Evolutionary and Functional Relationships in the Truncated Hemoglobin Family

Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends.Fil: Bustamante, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Radusky, Leandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Boechi, Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; ArgentinaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Ten Have, Arjen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentin

Designing and validation of adult socioemotional competences inventory (SECI)

Se presenta la construcción y validación de un Inventario para medir las Competencias Socioemocionales en adultos (ICSE). De acuerdo a Bisquerra Alzina (2003), tales competencias se definen como un conjunto de conocimientos, capacidades, habilidades y actitudes necesarias para comprender, expresar y regular apropiadamente los fenómenos emocionales. Dado que no existe consenso acerca de las variables que conforman las competencias socioemocionales, se efectuó un análisis de las dimensiones que los principales autores en el tema han investigado, a fin de integrar aquellas que resultaron comunes en los diferentes planteos teóricos. En función de este criterio se definió operacionalmente el concepto como un constructo multidimensional conformado por las siguientes dimensiones: asertividad, autoeficacia, autonomía, conciencia emocional, comunicación expresiva, empatía, optimismo, prosocialidad y regulación emocional. El proceso de construcción del ICSE siguió los lineamientos de la International Test Commission y comprendió: (a) definición conceptual y operacional del constructo, (b) elaboración de los ítemes, (c) análisis de la validez de contenido, (d) prueba piloto, (e) análisis y selección de reactivos y (f) estudio de las propiedades psicométricas de la versión depurada. Se obtuvieron evidencias favorables acerca de la discriminación de los ítemes, validez factorial, validez concurrente y consistencia interna del instrumento. Este inventario puede cubrir un vacío importante ya que no existen instrumentos diseñados y validados para medir este construc to, aportando así una herramienta valiosa, tanto pa ra ser utilizada en actividades de investigación como en programas de intervención y prevención.This study focuses on the design and validation of a psychometric instrument to assess Socioemotional Competences (SECI) in adults. According to Bisquerra Alzina (2003) such competences are defined as knowledge, abilities and attitudes necessary to understand, express and properly regulate emotions. Previous studies show positive association between socio-emotional competences and better academic and professional performance, higher levels of psychological and physical well-being and more satisfying interpersonal relationships (Bisquerra Alzina & Pérez Escoda, 2007; Pérez Escoda, Bisquerra, Filella, & Soldevila, 2010). Levy-Leboyer (1997) states that competences integrate aptitudes, knowledge and personality traits expressing behavior repertoires shown in people’s efficacy coping with specific situations. Therefore, assessment and training of such com - petences represent an important psychological topic. Though there is no agreement on which are the socio-emotional competences to be included, it is possible to analyze those considered by the main authors and researchers in the international liter - ature in the area. After analyzing different theoretical frameworks, nine competences were found to be in common to most of them: assertiveness, self-efficacy, autonomy, emotional awareness, expressive communication, empathy, optimism, pro-social behavior and emotional regulation. This construct, defined as a multidimensional concept, lacks of an instrument to operationalize and assess the whole set of socio-emotional competences in our local context. The Socio-emotional Compe - tences Inventory (SECI) was designed and built according to the International Test Commission Guidelines and included the following steps: (a) Conceptual and operational definition of the con - struct, as described above, (b) Elaboration of items, following recommendations on clarity, simplicity and comprehension, (c) Analysis of content valid ity, (d) Pilot test, (e) Depuration of items of low discrimination, and (f) Analysis of psychometric properties of the final version. Content validity (Step C) was obtained through agreement among judges method: 18 judges with expertise in psychometrics grouped items con - sider ing the nine competences definitions. They were also required to judge clearness of each item, syntactic correctness and adequacy to target population. Percentage of agreement was calculat - ed to depurate the first set of items. For the pilot test (Step D) a preliminary version of SECI was administered to 446 participants from Buenos Aires, ages between 18 and 55 (M = 26, SD = 7); same proportion of men and women. Items of low discrimination (under .30) were eliminated (Step E). A factors analysis was performed and items with loads under .30, as well as those not loading in any factor or in more than one, were eliminated, producing a final version of 72 items. To evaluate psychometric properties of SECI (Step F) this final version was administered to a new sample of 509 participants from Buenos Aires (M = 29, SD = 10, same proportion of men and women). A new factors analysis was performed and nine factors were found, in correspondence with the nine proposed competencies, showing evidence of construct validity. This final version proved to be reliable with an average alpha of .72. Evidence of concurrent validity was also obtained through significant and positive correlations between eight scales of SECI and other valid instruments that assess equivalent constructs. Expected significant differences according to gender in specific compe - ten cies (as suggested by previous studies) were considered evidence of external validity. In conclusion, the empirical data obtained in this study proved internal consistency, items discrim ination as well as factorial, content, external and con - current validity of the SECI. These findings support SECI as a psychometric valid and reliable instrument to be used with non-clinical population. It also can be useful for research and intervention purposes in different psychological areas, where socio-emotional competences should be assessed.Fil: Mikulic, Isabel Maria. Universidad de Buenos Aires. Facultad de Psicología; ArgentinaFil: Crespi, Melina Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Interdisciplinario de Investigaciones en Psicología Matemática y Experimental Dr. Horacio J. A. Rimoldi; ArgentinaFil: Radusky, Pablo David. Universidad de Buenos Aires. Facultad de Psicología; Argentin

