by structure of journal article and location of citations. In addition to citations appearing in the text, the phenomena of citation type will be compared and discussed in the latter part. The results of this study revealed articles of literature, history, philosophy and arts were mostly argumentative, while linguistic articles tended to comply with IMRAD (Introduction, Methods and Materials, Results,And Discussion formats. Introducing primary materials from original works, humanity scholars tended to cite for factual descriptions or to support authors’ perspectives. Secondary materials, such as later studies on the original works by other scholars, were seen the most in the disciplines of linguistics while the least in that of history. In general, the distribution of citation types is similar between articles in domestic and foreign journals; merely minor differences occurred among disciplines. While citing characteristics and information needs of humanities scholars revealed in this study may contribute to collection development of libraries or refinement of information services to researchers, suggestions based on analysis of research results may also serve as reference for standardization of writing and publication of journal articles in Taiwan. Aiming at further exploration of citations, this study is expected to provide a better understanding of the nature of citations and to serve as a foundation for future empirical studies.

  15. The pancreatic beta cells in human type 2 diabetes.

    Science.gov (United States)

    Marchetti, Piero; Bugliani, Marco; Boggi, Ugo; Masini, Matilde; Marselli, Lorella

    2012-01-01

    Bell-cell (beta-cell) impairment is central to the development and progression of human diabetes, as a result of the combined effects of genetic and acquired factors. Reduced islet number and/or reduced beta cells amount in the pancreas of individuals with Type 2 diabetes have been consistently reported. This is mainly due to increased beta cell death, not adequately compensated for by regeneration. In addition, several quantitative and/or qualitative defects of insulin secretion have been observed in Type 2 diabetes, both in vivo and ex vivo with isolated islets. All this is associated with modifications of islet cell gene and protein expression. With the identification of several susceptible Type 2 diabetes loci, the role of genotype in affecting beta-cell function and survival has been addressed in a few studies and the relationships between genotype and beta-cell phenotype investigated. Among acquired factors, the importance of metabolic insults (in particular glucotoxicity and lipotoxicity) in the natural history of beta-cell damage has been widely underlined. Continuous improvements in our knowledge of the beta cells in human Type 2 diabetes will lead to more targeted and effective strategies for the prevention and treatment of the disease.

  16. Human papillomavirus type 29 (HPV-29), an HPV type cross-hybridizing with HPV-2 and with HPV-3-related types.

    OpenAIRE

    Favre, M; Croissant, O; Orth, G

    1989-01-01

    The cloning and partial characterization of human papillomavirus (HPV) type 29 is presented. By hybridization analyses, this virus appears to be related to HPV types associated with common warts and HPV types associated with flat warts.

  17. The human respiratory syncytial virus nonstructural protein 1 regulates type I and type II interferon pathways.

    Science.gov (United States)

    Hastie, Marcus L; Headlam, Madeleine J; Patel, Nirav B; Bukreyev, Alexander A; Buchholz, Ursula J; Dave, Keyur A; Norris, Emma L; Wright, Cassandra L; Spann, Kirsten M; Collins, Peter L; Gorman, Jeffrey J

    2012-05-01

    Respiratory syncytial viruses encode a nonstructural protein (NS1) that interferes with type I and III interferon and other antiviral responses. Proteomic studies were conducted on human A549 type II alveolar epithelial cells and type I interferon-deficient Vero cells (African green monkey kidney cells) infected with wild-type and NS1-deficient clones of human respiratory syncytial virus to identify other potential pathway and molecular targets of NS1 interference. These analyses included two-dimensional differential gel electrophoresis and quantitative Western blotting. Surprisingly, NS1 was found to suppress the induction of manganese superoxide dismutase (SOD2) expression in A549 cells and to a much lesser degree Vero cells in response to infection. Because SOD2 is not directly inducible by type I interferons, it served as a marker to probe the impact of NS1 on signaling of other cytokines known to induce SOD2 expression and/or indirect effects of type I interferon signaling. Deductive analysis of results obtained from cell infection and cytokine stimulation studies indicated that interferon-γ signaling was a potential target of NS1, possibly as a result of modulation of STAT1 levels. However, this was not sufficient to explain the magnitude of the impact of NS1 on SOD2 induction in A549 cells. Vero cell infection experiments indicated that NS1 targeted a component of the type I interferon response that does not directly induce SOD2 expression but is required to induce another initiator of SOD2 expression. STAT2 was ruled out as a target of NS1 interference using quantitative Western blot analysis of infected A549 cells, but data were obtained to indicate that STAT1 was one of a number of potential targets of NS1. A label-free mass spectrometry-based quantitative approach is proposed as a means of more definitive identification of NS1 targets.

  18. Paula de Benavides: impresora del siglo XVII. El inicio de un linaje

    OpenAIRE

    Ana Cecilia Montiel Ontiveros

    2006-01-01

    En el artículo se presenta el caso de Paula de Benavides como la más importante impresora del siglo XVII y fundadora del linaje de impresores más duradero, productivo e influyente del periodo novohispano. Caso que se describe y argumenta con base en fuentes primarias hasta ahora desconocidas.

  19. 25 CFR 36.50 - Standard XVII-School program evaluation and needs assessment.

    Science.gov (United States)

    2010-04-01

    ... assessment. Each school shall complete a formal, formative evaluation at least once every seven (7) years... each school, Agency or Area, as appropriate, a standardized needs assessment and evaluation instrument... 25 Indians 1 2010-04-01 2010-04-01 false Standard XVII-School program evaluation and needs...

  20. Las enfermerías de damas y criadas en la corte del siglo XVII

    OpenAIRE

    Campos, Soledad

    2002-01-01

    El objeto del presente estudio institucional es la asistencia sanitaria y otros socorros que recibían los servidores de palacio en la corte española del siglo XVII, relacionados en la documentación que contiene el legajo 447 de la sección administrativa del Archivo General del Palacio Real de Madrid.

  1. O drama da alegoria no século XVII barroco

    Directory of Open Access Journals (Sweden)

    Tereza de Castro Callado

    2016-12-01

    Full Text Available Walter Benjamin; História; Século XVII; Cultura; Estagnação conceitual; Pensamento; Facies hippocratica; Trauerspiel; Política; Obra de Arte; Ethos histórico; imagens do pensamento; memória

  2. Human bile sorption by cancrinite-type zeolites

    Energy Technology Data Exchange (ETDEWEB)

    Linares, Carlos F. [Laboratorio de Catalisis y Metales de Transicion, Facultad de Ciencias y Tecnologia, Departamento de Quimica, Universidad de Carabobo, Valencia. Edo. Carabobo, Apartado Postal 3336 (Venezuela, Bolivarian Republic of)], E-mail: clinares@uc.edu.ve; Colmenares, Maryi; Ocanto, Freddy [Laboratorio de Catalisis y Metales de Transicion, Facultad de Ciencias y Tecnologia, Departamento de Quimica, Universidad de Carabobo, Valencia. Edo. Carabobo, Apartado Postal 3336 (Venezuela, Bolivarian Republic of); Valbuena, Oscar [Facultad de Ciencias y Tecnologia, Departamento de Biologia, Universidad de Carabobo, Valencia. Edo. Carabobo, Apartado Postal 3336 (Venezuela, Bolivarian Republic of)], E-mail: ovalbuena@uc.edu.ve

    2009-01-01

    A nitrated cancrinite-type zeolite was synthesized from zeolite X, NaOH and NaNO{sub 3} solutions under autogeneous pressure at 80 deg. C for 48 h. This zeolite was characterized by X-ray diffraction (XRD), FT-IR-spectroscopy, scanning electron microscopy (SEM) and BET surface area. XRD, SEM and FT-IR confirmed the presence of nitrated cancrinite-type zeolite without other collateral phases as sodalite. Then, this sodium zeolite was exchanged with potassium and calcium cations and finally, these modified zeolites were reacted with biliar solutions from human gallbladder. Several factors such as: mass of used cancrinite, nature of the exchanged cation and reaction time of the cancrinite-bile solution interactions were studied. The composition of bile solutions (bile acids, phospholipids and bilirubin) was analyzed before and after the cancrinite-bile solution reaction. Results showed that the components of the bile were notably reduced after the contact with solids. Ca-cancrinite, 120 min of reaction time and 500 mg of solids were the best conditions determined for the bile acid reduction in human bile. When the modified zeolites were compared with the commercial cholestyramine, it was found that zeolites were more active than the latter. These zeolites may be an alternative choice to diminish cholesterol levels in hypercholesterolemic patients.

  3. Mobile phone types and SAR characteristics of the human brain

    Science.gov (United States)

    Lee, Ae-Kyoung; Hong, Seon-Eui; Kwon, Jong-Hwa; Choi, Hyung-Do; Cardis, Elisabeth

    2017-04-01

    Mobile phones differ in terms of their operating frequency, outer shape, and form and location of the antennae, all of which affect the spatial distributions of their electromagnetic field and the level of electromagnetic absorption in the human head or brain. For this paper, the specific absorption rate (SAR) was calculated for four anatomical head models at different ages using 11 numerical phone models of different shapes and antenna configurations. The 11 models represent phone types accounting for around 86% of the approximately 1400 commercial phone models released into the Korean market since 2002. Seven of the phone models selected have an internal dual-band antenna, and the remaining four possess an external antenna. Each model was intended to generate an average absorption level equivalent to that of the same type of commercial phone model operating at the maximum available output power. The 1 g peak spatial SAR and ipsilateral and contralateral brain-averaged SARs were reported for all 11 phone models. The effects of the phone type, phone position, operating frequency, and age of head models on the brain SAR were comprehensively determined.

  4. Genomic Flexibility of Human Endogenous Retrovirus Type K

    Science.gov (United States)

    Dube, Derek; Contreras-Galindo, Rafael; He, Shirley; King, Steven R.; Gonzalez-Hernandez, Marta J.; Gitlin, Scott D.; Kaplan, Mark H.

    2014-01-01

    ABSTRACT Human endogenous retrovirus type K (HERV-K) proviruses are scattered throughout the human genome, but as no infectious HERV-K virus has been detected to date, the mechanism by which these viruses replicated and populated the genome remains unresolved. Here, we provide evidence that, in addition to the RNA genomes that canonical retroviruses package, modern HERV-K viruses can contain reverse-transcribed DNA (RT-DNA) genomes. Indeed, reverse transcription of genomic HERV-K RNA into the DNA form is able to occur in three distinct times and locations: (i) in the virus-producing cell prior to viral release, yielding a DNA-containing extracellular virus particle similar to the spumaviruses; (ii) within the extracellular virus particle itself, transitioning from an RNA-containing particle to a DNA-containing particle; and (iii) after entry of the RNA-containing virus into the target cell, similar to canonical retroviruses, such as murine leukemia virus and HIV. Moreover, using a resuscitated HERV-K virus construct, we show that both viruses with RNA genomes and viruses with DNA genomes are capable of infecting target cells. This high level of genomic flexibility historically could have permitted these viruses to replicate in various host cell environments, potentially assisting in their many integration events and resulting in their high prevalence in the human genome. Moreover, the ability of modern HERV-K viruses to proceed through reverse transcription and package RT-DNA genomes suggests a higher level of replication competency than was previously understood, and it may be relevant in HERV-K-associated human diseases. IMPORTANCE Retroviral elements comprise at least 8% of the human genome. Of all the endogenous retroviruses, HERV-K viruses are the most intact and biologically active. While a modern infectious HERV-K has yet to be found, HERV-K activation has been associated with cancers, autoimmune diseases, and HIV-1 infection. Thus, determining how this

  5. Collagen XVII is expressed in malignant but not in benign melanocytic tumors and it can mediate antibody induced melanoma apoptosis.

    Science.gov (United States)

    Krenacs, T; Kiszner, G; Stelkovics, E; Balla, P; Teleki, I; Nemeth, I; Varga, E; Korom, I; Barbai, T; Plotar, V; Timar, J; Raso, E

    2012-10-01

    The 180 kDa transmembrane collagen XVII is known to anchor undifferentiated keratinocytes to the basement membrane in hemidesmosomes while constitutively shedding a 120 kDa ectodomain. Inherited mutations or auto-antibodies targeting collagen XVII cause blistering skin disease. Collagen XVII is down-regulated in mature keratinocytes but re-expressed in skin cancer. By recently detecting collagen XVII in melanocyte hyperplasia, here we tested its expression in benign and malignant melanocytic tumors using endodomain and ectodomain selective antibodies. We found the full-length collagen XVII protein in proliferating tissue melanocytes, basal keratinocytes and squamous cell carcinoma whereas resting melanocytes were negative. Furthermore, the cell-residual 60 kDa endodomain was exclusively detected in 62/79 primary and 15/18 metastatic melanomas, 8/9 melanoma cell lines, HT199 metastatic melanoma xenografts and atypical nests in 8/63 dysplastic nevi. The rest of 19 nevi including common, blue and Spitz subtypes were also negative. In line with the defective ectodomain, sequencing of COL17A1 gene revealed aberrations in the ectodomain coding region including point mutations. Collagen XVII immunoreaction-stained spindle cell melanomas, showed partly overlapping profiles with those of S100B, Melan A and HMB45. It was concentrated at vertical melanoma fronts and statistically associated with invasive phenotype. Antibody targeting the extracellular aa507-529 terminus of collagen XVII endodomain promoted apoptosis and cell adhesion, while inhibiting proliferation in HT199 cells. These results suggest that the accumulation of collagen XVII endodomain in melanocytic tumors is associated with malignant transformation to be a potential marker of malignancy and a target for antibody-induced melanoma apoptosis.

  6. Mechanisms of human immunodeficiency virus type 2 RNA packaging

    DEFF Research Database (Denmark)

    Ni, Na; Nikolaitchik, Olga A; Dilley, Kari A

    2011-01-01

    Human immunodeficiency virus type 2 (HIV-2) has been reported to have a distinct RNA packaging mechanism, referred to as cis packaging, in which Gag proteins package the RNA from which they were translated. We examined the progeny generated from dually infected cell lines that contain two HIV-2...... that specifically recognize stem-loop motifs in the viral genomes, an assay termed single virion analysis. These studies revealed that >90% of the HIV-2 particles contained viral RNAs and that RNAs derived from different viruses were copackaged frequently. Furthermore, the frequencies of heterozygous particles...... do not support the cis-packaging hypothesis but instead indicate that trans packaging is the major mechanism of HIV-2 RNA packaging. To further characterize the mechanisms of HIV-2 RNA packaging, we visualized HIV-2 RNA in individual particles by using fluorescent protein-tagged RNA-binding proteins...

  7. Selective culture of different types of human parotid gland cells.

    Science.gov (United States)

    Chan, Yen-Hui; Huang, Tsung-Wei; Young, Tai-Horng; Lou, Pei-Jen

    2011-03-01

    Advances in salivary gland tissue engineering can benefit patients diagnosed with xerostomia. Complexity of the gland explains the urgent demand for a reliable protocol to isolate and expand various gland cells that can be used for further study. Three cells with different morphologies were isolated from the same human parotid glands using different culture medium systems and then were identified by the expressions from mRNA to the protein level. Among the 34 specimens, parotid gland acinar cells, myoepithelial cells, and fibroblasts expressing specific markers that belonged to individual cell types, were successfully isolated and expanded from 30 specimens without a complex mechanical process and expensive flow technique. The proposed protocol is simple with a high success rate to culture various gland cells, making it highly promising for use in future tissue engineering studies. Copyright © 2010 Wiley Periodicals, Inc.

  8. Human stem cell modeling in neurofibromatosis type 1 (NF1).

    Science.gov (United States)

    Wegscheid, Michelle L; Anastasaki, Corina; Gutmann, David H

    2017-04-06

    The future of precision medicine is heavily reliant on the use of human tissues to identify the key determinants that account for differences between individuals with the same disorder. This need is exemplified by the neurofibromatosis type 1 (NF1) neurogenetic condition. As such, individuals with NF1 are born with a germline mutation in the NF1 gene, but may develop numerous distinct neurological problems, ranging from autism and attention deficit to brain and peripheral nerve sheath tumors. Coupled with accurate preclinical mouse models, the availability of NF1 patient-derived induced pluripotent stem cells (iPSCs) provides new opportunities to define the critical factors that underlie NF1-associated nervous system disease pathogenesis and progression. In this review, we discuss the generation and potential applications of iPSC technology to the study of NF1. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Cytotoxicity of dietary flavonoids on different human cancer types.

    Science.gov (United States)

    Sak, Katrin

    2014-07-01

    Flavonoids are ubiquitous in nature. They are also in food, providing an essential link between diet and prevention of chronic diseases including cancer. Anticancer effects of these polyphenols depend on several factors: Their chemical structure and concentration, and also on the type of cancer. Malignant cells from different tissues reveal somewhat different sensitivity toward flavonoids and, therefore, the preferences of the most common dietary flavonoids to various human cancer types are analyzed in this review. While luteolin and kaempferol can be considered as promising candidate agents for treatment of gastric and ovarian cancers, respectively, apigenin, chrysin, and luteolin have good perspectives as potent antitumor agents for cervical cancer; cells from main sites of flavonoid metabolism (colon and liver) reveal rather large fluctuations in anticancer activity probably due to exposure to various metabolites with different activities. Anticancer effect of flavonoids toward blood cancer cells depend on their myeloid, lymphoid, or erythroid origin; cytotoxic effects of flavonoids on breast and prostate cancer cells are highly related to the expression of hormone receptors. Different flavonoids are often preferentially present in certain food items, and knowledge about the malignant tissue-specific anticancer effects of flavonoids could be purposely applied both in chemoprevention as well as in cancer treatment.

  10. "Buen alimento, mejor pensamiento": el consumo en un convento almeriense a fines del siglo XVII

    OpenAIRE

    Gómez Díaz, Donato

    2002-01-01

    Análisis de la alimentación a través de los libros de gastos de un convento a fines del siglo XVII. Valoración de los utensilios utilizados en la cocina; los productos y especias; las bebidas, dulces y tabaco. Se evalúa la alimentación como jerarquía, en las fiestas y con los enfermos. Y también como resultado del medio ecológico. Anàlisi de l'alimentació a través dels llibres de despeses d'un convent al final del segle XVII. Valoració de les eines utilitzades en la cuina; els productes i ...

  11. Is ageing associated with a shift in the balance between Type 1 and Type 2 cytokines in humans?

    DEFF Research Database (Denmark)

    Sandmand, M; Bruunsgaard, H; Kemp, K

    2002-01-01

    The balance between Type 1 and Type 2 cytokines is important for the outcome of several infectious diseases. As elderly humans show increased morbidity and mortality from infectious diseases, this study tests if ageing is associated with a change towards Type 2 dominance in T cells. Expression...

  12. XVII International AIDS Conference: From Evidence to Action - AIDS 2008 and the global response to AIDS

    OpenAIRE

    Kort, Rodney

    2009-01-01

    The impact of the XVII International AIDS Conference (AIDS 2008) was reflected in a number of commitments from political and business leaders, who announced initiatives ranging from implementing comprehensive sexual education for young people in Latin America to reducing regulatory barriers and the price of drugs in the host country. The unprecedented media coverage brought attention and public awareness to the epidemic in Latin America. Several meetings and sessions at AIDS 2008 also address...

  13. MISR Satellite Observations of Aerosol Types Affecting Human Health

    Science.gov (United States)

    Kalashnikova, O. V.; Franklin, M.; Garay, M. J.; Diner, D. J.

    2015-12-01

    Ground-based observations of pollutants and concentrations of particulate matter (PM), that includes small particles designated PM2.5 and dust-dominated PM10, are the gold standard in studies of environmental impacts on human health. However, because monitoring stations are costly, they typically provide only limited spatial coverage, especially in rural and remote areas. We will demonstrate how data from the Multi-angle Imaging SpectroRadiometer (MISR) instrument that has been flying on NASA's Terra Earth Observing System satellite since early 2000 can be used to provide estimates of surface PM types. The current MISR operational aerosol retrieval uses a combination of multi-spectral and multi-angle data to retrieve aerosol optical depth (AOD) and particle property information (including dust AOD) globally at 17.6 km spatial resolution. Using the same algorithm with data collected in all 36-channels at 275 m resolution (Local Mode), which is available over greater Los Angeles area, and also was activated during 2013 DISCOVER-AQ California field campaign, high-resolution 4.4 km aerosol retrievals were performed in addition to the standard 17.6 km retrievals. The 4.4 km spatial resolution of the PM information data is fine enough to be able to resolve local differences in PM loading that may be important for understanding regional health effects of pollution in the region. In particular, we demonstrate that MISR high-resolution AOD retrievals are in better agreement with ground-based aerosol observations and reveal more details about the aerosol spatial variability compared to the MISR standard 17.6 km product. Then we will discuss techniques and show examples of the application of high-resolution MISR data to provide estimates of surface PM for the greater Los Angeles area in 2008 and for California San Joaquin Valley during the 2013 DISCOVER-AQ field campaign. Finally, we will discuss future NASA instruments that will provide new information allowing for better

  14. Type 1 and type 2 cytokine profiles in children exposed to or infected with vertically transmitted human immunodeficiency virus.

    OpenAIRE

    Lee, B. N.; Lu, J. G.; Kline, M.W.; Paul, M.; Doyle, M; Kozinetz, C; Shearer, W T; Reuben, J. M.

    1996-01-01

    In human immunodeficiency virus (HIV)-infected adults, cytokine production profiles switch from predominantly type 1 (interleukin-2 [IL-2] and gamma interferon [IFN-gamma]) to type 2 (IL-4 and IL-10) cytokines with disease progression. To test this hypothesis in vertically HIV-infected children, we measured cytokine transcription and production in rapid progressors (RPs), seroreverters (SRs), and those children exposed to HIV in utero (P0s). Production of type 1 and type 2 cytokines was measu...

  15. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  16. Human Ubc9 Contributes to Production of Fully Infectious Human Immunodeficiency Virus Type 1 Virions▿

    OpenAIRE

    Jaber, Tareq; Bohl, Christopher R; Lewis, Gentry L.; Wood, Charles; West, John T.; Weldon, Robert A.

    2009-01-01

    Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold les...

  17. Induction of alpha interferon by human immunodeficiency virus type 1 in human monocyte-macrophage cultures.

    OpenAIRE

    Szebeni, J; Dieffenbach, C; Wahl, S M; Venkateshan, C N; Yeh, A; Popovic, M.; Gartner, S; Wahl, L M; Peterfy, M; Friedman, R. M.

    1991-01-01

    The induction of interferon (IFN) by human immunodeficiency virus type 1 (HIV-1) in primary, nonstimulated monocyte-macrophage cultures was studied. HIV-1 infection, as confirmed by p24 antigen levels in the cell supernatant, led to the production of alpha interferon (IFN-alpha) over 7 to 21 days following infection. In two of seven experiments, the IFN detected was acid labile. Coupled reverse transcription-polymerase chain reaction analysis confirmed the induction of IFN-alpha mRNA in cells...

  18. Revising ecological assumptions about Human papillomavirus interactions and type replacement.

    Science.gov (United States)

    Murall, Carmen Lía; McCann, Kevin S; Bauch, Chris T

    2014-06-07

    The controversy over whether vaccine-targeted HPV types will be replaced by other oncogenic, non-vaccine-targeted types remains unresolved. This is in part because little is known about the ecology of HPV types. Patient data has been interpreted to suggest independence or facilitative interactions between types and therefore replacement is believed to be unlikely. With a novel mathematical model, we investigated which HPV type interactions and their immune responses gave qualitatively similar patterns frequently observed in patients. To assess the possibility of type replacement, vaccination was added to see if non-vaccine-targeted types increased their 'niche'. Our model predicts that independence and facilitation are not necessary for the coexistence of types inside hosts, especially given the patchy nature of HPV infection. In fact, independence and facilitation inadequately represented co-infected patients. We found that some form of competition is likely in natural co-infections. Hence, non-vaccine-targeted types that are not cross-reactive with the vaccine could spread to more patches and can increase their viral load in vaccinated hosts. The degree to which this happens will depend on replication and patch colonization rates. Our results suggest that independence between types could be a fallacy, and so without conclusively untangling HPV within-host ecology, type replacement remains theoretically viable. More ecological thinking is needed in future studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Availability and Type of Human Resource for Health in Public ...

    African Journals Online (AJOL)

    adedamla

    1 care process. The implementation of PHC is primarily through services carried out at the primary health centres and this can only be achieved by the human force (Human Resources for Health) at these. 2-5 centres. Health workers are defined as all persons eligible to participate in the national health labour market by. 6.

  20. Prevalence of Human Papillomavirus Type 58 in Women With or ...

    African Journals Online (AJOL)

    most prevalent HPV types were HPVs 16, 58, 18, 31, and 45. HPV 16 was the most prevalent genotype, independently of the health status of patients. HPV 58 was the second most prevalent type in women with normal cytology and in those who had mild or moderate dysplasia. HPV 58 presented equal prevalence to HPV ...

  1. Neutralizing antibody response during human immunodeficiency virus type 1 infection: type and group specificity and viral escape

    DEFF Research Database (Denmark)

    Arendrup, M; Sönnerborg, A; Svennerholm, B

    1993-01-01

    demonstrated, suggesting that the majority of the change in neutralization sensitivity is driven by the selective pressure of type-specific NA. Furthermore, no differences were observed in sensitivity to neutralization by anti-carbohydrate neutralizing monoclonal antibodies or the lectin concanavalin A......The paradox that group-specific neutralizing antibodies (NA) exist in the majority of human immunodeficiency virus type 1 (HIV-1)-infected patients, whereas the NA response against autologous HIV-1 virus isolates is highly type-specific, motivated us to study the type- and group-specific NA...

  2. Alimentación e identidades en el Nuevo Reino de Granada, siglos XVI y XVII

    OpenAIRE

    Saldarriaga, Gregorio

    2011-01-01

    Este libro busca comprender la forma en que se crearon y transformaron identidades alimenticias en el Nuevo Reino de Granada, durante los siglos XVI y XVII. Para ello toma como punto de partida dos ejes centrales: las concepciones sobre la abundancia y las formas en las que el comercio hispánico modificó los panoramas alimenticios de los indígenas y de los españoles. Es un trabajo de Historia de la Alimentación que, dentro de su análisis, toma en cuenta las estructuras del gusto, los sistemas...

  3. Platería madrileña : Colecciones de la segunda mitad del s. XVII

    OpenAIRE

    Puerta Rosell, María Fernanda

    2011-01-01

    La presente investigación versa sobre el estudio de la platería civil madrileña realizado a través de los inventarios de la segunda mitad del siglo XVII. La obra se divide en varios apartados, siendo el fundamental el que recoge los diversos tipos de piezas de plata que formaban parte de los ajuares domésticos de algunos hogares madrileños de la época. Otros apartados se dedican a la función y frecuencia de uso de estas piezas; a su ubicación; a la singularidad de algunas de estas; a los mate...

  4. The Games of the XVII Olympiad Rome, 1960: the Official Report of the Organizing Committee

    OpenAIRE

    Garroni, Marcello

    2014-01-01

    The official report published after the 1960 Olympic Games in Rome, “The Games of the XVII Olympiad Rome, 1960”, consists of two volumes, published in English and Italian. Totalling almost 2,000 pages, it was the longest official report ever produced. Vol 1 Part I: The accomplishement of the task ; The Olympic venues ; Management of Olympic venues ; Technical services ; The journey of the Olympic torch ; The Olympic village.- Vol 1 Part II: Art and historical sports events ; The press service...

  5. Comparative genomics of human and non-human Listeria monocytogenes sequence type 121 strains.

    Directory of Open Access Journals (Sweden)

    Kathrin Rychli

    Full Text Available The food-borne pathogen Listeria (L. monocytogenes is able to survive for months and even years in food production environments. Strains belonging to sequence type (ST121 are particularly found to be abundant and to persist in food and food production environments. To elucidate genetic determinants characteristic for L. monocytogenes ST121, we sequenced the genomes of 14 ST121 strains and compared them with currently available L. monocytogenes ST121 genomes. In total, we analyzed 70 ST121 genomes deriving from 16 different countries, different years of isolation, and different origins-including food, animal and human ST121 isolates. All ST121 genomes show a high degree of conservation sharing at least 99.7% average nucleotide identity. The main differences between the strains were found in prophage content and prophage conservation. We also detected distinct highly conserved subtypes of prophages inserted at the same genomic locus. While some of the prophages showed more than 99.9% similarity between strains from different sources and years, other prophages showed a higher level of diversity. 81.4% of the strains harbored virtually identical plasmids. 97.1% of the ST121 strains contain a truncated internalin A (inlA gene. Only one of the seven human ST121 isolates encodes a full-length inlA gene, illustrating the need of better understanding their survival and virulence mechanisms.

  6. ANATOMY AND FIBER TYPE COMPOSITION OF HUMAN INTERARYTENOID MUSCLE

    OpenAIRE

    Tellis, Cari M.; Rosen, Clark; Thekdi, Apurva; Sciote, James J.

    2004-01-01

    Intrinsic laryngeal muscle investigations, especially those of the interarytenoid (IA) muscle, have been primarily teleologically based. We determined IA muscle anatomy and histochemical and immunohistochemical classification of extrafusal and intrafusal (muscle spindle) fibers in 5 patients. Extrafusal fibers were oxidative type I and glycolytic types IIA and IIX. Intrafusal fibers of muscle spindles were identified by the presence of tonic and neonatal myosin. The results demonstrate that t...

  7. CLINICAL AND VIROLOGIC FOUNDATION FOR PATHOGENETIC THERAPY OF HUMAN HERPES VIRUS TYPE 6 INFECTION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    N.A. Myukke

    2006-01-01

    Full Text Available Information about an infection caused by human herpes virus type 6, its' epidemiology, pathogenesis and clinical variants, is reviewed. Clinical cases, diagnosed at a time of study, are briefly reviewed.Key words: human herpes virus type 6, exanthema subitum (roseola infantum, fever of unknown origin, mononucleosis like syndrome, meningoencephalitis, children.

  8. Functional antagonism of different angiotensin II type I receptor blockers in human arteries

    NARCIS (Netherlands)

    Voors, AA; Buikema, H; van Buiten, A; Lubeck, RH; Boonstra, PW; van Veldhuisen, DJ; van Gilst, WH

    Objectives. To evaluate and compare the functional type and the degree of antagonism of the selective angiotensin II type I receptor blockers (ARB) losartan, EXP 3174 (the active metabolite of losartan), valsartan and candesartan in human internal mammary arteries. Methods. Human internal mammary

  9. Seroprevalence of human T-cell lymphotropic virus type 1 infection ...

    African Journals Online (AJOL)

    Human T-cell lymphotropic virus type-1 (HTLV1) is a lymphotropic virus which can contribute to carcinogenesis in adult T-cell leukemia, myleopathy and other disorders. 20 million people are affected by this virus in the world. The aim of this study was to determine the incidence of human T-cell lymph tropic virus type 1 ...

  10. Do type 1 fimbriae promote inflammation in the human urinary tract?

    DEFF Research Database (Denmark)

    Bergsten, G.; Wullt, B.; Schembri, Mark

    2007-01-01

    Type 1 fimbriae have been implicated as virulence factors in animal models of urinary tract infection (UTI), but the function in human disease remains unclear. This study used a human challenge model to examine if type 1 fimbriae trigger inflammation in the urinary tract. The asymptomatic....... This was unexpected, as type 1 fimbriae enhanced the inflammatory response to the same strain in the murine urinary tract and as P fimbrial expression by E. coli 83972 enhances adherence and inflammation in challenged patients. We conclude that type 1 fimbriae do not contribute to the mucosal inflammatory response...... in the human urinary tract....

  11. Prevalence of Human Papillomavirus Type 58 in Women With or ...

    African Journals Online (AJOL)

    18. Rabelo‑Santos SH, Zeferino L, Villa LL, Sobrinho JP,. Amaral RG, Magalhães AV. Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil. Mem Inst Oswaldo Cruz 2003;98:181‑4. 19. National Institute of Câncer José Alencar Gomes da.

  12. Human Rights Education in Israel: Four Types of Good Citizenship

    Science.gov (United States)

    Agbaria, Ayman K.; Katz-Pade, Revital

    2016-01-01

    This article examines the involvement of civil society organizations in human rights education (HRE) in Israel. Focussing on the educational programs of the Association for Civil Rights in Israel (ACRI), as a qualitative instrumental case study, this article examines the conceptions of good citizenship embedded in these programs. Specifically, the…

  13. Prevalence of Human Papillomavirus Type 58 in Women With or ...

    African Journals Online (AJOL)

    the anogenital tract and other mucosal areas of the human body. They are classified as high or low oncogenic risk according to their involvement in the genesis of benign or malignant lesions.[7,8] Among these, at least 15 are considered high‑risk. HPV (HR‑HPV) and are strongly associated with progression. Prevalence of ...

  14. Ascorbic acid enhances the expression of type 1 and type 4 collagen and SVCT2 in cultured human skin fibroblasts.

    Science.gov (United States)

    Kishimoto, Yuki; Saito, Norikatsu; Kurita, Katsumi; Shimokado, Kentaro; Maruyama, Naoki; Ishigami, Akihito

    2013-01-11

    Ascorbic acid (AA) is essential for collagen biosynthesis as a cofactor for prolyl and lysyl hydroxylase and as a stimulus for collagen gene expression. Many studies have evaluated the relationship between AA and collagen expression in short- and long-term effects on cells after a single administration of AA into the culture medium. However, no such study has monitored in detail the stability of AA in medium or the alterations of intracellular AA levels during a protracted interval. Therefore, we examined here intracellular AA levels and stability throughout its exposure to human skin fibroblasts in vitro. Moreover, we determined the effects on type 1 and type 4 collagen and sodium-dependent vitamin C transporter (SVCT) gene expression when medium containing 100 μM AA was replaced every 24h for 5 days to avoid depletion of AA. Throughout this long-term culture, intracellular AA levels remained constant; the expression of type 1 and type 4 collagens and SVCT2 mRNA was enhanced, and type 1 procollagen synthesis increased. Thus, these results indicate that human skin fibroblasts exposed to AA over time had rising levels of type 1/type 4 collagens and SVCT2 mRNA expression and type 1 procollagen synthesis. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

  15. Reconstruction of genome-scale active metabolic networks for 69 human cell types and 16 cancer types using INIT.

    Directory of Open Access Journals (Sweden)

    Rasmus Agren

    Full Text Available Development of high throughput analytical methods has given physicians the potential access to extensive and patient-specific data sets, such as gene sequences, gene expression profiles or metabolite footprints. This opens for a new approach in health care, which is both personalized and based on system-level analysis. Genome-scale metabolic networks provide a mechanistic description of the relationships between different genes, which is valuable for the analysis and interpretation of large experimental data-sets. Here we describe the generation of genome-scale active metabolic networks for 69 different cell types and 16 cancer types using the INIT (Integrative Network Inference for Tissues algorithm. The INIT algorithm uses cell type specific information about protein abundances contained in the Human Proteome Atlas as the main source of evidence. The generated models constitute the first step towards establishing a Human Metabolic Atlas, which will be a comprehensive description (accessible online of the metabolism of different human cell types, and will allow for tissue-level and organism-level simulations in order to achieve a better understanding of complex diseases. A comparative analysis between the active metabolic networks of cancer types and healthy cell types allowed for identification of cancer-specific metabolic features that constitute generic potential drug targets for cancer treatment.

  16. Islet Specific Wnt Activation in Human Type II Diabetes

    Directory of Open Access Journals (Sweden)

    Seung-Hee Lee

    2008-01-01

    Full Text Available The Wnt pathway effector gene TCF7L2 has been linked to type II diabetes, making it important to study the role of Wnt signaling in diabetes pathogenesis. We examined the expression of multiple Wnt pathway components in pancreases from normal individuals and type II diabetic individuals. Multiple members of the Wnt signaling pathway, including TCF7L2, Wnt2b, β-catenin, pGSK3β, TCF3, cyclinD1, and c-myc, were undetectable or expressed at low levels in islets from nondiabetic individuals, but were also upregulated specifically in islets of type II diabetic patients. Culture of pancreatic tissue and islet isolation led to Wnt activation that was reversed by the Wnt antagonist sFRP, demonstrating that Wnt activation in that setting was due to soluble Wnt factors. These data support a model in which the Wnt pathway plays a dynamic role in the pathogenesis of type II diabetes and suggest manipulation of Wnt signaling as a new approach to β-cell-directed diabetes therapy.

  17. Prevalence of Human Papillomavirus Type 58 in Women With or ...

    African Journals Online (AJOL)

    Chicago Il, USA). Results: Overall HPV prevalence was 65.2% (277/425), with 85.9% (238/277) single and 14.1% (39/277) multiple infection. The most prevalent HPV types were HPVs 16, 58, 18, 31, and 45. HPV 16 was the most prevalent ...

  18. Method for identifying type I diabetes mellitus in humans

    Energy Technology Data Exchange (ETDEWEB)

    Metz, Thomas O [Kennewick, WA; Qian, Weijun [Richland, WA; Jacobs, Jon M [Pasco, WA; Smith, Richard D [Richland, WA

    2011-04-12

    A method and system for classifying subject populations utilizing predictive and diagnostic biomarkers for type I diabetes mellitus. The method including determining the levels of a variety of markers within the serum or plasma of a target organism and correlating this level to general populations as a screen for predisposition or progressive monitoring of disease presence or predisposition.

  19. Human leukocyte antigen (HLA) polymorphism and type 1 diabetes ...

    African Journals Online (AJOL)

    Médecins

    distribution of class II HLA genes among Moroccan patients presenting type 1 diabetes coming from different regions of the country. A total of ... Subsequently,. DQB1 and DQA1 genes were shown to be more strongly associated with T1D, and ..... Genetic heterogeneity, mode of inheritance, and risk estimate for joint study of ...

  20. The Human Polycomb Group EED Protein Interacts with the Integrase of Human Immunodeficiency Virus Type 1

    Science.gov (United States)

    Violot, Sébastien; Hong, Saw See; Rakotobe, Dina; Petit, Caroline; Gay, Bernard; Moreau, Karen; Billaud, Geneviève; Priet, Stéphane; Sire, Joséphine; Schwartz, Olivier; Mouscadet, Jean-François; Boulanger, Pierre

    2003-01-01

    Human EED, a member of the superfamily of WD-40 repeat proteins and of the Polycomb group proteins, has been identified as a cellular partner of the human immunodeficiency virus type 1 (HIV-1) matrix (MA) protein (R. Peytavi et al., J. Biol. Chem. 274:1635-1645, 1999). In the present study, EED was found to interact with HIV-1 integrase (IN) both in vitro and in vivo in yeast. In vitro, data from mutagenesis studies, pull-down assays, and phage biopanning suggested that EED-binding site(s) are located in the C-terminal domain of IN, between residues 212 and 264. In EED, two putative discrete IN-binding sites were mapped to its N-terminal moiety, at a distance from the MA-binding site, but EED-IN interaction also required the integrity of the EED last two WD repeats. EED showed an apparent positive effect on IN-mediated DNA integration reaction in vitro, in a dose-dependent manner. In situ analysis by immunoelectron microscopy (IEM) of cellular distribution of IN and EED in HIV-1-infected cells (HeLa CD4+ cells or MT4 lymphoid cells) showed that IN and EED colocalized in the nucleus and near nuclear pores, with maximum colocalization events occurring at 6 h postinfection (p.i.). Triple colocalizations of IN, EED, and MA were also observed in the nucleoplasm of infected cells at 6 h p.i., suggesting the ocurrence of multiprotein complexes involving these three proteins at early steps of the HIV-1 virus life cycle. Such IEM patterns were not observed with a noninfectious, envelope deletion mutant of HIV-1. PMID:14610174

  1. Pious works as a Path to Salvation: the Bishopric of Albarracín (XVII century

    Directory of Open Access Journals (Sweden)

    José Manuel LATORRE CIRIA

    2015-12-01

    Full Text Available  This article intends to show the role that various pious works play as instruments of salvation and as an expression of certain forms of religiousness that had deep social repercussions. We highlight the case of the bishopric of Albarracín during the XVII century. The study is mainly concerned with the information furnished by pastoral visits, the book of chaplaincy institutions and two reports on the bishopric written toward the start and the end of the XVII century respectively. The founding of chaplaincies and benefices was effected as an answer to the search for spiritual graces; however these institutions which were offered to the faithful by the Church as paths to salvation provided clear social advantages. Through these institutions the future of a family member could be secured. The memory and name of the founder perpetuated and the vanity of the linages was satisfied. Pious works were instruments of salvation, but also of solidarity, and family support.

  2. Supino vartojimas XVI-XVII a. lietuvių rašto paminkluose

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    Jonas Palionis

    2011-05-01

    Full Text Available DER GEBRAUCH DES SUPINUM IN DEN LITAUISCHEN SPRACHDENKMÄLERN DES XVI.-XVII. JAHRHUNDERTSZusammen fassungDie Analyse des Gebrauchs des Supinum in den litauischen Sprachdenkmälern des XVI.—XVII. Jh. zeugt davon, daß diese Form in jener Zeit eine viel umfangreichere Verbreitung hatte als in der Gegenwartssprache: sie war nicht nur in den ostlitauischen, sondern auch in den süd-, west- und mittellitauischen Mundarten erhalten geblieben. Gleichzeitig ist aber das allmähliche Schwinden des Supinum und die Ausbreitung des Infinitivs zu beobachten. Allem Anschein nach war dieser Prozeß in dem žemaitischen Dialekt schon damals abgeschlossen.Das Supinum war in der Regel von den intransitiven Verben der Fortbewegung abhängig und regierte einen nominalen oder pronominalen Genitiv (selten einen Akkusativ. In einigen Fäl­len ging das Supinum auch mit den Verben, die eine Fortbewegung nur indirekt ausdrückten (siųsti „senden“ u. a..

  3. TERASING DALAM BUDAYA BARAT DAN TIMUR: POTRET “NYAI” HINDIA BELANDA, ABAD XVII-XX

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    FX. Domini BB Hera

    2014-09-01

    Full Text Available “Nyai” is the concept that refer to native woman (including Chinese and Japanese woman who life without married relationship with European, Chinese, or Arabian man. However the position of “Nyai” is not accepted by foreigner (commonly western society and indigenous people (commonly eastern society, but they have important role in the family and social-culture in Hindia Belanda, XVII-XX. Beside the negative image attaching to “Nyai”, they also have positive side in society life as cultural mediator between western and eastern culture. It is giving a chance for “Nyai” to give any cultural influence from one society or group to another. The study can give the reader a lot of understanding about development of sexuality in Nusantara (The past Indonesia and the point is the study like the basic form to explain the phenomena of unmarried couple today. In short, this study will focus on the image and role of “Nyai” in Hindia Belanda, XVII-XX

  4. Lack of enhancing effect of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of human blood monocytes and peritoneal macrophages.

    OpenAIRE

    Shadduck, P P; Weinberg, J B; Haney, A. F.; Bartlett, J. A.; Langlois, A J; Bolognesi, D P; Matthews, T J

    1991-01-01

    The influence of human anti-human immunodeficiency virus type 1 (HIV-1) antibody on HIV-1 infection of freshly isolated normal human peritoneal macrophages and blood monocytes was examined. Each of 14 HIV antibody-positive human serum samples was found to block the infection of four virus isolates (human T-cell lymphotropic virus type IIIBa-L [HTLV-IIIBa-L], HTLV-IIIB, D.U. 6587-7, and D.U. 7887-8) at serum dilutions ranging from 10(-1) to 10(-2). Three of these isolates (HTLV-IIIBa-L, D.U. 6...

  5. Characterization of Enteroviruses from non-human primates in cameroon revealed virus types widespread in humans along with candidate new types and species.

    Directory of Open Access Journals (Sweden)

    Serge Alain Sadeuh-Mba

    Full Text Available Enteroviruses (EVs infecting African Non-Human Primates (NHP are still poorly documented. This study was designed to characterize the genetic diversity of EVs among captive and wild NHP in Cameroon and to compare this diversity with that found in humans. Stool specimens were collected in April 2008 in NHP housed in sanctuaries in Yaounde and neighborhoods. Moreover, stool specimens collected from wild NHP from June 2006 to October 2008 in the southern rain forest of Cameroon were considered. RNAs purified directly from stool samples were screened for EVs using a sensitive RT-nested PCR targeting the VP1 capsid coding gene whose nucleotide sequence was used for molecular typing. Captive chimpanzees (Pan troglodytes and gorillas (Gorilla gorilla were primarily infected by EV types already reported in humans in Cameroon and elsewhere: Coxsackievirus A13 and A24, Echovirus 15 and 29, and EV-B82. Moreover EV-A119, a novel virus type recently described in humans in central and west Africa, was also found in a captive Chimpanzee. EV-A76, which is a widespread virus in humans, was identified in wild chimpanzees, thus suggesting its adaptation and parallel circulation in human and NHP populations in Cameroon. Interestingly, some EVs harbored by wild NHP were genetically distinct from all existing types and were thus assigned as new types. One chimpanzee-derived virus was tentatively assigned as EV-J121 in the EV-J species. In addition, two EVs from wild monkeys provisionally registered as EV-122 and EV-123 were found to belong to a candidate new species. Overall, this study indicates that the genetic diversity of EVs among NHP is more important than previously known and could be the source of future new emerging human viral diseases.

  6. Characterization of Enteroviruses from Non-Human Primates in Cameroon Revealed Virus Types Widespread in Humans along with Candidate New Types and Species

    Science.gov (United States)

    Sadeuh-Mba, Serge Alain; Bessaud, Maël; Joffret, Marie-Line; Endegue Zanga, Marie-Claire; Balanant, Jean; Mpoudi Ngole, Eitel; Njouom, Richard; Reynes, Jean-Marc; Delpeyroux, Francis; Rousset, Dominique

    2014-01-01

    Enteroviruses (EVs) infecting African Non-Human Primates (NHP) are still poorly documented. This study was designed to characterize the genetic diversity of EVs among captive and wild NHP in Cameroon and to compare this diversity with that found in humans. Stool specimens were collected in April 2008 in NHP housed in sanctuaries in Yaounde and neighborhoods. Moreover, stool specimens collected from wild NHP from June 2006 to October 2008 in the southern rain forest of Cameroon were considered. RNAs purified directly from stool samples were screened for EVs using a sensitive RT-nested PCR targeting the VP1 capsid coding gene whose nucleotide sequence was used for molecular typing. Captive chimpanzees (Pan troglodytes) and gorillas (Gorilla gorilla) were primarily infected by EV types already reported in humans in Cameroon and elsewhere: Coxsackievirus A13 and A24, Echovirus 15 and 29, and EV-B82. Moreover EV-A119, a novel virus type recently described in humans in central and west Africa, was also found in a captive Chimpanzee. EV-A76, which is a widespread virus in humans, was identified in wild chimpanzees, thus suggesting its adaptation and parallel circulation in human and NHP populations in Cameroon. Interestingly, some EVs harbored by wild NHP were genetically distinct from all existing types and were thus assigned as new types. One chimpanzee-derived virus was tentatively assigned as EV-J121 in the EV-J species. In addition, two EVs from wild monkeys provisionally registered as EV-122 and EV-123 were found to belong to a candidate new species. Overall, this study indicates that the genetic diversity of EVs among NHP is more important than previously known and could be the source of future new emerging human viral diseases. PMID:25079078

  7. El Buen Pastor y la Monarquía Católica en la segunda mitad del siglo XVII

    Directory of Open Access Journals (Sweden)

    Iván Sánchez Llanes

    2009-01-01

    Full Text Available En los siglos XVII y XVIII hay muchas maneras en las que se conceptualiza la relación entre el rey y la comunidad de vasallos, cada una de las cuales muestra algunos aspectos particulares de la teoría y metodología de la praxis del poder político. En este artículo, vamos a explorar la imagen del «Buen pastor» en la monarquía católica en la segunda mitad del siglo XVII y los modos en que apunta una nueva percepción de los deberes y obligaciones que vinculan al rey y su reino.In the XVI and XVII centuries, there are several ways in which the relationship between the king and the community of the vassals is conceptualized, everyone of them showing some particular aspects of the theoretical and methodological praxis of the political power. In this article, we are going to explore the image of the «Good shepherd» in the Catholic monarchy in the second half of the XVII century and the ways in which it points out a new perception of the duties and obligations that links the king and its kingdom.

  8. Human Ubc9 contributes to production of fully infectious human immunodeficiency virus type 1 virions.

    Science.gov (United States)

    Jaber, Tareq; Bohl, Christopher R; Lewis, Gentry L; Wood, Charles; West, John T; Weldon, Robert A

    2009-10-01

    Ubc9 was identified as a cellular protein that interacts with the Gag protein of Mason-Pfizer monkey virus. We show here that Ubc9 also interacts with the human immunodeficiency virus type 1 (HIV-1) Gag protein and that their interaction is important for virus replication. Gag was found to colocalize with Ubc9 predominantly at perinuclear puncta. While cells in which Ubc9 expression was suppressed with RNA interference produced normal numbers of virions, these particles were 8- to 10-fold less infectious than those produced in the presence of Ubc9. The nature of this defect was assayed for dependence on Ubc9 during viral assembly, trafficking, and Env incorporation. The Gag-mediated assembly of virus particles and protease-mediated processing of Gag and Gag-Pol were unchanged in the absence of Ubc9. However, the stability of the cell-associated Env glycoprotein was decreased and Env incorporation into released virions was altered. Interestingly, overexpression of the Ubc9 trans-dominant-negative mutant C93A, which is a defective E2-SUMO-1 conjugase, suggests that this activity may not be required for interaction with Gag, virion assembly, or infectivity. This finding demonstrates that Ubc9 plays an important role in the production of infectious HIV-1 virions.

  9. spa typing and antimicrobial resistance of Staphylococcus aureus from healthy humans, pigs and dogs in Tanzania.

    Science.gov (United States)

    Katakweba, Abdul Sekemani; Muhairwa, Amandus Pachificus; Espinosa-Gongora, Carmen; Guardabassi, Luca; Mtambo, Madundo M A; Olsen, John Elmerdahl

    2016-02-28

    Staphylococcus aureus is an opportunistic pathogen causing infections in humans and animals. Here we report for the first time the prevalence of nasal carriage, spa typing and antimicrobial resistance of S. aureus in a Tanzanian livestock community. Nasal swabs were taken from 100 humans, 100 pigs and 100 dogs in Morogoro Municipal. Each swab was enriched in Mueller Hinton broth with 6.5% NaCl and subcultured on chromogenic agar for S. aureus detection. Presumptive S. aureus colonies were confirmed to the species level by nuc PCR and analysed by spa typing. Antimicrobial susceptibility patterns were determined by disc diffusion method. S. aureus was isolated from 22% of humans, 4% of pigs and 11% of dogs. A total of 21 spa types were identified: 13, 7 and 1 in human, dogs, and pigs, respectively. Three spa types (t314, t223 and t084) were shared between humans and dogs. A novel spa type (t10779) was identified in an isolate recovered from a colonized human. Antimicrobials tested revealed resistance to ampicillin in all isolates, moderate resistances to other antimicrobials with tetracycline resistance being the most frequent. S. aureus carrier frequencies in dogs and humans were within the expected range and low in pigs. The S. aureus spa types circulating in the community were generally not shared by different hosts and majority of types belonged to known clones. Besides ampicillin resistance, moderate levels of antimicrobial resistance were observed irrespective of the host species from which the strains were isolated.

  10. Predictive data modeling of human type II diabetes related statistics

    Science.gov (United States)

    Jaenisch, Kristina L.; Jaenisch, Holger M.; Handley, James W.; Albritton, Nathaniel G.

    2009-04-01

    During the course of routine Type II treatment of one of the authors, it was decided to derive predictive analytical Data Models of the daily sampled vital statistics: namely weight, blood pressure, and blood sugar, to determine if the covariance among the observed variables could yield a descriptive equation based model, or better still, a predictive analytical model that could forecast the expected future trend of the variables and possibly eliminate the number of finger stickings required to montior blood sugar levels. The personal history and analysis with resulting models are presented.

  11. Three mutations switch H7N9 influenza to human-type receptor specificity

    Energy Technology Data Exchange (ETDEWEB)

    de Vries, Robert P.; Peng, Wenjie; Grant, Oliver C.; Thompson, Andrew J.; Zhu, Xueyong; Bouwman, Kim M.; de la Pena, Alba T. Torrents; van Breemen, Marielle J.; Ambepitiya Wickramasinghe, Iresha N.; de Haan, Cornelis A. M.; Yu, Wenli; McBride, Ryan; Sanders, Rogier W.; Woods, Robert J.; Verheije, Monique H.; Wilson, Ian A.; Paulson, James C.; Fernandez-Sesma, Ana

    2017-06-15

    The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells.

  12. Crystal structure of human quinone reductase type 2, a metalloflavoprotein.

    Science.gov (United States)

    Foster, C E; Bianchet, M A; Talalay, P; Zhao, Q; Amzel, L M

    1999-08-03

    In mammals, two separate but homologous cytosolic quinone reductases have been identified: NAD(P)H:quinone oxidoreductase type 1 (QR1) (EC 1.6.99.2) and quinone reductase type 2 (QR2). Although QR1 and QR2 are nearly 50% identical in protein sequence, they display markedly different catalytic properties and substrate specificities. We report here two crystal structures of QR2: in its native form and bound to menadione (vitamin K(3)), a physiological substrate. Phases were obtained by molecular replacement, using our previously determined rat QR1 structure as the search model. QR2 shares the overall fold of the major catalytic domain of QR1, but lacks the smaller C-terminal domain. The FAD binding sites of QR1 and QR2 are very similar, but their hydride donor binding sites are considerably different. Unexpectedly, we found that QR2 contains a specific metal binding site, which is not present in QR1. Two histidine nitrogens, one cysteine thiol, and a main chain carbonyl group are involved in metal coordination. The metal binding site is solvent-accessible, and is separated from the FAD cofactor by a distance of about 13 A.

  13. Different types of tremor in the human thumb.

    Science.gov (United States)

    Brown, T I; Rack, P M; Ross, H F

    1982-11-01

    1. The upper limbs of normal subjects were immobilized in a way that allowed measurement of forces and movements at the thumb interphalangeal joint without significant movement elsewhere in the limb. 2. When the subject attempted to maintain a steady flexing force at the joint against a rigid stop, the actual force showed the irregular 8-11 Hz fluctuations characteristic of a 'physiological tremor'. This force fluctuation increased when the mean flexing force increased. 3. If the subject exerted his flexing force against a light complaint spring, there was an analogous irregular 8-11 Hz movement at the joint. 4. When, however, an extra inertial load was added to the terminal phalanx, flexion against a complaint spring was often accompanied by a different type of tremor. This was a more regular oscillation, of lower frequency (3-6 Hz), and of much larger amplitude. 5. The precise frequency and amplitude of this type of tremor depended on the characteristics of the added inertia and spring, in a way that could have been predicted from the responses of the joint to an imposed sinusoidal movement (Brown, Rack & Ross, 1982a). The movement appeared to arise from re-excitation within stretch reflex pathways. 6. The irregular 8-11 Hz tremor at this joint could not be attributed to reflex re-excitation, since the responses to sinusoidal movement indicated a stretch reflex whose timing would not support a movement at that frequency. It is, however, emphasized that other joints of the hand and fingers may behave in different ways.

  14. Organization of fibrillar collagen in the human and bovine cornea: collagen types V and III.

    Science.gov (United States)

    White, J; Werkmeister, J A; Ramshaw, J A; Birk, D E

    1997-01-01

    The localization and fibrillar organization of collagen types V and III in the human and bovine corneal stromas were studied. In the chicken cornea, type V co-assembles with type I collagen as heterotypic fibrils and this interaction is involved in the regulation of fibril diameter necessary for corneal transparency. To determine whether this is a regulatory mechanism common to the corneas of different species the human and bovine corneal stroma were studied. Collagen type V was found in the epithelium and Bowman's membrane in the untreated adult human and bovine cornea using immunofluorescence microscopy. In the absence of any treatment, there was no type V reactivity within the stroma. However, type V collagen was detected homogeneously throughout the corneal stroma after treatments that partially disrupt fibril structure. The reactivity was strongest in the cornea, weaker in the limbus and weakest in the sclera. Fetal corneas showed similar reactivity for type V collagen, but unlike the adult, the stroma was slightly reactive. Immunoelectron microscopy demonstrated that type V collagen was associated with disrupted, but not with intact, fibrils in both human and bovine corneal stroma. Type III collagen reactivity was not detected in the cornea, but was present subepithelially in the limbus and in the scleral stroma. These data indicate that type V collagen is a component of striated collagen fibrils throughout the human and bovine corneal stromas. The interaction of type I and V collagen as heterotypic fibrils masks the helical epitope recognized by the monoclonal antibody against type V collagen. The heterotypic interactions of collagen type V indicate a role in the regulation of fibril diameter analogous to that described in the avian cornea.

  15. Oncogenic potential diverge among human papillomavirus type 16 natural variants

    Energy Technology Data Exchange (ETDEWEB)

    Sichero, Laura, E-mail: lsichero@gmail.com [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Simao Sobrinho, Joao [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Lina Villa, Luisa [Molecular Biology Laboratory, Center of Translational Oncology, Instituto do Cancer do Estado de Sao Paulo-ICESP, Sao Paulo 01246-000 (Brazil); Department of Virology, Ludwig Institute for Cancer Research, Sao Paulo 01323-903 (Brazil); Department of Radiology, School of Medicine, University of Sao Paulo (Brazil)

    2012-10-10

    We compared E6/E7 protein properties of three different HPV-16 variants: AA, E-P and E-350G. Primary human foreskin keratinocytes (PHFK) were transduced with HPV-16 E6 and E7 and evaluated for proliferation and ability to grow in soft agar. E-P infected keratinocytes presented the lowest efficiency in colony formation. AA and E-350G keratinocytes attained higher capacity for in vitro transformation. We observed similar degradation of TP53 among HPV-16 variants. Furthermore, we accessed the expression profile in early (p5) and late passage (p30) transduced cells of 84 genes commonly involved in carcinogenesis. Most differences could be attributed to HPV-16 E6/E7 expression. In particular, we detected different expression of ITGA2 and CHEK2 in keratinocytes infected with AA and AA/E-350G late passage cells, respectively, and higher expression of MAP2K1 in E-350G transduced keratinocytes. Our results indicate differences among HPV-16 variants that could explain, at least in part, differences in oncogenic potential attributed to these variants.

  16. Human papillomavirus prevalence and type-distribution in cervical glandular neoplasias

    DEFF Research Database (Denmark)

    Holl, Katsiaryna; Nowakowski, Andrzej M; Powell, Ned

    2015-01-01

    Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type-distribution in CGN vary, providi...

  17. spa typing and antimicrobial resistance of Staphylococcus aureus from healthy humans, pigs and dogs in Tanzania

    DEFF Research Database (Denmark)

    Katakweba, Abdul S.; Muhairwa, Amandus P.; Espinosa-Gongora, Carmen

    2016-01-01

    Introduction: Staphylococcus aureus is an opportunistic pathogen causing infections in humans and animals. Here we report for the first time the prevalence of nasal carriage, spa typing and antimicrobial resistance of S. aureus in a Tanzanian livestock community. Methodology: Nasal swabs were taken...... from 100 humans, 100 pigs and 100 dogs in Morogoro Municipal. Each swab was enriched in Mueller Hinton broth with 6.5% NaCl and subcultured on chromogenic agar for S. aureus detection. Presumptive S. aureus colonies were confirmed to the species level by nuc PCR and analysed by spa typing....... Antimicrobial susceptibility patterns were determined by disc diffusion method. Results: S. aureus was isolated from 22 % of humans, 4 % of pigs and 11 % of dogs. A total of 21 spa types were identified: 13, 7 and 1 in human, dogs, and pigs, respectively. Three spa types (t314, t223 and t084) were shared...

  18. Detection of hypermutated human papillomavirus type 16 genome by Next-Generation Sequencing

    National Research Council Canada - National Science Library

    Wakae, Kousho; Aoyama, Satoru; Wang, Zhe; Kitamura, Kouichi; Liu, Guangyan; Monjurul, Ahasan Md; Koura, Miki; Imayasu, Mieko; Sakamoto, Naoya; Nakamura, Mitsuhiro; Kyo, Satoru; Kondo, Satoru; Fujiwara, Hiroshi; Yoshizaki, Tomokazu; Kukimoto, Iwao; Yamaguchi, Katsushi; Shigenobu, Shuji; Nishiyama, Tomoaki; Muramatsu, Masamichi

    2015-01-01

    Human papillomavirus type 16 (HPV16) is a major cause of cervical cancer. We previously demonstrated that C-to-T and G-to-A hypermutations accumulated in the HPV16 genome by APOBEC3 expression in vitro...

  19. Las Competencias Legales del Racional en la Organización Administrativa y Contable del Municipio de Valencia (Comienzos del Siglo XVII)

    National Research Council Canada - National Science Library

    Francisco Mayordomo García-Chicote

    2005-01-01

    La organización administrativa y contable de los mayores municipios españoles, a comienzos del XVII, es un tema que apenas ha sido abordado por los investigadores de la historia de la Contabilidad y del Derecho...

  20. La republica de las letras y la predica jesuita novohispana del XVII. Los paratextos y la emergencia del arte como sistema

    National Research Council Canada - National Science Library

    Chinchilla Pawling, Perla

    2009-01-01

    .... Esta conclusion se apoya en un sintetico recorrido de los cambios que la propia predicacion presento a lo largo del siglo XVII ante las presiones de la sociedad de corte y la emergente cultura del impreso...

  1. Book review: Ham radio's technical culture. By K. Haring. Cambridge, MA: The MIT Press. 2007. xvii + 220 pp. #18.95. cloth. ISBN: 0262083558

    OpenAIRE

    Geoghegan, Hilary

    2008-01-01

    Book review: Ham radio's technical culture. By K. Haring. Cambridge, MA: The MIT Press. 2007. xvii + 220 pp. #18.95. cloth. ISBN: 0262083558 Department of Geography Royal Holloway, University of London - (Geoghegan, Hilary)

  2. Transient receptor potential canonical type 3 channels and blood pressure in humans

    DEFF Research Database (Denmark)

    Thilo, Florian; Baumunk, Daniel; Krause, Hans

    2009-01-01

    There is evidence that transient receptor potential canonical type 3 (TRPC3) cation channels are involved in the regulation of blood pressure, but this has not been studied using human renal tissue. We tested the hypothesis that the expression of TRPC3 in human renal tissue is associated with blo...

