Deciphering Structural Traits for Thermal and Kinetic Stability across Protein Family Evolution through Ancestral Sequence Reconstruction.

Natural proteins are frequently marginally stable, and an increase in environmental temperature can easily lead to unfolding. As a result, protein engineering to improve protein stability is an area of intensive research. Nonetheless, since there is usually a high degree of structural homology between proteins from thermophilic organisms and their mesophilic counterparts, the identification of structural determinants for thermoadaptation is challenging. Moreover, in many cases, it has become clear that the success of stabilization strategies is often dependent on the evolutionary history of a protein family. In the last few years, the use of ancestral sequence reconstruction (ASR) as a tool for elucidation of the evolutionary history of functional traits of a protein family has gained strength. Here, we used ASR to trace the evolutionary pathways between mesophilic and thermophilic kinases that participate in the biosynthetic pathway of vitamin B1 in bacteria. By combining biophysics approaches, X-ray crystallography, and molecular dynamics simulations, we found that the thermal stability of these enzymes correlates with their kinetic stability, where the highest thermal/kinetic stability is given by an increase in small hydrophobic amino acids that allow a higher number of interatomic hydrophobic contacts, making this type of interaction the main support for stability in this protein architecture. The results highlight the potential benefits of using ASR to explore the evolutionary history of protein sequence and structure to identify traits responsible for the kinetic and thermal stability of any protein architecture.

Anaerobiosis favors biosynthesis of single and multi-element nanostructures.

Herein we report the use of an environmental multimetal(loid)-resistant strain, MF05, to biosynthesize single- or multi-element nanostructures under anaerobic conditions. Inorganic nanostructure synthesis typically requires methodologies and conditions that are harsh and environmentally hazardous. Thus, green/eco-friendly procedures are desirable, where the use of microorganisms and their extracts as bionanofactories is a reliable strategy. First, MF05 was entirely sequenced and identified as an Escherichia coli-related strain with some genetic differences from the traditional BW25113. Secondly, we compared the CdS nanostructure biosynthesis by whole-cell in a design defined minimal culture medium containing sulfite as the only sulfur source to obtain sulfide reduction from a low-cost chalcogen reactant. Under anaerobic conditions, this process was greatly favored, and irregular CdS (ex. 370 nm; em. 520-530 nm) was obtained. When other chalcogenites were tested (selenite and tellurite), only spherical Se0 and elongated Te0 nanostructures were observed by TEM and analyzed by SEM-EDX. In addition, enzymatic-mediated chalcogenite (sulfite, selenite, and tellurite) reduction was assessed by using MF05 crude extracts in anaerobiosis; similar results for nanostructures were obtained; however Se0 and Te0 formation were more regular in shape and cleaner (with less background). Finally, the in vitro nanostructure biosynthesis was assessed with salts of Ag, Au, Cd, and Li alone or in combination with chalcogenites. Several single or binary nanostructures were detected. Our results showed that MF05 is a versatile anaerobic bionanofactory for different types of inorganic NS. synthesis.

SARS-CoV-2 en el adulto mayor con enfermedad neurodegenerativa / SARS-CoV-2 in older adult with neurodegenerative disease

Resumen A pesar de la gran cantidad de complicaciones neurológicas relacionadas con la infección por SARS-CoV-2, aún no está claro si estos síntomas son el resultado de una lesión neural directa o se deben a alguna otra razón. Actualmente, parece que la mayoría de los síntomas neurológicos del COVID-19 son inespecíficos y secundarios a la enfermedad sistémica. Hasta la fecha no se cuenta con suficiente evidencia científica que confirme que el virus del SARS-CoV-2 afecta de forma directa al sistema nervioso central o periférico en los seres humanos. En el presente artículo corto se presentan las implicaciones de SARS-CoV-2 en el adulto mayor con enfermedad neurodegenerativa, así como los mecanismos de acción relacionados en sistema nervioso.

Abstract Despite the many neurological complications associated with SARS-CoV-2 infection, it isn´t still clear whether these symptoms are the result of direct neural injury or due to some other reason. Currently, it appears that most of the neurological symptoms of COVID-19 are nonspecific and secondary to systemic disease. To date, there is not enough scientific evidence to confirm that SARS-CoV-2 virus directly affects the central or peripheral nervous system in humans. This short article presents the implications of SARS-CoV-2 in the elderly with neurodegenerative disease, as well as the related mechanisms of action in the nervous system.

Implementation of chromosomal microarrays in a cohort of patients with intellectual disability at the Argentinean public health system.

