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Pesquisa : B01.050.150.900.649.313.500.190 [Categoria DeCS]
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  1 / 7 MEDLINE  
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[PMID]:28718923
[Au] Autor:Bazzoli A; Vance DJ; Rudolph MJ; Rong Y; Angalakurthi SK; Toth RT; Middaugh CR; Volkin DB; Weis DD; Karanicolas J; Mantis NJ
[Ad] Endereço:Center for Computational Biology, University of Kansas, Lawrence, Kansas, 66045.
[Ti] Título:Using homology modeling to interrogate binding affinity in neutralization of ricin toxin by a family of single domain antibodies.
[So] Source:Proteins;85(11):1994-2008, 2017 Nov.
[Is] ISSN:1097-0134
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this report we investigated, within a group of closely related single domain camelid antibodies (V Hs), the relationship between binding affinity and neutralizing activity as it pertains to ricin, a fast-acting toxin and biothreat agent. The V1C7-like V Hs (V1C7, V2B9, V2E8, and V5C1) are similar in amino acid sequence, but differ in their binding affinities and toxin-neutralizing activities. Using the X-ray crystal structure of V1C7 in complex with ricin's enzymatic subunit (RTA) as a template, Rosetta-based homology modeling coupled with energetic decomposition led us to predict that a single pairwise interaction between Arg29 on V5C1 and Glu67 on RTA was responsible for the difference in ricin toxin binding affinity between V1C7, a weak neutralizer, and V5C1, a moderate neutralizer. This prediction was borne out experimentally: substitution of Arg for Gly at position 29 enhanced V1C7's binding affinity for ricin, whereas the reverse (ie, Gly for Arg at position 29) diminished V5C1's binding affinity by >10 fold. As expected, the V5C1 mutant was largely devoid of toxin-neutralizing activity (TNA). However, the TNA of the V1C7 mutant was not correspondingly improved, indicating that in the V1C7 family binding affinity alone does not account for differences in antibody function. V1C7 and V5C1, as well as their respective point mutants, recognized indistinguishable epitopes on RTA, at least at the level of sensitivity afforded by hydrogen-deuterium mass spectrometry. The results of this study have implications for engineering therapeutic antibodies because they demonstrate that even subtle differences in epitope specificity can account for important differences in antibody function.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes
Mapeamento de Epitopos/métodos
Modelos Moleculares
Engenharia de Proteínas/métodos
Ricina
Anticorpos de Domínio Único
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Anticorpos Neutralizantes/química
Anticorpos Neutralizantes/metabolismo
Camelidae
Ligação Proteica
Ricina/química
Ricina/isolamento & purificação
Ricina/metabolismo
Alinhamento de Sequência
Anticorpos de Domínio Único/química
Anticorpos de Domínio Único/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Single-Domain Antibodies); 9009-86-3 (Ricin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1002/prot.25353


  2 / 7 MEDLINE  
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[PMID]:28497227
[Au] Autor:Bártová E; Kobédová K; Lamka J; Kotrba R; Vodicka R; Sedlák K
[Ad] Endereço:Department of Biology and Wildlife Diseases, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences Brno, Palackého tr. 1946/1, 612 42, Brno, Czech Republic. bartovae@vfu.cz.
[Ti] Título:Seroprevalence of Neospora caninum and Toxoplasma gondii in exotic ruminants and camelids in the Czech Republic.
[So] Source:Parasitol Res;116(7):1925-1929, 2017 Jul.
[Is] ISSN:1432-1955
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Neospora caninum and Toxoplasma gondii are the protozoan parasites with definitive hosts from order Carnivora. Due to vertical transmission, both parasites can cause abortions and neonatal mortality that lead to significant productive and economic losses in the domestic ruminants. The aim of this study was to describe N. caninum and T. gondii seroprevalence in the group of frequently farmed captive exotic ruminants (n = 184) including Bovidae (barbary sheep, bezoar goat, common eland, American bison, water buffalo, and yak) and Camelidae (bactrian camel, guanaco, llama, and alpaca). Antibodies were tested by indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). Higher prevalence of T. gondii antibodies (31% in IFAT and 52% in ELISA) was detected compared to N. caninum (24% in IFAT and 17% in cELISA). Mixed infection was found in 18 (10%) and 22 (12%) animals by IFAT and ELISA, respectively. Higher seroprevalence of both N. caninum and T. gondii was found in Camelidae compared to Bovidae. To author knowledge, this is the first detection of T. gondii and N. caninum antibodies in common elands and bezoar goats.
[Mh] Termos MeSH primário: Camelidae/parasitologia
Coccidiose/veterinária
Neospora/imunologia
Ruminantes/parasitologia
Toxoplasma/imunologia
Toxoplasmose Animal/epidemiologia
[Mh] Termos MeSH secundário: Animais
Coccidiose/epidemiologia
Coccidiose/parasitologia
República Tcheca/epidemiologia
Ensaio de Imunoadsorção Enzimática/veterinária
Feminino
Técnica Indireta de Fluorescência para Anticorpo/veterinária
Masculino
Prevalência
Estudos Soroepidemiológicos
Toxoplasmose Animal/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170513
[St] Status:MEDLINE
[do] DOI:10.1007/s00436-017-5470-6