  3. Genetic instability of live, attenuated human immunodeficiency virus type 1 vaccine strains

    NARCIS (Netherlands)

    Berkhout, B.; Verhoef, K.; van Wamel, J. L.; Back, N. K.

    1999-01-01

    Live, attenuated viruses have been the most successful vaccines in monkey models of human immunodeficiency virus type 1 (HIV-1) infection. However, there are several safety concerns about using such an anti-HIV vaccine in humans, including reversion of the vaccine strain to virulence and

  4. Inhibition of human immunodeficiency virus type 1 by RNA interference using long-hairpin RNA

    NARCIS (Netherlands)

    Konstantinova, P.; de Vries, W.; Haasnoot, J.; ter Brake, O.; de Haan, P.; Berkhout, B.

    2006-01-01

    Inhibition of virus replication by means of RNA interference has been reported for several important human pathogens, including human immunodeficiency virus type 1 (HIV-1). RNA interference against these pathogens has been accomplished by introduction of virus-specific synthetic small interfering

  5. Availability and type of human resource for health in public primary ...

    African Journals Online (AJOL)

    Background: Health human resource capacity is one of the major determinants of an effective health care delivery system. It is more importantly so in the Primary Health Care system, which is the key component of every health system. This study assessed the available and type of human resource for health in public primary ...

  6. Antonio Roalas. Un pintor del primer tercio del siglo XVII en Madrid

    Directory of Open Access Journals (Sweden)

    Rodríguez Rebollo, Ángel

    2004-03-01

    Full Text Available El conocimiento que actualmente se tiene sobre los pintores del barroco madrileño ha avanzado mucho desde que Ángulo y Pérez Sánchez publicaran los dos volúmenes dedicados al primer y segundo tercio del siglo XVII. Posteriormente han ido viendo la luz estudios más pormenorizados, a veces en forma de exposiciones, que han clarificado aún más la importancia de los artistas que trabajaron en torno a la Corte de los llamados «los Austrias menores»; sin embargo, existen aún hoy un buen número de pintores sólo conocidos a través de contratos o inventarios de la época. La absoluta desinformación que tenemos de ellos, acrecentada por la inexistencia de obras firmadas, no permite a los historiadores dedicarles al menos un estudio parcial de su arte…

  7. Talis mater, talis filia: las malas madres en los siglos XVI y XVII

    Directory of Open Access Journals (Sweden)

    Amaia Nausia Pimoulier

    2013-12-01

    Full Text Available Este artículo presenta un tipo de violencia familiar protagonizado por madres e hijas navarras de los siglos XVI y XVII. Las acu-saciones por lenocinio o alcahuetería contra las madres que emplearon a sus propias hijas en sus tratos de mediadoras sirven para ilustrar una forma de violencia que supone, entre otras cosas, una ruptura del amor materno. La preca-ria situación de la madre y las dificultades tras el fallecimiento del esposo —la gran parte de los casos están protagonizados por madres viu-das— fue el contexto general en el que se desarrollaron los malos tratos. La historia de estas mujeres representa un mal ejercicio de la autoridad materna y una forma de violencia hacia las hijas; una violencia no siempre física, pero sí emocional y psicológica.

  8. El funcionamiento del tributo en Nueva Granada a finales del siglo XVII: Guatavita en 1690

    Directory of Open Access Journals (Sweden)

    Heraclio Bonilla

    2007-11-01

    Full Text Available Este ensayo examina los mecanismos de articulación política que se crearon entre el corregidor y los pueblos de indios que integraron el partido de Guatavita. Analiza la naturaleza y el monto del tributo que pagaron los indios y el manejo que el corregidor hizo de estos recursos. Estudia las cargas fiscales que se impusieron sobre la encomienda y los vínculos políticos que se desarrollaron entre encomenderos, corregidores y Estado colonial. La evidencia histórica que sirve de sustento a este trabajo proviene de la contabilidad que presentó el corregidor de Guatavita ante las autoridades coloniales a finales del siglo XVII.

  9. La diffusione delle opere antilatine di Nilo Cabasilas in manoscritti russi nel XVII secolo

    Directory of Open Access Journals (Sweden)

    Marco Scarpa

    2017-10-01

    Full Text Available The Spread of Neilos Kabasilas’s Anti-Latin Treaties in Russian Manuscripts in the 17th Century  In the 17th century, Neilos Kabasilas’s anti-Latin works, along with Gregory Palamas’s Contro Becco, were considerably widespread in Russia. The first copy was made for Arseniĭ Sukhanov in the 1630s, another copy – supplemented with several polemical texts – was then prepared for the Patriarchal Library. Four manuscripts are associated with the activity of the monks Simon Azar’in, Efrem Kvašnin and Sergij Šelonin, who were in Moscow in the 1640s, and are perhaps related to the question of the religious confession of Prince Valdemar, who was designated to marry the Tsar’s daughter. In mid-seventeenth century another manuscript appeared in Ukraine, marked at that time by the controversies which followed the Union of Brest. In the 1660s, two copies were made in the Solovetskiĭ Monastery. At the end of the century, Archbishop Atanasiĭ Kholmogorskij, involved in the controversy over Christ’s presence in the Eucharist, made further three copies of these works. Four manuscripts from the first half of the eighteenth century testify in their turn to the interest of particular individuals in this collection of texts on the Procession of the Holy Spirit.   Rozpowszechnienie antyłacińskich traktatów Nila Kabazylasa w rękopisach ruskich w XVII wieku  W XVII wieku antyłacińskie traktaty Nila Kabazylasa, obok Contro Becco Grzegorza Palamasa, były dość dobrze rozpowszechnione na Rusi. Pierwszy odpis został przygotowany przez Arsenija Suchanowa w latach trzydziestych XVII wieku. Drugi wzbogacony o kilka tekstów polemicznych powstał dla biblioteki patriarchalnej. Cztery kolejne rękopisy wiążą się z działalnością przebywających w latach czterdziestych w Moskwie mnichów Simona Azarina, Efrema Kwasznina i Sergija Szelonina i odsyłają prawdopodobnie do sprawy wyznania księcia Waldemara, kandydata na męża dla carskiej c

  10. La transición de periferia a frontera: mendoza en el siglo XVII

    Directory of Open Access Journals (Sweden)

    Margarita Gasc\\u00F3n

    2001-01-01

    Full Text Available El análisis de la evolución de Mendoza en el siglo XVII permite diferenciar las características de un asentamiento en la periferia de aquellas características que corresponden a una sociedad de frontera. Fundada en 1561 en la periferia imperio español en América a principios del siglo XVII, Mendoza era una comunidad con escasa población, con reducido comercio y de lento desarrollo urbano; todas características de las colonias periféricas. A lo largo de la primera parte del siglo XVII, sin embargo, Mendoza se fue configurando como una sociedad de frontera. Las causas de este devenir frontera se relacionan con la revuelta araucana y con las consecuencias del establecimiento de la frontera geográfico-militar en el río Biobio. El trabajo comienza con una revisión de los términos frontera y periferia tal como se encuentran empleados en los análisis de algunos autores representativos de la historiografía sobre fronteras para las Américas. Luego se reconstruye la evolución de periferia a frontera en Mendoza; un proceso que comenzó varias décadas después de su fundación en 1561. Tal fundación no estuvo guiada por la necesidad de consolidar o de proteger una zona de frontera, de modo que no fue fundada ni como presidio ni como misión, que son las típicas instituciones de frontera y que encontramos en numerosas fronteras del imperio español, como ser en la Florida y en el norte de México. A fines del siglo XVI Mendoza fue fundada como uno de los tantos asentamientos que permitirían a los españoles seguir avanzando en la conquista y colonización de nuevos territorios. Sin embargo, la revuelta araucana de 1598-1599 provocó el quiebre de tal desenvolvimiento de la conquista porque truncó la esperanza de una futura expansión española hacia el sur. Más allá del fiasco militar de la derrota de Curalaba, la rebelión nativa obligó a la coronaa establecer un ejército profesional de alrededor de 2.000 hombres, cuya permanencia

  11. Consideraciones sobre el comercio de libros en Lima a principios del siglo XVII

    Directory of Open Access Journals (Sweden)

    González Sánchez, Carlos Alberto

    1997-12-01

    Full Text Available Not available.

    El estudio de la circulación libraria en la América colonial continúa siendo un tema poco explotado, contrastando con el auge de las investigaciones sobre bibliotecas particulares o de instituciones de enseñanza. Las razones, muy diversas, vienen determinadas por la escasez de fuentes, entre las que destacan los inventarios de mercaderes libreros, cuya información es indispensable para el conocimiento de las inquietudes lectoras y, en definitiva, de los esquemas mentales de la sociedad de la Edad Moderna. En esta ocasión, dos interesantes inventarios de mercancía libraria, negociada en Lima a principios del siglo XVII, nos ofrecerán algunos indicios de una faceta crucial de la vida humana: libros y lecturas.

  12. Analysis of Insulin in Human Breast Milk in Mothers with Type 1 and Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    T. J. Whitmore

    2012-01-01

    Full Text Available Despite the important role that insulin plays in the human body, very little is known about its presence in human milk. Levels rapidly decrease during the first few days of lactation and then, unlike other serum proteins of similar size, achieve comparable levels to those in serum. Despite this, current guides for medical treatment suggest that insulin does not pass into milk, raising the question of where the insulin in milk originates. Five mothers without diabetes, 4 mothers with type 1, and 5 mothers with type 2 diabetes collected milk samples over a 24-hour period. Samples were analysed for total and endogenous insulin content and for c-peptide content. All of the insulin present in the milk of type 1 mothers was artificial, and c-peptide levels were 100x lower than in serum. This demonstrates that insulin is transported into human milk at comparable concentration to serum, suggesting an active transport mechanism. The role of insulin in milk is yet to be determined; however, there are a number of potential implications for the infant of the presence of artificial insulins in milk.

  13. Cultivating New-type Farmers Based on the Theory of Human Resources Development

    OpenAIRE

    Zhang, Li

    2010-01-01

    Under the direction of theory of human resources development, this thesis analyzes the impact of rural human resources development on cultivating new-type farmers. Firstly, it increases the input of rural basic education; secondly, it reinforces the vocational education and technology training; thirdly, it promotes the rural medical and public health services; fourthly, it quickens the rural labor transfer. The status quo of China’s rural human resources has been analyzed as follows: in ter...

  14. Endogenous and maximal sarcoplasmic reticulum calcium content and calsequestrin expression in type I and type II human skeletal muscle fibres.

    Science.gov (United States)

    Lamboley, C R; Murphy, R M; McKenna, M J; Lamb, G D

    2013-12-01

    The relationship between sarcoplasmic reticulum (SR) Ca(2+) content and calsequestrin (CSQ) isoforms was investigated in human skeletal muscle. A fibre-lysing assay was used to quantify the endogenous Ca(2+) content and maximal Ca(2+) capacity of the SR in skinned segments of type I and type II fibres from vastus lateralis muscles of young healthy adults. Western blotting of individual fibres showed the great majority contained either all fast or all slow isoforms of myosin heavy chain (MHC), troponins C and I, tropomyosin and SERCA, and that the strontium sensitivity of the force response was closely indicative of the troponin C isoform present. The endogenous SR Ca(2+) content was slightly lower in type I compared to type II fibres (0.76 ± 0.03 and 0.85 ± 0.02 mmol Ca(2+) per litre of fibre, respectively), with virtually all of this Ca(2+) evidently being in the SR, as it could be rapidly released with a caffeine-low [Mg(2+)] solution (only 0.08 ± 0.01 and fibres, respectively (P fibres, where the SR remained functional, repeated cycles of caffeine-induced Ca(2+) release and subsequent Ca(2+) reloading similarly indicated that (i) maximal SR Ca(2+) content was lower in type I fibres than in type II fibres (P fibres compared to type II fibres (∼59% and 41%, respectively, P fibres were found on average to contain ∼3-fold more CSQ1 and ∼5-fold less CSQ2 than type I fibres (P fibres being primarily determined by the CSQ1 abundance, and in type I fibres by the combined amounts of both CSQ1 and CSQ2.

  15. Differential In Vitro Immortalization Capacity of Eleven, Probable High-Risk Human Papillomavirus Types

    NARCIS (Netherlands)

    Schutze, Denise M.; Snijders, Peter J. F.; Bosch, Leontien; Kramer, Duco; Meijer, Chris J. L. M.; Steenbergen, Renske D. M.

    Epidemiological studies identified 12 high-risk HPV (hrHPV) types and 8 probable/possible hrHPV types that display different cancer risks. Functional studies on transforming properties of hrHPV are mainly limited to HPV16 and -18, which induce immortalization of human foreskin keratinocytes (HFKs)

  16. Pancreatic duct replication is increased with obesity and type 2 diabetes in humans.

    Science.gov (United States)

    Butler, A E; Galasso, R; Matveyenko, A; Rizza, R A; Dry, S; Butler, P C

    2010-01-01

    In a high-fat-fed rat model of type 2 diabetes we noted increased exocrine duct replication. This is a predisposing factor for pancreatitis and pancreatic cancer, both of which are more common in type 2 diabetes. The aim of the study reported here was to establish if obesity and/or type 2 diabetes are associated with increased pancreatic ductal replication in humans. We obtained pancreas at autopsy from 45 humans, divided into four groups: lean (BMI obese (BMI >27 kg/m(2)); non-diabetic; and with type 2 diabetes. Pancreases were evaluated after immunostaining for the duct cell marker cytokeratin and Ki67 for replication. We show for the first time that both obesity and type 2 diabetes in humans are associated with increased pancreatic ductal replication. Specifically, we report that (1) replication of pancreatic duct cells is increased tenfold by obesity, and (2) lean subjects with type 2 diabetes demonstrate a fourfold increase in replication of pancreatic duct cells compared with their lean non-diabetic controls. Pancreatic duct cell replication is increased in humans in response to both obesity and type 2 diabetes, potentially providing a mechanism for the increased risk of pancreatitis and pancreatic cancer in those with obesity and/or type 2 diabetes.

  17. Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA

    DEFF Research Database (Denmark)

    Barnathan, E S; Kuo, A; Karikó, K

    1990-01-01

    Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC...

  18. Identification of intermediate cell types by keratin expression in the developing human prostate

    NARCIS (Netherlands)

    Xue, Y; Smedts, F; Debruyne, FMJ; de la Rosette, JJMCH; Schalken, JA

    1998-01-01

    BACKGROUND. The secretory acini of the adult human prostate contain basal, luminal, and intermediate types of exocrine cells. Intermediate cells are thought to play an important role in normal growth and neoplastic transformation. In this study we investigated whether this cell type is present in

  19. Modelling epigenetic regulation of gene expression in 12 human cell types reveals combinatorial patterns of cell-type-specific genes.

    Science.gov (United States)

    Lu, Yiming; Qu, Wubin; Min, Bo; Liu, Zheyan; Chen, Changsheng; Zhang, Chenggang

    2014-06-01

    The maintenance of the diverse cell types in a multicellular organism is one of the fundamental mysteries of biology. Modelling the dynamic regulatory relationships between the histone modifications and the gene expression across the diverse cell types is essential for the authors to understand the mechanisms of the epigenetic regulation. Here, the authors thoroughly assessed the histone modification enrichment profiles at the promoters and constructed quantitative models between the histone modification abundances and the gene expression in 12 human cell types. The author's results showed that the histone modifications at the promoters exhibited remarkably cell-type-dependent variability in the cell-type-specific (CTS) genes. They demonstrated that the variable profiles of the modifications are highly predictive for the dynamic changes of the gene expression across all the cell types. Their findings revealed the close relationship between the combinatorial patterns of the histone modifications and the CTS gene expression. They anticipate that the findings and the methods they used in this study could provide useful information for the future studies of the regulatory roles of the histone modifications in the CTS genes.

  20. [Distribution of collagen types III and IV in human placental villi].

    Science.gov (United States)

    Nanaev, A K; Rukosuev, V S; Milovanov, A P; Fokin, E I; Shirinskiĭ, V P

    1989-02-01

    Immunofluorescent examination showed more significant accumulation of interstitial collagen type III in the stroma of mature placenta compared with immature one. Localization of membrane collagen type IV was found neither in basal membranes of epithelium and villous vessels of mature term placenta, nor in their stroma. The described patterns of distribution of collagen types III and IV in human placenta villi were proved by immunoelectronmicroscopic method.

  1. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K

    2011-01-01

    The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis...

  2. Anti-collagen XVII single-chain Fv antibody blocks the autoimmune reaction mediated by pathogenic autoantibodies in bullous pemphigoid.

    Science.gov (United States)

    Wu, Yan; Sun, Na-Na; Dang, Er-Le; Jin, Liang; Liu, Zhen-Feng; Zhang, Wei; Yang, Lu-Ting; Wang, Gang

    2013-10-01

    Pathogenic autoantibodies in bullous pemphigoid (BP) recognize the non-collagenous 16A domain (NC16A) of collagen XVII (COL17), a hemidesmosomal component at the skin membrane. This immune inflammation involves activation of the complement cascade via the classical pathway. With similar antigen binding activity, Fab and single-chain variable fragments (scFv) of pathogenic anti-COL17 antibodies can interfere with COL17 binding of autoantibodies, blocking subsequent complement activation and granulocyte activation. To characterize the biological functions of human anti-COL17 scFv antibody. We constructed scFv antibodies against the corresponding antigen from parental Fab by expression in Escherichia coli. IgG autoantibodies against COL17 were purified by affinity chromatography from serum of BP patients. The inhibitory effects of anti-COL17 scFv on binding of BP autoantibodies to the NC16A domain of human COL17 antigen were observed by inhibition ELISA, immunofluorescence, and inhibition of complement activation. Reactive oxygen production assay and BP cryosection model were performed to assess the inhibitory effect of scFv on granulocyte activation and then the dermal-epidermal separation. ELISA and Western blot showed specific binding of scFv to COL17. We found that anti-COL17 scFv can inhibit the binding of intact IgG purified from BP parents to the corresponding COL17 antigen and then subsequent C1q and C3 activation and granulocyte activation in vitro. Most importantly, we confirmed that recombinant scFv can inhibit BP-IgG induced dermal-epidermal separation by BP cryosection model. The anti-COL17 scFv antibody can inhibit the binding of BP-IgG autoantibodies to COL17, thereby affecting subsequent complement activation and granulocyte activation in vitro. Our results suggest that blocking pathogenic epitopes using engineered scFv is an efficient BP therapy. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All

  3. Synthetic-peptide-based enzyme-linked immunosorbent assay for screening human serum or plasma for antibodies to human immunodeficiency virus type 1 and type 2.

    OpenAIRE

    Gonzalez, L; Boyle, R W; M. Zhang; Castillo, J; Whittier, S; Della-Latta, P; Clarke, L M; George, J R; Fang, X; Wang, J G; Hosein, B; C. Y. Wang

    1997-01-01

    A synthetic-peptide-based enzyme-linked immunosorbent assay (EIA) capable of screening for antibodies to both human immunodeficiency virus type 1 (HIV-1) and HIV-2 has been developed for use in blood banks and diagnostic laboratories. Microtiter wells are coated with two synthetic peptides, one corresponding to the highly conserved envelope region of HIV-1 and another corresponding to the conserved envelope region of HIV-2. Overall, sensitivity was 100% in 303 individuals diagnosed with AIDS ...

  4. Tissue-engineered recombinant human collagen-based corneal substitutes for implantation: performance of type I versus type III collagen.

    Science.gov (United States)

    Merrett, Kimberley; Fagerholm, Per; McLaughlin, Christopher R; Dravida, Subhadra; Lagali, Neil; Shinozaki, Naoshi; Watsky, Mitchell A; Munger, Rejean; Kato, Yasuhiro; Li, Fengfu; Marmo, Christopher J; Griffith, May

    2008-09-01

    To compare the efficacies of recombinant human collagens types I and III as corneal substitutes for implantation. Recombinant human collagen (13.7%) type I or III was thoroughly mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide. The final homogenous solution was either molded into sheets for in vitro studies or into implants with the appropriate corneal dimensions for transplantation into minipigs. Animals with implants were observed for up to 12 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, and fundus examination. Histopathologic examinations were also performed on corneas harvested after 12 months. Both cross-linked recombinant collagens had refractive indices of 1.35, with optical clarity similar to that in human corneas. Their chemical and mechanical properties were similar, although RHC-III implants showed superior optical clarity. Implants into pig corneas over 12 months show comparably stable integration, with regeneration of corneal cells, tear film, and nerves. Optical clarity was also maintained in both implants, as evidenced by fundus examination. Both RHC-I and -III implants can be safely and stably integrated into host corneas. The simple cross-linking methodology and recombinant source of materials makes them potentially safe and effective future corneal matrix substitutes.

  5. Association between Toxoplasma gondii types and outcomes of human infection: A meta-analysis.

    Science.gov (United States)

    Xia, Jing; Cheng, Xin-Yu; Wang, Xiao-Jun; Peng, Hong-Juan

    2017-09-01

    The virulence and pathogenicity of various types of Toxoplasma gondii differ considerably in mice. Recent studies have claimed that similar phenomenon was observed in humans, but no relevant studies have been performed to validate this finding. In addition, reports showing association between a given T. gondii type and outcomes of human infection yielded conflicting results. To provide a more precise estimation of the association and a more reliable conclusion on this subject, we performed this meta-analysis. Relevant literatures were identified in multiple databases and selected based on strict screening. T. gondii-type proportions among different severities of infection were calculated and compared using Fisher's exact test. Pooled odds ratios (OR) were calculated. Our results showed that the difference among T. gondii-type proportions was significant (p < 0.0001). In addition, significant associations were detected between Type I strains infection and congenital toxoplasmosis (OR: 1.91, p = 0.0009), Type III strains infection and pulmonary toxoplasmosis (OR: 5.15, p = 0.04). In our subgroup analysis, Type I strains were significantly associated with cerebral toxoplasmosis in offspring (OR: 1.81, p = 0.02). This result indicated that different types of T. gondii exhibited different virulence and caused different outcomes in humans.

  6. Escolastica amerícana del siglo XVII y la supuesta "tibetización" de la cultura hispana

    OpenAIRE

    Marquínez Argote, Germán

    2014-01-01

    Este texto intenta desabsolutizar el fenómeno de "tibetinazación" de la cultura hispana del siglo XVII, tal como lo describe Ortega y Gasset. El aislamiento de España con respecto a los países europeos más avanzados de la época fue, según Payné, un fenómeno real, pero relativo. Hoy sabemos que en las dos últimas décadas del siglo XVII España empieza a recuperar el tiempo perdido, tratando de reinsertarse en la "culta Europa", mucho antes de la Ilustración francesa. El mismo proceso de reinser...

  7. Effect of fast-food Mediterranean-type diet on human plasma oxidation.

    Science.gov (United States)

    Aronis, Pantelis; Antonopoulou, Smaragdi; Karantonis, Haralabos C; Phenekos, Costas; Tsoukatos, Demokritos C

    2007-09-01

    Oxidation of lipoproteins, particularly of low-density lipoprotein (LDL), is of prime importance in the initiation and progression of atherosclerosis. The Mediterranean diet has been associated with an unexpectedly low rate of cardiovascular events. Type 2 diabetic patients are at high risk of developing atherosclerosis. Functional alterations in the endothelium, which lead to atherosclerosis, are stimulated by oxidized lipoproteins, particularly oxidized LDL. The present study investigated the effect of Greek quick casual Mediterranean-type diet (fast food Mediterranean-type diet) consumption on the resistance to oxidation in plasma from type 2 diabetic patients and healthy human subjects. Lipids from fast food Mediterranean-type foodstuffs were extracted and tested in vitro for their ability to inhibit copper (Cu2+)-induced LDL oxidation. Foodstuffs that exerted the most potent in vitro antioxidative activity were chosen for the diet of study groups. Eighteen type 2 diabetic patients (group A) and 10 healthy subjects (group B) were fed a 4-week diet contained the chosen foodstuffs, while 17 type 2 diabetic patients (group C) were kept on their regular diet that they were following before the study. Type 2 diabetic patients were treated with sulfonylureas or metformin and were under good glycemic control (hemoglobin A1C Fast food Mediterranean foodstuffs exerted antioxidant activities both in vitro and in vivo after consumption in type 2 diabetic patients and healthy human subjects. Therefore consumption of a fast food Mediterranean-type diet should contribute to prevention against cardiovascular diseases.

  8. Differential expression of type XIV collagen/undulin by human mammary gland intralobular and interlobular fibroblasts.

    Science.gov (United States)

    Atherton, A J; Warburton, M J; O'Hare, M J; Monaghan, P; Schuppan, D; Gusterson, B A

    1998-03-01

    Immunolocalisation of type XIV collagen/undulin in the human mammary gland revealed greater deposition in the interlobular stroma than in the intralobular stroma. The interlobular stroma is located between the breast lobules and their associated intralobular stroma. Fibroblasts isolated from the interlobular stroma synthesised 3- to 5-fold more type XIV collagen/undulin than intralobular fibroblasts, but synthesised type I and type IV collagens in similar amounts. The differential expression of type XIV collagen/undulin was maintained with passage in culture. The results suggest a role for type XIV collagen/undulin in stabilising dense collagen fibrils. The maintenance of two types of structurally distinct stromas may be important during developmental processes in the mammary gland.

  9. Types I and III procollagen extension peptides in serum respond to fracture in humans

    DEFF Research Database (Denmark)

    Joerring, S; Jensen, L T; Andersen, G R

    1992-01-01

    Markers of types I and III collagen turnover were measured in serial blood samples in 16 patients with a Colles' fracture. The collagen markers were the carboxy-terminal extension peptide of type I procollagen (PICP) and the amino-terminal extension peptide of type III procollagen (PIIINP......). Significant increases were found of PIIINP within 1 week and of PICP within 2 weeks. This sequential appearance of PIIINP and PICP was found to be in agreement with the appearance of types III and I collagen during early fracture healing as demonstrated in previous animal experimental studies. PICP had...... prove relevant as non-invasive markers of normal and pathological fracture healing in humans....

  10. Growth and characterization of different human rhinovirus C types in three-dimensional human airway epithelia reconstituted in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Tapparel, Caroline, E-mail: Caroline.Tapparel@hcuge.ch [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland); Sobo, Komla [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland); Constant, Samuel; Huang, Song [Epithelix sárl, 14 Chemin des Aulx, 1228 Plan les Ouates, Geneva (Switzerland); Van Belle, Sandra; Kaiser, Laurent [Laboratory of Virology, Division of Infectious Diseases and Division of Laboratory Medicine, University of Geneva Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1211 Geneva 14 (Switzerland)

    2013-11-15

    New molecular diagnostic tools have recently allowed the discovery of human rhinovirus species C (HRV-C) that may be overrepresented in children with lower respiratory tract complications. Unlike HRV-A and HRV-B, HRV-C cannot be propagated in conventional immortalized cell lines and their biological properties have been difficult to study. Recent studies have described the successful amplification of HRV-C15, HRV-C11, and HRV-C41 in sinus mucosal organ cultures and in fully differentiated human airway epithelial cells. Consistent with these studies, we report that a panel of clinical HRV-C specimens including HRV-C2, HRV-C7, HRV-C12, HRV-C15, and HRV-C29 types were all capable of mediating productive infection in reconstituted 3D human primary upper airway epithelial tissues and that the virions enter and exit preferentially through the apical surface. Similar to HRV-A and HRV-B, our data support the acid sensitivity of HRV-C. We observed also that the optimum temperature requirement during HRV-C growth may be type-dependent. - Highlights: • A 3D human upper airway epithelia reconstituted in vitro supports HRV-C growth. • HRV-Cs enter and exit preferentially at the apical side of this ALI culture system. • HRV-Cs are acid sensitive. • Temperature sensitivity may be type-dependent for HRV-Cs.

  11. A comparative study of Drosophila and human A-type lamins.

    Directory of Open Access Journals (Sweden)

    Sandra R Schulze

    Full Text Available Nuclear intermediate filament proteins, called lamins, form a meshwork that lines the inner surface of the nuclear envelope. Lamins contain three domains: an N-terminal head, a central rod and a C-terminal tail domain possessing an Ig-fold structural motif. Lamins are classified as either A- or B-type based on structure and expression pattern. The Drosophila genome possesses two genes encoding lamins, Lamin C and lamin Dm(0, which have been designated A- and B-type, respectively, based on their expression profile and structural features. In humans, mutations in the gene encoding A-type lamins are associated with a spectrum of predominantly tissue-specific diseases known as laminopathies. Linking the disease phenotypes to cellular functions of lamins has been a major challenge. Drosophila is being used as a model system to identify the roles of lamins in development. Towards this end, we performed a comparative study of Drosophila and human A-type lamins. Analysis of transgenic flies showed that human lamins localize predictably within the Drosophila nucleus. Consistent with this finding, yeast two-hybrid data demonstrated conservation of partner-protein interactions. Drosophila lacking A-type lamin show nuclear envelope defects similar to those observed with human laminopathies. Expression of mutant forms of the A-type Drosophila lamin modeled after human disease-causing amino acid substitutions revealed an essential role for the N-terminal head and the Ig-fold in larval muscle tissue. This tissue-restricted sensitivity suggests a conserved role for lamins in muscle biology. In conclusion, we show that (1 localization of A-type lamins and protein-partner interactions are conserved between Drosophila and humans, (2 loss of the Drosophila A-type lamin causes nuclear defects and (3 muscle tissue is sensitive to the expression of mutant forms of A-type lamin modeled after those causing disease in humans. These studies provide new insights on the

  12. Organization of the human keratin type II gene cluster at 12q13

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, S.J.; LeBlanc-Straceski, J.; Krauter, K. [Albert Einstein College of Medicine, Bronx, NY (United States)] [and others

    1994-12-01

    Keratin proteins constitute intermediate filaments and are the major differentiation products of mammalian epithelial cells. The epithelial keratins are classified into two groups, type I and type II, and one member of each group is expressed in a given epithelial cell differentiation stage. Mutations in type I and type II keratin genes have now been implicated in three different human genetic disorders, epidermolysis bullosa simplex, epidermolytic hyperkeratosis, and epidermolytic palmoplantar keratoderma. Members of the type I keratins are mapped to human chromosome 17, and the type II keratin genes are mapped to chromosome 12. To understand the organization of the type II keratin genes on chromosome 12, we isolated several yeast artificial chromosomes carrying these keratin genes and examined them in detail. We show that eight already known type II keratin genes are located in a cluster at 12q13, and their relative organization reflects their evolutionary relationship. We also determined that a type I keratin gene, KRT8, is located next to its partner, KRT18, in this cluster. Careful examination of the cluster also revealed that there may be a number of additional keratin genes at this locus that have not been described previously. 41 refs., 3 figs., 1 tab.

  13. Dynamics and associations of microbial community types across the human body.

    Science.gov (United States)

    Ding, Tao; Schloss, Patrick D

    2014-05-15

    A primary goal of the Human Microbiome Project (HMP) was to provide a reference collection of 16S ribosomal RNA gene sequences collected from sites across the human body that would allow microbiologists to better associate changes in the microbiome with changes in health. The HMP Consortium has reported the structure and function of the human microbiome in 300 healthy adults at 18 body sites from a single time point. Using additional data collected over the course of 12-18 months, we used Dirichlet multinomial mixture models to partition the data into community types for each body site and made three important observations. First, there were strong associations between whether individuals had been breastfed as an infant, their gender, and their level of education with their community types at several body sites. Second, although the specific taxonomic compositions of the oral and gut microbiomes were different, the community types observed at these sites were predictive of each other. Finally, over the course of the sampling period, the community types from sites within the oral cavity were the least stable, whereas those in the vagina and gut were the most stable. Our results demonstrate that even with the considerable intra- and interpersonal variation in the human microbiome, this variation can be partitioned into community types that are predictive of each other and are probably the result of life-history characteristics. Understanding the diversity of community types and the mechanisms that result in an individual having a particular type or changing types, will allow us to use their community types to assess disease risk and to personalize therapies.

  14. Novel Humanized mice to test Therapeutics for Human Type 1 Diabetes

    Science.gov (United States)

    2014-01-06

    helminthic infections and allergic reactions. TNFα: Tumor Necrosis Factor α. TR1: T regulatory cells expressing Il-10. Tregs: CD4+Foxp3+T regularoty... Immunomodulation for type 1 diabetes mellitus. International journal of clinical practice. Supplement:59-63 95. Sonderstrup G, Cope AP, Patel S, Congia M, Hain

  15. Detection of Human Papillomavirus in Human Focal Cortical Dysplasia Type IIB

    NARCIS (Netherlands)

    Chen, Julie; Tsai, Victoria; Parker, Whitney E.; Aronica, Eleonora; Baybis, Marianna; Crino, Peter B.

    2012-01-01

    Objective: Focal cortical dysplasia type IIB (FCDIIB) is a sporadic developmental malformation of the cerebral cortex highly associated with pediatric epilepsy. Balloon cells (BCs) in FCDIIB exhibit constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.

  16. Simple mucin-type carbohydrates in normal and malignant human endometrium

    DEFF Research Database (Denmark)

    Ravn, V; Mandel, U; Svenstrup, B

    1995-01-01

    The simple mucin-type carbohydrate antigens, Tn, sialosyl-Tn, and T, are tumor-associated antigens of adenocarcinomas. We evaluated by immunohistochemistry the expression of Tn, sialosyl-Tn (s-Tn), T, and sialosyl-T (s-T) antigens in normal nonsecretory, early gestational, and malignant human...... and malignant endometrium, and the expression of s-T antigen was positively correlated with E2 levels in serum. Our findings suggest a hormonal influence on expression of simple mucin-type carbohydrates in human endometrium. However, the accumulation of Tn and s-Tn antigens in malignant endometrial cells seem...

  17. Measurement of the Radiative Decay of the Longest-Lived Level in the Fe XVII Spectrum

    Science.gov (United States)

    Beiersdorfer, Peter

    Iron (Fe) is a very abundant element, and the Ne-like ion of this element (spectrum Fe XVII) with a number of prominent soft-X-ray lines plays an important role in the study of stellar coronae and other astrophysical objects. Among these lines, those emanating from a 3s level, i.e., lines 3F, 3G, and 3H, invariably appear too strong compared to the lines emanating from a 3d level, i.e., lines 3C and 3D, when compared to theory. In some cases, such as ? Pup, the line ratios involving purely the three 3s decay lines themselves are also not well reproduced by theory. Thus Fe XVII has been contentious for many years; while laboratory measurements using the Livermore electron beam ion trap (EBIT) have corroborated the intensity ratios found in astrophysical observations, reliable theory is still struggling. This indicates that the problems lie with theory, but the physical reason why theory is off in describing the intensity of the 3s decays has been elusive so far. In this proposed work, we will investigate the radiative decay paths of the 3s levels. Two of the four 3s levels are metastable, which means they have a rather long radiative decay time compared to collisional processes. The decay rate of the 3s J=2 level has very recently been measured at the Livermore EBIT, and the scatter of predictions by a factor of 1.7 has been reduced to a measurement uncertainty of merely a few percent. Even longer-lived is the J=0 level of the same 2p5 3s configuration. Theory predicts an exclusive magnetic dipole decay to the lowest J=1 level of the same 2p5 3s configuration. Various calculations yield a decay rate near 16 000 s-1 for this level (level lifetime near 63 μs). If this value is correct, electron-impact collisions affect line ratios tied to this level at densities between about 10^10 cm-3 and 10^13 cm-3, that is, exactly at coronal densities of present interest. This rate, however, has not yet been verified by measurement. Moreover, recent laboratory spectral

  18. Salmonella-Typhimurium phage types from human salmonellosis in denmark 1988 to 1993

    DEFF Research Database (Denmark)

    Wegener, Henrik Caspar; Baggesen, Dorte Lau; Gaarslev, K.

    1994-01-01

    A total of 989 isolates of Salmonella enterica ssp. enterica serovar Typhimurium from cases of human salmonellosis were investigated by phage typing, The isolates comprised all isolates recovered during the month of August in each of the years from 1988 to 1993. Phage typing assigned 82.......6% of the strains to 36 different definitive types, 11.9% of the strains belonged to types of unknown lysis pattern (RDNC), and 5.5% could not be typed by the phages used (NT). Three phage types (12, 66 and 110) made up approximately 50% of the isolates in each of the years investigated. During the period...... in question these types showed major changes in prevalence: phage type 12 increased from 4.0% in 1988 to a maximum of 55.2% in 1992, and phage type 66 and phage type 110 were reduced from 40.1% and 27.8% to a minimum of 3.9% and 4.8% in 1993 and 1992, respectively. The increasing prevalence of phage type 12...

  19. Human papillomavirus type 70 genome cloned from overlapping PCR products: complete nucleotide sequence and genomic organization.

    OpenAIRE

    Forslund, O; Hansson, B G

    1996-01-01

    The genome of human papillomavirus (HPV) type 70 (HPV 70), isolated from a cervical condyloma, was obtained by cloning overlapping PCR products. By automated DNA sequence analysis, the genome was found to consist of 7,905 bp with a G + C content of 40%. The genomic organization showed the characteristic features shared by other sequenced HPVs. Nucleotide sequence comparison with previously known HPV types demonstrated the closest homology with HPV 68 (82%), HPV 39 (82%), HPV 18 (70%), HPV 45 ...

  20. Identification of Multiple HPV Types on Spermatozoa from Human Sperm Donors

    OpenAIRE

    Kaspersen, Maja D; Peter B Larsen; Hans Jakob Ingerslev; Jens Fedder; Gert Bruun Petersen; Jesper Bonde; Per Höllsberg

    2011-01-01

    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of ...

  1. Direct Phenotypical and Functional Dysregulation of Primary Human B Cells by Human Immunodeficiency Virus (HIV) Type 1 In Vitro

    OpenAIRE

    Ana Judith Perisé-Barrios; María Ángeles Muñoz-Fernandez; Marjorie Pion

    2012-01-01

    BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. METHODS/PRINCIPAL FINDINGS: We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and pheno...

  2. Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle.

    OpenAIRE

    Shirazi, Y; Pitha, P M

    1992-01-01

    In this study, we have analyzed the effect of human alpha interferon (IFN-alpha) on a single replication cycle of human immunodeficiency virus type 1 (HIV-1) infection in the lymphocytic cell line CEM-174, which is highly sensitive to the antiviral effects of IFN. Pretreatment of cells with 50 to 500 U of recombinant human IFN-alpha per ml resulted in a marked reduction in viral RNA and protein synthesis. The effect of IFN-alpha was dose dependent and was amplified in multiple infection cycle...

  3. Identification of the type of human papillomavirus (HPV in patients with cervical cancer

    Directory of Open Access Journals (Sweden)

    Marlina Marlina

    2016-12-01

    Full Text Available Human Papillomavirus (HPV is the most significant risk factor for the cause of cervical cancer. The purpose of this study for identification of HPV types 16, 18, 31, 33, 45 and 52 in cervical cancer patients. HPV is a row of high-risk HPV types that can cause cervical cancer. Total sample of 78 diisolat DNA derived from FFPE, cervical smears and cervical cancer fresh tissue obtained from Dr. Dr. M. Djamil, Padang and hospitals. Arifin Achmad, Pekanbaru. HPV DNA detection is done by using Polymerase Chain Reaction (PCR using universal primers GP5 +/6 +. HPV types were identified by PCR with specific primers. Total sample types obtained with concentrations varying between 0.9 to 645 ng / ml with purity DNA in accordance with the specified purity for PCR amplification. The results of the study of 78 patients with cervical cancer samples, 42 samples (54% identified HPV DNA. HPV type 18 is more dominant and followed by HPV type 16 as compared to the other types, namely the percentage of 40.4% and 28.5%. HPV type 45 (7.1%, HPV type 52 (2.3% and HPV 31 and HPV type 33 was not detected.

  4. Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline

    Directory of Open Access Journals (Sweden)

    Buonaguro Franco M

    2009-06-01

    Full Text Available Abstract Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV. Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC Monographs Working Group to re-assess the carcinogenicity of different HPV types.

  5. Prognostic Implication of Human Papillomavirus Types and Species in Cervical Cancer Patients Undergoing Primary Treatment

    OpenAIRE

    Yat Ming Lau; Tak Hong Cheung; Winnie Yeo; Frankie Mo; Mei Yung Yu; Kun Min Lee; Ho, Wendy C. S.; Yeung, Apple C. M.; Priscilla T. Y. Law; Chan, Paul K. S.

    2015-01-01

    High-risk human papillomavirus (HPV) types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4) years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent t...

  6. Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline

    Science.gov (United States)

    Schiffman, Mark; Clifford, Gary; Buonaguro, Franco M

    2009-01-01

    Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV). Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC) Monographs Working Group to re-assess the carcinogenicity of different HPV types. PMID:19486508

  7. Identification of multiple HPV types on spermatozoa from human sperm donors

    DEFF Research Database (Denmark)

    Kaspersen, Maja D; Larsen, Peter B; Ingerslev, Hans Jakob

    2011-01-01

    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV...... according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive...

  8. Introducción al estudio tipológico de las espadas españolas: siglos XVI-XVII

    Directory of Open Access Journals (Sweden)

    Dueñas Beraiz, Germán

    2004-12-01

    Full Text Available This article pretends to reflect on the spanish swords from 16th and 17th centuries. The history of this production has been eclipsed by Toledo fame. The identification of spanish types have been mainly made according its marks, signatures and some typologies, but little is know about another centers. Therefore this article studies the variety and richness of the spanish contemporary productions, not only from Toledo.

    Este artículo pretende reflexionar sobre las espadas españolas de los siglos XVI y XVII. La historia de esta producción ha sido eclipsada por la fama de Toledo. La identificación de los tipos españoles se ha basado en sus marcas, firmas y algunas tipologías, pero se sabe muy poco sobre otros centros productores. Por ello este artículo aborda la variedad y riqueza de las producciones españolas contemporáneas, no sólo de Toledo.

  9. Gene polymorphisms and fiber-type composition of human skeletal muscle.

    Science.gov (United States)

    Ahmetov, Ildus I; Vinogradova, Olga L; Williams, Alun G

    2012-08-01

    The ability to perform aerobic or anaerobic exercise varies widely among individuals, partially depending on their muscle-fiber composition. Variability in the proportion of skeletal-muscle fiber types may also explain marked differences in aspects of certain chronic disease states including obesity, insulin resistance, and hypertension. In untrained individuals, the proportion of slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around 50% (range 5-90%), and it is unusual for them to undergo conversion to fast-twitch fibers. It has been suggested that the genetic component for the observed variability in the proportion of Type I fibers in human muscles is on the order of 40-50%, indicating that muscle fiber-type composition is determined by both genotype and environment. This article briefly reviews current progress in the understanding of genetic determinism of fiber-type proportion in human skeletal muscle. Several polymorphisms of genes involved in the calcineurin-NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia and angiogenesis, and circulatory homeostasis have been associated with fiber-type composition. As muscle is a major contributor to metabolism and physical strength and can readily adapt, it is not surprising that many of these gene variants have been associated with physical performance and athlete status, as well as metabolic and cardiovascular diseases. Genetic variants associated with fiber-type proportions have important implications for our understanding of muscle function in both health and disease.

  10. Types of coronary vasculature in the human fetus: an autopsy study.

    Science.gov (United States)

    Nowak, Dariusz; Gielecki, Jerzy; Rzeszowska, Mariola; Kiestrzyn-Wójcik, Alina

    2008-01-01

    The heart receives blood from 2 vessels: the right and the left coronary arteries. Depending on the relationship between these 2 vessels, types with the right, the left or with neither coronary artery predominating can be distinguished. The incidence of particular types varies according to different reports. All available data regarding this issue come from studies where adult subjects were examined. There is no research in this field involving human fetuses. We examined 199 fetuses of both sexes (101 males and 98 females), 3-8 months of intrauterine life. All cases were derived from the Department of Histology and Embryology, Nicolaus Copernicus University. Prior to examination, all fetuses had been conserved in a 9% formaldehyde solution for over 3 months. We obtained the following results: type I vasculature, having equally developed coronary arteries, was found in 59 cases (29.5%); type II, with the right coronary artery predominating, was found in 65 cases (32.5%), and type III, with the left coronary artery predominating, occurred in 76 cases (38%). The subtypes IIIA and IIIB were described in 50 (25%) and 26 (13%) of the type III subjects, respectively. These data differ from the adult material incidence of dominant left coronary artery. While it is the most frequently occurring type in human fetuses, it is the least common in adult subjects. Copyright 2008 S. Karger AG, Basel.

  11. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters

    NARCIS (Netherlands)

    Jonsson, Michele; Fusco, Jennifer S.; Cole, Stephen R.; Thomas, James C.; Porter, Kholoud; Kaufman, Jay S.; Davidian, Marie; White, Alice D.; Hartmann, Katherine E.; Eron, Joseph J.; del Amo, Julia; Meyer, Laurence; Bucher, Heiner C.; Chene, Geneviève; Pillay, Deenan; Prins, Maria; Rosinska, Magda; Sabin, Caroline; Touloumi, Giota; Lodi, Sara; Coughlin, Kate; Walker, Sarah; Babiker, Abdel; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Kaldor, John; Kelleher, Tony; Ramacciotti, Tim; Gelgor, Linda; Cooper, David; Smith, Don; Gill, John; Jørgensen, Louise Bruun; Nielsen, Claus; Pedersen, Court; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Guiguet, Marguerite; Vanhems, Philippe; Chaix, Marie-Laure; Ghosn, Jade; Boufassa, Faroudy; Hamouda, Osamah; Kücherer, Claudia; Bartmeyer, Barbara; Pantazis, Nikos; Hatzakis, Angelos; Paraskevis, Dimitrios; Karafoulidou, Anastasia; Rezza, Giovanni; Dorrucci, Maria; Balotta, Claudia; D'Arminio Monforte, Antonella; Cozzi-Lepri, Alessandro; Geskus, Ronald; van der Helm, Jannie; Schuitemaker, Hanneke; Sannes, Mette; Brubakk, Oddbjorn; Bakken Kran, Anne-Marte; Rosinska, Magdalena; Gniewosz, Joanna; Camacho, Ricardo; Smolskaya, Tatyana; Tor, Jordi; Garcia de Olalla, Patricia; Cayla, Joan; del Romero, Jorge; Pérez-Hoyos, Santiago; Rickenbach, Martin; Francioli, Patrick; Malyuta, Ruslan; Brettle, Ray; Delpech, Valerie; Lattimore, Sam; Murphy, Gary; Johnson, Anne; Phillips, Andrew; Jaffe, Harold; Morrison, Charles; Salata, Robert; Mugerwa, Roy; Chipato, Tsungai; Amornkul, Pauli

    2011-01-01

    To estimate the clinical benefit of highly active antiretroviral therapy (HAART) initiation vs deferral in a given month in patients with CD4 cell counts less than 800/μL. In this observational cohort study of human immunodeficiency virus type 1 seroconverters from CASCADE (Concerted Action on

  12. A new method for high yield purification of type beta transforming growth factor from human platelets

    NARCIS (Netherlands)

    Eijnden-van Raaij, A.J.M. van den; Koornneef, I.; Zoelen, E.J.J. van

    1988-01-01

    A new method was developed for the purification of type beta transforming growth factor from human platelets. This method is a three-step procedure including gel filtration, weak cation exchange HPLC and reverse phase HPLC. All steps are carried out at low pH using exclusively volatile acidic buffer

  13. Prevalence, distribution and correlates of endocervical human papillomavirus types in Brazilian women

    NARCIS (Netherlands)

    Lippman, S. A.; Sucupira, M. C. A.; Jones, H. E.; Luppi, C. G.; Palefsky, J.; van de Wijgert, J. H. H. M.; Oliveira, R. L. S.; Diaz, R. S.

    2010-01-01

    We determined the prevalence, distribution and correlates of human papillomavirus (HPV) types in 386 mixed-income, sexually active women in Sao Paulo, Brazil. Endocervical samples were tested for HPV DNA with L1 primers MY09 and MY11, negative and indeterminate samples were retested using GP 5+/6+

  14. Role of the DIS hairpin in replication of human immunodeficiency virus type 1

    NARCIS (Netherlands)

    Berkhout, B.; van Wamel, J. L.

    1996-01-01

    The virion-associated genome of human immunodeficiency virus type 1 consists of a noncovalently linked dimer of two identical, unspliced RNA molecules. A hairpin structure within the untranslated leader transcript is postulated to play a role in RNA dimerization through base pairing of the

  15. Training-induced changes in peritendinous type I collagen turnover determined by microdialysis in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Rosendal, L; Kjaer, M

    2001-01-01

    1. Acute exercise is found to increase collagen type I formation locally in peritendinous connective tissue of the Achilles' tendon in humans, as determined from changes in interstitial concentrations of collagen propeptide (PICP) and a collagen degradation product (ICTP) by the use of microdialy...

  16. The early noncoding region of human papillomavirus type 16 is regulated by cytoplasmic polyadenylation factors

    DEFF Research Database (Denmark)

    Glahder, Jacob-Andreas Harald; Kristiansen, Karen; Durand, Marjorie

    2010-01-01

    All human papillomavirus type 16 (HPV-16) early mRNAs are polyadenylated at the poly(A) signal within the early 3' untranslated region (3'UTR). The 3'end of the early E5 open reading frame and the 3'UTR of HPV-16 is very AU-rich, with five regions similar to cytoplasmic polyadenylation elements (...

  17. Gag sequence variation in a human immunodeficiency virus type 1 transmission cluster influences viral replication fitness

    NARCIS (Netherlands)

    Gijsbers, Esther F.; van Nuenen, Ad C.; Schuitemaker, Hanneke; Kootstra, Neeltje A.

    2013-01-01

    Three men from a proven homosexual human immunodeficiency virus type 1 (HIV-1) transmission cluster showed large variation in their clinical course of infection. To evaluate the effect of evolution of the same viral variant in these three patients, we analysed sequence variation in the capsid

  18. West Nile virus meningitis in a patient with human immunodeficiency virus type 1 infection

    Directory of Open Access Journals (Sweden)

    D. Pilalas

    2017-09-01

    Full Text Available The emergence of West Nile virus lineage 2 in central Macedonia, Greece, in 2010 resulted in large outbreaks for 5 consecutive years. We report a case of viral meningitis in an individual infected with human immunodeficiency virus type 1, which preceded the recognition of the outbreak and was confirmed retrospectively as West Nile virus neuroinvasive disease.

  19. Activities of E7 promoters in the human papillomavirus type 16 genome during cell differentiation

    DEFF Research Database (Denmark)

    Hansen, Christina Neigaard; Nielsen, Lone; Norrild, Bodil

    2010-01-01

    Worldwide, one of the most common cancer forms diagnosed in women is cervical cancer induced by infections with high-risk human papillomaviruses (HPVs) with HPV type 16 (HPV-16) being the most frequently identified. The oncogenicity is caused mainly by expression of the oncogenes E6 and E7 leading...

  20. Factors associated with type-specific persistence of high-risk human papillomavirus infection

    DEFF Research Database (Denmark)

    Stensen, Signe; Kjær, Susanne K; Jensen, Signe Marie

    2016-01-01

    Persistent genital infection with high-risk (HR) human papillomavirus (HPV) is a prerequisite for cervical cancer development. The aim of this study was to identify factors associated with type-specific persistence of HR HPV infections. From a population-based cohort of 40,399 women participating...

  1. DNA binding properties of the integrase proteins of human immunodeficiency viruses types 1 and 2

    NARCIS (Netherlands)

    D.C. van Gent (Dik); Y. Elgersma (Ype); M.W. Bolk; C. Vink (Cornelis); R.H. Plassterk

    1991-01-01

    textabstractIntegration of retroviral DNA into the host chromosome requires the integrase protein (IN). We overexpressed the IN proteins of human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) in E. coli and purified them. Both proteins were found to specifically cut two

  2. Mutational analysis of the integrase protein of human immunodeficiency virus type 2

    NARCIS (Netherlands)

    D.C. van Gent (Dik); A.A. Groeneger; A.A. Plassterk

    1992-01-01

    textabstractPurified integrase protein (IN) can nick linear viral DNA at a specific site near the ends and integrate nicked viral DNA into target DNA. We have made a series of 43 site-directed point mutants of human immunodeficiency virus type 2 IN and assayed purified mutant

  3. Meta-analysis reveals conserved cell cycle transcriptional network across multiple human cell types.

    Science.gov (United States)

    Giotti, Bruno; Joshi, Anagha; Freeman, Tom C

    2017-01-05

    Cell division is central to the physiology and pathology of all eukaryotic organisms. The molecular machinery underpinning the cell cycle has been studied extensively in a number of species and core aspects of it have been found to be highly conserved. Similarly, the transcriptional changes associated with this pathway have been studied in different organisms and different cell types. In each case hundreds of genes have been reported to be regulated, however there seems to be little consensus in the genes identified across different studies. In a recent comparison of transcriptomic studies of the cell cycle in different human cell types, only 96 cell cycle genes were reported to be the same across all studies examined. Here we perform a systematic re-examination of published human cell cycle expression data by using a network-based approach to identify groups of genes with a similar expression profile and therefore function. Two clusters in particular, containing 298 transcripts, showed patterns of expression consistent with cell cycle occurrence across the four human cell types assessed. Our analysis shows that there is a far greater conservation of cell cycle-associated gene expression across human cell types than reported previously, which can be separated into two distinct transcriptional networks associated with the G 1 /S-S and G 2 -M phases of the cell cycle. This work also highlights the benefits of performing a re-analysis on combined datasets.

  4. Determination of markers for collagen type I turnover in peritendinous human tissue by microdialysis

    DEFF Research Database (Denmark)

    Olesen, J L; Langberg, Henning; Heinemeier, K M

    2006-01-01

    Previous results from our group have shown that loading of human tendon elevates tendinous type I collagen production measured by microdialysis. However, exclusion of the observed elevation as a response to trauma from inserting the microdialysis catheters or a possible influence from the collagen...

  5. A continuous displacement immunoassay for human heart-type fatty acid-binding protein in plasma

    NARCIS (Netherlands)

    van der Voort, D; Pelsers, MMAL; Korf, J; Hermens, WT; Glatz, JFC

    2004-01-01

    Human heart-type fatty acid-binding protein (FABP) is suggested as an early plasma marker of acute myocardial infarction (AMI), and several studies have proved that, for early diagnosis of AMI, FABP performs better than myoglobin, which is a more often used early marker protein. Because serial

  6. Human Immunodeficiency Virus-Type 1 (HIV-1) and the Brain.

    Science.gov (United States)

    Grant, Igor; Heaton, Robert K.

    1990-01-01

    Provides update on what is currently known about neurobehavioral correlates of infection with human immunodeficiency virus-Type 1 (HIV-1), causative agent of acquired immunodeficiency syndrome. Discusses methodological and theoretical issues complicating interpretation of existing data and suggests strategies for future research in this area. (NB)

  7. Pathogenesis of primary R5 human immunodeficiency virus type 1 clones in SCID-hu mice

    NARCIS (Netherlands)

    Scoggins, R. M.; Taylor, J. R.; Patrie, J.; van't Wout, A. B.; Schuitemaker, H.; Camerini, D.

    2000-01-01

    We studied the replication and cytopathicity in SCID-hu mice of R5 human immunodeficiency virus type 1 (HIV-1) biological clones from early and late stages of infection of three patients who never developed MT-2 cell syncytium-inducing (SI; R5X4 or X4) viruses. Several of the late-stage non-MT-2

  8. Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Arendrup, M

    1991-01-01

    The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells...

  9. Structure and chromosomal localization of the human anti-mullerian hormone type II receptor gene

    NARCIS (Netherlands)

    J.A. Visser (Jenny); A. McLuskey; T. van Beers (T.); D.O. Weghuis (D. Olde); A.H.M. Geurts van Kessel (Ad); J.A. Grootegoed (Anton); A.P.N. Themmen (Axel)

    1995-01-01

    textabstractUsing the rat anti-müllerian hormone type II receptor (AMHRII) cDNA as a probe, two overlapping lambda phage clones containing the AMHRII gene were isolated from a human genomic library. Sequence analysis of the exons was performed and the exon/intron boundaries were determined. The

  10. Las Indias y la tratadística militar hispana de los siglos XVI y XVII

    Directory of Open Access Journals (Sweden)

    Espino López, Antonio

    2000-06-01

    Full Text Available En nuestro trabajo hemos pretendido vincular un aspecto muy poco tratado por parte de la historiografía hispana, la tratadística militar, con el ámbito americano. Hemos defendido que la forma de hacer la guerra de los hispanos en América, centrándonos en el caso de la conquista de México, siguió las pautas marcadas por el Gran Capitán en las Guerras de Italia. Es decir, se impuso el nuevo modelo de escuadrón y fue este factor, y no tanto la superioridad del arma de fuego o el uso de la caballería, lo que dio ventaja real a la hueste indiana sobre los ejércitos indios. En segundo lugar, se han tratado tres ejemplos de tratadística militar hispana: uno de los primeros impresos en México, el de D. García de Palacio; un segundo que versa sobre la guerra en América, el de B. de Vargas Machuca y un tercero, ejemplo del siglo XVII, redactado en la Península, pero también impreso finalmente en las Indias, el de A. de Heredia Estupiñán.

  11. Presentación. hacienda y economía en la castilla del siglo XVII

    Directory of Open Access Journals (Sweden)

    José Ignacio ANDRÉS UCENDO

    2011-07-01

    Full Text Available La fiscalidad ha sido la gran culpable de la suerte que siguió la economía castellana en el siglo XVII. La presión fiscal no fue probablemente más acusada que en otros países, pero junto con la aparición de nuevas figuras fiscales, el uso y abuso de expedientes y los cambios en las formas de recaudación crearon poderosos desincentivos económicos que incidieron negativamente sobre las actividades comerciales y urbanas, de las que dependía el desarrollo de los mercados. Los trabajos incluidos en este Informe analizan algunas cuestiones de gran interés acerca de las repercusiones de la fiscalidad sobre las economías rurales y urbanas, el donativo de 1629, la deuda pública y el gasto en infraestructuras de las haciendas locales, que nos dan una idea de cómo la economía pudo verse afectada por la política fiscal de la Monarquía.

  12. El padre Cubero y su viaje por Asia a fines del siglo XVII

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    Carreira Vérez, Antonio

    1996-06-01

    Full Text Available This is a brief review of Father Cubero's main writings. An Aragonese missionary, he travelled around the world in the last third of the 17th century, passing by such conflictive areas as Hungary and Morocco. The paper emphasizes the phase of his trip in which he traveled from Spain to Persia, going through Poland, Lituania, Russia, and Armenia. Father Cubero's ethnographic remarks on these territories are brought to bear with those concomitant of previous and contemporary travelers.Breve repaso a las principales obras del P. Cubero, misionero aragonés que, en el último tercio del siglo XVII, dio la vuelta al mundo y anduvo por zonas conflictivas como Hungría y Marruecos. Se destaca la parte de su itinerario desde España a Persia por tierra, atravesando Polonia, Lituania, Rusia y Armenia, y se señalan sus observaciones etnográficas, con testimonios concomitantes de viajeros anteriores y coetáneos.

  13. Identidades ambiguas. Movilidad social y conflictos en los Andes, siglo XVII

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    Lorandi, Ana María

    2000-06-01

    Full Text Available El trabajo aborda el proceso de complicación de la estructura de la población global en los Andes durante el siglo XVII, provocada por la movilidad social y aumento de la cantidad de niveles jerárquicos en cada uno de los sectores. Se analiza de qué manera importantes segmentos de población buscan crear sus propios espacios dentro de la estructura global y las disputas entre los miembros, las alianzas sectoriales y/o coyunturales provocan distintos tipos de conflictos en un siglo que hasta ahora ha sido considerado como el siglo donde tuvo un relativo éxito el llamado “pacto colonial”. Se señala la existencia de conflictos a causa de la explotación colonial del indígena, pero también aquellos que se suscitan entre agentes del sector español que buscan alianzas muy diversas y que son emergentes de la gran movilidad social.

  14. Conflictos entre linajes y comunidades de vecinos en el norte de Navarra en el siglo XVII

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    Fernando Mikelarena Peña

    1989-01-01

    Full Text Available En el período que cubre los siglos xvi y xvii, los valles montañeses del norte de Navarra atestiguaron una agudizada conflictividad social entre los linajes o «parientes mayores» y las comunidades de vecinos de cada localidad o valle por la cual éstas discutieron los privilegios de los primeros en un intento —conseguido casi siempre— de cercenar cualquier proceso tendente a la señorialización. Los rasgos tipológicos de esa conflictividad muestran la presencia de una triplicidad de variantes según el ámbito concreto de lo dirimido en cada pleito: conflictos por preferencias en las iglesias, conflictos por diezmos y construcción de molinos y conflictos por alcaldías perpetuas y concesiones jurisdiccionales. No obstante, la circunstancia de que en la mayoría de los casos que se describen a continuación consten dos o tres de esas variantes prueba el carácter para nada anecdótico de esas diferencias.

  15. El cultivo del trigo en Nueva Galicia durante el siglo XVII

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    René de León Meza

    2016-01-01

    Full Text Available Este artículo estudia los factores que determinaron el desarrollo y consolidación del cultivo del trigo en varias comarcas del reino de Nueva Galicia durante el siglo xvii tomando como referencia la última fundación de Guadalajara. Destaca lo vital que fue para esta industria la mano de obra indígena a través del sistema de repartimiento forzado y la vigencia de este hasta el siglo xviii en contraste con Nueva España donde fue suprimido desde 1633. La hipótesis aquí planteada es que la escasez de trigo y harina que constantemente sufrieron los habitantes de la ciudad de Guadalajara se debió a la confabulación de las autoridades del Cabildo con los comerciantes y productores para acapararlos, esconderlos y luego venderlos a precios elevados. La política que los regidores implementaron de no instalar una alhóndiga que concentrara y regulara la venta de esos productos confirma el anterior aserto.

