scholarly journals Computational-guided determination of the functional role of 447-52D long CDRH3

2018 ◽  
Vol 31 (12) ◽  
pp. 479-487
Author(s):  
Edwin Kamau ◽  
Richard Bonneau ◽  
Xiang-Peng Kong
Keyword(s):  
Human Monoclonal Antibody ◽  
Van Der Waals Interactions ◽  
Binding Surface ◽  
The Individual ◽  
Computational Mutagenesis ◽  
Hiv 1 ◽  
Complementarity Determining Region ◽  
Conserved Epitope

Abstract447-52D (447) is a human monoclonal antibody that recognizes a conserved epitope in the crown region of the third variable loop (V3) of HIV-1 gp120, and like many anti-HIV-1 antibodies with broad neutralization capabilities, it has a long heavy-chain complementarity determining region (CDRH3). Here, we use a combination of computational mutagenesis and modeling in tandem with fluorescence polarization assays to interrogate the molecular basis of 447 CDRH3 length and the individual contribution of selected CDRH3 residues to affinity. We observe that 447 CDRH3 length provides a large binding surface area and the best enthalpic contributions derived from hydrophobic packing, main-chain hydrogen bonds, electrostatic and van der Waals interactions. We also found out that CDRH3 residue Try100I is critical to 447 binding affinity.

scholarly journals Exploring Secondary Metabolite Profiles of Stachybotrys spp. by LC-MS/MS

Toxins ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 133 ◽  
Author(s):  
Annika Jagels ◽  
Viktoria Lindemann ◽  
Sebastian Ulrich ◽  
Christoph Gottschalk ◽  
Benedikt Cramer ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Future Research ◽  
Structural Modifications ◽  
Metabolite Profiles ◽  
The Individual ◽  
First Time ◽  
Analytical Standards ◽  
Respective Species

The genus Stachybotrys produces a broad diversity of secondary metabolites, including macrocyclic trichothecenes, atranones, and phenylspirodrimanes. Although the class of the phenylspirodrimanes is the major one and consists of a multitude of metabolites bearing various structural modifications, few investigations have been carried out. Thus, the presented study deals with the quantitative determination of several secondary metabolites produced by distinct Stachybotrys species for comparison of their metabolite profiles. For that purpose, 15 of the primarily produced secondary metabolites were isolated from fungal cultures and structurally characterized in order to be used as analytical standards for the development of an LC-MS/MS multimethod. The developed method was applied to the analysis of micro-scale extracts from 5 different Stachybotrys strains, which were cultured on different media. In that process, spontaneous dialdehyde/lactone isomerization was observed for some of the isolated secondary metabolites, and novel stachybotrychromenes were quantitatively investigated for the first time. The metabolite profiles of Stachybotrys species are considerably influenced by time of growth and substrate availability, as well as the individual biosynthetic potential of the respective species. Regarding the reported adverse effects associated with Stachybotrys growth in building environments, combinatory effects of the investigated secondary metabolites should be addressed and the role of the phenylspirodrimanes re-evaluated in future research.

scholarly journals Ablation of the Complementarity-Determining Region H3 Apex of the Anti-HIV-1 Broadly Neutralizing Antibody 2F5 Abrogates Neutralizing Capacity without Affecting Core Epitope Binding

2010 ◽  
Vol 84 (9) ◽  
pp. 4136-4147 ◽  
Author(s):  
Jean-Philippe Julien ◽  
Nerea Huarte ◽  
Rubén Maeso ◽  
Stefka G. Taneva ◽  
Annie Cunningham ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Hydrophobic Interactions ◽  
Neutralizing Antibody ◽  
Titration Calorimetry ◽  
Peptide Epitope ◽  
Neutralizing Capacity ◽  
Epitope Binding ◽  
Hiv 1 ◽  
Complementarity Determining Region

