Academic literature on the topic 'Protein Conformers'
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Journal articles on the topic "Protein Conformers"
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Schneider, Bohdan, Jiří Černý, Daniel Svozil, Petr Čech, Jean-Christophe Gelly, and Alexandre G. de Brevern. "Bioinformatic analysis of the protein/DNA interface." Nucleic Acids Research 42, no. 5 (December 11, 2013): 3381–94. http://dx.doi.org/10.1093/nar/gkt1273.
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Abstract To investigate the principles driving recognition between proteins and DNA, we analyzed more than thousand crystal structures of protein/DNA complexes. We classified protein and DNA conformations by structural alphabets, protein blocks [de Brevern, Etchebest and Hazout (2000) (Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks. Prots. Struct. Funct. Genet., 41:271–287)] and dinucleotide conformers [Svozil, Kalina, Omelka and Schneider (2008) (DNA conformations and their sequence preferences. Nucleic Acids Res., 36:3690–3706)], respectively. Assembling the mutually interacting protein blocks and dinucleotide conformers into ‘interaction matrices’ revealed their correlations and conformer preferences at the interface relative to their occurrence outside the interface. The analyzed data demonstrated important differences between complexes of various types of proteins such as transcription factors and nucleases, distinct interaction patterns for the DNA minor groove relative to the major groove and phosphate and importance of water-mediated contacts. Water molecules mediate proportionally the largest number of contacts in the minor groove and form the largest proportion of contacts in complexes of transcription factors. The generally known induction of A-DNA forms by complexation was more accurately attributed to A-like and intermediate A/B conformers rare in naked DNA molecules.
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Verdonk, Marcel L., Paul N. Mortenson, Richard J. Hall, Michael J. Hartshorn, and Christopher W. Murray. "Protein−Ligand Docking against Non-Native Protein Conformers." Journal of Chemical Information and Modeling 48, no. 11 (October 28, 2008): 2214–25. http://dx.doi.org/10.1021/ci8002254.
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Xu, Aoshuang, Fenglei Li, Howard Robinson, and Edward S. Yeung. "Can Protein Conformers Be Fractionated by Crystallization?" Analytical Chemistry 85, no. 13 (June 12, 2013): 6372–77. http://dx.doi.org/10.1021/ac400762x.
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Mahajan, Swapnil, and Yves-Henri Sanejouand. "Jumping between protein conformers using normal modes." Journal of Computational Chemistry 38, no. 18 (May 3, 2017): 1622–30. http://dx.doi.org/10.1002/jcc.24803.
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Ma, Jiyan, Jingjing Zhang, and Runchuan Yan. "Recombinant Mammalian Prions: The “Correctly” Misfolded Prion Protein Conformers." Viruses 14, no. 9 (August 31, 2022): 1940. http://dx.doi.org/10.3390/v14091940.
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Generating a prion with exogenously produced recombinant prion protein is widely accepted as the ultimate proof of the prion hypothesis. Over the years, a plethora of misfolded recPrP conformers have been generated, but despite their seeding capability, many of them have failed to elicit a fatal neurodegenerative disorder in wild-type animals like a naturally occurring prion. The application of the protein misfolding cyclic amplification technique and the inclusion of non-protein cofactors in the reaction mixture have led to the generation of authentic recombinant prions that fully recapitulate the characteristics of native prions. Together, these studies reveal that recPrP can stably exist in a variety of misfolded conformations and when inoculated into wild-type animals, misfolded recPrP conformers cause a wide range of outcomes, from being completely innocuous to lethal. Since all these recPrP conformers possess seeding capabilities, these results clearly suggest that seeding activity alone is not equivalent to prion activity. Instead, authentic prions are those PrP conformers that are not only heritable (the ability to seed the conversion of normal PrP) but also pathogenic (the ability to cause fatal neurodegeneration). The knowledge gained from the studies of the recombinant prion is important for us to understand the pathogenesis of prion disease and the roles of misfolded proteins in other neurodegenerative disorders.
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de Groot, J., and H. H. J. de Jongh. "The presence of heat-stable conformers of ovalbumin affects properties of thermally formed aggregates." Protein Engineering Design and Selection 16, no. 12 (December 1, 2003): 1035–40. http://dx.doi.org/10.1093/protein/gzg123.
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Beglov, Dmitri, David R. Hall, Ryan Brenke, Maxim V. Shapovalov, Roland L. Dunbrack, Dima Kozakov, and Sandor Vajda. "Minimal ensembles of side chain conformers for modeling protein-protein interactions." Proteins: Structure, Function, and Bioinformatics 80, no. 2 (November 22, 2011): 591–601. http://dx.doi.org/10.1002/prot.23222.
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Orellana, Laura, Johan Gustavsson, Cathrine Bergh, Ozge Yoluk, and Erik Lindahl. "eBDIMS server: protein transition pathways with ensemble analysis in 2D-motion spaces." Bioinformatics 35, no. 18 (February 19, 2019): 3505–7. http://dx.doi.org/10.1093/bioinformatics/btz104.
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Abstract Summary Understanding how proteins transition between different conformers, and how conformers relate to each other in terms of structure and function, is not trivial. Here, we present an online tool for transition pathway generation between two protein conformations using Elastic Network Driven Brownian Dynamics Importance Sampling, a coarse-grained simulation algorithm, which spontaneously predicts transition intermediates trapped experimentally. In addition to path-generation, the server provides an interactive 2D-motion landscape graphical representation of the transitions or any additional conformers to explore their structural relationships. Availability and implementation eBDIMS is available online: http://ebdims.biophysics.se/ or as standalone software: https://github.com/laura-orellana/eBDIMS, https://github.com/cabergh/eBDIMS. Supplementary information Supplementary data are available at Bioinformatics online.
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Walsh, Daniel J., Abigail M. Schwind, Geoffrey P. Noble, and Surachai Supattapone. "Conformational diversity in purified prions produced in vitro." PLOS Pathogens 19, no. 1 (January 10, 2023): e1011083. http://dx.doi.org/10.1371/journal.ppat.1011083.
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Prion diseases are caused by misfolding of either wild-type or mutant forms of the prion protein (PrP) into self-propagating, pathogenic conformers, collectively termed PrPSc. Both wild-type and mutant PrPSc molecules exhibit conformational diversity in vivo, but purified prions generated by the serial protein misfolding cyclic amplification (sPMCA) technique do not display this same diversity in vitro. This discrepancy has left a gap in our understanding of how conformational diversity arises at the molecular level in both types of prions. Here, we use continuous shaking instead of sPMCA to generate conformationally diverse purified prions in vitro. Using this approach, we show for the first time that wild type prions initially seeded by different native strains can propagate as metastable PrPSc conformers with distinguishable strain properties in purified reactions containing a single active cofactor. Propagation of these metastable PrPSc conformers requires appropriate shaking conditions, and changes in these conditions cause all the different PrPSc conformers to converge irreversibly into the same single conformer as that produced in sPMCA reactions. We also use continuous shaking to show that two mutant PrP molecules with different pathogenic point mutations (D177N and E199K) adopt distinguishable PrPSc conformations in reactions containing pure protein substrate without cofactors. Unlike wild-type prions, the conformations of mutant prions appear to be dictated by substrate sequence rather than seed conformation. Overall, our studies using purified substrates in shaking reactions show that wild-type and mutant prions use fundamentally different mechanisms to generate conformational diversity at the molecular level.