  16. Examen de una polémica sobre los intercambios exteriores a principios del siglo XVII

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    Miguel Ángel ECHEVARRÍA BACIGALUPE

    2009-12-01

    Full Text Available Dentro de la profusa literatura característica de la época mercantilista, es justo rescatar del olvido los diferentes puntos de vista sustentados alrededor del comercio internacional por dos personas muy vinculadas, cada una a su manera, con esa actividad. Uno es Juan de Gauna, arbitrista inspirador de la política económica del rey de España en los albores del siglo XVII; el otro es Mateo Welser, una de las cabezas de la conocida sociedad que lleva el nombre familiar, y Tesorero del Imperio. En uno y en otro hallamos numerosos rasgos de originalidad, tantos como para dedicarles este trabajo, aunque bien es cierto que parte de sus opiniones halla fundamento en ideas que por aquel tiempo circulaban entre hombres de negocios, mercaderes, teólogos, políticos; en suma, gentes preocupadas por la «república». Pero es preciso hacer constar que si hemos escogido esta cuestión se debe a lo relativamente insólito de las proposiciones de Gauna y de Welser, dentro de una época de arbitrios muchas veces sin consistencia intelectual alguna, y de salidas a la desesperada en busca de una solución económica a la pugna entre los intereses de España y de las Provincias Unidas, apoyadas estas últimas por potencias vecinas como Inglaterra o Francia.

  17. Frailes y clérigos en Yucatán. Siglo XVII

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    Rocher Salas, Adriana

    2003-12-01

    Full Text Available From 1601 until almost the end of the seventeenth century, the diocese of Yucatán were immersed in a long litigation by 10 rural curates, which involved both Franciscans and secular clerics. The importance of controlling the numerous indigenous population, meant that an ecclesiastical problem merited the intervention of practically all the social sectors of Yucatan, and of course, the Spanish Crown. It is for this reason that the analysis of this event permits the appreciation of how such diverse elements as royal ecclesiastical politics, the evangelization and the interests of different local groups, can converge.

    Desde 1601 hasta casi finalizar el siglo XVII, la diócesis de Yucatán se vio inmersa en un largo litigio por 10 curatos de indios, que involucró a franciscanos y clérigos seculares. La importancia de controlar a la numerosa población indígena hizo que un problema entre eclesiásticos ameritase la intervención de prácticamente todos los sectores que componían la sociedad yucateca y, por supuesto, de la Corona española. Es por eso que su estudio permite apreciar cómo convergían y se entrelazaban elementos tan diversos como la política eclesiástica regia, la cura de almas y los intereses de los distintos grupos locales.

  18. Tierras, encomiendas y élites. El caso de Jujuy en el siglo XVII

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    Ferreiro, Juan Pablo

    1995-06-01

    Full Text Available Not available.

    Este artículo describe y analiza los rasgos característicos y principales del grupo de encomenderos que componían el sector nuclear de la élite jujeña a principios del siglo XVII. Para esto se utilizaron fuentes de diversa índole procedentes del Archivo de Tribunales de Jujuy, entre ellas sobresalen testamentos, dotes, obligaciones de pago y poderes; documentación que por su contenido permite analizar la forma en la que esta élite se constituyó, así como los mecanismos utilizados para acceder y/o conservar un puesto privilegiado en la naciente sociedad jujeña. Desde esta perspectiva se presta particular atención a la dinámica establecida por las redes familiares que sustentan esas posiciones a través de la propiedad o posesión de tierras trabajadas por indios de encomienda, y a su participación activa en el Cabildo local.

  19. Type-dependent association between risk of cervical intraepithelial neoplasia and viral load of oncogenic human papillomavirus types other than types 16 and 18.

    Science.gov (United States)

    Fu Xi, Long; Schiffman, Mark; Ke, Yang; Hughes, James P; Galloway, Denise A; He, Zhonghu; Hulbert, Ayaka; Winer, Rachel L; Koutsky, Laura A; Kiviat, Nancy B

    2017-04-15

    Studies of the clinical relevance of human papillomavirus (HPV) DNA load have focused mainly on HPV16 and HPV18. Data on other oncogenic types are rare. Study subjects were women enrolled in the atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) triage study who had ≥1 of 11 non-HPV16/18 oncogenic types detected during a 2-year follow-up at 6-month intervals. Viral load measurements were performed on the first type-specific HPV-positive specimens. The association of cervical intraepithelial neoplasia grades 2-3 (CIN2/3) with type-specific HPV DNA load was assessed with discrete-time Cox regression. Overall, the increase in the cumulative risk of CIN2/3 per 1 unit increase in log 10 -transformed viral load was statistically significant for four types within species 9 including HPV31 (adjusted hazard ratio [HR adjusted ] = 1.32: 95% confidence interval [CI], 1.14-1.52), HPV35 (HR adjusted  = 1.47; 95% CI, 1.23-1.76), HPV52 (HR adjusted  = 1.14; 95% CI, 1.01-1.30) and HPV58 (HR adjusted  = 1.49; 95% CI, 1.23-1.82). The association was marginally significant for HPV33 (species 9) and HPV45 (species 7) and was not appreciable for other types. The per 1 log 10 -unit increase in viral load of a group of species 9 non-HPV16 oncogenic types was statistically significantly associated with risk of CIN2/3 for women with a cytologic diagnosis of within normal limits, ASC-US, or LSIL at the first HPV-positive visit but not for those with high-grade SIL. Findings suggest that the viral load-associated risk of CIN2/3 is type-dependent, and mainly restricted to the species of HPV types related to HPV16, which shares this association. © 2017 UICC.

  20. Single Muscle Fiber Proteomics Reveals Fiber-Type-Specific Features of Human Muscle Aging

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    Marta Murgia

    2017-06-01

    Full Text Available Skeletal muscle is a key tissue in human aging, which affects different muscle fiber types unequally. We developed a highly sensitive single muscle fiber proteomics workflow to study human aging and show that the senescence of slow and fast muscle fibers is characterized by diverging metabolic and protein quality control adaptations. Whereas mitochondrial content declines with aging in both fiber types, glycolysis and glycogen metabolism are upregulated in slow but downregulated in fast muscle fibers. Aging mitochondria decrease expression of the redox enzyme monoamine oxidase A. Slow fibers upregulate a subset of actin and myosin chaperones, whereas an opposite change happens in fast fibers. These changes in metabolism and sarcomere quality control may be related to the ability of slow, but not fast, muscle fibers to maintain their mass during aging. We conclude that single muscle fiber analysis by proteomics can elucidate pathophysiology in a sub-type-specific manner.

  1. Bioinformatics Analysis of the Human Surfaceome Reveals New Targets for a Variety of Tumor Types

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    André L. Fonseca

    2016-01-01

    Full Text Available It is estimated that 10 to 20% of all genes in the human genome encode cell surface proteins and due to their subcellular localization these proteins represent excellent targets for cancer diagnosis and therapeutics. Therefore, a precise characterization of the surfaceome set in different types of tumor is needed. Using TCGA data from 15 different tumor types and a new method to identify cancer genes, the S-score, we identified several potential therapeutic targets within the surfaceome set. This allowed us to expand a previous analysis from us and provided a clear characterization of the human surfaceome in the tumor landscape. Moreover, we present evidence that a three-gene set—WNT5A, CNGA2, and IGSF9B—can be used as a signature associated with shorter survival in breast cancer patients. The data made available here will help the community to develop more efficient diagnostic and therapeutic tools for a variety of tumor types.

  2. Multilocus Sequence Typing of Borrelia burgdorferi Suggests Existence of Lineages with Differential Pathogenic Properties in Humans

    Science.gov (United States)

    Hanincova, Klara; Mukherjee, Priyanka; Ogden, Nicholas H.; Margos, Gabriele; Wormser, Gary P.; Reed, Kurt D.; Meece, Jennifer K.; Vandermause, Mary F.; Schwartz, Ira

    2013-01-01

    The clinical manifestations of Lyme disease, caused by Borrelia burgdorferi, vary considerably in different patients, possibly due to infection by strains with varying pathogenicity. Both rRNA intergenic spacer and ospC typing methods have proven to be useful tools for categorizing B. burgdorferi strains that vary in their tendency to disseminate in humans. Neither method, however, is suitable for inferring intraspecific relationships among strains that are important for understanding the evolution of pathogenicity and the geographic spread of disease. In this study, multilocus sequence typing (MLST) was employed to investigate the population structure of B. burgdorferi recovered from human Lyme disease patients. A total of 146 clinical isolates from patients in New York and Wisconsin were divided into 53 sequence types (STs). A goeBURST analysis, that also included previously published STs from the northeastern and upper Midwestern US and adjoining areas of Canada, identified 11 major and 3 minor clonal complexes, as well as 14 singletons. The data revealed that patients from New York and Wisconsin were infected with two distinct, but genetically and phylogenetically closely related, populations of B. burgdorferi. Importantly, the data suggest the existence of B. burgdorferi lineages with differential capabilities for dissemination in humans. Interestingly, the data also indicate that MLST is better able to predict the outcome of localized or disseminated infection than is ospC typing. PMID:24069170

  3. Human APOBEC3 induced mutation of human immunodeficiency virus type-1 contributes to adaptation and evolution in natural infection.

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    Eun-Young Kim

    2014-07-01

    Full Text Available Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1 cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection.

  4. Differential decomposition of bacterial and viral fecal indicators in common human pollution types.

    Science.gov (United States)

    Wanjugi, Pauline; Sivaganesan, Mano; Korajkic, Asja; Kelty, Catherine A; McMinn, Brian; Ulrich, Robert; Harwood, Valerie J; Shanks, Orin C

    2016-11-15

    Understanding the decomposition of microorganisms associated with different human fecal pollution types is necessary for proper implementation of many water quality management practices, as well as predicting associated public health risks. Here, the decomposition of select cultivated and molecular indicators of fecal pollution originating from fresh human feces, septage, and primary effluent sewage in a subtropical marine environment was assessed over a six day period with an emphasis on the influence of ambient sunlight and indigenous microbiota. Ambient water mixed with each fecal pollution type was placed in dialysis bags and incubated in situ in a submersible aquatic mesocosm. Genetic and cultivated fecal indicators including fecal indicator bacteria (enterococci, E. coli, and Bacteroidales), coliphage (somatic and F+), Bacteroides fragilis phage (GB-124), and human-associated genetic indicators (HF183/BacR287 and HumM2) were measured in each sample. Simple linear regression assessing treatment trends in each pollution type over time showed significant decay (p ≤ 0.05) in most treatments for feces and sewage (27/28 and 32/40, respectively), compared to septage (6/26). A two-way analysis of variance of log10 reduction values for sewage and feces experiments indicated that treatments differentially impact survival of cultivated bacteria, cultivated phage, and genetic indicators. Findings suggest that sunlight is critical for phage decay, and indigenous microbiota play a lesser role. For bacterial cultivated and genetic indicators, the influence of indigenous microbiota varied by pollution type. This study offers new insights on the decomposition of common human fecal pollution types in a subtropical marine environment with important implications for water quality management applications. Published by Elsevier Ltd.

  5. Human type II pneumocyte chemotactic responses to CXCR3 activation are mediated by splice variant A.

    Science.gov (United States)

    Ji, Rong; Lee, Clement M; Gonzales, Linda W; Yang, Yi; Aksoy, Mark O; Wang, Ping; Brailoiu, Eugen; Dun, Nae; Hurford, Matthew T; Kelsen, Steven G

    2008-06-01

    Chemokine receptors control several fundamental cellular processes in both hematopoietic and structural cells, including directed cell movement, i.e., chemotaxis, cell differentiation, and proliferation. We have previously demonstrated that CXCR3, the chemokine receptor expressed by Th1/Tc1 inflammatory cells present in the lung, is also expressed by human airway epithelial cells. In airway epithelial cells, activation of CXCR3 induces airway epithelial cell movement and proliferation, processes that underlie lung repair. The present study examined the expression and function of CXCR3 in human alveolar type II pneumocytes, whose destruction causes emphysema. CXCR3 was present in human fetal and adult type II pneumocytes as assessed by immunocytochemistry, immunohistochemistry, and Western blotting. CXCR3-A and -B splice variant mRNA was present constitutively in cultured type II cells, but levels of CXCR3-B greatly exceeded CXCR3-A mRNA. In cultured type II cells, I-TAC, IP-10, and Mig induced chemotaxis. Overexpression of CXCR3-A in the A549 pneumocyte cell line produced robust chemotactic responses to I-TAC and IP-10. In contrast, I-TAC did not induce chemotactic responses in CXCR3-B and mock-transfected cells. Finally, I-TAC increased cytosolic Ca(2+) and activated the extracellular signal-regulated kinase, p38, and phosphatidylinositol 3-kinase (PI 3-kinase)/protein kinase B kinases only in CXCR3-A-transfected cells. These data indicate that the CXCR3 receptor is expressed by human type II pneumocytes, and the CXCR3-A splice variant mediates chemotactic responses possibly through Ca(2+) activation of both mitogen-activated protein kinase and PI 3-kinase signaling pathways. Expression of CXCR3 in alveolar epithelial cells may be important in pneumocyte repair from injury.

  6. Identification and quantitation of morphological cell types in electrophoretically separated human embryonic kidney cell cultures

    Science.gov (United States)

    Williams, K. B.; Kunze, M. E.; Todd, P. W.

    1985-01-01

    Four major cell types were identified by phase microscopy in early passage human embryonic kidney cell cultures. They are small and large epithelioid, domed, and fenestrated cells. Fibroblasts are also present in some explants. The percent of each cell type changes with passage number as any given culture grows. As a general rule, the fraction of small epithelioid cells increases, while the fraction of fenestrated cells, always small, decreases further. When fibroblasts are present, they always increase in percentage of the total cell population. Electrophoretic separation of early passage cells showed that the domed cells have the highest electrophoretic mobility, fibroblasts have an intermediate high mobility, small epithelioid cells have a low mobility, broadly distributed, and fenestrated cells have the lowest mobility. All cell types were broadly distributed among electrophoretic subfractions, which were never pure but only enriched with respect to a given cell type.

  7. Type I collagen synthesis and degradation in peritendinous tissue after exercise determined by microdialysis in humans

    DEFF Research Database (Denmark)

    Langberg, Henning; Skovgaard, D; Petersen, L J

    1999-01-01

    1. Physical activity is known to increase type I collagen synthesis measured as the concentration of biomarkers in plasma. By the use of microdialysis catheters with a very high molecular mass cut-off value (3000 kDa) we aimed to determine local type I collagen synthesis and degradation...... catheters were placed in the peritendinous space ventral to the Achilles' tendon under ultrasound guidance and perfused with a Ringer-acetate solution containing 3H-labelled human type IV collagen and [15-3H(N)]PGE2 for in vivo recovery determination. Relative recovery was 37-59 % (range of the s...... increased in blood during running, and returned to baseline in the recovery period, whereas interstitial PGE2 concentration was elevated in the early recovery phase. 4. The findings of the present study indicate that acute exercise induces increased formation of type I collagen in peritendinous tissue...

  8. Immunogenicity of human and bovine insulin in type 1 diabetes mellitus patients.

    Science.gov (United States)

    Himanshu, M; Bhat, Chetan B; Ramchandran, Sarita; Bhat, K Geetha; Kumar, Prasanna K M

    2008-08-01

    The advantages of synthetic insulin (human insulin) over bovine insulin in the treatment of type 1 diabetes mellitus (DM) are much debated in terms of potency and purity. Immunogenicity is one of several factors that determine potency and safety. This study was designed to investigate and study the difference in immunogenicity of human and bovine insulin. We investigated anti-insulin antibody (AIAB) status in 69 type 1 DM patients receiving insulin therapy. Group 1 had 33 patients treated with bovine insulin, and group 2 had 32 patients treated with human insulin. All patients had received their respective insulin therapy for a minimum period of 1 year and had no history of change in insulin type. Forty-three subjects from the normal population were the control group. AIABs were assayed in serum samples of all subjects using a semiquantitative radioimmunoassay kit. The Kruskal-Wallis non-parametric and Mann-Whitney U tests were used to study the difference in immunogenicity of human and bovine insulins. The Kruskal-Wallis test showed that antibody titers in the three groups significantly differed (P<0.001). The Mann-Whitney U test showed no significant difference in AIAB titer between the treatment groups. AIAB titers in the two treatment groups differed significantly from that of the control group, independently (P<0.001). High titers of AIABs are present in patients receiving bovine and human insulin compared to that of the normal population. Bovine and human insulins are antigenic, and there is no significant difference in AIAB titer. Prospective studies are required to determine the long-term clinical significance of these antibodies.

  9. The Nasal Mucosa Contains a Large Spectrum of Human Papillomavirus Types from the Betapapillomavirus and Gammapapillomavirus Genera

    DEFF Research Database (Denmark)

    Forslund, Ola; Johansson, Hanna; Madsen, Klaus Gregaard

    2013-01-01

    Human papillomavirus (HPV) types from the Betapapillomavirus and Gammapapillomavirus genera are common at cutaneous sites. The aim of this study was to analyze the prevalence of these HPV types in oral and nasal samples....... Human papillomavirus (HPV) types from the Betapapillomavirus and Gammapapillomavirus genera are common at cutaneous sites. The aim of this study was to analyze the prevalence of these HPV types in oral and nasal samples....

  10. Metabolism of the aminoterminal propeptide of type III procollagen in cultures of human proximal tubular cells

    DEFF Research Database (Denmark)

    Jensen, L T; Blaehr, H; Andersen, C B

    1992-01-01

    Degradation of the intact form of the aminoterminal propeptide of type III procollagen (PIIINP) has been established in the liver, whereas the col 1 domain of PIIINP is extracted by the kidneys. We used native human PIIINP and col 1 domain of PIIINP to investigate the degradation of PIIINP...... in cultures of human proximal tubular cells. Normal renal tissue was obtained from the healthy part of kidneys surgically removed and from biopsies from a total of 10 patients. The degradation was characterized by incubation of [125I]-PIIINP followed by gel filtration. We found that in physiological...

  11. Region and cell-type resolved quantitative proteomic map of the human heart

    OpenAIRE

    Doll, Sophia; Dreßen, Martina; Geyer, Philipp E.; Itzhak, Daniel N; Braun, Christian; Doppler, Stefanie A.; Meier, Florian; Deutsch, Marcus-Andre; Lahm, Harald; Lange, Rüdiger; Krane, Markus; Mann, Matthias

    2017-01-01

    The heart is a central human organ and its diseases are the leading cause of death worldwide, but an in-depth knowledge of the identity and quantity of its constituent proteins is still lacking. Here, we determine the healthy human heart proteome by measuring 16 anatomical regions and three major cardiac cell types by high-resolution mass spectrometry-based proteomics. From low microgram sample amounts, we quantify over 10,700 proteins in this high dynamic range tissue. We combine copy number...

  12. Single-stranded DNA catenation mediated by human EVL and a type I topoisomerase

    OpenAIRE

    Takaku, Motoki; Takahashi, Daisuke; Machida, Shinichi; Ueno, Hiroyuki; Hosoya, Noriko; Ikawa, Shukuko; Miyagawa, Kiyoshi; Shibata, Takehiko; Kurumizaka, Hitoshi

    2010-01-01

    The human Ena/Vasp-like (EVL) protein is considered to be a bifunctional protein, involved in both actin remodeling and homologous recombination. In the present study, we found that human EVL forms heat-stable multimers of circular single-stranded DNA (ssDNA) molecules in the presence of a type I topoisomerase in vitro. An electron microscopic analysis revealed that the heat-stable ssDNA multimers formed by EVL and topoisomerase were ssDNA catemers. The ssDNA catenation did not occur when eit...

  13. Mycobacterium massiliense Type II genotype leads to higher level of colony forming units and TNF-α secretion from human monocytes than Type I genotype.

    Science.gov (United States)

    Kim, Byoung-Jun; Shim, Tae Sun; Yi, Su-Yeon; Kim, Ho-Cheol; Kim, Bo-Ram; Lee, So-Young; Kook, Yoon-Hoh; Kim, Bum-Joon

    2015-10-01

    Recently, we introduced a novel Mycobacterium massiliense Type II genotype from Korean patients, in which all isolates showed only a rough (R) colony morphotype. In this study, we sought to compare clinical factors and virulence potentials of two genotypes of M. massiliense, Type I and Type II. Patients infected with Type II tend to be younger at infection than those infected with Type I (56.7 vs 62.3, p = 0.051). Type II was more significantly related to R colony type than Type I (34.1% vs 94.1%, p < 0.001). The Type II strain showed significantly more colony forming units (CFUs) and higher levels of TNF-α secretion in infection of human monocytes than the Type I strain. The challenge of extracted glycopeptidolipid (GPL) into human monocytes indicated that the loss of GPL from the cell wall of the Type II genotype led to a higher level of TNF-α secretion in a toll-like receptor 2(TLR2)-dependent manner. Taken together, our data suggest that the M. massiliense Type II genotype shows higher virulence than Type I, which may be due to the induction of TNF-α via the loss of GPL from the Type II cell wall. © 2015 APMIS. Published by John Wiley & Sons Ltd.

  14. Trypsin-mediated enzymatic degradation of type II collagen in the human vitreous

    Science.gov (United States)

    van Deemter, Mariëlle; Kuijer, Roel; Harm Pas, Hendri; Jacoba van der Worp, Roelofje; Hooymans, Johanna Martina Maria

    2013-01-01

    Purpose Aging of the vitreous body can result in sight-threatening pathology. One aspect of vitreous aging is liquefaction, which results from the vanishing of collagen fibrils. We investigated the possibility that trypsins are involved in vitreous type II collagen degradation. Methods Immunohistochemistry and western blotting were used for detecting and locating trypsin isoforms in the vitreous and retina of human donor eyes. The capability of the retina to produce these trypsins was analyzed with polymerase chain reaction. Whether the different trypsins degraded type II collagen was tested in vitro. The sizes of the in vitro induced type II collagen degradation products were compared to those present in the vitreous of human eyes of different ages. Results Trypsin-1 and trypsin-2 were detected in the vitreous. In the retina, messenger ribonucleic acid (mRNA) coding for trypsin-2, -3, and -4 was present. Using immunohistochemistry, trypsin-2 was detected in microglial cells located in the vitreous and the retina. All trypsin isoforms degraded type II collagen and produced degradation products of similar sizes as those present in the vitreous. Conclusions Trypsin-1 and trypsin-2 appear to have a function in the degradation of vitreous type II collagen. They could therefore have a role in the development of vitreous liquefaction. PMID:23882137

  15. Nitric oxide synthase in human skeletal muscles related to defined fibre types.

    Science.gov (United States)

    Punkt, Karla; Fritzsche, Matthias; Stockmar, Christoph; Hepp, Pierre; Josten, Christoph; Wellner, Maren; Schering, Stefan; Buchwalow, Igor B

    2006-05-01

    Skeletal muscle functions regulated by NO are now firmly established. However, the knowledge about the NO synthase (NOS) expression related to a defined fibre type in human skeletal muscles necessitates further clarification. To address this issue, we examined localization of NOS isoforms I, II and III, in human skeletal muscles employing immunocytochemical labeling with tyramide signal amplification complemented with enzyme histochemistry and Western blotting. The NOS immunoreactivity was related to fibre types of different classification systems: physiological classification into slow and fast, ATPase classification into I, IIA, IIAX, IIX, and physiological-metabolic classification into slow-oxidative (SO), fast-oxidative glycolytic (FOG) and fast-glycolytic (FG). We found a correlation of NOS I-III immunoreactivity to metabolic defined fibre types with strong expression in FOG fibres. This implies that NO as modulator of muscle function is involved in oxidative metabolism in connection with fast force development, which only occurs in FOG fibres. The NOS expression showed no correlation to ATPase fibre subtypes due to the metabolic heterogeneity of ATPase fibre types. Healthy and affected vastus medialis muscles after anterior cruciate ligament rupture revealed similar NOS expression level as shown by Western blotting with, however, different expression patterns related to the fibre types in affected muscles. This suggests an altered modulation of force development in the fibres of diseased muscles.

  16. p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

    Science.gov (United States)

    Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

    2012-01-01

    Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

  17. Bridging the species divide: transgenic mice humanized for type-I interferon response.

    Directory of Open Access Journals (Sweden)

    Daniel Harari

    Full Text Available We have generated transgenic mice that harbor humanized type I interferon receptors (IFNARs enabling the study of type I human interferons (Hu-IFN-Is in mice. These "HyBNAR" (Hybrid IFNAR mice encode transgenic variants of IFNAR1 and IFNAR2 with the human extracellular domains being fused to transmembrane and cytoplasmic segments of mouse sequence. B16F1 mouse melanoma cells harboring the HyBNAR construct specifically bound Hu-IFN-Is and were rendered sensitive to Hu-IFN-I stimulated anti-proliferation, STAT1 activation and activation of a prototypical IFN-I response gene (MX2. HyBNAR mice were crossed with a transgenic strain expressing the luciferase reporter gene under the control of the IFN-responsive MX2 promoter (MX2-Luciferase. Both the HyBNAR and HyBNAR/MX2-Luciferase mice were responsive to all Hu-IFN-Is tested, inclusive of IFNα2A, IFNβ, and a human superagonist termed YNSα8. The mice displayed dose-dependent pharmacodynamic responses to Hu-IFN-I injection, as assessed by measuring the expression of IFN-responsive genes. Our studies also demonstrated a weak activation of endogenous mouse interferon response, especially after high dose administration of Hu-IFNs. In sharp contrast to data published for humans, our pharmacodynamic readouts demonstrate a very short-lived IFN-I response in mice, which is not enhanced by sub-cutaneous (SC injections in comparison to other administration routes. With algometric differences between humans and mice taken into account, the HyBNAR mice provides a convenient non-primate pre-clinical model to advance the study of human IFN-Is.

  18. A New Chemical Approach to Human ABO Histo-Blood Group Type 2 Antigens

    Directory of Open Access Journals (Sweden)

    Atsushi Hara

    2013-12-01

    Full Text Available A new chemical approach to synthesizing human ABO histo-blood type 2 antigenic determinants was developed. N-Phthaloyl-protected lactosaminyl thioglycoside derived from lactulose via the Heyns rearrangement was employed to obtain a type 2 core disaccharide. Use of this scheme lowered the overall number of reaction steps. Stereoselective construction of the α-galactosaminide/galactoside found in A- and B-antigens, respectively, was achieved by using a unique di-tert-butylsilylene-directed α-glycosylation method. The proposed synthetic scheme provides an alternative to existing procedures for preparing ABO blood group antigens.

  19. Lambda Interferon Inhibits Human Immunodeficiency Virus Type 1 Infection of Macrophages ▿

    OpenAIRE

    Hou, Wei; Wang,Xu; Ye, Li; Zhou, Lin; Yang, Zhan-Qiu; Riedel, Eric; Ho, Wen-Zhe

    2009-01-01

    The newly identified type III interferon (IFN-λ) has antiviral activity against a broad spectrum of viruses. We thus examined whether IFN-λ has the ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection of blood monocyte-derived macrophages that expressed IFN-λ receptors. Both IFN-λ1 and IFN-λ2, when added to macrophage cultures, inhibited HIV-1 infection and replication. This IFN-λ-mediated anti-HIV-1 activity is broad, as IFN-λ could inhibit infection by both laboratory-ad...

  20. LAS CARRETAS DEL VINO: TRÁFICO Y FLETES EN EL SAN JUAN DE LA FRONTERA EN EL REINO DE CHILE (SIGLO XVII

    Directory of Open Access Journals (Sweden)

    Ana María Rivera Medina

    2011-10-01

    Full Text Available El presente artículo analiza la infraestructura del transporte que se genera desde San Juan en torno a la producción vitivinícola a lo largo del siglo XVII. Por estas fechas, se consolidaba el tráfico comercial de los caldos cuyanos hacia las Provincias del Este y Norte del actual territorio argentino. Para su elaboración hemos utilizado fondos documentales, hasta el momento inéditos, como lo son las fuentes correspondientes al siglo XVII del Archivo General de la Provincia de San Juan

  1. XVII Reunión del Consejo Directivo de la Asociación Latinoamericana de las Academias Nacionales de Medicina, Alanam, España y Portugal.

    OpenAIRE

    Consejo Directivo ALANAM

    2006-01-01

    Bogotá, 23 – 25 de Febrero de 2006 TEMA: EDUCACIÓN MÉDICA XVII reunión del Consejo Directivo de la ALANAM. La XVII reunión del Consejo Directivo de la ALANAM fue inaugurada por la Doctora Mirta Roses, Directora de la Oficina Sanitaria Panamericana, lo cual constituye un hito para ALANAM ya que por primera vez en su historia la Asociación inicia sus relaciones formales con la máxima institución internacional en aspectos de salud en el continente. ...

  2. The Role of Autophagy in Systemic Metabolism and Human-type Diabetes.

    Science.gov (United States)

    Kim, Jinyoung; Lim, Yu-Mi; Lee, Myung-Shik

    2018-01-23

    Autophagy is critical for the maintenance of organelle function and the intracellular nutrient environment. Autophagy is also involved in systemic metabolic homeostasis, and its dysregulation can lead to or accelerate the development of metabolic disorders. While the role of autophagy in the global metabolism of model organisms has been investigated mostly using site-specific genetic knockout technology, the impact of dysregulated autophagy on systemic metabolism has been unclear. Here, we review recent papers showing the role of autophagy in systemic metabolism and in the development of metabolic disorders. Also included are data suggesting the role of autophagy in human-type diabetes, which are different in several key aspects from murine models of diabetes. The results shown here support the view that autophagy modulation could be a new modality for the treatment of metabolic syndrome associated with lipid overload and human- type diabetes.

  3. Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency

    DEFF Research Database (Denmark)

    Simoni, Yannick; Fehlings, Michael; Kloverpris, Henrik N.

    2017-01-01

    Animal models have highlighted the importance of innate lymphoid cells (ILCs) in multiple immune responses. However, technical limitations have hampered adequate characterization of ILCs in humans. Here, we used mass cytometry including a broad range of surface markers and transcription factors...... to accurately identify and profile ILCs across healthy and inflamed tissue types. High dimensional analysis allowed for clear phenotypic delineation of ILC2 and ILC3 subsets. We were not able to detect ILC1 cells in any of the tissues assessed, however, we identified intra-epithelial (ie)ILC1-like cells...... that represent a broader category of NK cells in mucosal and non-mucosal pathological tissues. In addition, we have revealed the expression of phenotypic molecules that have not been previously described for ILCs. Our analysis shows that human ILCs are highly heterogeneous cell types between individuals...

  4. Fenton reaction induced cancer in wild type rats recapitulates genomic alterations observed in human cancer.

    Directory of Open Access Journals (Sweden)

    Shinya Akatsuka

    Full Text Available Iron overload has been associated with carcinogenesis in humans. Intraperitoneal administration of ferric nitrilotriacetate initiates a Fenton reaction in renal proximal tubules of rodents that ultimately leads to a high incidence of renal cell carcinoma (RCC after repeated treatments. We performed high-resolution microarray comparative genomic hybridization to identify characteristics in the genomic profiles of this oxidative stress-induced rat RCCs. The results revealed extensive large-scale genomic alterations with a preference for deletions. Deletions and amplifications were numerous and sometimes fragmented, demonstrating that a Fenton reaction is a cause of such genomic alterations in vivo. Frequency plotting indicated that two of the most commonly altered loci corresponded to a Cdkn2a/2b deletion and a Met amplification. Tumor sizes were proportionally associated with Met expression and/or amplification, and clustering analysis confirmed our results. Furthermore, we developed a procedure to compare whole genomic patterns of the copy number alterations among different species based on chromosomal syntenic relationship. Patterns of the rat RCCs showed the strongest similarity to the human RCCs among five types of human cancers, followed by human malignant mesothelioma, an iron overload-associated cancer. Therefore, an iron-dependent Fenton chemical reaction causes large-scale genomic alterations during carcinogenesis, which may result in distinct genomic profiles. Based on the characteristics of extensive genome alterations in human cancer, our results suggest that this chemical reaction may play a major role during human carcinogenesis.

  5. Human papillomavirus detection in Corrientes, Argentina: High prevalence of type 58 and its phylodynamics.

    Science.gov (United States)

    Marín, Héctor M; Torres, Carolina; Deluca, Gerardo D; Mbayed, Viviana A

    2015-01-01

    Human papillomavirus (HPV) has the highest mortality rate due to cervical cancer in Northeastern Argentina. The aim of this work was to detect and characterize HPV in samples from the Province of Corrientes, Argentina. HPV detection and typing was performed using PCR-RFLP on samples with different cervical lesions (n=255). Seventeen viruses typified as HPV-58 were sequenced (E6 and E7 genes) and mutations were analyzed. HPV DNA was detected in 56.1% of the cervical lesions (143/255). Twenty-two different HPV types were detected. The type most frequently found among the total number of samples and HPV-positive samples was HPV-16 (14.5% and 25.9%, respectively), followed by HPV-58 (8.2%/14.7%, respectively), which is also considered a high-risk viral type. Increased severity of the cytological status was associated with greater rates of HPV detection and, especially, with the detection of greater rates of high-risk types. In addition, the evolutionary dynamics of the alpha-9 species group and HPV-58 was studied. All HPV-58 viruses reported in this work belonged to lineage A, sublineage A2. The phylodynamic analysis indicated that diversification of main groups within lineage A might have accompanied or preceded human migrations across the globe. Given that the most prevalent viruses found belonged to high-risk HPV types, some concerns might arise about the extent of cross protection of the vaccines against the types not included in their design. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. [The image of Man and his care in the hygiene-dietetic tratises of the XVII and XVIII centuries].

    Science.gov (United States)

    Gonzalez de Pablo, A

    1993-01-01

    This work presents a study of the traditional hygienc-dietetic treatises of the XVII and XVIII centuries. Two characteristics define these treatises: the following of Aristotelian and Galenic postulates in their theoretical conception and, in the practical section, the preponderance of the care of the soul in relation to that of the body. This work firstly cover their theoretical foundation (the vision of Man derived from their conception of the body, their notion of the soul and the dynamic relationship established between both); and, secondly, the practical application derived from these concepts (the care of Man on both his planes; the corporal and the psychic).

  7. El Año Ritual en la España de los siglos XVI y XVII

    OpenAIRE

    Fernández-Romero, C. (Cayetano); Usunáriz, J.M. (Jesús María)

    2000-01-01

    Este artículo estudia los intentos de reforma tridentina del calendario en España durante los siglos XVI y XVII: reducción del número de fiestas, introducción de nuevos santos, errradicación de las supersticiones, etc. Al mismo tiempo trata de explicar las razones de la pervivencia del calendario: la tradición y la costumbre, la estrecha relación entre santoral, año litúrgico y año agrícola, y, por último, la importancia de los factores estéticos.

  8. La lucha por el mantenimiento de un huerto de simples en la universidad de Valencia durante el siglo XVII

    Directory of Open Access Journals (Sweden)

    Felipo, Amparo

    2005-12-01

    Full Text Available This article deepens on the efforts made during the 17th century by Medicine professors and students, Pharmacist Associations as well as surgeons and magistrates from Valencia directed toward the creation and mantenaince of a garden destinated to the growing of medicinal plants from worldwide.

    Este artículo profundiza en los esfuerzos realizados durante el siglo XVII por catedráticos y estudiantes de Medicina, colegios de boticarios y cirujanos y magistrados municipales de Valencia orientados a la creación y mantenimiento de un huerto destinado al cultivo de plantas medicinales procedentes de diferentes partes del mundo.

  9. Del corral al papel: estudio de impresores españoles de teatro en el siglo XVII

    OpenAIRE

    Gómez Sánchez-Ferrer, Guillermo

    2015-01-01

    Si la literatura española conoció en el siglo XVII lo que hoy llamaríamos un boom editorial, ese fue el que vivió el teatro. Innegable es la existencia de algunos precedentes concretos a lo largo del siglo XVI, pero no será hasta la siguiente centuria cuando se afiance la apuesta de los editores de literatura por el género teatral. Gracias a ellos se popularizaron en todos los estratos sociales las partes de comedias (a menudo vendidas también como desglosadas para llegar a todos los bolsillo...

  10. Cultura escrita, oralidade e gênero em conventos portugueses (séculos XVII e XVIII

    Directory of Open Access Journals (Sweden)

    Lígia Bellini

    2010-12-01

    Full Text Available O artigo aborda formatos e usos da escrita em mosteiros femininos e masculinos, no Portugal dos séculos XVII e XVIII, buscando explorar significados particulares do domínio de técnicas escriturais. Neste sentido, procura adaptar, à especificidade do contexto analisado, sugestões metodológicas dos estudos sobre as implicações do letramento e seus vínculos com a esfera da oralidade, noutros universos histórico-sociais.

  11. Propios, arbitrios y comunales: Hacienda municipal en el Reino de Aragón durante los siglos XVI y XVII

    OpenAIRE

    Mateos Royo, José Antonio

    2003-01-01

    Editada en la Fundación SEPI Este trabajo analiza la composición y administración de la hacienda municipal en el reino aragonés durante los siglos XVI y XVII. Favorecidos por el auge económico del Quinientos, los concejos alumbraron significativos proyectos en su afán de transformar las relaciones entre el hombre y el paisaje, potenciar las actividades económicas o manifestar su poder público. El progresivo endeudamiento generado por esta gestión provocó la quiebra de las ...

  12. Catálogo del Fondo documental del siglo XVII del archivo musical de las catedrales de Zaragoza (Zac)

    OpenAIRE

    Ezquerro, Antonio; González-Marín, Luis Antonio

    1991-01-01

    El archivo de música hoy recogido en El Pilar de Zaragoza conserva los fondos de la catedral del Salvador (La Seo) y de la antigua basílica de Santa María la Mayor (después Nuestra Señora de El Pilar). Todo el material musical se encuentra agrupado en diversos fondos, diferenciados mediante un criterio cronológico. El fondo B contiene la música en particellas del siglo XVII, más un legajo de documentos al que se referirá este trabajo. Para facilitar el uso y mejorar la conservación de estos p...

  13. Bovedas Encamonadas: Origen, Evolucion, Geometria y Construccion entre los Siglos XVII y XVIII en el Virreinato de Perú

    OpenAIRE

    Hurtado Valdez, Pedro

    2011-01-01

    Desde la creación del Virreinato del Perú, en el siglo XVI, los arcos, bóvedas y cúpulas se acostumbraban a levantar con piedra y fábrica. Sin embargo estas tierras eran sacudidas periodicamente por terremotos, produciendo el colapso de la mayoría de estas edificaciones. Para el siglo XVII los alarifes ya habían experimentado diversas maneras de levantar bóvedas, sin haberse encontrado una respuesta razonable en términos de tiempo, economía y estabilidad frente a los sismos. En medio de ...

  14. La cocina de los venenos. Aspectos de la criminalidad en el Nuevo Reino de Granada, siglos XVII-XVIII

    OpenAIRE

    Ariza Martínez, Juan Sebastián

    2013-01-01

    Durante los siglos XVII y XVIII se presentaron varias querellas ante el Tribunal de Justicia Criminal del Nuevo Reino de Granada, en las que se denunciaba que había personas que ejercían los oficios médicos sin tener títulos que los acreditaran como facultativos en las artes curativas. Por ese entonces, se creía que quienes utilizaban yerbas y conjuros como métodos terapéuticos, por lo general mujeres, debían ser juzgadas como yerbateras-envenenadoras, porque no pretendían curar sino matar a ...

  15. Diagnostic Detection of Human Immunodeficiency Virus Type 1 Antibodies in Urine: a Brazilian Study

    OpenAIRE

    Oelemann, Walter M. R.; Lowndes, Catherine M; Veríssimo Da Costa, Giovani C.; Morgado, Mariza G; Castello-Branco,Luiz Roberto R; Grinsztejn, Beatriz; Alary, Michel; Bastos, Francisco I

    2002-01-01

    We evaluated, for the first time in Latin America, the performance of a commercial enzyme immunoassay (EIA) (Calypte Biomedical Corporation, Berkeley, Calif.) that detects human immunodeficiency virus type 1 (HIV-1)-specific antibodies in urine in comparison to standard serological assays (two commercial EIAs and a commercial Western blot [WB] assay). Paired serum and urine specimens were collected from two different groups of Brazilian patients: 225 drug users with unknown HIV status who att...

  16. Virus-Specific Cytotoxic T Lymphocytes in Human Immunodeficiency Virus Type 1-Infected Chimpanzees

    OpenAIRE

    Santra, Sampa; Fultz, Patricia N.; Letvin, Norman L.

    1999-01-01

    Chimpanzees have been important in studies of human immunodeficiency virus type 1 (HIV-1) pathogenesis and in evaluation of HIV-1 candidate vaccines. However, little information is available about HIV-1-specific cytotoxic T lymphocytes (CTL) in these animals. In the present study, in vitro stimulation of peripheral blood mononuclear cells (PBMC) from infected chimpanzees with HIV-1 Gag peptides was shown to be a sensitive, reproducible method of expanding HIV-1-specific CD8+ effector CTL. Of ...

  17. Selection of peptides interfering with a ribosomal frameshift in the human immunodeficiency virus type 1

    OpenAIRE

    Dulude, Dominic; THÉBERGE-JULIEN, GABRIEL; Brakier-Gingras, Léa; Heveker, Nikolaus

    2008-01-01

    The human immunodeficiency virus of type 1 (HIV-1) uses a programmed -1 ribosomal frameshift to produce the precursor of its enzymes, and changes in frameshift efficiency reduce replicative fitness of the virus. We used a fluorescent two-reporter system to screen for peptides that reduce HIV-1 frameshift in bacteria, knowing that the frameshift can be reproduced in Escherichia coli. Expression of one reporter, the green fluorescent protein (GFP), requires the HIV-1 frameshift, whereas the sec...

  18. Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells

    OpenAIRE

    Bowen, James R.; Quicke, Kendra M; Maddur, Mohan S.; Justin T O'Neal; McDonald, Circe E.; Fedorova, Nadia B.; Vinita Puri; Reed S. Shabman; Bali Pulendran; Suthar, Mehul S.

    2017-01-01

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs...

  19. Primary infection by type 1 human immunodeficiency virus: diagnosis and prognosis.

    OpenAIRE

    Vanhems, P.; Beaulieu, R.

    1997-01-01

    Primary infection by type 1 human immunodeficiency virus (HIV) is symptomatic in about 70% of cases. The acute illness is a mononucleosis-like syndrome with characteristics such as mucosal ulcerations. The duration and severity of the symptoms appear to be related to the prognosis. After reviewing the most frequent signs and symptoms of primary HIV infection, we report different prognostic studies which examined the association between the acute illness and the progression of HIV disease.

  20. D-type cyclins in adult human testis and testicular cancer

    DEFF Research Database (Denmark)

    Bartkova, J; Rajpert-de Meyts, E; Skakkebaek, N E

    1999-01-01

    D-type cyclins are proto-oncogenic components of the 'RB pathway', a G1/S regulatory mechanism centred around the retinoblastoma tumour suppressor (pRB) implicated in key cellular decisions that control cell proliferation, cell-cycle arrest, quiescence, and differentiation. This study focused...... of proliferation and oncogenic aberrations in human tissues and tumours, this study may inspire further research into the emerging role of the cyclin D proteins in the establishment and/or maintenance of the differentiated phenotypes....

  1. Investigating the Human Immunodeficiency Virus Type One-Infected Monocyte-Derived Macrophage Secretome

    OpenAIRE

    Ciborowski, Pawel; Kadiu, Irena; Rozek, Wojciech; Smith, Lynette; Bernhardt, Kristen; Fladseth, Melissa; Ricardo-Dukelow, Mary; Gendelman, Howard E.

    2007-01-01

    Mononuclear phagocytes (bone marrow monocyte-derived macrophages, alveolar macrophages, perivascular macrophages, and microglia) are reservoirs and vehicles of dissemination for the human immunodeficiency virus type-1 (HIV-1). How virus alters mononuclear phagocyte immunoregulatory activities to complete its life cycle and influence disease is incompletely understood. In attempts to better understanding the influence of virus on macrophage functions, we used one-dimensional electrophoresis, a...

  2. Effect of a human-type communication robot on cognitive function in elderly women living alone

    OpenAIRE

    Tanaka, Masaaki; Ishii, Akira; Yamano, Emi; Ogikubo, Hiroki; Okazaki, Masatsugu; Kamimura, Kazuro; Konishi, Yasuharu; Emoto, Shigeru; Watanabe, Yasuyoshi

    2012-01-01

    Summary Background Considering the high prevalence of dementia, it would be of great value to develop effective tools to improve cognitive function. We examined the effects of a human-type communication robot on cognitive function in elderly women living alone. Material/Methods In this study, 34 healthy elderly female volunteers living alone were randomized to living with either a communication robot or a control robot at home for 8 weeks. The shape, voice, and motion features of the communic...

  3. Chronic Osteomyelitis Increases the Incidence of Type 2 Diabetes in Humans and Mice

    OpenAIRE

    Wang, Yicun; Wang, Jun; Deng, Zhantao; Jin, Jiewen; Jiang, Hui; Meng, Jia; Xu, Haidong; Zhao, Jianning; Sun, Guojing; Qian, Hongbo

    2017-01-01

    Background: To compare the risk of type 2 diabetes (T2DM) between patients with and without chronic osteomyelitis (COM), both in humans and in mice, and to explore risk factors in COM patients who developed T2DM. Methods: One hundred seven patients with COM and 114 patients without COM were consecutively enrolled and retrospectively analysed. Clinical data concerning the time to develop diabetes, glucose metabolism, lipid metabolism, inflammatory factors, mental health and frequency of specia...

  4. Pulmonary surfactant mitigates silver nanoparticle toxicity in human alveolar type-I-like epithelial cells.

    Science.gov (United States)

    Sweeney, Sinbad; Leo, Bey Fen; Chen, Shu; Abraham-Thomas, Nisha; Thorley, Andrew J; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng Jim; Shaffer, Milo S P; Chung, Kian Fan; Ryan, Mary P; Porter, Alexandra E; Tetley, Teresa D

    2016-09-01

    Accompanying increased commercial applications and production of silver nanomaterials is an increased probability of human exposure, with inhalation a key route. Nanomaterials that deposit in the pulmonary alveolar region following inhalation will interact firstly with pulmonary surfactant before they interact with the alveolar epithelium. It is therefore critical to understand the effects of human pulmonary surfactant when evaluating the inhalation toxicity of silver nanoparticles. In this study, we evaluated the toxicity of AgNPs on human alveolar type-I-like epithelial (TT1) cells in the absence and presence of Curosurf(®) (a natural pulmonary surfactant substitute), hypothesising that the pulmonary surfactant would act to modify toxicity. We demonstrated that 20nm citrate-capped AgNPs induce toxicity in human alveolar type I-like epithelial cells and, in agreement with our hypothesis, that pulmonary surfactant acts to mitigate this toxicity, possibly through reducing AgNP dissolution into cytotoxic Ag(+) ions. For example, IL-6 and IL-8 release by TT1 cells significantly increased 10.7- and 35-fold, respectively (Pion release and lysosomal disruption, but not with increased reactive oxygen species generation. This study provides a critical understanding of the toxicity of AgNPs in target human alveolar type-I-like epithelial cells and the role of pulmonary surfactant in mitigating this toxicity. The observations reported have important implications for the manufacture and application of AgNPs, in particular for applications involving use of aerosolised AgNPs. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Carnitine metabolism to trimethylamine by an unusual Rieske-type oxygenase from human microbiota.

    Science.gov (United States)

    Zhu, Yijun; Jameson, Eleanor; Crosatti, Marialuisa; Schäfer, Hendrik; Rajakumar, Kumar; Bugg, Timothy D H; Chen, Yin

    2014-03-18

    Dietary intake of L-carnitine can promote cardiovascular diseases in humans through microbial production of trimethylamine (TMA) and its subsequent oxidation to trimethylamine N-oxide by hepatic flavin-containing monooxygenases. Although our microbiota are responsible for TMA formation from carnitine, the underpinning molecular and biochemical mechanisms remain unclear. In this study, using bioinformatics approaches, we first identified a two-component Rieske-type oxygenase/reductase (CntAB) and associated gene cluster proposed to be involved in carnitine metabolism in representative genomes of the human microbiota. CntA belongs to a group of previously uncharacterized Rieske-type proteins and has an unusual "bridging" glutamate but not the aspartate residue, which is believed to facilitate intersubunit electron transfer between the Rieske center and the catalytic mononuclear iron center. Using Acinetobacter baumannii as the model, we then demonstrate that cntAB is essential in carnitine degradation to TMA. Heterologous overexpression of cntAB enables Escherichia coli to produce TMA, confirming that these genes are sufficient in TMA formation. Site-directed mutagenesis experiments have confirmed that this unusual "bridging glutamate" residue in CntA is essential in catalysis and neither mutant (E205D, E205A) is able to produce TMA. Taken together, the data in our study reveal the molecular and biochemical mechanisms underpinning carnitine metabolism to TMA in human microbiota and assign the role of this novel group of Rieske-type proteins in microbial carnitine metabolism.

  6. Nuclear DNA Content Varies with Cell Size across Human Cell Types

    Science.gov (United States)

    Gillooly, James F.; Hein, Andrew; Damiani, Rachel

    2015-01-01

    Variation in the size of cells, and the DNA they contain, is a basic feature of multicellular organisms that affects countless aspects of their structure and function. Within humans, cell size is known to vary by several orders of magnitude, and differences in nuclear DNA content among cells have been frequently observed. Using published data, here we describe how the quantity of nuclear DNA across 19 different human cell types increases with cell volume. This observed increase is similar to intraspecific relationships between DNA content and cell volume in other species, and interspecific relationships between diploid genome size and cell volume. Thus, we speculate that the quantity of nuclear DNA content in somatic cells of humans is perhaps best viewed as a distribution of values that reflects cell size distributions, rather than as a single, immutable quantity. PMID:26134319

  7. Nuclear DNA Content Varies with Cell Size across Human Cell Types.

    Science.gov (United States)

    Gillooly, James F; Hein, Andrew; Damiani, Rachel

    2015-07-01

    Variation in the size of cells, and the DNA they contain, is a basic feature of multicellular organisms that affects countless aspects of their structure and function. Within humans, cell size is known to vary by several orders of magnitude, and differences in nuclear DNA content among cells have been frequently observed. Using published data, here we describe how the quantity of nuclear DNA across 19 different human cell types increases with cell volume. This observed increase is similar to intraspecific relationships between DNA content and cell volume in other species, and interspecific relationships between diploid genome size and cell volume. Thus, we speculate that the quantity of nuclear DNA content in somatic cells of humans is perhaps best viewed as a distribution of values that reflects cell size distributions, rather than as a single, immutable quantity. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  8. Effects of HEMA on type I collagen protein in human gingival fibroblasts.

    Science.gov (United States)

    Falconi, M; Teti, G; Zago, M; Pelotti, S; Breschi, L; Mazzotti, G

    2007-09-01

    The cytotoxicity of dental composites has been attributed to the release of residual monomers from polymerized adhesive systems due to degradation processes or the incomplete polymerization of materials. 2-Hydroxyethyl methacrylate (HEMA) is one of the major components released from dental adhesives. Cytotoxic effects due to high concentrations of HEMA have already been investigated, but the influence of minor toxic concentrations on specific proteins such as type I collagen has not been studied in depth. The objective of this project was to study the effect of minor toxic concentrations of HEMA on human gingival fibroblasts (HGFs), investigating modification in cell morphology, cell viability, and the influence on type I collagen protein. Primary lines of human gingival fibroblasts were exposed to 3 mmol/L HEMA for different periods of time (24 h, 72 h, 96 h). The cell vitality was determined by MTT assay, and high-resolution scanning electron microscopy analysis was performed to evaluate differences in cell morphology before and after treatment. The presence and localization of type I collagen was determined by immunofluorescence in HGFs treated with HEMA for the same period of time. The vitality of the cells decreased after 72 h of exposure. The HGFs grown in monolayer and observed by field emission in-lens scanning electron microscopy demonstrated a preserved surface morphology after 24 h of treatment, while they showed an altered morphology after 96 h of treatment. Immunofluorescence demonstrated a reduction of type I collagen due to HEMA exposure after 96 h. From these results, we conclude that low concentrations of HEMA can significantly alter the morphology of human gingival fibroblasts and interfere with the presence of type I collagen protein.

  9. Geothermal Program Review XVII: proceedings. Building on 25 years of Geothermal Partnership with Industry

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-10-01

    The US Department of Energy's Office (DOE) of Geothermal Technologies conducted its annual Program Review XVII in Berkeley, California, on May 18--20, 1999. The theme this year was "Building on 25 Years of Geothermal Partnership with Industry". In 1974, Congress enacted Public Law 93-410 which sanctioned the Geothermal Energy Coordination and Management Project, the Federal Government's initial partnering with the US geothermal industry. The annual program review provides a forum to foster this federal partnership with the US geothermal industry through the presentation of DOE-funded research papers from leaders in the field, speakers who are prominent in the industry, topical panel discussions and workshops, planning sessions, and the opportunity to exchange ideas. Speakers and researchers from both industry and DOE presented an annual update on research in progress, discussed changes in the environment and deregulated energy market, and exchanged ideas to refine the DOE Strategic Plan for research and development of geothermal resources in the new century. A panel discussion on Climate Change and environmental issues and regulations provided insight into the opportunities and challenges that geothermal project developers encounter. This year, a pilot peer review process was integrated with the program review. A team of geothermal industry experts were asked to evaluate the research in progress that was presented. The evaluation was based on the Government Performance and Results Act (GPRA) criteria and the goals and objectives of the Geothermal Program as set forth in the Strategic Plan. Despite the short timeframe and cursory guidance provided to both the principle investigators and the peer reviewers, the pilot process was successful. Based on post review comments by both presenters and reviewers, the process will be refined for next year's program review.

  10. Molecular identification of 7 human papillomavirus types in recurrent respiratory papillomatosis.

    Science.gov (United States)

    Peñaloza-Plascencia, M; Montoya-Fuentes, H; Flores-Martínez, S E; Fierro-Velasco, F J; Peñaloza-González, J M; Sánchez-Corona, J

    2000-09-01

    Recurrent respiratory papillomatosis (RRP) is the most frequent benign neoplasm in childhood; it originates as a mild dysphonia and results in asphyxia. The RRP has been associated with an infection caused by human papillomavirus (HPV), mainly types 6 and 11, the latter being associated with more severe RRP. To analyze the frequency of the association of RRP with the HPV types in our juvenile population and to classify it according to severity. Observational descriptive trial. Forty-seven samples of paraffin-embedded papillomas, from 26 female and 21 male children (age range, 2 weeks to 17 years) were analyzed. DNA was isolated and a 188-base pair fragment was amplified from a consensus sequence in the E1 open reading frame of several HPVs by polymerase chain reaction. The corresponding band was recovered and reamplified. The fragment was digested with the restriction enzyme RsaI. The digestion products were compared with patterns of molecular weight markers for viral type identification. The patients' clinical records were reviewed, and RRP was classified as mild or aggressive. The presence of HPV types 6, 11, 16, 31, 33, 35, or 39 was confirmed in all the cases with different combinations. The chi(2) test showed no significant differences in clinical aggressiveness among the viral types. A logistic regression analysis demonstrated no association between clinical aggressiveness and any viral type or viral combination. These results show that RRP is caused by infection with HPV types 6 and 11 in addition to many other types, with no relationship between HPV type and clinical severity.

  11. Characterization of three novel human papillomavirus types isolated from oral rinse samples of healthy individuals.

    Science.gov (United States)

    Martin, Erin; Dang, Juliet; Bzhalava, Davit; Stern, Joshua; Edelstein, Zoe R; Koutsky, Laura A; Kiviat, Nancy B; Feng, Qinghua

    2014-01-01

    Despite the strong evidence of HPV infection as the etiological agent in a subset of oral cancer, oral α-HPV detection is rare in healthy individuals, and little is known of the existing of novel HPV types in oral cavity. We determined whether novel HPV types can be isolated from oral rinse samples collected from healthy individuals. We performed rolling circle amplification (RCA) coupled with degenerated PCR assay on 48 oral rinse samples to amplify novel HPV types. Full length HPV DNA was cloned using long range PCR. Quantitative type specific Taqman assays were used to determine the prevalence of novel HPV types in 158 archived oral tissue samples. We were able to isolate four novel human papillomavirus types. Full length HPV DNA was cloned for three of the four novel HPV types. All four HPV types belong to the genus Gammapapillomavirus (γ-PV), where HPV 171 is most closely related to HPV 169, showing 88% similarity; HPV 172 is most closely related to HPV 156, showing 70% similarity; HPV 173 is most closely related to HPV 4, showing 73% similarity; oral sample lavage (OSL) 37 is most closely related to HPV 144, showing 69% similarity. Finally, we showed that HPV 173 was rarely present in oral tissues (2/158), HPV 172 was only detected in normal oral tissues (25/76), and HPV 171 was more prevalent in malignant oral tissues (17/82 vs. 10/76, p=0.21). Novel γ-HPV types are present in oral cavity of healthy individuals. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Identification of multiple HPV types on spermatozoa from human sperm donors.

    Science.gov (United States)

    Kaspersen, Maja D; Larsen, Peter B; Ingerslev, Hans Jakob; Fedder, Jens; Petersen, Gert Bruun; Bonde, Jesper; Höllsberg, Per

    2011-03-29

    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive HPV array. To examine whether HPV was associated with the sperm, in situ hybridization were performed with HPV-6, HPV-16 and -18, and HPV-31-specific probes. The prevalence of HPV-positive sperm donors was 16.0% and in 66.7% of these individuals high-risk types of HPV were detected. In 5.3% of sperm donors, two or more HPV types were detected. Among all identified HPV types, 61.9% were high-risk types. In situ hybridization experiments identified HPV genomes particularly protruding from the equatorial segment and the tail of the sperm. Semen samples from more than one in seven healthy Danish donors contain HPV, most of them of high-risk types binding to the equatorial segment of the sperm cell. Most HPV-positive sperm showed decreased staining with DAPI, indicative of reduced content of DNA. Our data demonstrate that oncogenic HPV types are frequent in men.

  13. Identification of multiple HPV types on spermatozoa from human sperm donors.

    Directory of Open Access Journals (Sweden)

    Maja D Kaspersen

    Full Text Available Human papillomaviruses (HPV may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive HPV array. To examine whether HPV was associated with the sperm, in situ hybridization were performed with HPV-6, HPV-16 and -18, and HPV-31-specific probes. The prevalence of HPV-positive sperm donors was 16.0% and in 66.7% of these individuals high-risk types of HPV were detected. In 5.3% of sperm donors, two or more HPV types were detected. Among all identified HPV types, 61.9% were high-risk types. In situ hybridization experiments identified HPV genomes particularly protruding from the equatorial segment and the tail of the sperm. Semen samples from more than one in seven healthy Danish donors contain HPV, most of them of high-risk types binding to the equatorial segment of the sperm cell. Most HPV-positive sperm showed decreased staining with DAPI, indicative of reduced content of DNA. Our data demonstrate that oncogenic HPV types are frequent in men.

  14. Accurate and reproducible functional maps in 127 human cell types via 2D genome segmentation.

    Science.gov (United States)

    Zhang, Yu; Hardison, Ross C

    2017-09-29

    The Roadmap Epigenomics Consortium has published whole-genome functional annotation maps in 127 human cell types by integrating data from studies of multiple epigenetic marks. These maps have been widely used for studying gene regulation in cell type-specific contexts and predicting the functional impact of DNA mutations on disease. Here, we present a new map of functional elements produced by applying a method called IDEAS on the same data. The method has several unique advantages and outperforms existing methods, including that used by the Roadmap Epigenomics Consortium. Using five categories of independent experimental datasets, we compared the IDEAS and Roadmap Epigenomics maps. While the overall concordance between the two maps is high, the maps differ substantially in the prediction details and in their consistency of annotation of a given genomic position across cell types. The annotation from IDEAS is uniformly more accurate than the Roadmap Epigenomics annotation and the improvement is substantial based on several criteria. We further introduce a pipeline that improves the reproducibility of functional annotation maps. Thus, we provide a high-quality map of candidate functional regions across 127 human cell types and compare the quality of different annotation methods in order to facilitate biomedical research in epigenomics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Microbial Degradation of Forensic Samples of Biological Origin: Potential Threat to Human DNA Typing.

    Science.gov (United States)

    Dash, Hirak Ranjan; Das, Surajit

    2017-12-06

    Forensic biology is a sub-discipline of biological science with an amalgam of other branches of science used in the criminal justice system. Any nucleated cell/tissue harbouring DNA, either live or dead, can be used as forensic exhibits, a source of investigation through DNA typing. These biological materials of human origin are rich source of proteins, carbohydrates, lipids, trace elements as well as water and, thus, provide a virtuous milieu for the growth of microbes. The obstinate microbial growth augments the degradation process and is amplified with the passage of time and improper storage of the biological materials. Degradation of these biological materials carriages a huge challenge in the downstream processes of forensic DNA typing technique, such as short tandem repeats (STR) DNA typing. Microbial degradation yields improper or no PCR amplification, heterozygous peak imbalance, DNA contamination from non-human sources, degradation of DNA by microbial by-products, etc. Consequently, the most precise STR DNA typing technique is nullified and definite opinion can be hardly given with degraded forensic exhibits. Thus, suitable precautionary measures should be taken for proper storage and processing of the biological exhibits to minimize their decaying process by micro-organisms.

  16. Mutation of human molybdenum cofactor sulfurase gene is responsible for classical xanthinuria type II.

    Science.gov (United States)

    Ichida, K; Matsumura, T; Sakuma, R; Hosoya, T; Nishino, T

    2001-04-20

    Drosophila ma-l gene was suggested to encode an enzyme for sulfuration of the desulfo molybdenum cofactor for xanthine dehydrogenase (XDH) and aldehyde oxidase (AO). The human molybdenum cofactor sulfurase (HMCS) gene, the human ma-l homologue, is therefore a candidate gene responsible for classical xanthinuria type II, which involves both XDH and AO deficiencies. However, HMCS has not been identified as yet. In this study, we cloned the HMCS gene from a cDNA library prepared from liver. In two independent patients with classical xanthinuria type II, we identified a C to T base substitution at nucleotide 1255 in the HMCS gene that should cause a CGA (Arg) to TGA (Ter) nonsense substitution at codon 419. A classical xanthinuria type I patient and healthy volunteers lacked this mutation. These results indicate that a functional defect of the HMCS gene is responsible for classical xanthinuria type II, and that HMCS protein functions to provide a sulfur atom for the molybdenum cofactor of XDH and AO. Copyright 2001 Academic Press.