Intellectual disability is a neurodevelopmental disorder in which genetic, epigenetic and environmental factors are involved. In consequence, the determination of its etiology is usually complex. Though many countries have migrated from conventional cytogenetic analysis to chromosomal microarrays as the first-tier genetic test for patients with this condition, this last technique was implemented in our country a few years ago. We report on the results of the implementation of chromosomal microarrays in a cohort of 133 patients with intellectual disability and dysmorphic features, normal karyotype and normal subtelomeric MLPA results in an Argentinean public health institution. Clinically relevant copy number variants were found in 12% of the patients and one or more copy number variants classified as variants of uncertain significance were found in 5.3% of them. Although the diagnostic yield of chromosomal microarrays is greater than conventional cytogenetics for these patients, there are financial limitations to adopt this technique as a first-tier test in our country, especially in the public health system.

Percepción del riesgo mediante sus atributos psicosociales en trabajadores de la industria metalmecánica en la ciudad de Bogotá, D.C (Colombia) / Perception of the risk through its psychosocial attributes in workers of the metalmechanical industry in the city of Bogotá, D.C (Colombia)

Resumen Introducción. La percepción del riesgo en el ámbito laboral se convierte en un elemento crucial para entender las prácticas de trabajo inseguras de los trabajadores, teniendo en cuenta no solo las variables cognitivas sino también las psicosociales. Objetivo. Describir la percepción del riesgo mediante sus atributos psicosociales en trabajadores de la industria metalmecánica en la ciudad de Bogotá. Materiales y métodos. Estudio descriptivo transversal realizado en la ciudad de Bogotá, D.C, a través de una encuesta aplicada a los participantes del estudio. Resultados. La aplicación de la Guía NTP 578 a los trabajadores del sector metalmecánico permitió la realización del perfil comparativo de la magnitud del riesgo percibido y sus atributos para cada una de las actividades que se evaluaron. Conclusiones. Los trabajadores del sector metalmecánico, se sienten más vulnerables a las consecuencias que pueden generarles el uso de herramientas cortantes, la exposición al ruido y la exposición a gases y vapores, y le temen a la gravedad del daño que se puede derivar estos riesgos a los cuales están sometidos en su diario vivir en su entorno laboral.

Abstract Introduction. The perception of risk in the workplace becomes a crucial element to understand the unsafe work practices of workers, taking into account not only the cognitive variables but also the psychosocial ones. Objective. To describe the perception of risk through its psychosocial attributes in workers of the metal-mechanic industry in the city of Bogotá. Materials and methods: A cross-sectional descriptive study conducted in the city of Bogotá, D.C, through a survey applied to the study participants. Results. The application of the Guide NTP 578 to the workers of the metalworking sector allowed the realization of the comparative profile of the magnitude of the perceived risk and its attributes for each of the activities that were evaluated. Conclusions. Workers in the metalworking sector feel more vulnerable to the consequences that can result from the use of sharp tools, exposure to noise and exposure to gases and vapors, and fear the seriousness of the damage that can be derived from these risks to which they are subjected in their daily life in their work environment.

Genetic Imbalances in Argentinean Patients with Congenital Conotruncal Heart Defects.

Congenital conotruncal heart defects (CCHD) are a subset of serious congenital heart defects (CHD) of the cardiac outflow tracts or great arteries. Its frequency is estimated in 1/1000 live births, accounting for approximately 10⁻30% of all CHD cases. Chromosomal abnormalities and copy number variants (CNVs) contribute to the disease risk in patients with syndromic and/or non-syndromic forms. Although largely studied in several populations, their frequencies are barely reported for Latin American countries. The aim of this study was to analyze chromosomal abnormalities, 22q11 deletions, and other genomic imbalances in a group of Argentinean patients with CCHD of unknown etiology. A cohort of 219 patients with isolated CCHD or associated with other major anomalies were referred from different provinces of Argentina. Cytogenetic studies, Multiplex-Ligation-Probe-Amplification (MLPA) and fluorescent in situ hybridization (FISH) analysis were performed. No cytogenetic abnormalities were found. 22q11 deletion was found in 23.5% of the patients from our cohort, 66% only had CHD with no other major anomalies. None of the patients with transposition of the great vessels (TGV) carried the 22q11 deletion. Other 4 clinically relevant CNVs were also observed: a distal low copy repeat (LCR)D-E 22q11 duplication, and 17p13.3, 4q35 and TBX1 deletions. In summary, 25.8% of CCHD patients presented imbalances associated with the disease.