ABSTRACT The identification and characterization of broadly neutralizing antibodies (bnAbs) against HIV-1 has formed a major research focus, with the ultimate goal to help in the design of an effective AIDS vaccine. One of these bnAbs, 2F5, has been extensively characterized, and residues at the apex of its unusually long complementarity-determining region (CDR) H3 loop have been shown to be crucial for neutralization. Structural studies, however, have revealed that the 100TLFGVPI100F apex residues of the CDR H3 loop do not interact directly with residues of its core gp41 epitope. In an attempt to gain better insight into the functional role of this element, we have recombinantly expressed native 2F5 Fab and two mutants in which either the apical Phe100B(H) residue was changed to an alanine or the CDR H3 residues 100TLFGVPI100F were replaced by a Ser-Gly dipeptide linker. Isothermal titration calorimetry (ITC) and competitive-binding enzyme-linked immunosorbent assays (ELISAs) rendered strikingly similar affinity constants (Kd [dissociation constant] of ∼20 nM) for linear peptide epitope binding by 2F5 Fabs, independent of the presence or absence of the apex residues. Ablation of the CDR H3 apex residues, however, abolished the cell-cell fusion inhibition and pseudovirus neutralization capacities of 2F5 Fab. We report competitive ELISA data that suggest a role of 2F5 CDR H3 apex residues in mediating weak hydrophobic interactions with residues located at the C terminus of the gp41 membrane proximal external region and/or membrane components in the context of core epitope binding. The present data therefore imply an extended 2F5 paratope that includes weak secondary interactions that are crucial for neutralization of Env-mediated fusion.

scholarly journals Features of professional self-determination in various types of families (on the material of dynasties)

2019 ◽  
pp. 52-56
Author(s):  
Nikolay V. Shamanin ◽  
Vitaliy Ye. Lapshin
Keyword(s):  
Professional Development ◽  
Family Members ◽  
Self Determination ◽  
Lag Effect ◽  
The Family ◽  
Professional Self ◽  
The Individual ◽  
Determining Factor

This article addresses the problem of determining the professional self-determination of younger family members. The article provides an analysis of the views of researchers on the role of the family in the professional development of an individual. The article deals with the problems of professional self-determination in dynastic and non-dynastic families. The question arises, whether the family is a support for its younger members on the basis of which, successful formation of professional qualities of the individual takes place, or the family may produce a "lag effect", ignoring inclinations, flairs and interests of the child. The study allows the authors to conclude that there is a transgenerative transference in the professional self-determination of the individual. The authors suggest that transgenerative transference is the main determining factor of professional self-determination in dynastic families, determining the choice of a profession by younger members of a dynastic family. It has been suggested that transformational phenomena occur in the process of professional self-determination of younger family members according to the types "inversion" (inversion), "hypertrophy" (amplification) and "deformation (distortion)".

Features of socialization і individual expectation features

2021 ◽  
pp. 78-84
Author(s):  
Natalia Zavatska ◽  
Alina Bilianska ◽  
Lilia Ryndina ◽  
Valentina Shona
Keyword(s):  
Interpersonal Relationships ◽  
Psychological Adaptation ◽  
Social Adaptation ◽  
Self Assessment ◽  
The Past ◽  
Active Life ◽  
Opposite Pole ◽  
The Individual

The article considers the features of socialization and individual expectations of the individual as components of its spheres of life. It is shown that the peculiarities of the subject's self-attitude determine the attitudes to life. Transforming, creative activity is one pole. The opposite pole - passivity, expectations, dependence. The result of psychological "tightness" is a feeling of failure. To solve the corrective tasks of forming an active life position, it is important that this transformative, corrective process begins with the analysis and work with self-assessment judgments. Individuals who have, in general, a fairly positive experience of social adaptation and self-realization will tend to form positive, flexible, realistic and concrete expectations. At the same time, individuals who have experienced numerous disappointments and conflicts in the past will be more likely to have negative, rigid, unrealistic and diffuse expectations in their respective fields of activity. Accordingly, the selected indicators are expressed in the features of the expectations of the individual in such areas as significant interpersonal relationships, ideas about their own potential and prediction of the future. The role of individual expectations (as components of cognitive development), as well as their relationship with the process of self-determination of the individual, which provides an opportunity to develop new, more effective programs of socio-psychological adaptation of the younger generation. Key words: specialty, socialization, examination, life.

The role of TOG domains in microtubule plus end dynamics

2009 ◽  
Vol 37 (5) ◽  
pp. 1002-1006 ◽  
Author(s):  
Kevin C. Slep
Keyword(s):  
Elongation Factor ◽  
Tryptophan Residue ◽  
Lipid Kinase ◽  
Binding Surface ◽  
Phosphatase 2A ◽  
Elongation Factor 3 ◽  
Prime Determinant ◽  
A Subunit