  17. Sensitivity and specificity of four assays to detect human T-lymphotropic virus type I or type I/II antibodies

    NARCIS (Netherlands)

    Vrielink, H.; Reesink, H. W.; Zaaijer, H. L.; van der Poel, C. L.; Cuypers, H. T.; Lelie, P. N.

    1996-01-01

    BACKGROUND: Assays that detect human T-lymphotropic virus type I and type II antibody (HTLV-I/II) are widely used in the routine screening of blood donors. STUDY DESIGN AND METHODS: Four commercially available anti-HTLV-I (Fujirebio and Organon Teknika) or -HTLV-I/II assays (Murex and Ortho) were

  18. Distinct transduction difference between adeno-associated virus type 1 and type 6 vectors in human polarized airway epithelia.

    Science.gov (United States)

    Yan, Z; Lei-Butters, D C M; Keiser, N W; Engelhardt, J F

    2013-03-01

    Of the many biologically isolated adeno-associated virus (AAV) serotypes, AAV1 and AAV6 share the highest degree of sequence homology, with only six different capsid residues. We compared the transduction efficiencies of rAAV1 and rAAV6 in primary polarized human airway epithelia and found significant differences in their abilities to transduce epithelia from the apical and basolateral membranes. rAAV1 transduction was ~10-fold higher than rAAV6 following apical infection, whereas rAAV6 transduction was ~10-fold higher than rAAV1 following basolateral infection. Furthermore, rAAV6 demonstrated significant polarity of transduction (100-fold; basolateral » apical), whereas rAAV1 transduced from both membranes with equal efficiency. To evaluate capsid residues responsible for the observed serotype differences, we mutated the six divergent amino acids either alone or in combination. Results from these studies demonstrated that capsid residues 418 and 531 most significantly controlled membrane polarity differences in transduction between serotypes, with the rAAV6-D418E/K531E mutant demonstrating decreased (~10-fold) basolateral transduction and the rAAV1-E418D/E531K mutant demonstrating a transduction polarity identical to rAAV6-WT (wild type). However, none of the rAAV6 mutants obtained apical transduction efficiencies of rAAV1-WT, suggesting that all six divergent capsid residues in AAV1 act in concert to improve apical transduction of HAE.

  19. Patterns of cervical coinfection with multiple human papilloma virus types in a screening population in Denmark

    DEFF Research Database (Denmark)

    Goldman, Bryan; Rebolj, Matejka; Rygaard, Carsten

    2013-01-01

    Patterns of cervical human papillomavirus (HPV) infection suggest that HPV genotypes are not independent of each other. This may be explained by risk factors common to all HPV infections, but type-specific biological factors may also play a role. This raises the question of whether widespread use...... of the quadrivalent vaccine (covering HPV6, 11, 16, 18) may indirectly affect the prevalence of any non-vaccine types. Routine screening samples from 5014 Danish women were tested for 35 HPV genotypes (including 13 high-risk) using the Genomica CLART(®) HPV2 kit, which is a low-density microarray based on PCR.......9%. For 15 HPV types of primary interest (13 high-risk plus HPV6, 11), almost all pairs occurred more often than expected under independence; 33/105 (31.4%) were statistically significant (p...

  20. An atlas of active enhancers across human cell types and tissues

    DEFF Research Database (Denmark)

    Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene

    2014-01-01

    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples......, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which...... is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility...

  1. Human adenovirus type 8: the major agent of epidemic keratoconjunctivitis (EKC).

    Science.gov (United States)

    Adhikary, Arun Kumar; Banik, Urmila

    2014-12-01

    Human adenovirus type 8 (HAdV-8) is the most common causative agent of a highly contagious eye disease known as epidemic keratoconjunctivitis (EKC). HAdV-8 strains have been classified into genome types HAdV-8A to 8K and HAdV/D1 to D12 according to restriction endonuclease analysis. This review focuses on the significance of HAdV-8 as an agent of EKC. Molecular analysis of HAdV-8 genome types HAdV-53 and HAdV-54 was performed to reveal potential genetic variation in the hexon and fiber, which might affect the antigenicity and tropism of the virus, respectively. On the basis of the published data, three patterns of HAdV-8 genome type distribution were observed worldwide: (1) genome types restricted to a microenvironment, (2) genome types distributed within a country, and (3) globally dispersed genome types. Simplot and zPicture showed that the HAdV-8 genome types were nearly identical to each other. HAdV-54 is very close to the HAdV-8P, B and E genomes, except in the hexon. In a restriction map, HAdV-8P, B, and E share a very high percentage of restriction sites with each other. Hypervariable regions (HVRs) of the hexon were conserved and were 100% identical among the genome types. The fiber knob of HAdV-8P, A, E, J and HAdV-53 were 100% identical. In phylogeny, HVRs of the hexon and fiber knob of the HAdV-8 genome types segregated into monophyletic clusters. Neutralizing antibodies against one genome type will provide protection against other genome types, and the selection of future vaccine strains would be simple due to the stable HVRs. Molecular analysis of whole genomes, particularly of the capsid proteins of the remaining genome types, would be useful to substantiate our observations. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Human muscle fibre type-specific regulation of AMPK and downstream targets by exercise

    Science.gov (United States)

    Kristensen, Dorte E; Albers, Peter H; Prats, Clara; Baba, Otto; Birk, Jesper B; Wojtaszewski, Jørgen F P

    2015-01-01

    AMP-activated protein kinase (AMPK) is a regulator of energy homeostasis during exercise. Studies suggest muscle fibre type-specific AMPK expression. However, fibre type-specific regulation of AMPK and downstream targets during exercise has not been demonstrated. We hypothesized that AMPK subunits are expressed in a fibre type-dependent manner and that fibre type-specific activation of AMPK and downstream targets is dependent on exercise intensity. Pools of type I and II fibres were prepared from biopsies of vastus lateralis muscle from healthy men before and after two exercise trials: (1) continuous cycling (CON) for 30 min at 69 ± 1% peak rate of O2 consumption () or (2) interval cycling (INT) for 30 min with 6 × 1.5 min high-intensity bouts peaking at 95 ± 2% . In type I vs. II fibres a higher β1 AMPK (+215%) and lower γ3 AMPK expression (−71%) was found. α1, α2, β2 and γ1 AMPK expression was similar between fibre types. In type I vs. II fibres phosphoregulation after CON was similar (AMPKThr172, ACCSer221, TBC1D1Ser231 and GS2+2a) or lower (TBC1D4Ser704). Following INT, phosphoregulation in type I vs. II fibres was lower (AMPKThr172, TBC1D1Ser231, TBC1D4Ser704 and ACCSer221) or higher (GS2+2a). Exercise-induced glycogen degradation in type I vs. II fibres was similar (CON) or lower (INT). In conclusion, a differentiated response to exercise of metabolic signalling/effector proteins in human type I and II fibres was evident during interval exercise. This could be important for exercise type-specific adaptations, i.e. insulin sensitivity and mitochondrial density, and highlights the potential for new discoveries when investigating fibre type-specific signalling. PMID:25640469

  3. Active glass-type human augmented cognition system considering attention and intention

    Science.gov (United States)

    Kim, Bumhwi; Ojha, Amitash; Lee, Minho

    2015-10-01

    Human cognition is the result of an interaction of several complex cognitive processes with limited capabilities. Therefore, the primary objective of human cognitive augmentation is to assist and expand these limited human cognitive capabilities independently or together. In this study, we propose a glass-type human augmented cognition system, which attempts to actively assist human memory functions by providing relevant, necessary and intended information by constantly assessing intention of the user. To achieve this, we exploit selective attention and intention processes. Although the system can be used in various real-life scenarios, we test the performance of the system in a person identity scenario. To detect the intended face, the system analyses the gaze points and change in pupil size to determine the intention of the user. An assessment of the gaze points and change in pupil size together indicates that the user intends to know the identity and information about the person in question. Then, the system retrieves several clues through speech recognition system and retrieves relevant information about the face, which is finally displayed through head-mounted display. We present the performance of several components of the system. Our results show that the active and relevant assistance based on users' intention significantly helps the enhancement of memory functions.

  4. Differential distribution of the JC virus receptor-type sialic acid in normal human tissues.

    Science.gov (United States)

    Eash, Sylvia; Tavares, Rosemarie; Stopa, Edward G; Robbins, Scott H; Brossay, Laurent; Atwood, Walter J

    2004-02-01

    JC virus (JCV), a member of the polyomavirus family, causes a demyelinating disease of the central nervous system (CNS) in humans known as progressive multifocal leukoencephalopathy. Although glial cells are the principal target of JCV productive infection in progressive multifocal leukoencephalopathy patients, little is known regarding the site of JCV persistence and the mechanisms by which the virus spreads to the CNS to cause disease. Previous work has demonstrated the presence of replicating JCV DNA in B lymphocytes from peripheral blood, tonsil, and spleen and it has been hypothesized that lymphocytes may be one site of JCV persistence. Detection of viral gene products in renal tubules and excretion of JC virions in the urine suggests JCV persistence in the kidney. A respiratory route of viral transmission has also been hypothesized implicating the lung as another possible site of persistent JCV infection. Earlier studies from our laboratory have shown that terminal alpha 2,6-linked sialic acid is a critical component of the JCV receptor. In this report we examined the tissue distribution of this JCV receptor-type sialic acid in a panel of normal human tissues. Our results demonstrate that in normal brain JCV receptor-type sialic acids are expressed on oligodendrocytes and astrocytes, but not on cortical neurons. The receptor-type sialic acid is also more highly expressed on B lymphocytes than on T lymphocytes in normal human spleen and tonsil. In addition, both the kidney and lung express abundant levels of alpha 2-6-linked sialic acids. Our data show a striking correlation between the expression of the JCV receptor-type sialic acid on cells and their susceptibility to infection by the virus. These findings also support the hypothesis of JCV persistence in lymphoid tissue and B-cell-facilitated viral dissemination to the CNS.

  5. Inhibition of human scleral fibroblast cell attachment to collagen type I by TGFBIp.

    Science.gov (United States)

    Shelton, Lilian; Rada, Jody A Summers

    2009-08-01

    Transforming growth factor beta-induced protein (TGFBIp; 68 kDa) is a secreted extracellular matrix (ECM) protein that has been demonstrated to regulate cell attachment in a variety of cell types. The sclera synthesizes and secretes TGFBIp, which may function to facilitate scleral ECM remodeling events associated with myopia development. Here the authors report that human scleral fibroblasts (HSFs) express TGFBI and that its protein product, TGFBIp, mediates an effect on cell attachment. TGFBI/TGFBIp expression was evaluated by RT-PCR and immunoblot of HSF lysates and culture supernatants. The effect of rTGFBIp (50 microg/mL) on cell attachment to collagen type I was determined with the use of fluid-phase cell attachment assays in HSFs, human foreskin fibroblasts (HFFs), and human corneal stroma fibroblasts (HCFs). Binding assays using biotinylated rTGFBIp were used to assess TGFBIp binding to the HSF surface. Flow cytometry and immunocytochemistry were used to determine both alphavbeta3 and alphavbeta5 expression and localization to the HSF cell surface. HSFs expressed TGFBI and secreted TGFBIp (approximately 833 ng/h). rTGFBIp significantly decreased (25 microg/mL; P collagen type I, whereas rTGFBIp did not significantly affect cell attachment of HFFs (P = 0.50) or HCFs (P = 0.24) to collagen compared with BSA. Integrins alphavbeta3 and alphavbeta5 were detected on the cell surface, and both anti-alphavbeta3 and anti-alphavbeta5 functionally blocked rTGFBIp binding to HSFs. TGFBIp plays an inhibitory role in HSF attachment to collagen type I in vitro through interactions with alphavbeta3 and alphavbeta5 integrin receptors. These results suggest that TGFBIp may modulate scleral cell-matrix interactions in vivo, thereby affecting scleral viscoelasticity.

  6. The human adenovirus type 5 E1B 55 kDa protein obstructs inhibition of viral replication by type I interferon in normal human cells.

    Directory of Open Access Journals (Sweden)

    Jasdave S Chahal

    Full Text Available Vectors derived from human adenovirus type 5, which typically lack the E1A and E1B genes, induce robust innate immune responses that limit their therapeutic efficacy. We reported previously that the E1B 55 kDa protein inhibits expression of a set of cellular genes that is highly enriched for those associated with anti-viral defense and immune responses, and includes many interferon-sensitive genes. The sensitivity of replication of E1B 55 kDa null-mutants to exogenous interferon (IFN was therefore examined in normal human fibroblasts and respiratory epithelial cells. Yields of the mutants were reduced at least 500-fold, compared to only 5-fold, for wild-type (WT virus replication. To investigate the mechanistic basis of such inhibition, the accumulation of viral early proteins and genomes was compared by immunoblotting and qPCR, respectively, in WT- and mutant-infected cells in the absence or presence of exogenous IFN. Both the concentration of viral genomes detected during the late phase and the numbers of viral replication centers formed were strongly reduced in IFN-treated cells in the absence of the E1B protein, despite production of similar quantities of viral replication proteins. These defects could not be attributed to degradation of entering viral genomes, induction of apoptosis, or failure to reorganize components of PML nuclear bodies. Nor was assembly of the E1B- and E4 Orf6 protein- E3 ubiquitin ligase required to prevent inhibition of viral replication by IFN. However, by using RT-PCR, the E1B 55 kDa protein was demonstrated to be a potent repressor of expression of IFN-inducible genes in IFN-treated cells. We propose that a primary function of the previously described transcriptional repression activity of the E1B 55 kDa protein is to block expression of IFN- inducible genes, and hence to facilitate formation of viral replication centers and genome replication.

  7. Ensembled support vector machines for human papillomavirus risk type prediction from protein secondary structures.

    Science.gov (United States)

    Kim, Sun; Kim, Jeongmi; Zhang, Byoung-Tak

    2009-02-01

    Infection by the human papillomavirus (HPV) is regarded as the major risk factor in the development of cervical cancer. Detection of high-risk HPV is important for understanding its oncogenic mechanisms and for developing novel clinical tools for its diagnosis, treatment, and prevention. Several methods are available to predict the risk types for HPV protein sequences. Nevertheless, no tools can achieve a universally good performance for all domains, including HPV and nor do they provide confidence levels for their decisions. Here, we describe ensembled support vector machines (SVMs) to classify HPV risk types, which assign given proteins into high-, possibly high-, or low-risk type based on their confidence level. Our approach uses protein secondary structures to obtain the differential contribution of subsequences for the risk type, and SVM classifiers are combined with a simple but efficient string kernel to handle HPV protein sequences. In the experiments, we compare our approach with previous methods in accuracy and F1-score, and present the predictions for unknown HPV types, which provides promising results.

  8. Municipio y mercado en el Aragón Moderno : el abasto de pescado en Zaragoza (siglos XVI-XVII

    Directory of Open Access Journals (Sweden)

    José Antonio Mateos Royo

    2004-01-01

    Full Text Available Estudio relativo a la política desarrollada por el Concejo de Zaragoza sobre el comercio de pescado durante los siglos XVI y XVII. La prosperidad económica de la ciudad y del municipio permitieron crear durante el siglo xvi condiciones favorables para asegurar a los habitantes de Zaragoza un suministro suficiente a un precio asequible. Sin embargo, el declive económico y el creciente endeudamiento municipal forzarán durante el siglo xvii a aumentar los impuestos sobre las transacciones y reducir la protección al consumidor.This paper studies municipal politics carried out by the Zaragoza city council concerning the first trade during the sixteenth and seventeenth centuries. Economic prosperity in the city and council allowed to create during the sixteenth century favourable conditions in order to get a sufficient supply and a reasonable price for the population. However, economic decline and raising municipal indebtedness during the seventeenth century led to an increase of market taxation and a reduction of consumers' protection.

  9. Llamados a servir: los hospitalarios de San Juan de Dios en Zacatecas, México en el siglo XVII

    Directory of Open Access Journals (Sweden)

    González Fasani, Ana Mónica

    2007-12-01

    Full Text Available Consolidated the Order of San Juan of God in Spain, their religious soon were required to pass to American lands. With the purpose of lifting hospitals they arrived to beginnings of the XVII century and they were organized in three counties: one that would embrace the viceroyalty of New Spain and of overseas, the other one the viceroyalty of the Peru and a third, the denominated Mainland. To four years of having installed in Mexico, they were requested in the populous and rich mining city call Our Mrs. of the Zacatecas.Consolidada la Orden de San Juan de Dios en España, sus religiosos pronto fueron requeridos para pasar a tierras americanas. Con el fin de levantar hospitales llegaron a inicios del siglo XVII y se organizaron en tres provincias: una que abarcaría el virreinato de Nueva España y de ultramar, la otra el virreinato del Perú y una tercera, la denominada Tierra Firme. A cuatro años de instalados en México, fueron solicitados en la populosa y rica ciudad minera llamada Nuestra Señora de los Zacatecas.

  10. Comerciantes y redes mercantiles del siglo XVII en la frontera sur del Virreinato del Perú

    Directory of Open Access Journals (Sweden)

    Gascón, Margarita

    2000-12-01

    Full Text Available La revuelta de los araucanos de 1598-1599 implicó, como es bien conocido, un cambio profundo en la región sur de Chile y en su capital, Santiago. La influencia de Arauco en la evolución del Chile colonial ha sido analizada desde numerosas perspectivas historiográficas. Menos conocido es, sin embargo, el impacto que tuvo esta zona de frontera con Arauco en las colonias trasandinas, en el actual territorio argentino, durante el siglo XVII. En efecto, el establecimiento de un ejército profesional en esta periferia austral del imperio español en Indias impulsó cambios en Mendoza, Córdoba y finalmente Buenos Aires que se relacionan fundamentalmente (aunque no exclusivamente con el abastecimiento de las tropas. Este trabajo analiza las redes mercantiles dentro de las que operaron los principales comerciantes del siglo XVII de Santiago, Mendoza, Córdoba y Buenos Aires en relación con el ejército real establecido en la frontera del sur de Chile. Se describe, por una parte, cómo estos mercaderes operaron en las cuatro colonias de la periferia austral del Virreinato del Perú y, por otra parte, se verifica que un importante volumen de sus negocios se relaciona con el flujo de recursos materiales y humanos desde Cuyo, Tucumán, Río de la Plata e incluso Paraguay hacia los mercados chilenos.

  11. Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells.

    Science.gov (United States)

    Bowen, James R; Quicke, Kendra M; Maddur, Mohan S; O'Neal, Justin T; McDonald, Circe E; Fedorova, Nadia B; Puri, Vinita; Shabman, Reed S; Pulendran, Bali; Suthar, Mehul S

    2017-02-01

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors. Historic isolates from Africa and Asia also infected DCs with distinct viral replication kinetics between strains. African lineage viruses displayed more rapid replication kinetics and infection magnitude as compared to Asian lineage viruses, and uniquely induced cell death. Infection of DCs with both contemporary and historic ZIKV isolates led to minimal up-regulation of T cell co-stimulatory and MHC molecules, along with limited secretion of inflammatory cytokines. Inhibition of type I interferon (IFN) protein translation was observed during ZIKV infection, despite strong induction at the RNA transcript level and up-regulation of other host antiviral proteins. Treatment of human DCs with RIG-I agonist potently restricted ZIKV replication, while type I IFN had only modest effects. Mechanistically, we found all strains of ZIKV antagonized type I IFN-mediated phosphorylation of STAT1 and STAT2. Combined, our findings show that ZIKV subverts DC immunogenicity during infection, in part through evasion of type I IFN responses, but that the RLR signaling pathway is still capable of inducing an antiviral state, and therefore may serve as an antiviral therapeutic target.

  12. Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells

    Science.gov (United States)

    Maddur, Mohan S.; O’Neal, Justin T.; Fedorova, Nadia B.; Puri, Vinita; Pulendran, Bali; Suthar, Mehul S.

    2017-01-01

    Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs) are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors. Historic isolates from Africa and Asia also infected DCs with distinct viral replication kinetics between strains. African lineage viruses displayed more rapid replication kinetics and infection magnitude as compared to Asian lineage viruses, and uniquely induced cell death. Infection of DCs with both contemporary and historic ZIKV isolates led to minimal up-regulation of T cell co-stimulatory and MHC molecules, along with limited secretion of inflammatory cytokines. Inhibition of type I interferon (IFN) protein translation was observed during ZIKV infection, despite strong induction at the RNA transcript level and up-regulation of other host antiviral proteins. Treatment of human DCs with RIG-I agonist potently restricted ZIKV replication, while type I IFN had only modest effects. Mechanistically, we found all strains of ZIKV antagonized type I IFN-mediated phosphorylation of STAT1 and STAT2. Combined, our findings show that ZIKV subverts DC immunogenicity during infection, in part through evasion of type I IFN responses, but that the RLR signaling pathway is still capable of inducing an antiviral state, and therefore may serve as an antiviral therapeutic target. PMID:28152048

  13. Zika Virus Antagonizes Type I Interferon Responses during Infection of Human Dendritic Cells.

    Directory of Open Access Journals (Sweden)

    James R Bowen

    2017-02-01

    Full Text Available Zika virus (ZIKV is an emerging mosquito-borne flavivirus that is causally linked to severe neonatal birth defects, including microcephaly, and is associated with Guillain-Barre syndrome in adults. Dendritic cells (DCs are an important cell type during infection by multiple mosquito-borne flaviviruses, including dengue virus, West Nile virus, Japanese encephalitis virus, and yellow fever virus. Despite this, the interplay between ZIKV and DCs remains poorly defined. Here, we found human DCs supported productive infection by a contemporary Puerto Rican isolate with considerable variability in viral replication, but not viral binding, between DCs from different donors. Historic isolates from Africa and Asia also infected DCs with distinct viral replication kinetics between strains. African lineage viruses displayed more rapid replication kinetics and infection magnitude as compared to Asian lineage viruses, and uniquely induced cell death. Infection of DCs with both contemporary and historic ZIKV isolates led to minimal up-regulation of T cell co-stimulatory and MHC molecules, along with limited secretion of inflammatory cytokines. Inhibition of type I interferon (IFN protein translation was observed during ZIKV infection, despite strong induction at the RNA transcript level and up-regulation of other host antiviral proteins. Treatment of human DCs with RIG-I agonist potently restricted ZIKV replication, while type I IFN had only modest effects. Mechanistically, we found all strains of ZIKV antagonized type I IFN-mediated phosphorylation of STAT1 and STAT2. Combined, our findings show that ZIKV subverts DC immunogenicity during infection, in part through evasion of type I IFN responses, but that the RLR signaling pathway is still capable of inducing an antiviral state, and therefore may serve as an antiviral therapeutic target.

  14. Reduced CD4+ T-cell-specific gene expression in human type 1 diabetes mellitus.

    Science.gov (United States)

    Orban, Tihamer; Kis, Janos; Szereday, Laszlo; Engelmann, Peter; Farkas, Klara; Jalahej, Heyam; Treszl, Andras

    2007-06-01

    Type 1 diabetes mellitus (T1DM) in humans is characterized by the T-cell-dependent destruction of the insulin producing pancreatic beta cells; however, the precise pathogenesis of the disease, especially the initiation of pathologic immune response, is still largely unknown. We hypothesized that the function of human CD4+ T cells is altered in T1DM and analyzed unstimulated human peripheral blood CD4+ T-cell gene expression. We used a novel three-way comparison of DNA microarray data of CD4+ T cells isolated from patients with new onset T1DM, patients with long-term Type 2 diabetes (T2DM), and from healthy control subjects in order to eliminate any possible influence of glucose homeostasis on our findings. We analyzed the T1DM specific gene-expression changes and their functional relevance to T1DM autoimmunity. Our genetic and functional data show that T1DM CD4+ T cells are down-regulated specifically affecting key immune functions and cell cycle. Histone deacetylase gene expression, a key regulator of epigenetic modification is also reduced. The CD4+ T cells showed impaired function, including an abnormal immune response, which may be a key element that leads to the breakdown of self-tolerance.

  15. Role of C-type natriuretic peptide in the function of normal human sperm

    Directory of Open Access Journals (Sweden)

    Hui Xia

    2016-01-01

    Full Text Available C-type natriuretic peptide (CNP is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B (NPR-B. Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods (such as immunolocalization, real time polymerase chain reaction and Western Blot, and then to evaluate the influence of CNP on sperm function i n vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function.

  16. Human case of bacteremia caused by Streptococcus canis sequence type 9 harboring the scm gene.

    Science.gov (United States)

    Taniyama, Daisuke; Abe, Yoshihiko; Sakai, Tetsuya; Kikuchi, Takahide; Takahashi, Takashi

    2017-01-01

    Streptococcus canis (Sc) is a zoonotic pathogen that is transferred mainly from companion animals to humans. One of the major virulence factors in Sc is the M-like protein encoded by the scm gene, which is involved in anti-phagocytic activities, as well as the recruitment of plasminogen to the bacterial surface in cooperation with enolase, and the consequent enhancement of bacterial transmigration and survival. This is the first reported human case of uncomplicated bacteremia following a dog bite, caused by Streptococcus canis harboring the scm gene. The similarity of the 16S rRNA from the infecting species to that of the Sc type strain, as well as the amplification of the species-specific cfg gene, encoding a co-hemolysin, was used to confirm the species identity. Furthermore, the isolate was confirmed as sequence type 9. The partial scm gene sequence harbored by the isolate was closely related to those of other two Sc strains. While this isolate did not possess the erm(A), erm(B), or mef(A), macrolide/lincosamide resistance genes, it was not susceptible to azithromycin: its susceptibility was intermediate. Even though human Sc bacteremia is rare, clinicians should be aware of this microorganism, as well as Pasteurella sp., Prevotella sp., and Capnocytophaga sp., when examining and treating patients with fever who maintain close contact with companion animals.

  17. Characterizing Types of Human Mobility to Inform Differential and Targeted Malaria Elimination Strategies in Northeast Cambodia.

    Science.gov (United States)

    Peeters Grietens, Koen; Gryseels, Charlotte; Dierickx, Susan; Bannister-Tyrrell, Melanie; Trienekens, Suzan; Uk, Sambunny; Phoeuk, Pisen; Suon, Sokha; Set, Srun; Gerrets, René; Hoibak, Sarah; Muela Ribera, Joan; Hausmann-Muela, Susanna; Tho, Sochantha; Durnez, Lies; Sluydts, Vincent; d'Alessandro, Umberto; Coosemans, Marc; Erhart, Annette

    2015-11-23

    Human population movements currently challenge malaria elimination in low transmission foci in the Greater Mekong Subregion. Using a mixed-methods design, combining ethnography (n = 410 interviews), malariometric data (n = 4996) and population surveys (n = 824 indigenous populations; n = 704 Khmer migrants) malaria vulnerability among different types of mobile populations was researched in the remote province of Ratanakiri, Cambodia. Different structural types of human mobility were identified, showing differential risk and vulnerability. Among local indigenous populations, access to malaria testing and treatment through the VMW-system and LLIN coverage was high but control strategies failed to account for forest farmers' prolonged stays at forest farms/fields (61% during rainy season), increasing their exposure (p = 0.002). The Khmer migrants, with low acquired immunity, active on plantations and mines, represented a fundamentally different group not reached by LLIN-distribution campaigns since they were largely unregistered (79%) and unaware of the local VMW-system (95%) due to poor social integration. Khmer migrants therefore require control strategies including active detection, registration and immediate access to malaria prevention and control tools from which they are currently excluded. In conclusion, different types of mobility require different malaria elimination strategies. Targeting mobility without an in-depth understanding of malaria risk in each group challenges further progress towards elimination.

  18. Differences in fibre type composition between human masseter and biceps muscles in young and adults reveal unique masseter fibre type growth pattern.

    Science.gov (United States)

    Osterlund, Catharina; Thornell, Lars-Eric; Eriksson, Per-Olof

    2011-07-01

    The human jaw system is different from those of other primates, carnivores, ruminants, and rodents in temporomandibular joint and muscle anatomy. In adults, jaw muscles also differ markedly from limb and trunk muscles in composition and distribution of fibre types. It can be assumed that age-related changes between young age to adulthood in terms of craniofacial growth, teeth eruption, and improvement of jaw functions are paralleled by alterations also in composition and distribution of jaw muscle fibre types. To address this question, we have examined the fibre type composition of the human masseter, a jaw closing muscle, at young age. For comparison, the young biceps brachii was examined. The results were compared with previous data for adult masseter and biceps muscles. Young masseter and biceps were similar in that type I fibres outnumbered other fibre types and were of the same diameter. However, they differed in composition of other fibre types. Young masseter contained fibre types I, IM, IIC, IIAB, IIB, and scarce IIA, with regional differences, whereas young biceps showed types I, IIA, IIAB, and few IIB. Young masseter differed from young biceps also by smaller type II fibre diameter and by containing fetal MyHC. In addition, the masseter and biceps differed in age-related changes of composition and distribution of fibre types between young age and adulthood. We conclude that the human masseter is specialized in fibre types already at young age and shows a unique fibre type growth pattern, in concordance with being a separate allotype of muscle. Copyright © 2011 Wiley-Liss, Inc.

  19. Adenocarcinoma in situ and associated human papillomavirus type distribution observed in two clinical trials of a quadrivalent human papillomavirus vaccine

    DEFF Research Database (Denmark)

    Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K

    2011-01-01

    The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis......, we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2......, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total...

  20. Prognostic implication of human papillomavirus types and species in cervical cancer patients undergoing primary treatment.

    Directory of Open Access Journals (Sweden)

    Yat Ming Lau

    Full Text Available High-risk human papillomavirus (HPV types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4 years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent types found were HPV-16 (60.2%, HPV-18 (21.6%, HPV-52 (11.9%, and HPV-58 (9.3%. Overall, 19.5% of patients had multiple-type infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1% patients survived. The 3-year overall survival rate was 75.5%. Factors independently associated with a poorer 3-year overall survival were age >60 years, tumour size >4 cm, lymph node involvement and treatment with radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type infection was associated with a marginally poorer disease-specific survival (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01-2.90, whereas non-HPV-16 alpha-9 species was associated with a better disease-specific survival (90.0% vs. 76.2%, HR: 0.36, 95% CI = 0.16-0.79. However, on multivariate analysis, HPV infection status irrespective of different grouping methods, including individual types, species, single-type or co-infection, did not carry any significant prognostic significance. In conclusion, we did not observe any association between infection with a particular HPV type/species and survival. An HPV type-based stratification in treatment and follow-up plan could not be recommended.

  1. Prognostic implication of human papillomavirus types and species in cervical cancer patients undergoing primary treatment.

    Science.gov (United States)

    Lau, Yat Ming; Cheung, Tak Hong; Yeo, Winnie; Mo, Frankie; Yu, Mei Yung; Lee, Kun Min; Ho, Wendy C S; Yeung, Apple C M; Law, Priscilla T Y; Chan, Paul K S

    2015-01-01

    High-risk human papillomavirus (HPV) types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4) years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent types found were HPV-16 (60.2%), HPV-18 (21.6%), HPV-52 (11.9%), and HPV-58 (9.3%). Overall, 19.5% of patients had multiple-type infections, 78.4% harboured one or more alpha-9 species, and 28.8% harboured one or more alpha-7 species. After a median follow-up of 8.0 years, 156 (66.1%) patients survived. The 3-year overall survival rate was 75.5%. Factors independently associated with a poorer 3-year overall survival were age >60 years, tumour size >4 cm, lymph node involvement and treatment with radiotherapy+/-chemotherapy. Univariate analysis showed HPV-16 single-type infection was associated with a marginally poorer disease-specific survival (71.6% vs. 87.0%, HR: 1.71, 95% CI = 1.01-2.90), whereas non-HPV-16 alpha-9 species was associated with a better disease-specific survival (90.0% vs. 76.2%, HR: 0.36, 95% CI = 0.16-0.79). However, on multivariate analysis, HPV infection status irrespective of different grouping methods, including individual types, species, single-type or co-infection, did not carry any significant prognostic significance. In conclusion, we did not observe any association between infection with a particular HPV type/species and survival. An HPV type-based stratification in treatment and follow-up plan could not be recommended.

  2. Biological activity of probable/possible high-risk human papillomavirus types in cervical cancer.

    Science.gov (United States)

    Halec, Gordana; Schmitt, Markus; Dondog, Bolormaa; Sharkhuu, Enkhtuya; Wentzensen, Nicolas; Gheit, Tarik; Tommasino, Massimo; Kommoss, Friedrich; Bosch, Franz X; Franceschi, Silvia; Clifford, Gary; Gissmann, Lutz; Pawlita, Michael

    2013-01-01

    Judging the carcinogenicity of human papillomavirus (HPV) types rarely found in cervical cancer (CxCa) is hindered by lack of studies of their biological activity in cancer tissues. To asses transcriptional activity of HPV types, we have developed ultra-short amplimer, splice-site specific, E6*I mRNA RT-PCR assays for 12 high-risk (HR)-HPV (IARC Group 1) and eight probable/possible high-risk (pHR)-HPV types (IARC Group 2A/B carcinogens). Previously unreported E6*I splice sites of the six pHR-HPV types 26, 53, 67, 70, 73 and 82 were identified by cloning and sequencing. We analyzed 97 formalin-fixed paraffin-embedded (FFPE) Mongolian CxCa biopsies for presence of HPV DNA by two sensitive genotyping assays, for E6*I transcripts of all HR-/pHR-HPV types identified and for expression of HPV surrogate markers p16(INK4a), pRb and p53. E6*I of at least one HR-/pHR-HPV was expressed in 94 (98%) of cancer tissues including seven with pHR-HPV types 26, 66, 70 or 82 as single transcribed types. Fifty-eight of E6*I mRNA transcribing cases were analyzable by immunohistochemistry and displayed p16(INK4a) overexpression in 57 (98%), pRb downregulation in 56 (97%) and p53 downregulation in 36 (62%) tissues. The newly developed E6*I mRNA RT-PCR assays appeared to be highly sensitive method to analyze HPV transcription in FFPE materials. Our finding of viral oncogene transcription of pHR-HPV types 26, 66, 70 and 82 in cervical tumors, in the absence of any other transcriptionally active HR-type and with p16(INK4a) overexpression and pRb downregulation, may support a reassessment of the carcinogenicity classification of these pHR-HPV types. Copyright © 2012 UICC.

  3. Single-stranded DNA catenation mediated by human EVL and a type I topoisomerase

    Science.gov (United States)

    Takaku, Motoki; Takahashi, Daisuke; Machida, Shinichi; Ueno, Hiroyuki; Hosoya, Noriko; Ikawa, Shukuko; Miyagawa, Kiyoshi; Shibata, Takehiko; Kurumizaka, Hitoshi

    2010-01-01

    The human Ena/Vasp-like (EVL) protein is considered to be a bifunctional protein, involved in both actin remodeling and homologous recombination. In the present study, we found that human EVL forms heat-stable multimers of circular single-stranded DNA (ssDNA) molecules in the presence of a type I topoisomerase in vitro. An electron microscopic analysis revealed that the heat-stable ssDNA multimers formed by EVL and topoisomerase were ssDNA catemers. The ssDNA catenation did not occur when either EVL or topoisomerase was omitted from the reaction mixture. A deletion analysis revealed that the ssDNA catenation completely depended on the annealing activity of EVL. Human EVL was captured from a human cell extract by TOPO IIIα-conjugated beads, and the interaction between EVL and TOPO IIIα was confirmed by a surface plasmon resonance analysis. Purified TOPO IIIα catalyzed the ssDNA catenation with EVL as efficiently as the Escherichia coli topoisomerase I. Since the ssDNA cutting and rejoining reactions, which are the sub-steps of ssDNA catenation, may be an essential process in homologous recombination, EVL and TOPO IIIα may function in the processing of DNA intermediates formed during homologous recombination. PMID:20639531

  4. Collagen Type I Improves the Differentiation of Human Embryonic Stem Cells towards Definitive Endoderm

    DEFF Research Database (Denmark)

    Rasmussen, Camilla Holzmann; Petersen, Dorthe Roenn; Møller, Jonas Bech

    2015-01-01

    Human embryonic stem cells have the ability to generate all cell types in the body and can potentially provide an unlimited source of cells for cell replacement therapy to treat degenerative diseases such as diabetes. Current differentiation protocols of human embryonic stem cells towards insulin...... embryonic stem cells to the definitive endoderm lineage. The percentage of definitive endoderm cells after differentiation on collagen I and fibronectin was >85% and 65%, respectively. The cells on collagen I substrates displayed different morphology and gene expression during differentiation as assessed...... and consistent differentiation of stem cells to definitive endoderm. The results shed light on the importance of extracellular matrix proteins for differentiation and also points to a cost effective and easy method to improve differentiation....

  5. [Association between types of need, human development index, and infant mortality in Mexico, 2008].

    Science.gov (United States)

    Medina-Gómez, Oswaldo Sinoe; López-Arellano, Oliva

    2011-08-01

    The aim of this study was to assess the association between different types of economic and social deprivation and infant mortality rates reported in 2008 in Mexico. We conducted an ecological study analyzing the correlation and relative risk between the human development index and levels of social and economic differences in State and national infant mortality rates. There was a strong correlation between higher human development and lower infant mortality. Low schooling and poor housing and crowding were associated with higher infant mortality. Although infant mortality has declined dramatically in Mexico over the last 28 years, the decrease has not been homogeneous, and there are persistent inequalities that determine mortality rates in relation to different poverty levels. Programs with a multidisciplinary approach are needed to decrease infant mortality rates through comprehensive individual and family development.

  6. Expression of tissue-type transglutaminase correlates positively with metastatic properties of human melanoma cell lines.

    Science.gov (United States)

    van Groningen, J J; Klink, S L; Bloemers, H P; Swart, G W

    1995-01-27

    In this study the relationship between tissue-type transglutaminase (TGase2) activity and the propensity to metastasize was investigated in human melanoma cell lines with different metastatic behavior. TGase2 catalyzes an acyl-transfer reaction between peptide-bound glutamine residues and primary amines, including the epsilon-amino group of lysine residues. Northern-blot analysis demonstrated that TGase2 RNA-expression (3.7 kb) was elevated in highly metastatic cell lines (MV3 and BLM) as compared to weakly metastatic ones (IF6 and 530). Immunoprecipitation and enzyme assays of TGase2 showed that the differential expression at the mRNA level was also reflected at the protein level. These findings reveal a positive relation between the expression of TGase2 and the metastatic properties of the human melanoma cell lines.

  7. Soil-type influences human selenium status and underlies widespread selenium deficiency risks in Malawi.

    Science.gov (United States)

    Hurst, Rachel; Siyame, Edwin W P; Young, Scott D; Chilimba, Allan D C; Joy, Edward J M; Black, Colin R; Ander, E Louise; Watts, Michael J; Chilima, Benson; Gondwe, Jellita; Kang'ombe, Dalitso; Stein, Alexander J; Fairweather-Tait, Susan J; Gibson, Rosalind S; Kalimbira, Alexander A; Broadley, Martin R

    2013-01-01

    Selenium (Se) is an essential human micronutrient with critical roles in immune functioning and antioxidant defence. Estimates of dietary Se intakes and status are scarce for Africa although crop surveys indicate deficiency is probably widespread in Malawi. Here we show that Se deficiency is likely endemic in Malawi based on the Se status of adults consuming food from contrasting soil types. These data are consistent with food balance sheets and composition tables revealing that >80% of the Malawi population is at risk of dietary Se inadequacy. Risk of dietary Se inadequacy is >60% in seven other countries in Southern Africa, and 22% across Africa as a whole. Given that most Malawi soils cannot supply sufficient Se to crops for adequate human nutrition, the cost and benefits of interventions to alleviate Se deficiency should be determined; for example, Se-enriched nitrogen fertilisers could be adopted as in Finland.

  8. Transepithelial activation of human leukocytes by probiotics and commensal bacteria: role of Enterobacteriaceae-type endotoxin

    DEFF Research Database (Denmark)

    Bäuerlein, A.; Ackermann, S.; Parlesak, Alexandr

    2009-01-01

    The goal of the current study was to clarify whether commercially available probiotics induce greater trans-epithelial activation of human leukocytes than do commensal, food-derived and pathogenic bacteria and to identify the compounds responsible for this activation. Eleven different bacterial...... strains, and some of their pathogen-associated molecular patterns, were incubated apically on a confluent layer of intestinal epithelial cells (Caco-2), which were basolaterally co-cultured with human mononuclear leukocytes. Only Gram-negative bacteria having Enterobacteriaceae-type endotoxin (commensal...... fermenters (Lactobacillus spp.) did not stimulate leukocytes transepithelially. Endotoxin from E. coli and Salmonella enterica Typhimurium induced comparable transepithelial stimulation of leukocytes, but not endotoxin from B. vulgatus or lipoteichoic acid from E. faecalis. Endotoxin-binding agents...

  9. Transepithelial activation of human leukocytes by probiotics and commensal bacteria: Role of Enterobacteriaceae-type endotoxin

    DEFF Research Database (Denmark)

    Baeuerlein, Annette; Ackermann, Stefanie; Parlesak, Alexandr

    2009-01-01

    The goal of the current study was to clarify whether commercially available probiotics induce greater trans-epithelial activation of human leukocytes than do commensal, food-derived and pathogenic bacteria and to identify the compounds responsible for this activation. Eleven different bacterial...... strains, and some of their pathogen-associated molecular patterns, were incubated apically on a confluent layer of intestinal epithelial cells (Caco-2), which were basolaterally co-cultured with human mononuclear leukocytes. Only Gram-negative bacteria having Enterobacteriaceae-type endotoxin (commensal...... fermenters (Lactobacillus spp.) did not stimulate leukocytes transepithelially. Endotoxin from E. coli and Salmonella enterica Typhimurium induced comparable transepithelial stimulation of leukocytes, but not endotoxin from B. vulgatus or lipoteichoic acid from E. faecalis. Endotoxin-binding agents...

  10. The influence of surface type on the absorbed radiation by a human under hot, dry conditions

    Science.gov (United States)

    Hardin, A. W.; Vanos, J. K.

    2018-01-01

    Given the predominant use of heat-retaining materials in urban areas, numerous studies have addressed the urban heat island mitigation potential of various "cool" options, such as vegetation and high-albedo surfaces. The influence of altered radiational properties of such surfaces affects not only the air temperature within a microclimate, but more importantly the interactions of long- and short-wave radiation fluxes with the human body. Minimal studies have assessed how cool surfaces affect thermal comfort via changes in absorbed radiation by a human ( R abs) using real-world, rather than modeled, urban field data. The purpose of the current study is to assess the changes in the absorbed radiation by a human—a critical component of human energy budget models—based on surface type on hot summer days (air temperatures > 38.5∘C). Field tests were conducted using a high-end microclimate station under predominantly clear sky conditions over ten surfaces with higher sky view factors in Lubbock, Texas. Three methods were used to measure and estimate R abs: a cylindrical radiation thermometer (CRT), a net radiometer, and a theoretical estimation model. Results over dry surfaces suggest that the use of high-albedo surfaces to reduce overall urban heat gain may not improve acute human thermal comfort in clear conditions due to increased reflected radiation. Further, the use of low-cost instrumentation, such as the CRT, shows potential in quantifying radiative heat loads within urban areas at temporal scales of 5-10 min or greater, yet further research is needed. Fine-scale radiative information in urban areas can aid in the decision-making process for urban heat mitigation using non-vegetated urban surfaces, with surface type choice is dependent on the need for short-term thermal comfort, or reducing cumulative heat gain to the urban fabric.

  11. The influence of high temperature on the possibility of DNA typing in various human tissues.

    Science.gov (United States)

    Maciejewska, Agnieszka; Wlodarczyk, Renata; Pawlowski, Ryszard

    2015-01-01

    The identification of unknown victims of high temperatures (fire, terrorist attack, and other disasters) is one of the most difficult tasks faced by forensic geneticists. The main aim of this study was to in­vestigate the availability of DNA isolated from various human tissue samples exposed to high temperatures of 100–1000°C for 5 and 10 minutes. Samples of varying thickness of thigh muscle, liver, heart, adipose tissue, bone, teeth, hair and nails of 52 fresh cadavers and 59 healthy teeth of 29 volunteers were used. The study was performed using the following commercially available STR (Short Tandem Repeats) and miniSTR kits: AmpFlSTR®SGM Plus® and AmpFlSTR®MiniFilerTM. Hyper variable region I (HVI) of human mitochondrial DNA (mtDNA) was sequenced with BigDye Terminator Cycle Sequencing Kit 1.1. The PEP (Primer-Extension Preamplification) method was used for the whole human genome amplification. It was possible to obtain complete DNA profiles (AmpFlSTR®SGM Plus®, AmpFlSTR®MiniFilerTM Applied Biosystems, USA and mtDNA HVI region) for tissue samples of heart, liver and thigh muscle, exposed up to 900°C for 5 min. However, under the applied conditions, limited usefulness of hair, nails and teeth for identification purposes was shown. DNA stability in tissues subjected to incineration depends on many factors, like tissue type and its thickness, temperature and time of exposure. In the cases of human remains exposed to high temperatures, samples of soft tissues of the highest weight (thickness) provide the best chance of successful identification through the genetic analysis. In some cases of negative results, even if using mtDNA typing, application of the whole genome amplification (WGA) technique could provide the expected results for highly degraded DNA templates.

  12. The influence of surface type on the absorbed radiation by a human under hot, dry conditions

    Science.gov (United States)

    Hardin, A. W.; Vanos, J. K.

    2017-05-01

    Given the predominant use of heat-retaining materials in urban areas, numerous studies have addressed the urban heat island mitigation potential of various "cool" options, such as vegetation and high-albedo surfaces. The influence of altered radiational properties of such surfaces affects not only the air temperature within a microclimate, but more importantly the interactions of long- and short-wave radiation fluxes with the human body. Minimal studies have assessed how cool surfaces affect thermal comfort via changes in absorbed radiation by a human (R abs) using real-world, rather than modeled, urban field data. The purpose of the current study is to assess the changes in the absorbed radiation by a human—a critical component of human energy budget models—based on surface type on hot summer days (air temperatures > 38.5∘C). Field tests were conducted using a high-end microclimate station under predominantly clear sky conditions over ten surfaces with higher sky view factors in Lubbock, Texas. Three methods were used to measure and estimate R abs: a cylindrical radiation thermometer (CRT), a net radiometer, and a theoretical estimation model. Results over dry surfaces suggest that the use of high-albedo surfaces to reduce overall urban heat gain may not improve acute human thermal comfort in clear conditions due to increased reflected radiation. Further, the use of low-cost instrumentation, such as the CRT, shows potential in quantifying radiative heat loads within urban areas at temporal scales of 5-10 min or greater, yet further research is needed. Fine-scale radiative information in urban areas can aid in the decision-making process for urban heat mitigation using non-vegetated urban surfaces, with surface type choice is dependent on the need for short-term thermal comfort, or reducing cumulative heat gain to the urban fabric.

  13. Human B cells fail to secrete type I interferons upon cytoplasmic DNA exposure.

    Science.gov (United States)

    Gram, Anna M; Sun, Chenglong; Landman, Sanne L; Oosenbrug, Timo; Koppejan, Hester J; Kwakkenbos, Mark J; Hoeben, Rob C; Paludan, Søren R; Ressing, Maaike E

    2017-11-01

    Most cells are believed to be capable of producing type I interferons (IFN I) as part of an innate immune response against, for instance, viral infections. In macrophages, IFN I is potently induced upon cytoplasmic exposure to foreign nucleic acids. Infection of these cells with herpesviruses leads to triggering of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic GMP-AMP (cGAMP) synthase (cGAS). Thereby, the stimulator of interferon genes (STING) and the downstream molecules TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) are sequentially activated culminating in IFN I secretion. Human gamma-herpesviruses, such as Epstein-Barr virus (EBV), exploit B cells as a reservoir for persistent infection. In this study, we investigated whether human B cells, similar to macrophages, engage the cytoplasmic DNA sensing pathway to induce an innate immune response. We found that the B cells fail to secrete IFN I upon cytoplasmic DNA exposure, although they express the DNA sensors cGAS and IFI16 and the signaling components TBK1 and IRF3. In primary human B lymphocytes and EBV-negative B cell lines, this deficiency is explained by a lack of detectable levels of the central adaptor protein STING. In contrast, EBV-transformed B cell lines did express STING, yet both these lines as well as STING-reconstituted EBV-negative B cells did not produce IFN I upon dsDNA or cGAMP stimulation. Our combined data show that the cytoplasmic DNA sensing pathway is dysfunctional in human B cells. This exemplifies that certain cell types cannot induce IFN I in response to cytoplasmic DNA exposure providing a potential niche for viral persistence. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Nef protein of human immunodeficiency virus type 1: evidence against its role as a transcriptional inhibitor.

    OpenAIRE

    Hammes, S. R.; Dixon, E P; Malim, M H; Cullen, B R; Greene, W C

    1989-01-01

    The type 1 human immunodeficiency virus (HIV-1) encodes a 27-kDa protein termed Nef (negative factor). Nef has been reported to down-regulate viral gene transcription directed by the HIV-1 long terminal repeat. To assess the possible role of Nef in the initiation or maintenance of viral latency, we prepared two different nef expression vectors (pNEF from the HXB-3 proviral clone; pNEF-2/3 from HXB-2 and HXB-3) and a control vector containing a frameshift mutation in the HXB-3 nef coding seque...

  15. Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Arendrup, M

    1991-01-01

    The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells....... This inhibition was found in infection of both lymphocytic cells and monocytoid cells. Viruses tested included six HIV-1 and five HIV-2 isolates propagated in different cells, as well as infectious plasma from AIDS patients. The antiviral effect of anti-Tn MAbs occurred by specific binding of the MAb to the virus...

  16. Inhibition of Human Immunodeficiency Virus Type 1 Replication prior to Reverse Transcription by Influenza Virus Stimulation

    OpenAIRE

    Pinto, Ligia A.; Blazevic, Vesna; Patterson, Bruce K.; Mac Trubey, C.; Dolan, Matthew J.; Gene M Shearer

    2000-01-01

    It is now recognized that, in addition to drug-mediated therapies against human immunodeficiency virus type 1 (HIV-1), the immune system can exert antiviral effects via CD8+ T-cell-generated anti-HIV factors. This study demonstrates that (i) supernatants from peripheral blood mononuclear cells (PBMC) stimulated with influenza A virus inhibit replication of CCR5- and CXCR4-tropic HIV-1 isolates prior to reverse transcription; (ii) the HIV-suppressive supernatants can be generated by CD4- or CD...

  17. A systems genetics approach identifies genes and pathways for type 2 diabetes in human islets

    DEFF Research Database (Denmark)

    Taneera, Jalal; Lang, Stefan; Sharma, Amitabh

    2012-01-01

    Close to 50 genetic loci have been associated with type 2 diabetes (T2D), but they explain only 15% of the heritability. In an attempt to identify additional T2D genes, we analyzed global gene expression in human islets from 63 donors. Using 48 genes located near T2D risk variants, we identified......, whereas GPR120 affected apoptosis in islets. Expression variation of the top 20 genes explained 24% of the variance in HbA(1c) with no claim of the direction. The data present a global map of genes associated with islet dysfunction and demonstrate the value of systems genetics for the identification...

  18. Failure to demonstrate human T cell lymphotropic virus type I in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P

    1990-01-01

    The polymerase chain reaction (PCR) technique was employed in searching for human T cell lymphotropic virus type I (HTLV-I) gag, env and pol sequences in samples of DNA prepared from two HTLV-I seropositive patients with tropical spastic paraparesis (TSP), the Swedish multiple sclerosis (MS......) patients who recently have been reported to be PCR-positive for HTLV-I gag and env sequences, and eight healthy individuals. Precautions were taken in order to reduce the risk of cross-contamination in the PCR. In the two TSP patients strong signals were obtained with gag, env and pol amplification primers...

  19. [Complete human Klüver-Bucy syndrome after encephalitis caused by herpes simplex type 2].

    Science.gov (United States)

    Bakchine, S; Chain, F; Lhermitte, F

    1986-01-01

    A case of complete Klüver-Bucy syndrome is reported. A 42 year-old man developed Herpes Simplex type II (H.S.V.II) encephalitis. Good sparing of language functions allowed thorough neuropsychological testing. The troubles usually described in Klüver-Bucy syndrome as psychic blindness, colour agnosia, prosopagnosia, auditive and tactile agnosia were present. The authors theorize that these symptoms are mainly correlated with the amnestic syndrome, which is constantly reported in human Klüver-Bucy syndrome. Unfortunately, after 8 weeks, the encephalitis recurred and the patient was left demented and untestable.

  20. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults

    DEFF Research Database (Denmark)

    Larsen, Nadja; Vogensen, Finn Kvist; van der Berg, Franciscus Winfried J

    2010-01-01

    Background Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control....... Methods and Findings The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR) and in a subgroup of subjects (N = 20) by tag......-encoded amplicon pyrosequencing of the V4 region of the 16S rRNA gene. The proportions of phylum Firmicutes and class Clostridia were significantly reduced in the diabetic group compared to the control group (P = 0.03). Furthermore, the ratios of Bacteroidetes to Firmicutes as well as the ratios of Bacteroides...

  1. Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types.

    Directory of Open Access Journals (Sweden)

    Manfred Beleut

    Full Text Available Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers.

  2. Genetic diversity of human papillomavirus types 35, 45 and 58 in cervical cancer in Brazil.

    Science.gov (United States)

    Basto, Diogo Lisbôa; Vidal, João Paulo; Pontes, Valéria Barbosa; Felix, Shayany Pinto; Pinto, Laine Celestino; Soares, Bruno Moreira; Martins, Luis Felipe; Correa, Flávia Miranda; Montenegro, Raquel Carvalho; Chaves, Cláudia Bessa Pereira; Almeida, Liz Maria; Moreira, Miguel Ângelo Martins

    2017-09-01

    In Brazil, most studies of intra-type variants of human papillomavirus (HPV) have focused on HPV16 and HPV18, but other high-risk HPV types have not been studied. Here, we report the prevalence of lineages and variants of HPV35, HPV45 and HPV58 in cervical cancers from the Amazonian and Southeast Brazilian regions. The most frequent sublineages were A1 for HPV35, B2 for HPV45, and A2 for HPV58. The Southeast region had a higher frequency of the B2 sublineage of HPV45, and for HPV35, the genetic and nucleotide sequence diversity were higher in the Southeast region, suggesting that regional factors are influencing the diversity and lineage prevalence.

  3. Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle

    DEFF Research Database (Denmark)

    Gaster, M; Poulsen, P; Handberg, A

    2000-01-01

    GLUT-4 expression in individual fibers of human skeletal muscles in younger and older adults was studied. Furthermore, the dependency of insulin-stimulated glucose uptake on fiber type distribution was investigated. Fiber type distribution was determined in cryosections of muscle biopsies from 8...... younger (29 yr) and 8 older (64 yr) healthy subjects, and estimates of GLUT-4 expression in individual fibers were obtained by combining immunohistochemistry and stereology. GLUT-4 was more abundantly expressed in slow compared with fast muscle fibers in both younger (P ...) subjects. A 25% reduction of GLUT-4 density in fast fibers (P GLUT-4 density in slow fibers were demonstrated in older compared with younger subjects. Insulin-stimulated glucose uptake rates measured by hyperinsulinemic, euglycemic clamp were not correlated with the fraction...

  4. Different types of biotechnological wound coverages created with the application of alive human cells

    Directory of Open Access Journals (Sweden)

    Papuga A. Ye.

    2015-04-01

    Full Text Available Currently, the development and the implementation of the new biotechnological wound coverings (skin equivalents designed for temporal or permanent replacement of damaged or destroyed areas of human skin remains extremely actual relevant in clinical practice. Skin equivalents or equivalents of individual skin layers which include alive cells of different types take a special place among the artificial wound coverings. They mostly contain two basic types of cells – fibroblasts and keratinocytes (together or separately. Such bioconstructions are usually served as temporary coverings, which supply the damaged skin by biologically active substances and stimulate the regeneration of the patient's own tissues. In this review we consider as commercially available wound coverings and those which are still studied in the laboratories. Until now ideal substitutes of natural skin have not yet created, so the efforts of many researchers are focusing on the solution of this problem.

  5. Les relacions epistolars de les ciutats de Barcelona, València i Palma entre els segles XVI i XVII (c. 1510 – c. 1630

    Directory of Open Access Journals (Sweden)

    Vicent Baydal Sala

    2013-06-01

    Full Text Available Resum: L’article analitza les epístoles enviades pels Consells municipals de Barcelona, Valènciai Palma entre els segles XVI i XVII, a través de l’estudi detallat de tres talls cronològics triennalsentre 1510 i 1629. En concret, s’hi atén comparativament a quatre factors: les raons que motivaren la tramesa de cartes per part dels governs urbans, el tipus de destinataris a les quals s’adreçaren, la xarxa de connexions territorials que el seu enviament ocasionà i les formes epistolars emprades pels escrivans en la seua confecció. Així, s’hi pot observar que, compartint una mateixa cultura epistolar, l’activitat de cada Consell fou ben diversa en funció del seu propi poder polític i la seua relació amb la monarquia.Paraules clau: Epístoles, Edat Moderna, Barcelona, València, PalmaAbstract: This paper examines the epistles sent by the City Councils of Barcelona, Valènciaand Palma between the 16th and 17th centuries through the detailed study of three triennialchronological sections between 1510 and 1629. Specifically, it deals comparatively with four issues:the reasons that motivated the letters, the type of addressees, the network of territorial connectionsestablished by the sending of the letters and the epistolary forms used by the scribes. It is observedthat, sharing the same epistolary culture, the activity of each Council was very diverse dependingon its own political power and its relationship with the monarchy.Keywords: Epistles, Early Modern Ages, Barcelona, Valencia, Palma

  6. Botánica en los Horti Farnesiani del Palatino Romano, a inicios del Siglo XVII

    Directory of Open Access Journals (Sweden)

    Suárez Quevedo, Diego

    2012-01-01

    Full Text Available El Renacimiento fue un período de total sintonía entre arte y ciencia, evidente en los casos de la Anatomía y la Botánica, con apoyo tácito en las ilustraciones artísticas; éstas no sólo enriquecieron las publicaciones, sino que contribuyeron de modo importante a los propios avances científicos y su difusión. Este poder de las imágenes se mantuvo e incluso fue potenciado en el siglo XVII. Durante la segunda mitad del siglo XVI, bajo los auspicios de los cardenales Ranuccio y Alejandro Farnesio, se diseñan y realizan los Horti Farnesiani en el área del Palatino romano. Estos Horti, a la manera de los planteamientos de villeggiature de la Edad Moderna, quedaron conformados como arquitecturas y jardines en función del esparcimiento y el retiro, no olvidando la representatividad pero atendiendo también a la Botánica. Aquí fueron cultivadas especies exóticas, procedentes de las Indias Occidentales y traídas a Roma por los jesuitas. La obra del botánico Tobías Aldino, ya bajo el cardenal Odoardo Farnesio, describe algunas de estas especies y se convertirá en un importante referente para estudios botánicos posteriores. The Renaissance was a period of complete harmony between art and science. The images helped to improve the dissemination of scientific knowledge in subjects as Anatomy and Botany. The Horti Farnesiani were designed under the auspices of the cardinals Ranuccio and Alessandro Farnese. Pavillons and gardens devoted to leisure and retirement, with criterions of representation but also taking care of the Botany,. There, will be growing exotic plants, brought to Rome by the Jesuits from the West Indies. The Tobías Aldino work, commissioned by cardinal Odoardo Farnese, describes some of these species and will become a reference for subsequent botanical studies.

  7. La Radiología en la Pintura Santafereña del Siglo XVII

    Directory of Open Access Journals (Sweden)

    Hernando Morales

    1979-10-01

    Full Text Available

    Gregorio Vázquez de Arce y Ceballos, considerado como el más grande pintor que produjera América en el siglo XVII y sus obras como las más representativas de la América Virreinal, comparte con los Echaves de México y con -Miguel de Santiago del Ecuador el privilegio de haber legado a la posteridad una imagen del acaecer colonial, una crónica religiosa y un testimonio conmovedor del nacimiento de una raza, documentos que constituyen una de las bases históricas de nuestra cultura.

    Innumerables han sido los estudios publicados sobre tan insigne pintor, y si nos atrevemos a mostrar una nueva faceta de tan compleja personalidad, es por la discutible autoridad que nos confiere el haber trabajado con pinturas coloniales americanas durante varios
    años, y por el respaldo y apoyo que nos prestó el Profesor Francisco Gil Tovar, Director del Museo de Arte Colonial, profundo conocedor del tema, quien permitió el estudio, fotografía y radiografía de toda la colección del Museo de Arte Colonial de Bogotá, material sobre el cual basamos nuestro estudio. También incluímos algunas obras de colecciones privadas
    facilitadas por sus dueños.

    La producción pictórica de Gregorio Vázquez y la de su taller en Bogotá fue enorme, y más grande aún la influencia que ejerció sobre casi dos siglos de pintura neogranadina. Considerado "El Maestro" fue imitado y copiado; y aún en su taller se ejecutaron obras
    con poco o mucho de su mano que se distribuyeron ampliamente y que hoy llevan el interrogante de la autenticidad de muchas telas.

