Selection among site-dependent structurally constrained substitution models of protein evolution by approximate Bayesian computation

Motivation The selection among substitution models of molecular evolution is fundamental for obtaining accurate phylogenetic inferences. At the protein level, evolutionary analyses are traditionally based on empirical substitution models but these models make unrealistic assumptions and are being surpassed by structurally constrained substitution (SCS) models. The SCS models often consider site-dependent evolution, a process that provides realism but complicates their implementation into likelihood functions that are commonly used for substitution model selection. Results We present a method to perform selection among site-dependent SCS models, also among empirical and site-dependent SCS models, based on the approximate Bayesian computation (ABC) approach and its implementation into the computational framework ProteinModelerABC. The framework implements ABC with and without regression adjustments and includes diverse empirical and site-dependent SCS models of protein evolution. Using extensive simulated data, we found that it provides selection among SCS and empirical models with acceptable accuracy. As illustrative examples, we applied the framework to analyze a variety of protein families observing that SCS models fit them better than the corresponding best-fitting empirical substitution models. Availability and implementation ProteinModelerABC is freely available from https://github.com/DavidFerreiro/ProteinModelerABC, can run in parallel and includes a graphical user interface. The framework is distributed with detailed documentation and ready-to-use examples.Agencia Estatal de Investigación | Ref. PID2019-107931GA-I00Xunta de Galicia | Ref. ED481A-2020/192Universidade de Vigo/CISU

Authority Brings Responsibility: Feedback from Experts Promotes an Overweighting of Health-Related Pseudoscientific Beliefs

The popularity and spread of health-related pseudoscientific practices is a worldwide problem. Despite being counteracted by competent agents of our societies, their prevalence and spread continue to grow. Current research has focused on identifying which characteristics make us more likely to hold pseudoscientific beliefs. However, how we hold these beliefs despite all the available information against them is a question that remains unanswered. Here, we aimed to assess if the development of health-related pseudoscientific beliefs could be driven by a positive bias in belief updating. Additionally, we aimed to explore whether this bias could be exacerbated, depending on source credibility. In this study, participants (N = 116) underwent a belief updating task where they offered their agreement with various health-related pseudoscientific statements before and after receiving supporting and discrediting feedback from (a) experts (doctors), (b) peers, or (c) a random number generator. Our results suggest that when receiving feedback from experts (but not from peers or random feedback), the participants preferentially integrated supporting information relative to discrediting information about health-related pseudoscience. We discuss the implications of this biased belief updating pattern on health-related pseudoscientific research and suggest new strategies for intervention focused on increasing awareness, training, and consensus among healthcare practitioners

Substitution models of protein evolution with selection on enzymatic activity

Substitution models of evolution are necessary for diverse evolutionary analyses including phylogenetic tree and ancestral sequence reconstructions. At the protein level, empirical substitution models are traditionally used due to their simplicity, but they ignore the variability of substitution patterns among protein sites. Next, in order to improve the realism of the modeling of protein evolution, a series of structurally constrained substitution models were presented, but still they usually ignore constraints on the protein activity. Here, we present a substitution model of protein evolution with selection on both protein structure and enzymatic activity, and that can be applied to phylogenetics. In particular, the model considers the binding affinity of the enzyme–substrate complex as well as structural constraints that include the flexibility of structural flaps, hydrogen bonds, amino acids backbone radius of gyration, and solvent-accessible surface area that are quantified through molecular dynamics simulations. We applied the model to the HIV-1 protease and evaluated it by phylogenetic likelihood in comparison with the best-fitting empirical substitution model and a structurally constrained substitution model that ignores the enzymatic activity. We found that accounting for selection on the protein activity improves the fitting of the modeled functional regions with the real observations, especially in data with high molecular identity, which recommends considering constraints on the protein activity in the development of substitution models of evolution.Agencia Estatal de Investigación | Ref. PID2019-107931GA-I00Xunta de Galicia | Ref. ED481A-2020/192Fundação para a Ciência e a TecnologiaUniversidade de Vigo/CISU

Overcoming Undergraduate Nursing Education Challenges During the Pandemic

Despite the challenges encountered throughout the COVID-19 pandemic, undergraduate nursing education was able to pivot and prevent cessation as faculty and students utilized various virtual platforms to provide didactic, skills lab, and clinical exposure without delaying graduation for many students. Although nothing could replace the hands-on human interaction a clinical rotation provided, virtual experiences aligned with the course content helped students reinforce the concepts taught in the corresponding didactic portion proving this to be beneficial in its own way. As faculty, we rose to the challenge in fostering a supportive environment to keep students motivated to learn and engaged in coursework

