scholarly journals Structural biology of moonlighting: lessons from antibodies

2014 ◽  
Vol 42 (6) ◽  
pp. 1704-1708 ◽  
Author(s):  
Andrew C.R. Martin

Protein moonlighting is the property of a number of proteins to have more than one function. However, the definition of moonlighting is somewhat imprecise with different interpretations of the phenomenon. True moonlighting occurs when an individual evolutionary protein domain has one well-accepted role and a secondary unrelated function. The ‘function’ of a protein domain can be defined at different levels. For example, although the function of an antibody variable fragment (Fv) could be described as ‘binding’, a more detailed definition would also specify the molecule to which the Fv region binds. Using this detailed definition, antibodies as a family are consummate moonlighters. However, individual antibodies do not moonlight; the multiple functions they exhibit (first binding a molecule and second triggering the immune response) are encoded in different domains and, in any case, are related in the sense that they are a part of what an antibody needs to do. Nonetheless, antibodies provide interesting lessons on the ability of proteins to evolve binding functions. Remarkably similar antibody sequences can bind completely different antigens, suggesting that evolving the ability to bind a protein can result from very subtle sequence changes.

1996 ◽  
Vol 35 (04/05) ◽  
pp. 334-342 ◽  
Author(s):  
K.-P. Adlassnig ◽  
G. Kolarz ◽  
H. Leitich

Abstract:In 1987, the American Rheumatism Association issued a set of criteria for the classification of rheumatoid arthritis (RA) to provide a uniform definition of RA patients. Fuzzy set theory and fuzzy logic were used to transform this set of criteria into a diagnostic tool that offers diagnoses at different levels of confidence: a definite level, which was consistent with the original criteria definition, as well as several possible and superdefinite levels. Two fuzzy models and a reference model which provided results at a definite level only were applied to 292 clinical cases from a hospital for rheumatic diseases. At the definite level, all models yielded a sensitivity rate of 72.6% and a specificity rate of 87.0%. Sensitivity and specificity rates at the possible levels ranged from 73.3% to 85.6% and from 83.6% to 87.0%. At the superdefinite levels, sensitivity rates ranged from 39.0% to 63.7% and specificity rates from 90.4% to 95.2%. Fuzzy techniques were helpful to add flexibility to preexisting diagnostic criteria in order to obtain diagnoses at the desired level of confidence.


2016 ◽  
Vol 6 (2) ◽  
Author(s):  
Rosa Jaitin

This article covers several stages of the work of Pichon-Rivière. In the 1950s he introduced the hypothesis of "the link as a four way relationship" (of reciprocal love and hate) between the baby and the mother. Clinical work with psychosis and psychosomatic disorders prompted him to examine how mental illness arises; its areas of expression, the degree of symbolisation, and the different fields of clinical observation. From the 1960s onwards, his experience with groups and families led him to explore a second path leading to "the voices of the link"—the voice of the internal family sub-group, and the place of the social and cultural voice where the link develops. This brought him to the definition of the link as a "bi-corporal and tri-personal structure". The author brings together the different levels of the analysis of the link, using as a clinical example the process of a psychoanalytic couple therapy with second generation descendants of a genocide within the limits of the transferential and countertransferential field. Body language (the core of the transgenerational link) and the couple's absences and presence during sessions create a rhythm that gives rise to an illusion, ultimately transforming the intersubjective link between the partners in the couple and with the analyst.


2017 ◽  
Vol 17 (3) ◽  
pp. 651-685 ◽  
Author(s):  
Gilberto Antonelli ◽  
Pinuccia P Calia ◽  
Giovanni Guidetti

Abstract The article analyses the role of institutions in the determination of income inequality in a sample of OECD countries. Basing on the seminal approach by Amable, the article discusses the theoretical definition of model of capitalism. The basic idea is that each model of capitalism is defined by the cobweb of complementary relationships established among different institutions. Using a set of statistical indicators of the operation of institutions in two different years, 1995 and 2010, the empirical analysis points out five models of capitalism and exhibits how their composition has changed in this lapse of 15 years. In the following sections of the article, we investigate the role played by the model of capitalism in the determination of income distribution, measured through a standard Gini index. After controlling for a set of variables, the econometric evidence shows that different models of capitalism present significantly different levels of income inequality.