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Barreca, Maria, Nunzio Iraci, Silvia Biggi, Violetta Cecchetti, and Emiliano Biasini. "Pharmacological Agents Targeting the Cellular Prion Protein." Pathogens 7, no. 1 (March 7, 2018): 27. http://dx.doi.org/10.3390/pathogens7010027.
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Prion diseases are associated with the conversion of the cellular prion protein (PrPC), a glycoprotein expressed at the surface of a wide variety of cell types, into a misfolded conformer (the scrapie form of PrP, or PrPSc) that accumulates in brain tissues of affected individuals. PrPSc is a self-catalytic protein assembly capable of recruiting native conformers of PrPC, and causing their rearrangement into new PrPSc molecules. Several previous attempts to identify therapeutic agents against prion diseases have targeted PrPSc, and a number of compounds have shown potent anti-prion effects in experimental models. Unfortunately, so far, none of these molecules has successfully been translated into effective therapies for prion diseases. Moreover, mounting evidence suggests that PrPSc might be a difficult pharmacological target because of its poorly defined structure, heterogeneous composition, and ability to generate different structural conformers (known as prion strains) that can elude pharmacological intervention. In the last decade, a less intuitive strategy to overcome all these problems has emerged: targeting PrPC, the common substrate of any prion strain replication. This alternative approach possesses several technical and theoretical advantages, including the possibility of providing therapeutic effects also for other neurodegenerative disorders, based on recent observations indicating a role for PrPC in delivering neurotoxic signals of different misfolded proteins. Here, we provide an overview of compounds claimed to exert anti-prion effects by directly binding to PrPC, discussing pharmacological properties and therapeutic potentials of each chemical class.
Dissertations / Theses on the topic "Protein Conformers"
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Friedrich, Nils-Ole [Verfasser]. "Development and Validation of Algorithms for the Generation of Conformer Ensembles Representing Protein-Bound Ligand Conformations / Nils-Ole Friedrich." Hamburg : Staats- und Universitätsbibliothek Hamburg Carl von Ossietzky, 2020. http://d-nb.info/1223621014/34.
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Harb, Zeinab. "Détermination théorique des paramètres RMN de métabolites et protéines." Phd thesis, Université Claude Bernard - Lyon I, 2011. http://tel.archives-ouvertes.fr/tel-00740957.
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Ce travail présente une étude théorique des spectres RMN de molécules biologiques. Dans la première partie, les calculs DFT des paramètres RMN (déplacements chimiques et constantes de couplage spin-spin) pour les protons liés à des atomes de carbone ont été réalisés pour quatre métabolites de la prostate: la putrescine, la spermidine, la spermine, et la sarcosine, et trois métabolites du cerveau: l'acétate, l'alanine et la sérine. Une étude théorique systématique, dans l'approche DFT, des paramètres de RMN des métabolites a montré que la méthode B3LYP/6-311++G** est un bon compromis entre la précision et les coûts. Les contributions du solvant ont été évaluées en utilisant le modèle PCM, les effets des isomères, pondérés dans l'approximation de Boltzmann, ont été pris en compte, et les corrections de vibration de point zéro ont été estimées en utilisant une approche perturbative au second ordre. La comparaison avec l'expérience a démontré que tous ces effets sont nécessaires pour améliorer l'accord entre les données calculées et expérimentales, aboutissant à des résultats de grande précision. Dans la deuxième partie, nous avons développé un nouveau modèle, BioShift, qui permet la prédiction des déplacements chimiques des différents noyaux (H, N, C ...) pour des molécules biologiques (protéines, ADN, ARN, polyamine ...). Il est simple, rapide, et comporte un nombre limité de paramètres. La comparaison avec des modèles sophistiqués conçus spécialement pour la prédiction des déplacements chimiques des protéines a montré que Bioshift est concurrentiel avec de tels modèles.
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Muyrers, Janine Monique [Verfasser]. "Function and clearance of conformers of the prion protein / vorgelegt von Janine Monique Muyrers." 2008. http://d-nb.info/992717116/34.
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Senthil, Kuma DK. "Structural and Conformational Feature of RNA Duplexes." Thesis, 2014. http://etd.iisc.ernet.in/handle/2005/2770.
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In recent years, several interesting biological roles played by RNA have come to light. Apart from their known role in translation of genetic information from DNA to protein, they have been shown to act as enzymes as well as regulators of gene expression. Protein-RNA complexes are involved in regulating cellular processes like cell division, differentiation, growth, cell aging and death. A number of clinically important viruses have RNA as their genetic material. Defective RNA molecules have been linked to a number of human diseases. The ability of RNA to adopt stunningly complex three-dimensional structures aids in diverse functions like catalysis, metabolite sensing and transcriptional control. Several secondary structure motifs are observed in RNA, of which the double-helical RNA motif is ubiquitous and well characterized. Though DNA duplexes have been shown to be present in many polymorphic states, RNA duplexes are believed to exhibit conservatism. Early fibre diffraction analysis on molecular structures of natural and synthetically available oligo- and polynucleotides suggested that the double-helical structures of RNA might exist in two forms: A-form and A′-form. New improved crystallographic methods have contributed to the increased availability of atomic resolution structures of many biologically significant RNA molecules.
With the available structural information, it is feasible to try and understand the contribution of the variations at the base pair, base-pair step and backbone torsion angle level to the overall structure of the RNA duplex. Further, the effect of protein binding on RNA structure has not been extensively analysed. These studies have not been investigated in greater detail due to the focus of the research community on understanding conformational changes in proteins when bound to RNA, and due to the lack of a significant number of solved RNA structures in both free and protein-bound state. While studies on the conformation of the DNA double-helical stem have moved beyond the dinucleotide step into tri-, tetra-, hexa- and octanucleotide levels, similar knowledge for RNA even at the dinucleotide step level is lacking.
In this thesis, the results of detailed analyses to understand the contribution of the base sequence towards RNA conformational variability as well as the structural changes incurred upon protein binding are reported.
Objectives
The primary objective of this thesis is to understand the following through detailed analyses of all available high-resolution crystal structures of RNA.
1 Exploring sequence-dependent variations exhibited by dinucleotide steps formed by Watson-Crick (WC) base pairs in RNA duplexes.
2 Identifying sequence-dependent variations exhibited by dinucleotide steps containing non-Watson-Crick (NWC) base pairs in RNA duplexes.
3 Developing a web application for the generation of sequence-dependent non-uniform nucleic acid structures.
4 Investigating the relationship between base sequence and backbone torsion-angle preferences in RNA double helices followed by molecular dynamics simulation using various force fields, to check their ability to reproduce the above experimental findings.
Chapter 1 gives an overview of the structural features and polymorphic states of RNA duplexes and the present understanding of the structural architecture of RNA, thereby laying the background to the studies carried out subsequently. The chapter also gives a brief description on the methodologies applied. Relevant methodologies and protocols are dealt with in detail in the respective chapters.