  3 / 7 MEDLINE  
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[PMID]:28239762
[Au] Autor:Sounier R; Yang Y; Hagelberger J; Granier S; Déméné H
[Ad] Endereço:Institut de Genomique Fonctionnelle (IGF), CNRS, INSERM, Univ. Montpellier, F-34094, Montpellier, France. remy.sounier@igf.cnrs.fr.
[Ti] Título:H, C and N backbone chemical shift assignments of camelid single-domain antibodies against active state µ-opioid receptor.
[So] Source:Biomol NMR Assign;11(1):117-121, 2017 Apr.
[Is] ISSN:1874-270X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Nanobodies are single chain antibodies that have become a highly valuable and versatile tool for biomolecular and therapeutic research. One application field is the stabilization of active states of flexible proteins, among which G-protein coupled receptors represent a very important class of membrane proteins. Here we present the backbone and side-chain assignment of the H, C and N resonances of Nb33 and Nb39, two nanobodies that recognize and stabilize the µ-opioid receptor to opioids in its active agonist-bound conformation. In addition, we present a comparison of their secondary structures as derived from NMR chemical shifts.
[Mh] Termos MeSH primário: Camelidae
Ressonância Magnética Nuclear Biomolecular
Receptores Opioides mu/imunologia
Anticorpos de Domínio Único/química
Anticorpos de Domínio Único/imunologia
[Mh] Termos MeSH secundário: Animais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, Opioid, mu); 0 (Single-Domain Antibodies)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE
[do] DOI:10.1007/s12104-017-9733-z


  4 / 7 MEDLINE  
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[PMID]:28043352
[Au] Autor:Herrid M; Vajta G; Skidmore JA
[Ad] Endereço:Camel Reproduction Centre, Dubai, United Arab Emirates; School of Science and Technology, University of New England, Armidale, New South Wales, Australia.
[Ti] Título:Current status and future direction of cryopreservation of camelid embryos.
[So] Source:Theriogenology;89:20-25, 2017 Feb.
[Is] ISSN:1879-3231
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Over the past 3 decades, and similar to the horse industry, fresh embryo transfer has been widely practiced on large commercial scales in different camelid species, especially the dromedary camel and alpaca. However, the inability to cryopreserve embryos significantly reduces its broader application, and as such limits the capacity to utilize elite genetic resources internationally. In addition, cryopreservation of the semen of camelids is also difficult, suggesting an extreme sensitivity of the germplasm to cooling and freezing. As a result, genetic resources of camelids must continue to be maintained as living collections of animals. Due to concerns over disease outbreaks such as that of the highly pathogenic Middle East Respiratory Syndrome in the Middle East and Asia, there is an urgent need to establish an effective gene banking system for camelid species, especially the camel. The current review compares and summarizes recent progress in the field of camelid embryo cryopreservation, identifying four possible reasons for the slow development of an effective protocol and describing eight future directions to improve the current protocols. At the same time, the results of a recent dromedary camel embryo transfer study which produced a high morphologic integrity and survival rate of Open Pulled Straw-vitrified embryos are also discussed.
[Mh] Termos MeSH primário: Camelidae/embriologia
Criopreservação/veterinária
Embrião de Mamíferos
[Mh] Termos MeSH secundário: Animais
Camelidae/fisiologia
Criopreservação/métodos
Transferência Embrionária
Feminino
Congelamento
Masculino
Sêmen/fisiologia
Vitrificação
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170104
[St] Status:MEDLINE