The XMAP215 (Xenopus microtubule-associated protein 215) and CLASP [CLIP-170 (cytoskeletal linker protein 170) associated protein] microtubule plus end tracking families play central roles in the regulation of interphase microtubule dynamics and the proper formation of mitotic spindle architecture and flux. XMAP215 members comprise N-terminally-arrayed hexa-HEAT (huntingtin, elongation factor 3, the PR65/A subunit of protein phosphatase 2A and the lipid kinase Tor) repeats known as TOG (tumour overexpressed gene) domains. Higher eukaryotic XMAP215 members are monomeric and have five TOG domains. Yeast counterparts are dimeric and have two TOG domains. Structure determination of the TOG domain reveals that the six HEAT repeats are aligned to form an oblong scaffold. The TOG domain face composed of intra-HEAT loops forms a contiguous, conserved tubulin-binding surface. Nested within the conserved intra-HEAT loop 1 is an invariant, signature, surface-exposed tryptophan residue that is a prime determinant in the TOG domain–tubulin interaction. The arrayed organization of TOG domains is critical for the processive mechanism of XMAP215, indicative that multiple tubulin/microtubule-binding sites are required for plus end tracking activity. The CLASP family has been annotated as containing a single N-terminal TOG domain. Using XMAP215 TOG domain structure determinants as a metric to analyse CLASP sequence, it is anticipated that CLASP contains two additional cryptic TOGL (TOG-like) domains. The presence of additional TOGL domains implicates CLASP as an ancient XMAP215 relative that uses a similar, multi-TOG-based mechanism to processively track microtubule ends.

scholarly journals REFLEXÕES CRÍTICO-ONTOLÓGICAS SOBRE INDIVÍDUO E EDUCAÇÃO NA PERSPECTIVA DA EMANCIPAÇÃO HUMANA

2015 ◽  
Vol 22 (2) ◽  
pp. 16
Author(s):  
Betânea Moreira de Moraes ◽  
Frederico Jorge Ferreira Costa ◽  
Ruth Maria de Paula Gonçalves
Keyword(s):  
Human Nature ◽  
Second Phase ◽  
Core Business ◽  
The Core ◽  
Effective Role ◽  
Full Life ◽  
The Individual ◽  
Individual Education

O artigo trata de três questões centrais: 1) o que é indivíduo; 2) o que é educação; 3) as relações entreindivíduo e educação. Nesse sentido, buscamos inicialmente trazer para o debate a concepção naturalizada emnossas consciências de que os indivíduos são essencialmente egoístas, competidores, ou seja, que o egoísmo e oato de competir são inerentes à essência humana – Homo homini lupus –, daí a impossibilidade de superação daexploração do homem pelo homem. No segundo momento, intentamos discutir a atividade essencial da educaçãoe o seu real papel na formação do indivíduo. Por fim, problematizamos a concepção de atividade pedagógica comoprática redentora geral, isto é, questionamos a concepção de educação como a verdadeira tábua de salvação,capaz de sanar todas as formas de miséria vigentes em nossos dias. É, pois, no entendimento da contradição quemarca a determinação onto-histórica da educação: em seu sentido universal e instituída e historicamente determinada,que apanhamos o lugar e o papel efetivo da educação no processo de constituição do indivíduo livre e deuma vida plena de sentido, qual seja: uma formação assente na luta pela superação da exploração do homem pelohomem.Palavras-chave: Indivíduo. Educação. Ontologia do ser social. REFLECTIONS CRITICAL-ONTOLOGICAL ON INDIVIDUAL AND EDUCATION INVIEW OF HUMAN EMANCIPATIOAbstract: The article deals with three central questions: 1) what is individual; 2) What is education; 3) the relationshipbetween the individual and education. In this sense, we seek to initially bring to the debate the naturalizedconception in our consciousness that individuals are essentially selfish, competitors, or that selfishness and theact of competing are inherent in human nature – Homo homini lupus – there the impossibility of overcoming the exploitationof man by man. In the second phase, intend to discuss the core business of education and its role in theformation of the individual; finally, we question the design of pedagogical activity as general redemptive practice,that is, question the concept of education as the true lifeline, able to resolve all existing forms of poverty today. It istherefore, according to the contradiction that marks the onto-historical determination of education: in its universaland established and historically determined sense that caught the place and the effective role of education in thefree individual constitution process and a full life of meaning, namely, training based on the struggle to overcome theexploitation of man by man.Keywords: Individual. Education. Ontology marxian. REFLEXIONES CRÍTICO-ONTOLÓGICA SOBRE EL INDIVIDUO Y LA EDUCACIÓNEN LA PERSPECTIVA DE EMANCIPACIÓN HUMANAResumen: El artículo se ocupa de tres cuestiones centrales: 1) ¿Qué es individuo?; 2) ¿Qué es la educación?;3) las relaciones entre el individuo y la educación. En este sentido, buscamos, inicialmente, traer para el debate laconcepción naturalizada en nuestras conciencias de que los individuos son esencialmente egoístas, competidores,o sea, que el egoísmo y el acto de competir son inherentes a la esencia humana – Homo homini lupus – esta esla concepción de la imposibilidad de superación de la explotación del hombre por el hombre. En el segundo momento,intentamos discutir la actividad esencial de la educación y su real papel en la formación del individuo. Porfin, cuestionamos la concepción de educación como la verdadera línea de salvación, capaz de resolver todas lasformas de pobreza existentes en nuestros días. Es, por lo tanto, en el entendimiento de la contradicción que marcala determinación histórica onto-histórica de la educación: en su sentido universal y establecido y históricamentedeterminada, que cogimos el lugar y el papel efectivo de la educación en el proceso de constitución del individuolibre y de una vida plena de sentido, cual sea: una formación basada en la lucha por la superación de la exploracióndel hombre por lo hombre.Palabras clave: Individuo. Educación. Ontología del ser social.