Sequence-dependent base-pair step geometries in RNA duplexes
A complete understanding of the conformational variability seen in duplex RNA molecules at the dinucleotide step level can aid in the understanding of their function. This work was carried out to derive geometric information using a non-redundant RNA crystal structure dataset and to understand the conformational features (base pair and base-pair step parameters) involving all Watson-Crick (WC) (Chapter 2) and non-Watson-Crick (NWC) base pairs (Chapter 3). The sequence-dependent variations exhibited by the base-pair steps in RNA duplexes are elaborated. Further, potential non-canonical hydrogen bond interactions in the steps are identified and their relationship with dinucleotide step geometry is discussed. Comparison of the features of dinucleotide steps between free and protein-bound RNA datasets suggest variations at the base-pair step level on protein binding, which are more pronounced in non-Watson-Crick base pair containing steps.
Chapter 4 describes a web-server NUCGEN-Plus, developed for building and regeneration of curved and non-uniform DNA and RNA duplexes. The main algorithm is a modification of our earlier program NUCGEN that worked mainly for DNA. The WC step parameters and intra-base parameters for RNA were obtained from the work detailed in Chapter 2. The FORTRAN code and input sequence file format was modified. The program has two modules: a) Using the model-building module, the program can build duplex structures for a given input DNA/RNA sequence. Options are available for selecting various derived or user specified base-pair step parameters, and fibre diffraction parameters that can be used in the building process. The program can generate double-helical structures up to 2000 nucleotides in length. In addition, the program can calculate the curvature of the generated duplex at defined length scale. b) Using the regeneration module, double-helical structures of nucleic acids can be rebuilt from the existing solved structures. Further, variants of an existing structure can be generated by varying the input geometric parameters. The web-server has a user-friendly interface and is freely available in the public domain at: http://nucleix.mbu.iisc.ernet.in/nucgenplus/index.html
Sequence dependence of backbone torsion angle conformers in RNA duplexes
RNA molecules consist of covalently linked nucleotide units. Each of these units has six rigid torsional degrees of freedom (α, β, γ, δ, ε, and ζ) for the backbone and one (χ) around the glycosidic bond connecting the base to the ribose, thereby providing conformational flexibility. An understanding of the relationship between base sequence and structural variations along the backbone can help deduce the rationale for sequence conservation and also their functional importance. Chapter 5 describes in detail the torsion angle-dependent variations seen in dinucleotide steps of RNA duplex. A non-redundant, high resolution (≤2.5Å) crystal structure dataset was created. Base-specific preferences for the backbone and glycosidic torsion angles were observed. Non-A-form torsion angle conformers were found to have a greater prevalence in protein-bound duplexes. Further validation of the above observation was performed by analysing the RNA backbone conformers and the effect of protein binding, in the crystal structure of E. coli 70S ribosome.
Chapter 5 further describes the molecular dynamics simulation studies carried out to understand the effect of force fields on the RNA backbone conformer preferences. A 33mer long duplex was simulated using seven different force fields available in AMBER and CHARMM program, each for 100 ns. Trajectory analyses suggest the presence of sequence-dependent torsion angle preferences. Torsion angle conformer distribution closer to that of crystal structures was observed in the system simulated using parmbsc0 force field.
Molecular dynamics simulation studies of AU/AU base-pair step
A unique geometric feature, unlike that in other purine-pyrimidine (RY) steps in the crystal dataset analysis, was reported for AU/AU step (see Chapter 2). Appendix 1 describes the work carried out to validate these features observed in the crystal structures using simulation studies. Additionally, the effect of nearest-neighbor base pairs on the AU/AU step geometry were examined.
General Conclusion
Overall, the findings of this thesis work suggest that RNA duplexes exhibit sequence-dependent structural variations and sample a large volume of the double-helical conformational space. Further, protein binding affects the local base-pair step geometry and backbone conformation.
Books on the topic "Protein Conformers"
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Safar, Jiri G. Prion Paradigm of Human Neurodegenerative Diseases Caused by Protein Misfolding. Oxford University Press, 2016. http://dx.doi.org/10.1093/med/9780190233563.003.0005.
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Data accumulated from different laboratories argue that a growing number of proteins causing neurodegeneration share certain characteristics with prions. Prion-like particles were produced from synthetic amyloid beta (Aβ) peptides of Alzheimer’s disease (AD), from recombinant α-synuclein linked to Parkinson’s disease (PD), and from recombinant tau associated with frontotemporal dementias (FTD). Evidence from human prions reveals that variable disease phenotypes, rates of propagation, and targeting of different brain structures are determined by distinct conformers (strains) of pathogenic prion protein. Recent progress in the development of advanced biophysical tools identified the structural characteristics of Aβ in the brain cortex of phenotypically diverse AD patients and thus allowed an investigation of the prion paradigm of AD. The findings of distinctly structured strains of human brain Aβ, forming a unique spectrum of oligomeric particles in the cortex of rapidly progressive cases, implicates these structures in variable rates of propagation in the brain.
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Joshua, Castellino, and Keane David. Minority Rights in the Pacific Region. Oxford University Press, 2009. http://dx.doi.org/10.1093/acprof:oso/9780199574827.001.0001.
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The book examines the extent to which States in the Pacific region have put in place legislative and administrative measures designed to promote and protect the rights of minorities and indigenous peoples within their State. The book starts by identifying and classifying the various States in the region, and commenting on general trends that are visible across the region. This analysis includes Australia, New Zealand, and the Pacific Island Countries in the geographic boundaries of Micronesia, Melanesia, and Polynesia. The region is assessed against human rights standards, and the extent to which State practice conforms to international standards. There are five chapters in the book. The opening chapter conducts a tour d'horizon of the Pacific, identifying the states, delivering a history of the development of the region, comments on theories concerning the original migration of peoples, narrates colonial expeditions and enterprises, and assesses the emergence of independent government and institutions. The record of engagement with international human rights law is examined, in particular the States' ratification of human rights covenants. The attempt to implement a regional human rights mechanism for the Pacific is described with the merits of such a project debated. The subsequent four chapters are case-studies, designed to expose in detail, the extent to which indigenous and minority rights are implemented in the Pacific. Four states were chosen as representative of the challenges that face these groups in the region: Australia, New Zealand, Fiji, and Papua New Guinea. Each chapter is broken-down into four sections, according to the structure of the book series engaging with the history, identification of indigenous and minority groups, the rights of indigenous and minority groups, and the legal and other remedies available.
Book chapters on the topic "Protein Conformers"
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BaÑuelos, S., A. Galan, and A. Muga. "Membrane Binding of Different Water-Soluble Protein Conformers: Effect on Protein Structure and Stability." In Spectroscopy of Biological Molecules: Modern Trends, 305–6. Dordrecht: Springer Netherlands, 1997. http://dx.doi.org/10.1007/978-94-011-5622-6_135.
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Madison, Vincent S., David C. Fry, Bogda B. Wegrzynski, Michael P. Williamson, Robert M. Campbell, Waleed Danho, Edgar P. Heimer, and Arthur M. Felix. "Derivation of solution conformers of peptide hormones via constrained molecular dynamics based on 2D NMR data." In Proteins, 234–39. Dordrecht: Springer Netherlands, 1991. http://dx.doi.org/10.1007/978-94-010-9063-6_33.