Adaptation of the Posttraumatic Growth Inventory in people with HIV from Buenos Aires, Argentina

El crecimiento postraumático (CPT) involucra cambios psicológicos positivos resultantes de enfrentarse con circunstancias altamente desafiantes. El Inventario de Crecimiento Postraumático (ICPT) es el instrumento más difundido para su medición. Una proporción considerable de las personas con VIH experimenta algún grado de CPT como consecuencia del diagnóstico, lo que se asocia a una mejor salud mental y física. El objetivo fue adaptar el ICPT para su uso en personas con VIH del Área Metropolitana de Buenos Aires (AMBA), Argentina. Una versión preliminar, lingüística y conceptualmente equivalente a la original fue administrada a una muestra de 100 personas con VIH adultas del AMBA. El análisis factorial confirmatorio demostró que el modelo original de cinco dimensiones es el que muestra un mejor ajuste. De manera consistente con la evidencia internacional, las participantes de género femenino exhibieron puntuaciones significativamente más elevadas de CPT, lo que puede interpretarse como evidencia externa de validez. Se verificó la confiabilidad por consistencia interna de la escala y sus dimensiones mediante los coeficientes alfa y omega ordinal, obteniendo valores entre aceptables y excelentes. Esta versión del ICPT demostró adecuadas propiedades psicométricas y ajuste cultural para su uso en personas con VIH del AMBA.Posttraumatic growth (PTG) involves positive psychological changes resulting from coping with highly challenging circumstances. The Posttraumatic Growth Inventory (PTGI) is the most widespread instrument for its measurement. A substantial proportion of people with HIV experience some degree of PTG as a result of their diagnosis, which is associated with better mental and physical health. The objective was to adapt the PTGI for its use in people with HIV in the Metropolitan Area of Buenos Aires (MABA), Argentina. A preliminary version, linguistically and conceptually equivalent to the original one, was administered to a sample of 100 adults living with HIV from the MABA. According to the confirmatory factor analysis, the original model of five dimensions showed a better fit. Consistently with international evidence, female participants exhibited significantly higher PTG scores, which can be interpreted as external evidence of validity. Reliability and internal consistency of the scale and its dimensions were verified through the ordinal alpha and omega coefficients, obtaining acceptable and excellent values. This version of the PTGI demonstrated acceptable psychometric properties and cultural adequacy for its use in people with HIV from the MABA

Crecimiento postraumático en hombres gays con VIH en Buenos Aires, Argentina

Este estudio cualitativo tuvo como objetivo explorar los significados atribuidos al virus de inmunodeficiencia humana (VIH) y la experiencia de cambios positivos posteriores al diagnóstico (crecimiento postraumático) en hombres gays de Buenos Aires, Argentina. Se efectuaron catorce entrevistas individuales en profundidad. Se implementó un análisis temático asignando códigos a fragmentos de transcripciones y organizándolos en temas. La edad media de los participantes fue de 41.29 (D.E.=11.97) y una media de 8.42 (D.E.=7.08) años desde el diagnóstico, tres de los cuales lo habían recibido en el último año. La mayoría informó cambios positivos que atribuyeron al diagnóstico de VIH, los que se organizaron en tres temas: Cambios en la filosofía de vida, Cambios en las relaciones con los otros y Cambios en la percepción de sí mismos. Algunos de estos incluyen mayor aprecio por la vida y su salud, incremento de comportamientos más saludables, fortalecimiento de la red de apoyo social y conciencia de sus capacidades para el afrontamiento. Tales cambios parecen asociarse a la atribución al VIH de sentidos más favorables. La identificación de crecimiento postraumático puede orientar intervenciones psicoterapéuticas y psicosociales dirigidas a hombres gays con VIH en virtud de que funciona como un recurso para afrontar el estigma y se asocia con una mayor retención en la atención del VIH