Perfil morfológico de jugadoras profesionales de fútbol en Chile / Morphological Profile of Female Professional Soccer Players in Chile

Fundamentos: En deportes colectivos como el fútbol, el conocimiento de los perfiles de los jugadores puede permitir una mejor selección y entrenamiento. El fútbol femenino, si bien comenzó en los años 70, solo en las últimas décadas ha tenido un desarrollo profesional considerable.Objetivo: describir el perfil antropométrico y somatotipo de futbolistas mujeres.Métodos: estudio descriptivo, que consistió en evaluar a 72 jugadoras del sexo femenino, pertenecientes a la Federación Chilena de Fútbol Femenino. Para la obtención y análisis del perfil morfológico de estas, se midió masa corporal, estatura de pie, estatura sentado, sumatoria de seis pliegues cutáneos y sumatoria de ocho pliegues cutáneos, según el protocolo de marcaje y medición de la Sociedad Internacional para el Desarrollo de la Cineantropometría. También fueron calculados los tres componentes del somatotipo de Heath-Carter por cada posición de juego.Resultados: no se encontraron diferencias significativas a nivel de masa corporal, estura, sumatoria de seis y ocho pliegues, pero sí en la variable estatura sentado (p<0,05). No hubo diferencias significativas a niveles absolutos y relativos de masa muscular y adiposa, pero sí en la masa ósea relativa (p<0,05). El 66,7 % de las jugadoras presentó un mesomorfismo como componente principal.Conclusión: en todas las categorías predominó el somatotipo mesomórfico, y existen diferencias significativas en la composición corporal entre categorías, por ello sería importante considerar estrategias específicas para cada una de ellas a fin de optimizar el rendimiento deportivo de las atletas.

Foundation: In team sports as soccer, knowing the player´s profiles may allow a better choice and training. Female soccer, even though it started in the 70´s, only in the last decades it has had a considerable development.Objective: to describe the anthropometric and somatotype of soccer female players.Methods: descriptive study which consisted on evaluating 72 female soccer players pertaining to the Chilean Female Soccer Federation. For obtaining and analyzing their morphologic profile, their body mass, standing height, sitting height, the total sum of six cutaneous folders and eight cutaneous folders were measured according to the protocol of marking and measuring of the International Society for developing Cineanthropometry. There were also calculated the three components of Health-Carter somatotype for each game position.Results: There were not found significant differences of body mass, height, total of six and eight cutaneous folders, there were in the variable sitting height (p<0,05). There were not significant differences at absolute and relative levels of adipose and body mass but there was in relative bone mass (p<0, 05). The 66, 7 % of the players showed a mesomorphism as the main component.Conclusion: Mesomorphic somatotype predominated in all categories and there are significant differences among categories. That is why it is necessary to consider specific strategies for each of them aiming at optimizing the athlete's sport output

Estrategias para incrementar la demanda de vacunación infantil en países de ingresos bajos y medios: una revisión sistemática y un metanálisis / Strategies to increase the demand for childhood vaccination in low- and middle-income countries: a systematic review and meta-analysis / Estratégias para aumentar a demanda para a imunização infantil em renda baixa e média: uma revisão sistemática e meta-análise

Objetivo: investigar qué estrategias para aumentar la demanda de vacunación son efectivas a la hora de incrementar la cobertura de vacunación infantil en países de ingresos bajos y medios. Metodología: se realizaron búsquedas en las bases de datos de MEDLINE, EMBASE, Cochrane Library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science y Scopus para encontrar estudios pertinentes, publicados en alemán, español, francés, hindi, inglés y portugués hasta el 25 de marzo de 2014. Se incluyeron estudios de intervenciones que tenían como objetivo incrementar la demanda de vacunación infantil de rutina. Los estudios fueron considerados elegibles si se realizaron en países de ingresos bajos y medios y utilizaron un diseño de ensayo controlado aleatorizado, ensayo controlado no aleatorizado, estudio controlado antes y después o de series temporales interrumpidas. Se estimó un riesgo de sesgo mediante las directrices de colaboración de Cochrane y se realizaron metaanálisis de efectos aleatorios. Resultados: se identificaron 11 estudios que abarcan cuatro ensayos controlados aleatorizados, seis ensayos controlados aleatorizados por conglomerados y un estudio controlado antes y después, publicados en inglés entre 1996 y 2013. En general, los participantes fueron padres de niños pequeños expuestos a una intervención elegible. Seis estudios demostraron un bajo riesgo de sesgo y cinco estudios presentaron un riesgo de sesgo entre moderado y elevado. Se realizó un análisis agrupado teniendo en cuenta los 11 estudios, con datos de 11.512 participantes. Las intervenciones enfocadas en la demanda se relacionaron con una recepción de las vacunas significativamente superior, riesgo relativo (RR): 1,30, (intervalo de confianza, IC, del 95%: 1,17-1,44). Los análisis de los subgrupos también demostraron efectos importantes de siete estudios de educación y traslación de conocimientos, RR: 1,40 (IC del 95%: 1,20-1,63) y de cuatro estudios que utilizaron incentivos, RR: 1,28 (IC del 95%: 1,12-1,45). Conclusion: las intervenciones enfocadas en la demanda conducen a mejoras significativas en la cobertura de vacunación infantil en países de ingresos bajos y medios. Asimismo, los enfoques educativos y el uso de incentivos fueron estrategias efectivas.