Using EcoYieldSAFE to compare soil carbon dynamics under future climate in two contrasting agroforestry systems

N/

The evolution of the HIV-1 protease folding stability

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGThe evolution of structural proteins is generally constrained by the folding stability. However, little is known about the particular capacity of viral proteins to accommodate mutations that can potentially affect the protein stability and, in general, the evolution of the protein stability over time. As an illustrative model case, here, we investigated the evolution of the stability of the human immunodeficiency virus (HIV-1) protease (PR), which is a common HIV-1 drug target, under diverse evolutionary scenarios that include (1) intra-host virus evolution in a cohort of seventy-five patients sampled over time, (2) intra-host virus evolution sampled before and after specific PR-based treatments, and (3) inter-host evolution considering extant and ancestral (reconstructed) PR sequences from diverse HIV-1 subtypes. We also investigated the specific influence of currently known HIV-1 PR resistance mutations on the PR folding stability. We found that the HIV-1 PR stability fluctuated over time within a constant and wide range in any studied evolutionary scenario, accommodating multiple mutations that partially affected the stability while maintaining activity. We did not identify relationships between change of PR stability and diverse clinical parameters such as viral load, CD4+ T-cell counts, and a surrogate of time from infection. Counterintuitively, we predicted that nearly half of the studied HIV-1 PR resistance mutations do not significantly decrease stability, which, together with compensatory mutations, would allow the protein to adapt without requiring dramatic stability changes. We conclude that the HIV-1 PR presents a wide structural plasticity to acquire molecular adaptations without affecting the overall evolution of stability.Ministerio de Economía y Competitividad | Ref. RYC-2015-18241Xunta de Galicia | Ref. ED431F 2018/08Xunta de Galicia | Ref. ED481A-2020/19

Efectos del diseño y la construcción sobre la huella de carbono en columnas de hormigón armado para edificios residenciales

Constructing structural elements requires high performance materials. Important decisions about geometry and materials are made during the design and execution phases. This study analyzes and evaluates the relevant factors for reinforced concrete columns made in situ for residential buildings. This article identifies and highlights the most sensitive aspects in column design: geometry, type of cement, and concrete strength performance. Using C-40 concrete mixed with CEM-II proved to cut costs (up to 17.83%) and emissions (up to 13.59%). The ideal combination of rebar and concrete is between 1.47 and 1.73: this is the percentage of the ratio between the area of rebar and the area of the concrete section. The means used during the execution phase affect resource optimization. The location of a building has only a minor impact, wherein the wind zone exercises more influence than topographic altitude.La construcción de elementos estructurales requiere materiales de alto rendimiento. Las decisiones sobre la geometría y materiales se toman durante las fases de diseño y ejecución. Este estudio analiza y evalúa factores relevantes para columnas de hormigón armado en edificios residenciales. El trabajo identifica y resalta los aspectos más sensibles en el diseño de columnas: geometría, tipo de cemento y rendimiento de resistencia del concreto. El uso de hormigón C-40 mezclado con CEM-II demostró reducir costes (hasta 17.83%) y emisiones (hasta 13.59%). La combinación ideal de barras de refuerzo y concreto está entre 1.47 y 1.73: este es el porcentaje de la relación entre área de barras de refuerzo y área de la sección de hormigón. Los medios utilizados durante la fase de ejecución afectan la viabilidad de optimizar los recursos. La ubicación del edificio tiene un impacto menor, la zona eólica ejerce más influencia que la altitud topográfica

Evaluation of crumb rubber as aggregate for automated manufacturing of rubberized long hollow blocks and bricks

Waste tire rubber is a promising lightweight aggregate for building products that enhances their thermal and acoustic properties. Even the environmental benefits of its use are evident, higher cost and significant changes in compressive strength and workability hinder its widespread adoption. This article examines the use of crumb rubber (CR) as aggregate in dry-mix mortars to produce rubberized long hollow blocks and bricks using automated brick machines. CR was incorporated over a range of 10-40% with water/ cement ratio varying from 0.7 to 0.9. The production of rubberized bricks exhibited better performance than long hollow blocks in factory trials. Tests showed important deformations and drastic reduction in compressive strength, especially for crumb rubber percentages greater than 20%. Due to this and the high cost of CR, caution must be taken with the design of new rubberized building products to make sure they are profitable. (C) 2015 Elsevier Ltd. All rights reserved.Peer reviewe