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Gopalan, Anusha B., D. Flemming Hansen, and Pramodh Vallurupalli. "CPMG Experiments for Protein Minor Conformer Structure Determination." In Methods in Molecular Biology, 223–42. New York, NY: Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-7386-6_11.
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Akasaka, Kazuyuki. "High Pressure NMR Spectroscopy Characterizes Higher Energy Conformers of Proteins." In Advances in High Pressure Bioscience and Biotechnology II, 9–14. Berlin, Heidelberg: Springer Berlin Heidelberg, 2003. http://dx.doi.org/10.1007/978-3-662-05613-4_2.
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Akasaka, K., and T. Yamaguchi. "NMR Approaches to the Heat-, Cold-, and Pressure-Induced Unfolding of Proteins." In Biological NMR Spectroscopy. Oxford University Press, 1997. http://dx.doi.org/10.1093/oso/9780195094688.003.0018.
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Proteins are unique at least in two aspects. First, the atoms constituting a protein molecule act highly cooperatively in constructing its unique folded structure. As a result, their conformational transitions also occur in a highly cooperative fashion (often following a two-state transition). Secondly, the free energy balance between the folded (native) and unfolded (denatured) conformers are surprisingly marginal (usually less than 10 kcal/mole protein), despite the fact that interactions of thousands of atoms are involved in the folding. Such unique properties have been acquired by protein molecules through a countless number of random experiments and subsequent selections during the course of evolution of life, so that to our eyes, at present, they look as if they were carefully designed by Nature. It is important to recognize that such random experiments occurred in a dominantly aqueous environment. In order to understand the underlying principles of design as generally as possible, we need, at least, to characterize the factors that contribute to (1) the stability of protein structures, (2) the structural details of the folded and unfolded conformers, and (3) the kinetics of folding and unfolding reactions. In all these, the involvement, of water has crucial importance. NMR can provide unique information not only on aspect (2) above, but on all the above aspects when used under appropriate design. In this presentation, some examples will be shown from our current research. Our daily experience in the kitchen shows that proteins are easily deformed (denatured); a boiled egg can be prepared just by heating to not more than 100°C in water. The easy deformability (which is, in fact, a global conformational transition) in aqueous environment is not merely a matter of interest in a kitchen, but is a quality of design for proteins by Nature. A global conformational transition (unfolding) of a protein molecule occurs even under physiological conditions, although infrequently, as evidenced by hydrogen exchange of peptide NH protons that are completely buried in the folded structure.
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Azad, Iqbal. "Molecular Docking in the Study of Ligand-Protein Recognition: An Overview." In Biomedical Engineering. IntechOpen, 2023. http://dx.doi.org/10.5772/intechopen.106583.
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Molecular docking is a bioinformatics-based theoretical simulation strategy. It is employed to study ligand-protein interaction profiles and predict their binding conformers and affinity through computational tools. Since the 1980s, computational tools have been used in the drug discovery process. The initial molecular modeling approaches available at the time focused on a rigid view of the ligand-protein interaction due to the limited computational capabilities. The advancement of hardware technology has made it possible to simulate the dynamic character of the ligand-protein interactions throughout time. The current chapter deals with an outline of the progression of structure-based drug discovery methodologies in the investigation of the ligand-protein interaction profiles from static to improved molecular docking strategies.
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Hinck, A. P., and W. F. Walkenhorst. "NMR and Mutagenesis Investigations of a Model Cis: Trans Peptide tsomerization Reaction: Xaa116-Pro117of Staphylococcal Nuclease and its Role in Protein Stability and Folding." In Biological NMR Spectroscopy. Oxford University Press, 1997. http://dx.doi.org/10.1093/oso/9780195094688.003.0016.
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The slow rates of peptide bond isomerization in imino acids and the substantial population of the cis peptide bond isomer in Xaa-Pro linkages in peptides were first recognized in NMR studies of proline-containing model compounds (Maia et al., 1971). The important role of this isomerization in protein stability and folding (reviewed by Kim and Baldwin, 1982, 1990; Schmid, 1993) were recognized several years later (Brandts et al., 1975) and the biological relevance of this process was substantiated by the discovery of a ubiquitous enzyme that catalyzes Xaa-Pro peptide bond isomerization (Fischer et al., 1984, 1989; Takahashi et al., 1989). The strict evolutionary conservation of some prolyl residues and the observation that the kinetics of interconversion between alternative functional forms of some systems is consistent with the time scale of proline isomerization suggest that proline isomerization may play a wide role in protein structure and function. Suggestive examples include the sodium pump of Escherichia coli, the disulfide isomerase/thioredoxin class of enzymes, concanavalin A, and bovine prothrornbin fragment I (Brown et al., 1977; Marsh et al, 1979; Dunker, 1982; Brandland Deber, 1986; Langsetmo et al, 1989). NMR spectroscopy is one of the most suitable tools for studying this isomerization reaction. The rates generally are slow on the time scale of NMR chemical shifts but, in favorable cases, are comparable to longitudinal relaxation rates so that the isomerization process can be investigated by chemical exchange spectroscopy. NMR data obtained on calbindin D9k (Chazin et al., 1989), insulin (Higgins et al., 1988), and staphylococcal nuclease (nuclease) as discussed below have shown that each exists in solution under native conditions as a mixture of slowly exchanging conformers. The fact that dynamic molecular heterogeneity in nuclease was first observed in the laboratory of Oleg Jardetzky, as manifested by splitting of the histidyl 1H ε1 resonance from His46 in one-dimensional 1H NMR spectra recorded at 100 MHz (Markley et al., 1970), makes this topic particularly appropriate to a volume celebrating his scientific contributions.
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François, Yannis-Nicolas, Anne-Lise Marie, Coralie Ruel, Rabah Gahoual, Nguyet Thuy Tran, and Myriam Taverna. "Capillary Electrophoresis Coupled to Mass Spectrometry as a Powerful Tool to Investigate Heterogeneities, Conformers, and Oligomers of Intact Proteins." In Advances in Chromatography, 137–79. CRC Press, 2019. http://dx.doi.org/10.1201/9780429026171-5.
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Murphy, Dawn C. "Cooperating for Peace and Security?" In China's Rise in the Global South, 218–35. Stanford University Press, 2022. http://dx.doi.org/10.11126/stanford/9781503630093.003.0008.
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This chapter examines China's United Nations peacekeeping operations (UNPKO), conventional arms sales, antipiracy activities, and its military base in Djibouti. Its security behavior in these regions today is mostly cooperative and norm convergent with the liberal order. China stresses the need to use multilateral mechanisms such as the United Nations to address hot spots and threats to peace and security. Its conventional arms sales to these regions is minimal. Although China's base in Djibouti may be competitive, it is norm neutral and in alignment with the practice of great powers establishing military bases to protect their regional interest. All of China's military behavior in these regions today conforms to the rules of the liberal order. In contrast with the Mao era, China is not attempting to create its own military rules.
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McNally, Michael D. "Religion as Spirituality." In Defend the Sacred, 94–126. Princeton University Press, 2020. http://dx.doi.org/10.23943/princeton/9780691190907.003.0004.