    Material y Método
    Son muchos los estudios que pueden practicarse en una pintura colonial americana. Casi siempre en lo que toca con su procedencia, antigüedad, estado de conservación, posibles retoques y, naturalmente, su calidad artística. Son muchos los datos que proporcionan
    la tela, los pigmentos, la distribución de color, la composición, el

  8. Positional verbs in space meaning in the Russian language of XI- XVII centuries

    Directory of Open Access Journals (Sweden)

    Tabachenko Lyudmila Vladimirovna

    2015-09-01

    Full Text Available Positional verbs стояти, chdhmu, лежати in the Russian language of XI- XVII centuries are much broader than in the modern Russian language, were used in the spatial meaning of “пребывать, находиться где-л.”, indicating the location of living beings, inanimate objects, two-dimensional objects, administrative units. At the cognitive level, such properties of the subject, such as animation, mentality, sociality, the presence of goal-setting, enable the transfer situation from definite-spatial plan (to be where to the social plan, that is the source of certain transformations of generally location semantics to ‘располагаться на каком-л. участке местности для ведения боевых действий’, ‘осаждать’, ‘постоянно жить где-л.’ When the functional interchangeability of positional verbs retain individual semantic nuances: стояти contains the seme ‘быть готовым к военным действиям’ (based on the component 'to be in the upright position on your feet', which later will be developed in the seme 'functionality'; лежати on the one hand, focuses the subject in a noun-set of semantics, on the other - massiveness of semantics, that can spread, covering some surface; сhдhтu traditionally was used to mean ‘постоянно быть на одном месте’, and in this example it is focused the sema of prolonged staying.

  9. Creación divina y libertad humana en Jesuitas Novohispanos. Siglo XVII

    Directory of Open Access Journals (Sweden)

    Ramón Kuri Camacho

    2007-12-01

    Full Text Available The intention of this work is to study the novohispano seventeen century, especially those aspects related between thought and freedom, creativity and Jesuit spirituality, purification of the reason that entails the education of intelligence. The practice of the freedom and an asceticism of the subjectivity, accustoms to the idea that freedom and intelligence they overlap the one in the other, transferring them by excess of sense to the “spiritual senses”. To let itself strip of the sense origin, practice the freedom and the creativity, “transpose” an hidden sense, showing and hiding at the same time the latent sense in the manifest sense, representing not it reality that we see but the one that we do not see, the unit in the otherness, the unit in movement towards the infinite through the finite, the invisible through the visible, is the baroque enterprise of the Jesuit Company.//El propósito de este trabajo es estudiar el siglo XVII novohispano, especialmente aquellos aspectos de la relación entre pensamiento y libertad, creatividad y espiritualidad jesuitas, purificación de la razón que conlleva la educación de la inteligencia. La práctica de la libertad y una ascesis de la subjetividad, acostumbran a la idea de que libertad e inteligencia se imbrican el uno en el otro, transfiriéndolos por exceso de sentido a los “sentidos espirituales”. Dejarse desposeer del origen del sentido, practicar la libertad y la creatividad, “transponer” un sentido oculto, mostrando y ocultando al mismo tiempo el sentido latente en el sentido manifiesto, representando no la realidad que vemos sino la que no vemos, la unidad en la alteridad, la unidad en movimiento hacia lo infinito a través de lo finito, lo invisible a través de lo visible, es la empresa barroca de la Compañía de Jesús.

  10. Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors.

    Directory of Open Access Journals (Sweden)

    Sara Soto-De Leon

    Full Text Available BACKGROUND: Infection with multiple types of human papillomavirus (HPV is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. PRINCIPAL FINDINGS: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%, while this risk decreased in women who had given birth more than 4 times (-31.1%, or were of mestizo (-24.6% or black (-40.9% ethnicity. CONCLUSIONS: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.

  11. Type-specific human papillomavirus biological features: validated model-based estimates.

    Directory of Open Access Journals (Sweden)

    Iacopo Baussano

    Full Text Available Infection with high-risk (hr human papillomavirus (HPV is considered the necessary cause of cervical cancer. Vaccination against HPV16 and 18 types, which are responsible of about 75% of cervical cancer worldwide, is expected to have a major global impact on cervical cancer occurrence. Valid estimates of the parameters that regulate the natural history of hrHPV infections are crucial to draw reliable projections of the impact of vaccination. We devised a mathematical model to estimate the probability of infection transmission, the rate of clearance, and the patterns of immune response following the clearance of infection of 13 hrHPV types. To test the validity of our estimates, we fitted the same transmission model to two large independent datasets from Italy and Sweden and assessed finding consistency. The two populations, both unvaccinated, differed substantially by sexual behaviour, age distribution, and study setting (screening for cervical cancer or Chlamydia trachomatis infection. Estimated transmission probability of hrHPV types (80% for HPV16, 73%-82% for HPV18, and above 50% for most other types; clearance rates decreasing as a function of time since infection; and partial protection against re-infection with the same hrHPV type (approximately 20% for HPV16 and 50% for the other types were similar in the two countries. The model could accurately predict the HPV16 prevalence observed in Italy among women who were not infected three years before. In conclusion, our models inform on biological parameters that cannot at the moment be measured directly from any empirical data but are essential to forecast the impact of HPV vaccination programmes.

  12. Distribution Patterns of Infection with Multiple Types of Human Papillomaviruses and Their Association with Risk Factors

    Science.gov (United States)

    Soto-De Leon, Sara; Camargo, Milena; Sanchez, Ricardo; Munoz, Marina; Perez-Prados, Antonio; Purroy, Antonio; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso

    2011-01-01

    Background Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (−31.1%), or were of mestizo (−24.6%) or black (−40.9%) ethnicity. Conclusions According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2–4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies. PMID:21379574

  13. Cervicovaginal microbiota composition correlates with the acquisition of high-risk human papillomavirus types.

    Science.gov (United States)

    Huang, Xiaojie; Li, Chao; Li, Fang; Zhao, Junwei; Wan, Xiaoping; Wang, Kai

    2018-02-26

    High-risk (hr) human papillomavirus (HPV) infection is closely associated with the clinical conditions of both squamous intraepithelial lesions (SILs) and cervical carcinoma. However, it remains unclear what factors determine the type of hrHPV infection. Here, we have comprehensively investigated the bacterial composition of the cervicovaginal microbiota of 280 women infected with one type of hrHPV (HPV 16, 52, or 58) by the pyrosequencing of barcoded 16S rRNA genes. Differential microbiota composition was observed among various SIL groups and within the subgroups of each group. This result showed that it is not the microbiota diversity or the common microbiota, but rather agents that are specific to each SIL that might have a positive influence on the acquisition of hrHPV types, independent of abundance. Specifically, a composition of Oribacterium, Lachnobacterium and Thermus in the cervicovaginal microbiota is more likely to be associated with HPV 16, while a composition of Motilibacter in the cervicovaginal microbiota is more likely to be associated with HPV 52, and a composition of Litorilinea and Paludibaculum with a concomitant paucity of L. iners in the cervicovaginal microbiota is more likely to be associated with HPV 58. Furthermore, functional predictions regarding infectious diseases and cancer-related genes disclosed significant differences (P composition of the cervicovaginal microbiota and the type of hrHPV acquired. This article is protected by copyright. All rights reserved. © 2018 UICC.

  14. An overview of pancreatic beta-cell defects in human type 2 diabetes: implications for treatment.

    Science.gov (United States)

    Marchetti, Piero; Dotta, Francesco; Lauro, Davide; Purrello, Francesco

    2008-02-07

    Type 2 diabetes is the most common form of diabetes in humans. It results from a combination of factors that impair beta-cell function and tissue insulin sensitivity. However, growing evidence is showing that the beta-cell is central to the development and progression of this form of diabetes. Reduced islet and/or insulin-containing cell mass or volume in Type 2 diabetes has been reported by several authors. Furthermore, studies with isolated Type 2 diabetic islets have consistently shown both quantitative and qualitative defects of glucose-stimulated insulin secretion. The impact of genotype in affecting beta-cell function and survival is a very fast growing field or research, and several gene polymorphisms have been associated with this form of diabetes. Among acquired factors, glucotoxicity, lipotoxicity and altered IAPP processing are likely to play an important role. Interestingly, however, pharmacological intervention can improve several defects of Type 2 diabetes islet cells in vitro, suggesting that progression of the disease might not be relentless.

  15. Characterization of human papillomavirus type 154 and tissue tropism of gammapapillomaviruses.

    Science.gov (United States)

    Ure, Agustín Enrique; Forslund, Ola

    2014-01-01

    The novel human papillomavirus type 154 (HPV154) was characterized from a wart on the crena ani of a three-year-old boy. It was previously designated as the putative HPV type FADI3 by sequencing of a subgenomic FAP amplicon. We obtained the complete genome by combined methods including rolling circle amplification (RCA), genome walking through an adapted method for detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR), long-range PCR, and finally by cloning of four overlapping amplicons. Phylogenetically, the HPV154 genome clustered together with members of the proposed species Gammapapillomavirus 11, and demonstrated the highest identity in L1 to HPV136 (68.6%). The HPV154 was detected in 3% (2/62) of forehead skin swabs from healthy children. In addition, the different detection sites of 62 gammapapillomaviruses were summarized in order to analyze their tissue tropism. Several of these HPV types have been detected from multiple sources such as skin, oral, nasal, and genital sites, suggesting that the gammapapillomaviruses are generalists with a broader tissue tropism than previously appreciated. The study expands current knowledge concerning genetic diversity and tropism among HPV types in the rapidly growing gammapapillomavirus genus.

  16. Integration of human papilloma virus type 26 in laryngeal cancer of a child.

    Science.gov (United States)

    Muenscher, A; Feucht, H H; Kutta, H; Tesche, S; Wenzel, S

    2009-04-01

    Squamous cell carcinoma (SCC) in larynx is rare with children and adolescents. Usually larynx cancer is common with male smokers in the 7th decade. Among patients with no history of tobacco and/or alcohol consumption several factors have can play a role in the outbreak of laryngeal cancer: such as individual predisposition, radiation, gastroesophageal reflux, viral infection, dietary factors and environmental influences. In literature only few cases of laryngeal cancer with children are reported. Recent studies show that the most frequent laryngeal malignancy is the embryonal rhabdomyosarcoma. Besides the recurrent respiratory papillomatosis (RRP) based on an infection with human papilloma virus (HPV) types 6 and 11 (low risk) and types 16 and 18 (high risk) is known for a possible malignant transformation towards a SCC. HPV type 26 is only reported as low risk type HPV associated with cervical cancer. Final diagnosis often takes a long time. Initial symptoms such as hoarseness, cough or shortness of breath are often referred to more typical pediatric diseases or laryngeal development.

  17. Epidemiological and virological features of epidemic keratoconjunctivitis due to new human adenovirus type 54 in Japan.

    Science.gov (United States)

    Kaneko, Hisatoshi; Suzutani, Tatsuo; Aoki, Koki; Kitaichi, Nobuyoshi; Ishida, Susumu; Ishiko, Hiroaki; Ohashi, Tsutomu; Okamoto, Shigeki; Nakagawa, Hisashi; Hinokuma, Rikutaro; Asato, Yoshimori; Oniki, Shinobu; Hashimoto, Teiko; Iida, Tomohiro; Ohno, Shigeaki

    2011-01-01

    New human adenovirus (HAdV)-54 causes epidemic keratoconjunctivitis (EKC) and is virologically close to and has occasionally been detected as HAdV-8. Taking HAdV-54 into account, we re-determined HAdV type in EKC samples to determine its epidemiology in Japan, and examined the virological features of HAdV-54. HAdV type was re-determined in 776 conjunctival swabs from Japan and 174 from six other countries, obtained between 2000 and 2009. Using 115 HAdV strains obtained before 1999, trends regarding HAdV-8 and HAdV-54 were also determined. In addition, immunochromatography (IC) kit features, DNA copy numbers and viral isolation of HAdV-54 in samples were evaluated. Recently, HAdV-37 and HAdV-54 have been the major causative types of EKC in Japan. HAdV-54 has been isolated each year since 1995, whereas HAdV-8 has become less common since 1997, although it remains the most common cause of EKC in the six other countries investigated where HAdV-54 is yet to be detected. HAdV-54 is comparable to other EKC-related HAdV types in terms of IC kit sensitivity and DNA copy numbers, although HAdV-54 grows more slowly on viral isolation. EKC due to HAdV-54 can result in epidemics; therefore, it should be accurately diagnosed and monitored as an emerging infection worldwide.

  18. The experience of two European preimplantation genetic diagnosis centres on human leukocyte antigen typing.

    Science.gov (United States)

    Van de Velde, Hilde; De Rycke, Martine; De Man, Caroline; De Hauwere, Kim; Fiorentino, Francesco; Kahraman, Semra; Pennings, Guido; Verpoest, Willem; Devroey, Paul; Liebaers, Inge

    2009-03-01

    Two European centres report on human leukocyte antigen (HLA) typing of preimplantation embryos for haematopoietic stem cell (HSC) transplantation: 'UZ Brussel' in Brussels and 'Genoma' in Rome. Both centres have 6 years' experience with technical and clinical aspects of this type of genetic analysis on single blastomeres. Both centres apply a similar technique for preimplantation HLA typing using short tandem repeats linked to the HLA locus in multiplex PCR for haplotyping. At present, a conclusive HLA diagnosis could be assured in 92.8% and 90.3% of the embryos at UZ Brussel and at Genoma, respectively. The implantation rates were 32.4% and 28.2%, respectively, and the birth rates per cycle were 9.4% and 18.6%, respectively. The HLA programme at UZ Brussel and at Genoma resulted in the birth of 9 babies and 3 successful HSC transplantations, and 42 babies and 7 successful HSC transplantations, respectively, so far. Drastic embryo selection for preimplantation HLA typing (in theory 1/4 for HLA, 1/8 for HLA in combination with sexing for X-linked recessive diseases, 3/16 for HLA in combination with autosomal recessive disorders) resulted overall in the birth of 51 babies (15.9% live birth rate per started cycle) in two European centres.

  19. Human papillomavirus type-specific prevalence in the cervical cancer screening population of Czech women.

    Directory of Open Access Journals (Sweden)

    Ruth Tachezy

    Full Text Available BACKGROUND: Infection with high-risk human papillomavirus (HPVtypes has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice. OBJECTIVES: The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV. METHODS: Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2 and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB. RESULTS: Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393 of women were positive for any HPV type by BS-RLB, 18.2% (254/1393 by HR HC2, and 22.3% (310/1393 by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%. HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years. CONCLUSIONS: Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future.

  20. Type I Interferon Contributes to CD4+ T Cell Depletion Induced by Infection with HIV-1 in the Human Thymus▿

    OpenAIRE

    Sivaraman, Vijay; Zhang, Liguo; Su, Lishan

    2011-01-01

    Persistent induction of type 1 interferon (IFN) is associated with human immunodeficiency virus type 1 (HIV-1) infection. We report here that the pathogenic HIV strain R3A (HIV-R3A) induced high levels of type 1 IFN, while the nonpathogenic HIV-R3B showed no significant induction in human fetal thymus organ culture (HFTOC). We found that IFN contributed to the depletion of human T cells by HIV-R3A in a fusion-independent fashion. The R3B recombinant with the R3A Env V1V2 domain (R3B/A-V1V2) w...

  1. Structure of human POFUT2: insights into thrombospondin type 1 repeat fold and O-fucosylation

    Science.gov (United States)

    Chen, Chun-I; Keusch, Jeremy J; Klein, Dominique; Hess, Daniel; Hofsteenge, Jan; Gut, Heinz

    2012-01-01

    Protein O-fucosylation is a post-translational modification found on serine/threonine residues of thrombospondin type 1 repeats (TSR). The fucose transfer is catalysed by the enzyme protein O-fucosyltransferase 2 (POFUT2) and >40 human proteins contain the TSR consensus sequence for POFUT2-dependent fucosylation. To better understand O-fucosylation on TSR, we carried out a structural and functional analysis of human POFUT2 and its TSR substrate. Crystal structures of POFUT2 reveal a variation of the classical GT-B fold and identify sugar donor and TSR acceptor binding sites. Structural findings are correlated with steady-state kinetic measurements of wild-type and mutant POFUT2 and TSR and give insight into the catalytic mechanism and substrate specificity. By using an artificial mini-TSR substrate, we show that specificity is not primarily encoded in the TSR protein sequence but rather in the unusual 3D structure of a small part of the TSR. Our findings uncover that recognition of distinct conserved 3D fold motifs can be used as a mechanism to achieve substrate specificity by enzymes modifying completely folded proteins of very wide sequence diversity and biological function. PMID:22588082

  2. Involvement of the angiotensin II type 2 receptor in apoptosis during human fetal adrenal gland development.

    Science.gov (United States)

    Chamoux, E; Breault, L; Lehoux, J G; Gallo-Payet, N

    1999-12-01

    The aim of this study was to establish a link between the highly expressed angiotensin II (Ang II) type 2 receptor (AT2) in human fetal adrenal cells and the proposed apoptotic activity in the center of the gland. There was an important increase in apoptotic DNA fragmentation with age in adrenal glands of fetuses from 15-20 weeks gestation. Adrenal cells showing the characteristic apoptotic internucleosomal DNA fragmentation were localized in the central portion of the fetal zone. In cells cultured for 24 h, Ang II, via the AT2 receptor, induced DNA fragmentation and cleavage of the DNA repair enzyme, poly-(ADP-ribose) polymerase. Furthermore, characteristic membrane blebbing was observed specifically on cells of the fetal zone. Immunofluorescence studies demonstrated that stimulation with Ang II or CGP 42112 (an agonist of the AT2 receptor) strongly modified the actin network, now localized exclusively along the plasma membrane, with a predominance of labeling at the base of the bleb formation. This rearrangement of actin distribution was different in cells from the definitive zone, corroborating the observation that these cells express many more Ang II type 1 receptors (AT1) than AT2 receptors. Taken together, our data indicate that the AT2 receptor is involved in the apoptotic process observed in the human fetal adrenal gland and could participate in the morphological changes occurring after birth, leading to involution of the fetal zone.

  3. Type 2 diabetes, obesity, and sex difference affect the fate of glucose in the human heart.

    Science.gov (United States)

    Peterson, Linda R; Herrero, Pilar; Coggan, Andrew R; Kisrieva-Ware, Zulia; Saeed, Ibrahim; Dence, Carmen; Koudelis, Deborah; McGill, Janet B; Lyons, Matthew R; Novak, Eric; Dávila-Román, Víctor G; Waggoner, Alan D; Gropler, Robert J

    2015-06-15

    Type 2 diabetes, obesity, and sex difference affect myocardial glucose uptake and utilization. However, their effect on the intramyocellular fate of glucose in humans has been unknown. How the heart uses glucose is important, because it affects energy production and oxygen efficiency, which in turn affect heart function and adaptability. We hypothesized that type 2 diabetes, sex difference, and obesity affect myocardial glucose oxidation, glycolysis, and glycogen production. In a first-in-human study, we measured intramyocardiocellular glucose metabolism from time-activity curves generated from previously obtained positron emission tomography scans of 110 subjects in 3 groups: nonobese, obese, and diabetes. Group and sex difference interacted in the prediction of all glucose uptake, utilization, and metabolism rates. Group independently predicted fractional glucose uptake and its components: glycolysis, glycogen deposition, and glucose oxidation rates. Sex difference predicted glycolysis rates. However, there were fewer differences in glucose metabolism between diabetic patients and others when plasma glucose levels were included in the modeling. The potentially detrimental effects of obesity and diabetes on myocardial glucose metabolism are more pronounced in men than women. This sex difference dimorphism needs to be taken into account in the design, trials, and application of metabolic modulator therapy. Slightly higher plasma glucose levels improve depressed glucose oxidation and glycogen deposition rates in diabetic patients. Copyright © 2015 the American Physiological Society.

  4. Human immunodeficiency virus type-2-A milder, kinder virus: An update

    Directory of Open Access Journals (Sweden)

    R Kannangai

    2012-01-01

    Full Text Available Human immunodeficiency virus type-2 (HIV-2 belongs to the family retroviridae which is phylogenetically clusters with SIV SM from sooty mangabeys. This virus is morphologically similar to human immunodeficiency virus type-1 (HIV-1 but has got only a 40% homology at the nucleotide level. There is a distinct geographical distribution of HIV-2 unlike HIV-1. There are currently eight subtypes/groups identified with subtype/group A responsible for the majority of infections. HIV-2 shows a considerable difference in the course of the disease. Clinical, haematological and immunological evaluation of individuals infected with HIV-2 has shown the virus to be less pathogenic than HIV-1 although the exact mechanism underlying this difference is not well defined. Similar to HIV-1, the HIV-2 isolates also showed distinct replicative and cytopathic characteristics. The transmission rate for HIV-2 compared to HIV-1 is very low both by heterosexual route and mother to child transmission. The clinical signs and symptoms of immunodeficiency associated with HIV-2 are similar to the ones seen among the HIV-1-infected individuals and they can also progress to AIDS. It is naturally resistant to NNRTI and hence the diagnosis become important as it affects the treatment strategy. Similar to HIV-1, HIV-2 strains of infected individuals also show mutations that can cause drug resistance. The current evidence suggests that there is no protective effective for HIV-2 against HIV-1.

  5. Effect of a human-type communication robot on cognitive function in elderly women living alone.

    Science.gov (United States)

    Tanaka, Masaaki; Ishii, Akira; Yamano, Emi; Ogikubo, Hiroki; Okazaki, Masatsugu; Kamimura, Kazuro; Konishi, Yasuharu; Emoto, Shigeru; Watanabe, Yasuyoshi

    2012-09-01

    Considering the high prevalence of dementia, it would be of great value to develop effective tools to improve cognitive function. We examined the effects of a human-type communication robot on cognitive function in elderly women living alone. In this study, 34 healthy elderly female volunteers living alone were randomized to living with either a communication robot or a control robot at home for 8 weeks. The shape, voice, and motion features of the communication robot resemble those of a 3-year-old boy, while the control robot was not designed to talk or nod. Before living with the robot and 4 and 8 weeks after living with the robot, experiments were conducted to evaluate a variety of cognitive functions as well as saliva cortisol, sleep, and subjective fatigue, motivation, and healing. The Mini-Mental State Examination score, judgement, and verbal memory function were improved after living with the communication robot; those functions were not altered with the control robot. In addition, the saliva cortisol level was decreased, nocturnal sleeping hours tended to increase, and difficulty in maintaining sleep tended to decrease with the communication robot, although alterations were not shown with the control. The proportions of the participants in whom effects on attenuation of fatigue, enhancement of motivation, and healing could be recognized were higher in the communication robot group relative to the control group. This study demonstrates that living with a human-type communication robot may be effective for improving cognitive functions in elderly women living alone.

  6. [THE COMPARATIVE ANALYSIS OF RESULTS OF DETECTION OF CARCINOGENIC TYPES OF HUMAN PAPILLOMA VIRUS BY QUALITATIVE AND QUANTITATIVE TESTS].

    Science.gov (United States)

    Kuzmenko, E T; Labigina, A V; Leshenko, O Ya; Rusanov, D N; Kuzmenko, V V; Fedko, L P; Pak, I P

    2015-05-01

    The analysis of results of screening (n = 3208; sexually active citizen aged from 18 to 59 years) was carried out to detect oncogene types of human papilloma virus in using qualitative (1150 females and 720 males) and quantitative (polymerase chain reaction in real-time (843 females and 115 males) techniques. The human papilloma virus of high oncogene type was detected in 65% and 68.4% of females and in 48.6% and 53% of males correspondingly. Among 12 types of human papilloma virus the most frequently diagnosed was human papilloma virus 16 independently of gender of examined and technique of analysis. In females, under application of qualitative tests rate of human papilloma virus 16 made up to 18.3% (n = 280) and under application of quantitative tests Rte of human papilloma virus made up to 14.9% (n = 126; p ≤ 0.05). Under examination of males using qualitative tests rate of human papilloma virus 16 made up to 8.3% (n = 60) and under application of qualitative tests made up to 12.2% (n = 14; p ≥ 0.05). Under application of qualitative tests rate of detection on the rest ofoncogene types of human papilloma virus varied in females from 3.4% to 8.4% and in males from 1.8% to 5.9%. Under application of qualitative tests to females rate of human papilloma virus with high viral load made up to 68.4%, with medium viral load - 2.85% (n = 24) and with low viral load -0.24% (n = 2). Under application of quantitative tests in males rate of detection of types of human papilloma virus made up to 53% and at that in all high viral load was established. In females, the most of oncogene types of human papilloma virus (except for 31, 39, 59) are detected significantly more often than in males.

  7. Species identification and molecular typing of human Brucella isolates from Kuwait.

    Science.gov (United States)

    Mustafa, Abu S; Habibi, Nazima; Osman, Amr; Shaheed, Faraz; Khan, Mohd W

    2017-01-01

    Brucellosis is a zoonotic disease of major concern in Kuwait and the Middle East. Human brucellosis can be caused by several Brucella species with varying degree of pathogenesis, and relapses are common after apparently successful therapy. The classical biochemical methods for identification of Brucella are time-consuming, cumbersome, and provide information limited to the species level only. In contrast, molecular methods are rapid and provide differentiation at intra-species level. In this study, four molecular methods [16S rRNA gene sequencing, real-time PCR, enterobacterial repetitive intergenic consensus (ERIC)-PCR and multilocus variable-number tandem-repeat analysis (MLVA)-8, MLVA-11 and MLVA-16 were evaluated for the identification and typing of 75 strains of Brucella isolated in Kuwait. 16S rRNA gene sequencing of all isolates showed 90-99% sequence identity with B. melitensis and real-time PCR with genus- and species- specific primers identified all isolates as B. melitensis. The results of ERIC-PCR suggested the existence of 75 ERIC genotypes of B. melitensis with a discriminatory index of 0.997. Cluster classification of these genotypes divided them into two clusters, A and B, diverging at ~25%. The maximum number of genotypes (n = 51) were found in cluster B5. MLVA-8 analysis identified all isolates as B. melitensis, and MLVA-8, MLVA-11 and MLVA-16 typing divided the isolates into 10, 32 and 71 MLVA types, respectively. Furthermore, the combined minimum spanning tree analysis demonstrated that, compared to MLVA types discovered all over the world, the Kuwaiti isolates were a distinct group of MLVA-11 and MLVA-16 types in the East Mediterranean Region.

  8. Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia.

    Science.gov (United States)

    Bosch, F Xavier; Burchell, Ann N; Schiffman, Mark; Giuliano, Anna R; de Sanjose, Silvia; Bruni, Laia; Tortolero-Luna, Guillermo; Kjaer, Susanne Kruger; Muñoz, Nubia

    2008-08-19

    Worldwide human papillomavirus (HPV) prevalence in women with normal cytology at any given point in time is approximately 10% indicating that HPV is one of the most common sexually transmitted infections. HPV-16 is consistently the most common type and HPV-18 the second with some minor regional differences. Furthermore, across the spectrum of cervical lesions, HPV-16 is consistently the most common HPV type contributing to 50-55% of invasive cervical cancer cases strongly suggesting that this viral type has a biological advantage for transmission, persistency and transformation. The same phenomenon is observed albeit at a lower level for HPV-18 and HPV-45. Sexual behavioral patterns across age groups and populations are central to the description of the HPV circulation and of the risk of infection. The concept of group sexual behavior (in addition to individual sexual behavior) is important in exploring HPV transmission and has implications for defining and monitoring HPV and cancer prevention strategies. In natural history studies, the pattern of HPV DNA prevalence by age groups is similar to the patterns of HPV incidence. Rates of exposure in young women are high and often include multiple types. There is a spontaneous and rapid decrease of the HPV DNA detection rates in the middle-age groups followed by a second rise in the post-menopausal years. This article reviews: 1) the evidence in relation to the burden of HPV infections in the world and the contributions of each HPV type to the spectrum of cervical cellular changes spanning from normal cytology to invasive cervical cancer; 2) the critical role of the patterns of sexual behavior in the populations; and 3) selected aspects of the technical and methodological complexity of natural history studies of HPV and cervical neoplasia.

  9. A single mutation in Taiwanese H6N1 influenza hemagglutinin switches binding to human-type receptors

    Energy Technology Data Exchange (ETDEWEB)

    de Vries, Robert P.; Tzarum, Netanel; Peng, Wenjie; Thompson, Andrew J.; Ambepitiya Wickramasinghe, Iresha N.; de la Pena, Alba T. Torrents; van Breemen, Marielle J.; Bouwman, Kim M.; Zhu, Xueyong; McBride, Ryan; Yu, Wenli; Sanders, Rogier W.; Verheije, Monique H.; Wilson, Ian A.; Paulson, James C.

    2017-07-10

    In June 2013, the first case of human infection with an avian H6N1 virus was reported in a Taiwanese woman. Although this was a single non-fatal case, the virus continues to circulate in Taiwanese poultry. As with any emerging avian virus that infects humans, there is concern that acquisition of human-type receptor specificity could enable transmission in the human population. Despite mutations in the receptor-binding pocket of the human H6N1 isolate, it has retained avian-type (NeuAcα2-3Gal) receptor specificity. However, we show here that a single nucleotide substitution, resulting in a change from Gly to Asp at position 225 (G225D), completely switches specificity to human-type (NeuAcα2-6Gal) receptors. Significantly, G225D H6 loses binding to chicken trachea epithelium and is now able to bind to human tracheal tissue. Structural analysis reveals that Asp225 directly interacts with the penultimate Gal of the human-type receptor, stabilizing human receptor binding.

  10. Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

    Science.gov (United States)

    Schally, Andrew V.; Block, Norman L; Dezso, Balazs; Olah, Gabor; Rozsa, Bernadett; Fodor, Klara; Buglyo, Armin; Gardi, Janos; Berta, Andras; Halmos, Gabor

    2013-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma. PMID:24077773

  11. Biomarkers for non-human primate type-I hypersensitivity: antigen-specific immunoglobulin E assays.

    Science.gov (United States)

    Clark, Darcey; Shiota, Faith; Forte, Carla; Narayanan, Padma; Mytych, Daniel T; Hock, M Benjamin

    2013-06-28

    Immunoglobulin E (IgE) is the least abundant immunoglobulin in serum. However, development of an IgE immune response can induce IgE receptor-expressing cells to carry out potent effector functions. A reliable antigen-specific IgE biomarker method for use in non-human primate studies would facilitate (i) confirmation of Type-I hypersensitivity reactions during safety toxicology testing, and (ii) a better understanding of non-human primate models of allergic disease. We cloned and expressed a recombinant cynomolgus monkey IgE molecule in order to screen a panel of commercially available detection reagents raised against human IgE for cross-reactivity. The reagent most reactive to cynomolgus IgE was confirmed to be specific for IgE and did not bind recombinant cynomolgus monkey IgG1-4. A drug-specific IgE assay was developed on the MSD electrochemiluminescent (ECL) platform. The assay is capable of detecting 10 ng/mL drug-specific IgE. Importantly, the assay is able to detect IgE in the presence of excess IgG, the scenario likely to be present in a safety toxicology study. Using our ECL assay, we were able to confirm that serum from cynomolgus monkeys that had experienced clinical symptoms consistent with hypersensitivity responses contained IgE specific for a candidate therapeutic antibody. In addition, a bioassay for mast cell activation was developed using CD34(+)-derived cynomolgus monkey mast cells. This assay confirmed that plasma from animals identified as positive in the drug-specific IgE immunoassay contained biologically active IgE (i.e. could sensitize cultured mast cells), resulting in histamine release after exposure to the therapeutic antibody. These sensitive assays for Type-I hypersensitivity in the NHP can confirm that secondary events are downstream of immunogenicity. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Quantitative Expression of C-Type Lectin Receptors in Humans and Mice

    Directory of Open Access Journals (Sweden)

    Hans-Joachim Anders

    2012-08-01

    Full Text Available C-type lectin receptors and their adaptor molecules are involved in the recognition of glycosylated self-antigens and pathogens. However, little is known about the species- and organ-specific expression profiles of these molecules. We therefore determined the mRNA expression levels of Dectin-1, MR1, MR2, DC-SIGN, Syk, Card-9, Bcl-10, Malt-1, Src, Dec-205, Galectin-1, Tim-3, Trem-1, and DAP-12 in 11 solid organs of human and mice. Mouse organs revealed lower mRNA levels of most molecules compared to spleen. However, Dec-205 and Galectin-1 in thymus, Src in brain, MR2, Card-9, Bcl-10, Src, and Dec-205 in small intestine, MR2, Bcl-10, Src, Galectin-1 in kidney, and Src and Galectin-1 in muscle were at least 2-fold higher expressed compared to spleen. Human lung, liver and heart expressed higher mRNA levels of most genes compared to spleen. Dectin-1, MR1, Syk and Trem-1 mRNA were strongly up-regulated upon ischemia-reperfusion injury in murine kidney. Tim3, DAP-12, Card-9, DC-SIGN and MR2 were further up-regulated during renal fibrosis. Murine kidney showed higher DAP-12, Syk, Card-9 and Dectin-1 mRNA expression during the progression of lupus nephritis. Thus, the organ-, and species-specific expression of C-type lectin receptors is different between mice and humans which must be considered in the interpretation of related studies.

  13. The structural and optical properties of type III human collagen biosynthetic corneal substitutes

    Science.gov (United States)

    Hayes, Sally; Lewis, Phillip; Islam, M. Mirazul; Doutch, James; Sorensen, Thomas; White, Tomas; Griffith, May; Meek, Keith M.

    2015-01-01

    The structural and optical properties of clinically biocompatible, cell-free hydrogels comprised of synthetically cross-linked and moulded recombinant human collagen type III (RHCIII) with and without the incorporation of 2-methacryloyloxyethyl phosphorylcholine (MPC) were assessed using transmission electron microscopy (TEM), X-ray scattering, spectroscopy and refractometry. These findings were examined alongside similarly obtained data from 21 human donor corneas. TEM demonstrated the presence of loosely bundled aggregates of fine collagen filaments within both RHCIII and RHCIII-MPC implants, which X-ray scattering showed to lack D-banding and be preferentially aligned in a uniaxial orientation throughout. This arrangement differs from the predominantly biaxial alignment of collagen fibrils that exists in the human cornea. By virtue of their high water content (90%), very fine collagen filaments (2–9 nm) and lack of cells, the collagen hydrogels were found to transmit almost all incident light in the visible spectrum. They also transmitted a large proportion of UV light compared to the cornea which acts as an effective UV filter. Patients implanted with these hydrogels should be cautious about UV exposure prior to regrowth of the epithelium and in-growth of corneal cells into the implants. PMID:26159106

  14. Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanisms.

    Directory of Open Access Journals (Sweden)

    Aprille Seidel

    2010-03-01

    Full Text Available Defensins are antimicrobial peptides expressed by plants and animals. In mammals there are three subfamilies of defensins, distinguished by structural features: alpha, beta and theta. Alpha and beta-defensins are linear peptides with broad anti-microbial activity that are expressed by many mammals including humans. In contrast, theta-defensins are cyclic anti-microbial peptides made by several non-human primates but not humans. All three defensin types have anti-HIV-1 activity, but their mechanisms of action differ. We studied the anti-HIV-1 activity of one defensin from each group, HNP-1 (alpha, HBD-2 (beta and RTD-1 (theta. We examined how each defensin affected HIV-1 infection and demonstrated that the cyclic defensin RTD-1 inhibited HIV-1 entry, while acyclic HNP-1 and HBD-2 inhibited HIV-1 replication even when added 12 hours post-infection and blocked viral replication after HIV-1 cDNA formation. We further found that all three defensins downmodulated CXCR4. Moreover, RTD-1 inactivated X4 HIV-1, while HNP-1 and HBD-2 inactivated both X4 and R5 HIV-1. The data presented here show that acyclic and cyclic defensins block HIV-1 replication by shared and diverse mechanisms. Moreover, we found that HNP-1 and RTD-1 directly inhibited firefly luciferase enzymatic activity, which may affect the interpretation of previously published data.

  15. The structural and optical properties of type III human collagen biosynthetic corneal substitutes.

    Science.gov (United States)

    Hayes, Sally; Lewis, Phillip; Islam, M Mirazul; Doutch, James; Sorensen, Thomas; White, Tomas; Griffith, May; Meek, Keith M

    2015-10-01

    The structural and optical properties of clinically biocompatible, cell-free hydrogels comprised of synthetically cross-linked and moulded recombinant human collagen type III (RHCIII) with and without the incorporation of 2-methacryloyloxyethyl phosphorylcholine (MPC) were assessed using transmission electron microscopy (TEM), X-ray scattering, spectroscopy and refractometry. These findings were examined alongside similarly obtained data from 21 human donor corneas. TEM demonstrated the presence of loosely bundled aggregates of fine collagen filaments within both RHCIII and RHCIII-MPC implants, which X-ray scattering showed to lack D-banding and be preferentially aligned in a uniaxial orientation throughout. This arrangement differs from the predominantly biaxial alignment of collagen fibrils that exists in the human cornea. By virtue of their high water content (90%), very fine collagen filaments (2-9 nm) and lack of cells, the collagen hydrogels were found to transmit almost all incident light in the visible spectrum. They also transmitted a large proportion of UV light compared to the cornea which acts as an effective UV filter. Patients implanted with these hydrogels should be cautious about UV exposure prior to regrowth of the epithelium and in-growth of corneal cells into the implants. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Of decentralization of public power Ukrainian land that belonged to Lithuanian (XIII – the early XVII century

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    C. V. Manuilova

    2016-06-01

    Full Text Available A comprehensive crisis in Ukraine and continued military confrontation in the Donbass demonstrated the urgent need to establish effective governance, which would imply decentralization of public power. Note that in implementing the decentralization of power in Ukraine insists the International Monetary Fund; United Nations Development Program; the transfer of authority to the field and decentralization of power in Ukraine is one of the points of the Minsk agreements and obligations of Ukraine to the EU. The article deals with the Ukrainian lands topical issue features the decentralization of public power in the XIII - the beginning of XVII century. The importance of the topic due to the need to study the historical experience of the implementation of decentralization. It was, emphasized that the success of the reforms depends largely because of the historical experience and features of the decentralization of public power in the past. Characterized by the development of local government in the Ukrainian lands was part of the Lithuanian state. The purpose of the article is to clarify the characteristics of decentralization of public authority on Ukrainian lands were part of the Lithuanian state during the XVII century XIII. To address this goal, outline decentralization of public power in the state; analyze, competence of local government in the Ukrainian lands that belonged to the Lith uanian State; determine how close to the power of the people. The level of decentralization of public power in the Grand Duchy of Lithuania in the XIII - the beginning of XVII century was high. It was, found that Lithuania had not established a centralized state. It is, noted that the Board of the nobility limited the princely power. The effect of delegated deputies from different parts of the Lithuanian statehood solutions nobility Council.Clarified the facts that confirm the existence of decentralization of public power in Lithuania: the functioning of local

  17. Effect of propionyl-L-carnitine on L-type calcium channels in human heart sarcolemma

    Energy Technology Data Exchange (ETDEWEB)

    Bevilacqua, M.; Vago, T.; Norbiato, G. (Servizio di Endocrinologia, Milano, (Italy))

    1991-02-01

    Propionyl-L-carnitine (PC) protects perfused rat hearts against damage by ischemia-reperfusion. Activation of L-type calcium channel play a role on ischemia-reperfusion damage. Therefore, we studied the effect of PC on some properties of L-type calcium channels in an in vitro preparation from human myocardium sarcolemma (from patients with idiopathic dilated cardiomyopathy). Binding of the L-type calcium channel blockers isradipine ({sup 3}H)-PN 200-110 (PN) to plasma membrane preparations revealed a single population of binding sites (total number: Bmax = 213 +/- 34 fM/mg protein and affinity: Kd = 152 +/- 19 nM; n = 6). The characteristics of these binding sites were evaluated in the presence and in the absence of Ca{sup 2}{sup +} and of calcium blockers (D-888, a verapamillike drug, and diltiazem). Incubation in a Ca{sup 2}{sup +}-containing buffer increased the affinity of PN binding sites. Binding sites for PN were modulated by organic calcium channel blockers; in competition isotherms at 37{degree}C, D-888 (desmethoxyverapamil) decreased the PN binding, whereas diltiazem increased it. These results strongly suggest that the site labelled by PN is the voltage-operated calcium channel of the human myocardium. The addition of PC (1 mM) to plasma membranes labelled with PN at 37{degree}C decreased the affinity of the binding; this effect was counteracted by the addition of Ca{sup 2}{sup +} to the medium. This result was consistent with a competition between Ca{sup 2}{sup +} and PC. The effect of PC incubation at 4{degree}C was the opposite; at this temperature PC increased the affinity of the binding sites and the effect was obscured by Ca{sup 2}{sup +}.

  18. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults.

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    Nadja Larsen

    Full Text Available BACKGROUND: Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control. METHODS AND FINDINGS: The study included 36 male adults with a broad range of age and body-mass indices (BMIs, among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR and in a subgroup of subjects (N = 20 by tag-encoded amplicon pyrosequencing of the V4 region of the 16S rRNA gene. The proportions of phylum Firmicutes and class Clostridia were significantly reduced in the diabetic group compared to the control group (P = 0.03. Furthermore, the ratios of Bacteroidetes to Firmicutes as well as the ratios of Bacteroides-Prevotella group to C. coccoides-E. rectale group correlated positively and significantly with plasma glucose concentration (P = 0.04 but not with BMIs. Similarly, class Betaproteobacteria was highly enriched in diabetic compared to non-diabetic persons (P = 0.02 and positively correlated with plasma glucose (P = 0.04. CONCLUSIONS: The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to control metabolic diseases by modifying the gut microbiota.

  19. Wnt activation by wild type and mutant myocilin in cultured human trabecular meshwork cells.

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    Xiang Shen

    Full Text Available Myocilin is a gene linked to the most prevalent form of glaucoma, a major blinding disease. The trabecular meshwork (TM, a specialized eye tissue, is believed to be involved, at least in part, in the development of glaucoma. The Pro³⁷⁰ to Leu (P370L mutation of myocilin is associated with severe glaucoma phenotypes and Gln³⁶⁸ stop (Q368X is the most common myocilin mutation reported. Myocilin, upon overexpression, has been shown to induce phenotypes that include a loss of actin stress fibers, an increase in the cAMP level and protein kinase A (PKA activity, as well as a reduction in the RhoA activity. We examined herein whether Wnt signaling pathway is involved in the myocilin phenotypes and whether P370L and Q368X mutants also display biological effects similar to those of the wild type myocilin.Wild type myocilin, when transfected into cultured human TM cells, induced a loss of actin stress fibers as judged by phalloidin staining. Such a loss was averted by treatment of secreted Frizzled-related protein 1 (sFRP1, an inhibitor of Wnt signaling. Consistent with the notion that Wnt pathway mediates the myocilin phenotype, Wnt activation was demonstrated by TOP/FOP-Flash reporter assays. Treatment of human TM cells of a Wnt activator, SB216763, as well as transfection of myocilin P370L and Q368X mutants all resulted in actin stress fiber loss, PKA activation and RhoA inactivation. The PKA elevation was obviated by the sFRP1 treatment, indicating that Wnt signaling was upstream that of PKA.The present study demonstrated that following forced expression of wild type myocilin, Wnt was activated, triggering in turn other myocilin-related alterations. P370L and Q368X mutations induced similar phenotypes, suggesting one possible mechanism how the mutants may lead to TM cell damage and pathology.

  20. Dot/Icm Type IVB Secretion System Requirements for Coxiella burnetii Growth in Human Macrophages

    Science.gov (United States)

    Beare, Paul A.; Gilk, Stacey D.; Larson, Charles L.; Hill, Joshua; Stead, Christopher M.; Omsland, Anders; Cockrell, Diane C.; Howe, Dale; Voth, Daniel E.; Heinzen, Robert A.

    2011-01-01

    ABSTRACT Central to Q fever pathogenesis is replication of the causative agent, Coxiella burnetii, within a phagolysosome-like parasitophorous vacuole (PV) in mononuclear phagocytes. C. burnetii modulates PV biogenesis and other host cell functions, such as apoptotic signaling, presumably via the activity of proteins delivered to the host cytosol by a Dot/Icm type IVB secretion system (T4BSS). In this study, we utilized a C. burnetii strain carrying IcmD inactivated by the Himar1 transposon to investigate the requirements for Dot/Icm function in C. burnetii parasitism of human THP-1 macrophage-like cells. The icmD::Tn mutant failed to secrete characterized T4BSS substrates, a defect that correlated with deficient replication, PV development, and apoptosis protection. Restoration of type IVB secretion and intracellular growth of the icmD::Tn mutant required complementation with icmD, -J, and -B, indicating a polar effect of the transposon insertion on downstream dot/icm genes. Induction of icmDJB expression at 1 day postinfection resulted in C. burnetii replication and PV generation. Collectively, these data prove that T4BSS function is required for productive infection of human macrophages by C. burnetii. However, illustrating the metabolic flexibility of C. burnetti, the icmD::Tn mutant could replicate intracellularly when sequestered in a PV generated by wild-type bacteria, where Dot/Icm function is provided in trans, and within a phenotypically similar PV generated by the protozoan parasite Leishmania amazonensis, where host cells are devoid of Dot/Icm T4BSS effector proteins. PMID:21862628

  1. Epigenetic regulation of normal human mammary cell type-specific miRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Vrba, Lukas [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Inst. of Plant Molecular Biology, Ceske Budejovice (Czech Republic). Biology Centre ASCR; Garbe, James C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Stampfer, Martha R. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Futscher, Bernard W. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center and Dept. of Pharmacology & Toxicology

    2011-08-26

    Epigenetic mechanisms are important regulators of cell type–specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type–specific pattern of expression that was linked to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type–specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type–specific miRNA expression.

  2. Impacts of pavement types on in-vehicle noise and human health.

    Science.gov (United States)

    Li, Qing; Qiao, Fengxiang; Yu, Lei

    2016-01-01

    Noise is a major source of pollution that can affect the human physiology and living environment. According to the World Health Organization (WHO), an exposure for longer than 24 hours to noise levels above 70 dB(A) may damage human hearing sensitivity, induce adverse health effects, and cause anxiety to residents nearby roadways. Pavement type with different roughness is one of the associated sources that may contribute to in-vehicle noise. Most previous studies have focused on the impact of pavement type on the surrounding acoustic environment of roadways, and given little attention to in-vehicle noise levels. This paper explores the impacts of different pavement types on in-vehicle noise levels and the associated adverse health effects. An old concrete pavement and a pavement with a thin asphalt overlay were chosen as the test beds. The in-vehicle noise caused by the asphalt and concrete pavements were measured, as well as the drivers' corresponding heart rates and reported riding comfort. Results show that the overall in-vehicle sound levels are higher than 70 dB(A) even at midnight. The newly overlaid asphalt pavement reduced in-vehicle noise at a driving speed of 96.5 km/hr by approximately 6 dB(A). Further, on the concrete pavement with higher roughness, driver heart rates were significantly higher than on the asphalt pavement. Drivers reported feeling more comfortable when driving on asphalt than on concrete pavement. Further tests on more drivers with different demographic characteristics, along highways with complicated configurations, and an examination of more factors contributing to in-vehicle noise are recommended, in addition to measuring additional physical symptoms of both drivers and passengers. While there have been many previous noise-related studies, few have addressed in-vehicle noise. Most studies have focused on the noise that residents have complained about, such as neighborhood traffic noise. As yet, there have been no complaints by

  3. Functional proteomics screen enables enrichment of distinct cell types from human pancreatic islets.

    Directory of Open Access Journals (Sweden)

    Revital Sharivkin

    Full Text Available The current world-wide epidemic of diabetes has prompted attempts to generate new sources of insulin-producing cells for cell replacement therapy. An inherent challenge in many of these strategies is the lack of cell-surface markers permitting isolation and characterization of specific cell types from differentiating stem cell populations. Here we introduce an iterative proteomics procedure allowing tag-free isolation of cell types based on their function. Our method detects and associates specific cell-surface markers with particular cell functionality by coupling cell capture on antibody arrays with immunofluorescent labeling. Using this approach in an iterative manner, we discovered marker combinations capable of enriching for discrete pancreatic cell subtypes from human islets of Langerhans: insulin-producing beta cells (CD9high/CD56+, glucagon-producing alpha cells (CD9-/CD56+ and trypsin-producing acinar cells (CD9-/CD56-. This strategy may assist future beta cell research and the development of diagnostic tools for diabetes. It can also be applied more generally for function-based purification of desired cell types from other limited and heterogeneous biological samples.

  4. Human type VII collagen: cDNA cloning and chromosomal mapping of the gene

    Energy Technology Data Exchange (ETDEWEB)

    Parente, M.G.; Chung, L.C.; Ryynaenen, J.; Monli Chu; Uitto, J. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Woodley, D.T.; Wynn, K.C.; Bauer, E.A. (Stanford Univ., CA (United States)); Mattei, M.G. (Institute National de la Sante et de la Recherche Medicale, Marseille (France))

    1991-08-15

    A human keratinocyte cDNA expression library in bacteriophage {lambda}gt11 was screened with the purified IgG fraction of serum from a patient with epidermolysis bullosa acquisita, which had a high titer of anti-type VII collagen antibodies. Screening of {approx}3 {times} 10{sup 5} plaques identified 8 positive clones, the largest one (K-131) being {approx}1.9 kilobases in size. Dideoxynucleotide sequencing of K-131 indicated that it consisted of 1875 base pairs and contained an open reading frame coding for a putative N-terminal noncollagenous domain of 439 amino acids and a collagenous domain was characterized by repeating Gly-Xaa-Yaa sequences that were interrupted in several positions by insertions or deletions of 1-3 amino acids. The deduced amino acid sequence also revealed a peptide segment that had a high degree of identity with a published type VII collagen protein sequence. The results mapped the COL7A1 to the locus 3p21. The cDNA clones characterized in this study will be valuable for understanding the protein structure and gene expression of type VII collagen present in anchoring fibrils and its aberrations in the dystrophic forms of heritable epidermolysis bullosa.

  5. Localized-statistical quantification of human serum proteome associated with type 2 diabetes.

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    Rong-Xia Li

    Full Text Available BACKGROUND: Recent advances in proteomics have shed light to discover serum proteins or peptides as biomarkers for tracking the progression of diabetes as well as understanding molecular mechanisms of the disease. RESULTS: In this work, human serum of non-diabetic and diabetic cohorts was analyzed by proteomic approach. To analyze total 1377 high-confident serum-proteins, we developed a computing strategy called localized statistics of protein abundance distribution (LSPAD to calculate a significant bias of a particular protein-abundance between these two cohorts. As a result, 68 proteins were found significantly over-represented in the diabetic serum (p<0.01. In addition, a pathway-associated analysis was developed to obtain the overall pathway bias associated with type 2 diabetes, from which the significant over-representation of complement system associated with type 2 diabetes was uncovered. Moreover, an up-stream activator of complement pathway, ficolin-3, was observed over-represented in the serum of type 2 diabetic patients, which was further validated with statistic significance (p = 0.012 with more clinical samples. CONCLUSIONS: The developed LSPAD approach is well fit for analyzing proteomic data derived from biological complex systems such as plasma proteome. With LSPAD, we disclosed the comprehensive distribution of the proteins associated with diabetes in different abundance levels and the involvement of ficolin-related complement activation in diabetes.

  6. Neurotransmitter signalling via NMDA receptors leads to decreased T helper type 1-like and enhanced T helper type 2-like immune balance in humans.

    Science.gov (United States)

    Orihara, Kanami; Odemuyiwa, Solomon O; Stefura, William P; Ilarraza, Ramses; HayGlass, Kent T; Moqbel, Redwan

    2018-03-01

    Given the pivotal roles that CD4 + T cell imbalance plays in human immune disorders, much interest centres on better understanding influences that regulate human helper T-cell subset dominance in vivo. Here, using primary CD4 + T cells and short-term T helper type 1 (Th1) and Th2-like lines, we investigated roles and mechanisms by which neurotransmitter receptors may influence human type 1 versus type 2 immunity. We hypothesized that N-methyl-d-aspartate receptors (NMDA-R), which play key roles in memory and learning, can also regulate human CD4 + T cell function through induction of excitotoxicity. Fresh primary CD4 + T cells from healthy donors express functional NMDA-R that are strongly up-regulated upon T cell receptor (TCR) mediated activation. Synthetic and physiological NMDA-R agonists elicited Ca 2+ flux and led to marked inhibition of type 1 but not type 2 or interleukin-10 cytokine responses. Among CD4 + lines, NMDA and quinolinic acid preferentially reduced cytokine production, Ca 2+ flux, proliferation and survival of Th1-like cells through increased induction of cell death whereas Th2-like cells were largely spared. Collectively, the findings demonstrate that (i) NMDA-R is rapidly up-regulated upon CD4 + T cell activation in humans and (ii) Th1 versus Th2 cell functions such as proliferation, cytokine production and cell survival are differentially affected by NMDA-R agonists. Differential cytokine production and proliferative capacity of Th1 versus Th2 cells is attributable in part to increased physiological cell death among fully committed Th1 versus Th2 cells, leading to increased Th2-like dominance. Hence, excitotoxicity, beyond its roles in neuronal plasticity, may contribute to ongoing modulation of human T cell responses. © 2017 John Wiley & Sons Ltd.

  7. The E2 binding sites determine the efficiency of replication for the origin of human papillomavirus type 18.

    OpenAIRE

    Remm, M.; Brain, R.; Jenkins, J R

    1992-01-01

    Human papillomaviruses (HPV-s) have been shown to possess transforming and immortalizing activity for many different, mainly keratinocyte cell lines and they have been detected in 90% of anogenital cancer tissues, which suggests a causative role in the induction of anogenital and other tumours. We have exploited a quantitative assay to identify and characterize the origin of replication of the human papillomavirus type 18 (HPV-18), one of the most prevalent types in the high-risk HPV group. R...

  8. Human papillomavirus (HPV prevalence and types among Turkish women at a gynecology outpatient unit

    Directory of Open Access Journals (Sweden)

    Dursun Polat

    2009-01-01

    Full Text Available Abstract Background Human Papillomavirus (HPV is a well-known pathogen for lower genital tract neoplasias, yet little is known regarding HPV prevalence in Turkey. The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among women with normal and abnormal cytology. Methods A total of five hundred seven (n = 507 women were retrospectively evaluated between 2004-2008. Conventional polymerase chain reaction was used to detect the presence of HPV types in cervicovaginal samples obtained from patients during gynecologic examination. Results One hundred four (n = 104 of the women were excluded from the study because of the incomplete data and a total of 403 women were used for the final analysis. There were, 93 (23% women with cytologic abnormality and 310 (77% women with normal cytology. Overall, 23% of the women was HPV positive. The overall prevalence of HPV in women with abnormal Pap smears was 36% (93/403, of which in ASCUS 22%, LSIL 51% and HSIL 60%. Also, HPV DNA was positive in 20% of the women with normal cervical cytology. The most common HPV types in cytologically normal women were as follows; HPV 16 (36%, HPV 6 (22% and HPV 18 (13%. The rate of other HPV types were as follows; HPV11 4.4%, HPV45 4.4%, HPV90 4.4%, HPV35 2.2%, HPV67 2.2%, HPV81 2.2%, and multiple type HPVs 8.9%. The most common HPV types in cytologically abnormal women were HPV 16 (35%, HPV6 (19% and HPV18 (8%. The rate of multiple HPV infections in women with normal Pap test was 2.2%. Conclusion HPV prevalence and type distribution in this study were similar to that reported worldwide at least in our study population. Hovewer, HPV prevalence was more common compared with previous studies reported from Turkey. This might be related with methodology and hospital based patient accrual and high rate of women with abnormal cytology. Further population based prospective studies are needed to eliminate the drawbacks of our study

  9. Type 2 Diabetes Risk Alleles Demonstrate Extreme Directional Differentiation among Human Populations, Compared to Other Diseases

    Science.gov (United States)

    Chen, Rong; Corona, Erik; Sikora, Martin; Dudley, Joel T.; Morgan, Alex A.; Moreno-Estrada, Andres; Nilsen, Geoffrey B.; Ruau, David; Lincoln, Stephen E.; Bustamante, Carlos D.; Butte, Atul J.

    2012-01-01

    Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D) demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may contribute to the observed

  10. Direct Phenotypical and Functional Dysregulation of Primary Human B Cells by Human Immunodeficiency Virus (HIV) Type 1 In Vitro

    Science.gov (United States)

    Perisé-Barrios, Ana Judith; Muñoz-Fernandez, María Ángeles; Pion, Marjorie

    2012-01-01

    Background Human immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. Methods/Principal Findings We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID) mRNA that is responsible for class switch recombination (CSR) and somatic hypermutation (SHM). Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro. Conclusion/Significance We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease. PMID:22768302

  11. Direct phenotypical and functional dysregulation of primary human B cells by human immunodeficiency virus (HIV) type 1 in vitro.

    Science.gov (United States)

    Perisé-Barrios, Ana Judith; Muñoz-Fernandez, María Ángeles; Pion, Marjorie

    2012-01-01

    Human immunodeficiency virus type 1 (HIV-1) induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID) mRNA that is responsible for class switch recombination (CSR) and somatic hypermutation (SHM). Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro. We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease.

  12. Direct phenotypical and functional dysregulation of primary human B cells by human immunodeficiency virus (HIV type 1 in vitro.

    Directory of Open Access Journals (Sweden)

    Ana Judith Perisé-Barrios

    Full Text Available BACKGROUND: Human immunodeficiency virus type 1 (HIV-1 induces a general dysregulation of immune system. Dysregulation of B cell compartment is generally thought to be induced by HIV-related immune activation and lymphopenia. However, a direct influence of HIV-1 particles on B cells was recently proposed as the third pathway of B cells dysregulation. METHODS/PRINCIPAL FINDINGS: We evaluated the direct and specific consequences of HIV-1 contact on activation, survival, proliferation and phenotype of primary B cells in vitro. Moreover, we examined expression of activation-induced cytidine deaminase (AID mRNA that is responsible for class switch recombination (CSR and somatic hypermutation (SHM. Here, we report that changes observed in cellular proliferation, phenotypes and activation of B cells could be caused by direct contact between HIV-1 particles and primary B cells in vitro. Finally, direct HIV-1-derived B cells activation led to the increase of AID mRNA expression and its subsequent CSR function was detected in vitro. CONCLUSION/SIGNIFICANCE: We showed that HIV-1 could directly induce primary B cells dysregulation triggering phenotypical and functional abilities of B cells in vitro that could explain in some extent early B-cell abnormalities in HIV disease.

  13. Fetal antigen 2: an amniotic protein identified as the aminopropeptide of the alpha 1 chain of human procollagen type I

    DEFF Research Database (Denmark)

    Teisner, B; Rasmussen, H B; Højrup, P

    1992-01-01

    with the aminopropeptide of the alpha 1 chain of human procollagen type I as determined by nucleotide sequences. After oxidative procedures normally employed for radio-iodination (iodogen and chloramine-T), FA2 lost its immunoreactivity. An antigen which cross-reacted with polyclonal rabbit anti-human FA2 was demonstrated...... in fetal calf serum. Gel filtration with analysis of fractions by inhibition ELISA showed that the bovine homologue was present in the same molecular forms as those in human amniotic fluid, and immunohistochemical analysis with anti-human FA2 showed that its distribution in bovine skin was identical...... to that of FA2 in human skin. FA2 is a circulating form of the aminopropeptide of the alpha 1 chain of procollagen type I, and this is the first description of its isolation and structural characterization in humans. Udgivelsesdato: 1992-Dec...

  14. Phage types of Salmonella enterica ssp. enterica serovar Typhimurium isolated from production animals and humans in Denmark

    DEFF Research Database (Denmark)

    Baggesen, Dorte Lau; Wegener, Henrik Caspar

    1994-01-01

    S. Typhimurium is one of the 2 most common salmonella serotypes causing human salmonellosis in Denmark. In order to illustrate the significance of different production animals as a source of infection, 1461 isolates were characterized by phage typing. The isolates originated from human patients...

  15. The human immunodeficiency virus-reverse transcriptase inhibition activity of novel pyridine/pyridinium-type fullerene derivatives.

    Science.gov (United States)

    Yasuno, Takumi; Ohe, Tomoyuki; Takahashi, Kyoko; Nakamura, Shigeo; Mashino, Tadahiko

    2015-08-15

    In the present study, we describe the synthesis of a novel set of pyridine/pyridinium-type fullerene derivatives. The products were assessed for human immunodeficiency virus-reverse transcriptase inhibition activities. All novel fullerene derivatives showed potent human immunodeficiency virus-reverse transcriptase inhibition without cytotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Rapid, sensitive, type specific PCR detection of the E7 region of human papillomavirus type 16 and 18 from paraffin embedded sections of cervical carcinoma

    DEFF Research Database (Denmark)

    Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Steven

    2010-01-01

    ABSTRACT: Human papillomavirus (HPV) infection, and in particularly infection with HPVs 16 and 18, is a central carcinogenic factor in the uterine cervix. We established and optimized a PCR assay for the detection and discrimination of HPV types 16 and 18 in archival formaldehyde fixed and paraffin...

  17. Rapid, sensitive, type specific PCR detection of the E7 region of human papillomavirus type 16 and 18 from paraffin embedded sections of cervical carcinoma

    DEFF Research Database (Denmark)

    Lesnikova, Iana; Lidang, Marianne; Hamilton-Dutoit, Stephen Jacques

    2010-01-01

    ABSTRACT: Human papillomavirus (HPV) infection, and in particularly infection with HPVs 16 and 18 is a central carcinogenic factor in the uterine cervix. We established and optimized a PCR assay for the detection and discrimination of HPV types 16 and 18 in archival formaldehyde fixed and paraffin...

  18. El arte del bordado en Navarra en los siglos XVI y XVII: Andrés de Salinas

    Directory of Open Access Journals (Sweden)

    Andueza Pérez, Alicia

    2003-09-01

    Full Text Available Given its classification as a decorative art, and its perception as mere artisanal work, scarce attention has been given to embroidery. Nevertheless, fortunately, in recent years there has been a resurgence of studies on this theme. This article, following these new trends, attempts to clarify certain aspects of this activity in the Navarre region during the sixteenth and seventeenth centuries.

    Dada su condición de arte decorativa, y su consideración como una labor meramente artesanal, la atención que se le ha prestado al bordado es escasa. Por suerte, en los últimos años estamos asistiendo a un resurgir de los estudios sobre el tema. Este artículo, siguiendo estas nuevas tendencias, pretende esclarecer algunos aspectos sobre esta actividad en la Navarra de los siglos XVI y XVII.