  5 / 7 MEDLINE  
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[PMID]:27732648
[Au] Autor:Belotti López de Medina CR; López Geronazzo L; Otero C
[Ad] Endereço:Instituto de las Culturas (IDECU), Universidad de Buenos Aires, CONICET, Museo Etnográfico J. B. Ambrosetti (FFyL), Ciudad Autónoma de Buenos Aires, Argentina.
[Ti] Título:At the Feet of the Fortress: Analysis of Inka Period (ca. AD 1430-1536) Archaeofaunal Assemblages from Residential Unit 1 (RU1), Pucara de Tilcara (Jujuy, Argentina).
[So] Source:PLoS One;11(10):e0163766, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This paper reports the results of a zooarchaeological analysis conducted on the occupation layer of a compound structure (Residential Unit 1) of the Pucara de Tilcara archaeological site (Jujuy Province, northwestern Argentina). Its occupation span extends between the 13th and 15th centuries AD, but evidence diagnostic of the Inka Period (AD 1430-1536) is predominant. Residential Unit 1 was a house-workshop that hosted specialized crafts like metallurgy and lapidary during the Inka Period. It was proposed in previous works that artisans living at Pucara de Tilcara were provisioned with agropastoral products by the Inka administration. This paper aims to test that hypothesis against the zooarchaeological evidence of Residential Unit 1. Three variables were used as proxies for state-sponsored distribution: taxonomic diversity (family and species ranks), and skeletal and age profiles of the predominant zoological family (Camelidae) in the assemblage. The results show a high degree of continuity with the regional record, characterized by a herding-hunting strategy focused on domestic and wild species of Camelidae and a mixed mortality pattern. The skeletal profile shows a strong and negative correlation with the desiccation potential of elements, which could be indicative of local production of chalona. Overall, faunal evidence does not show any sign of centralized distribution.
[Mh] Termos MeSH primário: Arqueologia
Osso e Ossos/química
[Mh] Termos MeSH secundário: Animais
Argentina
Camelidae/classificação
Seres Humanos
Datação Radiométrica
Zoologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161013
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0163766


  6 / 7 MEDLINE  
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[PMID]:27386563
[Au] Autor:Metcalf JL; Turney C; Barnett R; Martin F; Bray SC; Vilstrup JT; Orlando L; Salas-Gismondi R; Loponte D; Medina M; De Nigris M; Civalero T; Fernández PM; Gasco A; Duran V; Seymour KL; Otaola C; Gil A; Paunero R; Prevosti FJ; Bradshaw CJ; Wheeler JC; Borrero L; Austin JJ; Cooper A
[Ad] Endereço:Australian Centre for Ancient DNA, School of Biological Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia.; Department of Ecology and Evolutionary Biology, Ramaley Biology, University of Colorado, Boulder, CO 80309-0334, USA.
[Ti] Título:Synergistic roles of climate warming and human occupation in Patagonian megafaunal extinctions during the Last Deglaciation.
[So] Source:Sci Adv;2(6):e1501682, 2016 06.
[Is] ISSN:2375-2548
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The causes of Late Pleistocene megafaunal extinctions (60,000 to 11,650 years ago, hereafter 60 to 11.65 ka) remain contentious, with major phases coinciding with both human arrival and climate change around the world. The Americas provide a unique opportunity to disentangle these factors as human colonization took place over a narrow time frame (~15 to 14.6 ka) but during contrasting temperature trends across each continent. Unfortunately, limited data sets in South America have so far precluded detailed comparison. We analyze genetic and radiocarbon data from 89 and 71 Patagonian megafaunal bones, respectively, more than doubling the high-quality Pleistocene megafaunal radiocarbon data sets from the region. We identify a narrow megafaunal extinction phase 12,280 ± 110 years ago, some 1 to 3 thousand years after initial human presence in the area. Although humans arrived immediately prior to a cold phase, the Antarctic Cold Reversal stadial, megafaunal extinctions did not occur until the stadial finished and the subsequent warming phase commenced some 1 to 3 thousand years later. The increased resolution provided by the Patagonian material reveals that the sequence of climate and extinction events in North and South America were temporally inverted, but in both cases, megafaunal extinctions did not occur until human presence and climate warming coincided. Overall, metapopulation processes involving subpopulation connectivity on a continental scale appear to have been critical for megafaunal species survival of both climate change and human impacts.
[Mh] Termos MeSH primário: Mudança Climática
Extinção Biológica
[Mh] Termos MeSH secundário: Animais
Osso e Ossos/química
Osso e Ossos/metabolismo
Camelidae/classificação
Camelidae/genética
DNA Mitocondrial/química
DNA Mitocondrial/genética
DNA Mitocondrial/metabolismo
Felidae/classificação
Felidae/genética
Atividades Humanas
Seres Humanos
Camada de Gelo
Datação Radiométrica
Análise de Sequência de DNA
América do Sul
Ursidae/classificação
Ursidae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Mitochondrial)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170504
[Lr] Data última revisão:
170504
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160708
[St] Status:MEDLINE
[do] DOI:10.1126/sciadv.1501682