Objective: To investigate which strategies to increase demand for vaccination are effective in increasing child vaccine coverage in low- and middle-income countries. Methodology: We searched MEDLINE, EMBASE, Cochrane library, POPLINE, ECONLIT, CINAHL, LILACS, BDSP, Web of Science and Scopus databases for relevant studies, published in English, French, German, Hindi, Portuguese and Spanish up to 25 March 2014. We included studies of interventions intended to increase demand for routine childhood vaccination. Studies were eligible if conducted in low- and middle-income countries and employing a randomized controlled trial, non-randomized controlled trial, controlled before-and-after or interrupted time series design. We estimated risk of bias using Cochrane collaboration guidelines and performed random-effects meta-analysis. Results: it was identified 11 studies comprising four randomized controlled trials, six cluster randomized controlled trials and one controlled before-and-after study published in English between 1996 and 2013. Participants were generally parents of young children exposed to an eligible intervention. Six studies demonstrated low risk of bias and five studies had moderate to high risk of bias. We conducted a pooled analysis considering all 11 studies, with data from 11 512 participants. Demand-side interventions were associated with significantly higher receipt of vaccines, relative risk (RR): 1.30, (95% confidence interval, CI: 1.17-1.44). Subgroup analyses also demonstrated significant effects of seven education and knowledge translation studies, RR: 1.40 (95% CI: 1.20-1.63) and of four studies which used incentives, RR: 1.28 (95% CI: 1.12-1.45). Conclusion: Demand-side interventions lead to significant gains in child vaccination coverage in low- and middle-income countries. Educational approaches and use of incentives were both effective strategies.

Objetivo: investigar quais as estratégias para aumentar a demanda para a vacinação é eficaz em aumentar a cobertura da vacinação infantil em renda baixa e média. Metodologia: Foram pesquisados os bancos de dados do MEDLINE, EMBASE, Cochrane Library, POPLINE, EconLit, CINAHL, LILACS, BDSP, Web of Science e Scopus foram feitas para encontrar estudos relevantes, publicadas em Alemão, Espanhol, Francês, Hindi, Inglês e Português até 25 de Março de 2014. estudos de intervenções que visam a aumentar a demanda para a vacinação infantil de rotina incluído. Os estudos foram considerados elegíveis se eles foram feitos em renda baixa e média utilizou um desenho randomizado controlado julgamento, sem estudo controlado randomizado, controlado antes e depois do estudo ou série temporal interrompida. um risco de viés foi estimado pelos efeitos aleatórios Cochrane Collaboration diretrizes e meta-análises foram realizadas. Resultados : 11 estudos abrangendo quatro ensaios clínicos randomizados, seis experimentos de aglomeração randômica controladas e controladas antes e depois de estudos publicados em Inglês, entre 1996 e 2013. Em geral identificados, os participantes foram pais de crianças pequenas expostas a uma intervenção elegíveis. Seis estudos mostraram um baixo risco de viés e cinco estudos mostraram um risco de viés moderado a elevado. Uma análise foi realizada tendo em conta conjunta dos 11 estudos com dados de 11.512 participantes. Intervenções focadas na demanda foram associados com significativamente maior recebimento de vacinas, o risco relativo (RR): 1,30 (intervalo de confiança, IC 95%: 1,17-1,44). O subgrupo análises também mostraram efeitos significativos de sete estudos de educação e tradução do conhecimento, RR 1,40 (IC 95%: 1,20 a 1,63) e quatro estudos utilizando incentivos, RR 1, (IC 95%: 1,12-1,45) 28. Conclusão: intervenções focadas na procura vai gerar melhorias significativas na cobertura de imunização infantil em renda baixa e média. Além disso, as abordagens educacionais e usando incentivos foram estratégias eficazes.