  19. La difusión de la poesía española impresa en el siglo XVII

    OpenAIRE

    Dadson, Trevor J.

    2013-01-01

    Depuis la publication en 1968 de Construcción crítica y realidad histórica en la poesía española de los siglos XVI y XVII de Antonio Rodríguez-Moñino, l’idée que la voie de transmission de la poésie à cette époque passait essentiellement par la copie manuscrite a été communément acceptée. L’inconvénient majeur de la thèse de Rodríguez-Moñino est de faire porter toute l’attention sur la diffusion manuscrite de l’œuvre poétique au détriment du rôle joué par l’imprimerie. L’examen des imprimerie...

  20. El clero y el delito de proposiciones en Zacatecas: los errores manifestados en los sermones, siglos XVI y XVII

    Directory of Open Access Journals (Sweden)

    Georgina Quiñones Flores

    2014-04-01

    Full Text Available El delito de proposiciones consistía en las expresiones que refl ejaban puntos contrarios con la doctrina de la Iglesia católica. Por ello, pertenecía a la jurisdicción del Santo Ofi cio, que recibió denuncias incluso contra el clero por cometer esta transgresión, sobre todo durante los sermones, por lo que se cree que causaban confusión entre los oyentes. Pero ¿realmente provocaban escándalo entre la población o solo entre los eclesiásticos?, ¿acaso se trataba de errores de entendimiento por la poca instrucción de los predicadores?, o ¿se usaba el púlpito para expresar los confl ictos de la Iglesia? A estas preguntas se les dará respuesta en este texto, que se ubica en Zacatecas en los siglos XVI y XVII.

  1. Laser-based systems for the structural diagnostic of artwork: an application to XVII-century Byzantine icons

    Science.gov (United States)

    Tornari, Vivi; Bonarou, Antonia; Castellini, Paolo; Esposito, Enrico; Osten, Wolfgang; Kalms, Michael K.; Smyrnakis, Nikos; Stasinopulos, Stergios

    2001-10-01

    Laser diagnostic systems based on shearography, vibrometry, and holography principles were employed to investigate the potential implementation of laser techniques in art conservation structural diagnostic field. The employed techniques offered the required measuring variability to allow a first discrimination on complex diagnostic uncertainties encountered often in art conservation. The systems were tested and used to assess the structural condition of well-documented Byzantine icons with known structural problems. Defects and mechanical deformations were identified in various distances from the artworks by alternative employment of techniques. In this way simultaneous eligibility classification of the used systems was also obtained. Results of the on-field application on the XVII century Byzantine icons are herein presented with discussion on the prospects of the techniques in the diagnostic field of art conservation.

  2. Prevalence of HIV, human papillomavirus type 16 and herpes simplex virus type 2 among female sex workers in Guinea and associated factors.

    Science.gov (United States)

    Aho, Joséphine; Koushik, Anita; Coutlée, François; Diakité, Soumaïla Laye; Rashed, Sélim

    2014-03-01

    Female sex workers are at high risk for HIV infection. Sexually transmitted infections are known to be co-factors for HIV infection. Our aims were (1) to assess the prevalence of HIV and other sexually transmitted infections in this population; (2) to determine the association between sociodemographic characteristics, behavioural variables, and variables related to HIV prevention and HIV infection. A cross-sectional study was conducted in Conakry, Guinea, among a convenience sample of 223 female sex workers. A questionnaire on sociodemographic characteristics, risk factors, and exposure to prevention was administered. Screening for HIV, herpes simplex virus type 2, human papillomavirus type 16, Neisseria gonorrhoeae, and Chlamydia trachomatis was performed. Prevalences of HIV, herpes simplex virus type 2, human papillomavirus type 16, N. gonorrhoeae, and C. trachomatis were 35.3%, 84.1%, 12.2%, 9.0%, and 13.6%, respectively. Having a child, lubricant use, and human papillomavirus type 16 infection were associated with HIV infection. Interventions that promote screening and treatment of sexually transmitted infections are needed in order to achieve successful interventions to prevent HIV among female sex workers in resource-limited settings.

  3. Human papillomavirus type 16 and TP53 mutation in oral cancer: matched analysis of the IARC multicenter study.

    NARCIS (Netherlands)

    Dai, M; Clifford, GM; Calvez, F le; Castellsague, X; Snijders, P.J.F.; Pawlita, M; Herrero, R; Hainaut, P; Franceschi, S

    2004-01-01

    TP53 mutations were analyzed in 35 human papillomavirus (HPV) type 16 DNA-positive cancers of the oral cavity and oropharynx and in 35 HPV DNA-negative cancers matched by subsite, country, sex, age, and tobacco and alcohol consumption. Wild-type TP53 was found more frequently in cancer specimens

  4. Prevalence and Type Distribution of Human Papillomavirus Among 1813 Men in Tanzania and the Relationship to HIV Status

    DEFF Research Database (Denmark)

    Olesen, Tina Bech; Iftner, Thomas; Mwaiselage, Julius

    2013-01-01

    Infection with high-risk (HR) human papillomavirus (HPV) is associated with penile cancer in men, cervical cancer in women, and anal cancer and certain types of head and neck cancers in both sexes. Few studies have assessed the prevalence and type distribution of HPV among men in sub-Saharan Africa...

  5. Role of TGF-beta1 in relation to exercise-induced type I collagen synthesis in human tendinous tissue

    DEFF Research Database (Denmark)

    Heinemeier, Katja; Langberg, Henning; Olesen, Jens L

    2003-01-01

    Mechanical loading of tissue is known to influence local collagen synthesis, and microdialysis studies indicate that mechanical loading of human tendon during exercise elevates tendinous type I collagen production. Transforming growth factor-beta1 (TGF-beta1), a potent stimulator of type I collagen...

  6. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, M. P.; van Leeuwen, A. M.; Hollema, H.; Quint, W. G.; Pieters, W. J.

    1997-01-01

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  7. Human papillomavirus type influences the extent of chromosomal lag during mitosis in cervical intraepithelial neoplasia grade III

    NARCIS (Netherlands)

    Burger, MPM; VanLeeuwen, AM; Hollema, H; Quint, WGV; Pieters, WJLM

    The level of risk for carcinoma in the uterine cervix depends on the type of human papillomavirus (HPV) present. We examined whether the HPV type influences the proliferation rate and occurrence of mitotic figures with lagging chromosomes in the precursor of cervical carcinoma. The study group

  8. Municipio y mercado en el Aragón moderno : el abasto de carne en Zaragoza (siglos XVI-XVII

    Directory of Open Access Journals (Sweden)

    José Antonio Mateos Royo

    2003-01-01

    Full Text Available Estudio relativo a la política desarrollada por el Concejo de Zaragoza sobre el mercado de carne durante los siglos XVI y XVII. La prosperidad económica del reino de Aragón, la ciudad y municipio de Zaragoza durante el siglo XVI permitieron aumentar el control público sobre las transacciones de carne para asegurar a la población un suministro suficiente, así como sustentar la demanda local. Sin embargo, el declive económico del reino de Aragón y el creciente endeudamiento municipal durante el siglo XVII obligaron a reducir la presencia pública en el mercado y la defensa de la demanda local en el mercado de carne. El reajuste de la política municipal promovió la paulatina integración del mercado aragonés, proceso que continuó en el siglo XVIII para afianzarse durante la crisis final del Antiguo Régimen.This paper studies municipal politics carried out by the Zaragoza city council concerning the meat market during the sixteenth and seventeenth centuries. Economic prosperity in the kingdom of Aragón, Zaragoza city and council during the sixteenth century allowed to increase public control of meat transactions in order to supply efficiently the population, as well as to support local demand. However, economic decline of the kingdom and raising municipal indebtedness during the seventeenth century led to reduce public intervention and support of local demand on the meat market. Readjustment of municipal politics gradually promoted the integration of the market in Aragón. This process continued during the eighteenth century and became firmly established during the final crisis of the "Ancien Régime".

  9. Fiber type specific expression of TNF-alpha, IL-6 and IL-18 in human skeletal muscles

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Penkowa, Milena; Pedersen, Bente K

    2005-01-01

    Skeletal muscle is now recognized as an endocrine organ with the capacity to produce signal peptides in response to muscle contractions. Here we demonstrate that resting healthy human muscles express cytokines in a fiber type specific manner. Human muscle biopsies from seven healthy young males...... differences between the three muscles with regard to MHC I and MHC IIa mRNA expression. Immunohistochemistry demonstrated that tumor necrosis factor (TNF)-alpha and interleukin (IL)-18 were solely expressed by type II fibers, whereas the expression of IL-6 was more prominent in type I compared to type II...... fibers. The fiber type specificity was found in triceps, vastus and soleus indicating that the level of daily muscle activity did not influence basal cytokine expression. The specificity of cytokine expression in different muscle fiber types in healthy young males suggests that cytokines may play...

  10. Human T cell leukaemia virus type I associated neuromuscular disease causing respiratory failure.

    Science.gov (United States)

    Littleton, E T; Man, W D; Holton, J L; Landon, D N; Hanna, M G; Polkey, M I; Taylor, G P

    2002-05-01

    Polymyositis and inclusion body myositis have rarely been described in association with human T cell leukaemia virus type I (HTLV-I) infection. Most of such patients have coexisting HTLV-I associated myelopathy (HAM). Two patients with HTLV-I infection, myopathy, and respiratory failure are described. The muscle biopsy specimen of the first patient bore the histological features of inclusion body myositis and there was no evidence of concurrent myelopathy. The second patient had HAM, and her muscle biopsy showed non-specific myopathic and neuropathic changes. Both patients developed respiratory muscle weakness over eight years after diagnosis of myopathy, leading to hypercapnic respiratory failure requiring mechanical ventilatory support. Respiratory failure as a complication of HTLV-I associated myopathy has not previously been described.

  11. Ligand modulation of sidechain dynamics in a wild-type human GPCR

    DEFF Research Database (Denmark)

    Clark, Lindsay D.; Dikiy, Igor; Chapman, Karen

    2017-01-01

    GPCRs regulate all aspects of human physiology, and biophysical studies have deepened our understanding of GPCR conformational regulation by different ligands. Yet there is no experimental evidence for how sidechain dynamics control allosteric transitions between GPCR conformations. To address...... this deficit, we generated samples of a wild-type GPCR (A2AR) that are deuterated apart from 1H/13C NMR probes at isoleucine δ1 methyl groups, which facilitated 1H/13C methyl TROSY NMR measurements with opposing ligands. Our data indicate that low [Na+] is required to allow large agonist-induced structural...... changes in A2AR, and that patterns of sidechain dynamics substantially differ between agonist (NECA) and inverse agonist (ZM241385) bound receptors, with the inverse agonist suppressing fast ps-ns timescale motions at the G protein binding site. Our approach to GPCR NMR creates a framework for exploring...

  12. Human Immunodeficiency Virus Type 1 Protease and the Emergence of Drug Resistance

    DEFF Research Database (Denmark)

    Poulsen, Nina Rødtness

    Human immunodeficiency virus type-1 (HIV-1) protease (PR) is responsible for cleaving ten different sites in the viral Gag and Gag-pol polyproteins, thereby releasing the structural proteins and enzymes necessary for the maturation and infectivity of the HIV-1 virus. The vital role of HIV-1 PR...... in the virus life cycle has made it a major target for drug development and active site competitive inhibitors have been successful in the battle against HIV. Unfortunately, the massive drug pressure along with high-level replication and lack of proofreading by the viral reverse transcriptase have resulted...... in multi-drug-resistant PRs. Computational analysis of a vast number of inhibitor-resistant HIV-1 PR variants can broaden the knowledge of how and why the mutations arise, which would be a great advantage in the design on resistance-evading inhibitors. Here we present a diverse system to select...

  13. Human T-Cell Leukemia Virus Type 1 Infection and Adult T-Cell Leukemia.

    Science.gov (United States)

    Chan, Chi-Ping; Kok, Kin-Hang; Jin, Dong-Yan

    2017-01-01

    Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus discovered to cause adult T-cell leukemia (ATL), a highly aggressive blood cancer. HTLV-1 research in the past 35 years has been most revealing in the mechanisms of viral oncogenesis. HTLV-1 establishes a lifelong persistent infection in CD4(+) T lymphocytes. The infection outcome is governed by host immunity. ATL develops in 2-5% of infected individuals 30-50 years after initial exposure. HTLV-1 encodes two oncoproteins Tax and HBZ, which are required for initiation of cellular transformation and maintenance of cell proliferation, respectively. HTLV-1 oncogenesis is driven by a clonal selection and expansion process during which both host and viral factors cooperate to impair genome stability, immune surveillance, and other mechanisms of tumor suppression. A better understanding of HTLV-1 biology and leukemogenesis will reveal new strategies and modalities for ATL prevention and treatment.

  14. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

    Directory of Open Access Journals (Sweden)

    Ilaria Turin

    2014-03-01

    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

  15. Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase

    Energy Technology Data Exchange (ETDEWEB)

    Ealy, Julie B. [Department of Medicine, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, PO Box 850, Mail Services H036, Hershey, PA 17033 (United States); Department of Chemistry, Penn State Lehigh Valley, 2809 E. Saucon Valley Road, Center Valley, PA 18034 (United States); Sudol, Malgorzata [Department of Medicine, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, PO Box 850, Mail Services H036, Hershey, PA 17033 (United States); Krzeminski, Jacek; Amin, Shantu [Department of Pharmacology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033 (United States); Katzman, Michael, E-mail: mkatzman@psu.edu [Department of Medicine, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, PO Box 850, Mail Services H036, Hershey, PA 17033 (United States); Department of Microbiology and Immunology, Penn State College of Medicine, Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033 (United States)

    2012-11-10

    Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase.

  16. Intranasal vaccination with AAV5 and 9 vectors against human papillomavirus type 16 in rhesus macaques.

    Science.gov (United States)

    Nieto, Karen; Stahl-Hennig, Christiane; Leuchs, Barbara; Müller, Martin; Gissmann, Lutz; Kleinschmidt, Jürgen A

    2012-07-01

    Cervical cancer is the second most common cancer in women worldwide. Persistent high-risk human papillomavirus (HPV) infection has been identified as the causative event for the development of this type of cancer. Recombinant adeno-associated viruses (rAAVs) are currently being developed and evaluated as vaccine vector. In previous work, we demonstrated that rAAVs administered intranasally in mice induced high titers and long-lasting neutralizing antibodies against HPV type 16 (HPV16). To extend this approach to a more human-related species, we immunized rhesus macaques (Macaca mulatta) with AAVs expressing an HPV16 L1 protein using rAAV5 and 9 vectors in an intranasal prophylactic setting. An rAAV5-L1 vector followed by a boost with rAAV9-L1 induced higher titers of L1-specific serum antibodies than a single rAAV5-L1 immunization. L1-specific antibodies elicited by AAV9 vector neutralized HPV16 pseudovirions and persisted for at least 7 months post immunization. Interestingly, nasal application of rAAV9 was immunogenic even in the presence of high AAV9 antibody titers, allowing reimmunization with the same serotype without prevention of the transgene expression. Two of six animals did not respond to AAV-mediated intranasal vaccination, although they were not tolerant, as both developed antibodies after intramuscular vaccination with HPV16 virus-like particles. These data clearly show the efficacy of an intranasal immunization using rAAV9-L1 vectors without the need of an adjuvant. We conclude from our results that rAAV9 vector is a promising candidate for a noninvasive nasal vaccination strategy.

  17. Cloning of the genes encoding two murine and human cochlear unconventional type I myosins

    Energy Technology Data Exchange (ETDEWEB)

    Crozet, F.; El Amraoui, Z.; Blanchard, S. [Institut Pasteur, Paris (France)] [and others

    1997-03-01

    Several lines of evidence indicate a crucial role for unconventional myosins in the function of the sensory hair cells of the inner ear. We report here the characterization of the cDNAs encoding two unconventional type I myosins from a mouse cochlear cDNA library. The first cDNA encodes a putative protein named Myo1c, which is likely to be the murine orthologue of the bullfrog myosin I{beta} and which may be involved in the gating of the mechanotransduction channel of the sensory hair cells. This myosin belongs to the group of short-tailed myosins I, with its tail ending shortly after a polybasic, TH-1-like domain. The second cDNA encodes a novel type I myosin Myo1f which displays three regions: a head domain with the conserved ATP- and actin-binding sites, a neck domain with a single IQ motif, and a tail domain with the tripartite structure initially described in protozoan myosins I. The tail of Myo1f includes (1) a TH-1 region rich in basic residues, which may interact with anionic membrane phospholipids; (2) a TH-2 proline-rich region, expected to contain an ATP-insensitive actin-binding site; and (3) an SH-3 domain found in a variety of cytoskeletal and signaling proteins. Northern blot analysis indicated that the genes encoding Myo1c and Myo1f display a widespread tissue expression in the adult mouse. Myo1c and Myo1f were mapped by in situ hybridization to the chromosomal regions 11D-11E and 17B-17C, respectively. The human orthologuous genes MYO1C and MYO1F were also characterized, and mapped to the human chromosomal regions 17p13 and 19p13.2- 19p1.3.3, respectively. 45 refs., 5 figs., 2 tabs.

  18. The MEK Inhibitors Trametinib and Cobimetinib Induce a Type I Interferon Response in Human Keratinocytes

    Directory of Open Access Journals (Sweden)

    Daniela Lulli

    2017-10-01

    Full Text Available Mitogen-activated protein kinase kinases (MEK 1 and 2 have crucial roles in tumorigenesis, cell proliferation, and protection from apoptosis, and their inhibition is therefore an attractive therapeutic strategy in cancer. Orally available and highly selective MEK inhibitors have been developed and assessed in numerous clinical trials, either alone or in combination with cytotoxic chemotherapy and/or other targeted agents. Of note, a complex picture of class-specific adverse effects associates with these drugs, frequently including inflammatory skin rash. Here, we investigated the response of normal human keratinocytes to the MEK inhibitors trametinib and cobimetinib, alone and in combination with the v-Raf murine sarcoma viral oncogene homolog B (BRAF inhibitors dabrafenib and vemurafenib, in terms of signal transduction and de novo gene expression. MEK inhibitors triggered enhanced expression of interferon regulatory factor 1 (IRF1 and phosphorylation of signal transducer and activator of transcription 1 (STAT1, and up-regulated the keratinocyte-specific type I interferon κ (IFN-κ, the anti-viral effectors interferon-induced tetratricopeptide repeats (IFIT 1 and 2, and the pro-inflammatory chemokine (C-C motif ligand 2 (CCL2 and the C-X-C motif chemokine 10 (CXCL10, both at the mRNA and protein level. Impairment of IRF1 expression, or abrogation of STAT1 phosphorylation due to IFN-κ gene silencing, suppressed anti-viral and pro-inflammatory gene expression. These data suggest that, similar to what we observed for epidermal growth factor receptor (EGFR blockade, MEK inhibition activates a type I interferon response, which is now recognized as an effective anti-cancer response, in human epidermal keratinocytes.

  19. Epidemiology and clinical presentation of the four human parainfluenza virus types

    Directory of Open Access Journals (Sweden)

    Liu Wen-Kuan

    2013-01-01

    Full Text Available Abstract Background Human parainfluenza viruses (HPIVs are important causes of upper respiratory tract illness (URTI and lower respiratory tract illness (LRTI. To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs, patients with acute respiratory tract illness (ARTI were studied in Guangzhou, southern China. Methods Throat swabs (n=4755 were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5% patients’ clinical presentations were recorded for further analysis. Results Of 4755 patients tested, 178 (3.7% were positive for HPIV. Ninety-nine (2.1% samples were positive for HPIV-3, 58 (1.2% for HPIV-1, 19 (0.4% for HPIV-2 and 8 (0.2% for HPIV-4. 160/178 (88.9% HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015, “abnormal pulmonary breathing sound” (p Conclusions HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.

  20. Urban Transit System Microbial Communities Differ by Surface Type and Interaction with Humans and the Environment.

    Science.gov (United States)

    Hsu, Tiffany; Joice, Regina; Vallarino, Jose; Abu-Ali, Galeb; Hartmann, Erica M; Shafquat, Afrah; DuLong, Casey; Baranowski, Catherine; Gevers, Dirk; Green, Jessica L; Morgan, Xochitl C; Spengler, John D; Huttenhower, Curtis

    2016-01-01

    Public transit systems are ideal for studying the urban microbiome and interindividual community transfer. In this study, we used 16S amplicon and shotgun metagenomic sequencing to profile microbial communities on multiple transit surfaces across train lines and stations in the Boston metropolitan transit system. The greatest determinant of microbial community structure was the transit surface type. In contrast, little variation was observed between geographically distinct train lines and stations serving different demographics. All surfaces were dominated by human skin and oral commensals such as Propionibacterium , Corynebacterium , Staphylococcus , and Streptococcus . The detected taxa not associated with humans included generalists from alphaproteobacteria, which were especially abundant on outdoor touchscreens. Shotgun metagenomics further identified viral and eukaryotic microbes, including Propionibacterium phage and Malassezia globosa . Functional profiling showed that Propionibacterium acnes pathways such as propionate production and porphyrin synthesis were enriched on train holding surfaces (holds), while electron transport chain components for aerobic respiration were enriched on touchscreens and seats. Lastly, the transit environment was not found to be a reservoir of antimicrobial resistance and virulence genes. Our results suggest that microbial communities on transit surfaces are maintained from a metapopulation of human skin commensals and environmental generalists, with enrichments corresponding to local interactions with the human body and environmental exposures. IMPORTANCE Mass transit environments, specifically, urban subways, are distinct microbial environments with high occupant densities, diversities, and turnovers, and they are thus especially relevant to public health. Despite this, only three culture-independent subway studies have been performed, all since 2013 and all with widely differing designs and conclusions. In this study, we

  1. Characterization of the Outer Domain of the gp120 Glycoprotein from Human Immunodeficiency Virus Type 1

    Science.gov (United States)

    Yang, Xinzhen; Tomov, Vesko; Kurteva, Svetla; Wang, Liping; Ren, Xinping; Gorny, Miroslaw K.; Zolla-Pazner, Susan; Sodroski, Joseph

    2004-01-01

    The core of the gp120 glycoprotein from human immunodeficiency virus type 1 (HIV-1) is comprised of three major structural domains: the outer domain, the inner domain, and the bridging sheet. The outer domain is exposed on the HIV-1 envelope glycoprotein trimer and contains binding surfaces for neutralizing antibodies such as 2G12, immunoglobulin G1b12, and anti-V3 antibodies. We expressed the outer domain of HIV-1YU2 gp120 as an independent protein, termed OD1. OD1 efficiently bound 2G12 and a large number of anti-V3 antibodies, indicating its structural integrity. Immunochemical studies with OD1 indicated that antibody responses against the outer domain of the HIV-1 gp120 envelope glycoprotein are rare in HIV-1-infected human sera that potently neutralize the virus. Surprisingly, such outer-domain-directed antibody responses are commonly elicited by immunization with recombinant monomeric gp120. Immunization with soluble, stabilized HIV-1 envelope glycoprotein trimers elicited antibody responses that more closely resembled those in the sera of HIV-1-infected individuals. These results underscore the qualitatively different humoral immune responses elicited during natural infection and after gp120 vaccination and help to explain the failure of gp120 as an effective vaccine. PMID:15542649

  2. Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease.

    Science.gov (United States)

    Maia, Ana Luiza; Goemann, Iuri Martin; Meyer, Erika L Souza; Wajner, Simone Magagnin

    2011-06-01

    Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T(4)) molecule, thus producing either the active form triiodothyronine (T(3); activation) or inactive metabolites (reverse T(3); inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T(3) production contributes to a portion of plasma T(3) in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T(3) concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

  3. Type III Interferons Produced by Human Placental Trophoblasts Confer Protection against Zika Virus Infection.

    Science.gov (United States)

    Bayer, Avraham; Lennemann, Nicholas J; Ouyang, Yingshi; Bramley, John C; Morosky, Stefanie; Marques, Ernesto Torres De Azeved; Cherry, Sara; Sadovsky, Yoel; Coyne, Carolyn B

    2016-05-11

    During mammalian pregnancy, the placenta acts as a barrier between the maternal and fetal compartments. The recently observed association between Zika virus (ZIKV) infection during human pregnancy and fetal microcephaly and other anomalies suggests that ZIKV may bypass the placenta to reach the fetus. This led us to investigate ZIKV infection of primary human trophoblasts (PHTs), which are the barrier cells of the placenta. We discovered that PHT cells from full-term placentas are refractory to ZIKV infection. In addition, medium from uninfected PHT cells protects non-placental cells from ZIKV infection. PHT cells constitutively release the type III interferon (IFN) IFNλ1, which functions in both a paracrine and autocrine manner to protect trophoblast and non-trophoblast cells from ZIKV infection. Our data suggest that for ZIKV to access the fetal compartment, it must evade restriction by trophoblast-derived IFNλ1 and other trophoblast-specific antiviral factors and/or use alternative strategies to cross the placental barrier. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Adenovirus hexon modifications influence in vitro properties of pseudotyped human adenovirus type 5 vectors.

    Science.gov (United States)

    Solanki, Manish; Zhang, Wenli; Jing, Liu; Ehrhardt, Anja

    2016-01-01

    Commonly used human adenovirus (HAdV)-5-based vectors are restricted by their tropism and pre-existing immunity. Here, we characterized novel HAdV-5 vectors pseudotyped with hypervariable regions (HVRs) and surface domains (SDs) of other HAdV types. Hexon-modified HAdV-5 vectors (HV-HVR5, HV-HVR12, HV-SD12 and HV-SD4) could be reconstituted and amplified in human embryonic kidney cells. After infection of various cell lines, we measured transgene expression levels by performing luciferase reporter assays or coagulation factor IX (FIX) ELISA. Dose-dependent studies revealed that luciferase expression levels were comparable for HV-HVR5, HV-SD12 and HV-SD4, whereas HV-HVR12 expression levels were significantly lower. Vector genome copy numbers (VCNs) from genomic DNA and nuclear extracts were then determined by quantitative real-time PCR. Surprisingly, determination of cell- and nuclear fraction-associated VCNs revealed increased VCNs for HV-HVR12 compared with HV-SD12 and HV-HVR5. Increased nuclear fraction-associated HV-HVR12 DNA molecules and decreased transgene expression levels were independent of the cell line used, and we observed the same effect for a hexon-modified high-capacity adenoviral vector encoding canine FIX. In conclusion, studying hexon-modified adenoviruses in vitro demonstrated that HVRs but also flanking hexon regions influence uptake and transgene expression of adenoviral vectors.

  5. E7 proteins from oncogenic human papillomavirus types transactivate p73: role in cervical intraepithelial neoplasia

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    Brooks, L A; Sullivan, A; O'Nions, J; Bell, A; Dunne, B; Tidy, J A; Evans, D J; Osin, P; Vousden, K H; Gusterson, B; Farrell, P J; Storey, A; Gasco, M; Sakai, T; Crook, T

    2002-01-01

    In common with other E2F1 responsive genes such as p14ARF and B-myb, the promoter of p73 is shown to be positively regulated in cell lines and primary human keratinocytes by E7 proteins from oncogenic human papillomavirus (HPV) types 16, 18, 31 and 33, but not HPV 6. Mutational analysis revealed that transactivation of the p73 promoter by HPV 16E7 requires association with pRb. Expression of p73 in normal cervical epithelium is confined to the basal and supra-basal layers. In contrast, expression in neoplastic lesions is detected throughout the epithelium and increases with grade of neoplasia, being maximal in squamous cell cancers (SCC). Deregulation of expression of the N-terminal splice variant p73Δ2 was observed in a significant proportion of cancers, but not in normal epithelium. The frequent over-expression of p73Δ2, which has recognized transdominant properties, in malignant and pre-malignant lesions suggests a role in the oncogenic process in cervical epithelium. British Journal of Cancer (2002) 86, 263–268. DOI: 10.1038/sj/bjc/6600033 www.bjcancer.com © 2002 The Cancer Research Campaign PMID:11870517

  6. A-Type Cranberry Proanthocyanidins Inhibit the RANKL-Dependent Differentiation and Function of Human Osteoclasts

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    Amy B. Howell

    2011-03-01

    Full Text Available This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP staining, while the secretion of interleukin-8 (IL-8 and matrix metalloproteinases (MMPs was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 µg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 µg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 µg/ml affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.

  7. Structure of Human M-type Phospholipase A2 Receptor Revealed by Cryo-Electron Microscopy.

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    Dong, Yue; Cao, Longxing; Tang, Hua; Shi, Xiangyi; He, Yongning

    2017-12-08

    M-type phospholipase A2 receptor (M-PLA2R) is a member of the mannose receptor family and known as the receptor of secretory phospholipase A2s. It has also been identified as the major autoantigen of idiopathic membranous nephropathy, one of the most common causes for nephrotic syndrome in adults. Here we determine the structure of human M-PLA2R ectodomain by cryo-electron microscopy. The results show that the ectodomain has high internal flexibility and forms a compact dual-ring-shaped conformation at acidic pH and adopts extended conformations at basic pH. The inter-domain interactions of human M-PLA2R are explored by the binding studies with individual domains, showing the mechanism of the conformational change. In addition, the biochemical data suggest that mouse M-PLA2R recognizes mouse secretory phospholipase A2-G1B only at physiological or basic pH, rather than at acidic pH. These results suggest that the pH-dependent conformational change might play important roles in the functional activities of M-PLA2R such as ligand binding and release, and may also be relevant to the immunogenicity in membranous nephropathy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Identification of cellular proteins required for replication of human immunodeficiency virus type 1.

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    Dziuba, Natallia; Ferguson, Monique R; O'Brien, William A; Sanchez, Anthony; Prussia, Andrew J; McDonald, Natalie J; Friedrich, Brian M; Li, Guangyu; Shaw, Michael W; Sheng, Jinsong; Hodge, Thomas W; Rubin, Donald H; Murray, James L

    2012-10-01

    Cellular proteins are essential for human immunodeficiency virus type 1 (HIV-1) replication and may serve as viable new targets for treating infection. Using gene trap insertional mutagenesis, a high-throughput approach based on random inactivation of cellular genes, candidate genes were found that limit virus replication when mutated. Disrupted genes (N=87) conferring resistance to lytic infection with several viruses were queried for an affect on HIV-1 replication by utilizing small interfering RNA (siRNA) screens in TZM-bl cells. Several genes regulating diverse pathways were found to be required for HIV-1 replication, including DHX8, DNAJA1, GTF2E1, GTF2E2, HAP1, KALRN, UBA3, UBE2E3, and VMP1. Candidate genes were independently tested in primary human macrophages, toxicity assays, and/or Tat-dependent β-galactosidase reporter assays. Bioinformatics analyses indicated that several host factors present in this study participate in canonical pathways and functional processes implicated in prior genome-wide studies. However, the genes presented in this study did not share identity with those found previously. Novel antiviral targets identified in this study should open new avenues for mechanistic investigation.

  9. Gene Expression Programs in Response to Hypoxia: Cell Type Specificity and Prognostic Significance in Human Cancers.

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    2006-01-01

    Full Text Available BACKGROUND: Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases. METHODS AND FINDINGS: We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use. CONCLUSIONS: The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis

  10. Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers.

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    Jen-Tsan Chi

    2006-03-01

    Full Text Available Inadequate oxygen (hypoxia triggers a multifaceted cellular response that has important roles in normal physiology and in many human diseases. A transcription factor, hypoxia-inducible factor (HIF, plays a central role in the hypoxia response; its activity is regulated by the oxygen-dependent degradation of the HIF-1alpha protein. Despite the ubiquity and importance of hypoxia responses, little is known about the variation in the global transcriptional response to hypoxia among different cell types or how this variation might relate to tissue- and cell-specific diseases.We analyzed the temporal changes in global transcript levels in response to hypoxia in primary renal proximal tubule epithelial cells, breast epithelial cells, smooth muscle cells, and endothelial cells with DNA microarrays. The extent of the transcriptional response to hypoxia was greatest in the renal tubule cells. This heightened response was associated with a uniquely high level of HIF-1alpha RNA in renal cells, and it could be diminished by reducing HIF-1alpha expression via RNA interference. A gene-expression signature of the hypoxia response, derived from our studies of cultured mammary and renal tubular epithelial cells, showed coordinated variation in several human cancers, and was a strong predictor of clinical outcomes in breast and ovarian cancers. In an analysis of a large, published gene-expression dataset from breast cancers, we found that the prognostic information in the hypoxia signature was virtually independent of that provided by the previously reported wound signature and more predictive of outcomes than any of the clinical parameters in current use.The transcriptional response to hypoxia varies among human cells. Some of this variation is traceable to variation in expression of the HIF1A gene. A gene-expression signature of the cellular response to hypoxia is associated with a significantly poorer prognosis in breast and ovarian cancer.

  11. Molecular typing of human platelet antigens in immune thrombocytopenia patients in northern Brazil.

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    Carmo, Julia Cavalcante do; Klippel, Prissyla de Souza; Cordeiro, Sabrine da Costa; Fernandes, Ângela Maria Dos Santos; Pinto, Raquel Medeiros; Weber, Simone Schneider; Fantin, Cleiton

    Immune thrombocytopenia is an immune disease characterized by thrombocytopenia and bleeding due to platelet antibodies against platelet membrane glycoproteins. Human platelet antigens are derived from polymorphisms of these glycoproteins. The aim of this study was to investigate human platelet antigen frequencies in immune thrombocytopenia patients from the state of Amazonas, Brazil and investigate the potential association between specific antigens and risk for immune thrombocytopenia. Human platelet antigen typing was performed by BeadChip technology to determine allelic variants of 11 systems (HPA-1 to HPA-9, HPA-11 and HPA-15). Thirty-six patients (8 male and 28 female) with a median age of 34 years (range: 9-69 years) were evaluated and compared with data from Amazonas blood donors. Platelet counts varied from 3 to 98×109/L. The allele frequencies were 0.944 for HPA-1a, 0.056 for HPA-1b, 0.847 for HPA-2a, 0.153 for HPA-2b, 0.555 for HPA-3a, 0.444 for HPA-3b, 0.805 for HPA-5a, 0.222 for HPA-5b, 0.9975 for HPA-9a, 0.025 for HPA-9b, 0.486 for HPA-15a and 0.513 for HPA-15b. Among immune thrombocytopenia individuals, no b allele of the HPA-4, -6, -7, -8 and -11 were found. The results suggest HPA-1a, HPA-3b and HPA-5b are immune thrombocytopenia-specific autoepitopes. Copyright © 2017 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

  12. Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus-type I.

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    Yeaman, Grant R; Asin, Susana; Weldon, Sally; Demian, Douglas J; Collins, Jane E; Gonzalez, Jorge L; Wira, Charles R; Fanger, Michael W; Howell, Alexandra L

    2004-12-01

    Human immunodeficiency virus-type 1 (HIV-1) is a sexually transmitted pathogen that can infect cells in the female reproductive tract (FRT). The mechanism of viral transmission within the FRT and the mode of viral spread to the periphery are not well understood. To characterize the frequency of potential targets of HIV infection within the FRT, we performed a systematic study of the expression of HIV receptors (CD4, galactosyl ceramide (GalCer)) and coreceptors (CXCR4 and CCR5) on epithelial cells and leucocytes from the ectocervix. The ectocervix is a likely first site of contact with HIV-1 following heterosexual transmission, and expression of these receptors is likely to correlate with susceptibility to viral infection. We obtained ectocervical tissue specimens from women undergoing hysterectomy, and compared expression of these receptors among patients who were classified as being in the proliferative or secretory phases of their menstrual cycle at the time of hysterectomy, as well as from postmenopausal tissues. Epithelial cells from tissues at early and mid-proliferative stages of the menstrual cycle express CD4, although by late proliferative and secretory phases, CD4 expression was absent or weak. In contrast, GalCer expression was uniform in all stages of the menstrual cycle. CXCR4 expression was not detected on ectocervical epithelial cells and positive staining was only evident on individual leucocytes. In contrast, CCR5 expression was detected on ectocervical epithelial cells from tissues at all stages of the menstrual cycle. Overall, our results suggest that HIV infection of cells in the ectocervix could most likely occur through GalCer and CCR5. These findings are important to define potential targets of HIV-1 infection within the FRT, and for the future design of approaches to reduce the susceptibility of women to infection by HIV-1.

  13. Quantifying the human vaginal community state types (CSTs with the species specificity index

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    Zhanshan (Sam Ma

    2017-06-01

    Full Text Available The five community state types (CSTs first identified by Ravel et al. (2011 offered a powerful scheme to classify the states of human vaginal microbial communities (HVMC. The classification is a significant advance because it devised an effective handle to deal with the enormous inter-subject heterogeneity and/or intra-subject temporal variability, the quantification of which is extremely difficult but of critical importance such as the understanding of BV (bacterial vaginosis etiology. Indeed, arguably the most plausible ecological hypothesis for interpreting the BV etiology heavily depends on the CST classification (Gajer et al., 2012; Ma, Forney & Ravel, 2012; Ravel et al., 2011. Nevertheless, the current form of CSTs is still qualitative and lacks a quantitative criterion to determine the CSTs. In this article, we develop a quantitative tool that can reliably distinguish the CSTs by applying the species specificity of Mariadassou, Pichon & Ebert (2015 and the specificity aggregation index (SAI we propose in this study. The new tool accurately characterized the classifications of the five CSTs with both 400-crosssectional cohort (Ravel et al., 2011 and 32-longitudinal cohort (Gajer et al., 2012 studies originally utilized to develop the CST scheme. Furthermore, it offers a mechanistic interpretation of the original CST scheme by invoking the paradigm of specificity continuum for species adaptation and distribution. The advances we made may not only facilitate the accurate applications of the CST scheme, but also offer hints towards an effective tool for microbiome typing such as classifying gut enterotypes.

  14. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

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    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. Copyright © 2015 by The American Association of Immunologists, Inc.

  15. Dynamics of High-Risk Nonvaccine Human Papillomavirus Types after Actual Vaccination Scheme

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    Raúl Peralta

    2014-01-01

    Full Text Available Human papillomavirus (HPV has been identified as the main etiological factor in the developing of cervical cancer (CC. This finding has propitiated the development of vaccines that help to prevent the HPVs 16 and 18 infection. Both genotypes are associated with 70% of CC worldwide. In the present study, we aimed to determine the emergence of high-risk nonvaccine HPV after actual vaccination scheme to estimate the impact of the current HPV vaccines. A SIR-type model was used to study the HPV dynamics after vaccination. According to the results, our model indicates that the application of the vaccine reduces infection by target or vaccine genotypes as expected. However, numerical simulations of the model suggest the presence of the phenomenon called vaccine—induced pathogen strain replacement. Here, we report the following replacement mechanism: if the effectiveness of cross-protective immunity is not larger than the effectiveness of the vaccine, then the high-risk nonvaccine genotypes emerge. In this scenario, further studies of infection dispersion by HPV are necessary to ascertain the real impact of the current vaccines, primarily because of the different high-risk HPV types that are found in CC.

  16. Exosomes in Human Immunodeficiency Virus Type I Pathogenesis: Threat or Opportunity?

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    Sin-Yeang Teow

    2016-01-01

    Full Text Available Nanometre-sized vesicles, also known as exosomes, are derived from endosomes of diverse cell types and present in multiple biological fluids. Depending on their cellular origins, the membrane-bound exosomes packed a variety of functional proteins and RNA species. These microvesicles are secreted into the extracellular space to facilitate intercellular communication. Collective findings demonstrated that exosomes from HIV-infected subjects share many commonalities with Human Immunodeficiency Virus Type I (HIV-1 particles in terms of proteomics and lipid profiles. These observations postulated that HIV-resembled exosomes may contribute to HIV pathogenesis. Interestingly, recent reports illustrated that exosomes from body fluids could inhibit HIV infection, which then bring up a new paradigm for HIV/AIDS therapy. Accumulative findings suggested that the cellular origin of exosomes may define their effects towards HIV-1. This review summarizes the two distinctive roles of exosomes in regulating HIV pathogenesis. We also highlighted several additional factors that govern the exosomal functions. Deeper understanding on how exosomes promote or abate HIV infection can significantly contribute to the development of new and potent antiviral therapeutic strategy and vaccine designs.

  17. Sexual transmission of human T-cell lymphotropic virus type 1

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    Arthur Paiva

    2014-06-01

    Full Text Available Human T-cell lymphotropic virus type 1 (HTLV-1 is endemic in many parts of the world and is primarily transmitted through sexual intercourse or from mother to child. Sexual transmission occurs more efficiently from men to women than women to men and might be enhanced by sexually transmitted diseases that cause ulcers and result in mucosal ruptures, such as syphilis, herpes simplex type 2 (HSV-2, and chancroid. Other sexually transmitted diseases might result in the recruitment of inflammatory cells and could increase the risk of HTLV-1 acquisition and transmission. Additionally, factors that are associated with higher transmission risks include the presence of antibodies against the viral oncoprotein Tax (anti-Tax, a higher proviral load in peripheral blood lymphocytes, and increased cervicovaginal or seminal secretions. Seminal fluid has been reported to increase HTLV replication and transmission, whereas male circumcision and neutralizing antibodies might have a protective effect. Recently, free virions were discovered in plasma, which reveals a possible new mode of HTLV replication. It is unclear how this discovery might affect the routes of HTLV transmission, particularly sexual transmission, because HTLV transmission rates are significantly higher from men to women than women to men.

  18. Functional and cytometric examination of different human lung epithelial cell types as drug transport barriers.

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    Min, Kyoung Ah; Rosania, Gus R; Kim, Chong-Kook; Shin, Meong Cheol

    2016-03-01

    To develop inhaled medications, various cell culture models have been used to examine the transcellular transport or cellular uptake properties of small molecules. For the reproducible high throughput screening of the inhaled drug candidates, a further verification of cell architectures as drug transport barriers can contribute to establishing appropriate in vitro cell models. In the present study, side-by-side experiments were performed to compare the structure and transport function of three lung epithelial cells (Calu-3, normal human bronchial primary cells (NHBE), and NL-20). The cells were cultured on the nucleopore membranes in the air-liquid interface (ALI) culture conditions, with cell culture medium in the basolateral side only, starting from day 1. In transport assays, paracellular transport across all three types of cells appeared to be markedly different with the NHBE or Calu-3 cells, showing low paracellular permeability and high TEER values, while the NL-20 cells showed high paracellular permeability and low TEER. Quantitative image analysis of the confocal microscope sections further confirmed that the Calu-3 cells formed intact cell monolayers in contrast to the NHBE and NL-20 cells with multilayers. Among three lung epithelial cell types, the Calu-3 cell cultures under the ALI condition showed optimal cytometric features for mimicking the biophysical characteristics of in vivo airway epithelium. Therefore, the Calu-3 cell monolayers could be used as functional cell barriers for the lung-targeted drug transport studies.

  19. High Whole-Genome Sequence Diversity of Human Papillomavirus Type 18 Isolates

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    Pascal van der Weele

    2018-02-01

    Full Text Available Background: The most commonly found human papillomavirus (HPV types in cervical cancer are HPV16 and HPV18. Genome variants of these types have been associated with differential carcinogenic potential. To date, only a handful of studies have described HPV18 whole genome sequencing results. Here we describe HPV18 variant diversity and conservation of persistent infections in a longitudinal retrospective cohort study. Methods: Cervical self-samples were obtained annually over four years and genotyped on the SPF10-DEIA-LiPA25 platform. Clearing and persistent HPV18 positive infections were selected, amplified in two overlapping fragments, and sequenced using 32 sequence primers. Results: Complete viral genomes were obtained from 25 participants with persistent and 26 participants with clearing HPV18 infections, resulting in 52 unique HPV18 genomes. Sublineage A3 was predominant in this population. The consensus viral genome was completely conserved over time in persistent infections, with one exception, where different HPV18 variants were identified in follow-up samples. Conclusions: This study identified a diverse set of HPV18 variants. In persistent infections, the consensus viral genome is conserved. The identification of only one HPV18 infection with different major variants in follow-up implies that this is a potentially rare event. This dataset adds 52 HPV18 genome variants to Genbank, more than doubling the currently available HPV18 information resource, and all but one variant are unique additions.

  20. Unique human papillomavirus-type distribution in South African women with invasive cervical cancer and the effect of human immunodeficiency virus infection.

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    van Aardt, Matthys Cornelis; Dreyer, Greta; Pienaar, Hannelie Francina; Karlsen, Frank; Hovland, Siri; Richter, Karin Louise; Becker, Piet

    2015-06-01

    Cervical cancer is the most common cause of cancer-related deaths among South African women. Viral types associated with cervical cancer may differ not only between countries and regions, but possibly also between human immunodeficiency virus (HIV)-infected and noninfected women. In a population with high HIV prevalence, human papillomavirus (HPV)-type infections detected with DNA analyses were reported in a cohort of 299 women diagnosed with invasive cervical cancer. One hundred fifty-four women tested HIV negative, 77 tested HIV positive, and HIV status was unknown for 68 women. The mean age for HIV-positive women was 41.3 years, and that for HIV-negative women was 55.8 years (P < 0.001). Ninety-two percent of women tested HPV-DNA positive. Human papillomavirus types 16 and/or 18 were present in 62% of HIV-negative women and 65% of HIV-positive women. The 5 most common HPV types in HIV-positive women were, in decreasing frequency, HPV 16, 18, 45, 33, and 58. In HIV-negative women, the most common HPV types were HPV 16, 18, 35, and 45, followed by HPV 33 and 52. Human papillomavirus type 45 was more likely in the HIV positive compared with the HIV negative (odds ratio, 3.07; 95% confidence interval, 1.07-8.77). The HIV-positive women had more multiple high-risk HPV-type infections than did the HIV-negative women (27% vs 8%, P = 0.001). A high number of women in South Africa with cervical cancer are HIV positive. Without viral cross-protection, HPV vaccines should prevent around 65% of cervical cancers in this population. Human papillomavirus type 45 infection is significantly linked to HIV and important for future vaccine developments.

  1. Patterns of cervical coinfection with multiple human papilloma virus types in a screening population in Denmark.

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    Goldman, Bryan; Rebolj, Matejka; Rygaard, Carsten; Preisler, Sarah; Ejegod, Ditte Møller; Lynge, Elsebeth; Bonde, Jesper

    2013-03-15

    Patterns of cervical human papillomavirus (HPV) infection suggest that HPV genotypes are not independent of each other. This may be explained by risk factors common to all HPV infections, but type-specific biological factors may also play a role. This raises the question of whether widespread use of the quadrivalent vaccine (covering HPV6, 11, 16, 18) may indirectly affect the prevalence of any non-vaccine types. Routine screening samples from 5014 Danish women were tested for 35 HPV genotypes (including 13 high-risk) using the Genomica CLART(®) HPV2 kit, which is a low-density microarray based on PCR amplification. Simulation studies were performed both under independence between genotypes and under a common dependence structure as would arise from common risk factors, and simulation results were compared to observed coinfection patterns. Overall HPV prevalence was 37.4%, with multiple infections in 17.9%. For 15 HPV types of primary interest (13 high-risk plus HPV6, 11), almost all pairs occurred more often than expected under independence; 33/105 (31.4%) were statistically significant (p<0.05 after adjustment for multiple comparisons). The pairwise odds ratios showed significant heterogeneity (Woolf's test p<0.0001). For simulations based on common dependence, three pairs had observed to expected (O/E) ratios significantly different than 1 (31/68, O/E=4.20; 51/68, O/E=2.52; 33/58, O/E=3.27; all p<0.05 after adjustment for multiple comparisons). HPV68 occurred in multiple infections nearly four times as often as expected under common dependence (p<0.005 after adjustment for multiple comparisons). These results indicate some interaction between HPV types, and suggest that common risk factors do not entirely explain the observed HPV coinfection pattern, although no evidence is found that the prevalence of any types not targeted by the quadrivalent vaccine may be indirectly increased or decreased after widespread use of the vaccine. Copyright © 2013 Elsevier Ltd

  2. Characterization of neutralizing epitopes within the major capsid protein of human papillomavirus type 33

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    Sapp Martin

    2006-10-01

    Full Text Available Abstract Background Infections with papillomaviruses induce type-specific immune responses, mainly directed against the major capsid protein, L1. Based on the propensity of the L1 protein to self-assemble into virus-like particles (VLPs, type-specific vaccines have already been developed. In order to generate vaccines that target a broader spectrum of HPV types, extended knowledge of neutralizing epitopes is required. Despite the association of human papillomavirus type 33 (HPV33 with cervical carcinomas, fine mapping of neutralizing conformational epitopes on HPV33 has not been reported yet. By loop swapping between HPV33 and HPV16 capsid proteins, we have identified amino acid sequences critical for the binding of conformation-dependent type-specific neutralizing antibodies to surface-exposed hyper variable loops of HPV33 capsid protein L1. Results Reactivities of monoclonal antibodies (mAbs H33.B6, H33.E12, H33.J3 and H16.56E with HPV16:33 and HPV33:16 hybrid L1 VLPs revealed the complex structures of their conformational epitopes as well as the major residues contributing to their binding sites. Whereas the epitope of mAb H33.J3 was determined by amino acids (aa 51–58 in the BC loop of HPV33 L1, sequences of at least two hyper variable loops, DE (aa 132–140 and FGb (aa 282–291, were found to be essential for binding of H33.B6. The epitope of H33.E12 was even more complex, requiring sequences of the FGa loop (aa 260–270, in addition to loops DE and FGb. Conclusion These data demonstrate that neutralizing epitopes in HPV33 L1 are mainly located on the tip of the capsomere and that several hyper variable loops contribute to form these conformational epitopes. Knowledge of the antigenic structure of HPV is crucial for designing hybrid particles as a basis for intertypic HPV vaccines.

  3. Human papillomavirus type 58: the unique role in cervical cancers in East Asia

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    Chan Paul KS

    2012-05-01

    Full Text Available Abstract Background About 15 types of human papillomavirus (HPV are classified as high-risk based on their epidemiological link with cervical cancer. These HPV types have deferent degrees of oncogenicity and their distribution among cervical precancers and cancers varies ethnogeographically. HPV58 is rare worldwide but being found more commonly in East Asia. Findings A high prevalence of HPV58 among squamous cell carcinoma has been reported from China (28% in Shanghai, 10% in Hong Kong and 10% in Taiwan and other countries in East Asia including Korea (16% and Japan (8%. HPV58 ranks the third in Asia overall, but contributes to only 3.3% of cervical cancers globally. The reasons for a difference in disease attribution may lie on the host as well as the virus itself. HLA-DQB1*06 was found to associate with a higher risk of developing HPV58-positive cervical neoplasia in Hong Kong women, but not neoplasia caused by other HPV types. An HPV58 variant (E7 T20I, G63S commonly detected in Hong Kong was found to confer a 6.9-fold higher risk of developing cervical cancer compared to other variants. A study involving 15 countries/cities has shown a predilection in the distribution of HPV58 variant lineages. Sublineage A1, the prototype derived from a cancer patient in Japan, was rare worldwide except in Asia. Conclusions HPV58 accounts for a larger share of disease burden in East Asia, which may be a result of differences in host genetics as well as the oncogenicity of circulating variants. These unique characteristics of HPV58 should be considered in the development of next generation vaccines and diagnostic assays.

  4. Interplay between chromatin state, regulator binding, and regulatory motifs in six human cell types

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    Ernst, Jason; Kellis, Manolis

    2013-01-01

    The regions bound by sequence-specific transcription factors can be highly variable across different cell types despite the static nature of the underlying genome sequence. This has been partly attributed to changes in chromatin accessibility, but a systematic picture has been hindered by the lack of large-scale data sets. Here, we use 456 binding experiments for 119 regulators and 84 chromatin maps generated by the ENCODE in six human cell types, and relate those to a global map of regulatory motif instances for these factors. We find specific and robust chromatin state preferences for each regulator beyond the previously reported open-chromatin association, suggesting a much richer chromatin landscape beyond simple accessibility. The preferentially bound chromatin states of regulators were enriched for sequence motifs of regulators relative to all states, suggesting that these preferences are at least partly encoded by the genomic sequence. Relative to all regions bound by a regulator, however, regulatory motifs were surprisingly depleted in the regulator's preferentially bound states, suggesting additional non-sequence-specific binding beyond the level predicted by the regulatory motifs. Such permissive binding was largely restricted to open-chromatin regions showing histone modification marks characteristic of active enhancer and promoter regions, whereas open-chromatin regions lacking such marks did not show permissive binding. Lastly, the vast majority of cobinding of regulator pairs is predicted by the chromatin state preferences of individual regulators. Overall, our results suggest a joint role of sequence motifs and specific chromatin states beyond mere accessibility in mediating regulator binding dynamics across different cell types. PMID:23595227

  5. Randomization modeling to ascertain clustering patterns of human papillomavirus types detected in cervicovaginal samples in the United States.

    Directory of Open Access Journals (Sweden)

    Troy David Querec

    Full Text Available Detection of multiple human papillomavirus (HPV types in the genital tract is common. Associations among HPV types may impact HPV vaccination modeling and type replacement. The objectives were to determine the distribution of concurrent HPV type infections in cervicovaginal samples and examine type-specific associations. We analyzed HPV genotyping results from 32,245 cervicovaginal specimens collected from women aged 11 to 83 years in the United States from 2001 through 2011. Statistical power was enhanced by combining 6 separate studies. Expected concurrent infection frequencies from a series of permutation models, each with increasing fidelity to the real data, were compared with the observed data. Statistics were computed based on the distributional properties of the randomized data. Concurrent detection occurred more than expected with 0 or ≥3 HPV types and less than expected with 1 and 2 types. Some women bear a disproportionate burden of the HPV type prevalence. Type associations were observed that exceeded multiple hypothesis corrected significance. Multiple HPV types were detected more frequently than expected by chance and associations among particular HPV types were detected. However vaccine-targeted types were not specifically affected, supporting the expectation that current bivalent/quadrivalent HPV vaccination will not result in type replacement with other high-risk types.

  6. Sarcoplasmic reticulum Ca2+ uptake and leak properties, and SERCA isoform expression, in type I and type II fibres of human skeletal muscle.

    Science.gov (United States)

    Lamboley, C R; Murphy, R M; McKenna, M J; Lamb, G D

    2014-03-15

    The Ca(2+) uptake properties of the sarcoplasmic reticulum (SR) were compared between type I and type II fibres of vastus lateralis muscle of young healthy adults. Individual mechanically skinned muscle fibres were exposed to solutions with the free [Ca(2+)] heavily buffered in the pCa range (-log10[Ca(2+)]) 7.3-6.0 for set times and the amount of net SR Ca(2+) accumulation determined from the force response elicited upon emptying the SR of all Ca(2+). Western blotting was used to determine fibre type and the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) isoform present in every fibre examined. Type I fibres contained only SERCA2 and displayed half-maximal Ca(2+) uptake rate at ∼pCa 6.8, whereas type II fibres contained only SERCA1 and displayed half-maximal Ca(2+) uptake rate at ∼pCa 6.6. Maximal Ca(2+) uptake rate was ∼0.18 and ∼0.21 mmol Ca(2+) (l fibre)(-1) s(-1) in type I and type II fibres, respectively, in good accord with previously measured SR ATPase activity. Increasing free [Mg(2+)] from 1 to 3 mM had no significant effect on the net Ca(2+) uptake rate at pCa 6.0, indicating that there was little or no calcium-induced calcium release occurring through the Ca(2+) release channels during uptake in either fibre type. Ca(2+) leakage from the SR at pCa 8.5, which is thought to occur at least in part through the SERCA, was ∼2-fold lower in type II fibres than in type I fibres, and was little affected by the presence of ADP, in marked contrast to the larger SR Ca(2+) leak observed in rat muscle fibres under the same conditions. The higher affinity of Ca(2+) uptake in the type I human fibres can account for the higher relative level of SR Ca(2+) loading observed in type I compared to type II fibres, and the SR Ca(2+) leakage characteristics of the human fibres suggest that the SERCAs are regulated differently from those in rat and contribute comparatively less to resting metabolic rate.

  7. Identification of genes associated with the penetration activity of the human type of Edwardsiella tarda EdwGII through human colon epithelial cell monolayers.

    Science.gov (United States)

    Suezawa, Chigusa; Yasuda, Masashi; Negayama, Kiyoshi; Kameyama, Taeko; Hirauchi, Misato; Nakai, Toshihiro; Okuda, Jun

    2016-06-01

    Edwardsiella tarda is a Gram-negative pathogen with a broad host range including fish and humans. E. tarda causes gastrointestinal and extraintestinal infections in humans. In present study, the penetration activities of 22 strains of E. tarda, including 10 human isolates and 12 diseased fish isolates, through Caco-2 cell monolayers were evaluated. All the human isolates exhibited penetration activity in contrast to the fish isolates, which did not. In order to identify genes responsible for penetration activity, we screened transposon (Tn) insertion mutants for reduced penetration activity. Two Tn insertion mutants showed markedly reduced penetration activity, and we identified the wecC and fliF genes as Tn insertion sites. The wecC and fliF genes encode UDP-N-acetyl-d-mannosamine dehydrogenase, which is involved in synthesis of enterobacterial common antigen and flagellar basal body M-ring protein, respectively. Motility activity, including swarming and swimming, by the wecC mutant was weaker than that by the wild-type strain, while the fliF mutant was immotile. These results indicated that the swarming and swimming abilities mediated by the wecC and fliF genes appeared to be essential for penetration activity of E. tarda through Caco-2 cell monolayers. We also demonstrated that it was possible to group E. tarda strains into two types of human isolates and diseased fish isolates based on distribution of the wecC gene, type III and type VI secretion system genes. PCR detection of the wecC gene may represent a useful method for detecting the human type of E. tarda, which may have the ability to cause human infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Characterization of blood group ABO(H)-active gangliosides in type AB erythrocytes and structural analysis of type A-active ganglioside variants in type A human erythrocytes.

    Science.gov (United States)

    Kushi, Y; Shimizu, M; Watanabe, K; Kasama, T; Watarai, S; Ariga, T; Handa, S

    2001-02-16

    Several monosialogangliosides containing the type A-active epitope have been detected in type A erythrocytes on immunological analysis with a monoclonal antibody, and three of them were purified by repeated silica bead column chromatography and by scraping from the TLC plate. Two of these A-active gangliosides were characterized by methylation analysis by GC/MS, negative SIMS, MALDI-TOF/MS, proton nuclear magnetic resonance spectroscopy, and immunological assays, and their structures were concluded to be as follows. A-active ganglioside I:A-active ganglioside II:The reactivity of the purified gangliosides to the anti-A monoclonal antibodies (mAbs) exhibited enhancement after removal of the sialic acid. Therefore, the sialic residue has been shown to inhibit the binding to the terminal A-active epitope through the formation of an immune complex. To confirm the presence of A- (including S-A-I, -II and -III) and B-active gangliosides, the reactivity of anti-A and -B mAbs were investigated using total gangliosides from type A, -B and -AB erythrocytes on TLC plate. The results were that the gangliosides from types A and AB showed positive reaction to anti-A mAbs, whereas in the anti-B mAbs binding the gangliosides from types B and AB were positive. Thus, it revealed that A-active gangliosides were present in type A and -AB, and B-active gangliosides in types B and AB. As there was no difference in respective gangliosides on type AB erythrocytes of 22 individuals, both A- and B-active gangliosides are equally present in type AB erythrocytes. The biological significance of these A- and B-active ganglioside variants remains vague at present. As these molecules exhibit different reactivities to the anti-A mAbs, it is very likely that they can regulate the antigenicity of the A-epitope on the cell surface.

  9. Glycemic responses to sweetened dried and raw cranberries in humans with type 2 diabetes.

    Science.gov (United States)

    Wilson, Ted; Luebke, Justin L; Morcomb, Erin F; Carrell, Emily J; Leveranz, Megan C; Kobs, Lisa; Schmidt, Travis P; Limburg, Paul J; Vorsa, Nicholi; Singh, Ajay P

    2010-10-01

    This study assessed the metabolic response to sweetened dried cranberries (SDC), raw cranberries (RC), and white bread (WB) in humans with type 2 diabetes. Development of palatable cranberry preparations associated with lower glycemic responses may be useful for improving fruit consumption and glycemic control among those with diabetes. In this trial, type 2 diabetics (n= 13) received WB (57 g, 160 cal, 1 g fiber), RC (55 g, 21 cal, 1 g fiber), SDC (40 g, 138 cal, 2.1 g fiber), and SDC containing less sugar (SDC-LS, 40 g, 113 cal, 1.8 g fiber + 10 g polydextrose). Plasma glucose (mmol/L) peaked significantly at 60 min for WB, and at 30 min for RC, SDC, and SDC-LS at 9.6 ± 0.4, 7.0 ± 0.4, 9.6 ± 0.5, and 8.7 ± 0.5, respectively, WB remained significantly elevated from the other treatments at 120 min. Plasma insulin (pmol/mL) peaked at 60 min for WB and SDC and at 30 min for RC and SDC-LS at 157 ± 15, 142 ± 27, 61 ± 8, and 97 ± 11, respectively. Plasma insulin for SDC-LS was significantly lower at 60 min than either WB or SDC. Insulin area under the curve (AUC) values for RC and SDC-LS were both significantly lower than WB or SDC. Phenolic content of SDC and SDC-LS was determined following extraction with 80% acetone prior to high-performance liquid chromatography (HPLC) and electronspray ionization-mass spectrometry (ESI-MS) and found to be rich in 5-caffeoylquinic cid, quercetin-3-galactoside, and quercetin-3-galactoside, and the proanthocyanidin dimer epicatechin. In conclusion, SDC-LS was associated with a favorable glycemic and insulinemic response in type 2 diabetics. Practical Application: This study compares phenolic content and glycemic responses among different cranberry products. The study seeks to expand the palatable and portable healthy food choices for persons with type 2 diabetes. The novel use of polydextrose as a bulking agent making possible a reduction in caloric content and potential glycemic response is also characterized in this study.