scholarly journals Spirituality and spiritual world of personality

2003 ◽  
pp. 14-22
Author(s):  
O.S. Vasilyeva
Keyword(s):  
Social Transformation ◽  
World View ◽  
Self Determination ◽  
Social Self ◽  
Life Choices ◽  
Spiritual World ◽  
Life Phenomena ◽  
The Individual

The problem of spirituality is one of those philosophical problems that are commonly called "eternal." It is particularly relevant in the dramatic periods of human history that Ukraine is experiencing today, when fundamentally new life phenomena and circumstances adjust the ways and means of life choices, social self-determination of individuals. Radical changes in a person's world-view make everyone personally think of new social realities, define their world-view settings, realize the place and role of the person in the process of social transformation. In such circumstances, the problem of spirituality acquires the most important status in the structure of the spiritual world of the individual.

Relevant information and the Mental Capacity Act

2019 ◽  
Vol 24 (2) ◽  
pp. 71-75 ◽  
Author(s):  
Oluwatoyin A Sorinmade
Keyword(s):  
Decision Making ◽  
Relevant Information ◽  
Decision Making Process ◽  
Patient Needs ◽  
Decisional Capacity ◽  
Correct Determination ◽  
Mental Capacity Act ◽  
The Individual

Implicit in the assertion that an individual has consented to/has capacity to decide, is the concept that the individual has understood that which needed to be understood, retained the same and used/weighed this information as part of their decision-making process and thereafter communicated their wishes in whatever way possible. What invariably underpins the decision-making process is the information available to the individual (relevant information) and how this information is influenced by the functioning of their mind/brain. Consent given without an individual having processed the information relevant to the decision at hand is arguably invalid. This paper seeks to draw attention to the underpinning role of “what the patient needs to know” – (relevant information) in the correct determination of an individual's decisional capacity.

The study of professional self-determination of psychology students

10.12737/1835 ◽  
2013 ◽  
Vol 7 (4) ◽  
pp. 51-55
Author(s):  
Тимур Абдурасулов ◽  
Timur Abdurasulov
Keyword(s):  
Psychology Students ◽  
Self Determination ◽  
Professional Self ◽  
The Individual

This paper describes the study of a number of issues relating to professional self-determination of psychology students. The role of «I»-concept of the individual in choosing a career, and preferred activities in the profession of a psychologist. The model of the influence of the «I»-concept in a permanent process of professional self-determination of psychology students is offered.

PROCEDIMENTOS PARA DETERMINAÇÃO DE DENSIDADE RELATIVA DOS MINERAIS: UMA VIVÊNCIA NOS LABORATÓRIOS DE MINERALOGIA DO MUSEU DE GEOCIÊNCIAS DA UFPA

2021 ◽  
Vol 8 (2021) (1) ◽  
pp. 1-12
Author(s):  
Milson XAVIER ◽  
Keyword(s):  
Relative Density ◽  
Undergraduate Students ◽  
External Environment ◽  
Mineral Industry ◽  
Mineral Substances ◽  
The Individual

The role of Mineralogy in society has an extraordinary and unique importance, to the point of verifying its presence both on the wall of the environment where the individual is, in times of pandemic, or on the unoccupied asphalt of the external environment. In the study of Mineralogy, the determination of the relative density of minerals is a constant assignment of professionals in the mineral industry, either for the purpose of identifying mineral substances or for solving storage and transportation issues. Therefore, knowing the equipment and which procedures for determining it are fundamental issues for solving these problems. In this way, descriptions of operational procedures of some equipment are presented, built with the purpose of determining the relative density of minerals, as a way to contribute to undergraduate students in Geology or similar sciences.

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