Progress in the construction of the Stigma related to HIV Inventory (SI-HIV)

La expresión del estigma relacionado con el VIH, siendo culturalmente determinada, ha sufrido cambios a través de las décadas, asumiendo formas más sutiles, aunque igualmente perjudiciales. Por consiguiente, con el fin de medir este constructo, deben ser desarrollados nuevos instrumentos más actualizados y que capturen sus particularidades en contextos específicos. Tres dimensiones del estigma son reconocidas por los principales marcos teóricos: internalizado, anticipado y experimentado. Los objetivos de este estudio fueron explorar el funcionamiento de un conjunto inicial de ítems de un nuevo instrumento para medir estigma, obtener evidencia de confiabilidad y validez del instrumento y describir los niveles de estigma en personas con VIH adultas del Área Metropolitana de Buenos Aires (AMBA). Cinco expertos evaluaron la claridad, relevancia y validez de contenido de 88 reactivos preliminares. Una versión depurada de 77 ítems fue administrada a una muestra piloto. El análisis estadístico incluyó el análisis descriptivo de los ítems, alfas de Cronbach para establecer la confiabilidad y correlaciones con la Escala de Estigma de VIH, para verificar la validez de criterio. La muestra final consistió en 46 personas con VIH, adultas, residentes en el AMBA (67% hombres, 31% mujeres y 2% mujeres transgénero). La media de edad fue de 41 años (DE = 10.68). Cincuenta ítems con adecuada asimetría, curtosis y correlación ítem-total fueron conservados. Las escalas mostraron buena confiabilidad: Internalizado.86; Anticipado = .85 y Experimentado = .86. Cada escala correlacionó positiva y significativamente con su criterio. Se hallaron niveles más elevados de estigma anticipado, que de estigma internalizado y experimentado. Este nuevo instrumento diseñado para medir estigma relacionado con el VIH considerando sus particularidades locales, ha demostrado adecuada confiabilidad y validez, en esta primera etapa de su construcción. La etapa siguiente consistirá en un análisis factorial con una muestra de mayor tamaño con el fin de incrementar la evidencia de validez.The expression of stigma related to HIV is culturally determined and has changed through decades, assuming subtler, but still harmful forms. Therefore, aiming at assessing this construct, updated instruments that capture its particularities in specific contexts should be designed. Most theoretical frameworks recognize three dimensions of stigma: internalized, anticipated and enacted. The objectives of this study were: to explore an initial set of items of a new measurement of stigma, to obtain evidence of reliability and validity, and to describe the levels of stigma among adults with HIV from Buenos Aires city. Five experts evaluated the clarity, relevance and content validity of 88 preliminary items. A depurated version of 77 items was administered to a pilot sample. The statistical analysis included a descriptive item analysis, Cronbach´s alphas to evaluate reliability and, to establish criterion-related validity, correlations with the HIV Stigma Scale. The final sample consisted of 46 individuals with HIV (67% men, 31% women and 2% transgender women). Mean age was 41 years (SD = 10.68). Fifty items with adequate skewness, kurtosis and item-total correlation were retained. Scales showed good reliability: Internalized = .86; Anticipated = .85 and Enacted = .86). Each scale significantly and positively correlated with its criterion. Higher levels of anticipated stigma were observed, followed by internalized and enacted stigma. This newly developed instrument, designed to measure HIV stigma considering local particularities, demonstrated adequate validity and reliability in the first stage of its construction. The following step will consist of a factor analysis with a larger sample to increase evidence of validity

Construcción de la Breve Escala sobre la Estigmatización hacia el VIH en la población general de Buenos Aires