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This chapter examines the failure in the courts of Native appeals to religious freedom protections for sacred lands, and it extends the previous chapter's analysis of the reception of Native claims to religion as religion. Where a religious claim conforms to the subjective, interior spirituality that has become naturalized in the United States, it has worked reasonably well in the courts. This is emphatically not the case where claims involve religious relationships with, uses of, and obligations to, land. The chapter explains how courts reason their way out of taking steps to protect Native American religious freedom when sacred places are threatened, a puzzling matter in that courts consistently acknowledge the sincerity of the religious beliefs and practices associated with those sacred places. Along the way the chapter develops a fuller sense of the workings of the discourse of Native American spirituality as it comes to control judicial comprehension of Native religious freedom claims.
Conference papers on the topic "Protein Conformers"
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Sugo, T., S. Tanabe, K. Shinoda, and M. Matsuda. "MONOCLONAL ANTIBODIES THAT RECOGNIZE Ca2+-INDUCED CONFORMER OF PROTEIN C, INDEPENDENT OF GLA RESIDUES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643644.
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Monoclonal antibodies (MCA’s) were prepared against human protein C (PC) according to Köhler & Milstein, and those that recognize the Ca2+-dependent PC conformers were screened by direct ELISA in the presence of 2 mM either CaCl2 or EDTA. Out of nine MCAߣs thus screened, five MCA's designated as HPC-1˜5, respectively, were found to react with PC in the presence of Ca2+ but not EDTA. By SDS-PAGE coupled with Western Blotting performed in the presence of 2 mM CaCl2, we found that two MCA’s HPC-1 and 2, recognized the light chain, and two others, HPC-3 and 4, recognized the heavy chain of PC. But another MCA, HPC-5 was found to react with only non-reduced antigens. Further study showed that HPC-1 and 5 failed to react with the Gla-domainless PC, i.e. PC from which the N-terminal Gla-domain of the light chain had been cleaved off by α-chymotrypsin. However, all the other three MCA's retained the reactivity with the antigen in the presence of Ca2+ even after the Gla-domain had been removed. The binding of these MCA’s to PC in the presence of Ca2+ was found to be saturable with respect to the Ca2+ concentration and the half maximal binding for each MCA was calculated to be about 0.5+mM. Moreover, many other divalent cations such as Mg2+, Mn2+ , Ba2+, Zn2+, Co2+, Sr2+, were found to substitute for Ca2+ in inducing the metal ion-dependent but Gla-domain-independent conformer of PC.Cross-reactivity to other vitamin K-aependent plasma proteins was examined by direct ELISA; HPC-2 and 3 reacted solely to PC, but HPC-1 and 4 also reacted with prothrombin and HPC-5 with both prothrombin and factor X.These findings indicated that there are two or more metal binding sites besides the Gla-domain, possibly one in the light chain and the other(s) in the heavy chain. The presence of these metal binding sites may contribute to the unique conformer of vitamin K-dependent plasma proteins including protein C.
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Schlyer, Bruce D., Joseph A. Schauerte, Duncan G. Steel, and Ari Gafni. "Nonexponential decay of room-temperature phosphorescence: evidence for several slowly interconverting or static protein conformers." In OE/LASE '94, edited by Joseph R. Lakowicz. SPIE, 1994. http://dx.doi.org/10.1117/12.182720.
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BRAGA, Luiza Kopchinski. "A Mandioca na Alimentação de Ruminantes." In Congresso Online de Zootecnia. CONGRESSE.ME, 2021. http://dx.doi.org/10.54265/shgk1198.
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O objetivo deste estudo foi analisar a utilização da mandioca na alimentação de ruminantes, sua viabilidade e seus efeitos sobre a saúde e sobre a carne desses animais. A metodologia utilizada envolveu experimentos e estudos de caso para identificar o porquê dos fenômenos. Os experimentos de maior relevância foram realizados por Silva et al. (2003) em campo e avaliaram a substituição do milho pelos componentes extraídos da mandioca em diferentes proporções na dieta de diversos ruminantes, com os quais foram utilizadas quatro variáveis fontes de energia: 1) milho; 2) raiz de mandioca; 3) casca de mandioca; e, 4) farelo de mandioca. Novilhas Aberdeen Angus x Nelore, alimentadas com casca de mandioca, apresentaram maior teor de umidade e menor de proteína em determinado músculo quando comparadas àquelas alimentadas por milho. Nesse mesmo grupo de animais, os analistas observaram que dietas compostas por casca e farelo de mandioca proporcionaram menor deposição de lipídeos totais em relação às dietas de milho. Cabe mencionar que, conquanto seja fonte de energia de elevada produtividade portadora de nutrientes indispensáveis para melhorar o desempenho animal, a mandioca contém fatores antinutricionais que podem comprometer a produtividade de um rebanho e, portanto, para seu uso adequado requer conhecimento acerca da biossíntese e do mecanismo de ação de seus compostos, bem como de técnicas de destoxificação. Uma das grandes limitações nutricionais quanto ao uso da mandioca e de seus subprodutos na alimentação animal é a presença de glicosídeos cianogênicos, compostos do metabolismo secundário da planta que funcionam como mecanismos de defesa contra determinadas doenças, pois, sendo potencialmente tóxicos, podem ser convertidos em ácido cianídrico (HCN). Considerando o potencial valor nutritivo da mandioca, algumas opções são propostas e avaliadas para permitir a utilização segura do alimento, tais como o melhoramento e uso de variedades com menor teor de cianoglicosídeos, conforme Santos et al. (2001), e o processamento, método destoxificante proposto por Corrêa et al. (2002). A consideração final deste estudo foi no sentido de que as experiências na utilização de coprodutos da mandioca, como aditivos de uma dieta alimentar, em substituição aos alimentos tradicionais revelaram resultados satisfatórios. Embora a mandioca contenha fatores antinutricionais, os métodos de conservação do produto são eficientes a reduzi-los a níveis inócuos; e, por se tratar de uma forrageira completa, com alto valor alimentar, de grande disponibilidade, com elevado teor proteico e baixo custo de produção, vêm destacando-se cada vez mais na alimentação de ruminantes. PALAVRAS-CHAVE: Nutrição Animal, Ruminantes, Mandioca
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Polyanna Bastos Silva Campos, Myrela, Valentina Silva Rodrigues, Pedro Henrique Silveira de Sousa, Ester Almeida Carneiro Rodrigues da Silva, and Adson Kevin Cunha Negidio. "ALTERAÇÕES LABORATORIAIS MAIS FREQUENTES EM PACIENTES COM COVID-19, UMA REVISÃO DE LITERATURA." In II Congresso Online Brasileiro de Medicina. Congresse.me, 2022. http://dx.doi.org/10.54265/zxkl9002.