  7 / 7 MEDLINE  
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[PMID]:26839377
[Au] Autor:Webster CI; Caram-Salas N; Haqqani AS; Thom G; Brown L; Rennie K; Yogi A; Costain W; Brunette E; Stanimirovic DB
[Ad] Endereço:Antibody Discovery and Protein Engineering, MedImmune, Cambridge, United Kingdom; websterc@medimmune.com.
[Ti] Título:Brain penetration, target engagement, and disposition of the blood-brain barrier-crossing bispecific antibody antagonist of metabotropic glutamate receptor type 1.
[So] Source:FASEB J;30(5):1927-40, 2016 05.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Receptor mediated transcytosis harnessing the cellular uptake and transport of natural ligands across the blood-brain barrier (BBB) has been identified as a means for antibody delivery to the CNS. In this study, we characterized bispecific antibodies in which a BBB-crossing antibody fragment FC5 was used as a BBB carrier. Cargo antibodies were either a high-affinity, selective antibody antagonist of the metabotropic glutamate receptor-1 (BBB-mGluR1), a widely abundant CNS target, or an IgG that does not bind the CNS target (BBB-NiP). Both BBB-NiP and BBB-mGluR1 demonstrated a similar 20-fold enhanced rate of transcytosis across an in vitro BBB model compared with mGluR1 IgG fused to a control antibody fragment. All 3 bispecific antibodies exhibited identical pharmacokinetics in vivo Comparative assessment of BBB-NiP and BBB-mGluR1 revealed that, whereas their serum pharmacokinetics and BBB penetration were identical, their central disposition (brain levels) and elimination (cerebrospinal fluid levels) were widely different, due to central target-mediated removal of the mGluR1-engaging antibody. Central mGluR1 target engagement after systemic administration was demonstrated by a dose-dependent inhibition of mGluR-1-mediated thermal hyperalgesia and by colocalization of the antibody with thalamic neurons involved in mGluR1-mediated pain processing. We demonstrate the feasibility of targeting central G-protein-coupled receptors using a BBB-crossing bispecific antibody approach and emerging principles that govern brain distribution and disposition of these antibodies. These data will be important for designing safe and selective CNS antibody therapeutics.-Webster, C. I., Caram-Salas, N., Haqqani, A. S., Thom, G., Brown, L., Rennie, K., Yogi, A., Costain, W., Brunette, E., Stanimirovic, D. B. Brain penetration, target engagement, and disposition of the blood-brain barrier-crossing bispecific antibody antagonist of metabotropic glutamate receptor type 1.
[Mh] Termos MeSH primário: Anticorpos Biespecíficos/farmacologia
Encéfalo/metabolismo
Dor/tratamento farmacológico
Receptores de Glutamato Metabotrópico/antagonistas & inibidores
[Mh] Termos MeSH secundário: Analgésicos
Animais
Produtos Biológicos/metabolismo
Transporte Biológico
Barreira Hematoencefálica/metabolismo
Encéfalo/efeitos dos fármacos
Camelidae
Membrana Celular
Células HEK293
Temperatura Alta/efeitos adversos
Seres Humanos
Imunoconjugados/metabolismo
Imunoglobulina G/imunologia
Dor/etiologia
Engenharia de Proteínas/métodos
Ratos
Receptores de Glutamato Metabotrópico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Analgesics); 0 (Antibodies, Bispecific); 0 (Biological Products); 0 (Immunoconjugates); 0 (Immunoglobulin G); 0 (Receptors, Metabotropic Glutamate); 0 (metabotropic glutamate receptor type 1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160204
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201500078



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