  10. Characterisation of L-Type Amino Acid Transporter 1 (LAT1 Expression in Human Skeletal Muscle by Immunofluorescent Microscopy

    Directory of Open Access Journals (Sweden)

    Nathan Hodson

    2017-12-01

    Full Text Available The branch chain amino acid leucine is a potent stimulator of protein synthesis in skeletal muscle. Leucine rapidly enters the cell via the L-Type Amino Acid Transporter 1 (LAT1; however, little is known regarding the localisation and distribution of this transporter in human skeletal muscle. Therefore, we applied immunofluorescence staining approaches to visualise LAT1 in wild type (WT and LAT1 muscle-specific knockout (mKO mice, in addition to basal human skeletal muscle samples. LAT1 positive staining was visually greater in WT muscles compared to mKO muscle. In human skeletal muscle, positive LAT1 staining was noted close to the sarcolemmal membrane (dystrophin positive staining, with a greater staining intensity for LAT1 observed in the sarcoplasmic regions of type II fibres (those not stained positively for myosin heavy-chain 1, Type II—25.07 ± 5.93, Type I—13.71 ± 1.98, p < 0.01, suggesting a greater abundance of this protein in these fibres. Finally, we observed association with LAT1 and endothelial nitric oxide synthase (eNOS, suggesting LAT1 association close to the microvasculature. This is the first study to visualise the distribution and localisation of LAT1 in human skeletal muscle. As such, this approach provides a validated experimental platform to study the role and regulation of LAT1 in human skeletal muscle in response to various physiological and pathophysiological models.

  11. Analysis of Clonal Type-Specific Antibody Reactions in Toxoplasma gondii Seropositive Humans from Germany by Peptide-Microarray

    Science.gov (United States)

    Maksimov, Pavlo; Zerweck, Johannes; Maksimov, Aline; Hotop, Andrea; Groß, Uwe; Spekker, Katrin; Däubener, Walter; Werdermann, Sandra; Niederstrasser, Olaf; Petri, Eckhardt; Mertens, Marc; Ulrich, Rainer G.; Conraths, Franz J.; Schares, Gereon

    2012-01-01

    Background Different clonal types of Toxoplasma gondii are thought to be associated with distinct clinical manifestations of infections. Serotyping is a novel technique which may allow to determine the clonal type of T. gondii humans are infected with and to extend typing studies to larger populations which include infected but non-diseased individuals. Methodology A peptide-microarray test for T. gondii serotyping was established with 54 previously published synthetic peptides, which mimic clonal type-specific epitopes. The test was applied to human sera (n = 174) collected from individuals with an acute T. gondii infection (n = 21), a latent T. gondii infection (n = 53) and from T. gondii-seropositive forest workers (n = 100). Findings The majority (n = 124; 71%) of all T. gondii seropositive human sera showed reactions against synthetic peptides with sequences specific for clonal type II (type II peptides). Type I and type III peptides were recognized by 42% (n = 73) or 16% (n = 28) of the human sera, respectively, while type II–III, type I–III or type I–II peptides were recognized by 49% (n = 85), 36% (n = 62) or 14% (n = 25) of the sera, respectively. Highest reaction intensities were observed with synthetic peptides mimicking type II-specific epitopes. A proportion of the sera (n = 22; 13%) showed no reaction with type-specific peptides. Individuals with acute toxoplasmosis reacted with a statistically significantly higher number of peptides as compared to individuals with latent T. gondii infection or seropositive forest workers. Conclusions Type II-specific reactions were overrepresented and higher in intensity in the study population, which was in accord with genotyping studies on T. gondii oocysts previously conducted in the same area. There were also individuals with type I- or type III-specific reactions. Well-characterized reference sera and further specific peptide markers are needed to establish and

  12. Participation of collagen types I, III, IV, V, and fibronectin in the formation of villi fibrosis in human term placenta.

    Science.gov (United States)

    Rukosuev, V S; Nanaev, A K; Milovanov, A P

    1990-01-01

    The indirect immunofluorescence method was used to study the human term placenta in pathological pregnancy for the distribution of collagen types I, III, IV, V, and fibronectin in fibrosis stromatis villi. All collagen types and fibronectin were shown to participate in fibrosis villorum formation. Fibronectin was also detected in the fibrinoid that surrounded villi at stroma. The presence of free cytotrophoblast cells in the fibrinoid was accompanied by a noticeable increase in fibronectin fluorescence. A significant amount of collagen types IV and V and a less amount of collagen types I and III were identified.

  13. Distinct Transduction Difference Between Adeno-Associated Virus Type 1 and Type 6 Vectors in Human Polarized Airway Epithelia

    OpenAIRE

    Yan, Ziying; Lei-Butters, Diana Chi Man; Keiser, Nicholas W; Engelhardt, John F.

    2012-01-01

    Of the many biologically isolated AAV serotypes, AAV1 and AAV6 share the highest degree of sequence homology, with only six different capsid residues. We compared the transduction efficiencies of rAAV1 and rAAV6 in primary polarized human airway epithelia (HAE) and found significant differences in their abilities to transduce epithelia from the apical and basolateral membranes. rAAV1 transduction was ~10-fold higher than rAAV6 following apical infection, while rAAV6 transduction was ~10-fold ...

  14. Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2)

    Energy Technology Data Exchange (ETDEWEB)

    Kawagoe, Hiroyuki; Soma, Osamu; Goji, Junko [Kobe Univ. School of Medicine (Japan)] [and others

    1995-11-20

    Phosphodiesterase I/nucleotide pyrophosphatase is a widely expressed membrane-bound enzyme that cleaves diester bonds of a variety of substrates. We have cloned brain-type cDNA for this enzyme from rat brain and designated it PD-I{alpha}. In this study we have isolated cDNA and genomic DNA encoding human PD-I{alpha}. Human PD-I{alpha} cDNA, designated PDNP2 in HGMW nomenclature, has a 2589-nucleotide open reading frame encoding a polypeptide of 863 amino acids with a calculated M{sub r} of 99,034. Northern blot analysis revealed that human PD-I{alpha} transcript was present in brain, lung, placenta, and kidney. The database analysis showed that human PD-I{alpha} was identical with human autotaxin (ATX), a novel tumor motility-stimulating factor, except that human PD-I{alpha} lacks 156 nucleotides and 52 amino acids of human ATX. Human PD-I{alpha} and human ATX are likely to be alternative splicing products from the same gene. The 5{prime} region of the human PDNP2 gene contains four putative binding sites of transcription factor Sp1 without typical TATA or CAAT boxes, and there is a potential octamer binding motif in intron 2. From the results of fluorescence in situ hybridization, the human PDNP2 gene is located at chromosome 8q24.1. 17 refs., 3 figs.

  15. DNA Delivery and Genomic Integration into Mammalian Target Cells through Type IV A and B Secretion Systems of Human Pathogens.

    Science.gov (United States)

    Guzmán-Herrador, Dolores L; Steiner, Samuel; Alperi, Anabel; González-Prieto, Coral; Roy, Craig R; Llosa, Matxalen

    2017-01-01

    We explore the potential of bacterial secretion systems as tools for genomic modification of human cells. We previously showed that foreign DNA can be introduced into human cells through the Type IV A secretion system of the human pathogen Bartonella henselae. Moreover, the DNA is delivered covalently attached to the conjugative relaxase TrwC, which promotes its integration into the recipient genome. In this work, we report that this tool can be adapted to other target cells by using different relaxases and secretion systems. The promiscuous relaxase MobA from plasmid RSF1010 can be used to deliver DNA into human cells with higher efficiency than TrwC. MobA also promotes DNA integration, albeit at lower rates than TrwC. Notably, we report that DNA transfer to human cells can also take place through the Type IV secretion system of two intracellular human pathogens, Legionella pneumophila and Coxiella burnetii, which code for a distantly related Dot/Icm Type IV B secretion system. This suggests that DNA transfer could be an intrinsic ability of this family of secretion systems, expanding the range of target human cells. Further analysis of the DNA transfer process showed that recruitment of MobA by Dot/Icm was dependent on the IcmSW chaperone, which may explain the higher DNA transfer rates obtained. Finally, we observed that the presence of MobA negatively affected the intracellular replication of C. burnetii, suggesting an interference with Dot/Icm translocation of virulence factors.

  16. La devaluación de los prioratos de la orden de San Juan en Castilla y León a mediados del siglo XVII

    OpenAIRE

    Josefina Castilla Soto

    1994-01-01

    A lo largo del siglo xvii tuvo lugar una importante crisis en la economía castellana, que los distintos especialistas en el tema se han ocupado de destacar, señalando sus motivaciones y cuantificando sus efectos. Naturalmente los Prioratos de la Orden de San Juan en Castilla y León no escaparon a estas circunstancias, aunque mostraron unas connotaciones muy particulares que trataremos ahora de exponer a grandes rasgos.

  17. Book review: Ham radio's technical culture. By K. Haring. Cambridge, MA: The MIT Press. 2007. xvii + 220 pp. £18.95. cloth. ISBN: 0262083558

    OpenAIRE

    Geoghegan, Hilary

    2008-01-01

    284 Book reviewHam radio's technical culture. By K. Haring. Cambridge, MA: The MIT Press. 2007. xvii + 220 pp. £18.95. cloth. ISBN: 0262083558 SAGE Publications, Inc.2008DOI: 10.1177/14744740080150020805 HilaryGeoghegan Department of Geography Royal Holloway, University of London `G4PDH, G4PDH, this is 2M1QQQ calling you. How do you copy?' Music to the amateur radio enthusiast's ears. Radio hams are the subject of Kristen Haring's enjoyab...

  18. Simultaneous expression of 70 kilodalton type IV collagenase and type IV collagen alpha 1 (IV) chain genes by cells of early human placenta and gestational endometrium.

    Science.gov (United States)

    Autio-Harmainen, H; Hurskainen, T; Niskasaari, K; Höyhtyä, M; Tryggvason, K

    1992-08-01

    In this study we used in situ hybridization to investigate the expression of the genes 70 kilodalton (kd) collagenase and the alpha 1(IV) collagen chain of type IV collagen in cells of early human placenta and gestational endometrium. The aim was to study the spatial distribution of these gene expressions within a developing tissue which possesses physiologic invasive potential. The results obtained for the 70 kd type IV collagenase mRNA expression were also compared with the immunohistochemical distribution of the corresponding antigen. Expression of mRNAs for these proteins was found in cells of trophoblastic columns, stromal cells of villi and in cells of decidua and endometrial stroma. The only differences between the expressions was the lower level of signals for 70 kd type IV collagenase in fibroblastic stromal cells and endothelial cells of villi and in the pericytic cells of spiral arteries. Otherwise the results for both types of mRNA were comparable. We also studied the immunohistochemical distribution of the 70 kd type IV collagenase using specific monoclonal antibodies against the enzyme. Immunohistochemistry supported well the findings obtained by in situ hybridization. The results indicate that the genes for the 70 kd type IV collagenase and for the alpha 1(IV) collagen chain are simultaneously active in cells of placenta and gestational endometrium and the same cells which produce type IV collagen also can produce the cleaving enzyme, the 70 kd type IV collagenase. The results also show that the cytotrophoblastic cells, which during early pregnancy invade the extracellular matrix and spiral arteries of uterine wall contain significant amount of mRNA for the 70 kd type IV collagenase. This finding supports the concept that the 70 kd type IV collagenase would be important for invasion, and in the case of this study, also for the physiologic invasion of placental cytotrophoblasts.

  19. Biodritin microencapsulated human islets of Langerhans and their potential for type 1 diabetes mellitus therapy.

    Science.gov (United States)

    Campos-Lisbôa, A C V; Mares-Guia, T R; Grazioli, G; Goldberg, A C; Sogayar, M C

    2008-03-01

    Microencapsulation of pancreatic islets with polymeric compounds constitutes an attractive alternative therapy for type 1 diabetes mellitus. The major limiting factor is the availability of a biocompatible and mechanically stable polymer. We investigated the potential of Biodritin, a novel polymer constituted of alginate and chondroitin sulfate, for islet microencapsulation. Biodritin microcapsules were obtained using an air jet droplet generator and gelated with barium or calcium chloride. Microencapsulated rat insulinoma RINm5F cells were tested for viability using the [3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide] [MTT] colorimetric assay. Microencapsulated rat pancreatic islets were coincubated with macrophages derived from mouse peritoneal liquid to assess the immunomodulatory potential of the microcapsules, using quantitative real time-PCR (qPCR). Biodritin biocompatibility was demonstrated by subcutaneous injection of empty microcapsules into immunocompetent Wistar rats. Insulin secretion by microencapsulated human pancreatic islets was evaluated using an electrochemoluminescent assay. Microencapsulated human islets transplanted into chemically induced diabetic mice were monitored for reversal of hyperglycemia. The metabolic activity of microencapsulated RINm5F cells persisted for at least 15 days. Interleukin-1beta expression by macrophages was observed during coculture with islets microencapsulated with Biodritin-CaCl2, but not with Biodritin-BaCl2. No statistical difference in glucose-stimulated insulin secretion was observed between nonencapsulated and microencapsulated islets. Upon microencapsulated islet transplantation, the blood glucose level of diabetic mice normalized; they remained euglycemic for at least 60 days, displaying normal oral glucose tolerance tests. This study demonstrated that Biodritin can be used for islet microencapsulation and reversal of diabetes; however, further investigations are required to assess its

  20. Adaptation of Subtype A Human Immunodeficiency Virus Type 1 Envelope to Pig-Tailed Macaque Cells▿

    Science.gov (United States)

    Humes, Daryl; Overbaugh, Julie

    2011-01-01

    The relevance of simian/human immunodeficiency virus (SHIV) infection of macaques to HIV-1 infection in humans depends on how closely SHIVs mimic HIV-1 transmission, pathogenesis, and diversity. Circulating HIV-1 strains are predominantly subtypes C and A and overwhelmingly require CCR5 for entry, yet most SHIVs incorporate CXCR4-using subtype B envelopes (Envs). While pathogenic subtype C-based SHIVs have been constructed, the subtype A-based SHIVs (SHIV-As) constructed to date have been unable to replicate in macaque cells. To understand the barriers to SHIV-A replication in macaque cells, HIVAQ23/SIVvif was constructed by engineering a CCR5-tropic subtype A provirus to express SIV vif, which counters the macaque APOBEC3G restriction. HIVAQ23/SIVvif replicated poorly in pig-tailed macaque (Ptm) lymphocytes, but viruses were adapted to Ptm lymphocytes. Two independent mutations in gp120, G312V (V3 loop) and A204E (C2 region), were identified that increased peak virus levels by >100-fold. Introduction of G312V and A204E to multiple subtype A Envs and substitution of G312 and A204 with other residues increased entry into Ptm cells by 10- to 100-fold. G312V and A204E Env variants continued to require CCR5 for entry but were up to 50- and 200-fold more sensitive to neutralization by IgG1b12 and soluble CD4 and had a 5- to 50-fold increase in their ability to utilize Ptm CD4 compared to their wild-type counterparts. These findings identify the inefficient use of Ptm CD4 as an unappreciated restriction to subtype A HIV-1 replication in Ptm cells and reveal amino acid changes to gp120 that can overcome this barrier. PMID:21325401

  1. Necroptosis takes place in human immunodeficiency virus type-1 (HIV-1-infected CD4+ T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Ting Pan

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD, indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1, a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis.

  2. Comparative marker analysis of extracellular vesicles in different human cancer types

    Directory of Open Access Journals (Sweden)

    Yusuke Yoshioka

    2013-06-01

    Full Text Available Several cell types, including tumour cells, secrete extracellular vesicles (EVs, and tumour-derived EVs play a role in cancer initiation and progression. These vesicles include both a common set of membrane and cytosolic proteins and origin-specific subsets of proteins that likely correlated to cell type–associated functions. To confirm the presence of EVs in the preparations, researchers have identified so-called EV marker proteins, including the tetraspanin family proteins and such cytosolic proteins as heat shock 70 kDa protein 4 (HSP70 and tumour susceptibility gene 101 (TSG101. However, studies have shown that some EV markers are not always present in all EVs, which not only complicates the identification of EVs but also precludes the quantitative evaluation of EV proteins. Thus, it is strongly required to explore well-conserved EV marker proteins that are present at similar levels, regardless of their tissue or cellular origin. In this study, we compared the presence of 11 well-known EV marker proteins by immunoblotting using EVs isolated from 4 human prostate cell lines and 5 human breast cell lines, including cancer cells with different phenotypes. We found that all the tested EVs were positive for CD9 and CD81, with similar abundance that was irrespective of the EV origin. In contrast, other EV marker proteins, such as TSG101, Rab-5b and CD63, were detected in an inconsistent manner, depending on the origin of the EVs. Thus, we propose that the detection of CD9 and/or CD81 should ensure the presence of EVs.

  3. Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia.

    Science.gov (United States)

    Hering, Bernhard J; Clarke, William R; Bridges, Nancy D; Eggerman, Thomas L; Alejandro, Rodolfo; Bellin, Melena D; Chaloner, Kathryn; Czarniecki, Christine W; Goldstein, Julia S; Hunsicker, Lawrence G; Kaufman, Dixon B; Korsgren, Olle; Larsen, Christian P; Luo, Xunrong; Markmann, James F; Naji, Ali; Oberholzer, Jose; Posselt, Andrew M; Rickels, Michael R; Ricordi, Camillo; Robien, Mark A; Senior, Peter A; Shapiro, A M James; Stock, Peter G; Turgeon, Nicole A

    2016-07-01

    Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA1c 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for

  4. Highly efficient inhibition of human immunodeficiency virus type 1 reverse transcriptase by aptamers functionalized gold nanoparticles

    Science.gov (United States)

    Shiang, Yen-Chun; Ou, Chung-Mao; Chen, Shih-Ju; Ou, Ting-Yu; Lin, Han-Jia; Huang, Chih-Ching; Chang, Huan-Tsung

    2013-03-01

    We have developed aptamer (Apt)-conjugated gold nanoparticles (Apt-Au NPs, 13 nm in diameter) as highly effective inhibitors for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Two Apts, RT1t49 (Aptpol) and ODN 93 (AptRH), which recognize the polymerase and RNase H regions of HIV-1 RT, are used to conjugate Au NPs to prepare Aptpol-Au NPs and AptRH-Au NPs, respectively. In addition to DNA sequence, the surface density of the aptamers on Au NPs (nApt-Au NPs; n is the number of aptamer molecules on each Au NP) and the linker length number (Tm; m is the base number of the deoxythymidine linker) between the aptamer and Au NPs play important roles in determining their inhibition activity. A HIV-lentiviral vector-based antiviral assay has been applied to determine the inhibitory effect of aptamers or Apt-Au NPs on the early stages of their replication cycle. The nuclease-stable G-quadruplex structure of 40AptRH-T45-Au NPs shows inhibitory efficiency in the retroviral replication cycle with a decreasing infectivity (40.2%).We have developed aptamer (Apt)-conjugated gold nanoparticles (Apt-Au NPs, 13 nm in diameter) as highly effective inhibitors for human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT). Two Apts, RT1t49 (Aptpol) and ODN 93 (AptRH), which recognize the polymerase and RNase H regions of HIV-1 RT, are used to conjugate Au NPs to prepare Aptpol-Au NPs and AptRH-Au NPs, respectively. In addition to DNA sequence, the surface density of the aptamers on Au NPs (nApt-Au NPs; n is the number of aptamer molecules on each Au NP) and the linker length number (Tm; m is the base number of the deoxythymidine linker) between the aptamer and Au NPs play important roles in determining their inhibition activity. A HIV-lentiviral vector-based antiviral assay has been applied to determine the inhibitory effect of aptamers or Apt-Au NPs on the early stages of their replication cycle. The nuclease-stable G-quadruplex structure of 40AptRH-T45

  5. Wild-type rabies virus induces autophagy in human and mouse neuroblastoma cell lines.

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    Peng, Jiaojiao; Zhu, Shenghe; Hu, Lili; Ye, Pingping; Wang, Yifei; Tian, Qin; Mei, Mingzhu; Chen, Hao; Guo, Xiaofeng

    2016-10-02

    Different rabies virus (RABV) strains have their own biological characteristics, but little is known about their respective impact on autophagy. Therefore, we evaluated whether attenuated RABV HEP-Flury and wild-type RABV GD-SH-01 strains triggered autophagy. We found that GD-SH-01 infection significantly increased the number of autophagy-like vesicles, the accumulation of enhanced green fluorescent protein (EGFP)-LC3 fluorescence puncta and the conversion of LC3-I to LC3-II, while HEP-Flury was not able to induce this phenomenon. When evaluating autophagic flux, we found that GD-SH-01 infection triggers a complete autophagic response in the human neuroblastoma cell line (SK), while autophagosome fusion with lysosomes was inhibited in a mouse neuroblastoma cell line (NA). In these cells, GD-SH-01 led to apoptosis and mitochondrial dysfunction while triggering autophagy, and apoptosis could be decreased by enhancing autophagy. To further identify the virus constituent causing autophagy, 5 chimeric recombinant viruses carrying single genes of HEP-Flury instead of those of GD-SH-01 were rescued. While the HEP-Flury virus carrying the wild-type matrix protein (M) gene of RABV triggered LC3-I to LC3-II conversion in SK and NA cells, replacement of genes of nucleoprotein (N), phosphoprotein (P) and glycoprotein (G) produced only minor autophagy. But no one single structural protein of GD-SH-01 induced autophagy. Moreover, the AMPK signaling pathway was activated by GD-SH-01 in SK. Therefore, our data provide strong evidence that autophagy is induced by GD-SH-01 and can decrease apoptosis in vitro. Furthermore, the M gene of GD-SH-01 may cooperatively induce autophagy.

  6. Aberrant Food Choices after Satiation in Human Orexin-Deficient Narcolepsy Type 1.

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    van Holst, Ruth Janke; van der Cruijsen, Lisa; van Mierlo, Petra; Lammers, Gert Jan; Cools, Roshan; Overeem, Sebastiaan; Aarts, Esther

    2016-11-01

    Besides influencing vigilance, orexin neurotransmission serves a variety of functions, including reward, motivation, and appetite regulation. As obesity is an important symptom in orexin-deficient narcolepsy, we explored the effects of satiety on food-related choices and spontaneous snack intake in patients with narcolepsy type 1 (n = 24) compared with healthy matched controls (n = 19). In additional analyses, we also included patients with idiopathic hypersomnia (n = 14) to assess sleepiness-related influences. Participants were first trained on a choice task to earn salty and sweet snacks. Next, one of the snack outcomes was devalued by having participants consume it until satiation (i.e., sensory-specific satiety). We then measured the selective reduction in choices for the devalued snack outcome. Finally, we assessed the number of calories that participants consumed spontaneously from ad libitum available snacks afterwards. After satiety, all participants reported reduced hunger and less wanting for the devalued snack. However, while controls and idiopathic hypersomnia patients chose the devalued snack less often in the choice task, patients with narcolepsy still chose the devalued snack as often as before satiety. Subsequently, narcolepsy patients spontaneously consumed almost 4 times more calories during ad libitum snack intake. We show that the manipulation of food-specific satiety has reduced effects on food choices and caloric intake in narcolepsy type 1 patients. These mechanisms may contribute to their obesity, and suggest an important functional role for orexin in human eating behavior. Study registered at Netherlands Trial Register. URL: www.trialregister.nl. Trial ID: NTR4508.

  7. Development of a DNA vaccine targeting human papillomavirus type 16 oncoprotein E6.

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    Peng, Shiwen; Ji, Hongxiu; Trimble, Cornelia; He, Liangmei; Tsai, Ya-Chea; Yeatermeyer, Jessica; Boyd, David A K; Hung, Chien-Fu; Wu, T-C

    2004-08-01

    Human papillomavirus (HPV), particularly type 16 (HPV-16), is present in more than 99% of cervical cancers. The HPV oncoproteins E6 and E7 are constantly expressed and therefore represent ideal targets for HPV vaccine development. We previously developed DNA vaccines encoding calreticulin (CRT) linked to HPV-16 E7 and generated potent E7-specific CD8(+) T-cell immune responses and antitumor effects against an E7-expressing tumor. Since vaccines targeting E6 also represent an important strategy for controlling HPV-associated lesions, we developed a DNA vaccine encoding CRT linked to E6 (CRT/E6). Our results indicated that the CRT/E6 DNA vaccine, but not a wild-type E6 DNA vaccine, generated significant E6-specific CD8(+) T-cell immune responses in vaccinated mice. Mapping of the immunodominant epitope of E6 revealed that an E6 peptide comprising amino acids (aa) 48 to 57 (E6 aa48-57), presented by H-2K(b), is the optimal peptide and that the region of E6 comprising aa 50 to 57 represents the minimal core sequence required for activating E6-specific CD8(+) T lymphocytes. We also demonstrated that E6 aa48-57 contains cytotoxic T-lymphocyte epitopes naturally presented by E6-expressing TC-1 cells. Vaccination with a CRT/E6 but not a CRT/mtE6 (lacking aa 50 to 57 of E6) DNA vaccine could protect vaccinated mice from challenge with E6-expressing TC-1 tumors. Thus, our data indicate that E6 aa48-57 contains the immunodominant epitope and that a CRT/E6 DNA vaccine may be useful for control of HPV infection and HPV-associated lesions.

  8. Evolutionary analysis of human immunodeficiency virus type 1 therapies based on conditionally replicating vectors.

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    Ruian Ke

    Full Text Available Efforts to reduce the viral load of human immunodeficiency virus type 1 (HIV-1 during long-term treatment are challenged by the evolution of anti-viral resistance mutants. Recent studies have shown that gene therapy approaches based on conditionally replicating vectors (CRVs could have many advantages over anti-viral drugs and other approaches to therapy, potentially including the ability to circumvent the problem of evolved resistance. However, research to date has not explored the evolutionary consequences of long-term treatment of HIV-1 infections with conditionally replicating vectors. In this study, we analyze a computational model of the within-host co-evolutionary dynamics of HIV-1 and conditionally replicating vectors, using the recently proposed 'therapeutic interfering particle' as an example. The model keeps track of the stochastic process of viral mutation, and the deterministic population dynamics of T cells as well as different strains of CRV and HIV-1 particles. We show that early in the co-infection, mutant HIV-1 genotypes that escape suppression by CRV therapy appear; this is similar to the dynamics observed in drug treatments and other gene therapies. In contrast to other treatments, however, the CRV population is able to evolve and catch up with the dominant HIV-1 escape mutant and persist long-term in most cases. On evolutionary grounds, gene therapies based on CRVs appear to be a promising tool for long-term treatment of HIV-1. Our model allows us to propose design principles to optimize the efficacy of this class of gene therapies. In addition, because of the analogy between CRVs and naturally-occurring defective interfering particles, our results also shed light on the co-evolutionary dynamics of wild-type viruses and their defective interfering particles during natural infections.

  9. Interferon Lambda Inhibits Herpes Simplex Virus Type I Infection of Human Astrocytes and Neurons

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    LI, JIELIANG; HU, SHUXIAN; ZHOU, LIN; YE, LI; WANG, XU; HO, JIE; HO, WENZHE

    2010-01-01

    Herpes simplex virus type I (HSV-1) is a neurotropic virus that is capable of infecting not only neurons, but also microglia and astrocytes and can establish latent infection in the central nervous system (CNS). We investigated whether IFN lambda (IFN-λ), a newly identified member of IFN family, has the ability to inhibit HSV-1 infection of primary human astrocytes and neurons. Both astrocytes and neurons were found to be highly susceptible to HSV-1 infection. However, upon IFN-λ treatment, HSV-1 replication in both astrocytes and neurons was significantly suppressed, which was evidenced by the reduced expression of HSV-1 DNA and proteins. This IFN-λ-mediated action on HSV-1 could be partially neutralized by antibody to IFN-λ receptor. Investigation of the mechanisms showed that IFN-λ treatment of astrocytes and neurons resulted in the upregulation of endogenous IFN-α/β and several IFN-stimulated genes (ISGs). To block IFN-α/β receptor by a specific antibody could compromise the IFN-λ actions on HSV-1 inhibition and ISG induction. In addition, IFN-λ treatment induced the expression of IFN regulatory factors (IRFs) in astrocytes and neurons. Furthermore, IFN-λ treatment of astrocytes and neurons resulted in the suppression of suppressor of cytokine signaling 1 (SOCS-1), a key negative regulator of IFN pathway. These data suggest that IFN-λ possesses the anti-HSV-1 function by promoting type I IFN-mediated innate antiviral immune response in the CNS cells. PMID:20878770

  10. Human immunodeficiency virus type-1 induces a regulatory B cell-like phenotype in vitro.

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    Lopez-Abente, Jacobo; Prieto-Sanchez, Adrián; Muñoz-Fernandez, Maria-Ángeles; Correa-Rocha, Rafael; Pion, Marjorie

    2017-07-17

    Individuals infected with human immunodeficiency virus type-1 (HIV-1) usually show a general dysregulation and hyper-activation of the immune system. A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described. However, the consequences of B-cell dysregulation are still poorly understood. We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli. The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+ and CD8+ T cells. We demonstrated that HIV-1 induces a phenotypic change in B cells towards a regulatory B-cell phenotype, showing a higher level of IL-10, TGF-β1, EBI3 or IL-12(p35) mRNA expression and acquiring an immunosuppressive profile. The acquisition of a Breg phenotype was confirmed by co-culture experiments where HIV-treated B cells reduced the proliferation and the TNFα production of CD4+ or CD8+ T cells. This suppressive ability of HIV-treated B cells was dependent on cell-to-cell contact between these B cells and effector cells. To our knowledge, these data provide the first evidence that HIV-1 can directly induce a regulatory B cell-like immunosuppressive phenotype, which could have the ability to impair specific immune responses. This dysregulation could constitute one of the mechanisms underlying unsuccessful efforts to develop an efficient vaccine against HIV-1.Cellular &Molecular Immunology advance online publication, 17 July 2017; doi:10.1038/cmi.2017.48.

  11. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

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    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Özcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M; Mahmoudi, Morteza; De Rooij, Felix W M; Sijbrands, Eric; Peppelenbosch, Maikel P; Rezaee, Farhad

    2015-10-06

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.

  12. Seroprevalence of Human Papillomavirus Types 6, 11, 16 and 18 in Chinese Women

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    Ji Jia

    2012-06-01

    Full Text Available Abstract Background Human papillomavirus (HPV seroprevalence data have not previously been reported for different geographical regions of China. This study investigated the cross-sectional seroprevalence of antibodies to HPV 6, 11, 16, and 18 virus-like particles in Chinese women. Methods Population-based samples of women were enrolled from 2006 to 2007 in 3 rural and 2 urban areas of China. Each consenting woman completed a questionnaire and provided a blood sample. Serum antibodies were detected using a competitive Luminex immunoassay that measures antibodies to type-specific, neutralizing epitopes on the virus-like particles. Results A total of 4,731 women (median age 35, age range 14-54 were included, of which 4,211 were sexually active women (median age 37 and 520 virgins (median age 18. Low risk HPV 6 was the most common serotype detected (7.3%, followed by HPV 16 (5.6%, HPV 11 (2.9%, and HPV 18 (1.9%. Overall HPV seroprevalence to any type was significantly higher among sexually active women (15.8% than virgins (2.5% (P = 0.005. Overall seroprevalence among sexually active women gradually increased with age. Women from rural regions had significantly lower overall seroprevalence (Odds Ratio (OR = 0.7; 95% CI: 0.6-0.9, versus metropolitan regions, P  = 4 partners versus 1 partner, P  Conclusions HPV seroprevalence differed significantly by age, geography, and sexual behavior within China, which all should be considered when implementing an optimal prophylactic HPV vaccination program in China.

  13. Z dziejów drukarstwa i handlu książką w Kołobrzegu w drugiej połowie XVII wieku

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    Radosław Gaziński

    2009-01-01

    Full Text Available W Archiwum Krajowym w Greifswaldzie w zespole archiwalnym Staatskanzelei zachowały się trzy jednostki archiwalne dotyczące drukarstwa i handlu książką w Kołobrzegu w drugiej połowie XVII wieku. Są to materiały o charakterze instytucjonalnym pokazujące problemy drukarstwa i handlu książką od strony brandenburskiej administracji prowincjonalnej. Drukarnię założono w Kołobrzegu za zgodą elektora Fryderyka Wilhelma w maju 1653 roku, a pierwszym drukarzem został Henryk Heissen. Po nim do końca XVII wieku drukarnię prowadzili: Jakub Kusen, Berger Campen i Johann Mikołaj Ernst. Drukarze w Kołobrzegu nie tylko drukowali książki, ale również sprzedawali je na terenie miasta. Obok nich w omawianym okresie działali tu także profesjonalni handlarze książkami: Jeremiasz Amphras, Jeremiasz Mamfass, Jakub Henning, Johan Danhardt i Jeremiasz Schrey. W drugiej połowie XVII wieku Kołobrzeg był, jak na warunki pomorskie, znaczącym centrum drukarstwa i handlu książką. Znaczenie to pomniejszyło przeniesienie stolicy prowincji do Stargardu (1668 rok.

  14. PRODUCEREA ŞI COMERCIALIZAREA BĂUTURILOR ALCOOLICE ÎN ORAŞELE DIN RZECZPOSPOLITA ŞI ŢARA MOLDOVEI (SEC.XVI-XVII

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    Nicolae DUDNICENCO

    2016-12-01

    Full Text Available Articolul vizează producerea, comercializarea şi consumul băuturilor alcoolice în oraşele din Rzeczpospolita (a berii, a votcii, a miedului şi din Ţara Moldovei (a vinului, a rachiului, a berii, a brăgii în sec. XVI-XVII. Se investighează mo­dul de producere, comercializare, precum şi taxele care se percepeau pentru băuturile alcoolice în oraşele din teri­toriul dat. Producerea băuturilor alcoolice aducea venituri mari economiei oraşelor din spaţiul indicat supra.PRODUCTION AND COMMERCIALISATION OF ALCOHOLIC DRINKS IN RZECZPOSPOLITA AND MOLDOVA PRINCIPALITY CITIES (XVI-XVII C.The article targeting the production, marketing and consumption of alcoholic drinks in the cities from Rzeczpospolita (beer, vodka, mead and from Moldova (wine, spirits, beer, braga in the XVI-XVII c. It have been investigated the mode of production, sell and taxes at which were subjected the alcoholic drinks in the cities on that territory. Production of alcoholic drinks brought substantial revenues to the economy of the cities from the indicated area.

  15. Effects of human PrPSc type and PRNP genotype in an in-vitro conversion assay.

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    Jones, Michael; Peden, Alexander H; Wight, Darren; Prowse, Christopher; Macgregor, Ian; Manson, Jean; Turner, Marc; Ironside, James W; Head, Mark W

    2008-12-03

    Prion protein type and codon 129 genotype are thought to be major determinants of susceptibility and phenotype in human prion diseases. Using an in-vitro system (protein misfolding cyclic amplification) we have attempted to model human prion protein conversion using the abnormal prion protein associated with each of the major sporadic Creutzfeldt-Jakob disease subtypes, in substrates containing the normal cellular form of the prion protein of each of the three possible human PRNP codon 129 polymorphic genotypes. The prion protein type is converted with fidelity in these amplification reactions, but the efficiency of conversion depends both on the methionine/valine polymorphic status of the sporadic Creutzfeldt-Jakob disease seed and substrate homogenate, and on the abnormal prion protein type.

  16. A new class of dual-targeted antivirals: monophosphorylated acyclovir prodrug derivatives suppress both human immunodeficiency virus type 1 and herpes simplex virus type 2.

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    Vanpouille, Christophe; Lisco, Andrea; Derudas, Marco; Saba, Elisa; Grivel, Jean-Charles; Brichacek, Beda; Scrimieri, Francesca; Schinazi, Raymond; Schols, Dominique; McGuigan, Christopher; Balzarini, Jan; Margolis, Leonid

    2010-02-15

    Human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2) are responsible for 2 intersecting epidemics in which the disease caused by 1 virus facilitates the transmission of and pathogenesis by the other. Therefore, suppression of one virus infection will affect the other. Acyclovir, a common antiherpetic drug, was shown to directly suppress both viruses in coinfected tissues. However, both antiviral activities of acyclovir are dependent on phosphorylation by the nucleoside kinase activity of coinfecting human herpesviruses. We developed acyclovir ProTides, monophosphorylated acyclovir with the phosphate group masked by lipophilic groups to allow efficient cellular uptake, and investigated their antiviral potential in cell lines and in human tissues ex vivo. Acyclovir ProTides suppressed both HIV-1 and HSV-2 at median effective concentrations in the submicromolar range in ex vivo lymphoid and cervicovaginal human tissues and at 3-12 micromol/L in CD4(+) T cells. Acyclovir ProTides retained activity against acyclovir-resistant HSV-2. Acyclovir ProTides represent a new class of antivirals that suppress both HIV-1 and HSV-2 by directly and independently blocking the key replicative enzymes of both viruses. Further optimization of such compounds may lead to double-targeted antivirals that can prevent viral transmission and treat the 2 synergistic diseases caused by HIV-1 and HSV-2. To our knowledge, the acyclovir ProTides described here represent the first example of acyclic nucleoside monophosphate prodrugs being active against HIV-1.

  17. Extended-spectrum β-lactamase producing Klebsiella spp. in chicken meat and humans: a comparison of typing methods.

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    Overdevest, I T M A; Heck, M; van der Zwaluw, K; Huijsdens, X; van Santen, M; Rijnsburger, M; Eustace, A; Xu, L; Hawkey, P; Savelkoul, P; Vandenbroucke-Grauls, C; Willemsen, I; van der Ven, J; Verhulst, C; Kluytmans, J A J W

    2014-03-01

    Recently, chicken meat was identified as a plausible source of extended-spectrum β-lactamase (ESBL) -producing Escherichia coli in humans. We investigated the relatedness of ESBL-producing Klebsiella spp. in chicken meat and humans. Furthermore, we tested the performance of SpectraCell RA(®) (River Diagnostics), a new typing method based on Raman spectroscopy, in comparison with multilocus sequence typing (MLST) for Klebsiella pneumoniae. Twenty-seven phenotypically and genotypically confirmed ESBL-producing Klebsiella spp. isolates were typed with MLST and SpectraCell RA. The isolates derived from chicken meat, human rectal swabs and clinical blood cultures. In the 22 ESBL-producing K. pneumoniae isolates, CTX-M15 was the predominant genotype, found in five isolates of human origin and in one chicken meat isolate. With MLST, 16 different STs were found, including five new STs. Comparing the results of SpectraCell RA with MLST, we found a sensitivity of 70.0% and a specificity of 81.8% for the new SpectraCell RA typing method. Therefore, we conclude that SpectraCell RA is not a suitable typing method when evaluating relationships of ESBL-producing Klebsiella spp. at the population level. Although no clustering was found with isolates of chicken meat and human origin containing the same ESBL genes, MLST showed no clustering into distinctive clones of isolates from chicken meat and human origin. More studies are needed to elucidate the role of chicken meat in the rise of ESBL-producing Klebsiella spp. in humans. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

  18. Progressive neurologic and somatic disease in a novel mouse model of human mucopolysaccharidosis type IIIC

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    Sara Marcó

    2016-09-01

    Full Text Available Mucopolysaccharidosis type IIIC (MPSIIIC is a severe lysosomal storage disease caused by deficiency in activity of the transmembrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT that catalyses the N-acetylation of α-glucosamine residues of heparan sulfate. Enzyme deficiency causes abnormal substrate accumulation in lysosomes, leading to progressive and severe neurodegeneration, somatic pathology and early death. There is no cure for MPSIIIC, and development of new therapies is challenging because of the unfeasibility of cross-correction. In this study, we generated a new mouse model of MPSIIIC by targeted disruption of the Hgsnat gene. Successful targeting left LacZ expression under control of the Hgsnat promoter, allowing investigation into sites of endogenous expression, which was particularly prominent in the CNS, but was also detectable in peripheral organs. Signs of CNS storage pathology, including glycosaminoglycan accumulation, lysosomal distension, lysosomal dysfunction and neuroinflammation were detected in 2-month-old animals and progressed with age. Glycosaminoglycan accumulation and ultrastructural changes were also observed in most somatic organs, but lysosomal pathology seemed most severe in liver. Furthermore, HGSNAT-deficient mice had altered locomotor and exploratory activity and shortened lifespan. Hence, this animal model recapitulates human MPSIIIC and provides a useful tool for the study of disease physiopathology and the development of new therapeutic approaches.

  19. Cloning and expression of human papilloma virus type 6b-L1 gene

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    Lie-hua DENG

    2011-03-01

    Full Text Available Objective To investigate the expression of green fluorescent protein plasmid of human papilloma virus 6b L1 gene(HPV6bL1 in eukaryotic cells.Methods The L1 gene of PQE40-HPV6bL1 was amplified by PCR,purified by restriction enzyme digestion,and then connected to eukaryotic expression plasmid PEGFP-C1.The recombinant expression vector was then transformed into E.coli DH5a,which was identified by BamH Ⅰ and Hand Ⅲ digestion and the positive vector was selected.The recombinant plasmid PEGFP-HPV6bL1 was transfected into COS-7 cells by liposomal transfection technique and the expression of fusion protein was observed under fluorescence microscope.The generation of HPV6bL1 mRNA was detected by RT-PCR.Results Identification of PEGFP-HPV6bL1 by enzyme digestion and sequencing showed that the length,direction and inserted location of target,which was inserted into the recombinant,was correct and the expression of EGFP in transfected cell was observed.Conclusions A new type of green fluorescent HPV6bL1 eukaryotic expression system has been established.It may provide a research foundation for the study of the protein.

  20. Acute Alithiasic Cholecystitis and Human Herpes Virus Type-6 Infection: First Case

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    Maria Miguel Gomes

    2016-01-01

    Full Text Available A three-year-old male child presented with erythematous maculopapular nonpruritic generalized rash, poor feeding, vomiting, and cramping generalized abdominal pain. He was previously healthy and there was no family history of immunologic or other diseases. On examination he was afebrile, hemodynamically stable, with painful palpation of the right upper quadrant and positive Murphy’s sign. Laboratory tests revealed elevated inflammatory markers, elevated aminotransferase activity, and features of cholestasis. Abdominal ultrasound showed gallbladder wall thickening of 8 mm with a positive sonographic Murphy’s sign, without gallstones or pericholecystic fluid. Acute Alithiasic Cholecystitis (AAC was diagnosed. Tests for underlying infectious causes were negative except positive blood specimen for Human Herpes Virus Type-6 (HHV-6 by polymerase chain reaction. With supportive therapy the child became progressively less symptomatic with gradual improvement. The child was discharged on the sixth day, asymptomatic and with improved analytic values. Two months later he had IgM negative and IgG positive antibodies (1/160 for HHV-6, which confirmed the diagnosis of previous infection. In a six-month follow-up period he remains asymptomatic. To the best of our knowledge, this represents the first case of AAC associated with HHV-6 infection.

  1. Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study.

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    de Groot, Pieter F; Belzer, Clara; Aydin, Ömrüm; Levin, Evgeni; Levels, Johannes H; Aalvink, Steven; Boot, Fransje; Holleman, Frits; van Raalte, Daniël H; Scheithauer, Torsten P; Simsek, Suat; Schaap, Frank G; Olde Damink, Steven W M; Roep, Bart O; Hoekstra, Joost B; de Vos, Willem M; Nieuwdorp, Max

    2017-01-01

    Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking. We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured. Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA. We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.

  2. Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients

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    Mariann Kremlitzka

    2016-01-01

    Full Text Available Complement receptors (CRs play an integral role in innate immunity and also function to initiate and shape the adaptive immune response. Our earlier results showed that complement receptor type 1 (CR1, CD35 is a potent inhibitor of the B cell receptor- (BCR- induced functions of human B lymphocytes. Here we show that this inhibition occurs already at the initial steps of B cell activation since ligation of CR1 reduces the BCR-induced phosphorylation of key signaling molecules such as Syk and mitogen activated protein kinases (MAPKs. Furthermore, our data give evidence that although B lymphocytes of active systemic lupus erythematosus (SLE patients express lower level of CR1, the inhibitory capacity of this complement receptor is still maintained and its ligand-induced clustering results in significant inhibition of the main B cell functions, similar to that found in the case of healthy individuals. Since we have found that reduced CR1 expression of SLE patients does not affect the inhibitory capacity of the receptor, our results further support the therapeutical potential of CD35 targeting the decrease of B cell activation and autoantibody production in autoimmune patients.

  3. Complement Receptor Type 1 Suppresses Human B Cell Functions in SLE Patients.

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    Kremlitzka, Mariann; Mácsik-Valent, Bernadett; Polgár, Anna; Kiss, Emese; Poór, Gyula; Erdei, Anna

    2016-01-01

    Complement receptors (CRs) play an integral role in innate immunity and also function to initiate and shape the adaptive immune response. Our earlier results showed that complement receptor type 1 (CR1, CD35) is a potent inhibitor of the B cell receptor- (BCR-) induced functions of human B lymphocytes. Here we show that this inhibition occurs already at the initial steps of B cell activation since ligation of CR1 reduces the BCR-induced phosphorylation of key signaling molecules such as Syk and mitogen activated protein kinases (MAPKs). Furthermore, our data give evidence that although B lymphocytes of active systemic lupus erythematosus (SLE) patients express lower level of CR1, the inhibitory capacity of this complement receptor is still maintained and its ligand-induced clustering results in significant inhibition of the main B cell functions, similar to that found in the case of healthy individuals. Since we have found that reduced CR1 expression of SLE patients does not affect the inhibitory capacity of the receptor, our results further support the therapeutical potential of CD35 targeting the decrease of B cell activation and autoantibody production in autoimmune patients.

  4. Gastrointestinal transit in nonobese diabetic mouse: an animal model of human diabetes type 1.

    Science.gov (United States)

    El-Salhy, M

    2001-01-01

    Gastrointestinal transit (GI) in the nonobese diabetic (NOD) mouse, an animal model of human diabetes type 1, was examined in animals with short- (duration 1-5 days) and long-term (duration 28-35 days) diabetes. Blood glucose level, serum insulin concentration, and gut neuroendocrine peptide content were also measured. GI was significantly rapid in NOD mice with long-term diabetes (LTD), but was not correlated with blood glucose level, serum insulin concentration, or pancreatic insulin content. GI was correlated with duodenal secretin content, but not with the content of other neuroendocrine peptides in the different segments investigated. Whereas antral vasoactive intestinal peptide (VIP) content in NOD mice with LTD was significantly higher, colonic VIP was lower in NOD mice with short-term diabetes (STD). In the duodenum, whereas the concentration of secretin in NOD mice with both STD and LTD was lower, the gastrin content was higher. Duodenal somatostatin content in NOD mice with LTD was lower. In colon, the content of galanin in NOD mice with LTD was higher than in controls. The decreased content of secretin may be among the factors that cause rapid GI in NOD mice with LTD. Changes in the antral content of VIP, duodenal somatostatin, and colonic galanin in NOD mice with LTD may cause low intestinal secretion and, together with rapid GI, give rise to diarrhoea, which is a common symptom in diabetes.

  5. Ligand modulation of sidechain dynamics in a wild-type human GPCR.

    Science.gov (United States)

    Clark, Lindsay D; Dikiy, Igor; Chapman, Karen; Rödström, Karin Ej; Aramini, James; LeVine, Michael V; Khelashvili, George; Rasmussen, Søren Gf; Gardner, Kevin H; Rosenbaum, Daniel M

    2017-10-06

    GPCRs regulate all aspects of human physiology, and biophysical studies have deepened our understanding of GPCR conformational regulation by different ligands. Yet there is no experimental evidence for how sidechain dynamics control allosteric transitions between GPCR conformations. To address this deficit, we generated samples of a wild-type GPCR (A 2A R) that are deuterated apart from 1 H/ 13 C NMR probes at isoleucine δ1 methyl groups, which facilitated 1 H/ 13 C methyl TROSY NMR measurements with opposing ligands. Our data indicate that low [Na + ] is required to allow large agonist-induced structural changes in A 2A R, and that patterns of sidechain dynamics substantially differ between agonist (NECA) and inverse agonist (ZM241385) bound receptors, with the inverse agonist suppressing fast ps-ns timescale motions at the G protein binding site. Our approach to GPCR NMR creates a framework for exploring how different regions of a receptor respond to different ligands or signaling proteins through modulation of fast ps-ns sidechain dynamics.

  6. Oligomerization within Virions and Subcellular Localization of Human Immunodeficiency Virus Type 1 Integrase

    Science.gov (United States)

    Petit, Caroline; Schwartz, Olivier; Mammano, Fabrizio

    1999-01-01

    Previous biochemical and genetic evidence indicated that the functional form of retroviral integrase protein (IN) is a multimer. A direct demonstration of IN oligomerization during the infectious cycle was, however, missing, due to the absence of a sensitive detection method. We describe here the generation of infectious human immunodeficiency virus type 1 (HIV-1) viral clones carrying IN protein tagged with highly antigenic epitopes. In this setting, we could readily visualize IN both in producer cells and in viral particles. More interestingly, we detected IN oligomers, the formation of which was dependent on disulfide bridges and took place inside virions. Additionally, expression of a tagged HIV-1 IN in the absence of other viral components resulted in almost exclusive nuclear accumulation of the protein. Mutation of a conserved cysteine in the proposed dimer interface determined the loss of viral infectivity, associated with a reduction of IN oligomer formation and the redistribution of the mutated protein in the nucleus and cytoplasm. Epitope tagging of HIV-1 IN expressed alone or in the context of a replication-competent viral clone provides powerful tools to validate debated issues on the implication of this enzyme in different steps of the viral cycle. PMID:10233971

  7. Updates on the treatment of human epidermal growth factor receptor type 2-positive breast cancer.

    Science.gov (United States)

    Kim, Miriam; Agarwal, Surbhi; Tripathy, Debu

    2014-02-01

    To review the most recent developments in the treatment of human epidermal growth factor receptor type 2 (HER2)-positive breast cancer with novel HER2-targeting agents and combinations that have significantly improved clinical outcomes. Since the approval of trastuzumab 15 years ago, the natural history of HER2-positive breast cancer has been altered with improvements in survival for both early and advanced disease with the addition of this agent to standard chemotherapy. The HER2 receptor pathway drives breast cancer growth and aggressiveness, and HER2-targeted agents can improve survival in early and advanced disease. In the advanced setting, two new drugs have been approved since 2012, pertuzumab and ado-trastuzumab emtansine (T-DM1), both of which improve survival without any reciprocal increase in toxicity. However, resistance almost always ensues, pointing to the need to understand the driving mechanisms and to biomarkers that will help individualize therapy and point to newer signal transduction and other modulators. HER2-positive breast cancer represents a distinct subtype with more aggressive clinical characteristics. HER2-targeted therapies, usually in combination with chemotherapy, are the standard of care, improving the cure rate in early-stage breast cancer and lengthening survival in the advanced setting.

  8. Imaging of human T-lymphotropic virus type I-associated chronic progressive myeloneuropathies

    Energy Technology Data Exchange (ETDEWEB)

    Alcindor, F. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Valderrama, R. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Canavaggio, M. (Abbott Labs., North Chicago, IL (United States)); Lee, H. (Abbott Labs., North Chicago, IL (United States)); Katz, A. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States)); Montesinos, C. (Beth Israel Medical Center, Dept. of Neurology and Clinical Electrophysiology, New York, NY (United States)); Madrid, R.E. (New York State Office of Mental Retardation and Developmental Disabilities, Inst. for Basic Research in Developmental Disabilities, NY (United States)); Merino, R.R. (Beth Israel Medical Center, Dept. of Neurology and Clinical Electrophysiology, New York, NY (United States)); Pipia, P.A. (Dept. of Neurology, State Univ. of New York, Health Science Center, Brooklyn, NY (United States))

    1992-12-01

    We studied magnetic resonance imaging (MRI) of the head and cervical spine and CT of the head in 46 patients (14 men, 32 women) with chronic progressive myeloneuropathy. The findings were correlated with human T-lymphotropic virus type I (HTLV-I) serology, race, country of origin, and age. We found a female predominance of 2:1. Most patients were aged between 30 and 50 years, and most were Caribbean immigrants and black. There were 9 men and 17 women with blood antibody titers to HTLV-I and 7 mem and 15 women with cerebrospinal fluid (CSF) titers. All patients with virus or antibodies in blood or CSF were Caribbean immigrants or black. T2-weighted cranial MRI showed scattered areas of high signal intensity in the cerebral white matter, usually in the periventricular and subcortical areas, but not in the posterior cranial fossa. Cranial CT revealed periventricular low density areas, ventricular enlargement, and atrophy MRI of the cervical spine showed atrophy of the cord. Myelography was normal in all 15 patients examined. No imaging differences were observed between the HTLV-I-positive and -negative patients. These findings, although consistent with demyelination, are not specific. (orig.)

  9. MDP Up-Regulates the Gene Expression of Type I Interferons in Human Aortic Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Xiumei Xie

    2012-03-01

    Full Text Available Muramyldipeptide (MDP, the minimum essential structure responsible for the immuno-adjuvant activity of peptidoglycan, is recognized by intracellular nuclear-binding oligomerization domain 2 (NOD2. Here, we obtained evidence that the treatment of human aortic endothelial cells (HAECs with MDP up-regulated the gene expression of type I interferons in a dose- and time-dependent manner. MDP also up-regulated the expression of the receptor NOD2, suggesting that MDP may induce a positive feedback response. The up-regulation of interferons was not dependent on the TNFa signaling, as HAECs did not express TNFa with the stimulation of MDP, and TNFa neutralizing antibody did not decrease the induction of IFNs induced by MDP. RT-PCR results showed that HAECs expressed the gene transcripts of interferon regulatory factor (IRF 1, 2, 3, 9. The western blot results showed that MDP induced the phosphorylation of IRF3. These results suggested that MDP induced the up-regulation of gene transcript of interferons through the activation of IRF3 signaling pathway. Meanwhile, MDP induced the gene expression of pro-inflammatory cytokines, including IL-1ß, IL-8, and MCP-1. Taken together, these results suggested that HAECs may play roles in the anti-infection immune response and in the induction of innate immunity.

  10. Selective susceptibility to nanosecond pulsed electric field (nsPEF) across different human cell types.

    Science.gov (United States)

    Gianulis, Elena C; Labib, Chantelle; Saulis, Gintautas; Novickij, Vitalij; Pakhomova, Olga N; Pakhomov, Andrei G

    2017-05-01

    Tumor ablation by nanosecond pulsed electric fields (nsPEF) is an emerging therapeutic modality. We compared nsPEF cytotoxicity for human cell lines of cancerous (IMR-32, Hep G2, HT-1080, and HPAF-II) and non-cancerous origin (BJ and MRC-5) under strictly controlled and identical conditions. Adherent cells were uniformly treated by 300-ns PEF (0-2000 pulses, 1.8 kV/cm, 50 Hz) on indium tin oxide-covered glass coverslips, using the same media and serum. Cell survival plotted against the number of pulses displayed three distinct regions (initial resistivity, logarithmic survival decline, and residual resistivity) for all tested cell types, but with differences in LD 50 spanning as much as nearly 80-fold. The non-cancerous cells were less sensitive than IMR-32 neuroblastoma cells but more vulnerable than the other cancers tested. The cytotoxic efficiency showed no apparent correlation with cell or nuclear size, cell morphology, metabolism level, or the extent of membrane disruption by nsPEF. Increasing pulse duration to 9 µs (0.75 kV/cm, 5 Hz) produced a different selectivity pattern, suggesting that manipulation of PEF parameters can, at least for certain cancers, overcome their resistance to nsPEF ablation. Identifying mechanisms and cell markers of differential nsPEF susceptibility will critically contribute to the proper choice and outcome of nsPEF ablation therapies.

  11. Legume Lectins Inhibit Human Parainfluenza Virus Type 2 Infection by Interfering with the Entry

    Directory of Open Access Journals (Sweden)

    Myles O’Brien

    2012-07-01

    Full Text Available Three lectins with different sugar binding specificities were investigated for anti-viral activity against human parainfluenza virus type 2 (hPIV-2. The lectins, concanavalin A (Con A, lens culinaris agglutinin (LCA and peanut agglutinin (PNA, inhibited cell fusion and hemadsorption induced by hPIV-2. Virus nucleoprotein (NP gene synthesis was largely inhibited, but fusion (F and hemagglutinin-neuraminidase (HN gene syntheses were not. An indirect immunofluorescence study showed that Con A inhibited virus NP, F and HN protein syntheses, but LCA did not completely inhibit them, and that PNA inhibited only NP protein synthesis. Using a recombinant green fluorescence protein-expressing hPIV-2, without matrix protein (rghPIV-2ΔM, it was found that virus entry into the cells was not completely prevented. The lectins considerably reduced the number of viruses released compared with that of virus infected cells. The lectins bound to cell surface within 10 min, and many aggregates were observed at 30 min. Con A and LCA slightly disrupted actin microfilaments and microtubules, but PNA had almost no effect on them. These results indicated that the inhibitory effects of the lectins were caused mainly by the considerable prevention of virus adsorption to the cells by the lectin binding to their receptors.

  12. A rare association between leukocyte adhesion deficiency type I and psoriasis in humans.

    Science.gov (United States)

    El-Sayed, Zeinab A; El-Ghoneimy, Dalia H; Abd-Allah, Heba; Afifi, Hanaa M

    2011-04-01

    The β2 integrins are expressed exclusively on leukocytes and participate in many immune and inflammatory processes. This subfamily comprises four heterodimeric glycoproteins with a common β-subunit, designated β2 (CD18). Spontaneous mutations of the CD18 gene result in leukocyte adhesion deficiency type I (LAD-I). Low level of CD18 expression has also been implicated in the pathogenesis of psoriasis. We here describe a child with recurrent skin infections without pus formation, persistent gingivitis and periodontitis. His blood counts showed persistent leukocytosis (neutrophilia). CD11b expression was defective on neutrophils, while that of CD18 was normal. So, our patient represents a mild variant of LAD-I with possible dysfunctional CD18. Moreover, he developed psoriasis with reduced CD18 expression on CD4(+) T-cells. Psoriasiform dermatitis has been described before in association with LAD-I, however, clinically and histologically confirmed psoriasis in association with LAD-I has been described only in CD18 hypomorphic mice. Therefore, our patient represents the first clinically and histopathologically documented association between LAD-I and psoriasis in humans. It lends support to the role of β2 integrins in the etiopathogenesis of psoriasis.

  13. Heterologous production of human papillomavirus type-16 L1 protein by a lactic acid bacterium

    Directory of Open Access Journals (Sweden)

    Bermúdez-Humarán Luis G

    2009-08-01

    Full Text Available Abstract Background The expression of vaccine antigens in lactic acid bacteria (LAB is a safe and cost-effective alternative to traditional expression systems. In this study, we investigated i the expression of Human papillomavirus type 16 (HPV-16 L1 major capsid protein in the model LAB Lactococcus lactis and ii the ability of the resulting recombinant strain to produce either capsomer-or virus-like particles (VLPs. Results and conclusion HPV-16 L1 gene was cloned into two vectors, pCYT and pSEC, designed for controlled intra- or extracellular heterologous expression in L. lactis, respectively. The capacity of L. lactis harboring either pCYT:L1 or pSEC:L1 plasmid to accumulate L1 in the cytoplasm and supernatant samples was confirmed by Western blot assays. Electron microscopy analysis suggests that, L1 protein produced by recombinant lactococci can self-assemble into structures morphologically similar to VLPs intracellularly. The presence of conformational epitopes on the L. lactis-derived VLPs was confirmed by ELISA using an anti-HPV16 L1 capsid antigen antibody. Our results support the feasibility of using recombinant food-grade LAB, such as L. lactis, for the production of L1-based VLPs and open the possibility for the development of a new safe mucosal vector for HPV-16 prophylactic vaccination.

  14. Human papillomavirus type 16 entry: retrograde cell surface transport along actin-rich protrusions.

    Directory of Open Access Journals (Sweden)

    Mario Schelhaas

    Full Text Available The lateral mobility of individual, incoming human papillomavirus type 16 pseudoviruses (PsV bound to live HeLa cells was studied by single particle tracking using fluorescence video microscopy. The trajectories were computationally analyzed in terms of diffusion rate and mode of motion as described by the moment scaling spectrum. Four distinct modes of mobility were seen: confined movement in small zones (30-60 nm in diameter, confined movement with a slow drift, fast random motion with transient confinement, and linear, directed movement for long distances. The directed movement was most prominent on actin-rich cell protrusions such as filopodia or retraction fibres, where the rate was similar to that measured for actin retrograde flow. It was, moreover, sensitive to perturbants of actin retrograde flow such as cytochalasin D, jasplakinolide, and blebbistatin. We found that transport along actin protrusions significantly enhanced HPV-16 infection in sparse tissue culture, cells suggesting a role for in vivo infection of basal keratinocytes during wound healing.

  15. Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

    Directory of Open Access Journals (Sweden)

    Haidar A. Shamran

    2015-01-01

    Full Text Available Human Cytomegalovirus (HCMV is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n=50 and from benign meningioma patients (n=30 were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG compared to 72.5% among control samples (P=0.04. These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis.

  16. The Vif accessory protein alters the cell cycle of human immunodeficiency virus type 1 infected cells.

    Science.gov (United States)

    Wang, Jiangfang; Shackelford, Jason M; Casella, Carolyn R; Shivers, Debra K; Rapaport, Eric L; Liu, Bindong; Yu, Xiao-Fang; Finkel, Terri H

    2007-03-15

    The viral infectivity factor gene (vif) of HIV-1 increases the infectivity of viral particles by inactivation of cellular anti-viral factors, and supports productive viral replication in primary human CD4 T cells and in certain non-permissive T cell lines. Here, we demonstrate that Vif also contributes to the arrest of HIV-1 infected cells in the G(2) phase of the cell cycle. Viruses deleted in Vif or Vpr induce less cell cycle arrest than wild-type virus, while cells infected with HIV-1 deleted in both Vif and Vpr have a cell cycle profile equivalent to that of uninfected cells. Furthermore, expression of Vif alone induces accumulation of cells in the G(2) phase of the cell cycle. These data demonstrate a novel role for Vif in cell cycle regulation and suggest that Vif and Vpr independently drive G(2) arrest in HIV-1 infected cells. Our results may have implications for the actions and interactions of key HIV-1 accessory proteins in AIDS pathogenesis.