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Introdução: A Covid-19 é uma doença infecciosa causada pelo vírus SARSCov-2, e desenvolve a síndrome respiratória aguda no paciente, podendo ser percebido por meio dos principais sintomas como: cefaleia, febre, tosse e coriza. Além da análise dos sintomas, a Covid-19 pode ser investigada por meio de exames laboratoriais, e a posterior análise dos indicadores. Assim, a procura e leitura de fatores como Proteína C Reativa (PCR), Leucócitos, D-Dímero, e a razão plaqueta/linfócitos, podem se configurar como parâmetros importantes na investigação patológica do paciente, tendo em vista que o coronavírus é responsável por alterações inflamatórias e de coagulação que podem levar ao dano tecidual e morte. Objetivo: Analisar as alterações laboratoriais mais frequentes em pacientes com Covid-19. Métodos: Foi realizada uma busca qualitativa de artigos considerados de referência métrica e de classificação no SciELOAnalytics. Foram selecionados três artigos na base de dados Scientific Electronic Library Online (SCIELO) e na Biblioteca Virtual em Saúde (BVS) publicados no ano de 2020. O eixo temático é Clínica Médica. Resultados: Foram selecionados três artigos para a realização do estudo. Os exames laboratoriais fornecem suporte crítico para o manejo clínico adequado da COVID-19, desde a triagem ao diagnóstico, prognóstico e monitoramento. Dessa forma, Xavier et al. (2020), afirmam que as alterações laboratoriais mais frequentes em pacientes com COVID-19 são aumento de 75%-93% da proteína C reativa (PCR) com diminuição da albumina sérica em 50%- 98% e contagem total de leucócitos com considerável variação, conforme relatos na literatura, por vezes aparecendo alta ou diminuída, mas com evidente presença de linfopenia (35%-75%). Há também diminuição da hemoglobina de cerca de 41% a 50% e aumento da taxa de sedimentação de eritrócitos (VHS) em 15%-85%, alanina aminotransferase (ALT) e aspartato aminotransferase (AST) de cerca de 8%-37% e lactato desidrogenase (LDH) em aproximadamente 12%. De semelhante modo, o estudo de Junior et. al (2020), demonstra alterações laboratoriais significativas em relação à proteína C reativa (PCR), leucócitos, albumina, hemoglobina, alanina aminotransferase (ALT), aspartato aminotransferase (AST) e lactato desidrogenase (LDH). Assim também, com menor desvio padrão, segundo Carelli et. al (2020), há aumento da bilirrubina total (1,12 mg/dL), aumento da creatinina (3,93 mg/dL), aumento do D-dímero (3.505 ng/mL), aumento da PCR (20,65 mg/dL) e de leucócitos (26.036/mm³), nesse mesmo estudo foi identificado uma linfopenia significativa (2.225/mm³). Logo, os artigos encontram alterações similares. Conclusão: Desse modo, as alterações mais frequentes foram destaques em todos os artigos utilizados, sendo elas: o aumento da proteína C reativa (PCR), diminuição da albumina sérica, leucocitose, linfopenia, aumento da taxa de AST e ALT, aumento da creatinina e do D-Dímero. É certo que cada alteração está envolvida com uma fase da doença, porém, de modo geral, essas são as mais presentes entre os pacientes sintomáticos. Resumo sem apresentação oral. PALAVRAS-CHAVE: COVID-19, Exames e Diagnósticos Laboratoriais, SARS-CoV-2
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OLIVEIRA, Gabrielle Cordeiro Beltrão de, and João Pedro Abrahão NICOLETT. "Doença Meningocócica complicada com choque séptico e coagulopatia em adolescente de 17 anos." In Semana Online Científica de Medicina. CONGRESSE.ME, 2021. http://dx.doi.org/10.54265/yopj7062.
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A Doença Meningocócica (DM) é uma infecção bacteriana aguda, causada pela Neisseria meningitidis, altamente fatal, que necessita diagnóstico e intervenção precoce. Sua apresentação clínica varia desde a forma assintomática, até a doença invasiva, como meningococcemia e meningite (com ou sem meningococcemia). O devido caso, trata-se de uma paciente, feminina, 17 anos, com quadro de astenia, febre, náuseas, vômitos, além de rash violáceo em membros inferiores, superiores e face, evoluindo com cefaleia intensa, confusão mental e sinais de irritação meníngea. Ao exame paciente encontrava-se em grave estado geral, rash violáceo em membros inferiores, superiores, face, com necrose de quarto e quinto quirodáctilos direito, pouco colaborativa, confusão mental, rigidez de nuca e hipotensa (81x41 mmHg). Análise de líquor mostrou glicose < 5 mg/ 100ml, proteína 346 mg/100ml, células nucleadas 10.441 (neutrofilos 85%/ Linfocitos 5% / Monocitos 10%). Pesquisa para BAAR e fungo negativos. Isolamento de diplococo gram (-) à microscopia direta. Aglutinação pelo látex ((H.influenza/S.pneumoniae/ N.Meningitidis A/B/C): Neisseria meningitidis C: Positivo. Solicitado avaliação da cirurgia vascular, onde foi sugerido, devido a ausência de perfusão nos membros, amputação do antepé esquerdo. O quadro clínico da paciente seguiu conforme a apresentação clássica da DM, inicialmente com sintomas nãoespecíficos, como febre, sonolência, náuseas, vômitos e irritabilidade, que geralmente se apresentam dentro de 4 a 6 horas seguido de rash purpúrico clássico, dor e rigidez de nuca, que geralmente aparecem depois de 12 horas. A coagulopatia apresentada, está associada à trombose microvascular, lesão endotelial e risco elevado de sangramento. Infelizmente, a maioria dos casos de DM é diagnosticada após o aparecimento dos sinais tardios. PALAVRAS-CHAVE: Doença Meningocócica, necrose, amputacão
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Tejo, Debora Perdigão, Carlos Henrique Dos Santos Fernandes, Caroline Aparecida Moreira Leite, Guilherme Neves De Macedo, and Lúcia Sadayo Assari Takahashi. "INFLUÊNCIA DA DIMENSÃO DE SEMENTES NA QUALIDADE FISIOLÓGICA DE SEMENTES DE SOJA." In I Congresso Nacional de Ciências Agrárias On-line. Revista Multidisciplinar de Educação e Meio Ambiente, 2021. http://dx.doi.org/10.51189/rema/1610.
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Introdução: A soja (Glycine max) é uma cultura de relevância para a alimentação humana e animal devido aos elevados teores de proteína e óleo presente em seus grãos. Possui importância no cenário econômico sendo a principal cultura agrícola do Brasil, o país também se destaca a nível mundial em sua produção e exportação. No entanto para se obter sucesso na produção é crucial um estabelecimento de estande adequado e para isso é necessário a utilização de sementes com qualidade fisiológica, e muito se discute se a dimensão das sementes classificadas em diferentes peneiras comerciais influência nos níveis de viabilidade e vigor. O objetivo deste estudo foi verificar a influência de diferentes peneiras comerciais, ou seja, diferentes tamanhos de sementes na qualidade fisiológica de sementes de soja. Materiais e métodos: O experimento foi conduzido no Laboratório de análise de sementes em Londrina-PR, foram utilizados quatro lotes de sementes de soja que sendo submetidos incialmente ao teste de retenção de peneiras para segregação das sementes em função de sua dimensão, para isso contou-se com auxílio de um jogo de peneiras de laboratório. Foram selecionadas duas peneiras onde estava retido a maior quantidade de sementes de cada lote, totalizando oito tratamentos. Aplicou-se as metodologias de teste de germinação em rolos de papel e de comprimento de plântulas, conforme recomendação para a cultura. O experimento seguiu o delineamento inteiramente casualizado. Resultados: Os resultados do teste de germinação demonstraram não haver diferença estatística nos dados de viabilidade em função das diferenças de tamanho das sementes dentro de cada lote, apenas diferença entre os lotes, sendo que a dimensão da semente estivesse atrelada, ele foi verificado nos dados obtidos no teste de comprimento de plântula. Conclusão: Concluiu-se que nas condições nas quais foi desenvolvido o presente experimento a qualidade fisiológica de sementes de soja não é influenciada significativamente pela dimensão (peneiras comerciais).