Author(s):  
Slavica Bašić

The analysis of pedagogical statements in which we include definitions of pcdaogical concepts brings us Io the conclusion I hat pedagogy uses the same categorical apparatus when it forms the theoretical thought about education and when it forms opinions about moral and practical questions of education, in other words, in pedagogical discourse the differentiation of theoretical from practical language about education is not even mentioned. The fact that different levels of language are not distinguished is supported by the use of pragmatic and prescriptive concepts of education in the so-called general pedagogical (theoretical and epistemological) discourse. The author stresses the point that the programatic concept of education in the science which goes under the definition of »science about the laws of upbringing and education« is completely useless.


2020 ◽  
Vol 11 (1) ◽  
pp. 86-116
Author(s):  
Philippe Lacour

In this article, I investigate Ricœur’s definition of philosophy by addressing two of its most fundamental conditions: meaning, which somehow constitutes its inner material, and reflexivity, which is the principle of its dynamic articulation. I proceed in two steps. First, I distinguish five different levels of discourse, underlining the originality of each of them: descriptive, transphrastic, self-comprehensive, anthropological, metaphysical. Then I explain the role played by reflexivity, both in its intra- and inter-semiotic dimension, in delimitating these various levels and helping the transition from one to another. In conclusion, I show that the whole of Ricœur’s philosophy can be characterized by a confidence in language, in its both obstinate and cautious effort to “enlighten existence” by pushing the limits of its fontiers.


Author(s):  
Davide Ferrari ◽  
Alessandra Mangia ◽  
Maria Sestina Spanò ◽  
Lucia Zaffarano ◽  
Marco Viganò ◽  
...  

Abstract Objectives After exceptional research efforts, several vaccines were developed against SARS-CoV-2 which sustains the pandemic COVID-19. The Comirnaty vaccine showed high efficacy in clinical trials and was the first to be approved for its distribution to the general population. We evaluated the immune response induced by the first vaccine dose in different sex/age groups and subjects with or without naturally present anti-SARS-CoV-2 antibodies. Methods As part of an Italian multicenter project (Covidiagnostix), serum samples from 4,290 health-professionals were serologically tested the day of the first vaccination dose, and 21 days later, using two different instrumentations (Siemens-Healthineers and Roche). Results In total, 97% of samples showed the presence of specific antibodies 21 days after the vaccination dose; the percentage of non-responders increased with age in both genders. Remarkably, naturally seropositive individuals showed antibody persistence up to 11 months and an exceptionally higher vaccination response compared to subjects never infected by SARS-CoV-2. Conclusions This study highlighted the importance of the serological test i) to identify naturally SARS-CoV-2 seropositive individuals and ii) to evaluate the antibody level elicited by the first vaccination dose. Both tests, highlighted differences in the immune response, when subjects were stratified by sex and age, and between naturally seropositive and seronegative subjects. The data obtained show how serological tests could play a crucial role in the triage of the population subjected to the vaccination campaign for COVID-19. The definition of suitable instrumentation-specific thresholds is needed to correctly follow eventually acquired post-vaccination immunity in the general population.


2021 ◽  
Vol 33 ◽  
pp. 1-23
Author(s):  
Jean-Pierre Desclés

The future of linguistics implies a better definition of concepts, especially in the semantic analysis. The notion of operator plays an important role in several areas of linguistics, for instance categorical grammars and representations of the meanings of grammatical categories. The general topology makes it possible to mathematize the grammatical concepts (time, aspects, modalities, enunciative operations) by means of operators. Curry’s Combinatorial Logic is an adequate formalism for composing and transforming operators at different levels of analysis that connect the semiotic expressions of languages (the observables) with their semantico-cognitive interpretations. The article refers to many studies that develop the points discussed.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Daniel Perovich ◽  
Leonardo Rodrıguez Rodrıguez ◽  
Andres Vignaga

Component-based development can be addressed from two different fronts, or more precisely, from two different levels. One of them regards the technology used for system implementation, and the other is a previous and more abstract level, where the focus is set to the logical structure of the solution and where technological issues are not considered. Model Driven Architecture promotes such separation by distinguishing platform independent models from platform specific models. In alignment with this approach, this article proposes a mapping from the tiered and platform independent architecture for information systems resulting from the application of a widely known methodological approach, to the available constructs in the J2EE platform. This mapping allows the definition of transformations between platform independent models, resulting from the referred methodology where it is possible to abstractly reason about the solution, and platform specific models which are aligned with technological constructs and are directly implemented.


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