Stigmatization has accompanied the HIV pandemic since its origins, having negative consequences on the health of people with HIV and discouraging regular testing in the general population. Any design, monitoring, and readjustment of policies aimed at reducing stigmatization towards HIV require having rigorous instruments for its measurement. The objective of this study was to build and validate a Brief Scale on HIV Stigmatization (BESEHIV) in a representative sample of the Autonomous City of Buenos Aires (CABA), taking into account its linguistic particularities. Four hundred (n = 400) participants between 18 and 60 years old were surveyed on public roads in a quota design to achieve representativeness of gender, age, level of education, and socioeconomic level. The BESE-HIV was made up of nine items and showed very good levels of reliability and evidence of adequate internal and external validity, which indicates it is a promising instrument.La estigmatización ha acompañado la pandemia del VIH desde sus orígenes, lo cual ha tenido consecuencias negativas en la salud de las personas con VIH y ha desalentado el testeo regular en la población general. Cualquier diseño, monitoreo y readecuación de políticas dirigidas a reducir la estigmatización hacia el VIH requiere contar con instrumentos rigurosos para su medición. El objetivo del trabajo fue construir y validar una Breve Escala sobre Estigmatización hacia el VIH (BESE-VIH) en una muestra representativa de la Ciudad Autónoma de Buenos Aires (CABA), respetando sus particularidades lingüísticas. Se encuestó en la vía pública a 400 participantes de entre 18 y 60 años en un diseño muestral por cuotas y se logró la representatividad de género, edad, nivel educativo y nivel socioeconómico. La BESE-VIH quedó compuesta por nueve reactivos y mostró muy buenos niveles de confiabilidad y evidencias de validez interna y externa adecuadas, por lo que la escala resulta un instrumento prometedor

PDBe-KB: a community-driven resource for structural and functional annotations.

The Protein Data Bank in Europe-Knowledge Base (PDBe-KB, https://pdbe-kb.org) is a community-driven, collaborative resource for literature-derived, manually curated and computationally predicted structural and functional annotations of macromolecular structure data, contained in the Protein Data Bank (PDB). The goal of PDBe-KB is two-fold: (i) to increase the visibility and reduce the fragmentation of annotations contributed by specialist data resources, and to make these data more findable, accessible, interoperable and reusable (FAIR) and (ii) to place macromolecular structure data in their biological context, thus facilitating their use by the broader scientific community in fundamental and applied research. Here, we describe the guidelines of this collaborative effort, the current status of contributed data, and the PDBe-KB infrastructure, which includes the data exchange format, the deposition system for added value annotations, the distributable database containing the assembled data, and programmatic access endpoints. We also describe a series of novel web-pages-the PDBe-KB aggregated views of structure data-which combine information on macromolecular structures from many PDB entries. We have recently released the first set of pages in this series, which provide an overview of available structural and functional information for a protein of interest, referenced by a UniProtKB accession

PDBe-KB: collaboratively defining the biological context of structural data

The Protein Data Bank in Europe - Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the Protein Data Bank (PDB). The goal of PDBe-KB is to place macromolecular structure data in their biological context by developing standardised data exchange formats and integrating functional annotations from the contributing partner resources into a knowledge graph that can provide valuable biological insights. Since we described PDBe-KB in 2019, there have been significant improvements in the variety of available annotation data sets and user functionality. Here, we provide an overview of the consortium, highlighting the addition of annotations such as predicted covalent binders, phosphorylation sites, effects of mutations on the protein structure and energetic local frustration. In addition, we describe a library of reusable web-based visualisation components and introduce new features such as a bulk download data service and a novel superposition service that generates clusters of superposed protein chains weekly for the whole PDB archive

Bioinformatics in translational drug discovery

Bioinformatics approaches are becoming ever more essential in translational drug discovery both in academia and within the pharmaceutical industry. Computational exploitation of the increasing volumes of data generated during all phases of drug discovery is enabling key challenges of the process to be addressed. Here, we highlight some of the areas in which bioinformatics resources and methods are being developed to support the drug discovery pipeline. These include the creation of large data warehouses, bioinformatics algorithms to analyse ‘big data’ that identify novel drug targets and/or biomarkers, programs to assess the tractability of targets, and prediction of repositioning opportunities that use licensed drugs to treat additional indications

PDBe-KB: collaboratively defining the biological context of structural data

The Protein Data Bank in Europe – Knowledge Base (PDBe-KB, https://pdbe-kb.org) is an open collaboration between world-leading specialist data resources contributing functional and biophysical annotations derived from or relevant to the Protein Data Bank (PDB). The goal of PDBe-KB is to place macromolecular structure data in their biological context by developing standardised data exchange formats and integrating functional annotations from the contributing partner resources into a knowledge graph that can provide valuable biological insights. Since we described PDBe-KB in 2019, there have been significant improvements in the variety of available annotation data sets and user functionality. Here, we provide an overview of the consortium, highlighting the addition of annotations such as predicted covalent binders, phosphorylation sites, effects of mutations on the protein structure and energetic local frustration. In addition, we describe a library of reusable web-based visualisation components and introduce new features such as a bulk download data service and a novel superposition service that generates clusters of superposed protein chains weekly for the whole PDB archive