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Balzana, Mariana Fortes, Carolina Carvalho Mocarzel, Beatriz Ramiro Garcia Carneiro, Carolina Horstmann de Carvalho, Giulia Bastos Buscema, and Flavia Duraes Gonçalves. "Gestante obesa com Covid-19 e pré-eclâmpsia: relato de caso." In 44° Congresso da SGORJ - XXIII Trocando Ideias. Zeppelini Editorial e Comunicação, 2020. http://dx.doi.org/10.5327/jbg-0368-1416-2020130281.
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Introdução: A Covid-19 é uma doença infecciosa declarada como emergência da saúde pública em 2020. Gestantes representam um grupo com vulnerabilidade única em razão de suas alterações fisiológicas, susceptibilidade a infecções e comprometimento de funções imunológicas. Relato de Caso: P.S.S., 25 anos, branca, residente do Rio de Janeiro, gestante de 34 semanas e 3 dias, hipertensa em uso de metildopa, índice de massa corpórea (IMC) 42 kg/m2. Admitida na Unidade Materno-Fetal do Hospital Federal dos Servidores do Estado (UMF-HFSE) com queixa de febre há 7 dias e tosse produtiva. Na avaliação inicial, estava hemodinamicamente estável, afebril, taquipneica (28 irpm), com saturação de oxigênio (SatO2) de 98% e estertores em base pulmonar direita. Exame obstétrico e avaliação fetal sem alterações. Evoluiu com letargia, SatO2 95% em cateter de O2 3 L/min com sinais de esforço respiratório, pressão arterial de 150×90 mmHg, gasometria arterial com hipoxemia e acidose respiratória compensada. Laboratório com linfopenia, 120.000 plaquetas/mm3, lactato desidrogenase (LDH) de 259 U/L, bilirrubina direta 1,87 mg/dL e indireta de 1,06 mg/dL. Fez uso de azitromicina, ceftriaxone, oseltamivir e clexane com aumento progressivo no suporte de oxigênio e necessidade de reposição de bicarbonato. Tomografia de tórax com padrão de vidro fosco com acometimento de 50‒75%. Em função da piora do quadro respiratório e persistência da acidose metabólica, foi transferida para Unidade de Terapia Intensiva (UTI) para planejamento de parto ainda em ventilação não invasiva. Parto cesáreo realizado, recém-nascido (RN) com Apgar 8/9, encaminhado à UTI neonatal. Piora ventilatória e laboratorial no quarto dia pós-parto (LDH 877 U/L e transaminase glutâmico-oxalacética — TGO 372 mg/dL) com necessidade de suporte com ventilação mecânica (VM), posição prona, corticoterapia, infusão de aminas e diálise. Permaneceu em UTI por 14 dias, com posterior alta para enfermaria. Discussão: A paciente apresentou quadro de infecção por Covid-19 confirmada por polymerase chain reaction (PCR) positivo durante internação, com evolução grave e necessidade de UTI e VM, conforme a maioria dos pacientes de estudos publicados. Além da gestação, fator de risco já estabelecido, a paciente era hipertensa crônica e obesa, sendo ambas as condições associadas a casos severos. A indicação do parto foi iminentemente materna, sem evidências de sofrimento fetal, em função da piora progressiva do quadro materno, sendo a via alta escolhida e ocorrendo antes do termo, conforme relatos publicados. A evolução laboratorial apresentada tem dados que podem gerar dúvidas quanto a uma pré-eclâmpsia (PE) grave associada (relação proteína/creatinina urinária 0,79), e esse diagnóstico diferencial deve ser avaliado, pois 75% dos casos mais graves desenvolveram sinais e sintomas de PE. Porém, em razão da piora clínica e da instabilidade hemodinâmica com necessidade de múltiplas intervenções, essa avaliação foi prejudicada. RN com PCR para Covid-19 negativo. Altas hospitalares do RN e da puérpera com 8 e 35 dias, respectivamente, ambos em boas condições clínicas e com agendamento de seguimento.
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Beckert, Helen Cristina. "EFEITOS PRÓ-TUMORAIS DAS ARMADILHAS EXTRACELULARES DE NEUTRÓFILOS (NETS): UMA REVISÃO DE LITERATURA." In II Congresso Brasileiro de Imunologia On-line. Revista Multidisciplinar em Saúde, 2022. http://dx.doi.org/10.51161/ii-conbrai/5822.
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Introdução: Armadilhas extracelulares de neutrófilos (NETs) são compostas por DNA descondensado com proteases associadas, como elastase de neutrófilos (NE) e metaloproteinase de matriz 9 (MMP9). Tumores são compostos por células que se multiplicam descontroladamente através da deturpação de mecanismos imunitários, como o recrutamento de neutrófilos secretores de NETs por células cancerígenas. Porém, há poucos estudos acerca da relação entre NETs e progressão tumoral. Objetivo: Sintetizar informações sobre os efeitos pró-tumorais das NETs. Material e Métodos: O estudo consiste em uma revisão descritiva, fundamentado na análise de 11 artigos indexados nas bases de dados Google Scholar e PubMed. Resultados: Estudos com modelos animais demonstraram que proteases associadas as NETs processam moléculas derivadas de inflamossomos e aumentam o potencial metastático -com remodelação da matriz extracelular, liberação de fatores pró-angiogênicos, aumento da permeabilidade vascular e da transição epitélio-mesenquimal. Além disso, o DNA das NETs atua como fator quimiotático de células cancerígenas de câncer de mama e de cólon, que expressam a proteína CCDC25 que se liga ao DNA, para nichos metastáticos no fígado. Em modelos animais e culturas celulares de câncer de mama e de próstata, a inflamação pulmonar persistente estimulou a clivagem da laminina da matriz extracelular pela NE e pela MMP9, o que desencadeou sinalizações que despertaram células tumorais dormentes. Em culturas celulares de melanoma e de carcinoma de cólon, a ativação de CXCR1 e CXCR2 em células tumorais induziu liberação de NETs pelos neutrófilos para proteção das células cancerígenas do contato com linfócitos T CD8+. Estudos in vitro demonstraram que NETs promovem trombose associada ao tumor funcionando como arcabouço para plaquetas, hemácias e moléculas pró-coagulantes. Estudos em pacientes demonstraram que indicadores de NETs no soro aumentam conforme a progressão de estágios de cânceres de mama, gástrico e glioma. Conclusão: As NETs contribuem para a progressão de diferentes cânceres, porém ainda são necessários mais estudos. Interessantemente, vários ensaios clínicos em andamento possuem como alvos terapêuticos constituintes das NETs ou moléculas responsivas as NETs, como NE, DNA, CXCR1, CCDC25. Assim, quanto maior a compreensão dos efeitos pró-tumorais das NETs, melhores métodos de acompanhamento e tratamento de cânceres poderão ser desenvolvidos.