  17. Enhanced replication of herpes simplex virus type 1 in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Miller, C.S.; Smith, K.O. (Univ. of Kentucky College of Dentistry, Lexington (USA))

    1991-02-01

    The effects of DNA-damaging agents on the replication of herpes simplex virus type 1 (HSV-1) were assessed in vitro. Monolayers of human lung fibroblast cell lines were exposed to DNA-damaging agents (methyl methanesulfonate (MMS), methyl methanethiosulfonate (MMTS), ultraviolet light (UV), or gamma radiation (GR)) at specific intervals, before or after inoculation with low levels of HSV-1. The ability of cell monolayers to support HSV-1 replication was measured by direct plaque assay and was compared with that of untreated control samples. In this system, monolayers of different cell lines infected with identical HSV-1 strains demonstrated dissimilar levels of recovery of the infectious virus. Exposure of DNA-repair-competent cell cultures to DNA-damaging agents produced time-dependent enhanced virus replication. Treatment with agent before virus inoculation significantly (p less than 0.025) increased the number of plaques by 10 to 68%, compared with untreated control cultures, while treatment with agent after virus adsorption significantly increased (p less than 0.025) the number of plaques by 7 to 15%. In a parallel series of experiments, cells deficient in DNA repair (xeroderma pigmentosum) failed to support enhanced virus replication. These results suggest that after exposure to DNA-damaging agents, fibroblasts competent in DNA repair amplify the replication of HSV-1, and that DNA-repair mechanisms that act on a variety of chromosomal lesions may be involved in the repair and biological activation of HSV-1 genomes.

  18. Chronic Osteomyelitis Increases the Incidence of Type 2 Diabetes in Humans and Mice.

    Science.gov (United States)

    Wang, Yicun; Wang, Jun; Deng, Zhantao; Jin, Jiewen; Jiang, Hui; Meng, Jia; Xu, Haidong; Zhao, Jianning; Sun, Guojing; Qian, Hongbo

    2017-01-01

    Background: To compare the risk of type 2 diabetes (T2DM) between patients with and without chronic osteomyelitis (COM), both in humans and in mice, and to explore risk factors in COM patients who developed T2DM. Methods: One hundred seven patients with COM and 114 patients without COM were consecutively enrolled and retrospectively analysed. Clinical data concerning the time to develop diabetes, glucose metabolism, lipid metabolism, inflammatory factors, mental health and frequency of specialist visits were collected. A mouse model of osteomyelitis was used to verify the presence of impaired glucose metabolism and depression. All data were processed by SPSS. Results: The incidence of T2DM was 2.37-fold higher in patients with COM than in those without. In COM patients, subjects with T2DM (DDM) had higher BMI, less exercise and more frequent visits to specialists than those without (Con). Glucose and lipid metabolism were worse in patients with DDM. Patients with DDM had higher levels of white blood cells (12.9±2.1×109/L vs. 11.7±2.2×109/L, p=0.027), CRP (28.4±4.5 mg/L vs. 22.0±4.8 mg/L, pmental illness and lack of exercise were risk factors for the occurrence of T2DM in osteomyelitis. Comprehensive consideration of patient history, including metabolism and mental health, is needed in planning future treatment.

  19. Proviral Progeny of Heterodimeric Virions Reveal a High Crossover Rate for Human Immunodeficiency Virus Type 2▿

    OpenAIRE

    Mukherjee, Sayandip; Lee, Hui-Ling Rose; Ron, Yacov; Dougherty, Joseph P.

    2006-01-01

    Human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS in humans, exhibits a very high rate of recombination. Bearing in mind the significant epidemiological and clinical contrast between HIV-2 and HIV-1 as well as the critical role that recombination plays in viral evolution, we examined the nature of HIV-2 recombination. Towards this end, a strategy was devised to measure the rate of crossover of HIV-2 by evaluating recombinant progeny produced exclusively by heterodimeric...

  20. Production of Interferon α by Human Immunodeficiency Virus Type 1 in Human Plasmacytoid Dendritic Cells Is Dependent on Induction of Autophagy

    OpenAIRE

    Zhou, Dejiang; Kang, Kyung Hee; Spector, Stephen A.

    2012-01-01

    Background. The mechanisms responsible for interferon α (IFN-α) production by plasmacytoid dendritic cells (pDCs) during human immunodeficiency virus type 1 (HIV-1) infection are unknown. This research examined the roles of Toll-like receptor 7 (TLR7) and autophagy in IFN-α production by pDCs during HIV-1 infection.

  1. Bile salt-stimulated lipase from human milk binds DC-SIGN and inhibits human immunodeficiency virus type 1 transfer to CD4+ T cells

    NARCIS (Netherlands)

    Naarding, Marloes A.; Dirac, Annette M.; Ludwig, Irene S.; Speijer, Dave; Lindquist, Susanne; Vestman, Eva-Lotta; Stax, Martijn J.; Geijtenbeek, Teunis B. H.; Pollakis, Georgios; Hernell, Olle; Paxton, William A.

    2006-01-01

    A wide range of pathogens, including human immunodeficiency virus type 1 (HIV-1), hepatitis C virus, Ebola virus, cytomegalovirus, dengue virus, Mycobacterium, Leishmania, and Helicobacter pylori, can interact with dendritic cell (DC)-specific ICAM3-grabbing nonintegrin (DC-SIGN), expressed on DCs

  2. Simultaneous human papilloma virus type 16 E7 and cdk inhibitor p21 expression induces apoptosis and cathepsin B activation

    DEFF Research Database (Denmark)

    Kaznelson, Dorte Wissing; Bruun, Silas; Monrad, Astrid

    2004-01-01

    Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation and induc......Human papillomavirus type 16 (HPV-16) is the major risk factor for development of cervical cancer. The major oncoprotein E7 enhances cell growth control. However, E7 has in some reports been shown to induce apoptosis suggesting that there is a delicate balance between cell proliferation...

  3. Stoichiometry of monoclonal antibody neutralization of T-cell line-adapted human immunodeficiency virus type 1

    DEFF Research Database (Denmark)

    Schønning, Kristian; Lund, O; Lund, O S

    1999-01-01

    In order to study the stoichiometry of monoclonal antibody (MAb) neutralization of T-cell line-adapted human immunodeficiency virus type 1 (HIV-1) in antibody excess and under equilibrium conditions, we exploited the ability of HIV-1 to generate mixed oligomers when different env genes are coexpr......In order to study the stoichiometry of monoclonal antibody (MAb) neutralization of T-cell line-adapted human immunodeficiency virus type 1 (HIV-1) in antibody excess and under equilibrium conditions, we exploited the ability of HIV-1 to generate mixed oligomers when different env genes...

  4. Confocal and conventional immunofluorescent and immunogold electron microscopic localization of collagen types III and IV in human placenta.

    Science.gov (United States)

    Nanaev, A K; Rukosuev, V S; Shirinsky, V P; Milovanov, A P; Domogatsky, S P; Duance, V C; Bradbury, F M; Yarrow, P; Gardiner, L; d'Lacey, C

    1991-01-01

    Confocal and conventional indirect immunofluorescence and immunogold electron microscopic methods were applied to examine the distribution of extracellular matrix constituents (collagens types III and IV) in the villi of immature and term human placentae. The immunofluorescence study revealed that collagen type III is more distinct in the villous stroma of term placenta as compared with that of the first trimester. Collagen type IV was detected mainly in endothelial and epithelial basement membranes and interestingly also to a certain extent in the stroma. Results obtained using immunoelectron microscopy support the proposal that collagen types III and IV are characteristic of stromal and basement membranes, respectively. Stromal collagen type IV is apparently localized in association with the interstitial types of collagen (I and III), in the villous stroma of term placenta.

  5. Source attribution of human Campylobacter isolates by MLST and fla-typing and association of genotypes with quinolone resistance.

    Directory of Open Access Journals (Sweden)

    Sonja Kittl

    Full Text Available Campylobacteriosis is the most frequent zoonosis in developed countries and various domestic animals can function as reservoir for the main pathogens Campylobacter jejuni and Campylobacter coli. In the present study we compared population structures of 730 C. jejuni and C. coli from human cases, 610 chicken, 159 dog, 360 pig and 23 cattle isolates collected between 2001 and 2012 in Switzerland. All isolates had been typed with multi locus sequence typing (MLST and flaB-typing and their genotypic resistance to quinolones was determined. We used complementary approaches by testing for differences between isolates from different hosts with the proportion similarity as well as the fixation index and by attributing the source of the human isolates with Bayesian assignment using the software STRUCTURE. Analyses were done with MLST and flaB data in parallel and both typing methods were tested for associations of genotypes with quinolone resistance. Results obtained with MLST and flaB data corresponded remarkably well, both indicating chickens as the main source for human infection for both Campylobacter species. Based on MLST, 70.9% of the human cases were attributed to chickens, 19.3% to cattle, 8.6% to dogs and 1.2% to pigs. Furthermore we found a host independent association between sequence type (ST and quinolone resistance. The most notable were ST-45, all isolates of which were susceptible, while for ST-464 all were resistant.

  6. Source attribution of human Campylobacter isolates by MLST and fla-typing and association of genotypes with quinolone resistance.

    Science.gov (United States)

    Kittl, Sonja; Heckel, Gerald; Korczak, Bożena M; Kuhnert, Peter

    2013-01-01

    Campylobacteriosis is the most frequent zoonosis in developed countries and various domestic animals can function as reservoir for the main pathogens Campylobacter jejuni and Campylobacter coli. In the present study we compared population structures of 730 C. jejuni and C. coli from human cases, 610 chicken, 159 dog, 360 pig and 23 cattle isolates collected between 2001 and 2012 in Switzerland. All isolates had been typed with multi locus sequence typing (MLST) and flaB-typing and their genotypic resistance to quinolones was determined. We used complementary approaches by testing for differences between isolates from different hosts with the proportion similarity as well as the fixation index and by attributing the source of the human isolates with Bayesian assignment using the software STRUCTURE. Analyses were done with MLST and flaB data in parallel and both typing methods were tested for associations of genotypes with quinolone resistance. Results obtained with MLST and flaB data corresponded remarkably well, both indicating chickens as the main source for human infection for both Campylobacter species. Based on MLST, 70.9% of the human cases were attributed to chickens, 19.3% to cattle, 8.6% to dogs and 1.2% to pigs. Furthermore we found a host independent association between sequence type (ST) and quinolone resistance. The most notable were ST-45, all isolates of which were susceptible, while for ST-464 all were resistant.

  7. Development of a Transgenic Mouse with R124H Human TGFBI Mutation Associated with Granular Corneal Dystrophy Type 2.

    Science.gov (United States)

    Yamazoe, Katsuya; Yoshida, Satoru; Yasuda, Miyuki; Hatou, Shin; Inagaki, Emi; Ogawa, Yoko; Tsubota, Kazuo; Shimmura, Shigeto

    2015-01-01

    To investigate the phenotype and predisposing factors of a granular corneal dystrophy type 2 transgenic mouse model. Human TGFBI cDNA with R124H mutation was used to make a transgenic mouse expressing human protein (TGFBIR124H mouse). Reverse transcription PCR (RT-PCR) was performed to analyze TGFBIR124H expression. A total of 226 mice including 23 homozygotes, 106 heterozygotes and 97 wild-type mice were examined for phenotype. Affected mice were also examined by histology, immunohistochemistry and electron microcopy. RT-PCR confirmed the expression of TGFBIR124H in transgenic mice. Corneal opacity defined as granular and lattice deposits was observed in 45.0% of homozygotes, 19.4% of heterozygotes. The incidence of corneal opacity was significantly higher in homozygotes than in heterozygotes (p = 0.02). Histology of affected mice was similar to histology of human disease. Lesions were Congo red and Masson Trichrome positive, and were observed as a deposit of amorphous material by electron microscopy. Subepithelial stroma was also stained with thioflavin T and LC3, a marker of autophagy activation. The incidence of corneal opacity was higher in aged mice in each group. Homozygotes were not necessarily more severe than heterozygotes, which deffers from human cases. We established a granular corneal dystrophy type 2 mouse model caused by R124H mutation of human TGFBI. Although the phenotype of this mouse model is not equivalent to that in humans, further studies using this model may help elucidate the pathophysiology of this disease.

  8. Evolution of type-specific immunoassays to evaluate the functional immune response to Gardasil: a vaccine for human papillomavirus types 16, 18, 6 and 11.

    Science.gov (United States)

    Smith, Judith F; Kowalski, Rose; Esser, Mark T; Brown, Martha J; Bryan, Janine T

    2008-01-01

    Epidemiological studies and clinical trials of vaccines depend on the accurate measurement of antibodies within the polyclonal response to infection or vaccination. The assay currently used to measure the antibody response to vaccination with GARDASIL [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]--a quadrivalent vaccine used against human papillomavirus (HPV) types 6, 11, 16, and 18--is a competitive Luminex assay (cLIA) that uses multiplex technology to detect type-specific neutralizing antibodies against all four HPV types in a single serum sample. Here we describe how the cLIA was developed, as well as how the monoclonal antibodies (mAbs), used as competitors in the assay, were characterized. An enzyme-linked immunosorbent assay (ELISA) was used to screen eight previously-identified mAbs for their ability to bind to HPV virus-like particles (VLPs) in a type-specific and conformation-dependent manner. Four of these mAbs, H6.M48, K11.B2, H16.V5, and H18.J4, met our specifications and were shown to have the potential to neutralize HPV infection in hemagglutination inhibition and pseudovirus neutralization assays. The competitive immunoassay format was able to distinguish type-specific antibodies in the sera of nonhuman primates vaccinated with HPV VLPs, whereas a traditional direct-bind ELISA could not. In addition, the serum antibodies measured by the competitive assay are known to be neutralizing, whereas the ELISA does not distinguish neutralizing and nonneutralizing antibodies in a serum sample. By detecting antibodies to neutralizing epitopes, the competitive assay both demonstrates sero-conversion and provides a potential functional link between sero-conversion and protective immunity in response to vaccination with GARDASIL.

  9. Two novel genital human papillomavirus (HPV) types, HPV68 and HPV70, related to the potentially oncogenic HPV39.

    OpenAIRE

    Longuet, M; Beaudenon, S; Orth, G

    1996-01-01

    The genomes of two novel human papillomavirus (HPV) types, HPV68 and HPV70, were cloned from a low-grade cervical intraepithelial neoplasia and a vulvar papilloma, respectively, and partially sequenced. Both types are related to HPV39, a potentially oncogenic virus. HPV68 and HPV70 were also detected in genital intraepithelial neoplasia from three patients and one patient, respectively. Comparison with sequence data in the literature indicates that the subgenomic ME180-HPV DNA fragment, clone...

  10. Adults Play but Not Like Their Young: The Frequency and Types of Play by Belugas (Delphinapterus leucas) in Human Care

    OpenAIRE

    Heather Hill; Domonique Ramirez

    2014-01-01

    While play occurs in many taxa with younger conspecifics engaging in play behaviors more often than older conspecifics, little empirical research currently exists on play by white whales, or belugas, (Delphinapterus leucas). The purpose of the current study was to explore the types of play exhibited by a group of belugas in human care. Archived video footage representing 24.5 hours of observation time collected over three years for 14 belugas (5 immature and 9 adults) was coded for type, freq...

  11. Against which human papillomavirus types shall we vaccinate and screen? The international perspective.

    NARCIS (Netherlands)

    Munoz, N.; Bosch, F.X.; Castellsague, X; Diaz, M; Sanjose, de S; Hammouda, D; Shah, K.V.; Meijer, C.J.L.M.

    2004-01-01

    At least 15 types of HPV have been associated with cervical cancer, but current HPV vaccines confer only type-specific immunity. To determine geographic variations in the HPV type distribution in cervical cancer, we carried out a pooled analysis of data from an international survey of HPV types in

  12. Oncogenic Human Papillomavirus (HPV) Type Distribution and HPV Type 16 E6 Variants in Two Spanish Population Groups with Different Levels of HPV Infection Risk

    Science.gov (United States)

    Ortiz, M.; Torres, M.; Muñoz, L.; Fernández-García, E.; Canals, J.; Cabornero, A. I.; Aguilar, E.; Ballesteros, J.; del Amo, J.; García-Sáiz, A.

    2006-01-01

    The aim of this study is to determine oncogenic human papillomavirus (HPV) types and HPV type 16 (HPV16) variant distribution in two Spanish population groups, commercial sex workers and imprisoned women (CSW/IPW) and the general population. A multicenter cross-sectional study of 1,889 women from five clinical settings in two Spanish cities was conducted from May to November 2004. Oncogenic HPV infection was tested by an Hybrid Capture II (HC2) test, and positive samples were genotyped by direct sequencing using three different primer sets in L1 (MY09/11 and GP5+/GP6+) and E6/E7. HPV16 variants were identified by sequencing the E6, E2, and L1 regions. Four hundred twenty-five samples were positive for the HC2 test, 31.5% from CSW/IPW and 10.7% from the general population. HPV16 was the most frequent type. Distinct profiles of oncogenic HPV type prevalence were observed across the two populations. In order of decreasing frequency, HPV types 16, 31, 58, 66, 56, and 18 were most frequent in CSW/IPW women, and types 16, 31, 52, 68, 51, and 53 were most frequent in the general population. We analyzed HPV16 intratype variants, and a large majority (78.7%) belonged to the European lineage. AA variants were detected in 16.0% of cases. African variants belonging to classes Af1 (4.0%) and Af2 (1.3%) were detected. Different HPV types and HPV16 intratype variants are involved in oncogenic HPV infections in our population. These results suggest that HPV type distribution differs in CSW/IPW women and in the general population, although further analysis is necessary. PMID:16597872

  13. Experimental adaptation of wild-type canine distemper virus (CDV) to the human entry receptor CD150.

    Science.gov (United States)

    Bieringer, Maria; Han, Jung Woo; Kendl, Sabine; Khosravi, Mojtaba; Plattet, Philippe; Schneider-Schaulies, Jürgen

    2013-01-01

    Canine distemper virus (CDV), a close relative of measles virus (MV), is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17(red) adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F) genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (10(2) pfu/ml) in Vero cells expressing human CD150 (Vero-hSLAM). After three passages using these cells virus was adapted to human CD150 and replicated to high titres (10(5) pfu/ml). Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G) was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L) and Gly to Glu (G71E), and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.

  14. Experimental adaptation of wild-type canine distemper virus (CDV to the human entry receptor CD150.

    Directory of Open Access Journals (Sweden)

    Maria Bieringer

    Full Text Available Canine distemper virus (CDV, a close relative of measles virus (MV, is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17(red adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (10(2 pfu/ml in Vero cells expressing human CD150 (Vero-hSLAM. After three passages using these cells virus was adapted to human CD150 and replicated to high titres (10(5 pfu/ml. Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L and Gly to Glu (G71E, and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.

  15. NARRATIVAS HAGIOGRÁFICAS Y REPRESENTACIONES DEMONOLÓGICAS: EL DEMONIO EN LOS CLAUSTROS DEL PERÚ VIRREINAL. SIGLO XVII

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    René Millar Carvacho

    2011-12-01

    Full Text Available En el Perú del siglo XVII, caracterizado por una intensa religiosidad, los hombres y mujeres virtuosos vivieron en una permanente confrontación con el demonio, la que fue entendida como expresión del conflicto que se daba entre el Bien y el Mal desde el comienzo de los tiempos y que no culminaría sino hasta el término de ellos. El demonio, al intentar la perdición de los "santos", pretendía destruir la obra de Dios, en la medida en que aquellos eran sus elegidos. Pero, por otra parte, el demonio actuaba en estas materias con permiso de Dios, que buscaba de esa manera probar la fortaleza de sus hijos predilectos. En el presente artículo, utilizando los relatos hagiográficos, se analizan esos fenómenos y se describen las estrategias que utilizaba el demonio para hacer caer a los "santos", se examinan los medios a los que estos recurrían en sus luchas y el significado que tenían esas confrontaciones. Buscamos comprender por qué para la sociedad peruana del siglo XVII, y todavía más para los "santos", el demonio mantuvo un protagonismo en la cotidianeidad a lo largo de toda la centuria, mientras que en Europa su imagen tendía a diluirse.In seventeenth century Peru, which was characterized by an intense religiosity, virtuous men and women lived in a permanent confrontation with the devil that was understood as an expression of the conflict between Good and Evil that existed from the beginning of time and would last until the end of time. The devil, attempting the perdition of the "saints", tried to destroy the work of God, because they were his chosen. But, on the other hand, the devil acted in these matters with Gods permission who in this way tried to test the strength of his favored children. Using hagiographic accounts, this article analyzes these phenomena and describes the strategies that the devil used in order to make the "saints" fall. It also examines the means those turned to in their struggles and the meaning that those

  16. "Teorías de la percepción visual y aristotelismo entre los siglos XV y XVII: una aproximación" [A preliminary approach on theories of visual perception and aristotelianism in the fifteenth to seventeenth centuries

    Directory of Open Access Journals (Sweden)

    José Javier Benéitez Prudencio

    2011-01-01

    Full Text Available RESUMEN:Entre los siglos XV y principios del XVII la explicación aristotélica todavía garantizaba una idea de percepción visual exacta y digna de confianza, en especial la que se refiere a aquellas facultades humanas pertenecientes a la conocida como ‘alma sensitiva’. Considerando los términos generales en que dicha teoría se planteaba, reputada por otro lado por la literatura médica, psicológica y moral del momento, lo que en este ensayo pretendo poner de relieve son las influencias de dicha teoría aristotélica en el panorama intelectual europeo antes de Descartes.ABSTRACT:Visual perception and cognition deemed to be accurate and reliable were secured between the fifteenth and the very beginning seventeenth centuries largely by the Aristotelian theory, especially those human faculties belonging to what was called the ‘sensible soul’. In terms of this theory, recounted throughout the medical, psychological and moral literature of early Modern Age, I wish to emphasize in this paper the Aristotelian theoretical influences in the intellectual culture of pre-Cartesian Europe.

  17. Resistant mechanism against nelfinavir of subtype C human immunodeficiency virus type 1 proteases

    Science.gov (United States)

    Liu, Xiaoqing; Dai, Qi; Li, Lihua; Xiu, Zhilong

    2011-02-01

    Human immunodeficiency virus type 1 protease (HIV-1 PR) is one of the major targets of anti-AIDS drug discovery, and the subtype C HIV-1 is infecting more and more humans. In this work, we executed computational simulations of subtype B (labeled B(WT)) HIV-1 PR, D30N mutant B (labeled B(D30N)) HIV-1 PR, subtype C (labeled C(Ref)) HIV-1 PR, D30N mutant C (labeled C(D30N)) HIV-1 PR, and D30N/N83T mutant C (labeled C(D30N/N83T)) HIV-1 PR with drug nelfinavir (NFV), aiming at clarifying (1) the resistant mechanism against NFV due to D30N mutation in subtype C HIV-1 PR; (2) the reason that the emergence rate of N83T mutation in C(D30N) HIV-1 PR is higher than that in B(D30N) HIV-1 PR; (3) the affinity of NFV with C(D30N/N83T) HIV-1 PR is higher than B(D30N) and C(D30N) HIV-1 PRs. The results indicate: (1) D30N mutation in subtype C HIV-1 PR reduces the hydrogen bond between the 30th residue and NFV, and the binding free energy contributions of some residues decrease; (2) the hydrogen bonds between the 83th/83'th residue and the 34th/34'th residue exist in both B(D30N) and C(D30N/N83T) HIV-1 PRs, while they disappear in C(D30N) HIV-1 PR. Meanwhile, the binding free energy contribution of N30 in C(D30N) is lower than that in B(D30N) and C(D30N/N83T); (3) N83T mutation makes some residues dislocate, and the contributions of these residues to binding free energy in C(D30N/N83T) increase comparing to those in B(D30N) and C(D30N). Our findings suggest that despite the nonactive site mutations, the polymorphisms regulate the emergence rates of these drug-resistant mutants.

  18. Type XV collagen exhibits a widespread distribution in human tissues but a distinct localization in basement membrane zones.

    Science.gov (United States)

    Myers, J C; Dion, A S; Abraham, V; Amenta, P S

    1996-12-01

    The collagen family of proteins consists of 19 types encoded by 33 genes. One of the more recently discovered collagens is the alpha1 chain of type XV. Type XV collagen is comprised of a 577-amino-acid, highly interrupted, triple-helical region that is flanked by amino and carboxy noncollagenous domains of 555 and 256 residues, respectively. To address questions of where this collagen is localized and what its function may entail, we produced a bacteria-expressed recombinant protein representing the first half of the type XV collagen carboxy-terminal domain in order to generate highly specific polyclonal antisera. Immunoscreening of an expression library with the affinity-purified antibody revealed three clones coding for part of the type XV triple-helical region and the entire noncollagenous carboxy-terminus. Western blot analysis of human tissue homogenates identified a 116-kDa collagenase-sensitive protein and a 27-kDa collagenase-resistant fragment, whose electrophoretic mobilities were unchanged in the presence and absence of reductant. Northern blot hybridization to human tissue RNAs indicated that type XV has a prevalent and widespread distribution. To determine the precise localization of type XV collagen, immunohistochemical analyses at the light- and electron-microscopic levels were performed. Type XV exhibited a surprisingly restricted and uniform presence in many human tissues as evidenced by a strong association with vascular, neuronal, mesenchymal, and some epithelial basement membrane zones. These data suggest that type XV collagen may function in some manner to adhere basement membrane to the underlying connective tissue stroma.

  19. Monomeric, porous type II collagen scaffolds promote chondrogenic differentiation of human bone marrow mesenchymal stem cells in vitro

    Science.gov (United States)

    Tamaddon, M.; Burrows, M.; Ferreira, S. A.; Dazzi, F.; Apperley, J. F.; Bradshaw, A.; Brand, D. D.; Czernuszka, J.; Gentleman, E.

    2017-03-01

    Osteoarthritis (OA) is a common cause of pain and disability and is often associated with the degeneration of articular cartilage. Lesions to the articular surface, which are thought to progress to OA, have the potential to be repaired using tissue engineering strategies; however, it remains challenging to instruct cell differentiation within a scaffold to produce tissue with appropriate structural, chemical and mechanical properties. We aimed to address this by driving progenitor cells to adopt a chondrogenic phenotype through the tailoring of scaffold composition and physical properties. Monomeric type-I and type-II collagen scaffolds, which avoid potential immunogenicity associated with fibrillar collagens, were fabricated with and without chondroitin sulfate (CS) and their ability to stimulate the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells was assessed. Immunohistochemical analyses showed that cells produced abundant collagen type-II on type-II scaffolds and collagen type-I on type-I scaffolds. Gene expression analyses indicated that the addition of CS - which was released from scaffolds quickly - significantly upregulated expression of type II collagen, compared to type-I and pure type-II scaffolds. We conclude that collagen type-II and CS can be used to promote a more chondrogenic phenotype in the absence of growth factors, potentially providing an eventual therapy to prevent OA.

  20. Human papillomavirus vaccines and the potential for cross-protection between related HPV types.

    Science.gov (United States)

    Ault, Kevin A

    2007-11-01

    The majority of human papillomavirus (HPV) belong to the genus alpha-papillomavirus, which can be further subdivided into species and then strains. Approximately 200 strains of HPV have been identified, and the whole genomes of approximately 100 strains have been (discovered) and completely sequenced. Between 13 and 18 HPV strains have been characterized as conferring a high oncogenic risk, with 12 of these strains belonging to the HPV species 7 (HPV-18, -39, -45, -59, -68) and species 9 (HPV-16, -31, -33, -35, -52, -58, -67). While strains belonging to the same species are phylogenetically related, they may differ biologically. The available data on whether natural HPV infection infers cross protection against other related strains from the same species are equivocal. There are data to indicate that following HPV infection, there appears to be a reduced risk of contracting the same strain of HPV. However, there is also evidence to indicate that natural infection with HPV does not confer group-specific immune protection or general protection from reinfection with genital HPV mucosal types. Recent studies conducted with HPV vaccines show data on cross-protection against related HPV strains. In vitro experiments with serum from recipients of the quadrivalent HPV vaccine (HPV-6/8/16/18) show neutralization of HPV 45 pseudovirions. Cross-protection following vaccination of women (n=776) with three doses of bivalent HPV vaccine (HPV-16/18) demonstrated that, over a period of up to 4.5 years, long-term vaccine efficacy was observed for HPV-16 and -18, and vaccine efficacy was also observed against incident infection with HPV-31 and -45. These findings are supported by the results of a large study (n=18,644) in women aged 15 to 25 years vaccinated with the adjuvant bivalent HPV vaccine (HPV-16/18). Over a period of 6 months, cross-protection was observed against persistent infections with HPV-45, -31 and -52, and at 12 months, modest protection was demonstrated against

  1. Immunofluorescent localization of collagen types I, III, IV, V, fibronectin, laminin, entactin, and heparan sulphate proteoglycan in human immature placenta.

    Science.gov (United States)

    Rukosuev, V S

    1992-03-15

    The distribution of eight components of the extracellular matrix in immature human placenta was studied by an indirect immunofluorescence method with monospecific antibodies. In the stroma of the term chorionic villi, collagen types I, III, IV, V, and fibronectin formed a mesh of fibers and conglomerates. Heparan sulphate proteoglycan formed multiple conglomerates, whereas laminin comprised small, scanty, discrete granules. Collagen type IV, laminin, entactin, and heparan sulphate proteoglycan were confined to the basement membrane of the trophoblast. Sometimes, only collagen type IV was identified in fetal vascular basement membrane.

  2. The role of valence on the high-affinity binding of Griffonia simplicifolia isolectins to type A human erythrocytes.

    Science.gov (United States)

    Knibbs, R N; Takagaki, M; Blake, D A; Goldstein, I J

    1998-12-01

    The Griffonia simplicifolia-I (GS-I) isolectins have been used to probe the effect of lectin valence on their high-affinity binding to human erythrocytes. These tetrameric lectins are composed of A and B subunits and constitute a series of five isolectins (A4, A3B, A2B2, AB3, B4). The A subunit is specific for alpha-D-GalNAc end groups and binds to the blood type A determinant GalNAcalpha1, as well as to terminal alpha-D-Gal groups found on type B cells. The B subunit is specific for alpha-D-Gal end groups, and binds very specifically to type B erythrocytes. This series of isolectins is tetravalent (A4), trivalent (A3B), divalent (A2B2), and monovalent (AB3) for type A erythrocytes; thus, this system provides the opportunity to examine the effect of lectin valency on the association constants of these GS-I isolectins binding to cells. Cell binding experiments carried out using 125I-labeled GS-I isolectins and type A human erythrocytes allowed us to demonstrate that (1) the association constant of the isolectin monovalent for alpha-D-GalNAc (AB3) is virtually identical to its association constant for the haptenic sugar methyl-N-acetyl-alpha-D-galactosaminide, reported previously, and (2) the association constant of the GS-I isolectins for human type A erythrocytes increases with increasing valency of the isolectin. These results indicate that the increased affinity displayed by the GS-I isolectins for human type A erythrocytes is dependent on their multivalency, and not on an extended binding site nor on nonspecific, or noncarbohydrate, interactions of the lectin with the cell surface. These findings should be of general relevance to understanding the high-affinity interactions observed between other multivalent proteins and multivalent ligands (e.g., cell surfaces).

  3. Molecular typing by pulsed-field gel electrophoresis of Flavobacterium psychrophilum isolates derived from Japanese fish.

    Science.gov (United States)

    Arai, H; Morita, Y; Izumi, S; Katagiri, T; Kimura, H

    2007-06-01

    Sixty-four isolates of Flavobacterium psychrophilum from ayu, Plecoglossus altivelis altivelis (Temminck & Schlegel), and other fish (n=16) in Japan and the type strain (NCIMB 1947(T)) were typed using pulsed-field gel electrophoresis (PFGE) with endonuclease BlnI and XhoI. These isolates were classified into 20 clusters and 42 genotypes by PFGE analysis. The most predominant cluster of isolates from ayu was cluster XII (n=20), followed by clusters XVII, XVI, XX, XI, IX, X, XIII and XV; the remaining 17 isolates from other fish were divided into clusters I, II, III, IV, V, VI, VII, VIII, XIV, XVIII and XIX. The PFGE genotype of isolates from ayu clearly differed from those of other fish. The isolates from ayu in Gunma Prefecture belonged to clusters XII, XVI, XVII and XX, and the strains of three of these clusters (XII, XVII and XX) were isolated from ayu in 15 of 19 prefectures. PFGE typing enabled more accurate classification of isolates into clusters than previously achieved by analysing the restriction fragment length polymorphism of PCR products. These results suggest that F. psychrophilum isolated from ayu and other fish are genetically different and strains with several PFGE types have spread within Japan.

  4. Unique cell type-specific junctional complexes in vascular endothelium of human and rat liver sinusoids.

    Directory of Open Access Journals (Sweden)

    Cyrill Géraud

    Full Text Available Liver sinusoidal endothelium is strategically positioned to control access of fluids, macromolecules and cells to the liver parenchyma and to serve clearance functions upstream of the hepatocytes. While clearance of macromolecular debris from the peripheral blood is performed by liver sinusoidal endothelial cells (LSECs using a delicate endocytic receptor system featuring stabilin-1 and -2, the mannose receptor and CD32b, vascular permeability and cell trafficking are controlled by transcellular pores, i.e. the fenestrae, and by intercellular junctional complexes. In contrast to blood vascular and lymphatic endothelial cells in other organs, the junctional complexes of LSECs have not yet been consistently characterized in molecular terms. In a comprehensive analysis, we here show that LSECs express the typical proteins found in endothelial adherens junctions (AJ, i.e. VE-cadherin as well as α-, β-, p120-catenin and plakoglobin. Tight junction (TJ transmembrane proteins typical of endothelial cells, i.e. claudin-5 and occludin, were not expressed by rat LSECs while heterogenous immunreactivity for claudin-5 was detected in human LSECs. In contrast, junctional molecules preferentially associating with TJ such as JAM-A, B and C and zonula occludens proteins ZO-1 and ZO-2 were readily detected in LSECs. Remarkably, among the JAMs JAM-C was considerably over-expressed in LSECs as compared to lung microvascular endothelial cells. In conclusion, we show here that LSECs form a special kind of mixed-type intercellular junctions characterized by co-occurrence of endothelial AJ proteins, and of ZO-1 and -2, and JAMs. The distinct molecular architecture of the intercellular junctional complexes of LSECs corroborates previous ultrastructural findings and provides the molecular basis for further analyses of the endothelial barrier function of liver sinusoids under pathologic conditions ranging from hepatic inflammation to formation of liver metastasis.

  5. Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects.

    Science.gov (United States)

    Braat, E A; Levi, M; Bos, R; Haverkate, F; Lassen, M R; de Maat, M P; Rijken, D C

    1999-08-01

    Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process that may protect a blood clot from early fibrinolysis. It is not known under what circumstances tcu-PA/T can be generated in vivo. We have studied the occurrence of tcu-PA/T in human subjects with a varying degree of hypercoagulability. tcu-PA/T was assessed in the plasma of patients with disseminated intravascular coagulation (DIC), endotoxin-treated volunteers, patients with unstable angina pectoris, and patients selected for hip replacement. Relationships between tcu-PA/T and several markers reflecting thrombin generation were examined. tcu-PA/T was observed only in the plasma of patients with DIC and was associated with all thrombin markers and with scu-PA and urokinase antigen. Prothrombin fragment 1 + 2 and urokinase antigen were independent predictors of tcu-PA/T. The fact that tcu-PA/T could not be detected in the other three groups was explained by a lower extent of thrombin generation, a greater inhibition of thrombin by antithrombin, or less available urokinase antigen in these groups. The contribution of scu-PA to total urokinase antigen was decreased in the patients with DIC because of inactivation by thrombin, which may be an additional explanation for the inadequate fibrinolysis observed in these patients. These findings show that scu-PA can be inactivated in the circulation under severe pathophysiologic circumstances and that the process of inactivation depends not only on the generation of thrombin but also on the control of thrombin activity by its inhibitor antithrombin.

  6. Synthetic genes for human muscle-type adenylate kinase in Escherichia coli.

    Science.gov (United States)

    Kim, H J; Nishikawa, S; Tanaka, T; Uesugi, S; Takenaka, H; Hamada, M; Kuby, S A

    1989-01-01

    An artificial gene coding for the human muscle-type cytosolic adenylate kinase (hAK1) was chemically synthesized and directly expressed in Escherichia coli under the control of trp promoter. The DNA duplex of 596 bp was designed and constructed from 40 oligonucleotide fragments of typically 30 nucleotides in length. Twelve unique restriction sites were fairly evenly spaced in the synthetic gene to facilitate site-specific mutagenesis at any part of this recombinant protein. The genes for mutant hAK1 (Tyr 95----Phe 95, Y95F hAK1; Arg 97----Ala 97, R97A hAK1) were constructed by cassette mutagenesis and utilized restriction sites incorporated in the hAK1 gene. The recombinant hAK1 was purified to homogeneity by a two-step chromatographic procedure with a good yield, and showed the same adenylate kinase activity as that of authentic hAK1. Preliminary kinetic studies show that the enzymatic activity (Vmax app,cor/Et) of Y95F hAK1 was slightly greater than that of recombinant hAK1, whereas R97A hAK1 still possessed approximately 4% of recombinant hAK1 activity. These results suggest that the Arg-97 residue is important but not essential for catalytic activity, and that Tyr-95 can be replaced by phenylalanine without substantial effects on the enzymatic activity. Moreover, preliminary estimates of the apparent kinetic parameters suggest that these residues are not required for MgATP binding, and therefore they do not appear to be part of the MgATP binding site.

  7. Quantitative assessment of subclinical spasticity in human T-cell lymphotropic virus type I infection

    Science.gov (United States)

    Zunt, J.R.; Alarcón, J.O.V.; Montano, S.; Longstreth, W.T.; Price, R.; Holmes, K.K.

    2009-01-01

    Objective To compare human T-cell lymphotrophic virus type I (HTLV-I) seropositive and seronegative women for symptoms and signs of spasticity. Background Infection with HTLV-I causes tropical spastic paraparesis/ HTLV-I–associated myelopathy (TSP/HAM). Certain populations, including female commercial sex workers (FSW), are at increased risk of developing this infection. Fewer than 5% of HTLV-I–seropositive persons develop TSP/HAM, which is typically associated with spasticity. Methods Cross-sectional study of 255 registered FSW in Callao, Perú, involving a questionnaire detailing demographics and neurologic symptoms, standard neurologic examination, quantitative assessment of spasticity (QSA) of muscle tone, and serologic testing for HTLV-I. Participants and examiners were blinded to serology results. Results On the questionnaire and neurologic examination, none of the 32 HTLV-I–seropositive or 223 seronegative women had signs or symptoms of spasticity. However, mean values on QSA were significantly higher among seropositive women (27.1 Newton-meters/radian [N-m/r]) than among seronegative women (21.6 N-m/r, p = 0.01), indicating a subclinical increase in lower extremity tone. With values of QSA divided into tertiles, and the first tertile serving as the comparison group, the odds ratio for seropositivity was 1.4 (95% confidence interval [CI] 1.0 to 2.0) in the second and 3.1 (95% CI 2.2 to 4.3) in the third tertile, after adjusting for age and place of birth. Conclusions Although a standard neurologic evaluation could not distinguish between women with and without HTLV-I infection, QSA indicated significantly increased lower extremity tone in those with infection. Long-term follow-up will determine whether these subclinical findings in asymptomatic women progress to overt TSP/HAM. PMID:10430431

  8. Ultrasensitive quantitation of human papillomavirus type 16 E6 oncogene sequences by nested real time PCR

    Directory of Open Access Journals (Sweden)

    López-Revilla Rubén

    2010-05-01

    Full Text Available Abstract Background We have developed an ultrasensitive method based on conventional PCR preamplification followed by nested amplification through real time PCR (qPCR in the presence of the DNA intercalating agent EvaGreen. Results Amplification mixtures calibrated with a known number of pHV101 copies carrying a 645 base pair (bp-long insert of the human papillomavirus type 16 (HPV16 E6 oncogene were used to generate the E6-1 amplicon of 645 bp by conventional PCR and then the E6-2 amplicon of 237 bp by nested qPCR. Direct and nested qPCR mixtures for E6-2 amplification corresponding to 2.5 × 102-2.5 × 106 initial pHV101 copies had threshold cycle (Ct values in the ranges of 18.7-29.0 and 10.0-25.0, respectively. The Ct of qPCR mixtures prepared with 1/50 volumes of preamplified mixtures containing 50 ng of DNA of the SiHa cell line (derived from an invasive cervical cancer with one HPV16 genome per cell was 19.9. Thermal fluorescence extinction profiles of E6-2 amplicons generated from pHV101 and SiHa DNA were identical, with a peak at 85.5°C. Conclusions Our method based on conventional preamplification for 15 cycles increased 10,750 times the sensitivity of nested qPCR for the quantitation of the E6 viral oncogene and confirmed that the SiHa cell line contains one E6-HPV16 copy per cell.

  9. Clinical manifestations of human T lymphotropic virus type I-infected patients with systemic lupus erythematosus.

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    Akimoto, Masaki; Matsushita, Kakushi; Suruga, Yukio; Aoki, Noriko; Ozaki, Atsuo; Uozumi, Kimiharu; Tei, Chuwa; Arima, Naomichi

    2007-09-01

    Human T lymphotropic virus type I (HTLV-I) may be associated with some connective tissue autoimmune diseases, including systemic lupus erythematosus (SLE). To determine the relationship between HTLV-I infection and SLE, we examined the clinical manifestations of SLE patients with HTLV-I infection. Eighty-nine patients with SLE were screened for antibodies to HTLV-I by electrochemiluminescence immunoassay. The presence of HTLV-I proviral sequences in peripheral blood mononuclear cells (PBMC) was determined by real-time polymerase chain reaction (PCR) quantification and Southern blotting analysis. The differences in clinical manifestations between HTLV-I-seropositive and seronegative patients with SLE were analyzed statistically. Fourteen of 89 (15.7%) patients were HTLV-I seropositive. All PBMC samples from 11 patients tested by PCR and 3 samples from 10 patients tested by Southern blotting analysis were positive for HTLV-I-related sequences. The age of HTLV-I-seropositive patients with SLE was significantly higher than that of seronegative patients (median 60 vs 42 yrs; p seronegative patients (median 45.5 vs 30 yrs; p seronegative patients (median 1740 vs 1066/microl; p = 0.027). The maintenance dose of prednisolone in HTLV-I-seropositive patients with SLE was significantly lower than that in seronegative patients (median 5 vs 9 mg/day; p = 0.012). This is the first report of the differences in clinical manifestations between SLE patients with and without HTLV-I infection. Our results suggest some involvement of HTLV-I in the pathogenesis of SLE.

  10. Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein.

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    Jaworski, Elizabeth; Narayanan, Aarthi; Van Duyne, Rachel; Shabbeer-Meyering, Shabana; Iordanskiy, Sergey; Saifuddin, Mohammed; Das, Ravi; Afonso, Philippe V; Sampey, Gavin C; Chung, Myung; Popratiloff, Anastas; Shrestha, Bindesh; Sehgal, Mohit; Jain, Pooja; Vertes, Akos; Mahieux, Renaud; Kashanchi, Fatah

    2014-08-08

    Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. The HTLV-1 transactivator protein Tax controls many critical cellular pathways, including host cell DNA damage response mechanisms, cell cycle progression, and apoptosis. Extracellular vesicles called exosomes play critical roles during pathogenic viral infections as delivery vehicles for host and viral components, including proteins, mRNA, and microRNA. We hypothesized that exosomes derived from HTLV-1-infected cells contain unique host and viral proteins that may contribute to HTLV-1-induced pathogenesis. We found exosomes derived from infected cells to contain Tax protein and proinflammatory mediators as well as viral mRNA transcripts, including Tax, HBZ, and Env. Furthermore, we observed that exosomes released from HTLV-1-infected Tax-expressing cells contributed to enhanced survival of exosome-recipient cells when treated with Fas antibody. This survival was cFLIP-dependent, with Tax showing induction of NF-κB in exosome-recipient cells. Finally, IL-2-dependent CTLL-2 cells that received Tax-containing exosomes were protected from apoptosis through activation of AKT. Similar experiments with primary cultures showed protection and survival of peripheral blood mononuclear cells even in the absence of phytohemagglutinin/IL-2. Surviving cells contained more phosphorylated Rb, consistent with the role of Tax in regulation of the cell cycle. Collectively, these results suggest that exosomes may play an important role in extracellular delivery of functional HTLV-1 proteins and mRNA to recipient cells. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Human T-lymphotropic Virus Type 1-infected Cells Secrete Exosomes That Contain Tax Protein*

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    Jaworski, Elizabeth; Narayanan, Aarthi; Van Duyne, Rachel; Shabbeer-Meyering, Shabana; Iordanskiy, Sergey; Saifuddin, Mohammed; Das, Ravi; Afonso, Philippe V.; Sampey, Gavin C.; Chung, Myung; Popratiloff, Anastas; Shrestha, Bindesh; Sehgal, Mohit; Jain, Pooja; Vertes, Akos; Mahieux, Renaud; Kashanchi, Fatah

    2014-01-01

    Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. The HTLV-1 transactivator protein Tax controls many critical cellular pathways, including host cell DNA damage response mechanisms, cell cycle progression, and apoptosis. Extracellular vesicles called exosomes play critical roles during pathogenic viral infections as delivery vehicles for host and viral components, including proteins, mRNA, and microRNA. We hypothesized that exosomes derived from HTLV-1-infected cells contain unique host and viral proteins that may contribute to HTLV-1-induced pathogenesis. We found exosomes derived from infected cells to contain Tax protein and proinflammatory mediators as well as viral mRNA transcripts, including Tax, HBZ, and Env. Furthermore, we observed that exosomes released from HTLV-1-infected Tax-expressing cells contributed to enhanced survival of exosome-recipient cells when treated with Fas antibody. This survival was cFLIP-dependent, with Tax showing induction of NF-κB in exosome-recipient cells. Finally, IL-2-dependent CTLL-2 cells that received Tax-containing exosomes were protected from apoptosis through activation of AKT. Similar experiments with primary cultures showed protection and survival of peripheral blood mononuclear cells even in the absence of phytohemagglutinin/IL-2. Surviving cells contained more phosphorylated Rb, consistent with the role of Tax in regulation of the cell cycle. Collectively, these results suggest that exosomes may play an important role in extracellular delivery of functional HTLV-1 proteins and mRNA to recipient cells. PMID:24939845

  12. Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes.

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    Väremo, Leif; Henriksen, Tora Ida; Scheele, Camilla; Broholm, Christa; Pedersen, Maria; Uhlén, Mathias; Pedersen, Bente Klarlund; Nielsen, Jens

    2017-05-25

    Skeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). The close association between obesity and T2D makes it difficult to isolate specific effects attributed to the disease alone. Therefore, here we set out to identify and characterize intrinsic properties of myocytes, associated independently with T2D or obesity. We generated and analyzed RNA-seq data from primary differentiated myotubes from 24 human subjects, using a factorial design (healthy/T2D and non-obese/obese), to determine the influence of each specific factor on genome-wide transcription. This setup enabled us to identify intrinsic properties, originating from muscle precursor cells and retained in the corresponding myocytes. Bioinformatic and statistical methods, including differential expression analysis, gene-set analysis, and metabolic network analysis, were used to characterize the different myocytes. We found that the transcriptional program associated with obesity alone was strikingly similar to that induced specifically by T2D. We identified a candidate epigenetic mechanism, H3K27me3 histone methylation, mediating these transcriptional signatures. T2D and obesity were independently associated with dysregulated myogenesis, down-regulated muscle function, and up-regulation of inflammation and extracellular matrix components. Metabolic network analysis identified that in T2D but not obesity a specific metabolite subnetwork involved in sphingolipid metabolism was transcriptionally regulated. Our findings identify inherent characteristics in myocytes, as a memory of the in vivo phenotype, without the influence from a diabetic or obese extracellular environment, highlighting their importance in the development of T2D.

  13. Molecular epidemiology of human immunodeficiency virus type 1 in Guangdong province of southern China.

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    Song Chen

    Full Text Available BACKGROUND: Although the outbreak of human immunodeficiency virus type 1 (HIV-1 in Guangdong has been documented for more than a decade, the molecular characteristics of such a regional HIV-1 epidemic remained unknown. METHODOLOGY/PRINCIPAL FINDINGS: By sequencing of HIV-1 pol/env genes and phylogenetic analysis, we performed a molecular epidemiologic study in a representative subset (n  = 200 of the 508 HIV-1-seropositive individuals followed up at the center for HIV/AIDS care and treatment of Guangzhou Hospital of Infectious Diseases. Of 157 samples (54.1% heterosexual acquired adults, 20.4% needle-sharing drug users, 5.7% receivers of blood transfusion, 1.3% men who have sex with men, and 18.5% remained unknown with successful sequencing for both pol and env genes, 105 (66.9% HIV-1 subtype CRF01_AE and 24 (15.3% CRF07_BC, 9 (5.7% B', 5 (3.2% CRF08_BC, 5 (3.2% B, 1 (0.6% C, 3 (1.9% CRF02_AG, and 5 (3.2% inter-region recombinants were identified within pol/env sequences. Thirteen (8.3% samples (3 naïves, 6 and 5 received with antiretroviral treatment [ART] 1-21 weeks and ≥24 weeks respectively showed mutations conferring resistance to nucleoside/nonnucleoside reverse transcriptase inhibitors or protease inhibitors. Among 63 ART-naïve patients, 3 (4.8% showed single or multiple drug resistant mutations. Phylogenetic analysis showed 8 small clusters (2-3 sequences/cluster with only 17 (10.8% sequences involved. CONCLUSION/SIGNIFICANCE: This study confirms that sexual transmission with dominant CRF01_AE strain is a major risk for current HIV-1 outbreak in the Guangdong's general population. The transmission with drug-resistant variants is starting to emerge in this region.

  14. Prevalence of human T-lymphotropic virus type 1 among blood donors from Mashhad, Iran.

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    Abbaszadegan, Mohammad Reza; Gholamin, Mehran; Tabatabaee, Abbas; Farid, Reza; Houshmand, Massoud; Abbaszadegan, Morteza

    2003-06-01

    The city of Mashhad is the capital of Khorasan, the northeastern province of Iran, which has been recognized as an area where human T-lymphotropic virus type 1 (HTLV-1) infection is endemic. All serum samples from blood donors are routinely screened for HTLV-1 by using enzyme-linked immunosorbent assay (ELISA). In the present study, 28,926 donors (81.86% male and 18.14% female) with a mean age of 32 years (range, 18 to 65 years) were screened in a 6 months period (July to December 1999). Of these donors in the primary screening, 228 (0.78%) tested positive by ELISA. The positive samples were confirmed by Western blot (WB) analysis. The WB results indicated that, of 228 positive ELISA specimens, 91.2% (208 specimens) were HTLV-1, 4.82% (11 specimens) were HTLV, 3.5% (8 specimens) were indeterminate, and 0.44% (1 specimen) was not confirmed. HTLV refers to samples in which the complete viral antigen banding patterns on WB strips were not present. In order to further evaluate the detection methodologies used, the HTLV-1-seropositive samples, the indeterminant samples, and/or HTLV samples were examined and confirmed by PCR. The HTLV samples were determined to be HTLV-1, the remaining samples were indeterminant, and the negative sample could not be confirmed for HTLV-1 by PCR. The prevalence of HTLV-1 infection in our study was 0.77% among blood bank donors, which reconfirms the city of Mashhad as an area where the virus is endemic compared to other regions in the world. The incidence was correlated with increasing age, and it was higher in females than in males.

  15. Human T-lymphotropic virus type 1 infection and disease in Spain.

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    de Mendoza, Carmen; Caballero, Estrella; Aguilera, Antonio; Requena, Silvia; de Lejarazu, Raúl Ortiz; Pirón, María; González, Rocío; Jiménez, Ana; Roc, Lourdes; Treviño, Ana; Benito, Rafael; Fernández-Alonso, Miriam; Aguinaga, Aitziber; Rodríguez, Carmen; García-Costa, Juan; Blanco, Lidia; Ramos, José M; Calderón, Enrique; Eirós, José M; Sauleda, Silvia; Barreiro, Pablo; Soriano, Vicente

    2017-07-31

    : Human T-lymphotropic virus type 1 (HTLV-1) infection is a neglected disease despite roughly 15 million people are chronically infected worldwide. Lifelong less than 10% of carriers develop life-threatening diseases, mostly a subacute myelopathy known as tropical spastic paraparesis (TSP) and a lymphoproliferative disorder named adult T-cell leukemia (ATL). HTLV-1 is efficiently transmitted perinatally (breastfeeding), sexually (more from men to women) and parenterally (transfusions, injection drug user (IDU), and transplants). To date there is neither prophylactic vaccine nor effective antiviral therapy. A total of 327 cases of HTLV-1 infection had been reported at the HTLV-1 Spanish registry until December 2016, of whom 34 had been diagnosed with TSP and 25 with ATL. Overall 62% were Latin American immigrants and 13% were persons of African origin. The incidence of HTLV-1 in Spain has remained stable for nearly a decade with 20-25 new cases yearly. Of the 21 newly diagnosed HTLV-1 cases during year 2016, one was a native Spaniard pregnant woman, and four presented with symptomatic disease, including three with ATL and one with TSP. Underdiagnosis of HTLV-1 in Spain must be high (iceberg model), which may account for the disproportionate high rate of symptomatic cases (almost 20%) and the late recognition of preventable HTLV-1 transmissions in special populations, such as newborns and transplant recipients. Our current estimate is of 10 000 persons living with HTLV-1 infection in Spain. Given the large flux of immigrants and visitors from HTLV-1 endemic regions to Spain, the expansion of HTLV-1 screening policies is warranted. At this time, it seems worth recommending HTLV testing to all donor/recipient organ transplants and pregnant women regardless place of birth. Although current leukoreduction procedures largely prevent HTLV-1 transmission by blood transfusions, HTLV testing of all first-time donors should be cost-effective contributing to unveil

  16. The role of NH4Cl and cysteine proteases in Human Papillomavirus type 16 infection

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    Meneses Patricio I

    2009-07-01

    Full Text Available Abstract Background The infectious pathway of the non-enveloped Human Papillomavirus Type 16 (HPV16 includes binding to the cell surface, clathrin-mediated endocytosis, and penetration into an endosome. HPV16 infection was shown to decrease in the presence of the lysosomotrophic neutralizing agent ammonium chloride (NH4Cl. NH4Cl neutralizes acidic endo-lysosome compartments, thus suggesting that pH was responsible for PV capsid conformational changes leading endosome escape. Results However, our data suggested that NH4Cl blocked infection by preventing the movement of PV viral particles from the early endosome to the caveosome as was shown for JC virus 12. We have confirmed that HPV 16 infection requires the trafficking of reporter-virions to the caveosome as is the case for BPV1 34. In this manuscript we propose that the observed decrease in infection of PV in the presence of NH4Cl was due to a loss of movement of reporter-virions to caveosomes. We also demonstrate that cysteine proteases are involved in the infectious process, and that cathepsin B treatment of viral particles was shown to overcome the block of infection observed in the presence of furin inhibition. We confirmed the need for cathepsin B in HPV16 infection using cathepsin B null mouse embryonic fibroblasts. Conclusion We present data that suggest HPV16 infection is in part mediated by cysteine proteases, and that NH4Cl blocks the intracellular trafficking of infectious viral particles. To our knowledge this is the first demonstration that cysteine proteases influence the infection of a non-enveloped virus.

  17. The Vpr gene polymorphism of human immunodeficiency virus type 1 in China and its clinical significance.

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    Chen, Xia; Zheng, Yuhuang; Li, Hui; Mamadou, Diallo; Zhang, Chunying; He, Yan; Zhou, Huaying; Chen, Zi; Liu, Meng

    2011-07-01

    Recent studies have explored that mutated Human immunodeficiency virus type 1(HIV-1) Vpr genes likely influence clinical manifestations of HIV infected patients. However, the relationship between the mutation sites on HIV Vpr gene and subsequent function changes is still not clear. In this study we investigated such relationship in analyzing the Vpr genes of HIV-1 viruses isolated from 208 HIV-1 infected patients from different regions in China. Reverse transcription polymerase chain reaction (RT-PCR) and nested PCR were used to amplify HIV-1 Vpr gene extracted from plasma of 208 HIV-1 infected patients and 153 isolates displayed the target gene sequences. Biological analysis software analyzed the deduced amino acid sequence, and identified the characteristics of the polymorphism of HIV-1 Vpr gene and its clinical significance. Results show the sequence subtypes as follows: CRF01-AE is 51.63%, subtype C is 24.84%, ubtype B is 17.65%, CRF03-AB is 3.92% and CRF08-BC is 1.31%. This paper revealed for the first time the HIV-1 Vpr gene polymorphism in HIV-1 positive individuals in China.: the subtype CRF01-AE is the main Vpr gene subtype in this region. The mutations in the C-terminal were more obvious than those observed in the N-terminal. It was also discovered that in the 77th position, 84.3% of the 153 amino acid sequences were glutamine (Q), which differ from overseas reports. Our data showed that the mutations 63, 70, 85, 86, 89 and 94 of the Vpr gene were possibly correlated with the clinical manifestations of the HIV-1 infected individuals.

  18. Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms

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    Mueller Nancy

    2005-10-01

    Full Text Available Abstract Background Human T-cell leukemia virus type I (HTLV-I causes adult T-cell leukemia (ATL after a long latent period. Among accessory genes encoded by HTLV-I, the tax gene is thought to play a central role in oncogenesis. However, Tax expression is disrupted by several mechanims including genetic changes of the tax gene, deletion/hypermethylation of 5'-LTR. To clarify the role of epigenetic changes, we analyzed DNA methylation and histone modification in the whole HTLV-I provirus genome. Results The gag, pol and env genes of HTLV-I provirus were more methylated than pX region, whereas methylation of 5'-LTR was variable and 3'-LTR was not methylated at all. In ATL cell lines, complete DNA methylation of 5'-LTR was associated with transcriptional silencing of viral genes. HTLV-I provirus was more methylated in primary ATL cells than in carrier state, indicating the association with disease progression. In seroconvertors, DNA methylation was already observed in internal sequences of provirus just after seroconversion. Taken together, it is speculated that DNA methylation first occurs in the gag, pol and env regions and then extends in the 5' and 3' directions in vivo, and when 5'-LTR becomes methylated, viral transcription is silenced. Analysis of histone modification in the HTLV-I provirus showed that the methylated provirus was associated with hypoacetylation. However, the tax gene transcript could not be detected in fresh ATL cells regardless of hyperacetylated histone H3 in 5'-LTR. The transcription rapidly recovered after in vitro culture in such ATL cells. Conclusion These results showed that epigenetic changes of provirus facilitated ATL cells to evade host immune system by suppressing viral gene transcription. In addition, this study shows the presence of another reversible mechanism that suppresses the tax gene transcription without DNA methylation and hypoacetylated histone.

  19. Pseudodiploid genome organization AIDS full-length human immunodeficiency virus type 1 DNA synthesis.

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    King, Steven R; Duggal, Nisha K; Ndongmo, Clement B; Pacut, Crystal; Telesnitsky, Alice

    2008-03-01

    Template switching between copackaged human immunodeficiency virus type 1 (HIV-1) genomic RNAs is genetically silent when identical RNAs are copackaged but yields recombinants when virions contain two distinct RNAs. Sequencing has revealed that errors at retroviral recombination junctions are infrequent, suggesting that template switching is not intrinsically mutagenic. Here, we tested the hypothesis that template switching may instead contribute to replication fidelity. This hypothesis predicts that reverse transcription of a single-copy gene will be more error prone than replication in the presence of a second copy. To test this, HIV-1-based vectors containing both lacZ and the puromycin resistance marker were expressed either alone or with an excess of an "empty" vector lacking lacZ and puro. This resulted in virions with either RNA homodimers or haploid genomes with only a single lacZ-puro RNA. In untreated cells, lacZ inactivation rates suggested that haploid vector reverse transcription was slightly more error prone than that of homodimerized pseudodiploid vectors. Haploid reverse transcription was at least threefold more error prone than pseudodiploid-templated synthesis when slowed by hydroxyurea treatment or stopped prematurely with zidovudine. Individual products of one- and two-copy genes revealed both nucleotide substitutions and deletions, with deletions more frequent than point mutations among haploid genome products. Similar spectra of defective products were observed at early reverse transcription time points and among products of haploid virions. These results indicate that faithful, full-length reverse transcription products were underrepresented in the absence of a reserve of genetic information and suggest that template switching contributes to HIV-1 genomic integrity.

  20. Retinal Nerve Fiber Layer Thickness in Human T-cell Lymphotropic Virus Type 1 Patients.

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    Merle, Harold; Hage, Rabih; Jeannin, Séverine; Cabre, Philippe; Olindo, Stéphane

    2017-10-06

    To determine whether there is an optic neuropathy (ON) in patients with human T-cell lymphotropic virus type 1 (HTLV-1) infection. We included HTLV-1 asymptomatic carriers (a.c.HTLV-1) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) patients between January 1st, 2014 and March 31st, 2015. All patients had complete eye examination. The visual acuity (VA) and retinal nerve fiber layer (RNFL) thickness were measured and compared to age- and sex-matched control groups including patients seen in our refraction clinic with no previous medical or surgical history. Thirty-one a.c.HTLV-1 (group 1) and 29 TSP/HAM patients (group 2) were included. The average RNFL thickness was 99.9 ± 14.3 µm in group 1 and 87.8 ± 19.2 µm in group 2. The average RFNL thicknesses were lower in both groups, when compared to controls. The difference was significant in patients with TSP/HAM (87.8 ± 19.2 µm vs. 97 ± 7.8 µm; p = 0.003) who also had significantly decreased VA. We report here the first study about the RNFL thickness in patients with TSP/HAM. In these patients, there is decrease of the RNFL thickness with subtle but definite decrease of VA. This suggests that subclinical ON occurs in the natural history of the disease. The diagnosis of TSP/HAM must be evoked as a differential of primary progressive multiple sclerosis in a population at risk. Moreover, RNFL thinning with no evidence of glaucoma should raise suspicion for HTLV-1 infection and TSP/HAM in a population at risk.