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Ferreira da Silva, Giovanna, Marcello do Couto Dias, Irley Karoline Seixas Paiva, Mércia Ferreira Ribeiro, Katarine Antonia dos Santos Barile, and Carlos Eduardo de Melo Amaral. "AVALIAÇÃO DO TESTE SUPLEMENTAR GEENIUS HCV SUPPLEMENTAL ASSAY NA DISPARIDADE ENTRE RESULTADO DE TRIAGEM SOROLÓGICO-MOLECULAR PARA O VÍRUS DA HEPATITE C." In Congresso Brasileiro de Inovação em Microbiologia. Congresse.me, 2022. http://dx.doi.org/10.54265/rnfk1700.
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INTRODUÇÃO: A detecção de HCV na triagem, em doadores de sangue da Fundação Hemopa, é realizada simultaneamente por um teste sorológico e um teste molecular. No caso de discordância entre estes, é realizado um teste confirmatório. Geenius HCV Supplemental Assay é utilizado como teste confirmatório suplementar para análise da presença de anticorpos específicos para HCV, utilizando os antígenos específicos NS3, NS4, NS5 e capsídeo. OBJETIVO: Determinar a freqüência de resultado de imunocromatografia Geenius HCV Confirmatory Assay (BioRad) em amostras Eclesys Anti-HCV reagentes (positivos e inconclusivos) e teste de ácido nucléico (NAT) para HCV indetectáveis. MATERIAIS E MÉTODOS: Foram avaliadas 55 amostras entre o período de Setembro de 2021 a Março de 2022. Para este estudo, todas as amostras selecionadas apresentaram sorologia Anti HCV reagente (valor de leitura da amostra/ valor de “cut off” (S/CO) >0,8) e NAT indetectável. Foram utilizados, para detecção de anticorpos anti-HCV, o ensaio Eclesys Anti-HCV com metodologia de eletroquimioluminescência, e para detecção de material genético de HCV, o Kit NAT HIV/HCV Bio-Manguinhos com metodologia de PCR em tempo real. A realização do teste Geenius HCV Supplemental Assay se dá de acordo com a utilização da proteína A de ligação ao anticorpo, conjugada com partículas coloridas de celulose e os antígenos específicos ligados à membrana da fita. Como resultado, pode haver a captura dos anticorpos Anti-HCV, produzindo uma reação colorimétrica na área teste do cassete e na área de controle da reação. RESULTADOS: Conforme o ensaio sorológico Eclesys Anti-HCV, de 55 amostras, 32,8% (17/55) apresentaram resultado de sorologia inconclusivo (valor de “cut off” (S/CO) 0,8 a 1,2) e 67,2% (37/55) apresentaram resultado de sorologia positivo (valor de “cut off” (S/CO) > 1,2) . Entre as amostras que tiveram resultado de sorologia inconclusiva, 100% (17/17) apresentaram resultados de imunocromatografia negativos. Entre as amostras que tiveram sorologia positiva, 97,2% (36/37) apresentaram resultados de imunocromatografia negativos e 2,8% (1/37) apresentaram resultados de imunocromatografia indeterminados. Não houveram resultados positivos.CONCLUSÃO: A imunocromatografia mostrou-se ferramenta eficiente para confirmar a não exposição ao HCV em 98% (54/55) dos doadores de sangue com resultados discordantes do teste de triagem sorológico-molecular para o HCV, permitindo que os doadores recebessem a devida orientação. PALAVRAS-CHAVE: HCV, IMUNOCROMATOGRAFIA, TESTE
Reports on the topic "Protein Conformers"
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Eldar, Avigdor, and Donald L. Evans. Streptococcus iniae Infections in Trout and Tilapia: Host-Pathogen Interactions, the Immune Response Toward the Pathogen and Vaccine Formulation. United States Department of Agriculture, December 2000. http://dx.doi.org/10.32747/2000.7575286.bard.
Full textAbstract:
In Israel and in the U.S., Streptococcus iniae is responsible for considerable losses in various fish species. Poor understanding of its virulence factors and limited know-how-to of vaccine formulation and administration are the main reasons for the limited efficacy of vaccines. Our strategy was that in order to Improve control measures, both aspects should be equally addressed. Our proposal included the following objectives: (i) construction of host-pathogen interaction models; (ii) characterization of virulence factors and immunodominant antigens, with assessment of their relative importance in terms of protection and (iii) genetic identification of virulence factors and genes, with evaluation of the protective effect of recombinant proteins. We have shown that two different serotypes are involved. Their capsular polysaccharides (CPS) were characterized, and proved to play an important role in immune evasion and in other consequences of the infection. This is an innovative finding in fish bacteriology and resembles what, in other fields, has become apparent in the recent years: S. iniae alters surface antigens. By so doing, the pathogen escapes immune destruction. Immunological assays (agar-gel immunodiffusion and antibody titers) confirmed that only limited cross recognition between the two types occurs and that capsular polysaccharides are immunodominant. Vaccination with purified CPS (as an acellular vaccine) results in protection. In vitro and ex-vivo models have allowed us to unravel additional insights of the host-pathogen interactions. S. iniae 173 (type II) produced DNA fragmentation of TMB-8 cells characteristic of cellular necrosis; the same isolate also prevented the development of apoptosis in NCC. This was determined by finding reduced expression of phosphotidylserine (PS) on the outer membrane leaflet of NCC. NCC treated with this isolate had very high levels of cellular necrosis compared to all other isolates. This cellular pathology was confirmed by observing reduced DNA laddering in these same treated cells. Transmission EM also showed characteristic necrotic cellular changes in treated cells. To determine if the (in vitro) PCD/apoptosis protective effects of #173 correlated with any in vivo activity, tilapia were injected IV with #173 and #164 (an Israeli type I strain). Following injection, purified NCC were tested (in vitro) for cytotoxicity against HL-60 target cells. Four significant observations were made : (i) fish injected with #173 had 100-400% increased cytotoxicity compared to #164 (ii) in vivo activation occurred within 5 minutes of injection; (iii) activation occurred only within the peripheral blood compartment; and (iv) the isolate that protected NCC from apoptosis in vitro caused in vivo activation of cytotoxicity. The levels of in vivo cytotoxicity responses are associated with certain pathogens (pathogen associated molecular patterns/PAMP) and with the tissue of origin of NCC. NCC from different tissue (i.e. PBL, anterior kidney, spleen) exist in different states of differentiation. Random amplified polymorphic DNA (RAPD) analysis revealed the "adaptation" of the bacterium to the vaccinated environment, suggesting a "Darwinian-like" evolution of any bacterium. Due to the selective pressure which has occurred in the vaccinated environment, type II strains, able to evade the protective response elicited by the vaccine, have evolved from type I strains. The increased virulence through the appropriation of a novel antigenic composition conforms with pathogenic mechanisms described for other streptococci. Vaccine efficacy was improved: water-in-oil formulations were found effective in inducing protection that lasted for a period of (at least) 6 months. Protection was evaluated by functional tests - the protective effect, and immunological parameters - elicitation of T- and B-cells proliferation. Vaccinated fish were found to be resistant to the disease for (at least) six months; protection was accompanied by activation of the cellular and the humoral branches.