Simultaneous mapping of multiple gene loci with pooled segregants

The analysis of polygenic, phenotypic characteristics such as quantitative traits or inheritable diseases remains an important challenge. It requires reliable scoring of many genetic markers covering the entire genome. The advent of high-throughput sequencing technologies provides a new way to evaluate large numbers of single nucleotide polymorphisms (SNPs) as genetic markers. Combining the technologies with pooling of segregants, as performed in bulked segregant analysis (BSA), should, in principle, allow the simultaneous mapping of multiple genetic loci present throughout the genome. The gene mapping process, applied here, consists of three steps: First, a controlled crossing of parents with and without a trait. Second, selection based on phenotypic screening of the offspring, followed by the mapping of short offspring sequences against the parental reference. The final step aims at detecting genetic markers such as SNPs, insertions and deletions with next generation sequencing (NGS). Markers in close proximity of genomic loci that are associated to the trait have a higher probability to be inherited together. Hence, these markers are very useful for discovering the loci and the genetic mechanism underlying the characteristic of interest. Within this context, NGS produces binomial counts along the genome, i.e., the number of sequenced reads that matches with the SNP of the parental reference strain, which is a proxy for the number of individuals in the offspring that share the SNP with the parent. Genomic loci associated with the trait can thus be discovered by analyzing trends in the counts along the genome. We exploit the link between smoothing splines and generalized mixed models for estimating the underlying structure present in the SNP scatterplots

Innovación de la metodología docente en Farmacología a través del cine como recurso formativo.

Estudio interuniversitario del uso de las películas comerciales, como recurso educativo innovador, en la enseñanza de la Farmacología de manera sistemática en los alumnos de dicha asignatura de las universidades de Cádiz y Málaga. Cabello MR, Medina I, Moreno R. Innovación de la metodología docente en Farmacología a través del cine como recurso formativo.FEMVol. 20 (S2) Suplemento 2, Octubre 2017 ISSN: 2014-9832Objetivo Analizar la adquisición de competencias transversales, el grado de satisfacción y motivación de los alumnos de Farmacología con la utilización de las películas comerciales como recurso docente. MATERIAL Y METODOS Se realizó: 1- Preevaluación. Presentación y visualización de la película. 2- Resolución de las cuestiones planteadas con el trabajo personal y de grupo. 3- Debate. Realización de un postest, encuesta de satisfacción y valoración de la actividad por los estudiantes participantes. Valoración y análisis de los cuestionarios y análisis textual qualitativo de las observaciones de las encuestas de satisfacción. Resultados En todas las cuestiones de satisfacción de la actividad han considerado estar satisfechos/muy satisfechos el 70% de los estudiantes participantes. Confirmación de adquisición de competencias transversales y específicas de farmacología. Conclusión El recurso visual aumenta la motivación y el grado de satisfacción de los estudiantes. Se facilita el debate y discusión de puntos propuestos por el docente y los estudiantes, con un mayor aprovechamiento de la actividad. Consideramos una metodología muy útil y eficaz en el aprendizaje activo de los estudiantes.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

QTL analysis of high thermotolerance with superior and downgraded parental yeast strains reveals new minor QTLs and converges on novel causative alleles involved in RNA processing

Revealing QTLs with a minor effect in complex traits remains difficult. Initial strategies had limited success because of interference by major QTLs and epistasis. New strategies focused on eliminating major QTLs in subsequent mapping experiments. Since genetic analysis of superior segregants from natural diploid strains usually also reveals QTLs linked to the inferior parent, we have extended this strategy for minor QTL identification by eliminating QTLs in both parent strains and repeating the QTL mapping with pooled-segregant whole-genome sequence analysis. We first mapped multiple QTLs responsible for high thermotolerance in a natural yeast strain, MUCL28177, compared to the laboratory strain, BY4742. Using single and bulk reciprocal hemizygosity analysis we identified MKT1 and PRP42 as causative genes in QTLs linked to the superior and inferior parent, respectively. We subsequently downgraded both parents by replacing their superior allele with the inferior allele of the other parent. QTL mapping using pooled-segregant whole-genome sequence analysis with the segregants from the cross of the downgraded parents, revealed several new QTLs. We validated the two most-strongly linked new QTLs by identifying NCS2 and SMD2 as causative genes linked to the superior downgraded parent and we found an allele-specific epistatic interaction between PRP42 and SMD2. Interestingly, the related function of PRP42 and SMD2 suggests an important role for RNA processing in high thermotolerance and underscores the relevance of analyzing minor QTLs. Our results show that identification of minor QTLs involved in complex traits can be successfully accomplished by crossing parent strains that have both been downgraded for a single QTL. This novel approach has the advantage of maintaining all relevant genetic diversity as well as enough phenotypic difference between the parent strains for the trait-of-interest and thus maximizes the chances of successfully identifying additional minor QTLs that are relevant for the phenotypic difference between the original parents

Modeling TiO2/UV–vis bacterial inactivation: Useful tools for reactor optimization and design

Heterogeneous photocatalysis applying TiO2 based catalysts has been widely studied for removing inorganic and organic compounds from water and for bacterial inactivation. This available and low-cost catalyst has demonstrated to be effective in the removal of organic pollutants and inactivation of pathogenic bacteria from water. The design of proper types of industrial-scale photoreactors has not been yet successfully implemented, probably due to the conceptual complexity of modeling this process in real wastewater. As a result, TiO2 based photocatalysis is still considered an effective but energetic-inefficient process. In this work, Escherichia coli (gram-positive) and Enterococcus sp (gram-negative) were selected for studying the kinetics of TiO2 photocatalysis. Since several approaches, such as fist-order kinetics, are not truly representative of the bacterial inactivation process, the experimental data were fitted to different mathematical models, such as Gompertz model, which has demonstrated to describe the process properly. Moreover, the effect of the main variables of the process in the inactivation kinetic constant of the Gompertz model has ben studied. More precisely, light intensity, water matrix, catalyst concentration and bacteria have been under study and their effect has been included in the kinetic equation. Finally, operational and construction parameters of a 20 m3/d annular photoreactor for bacterial inactivation has been successfully optimized applying the proposed kinetic model

Molecular and thermodynamic properties of zwitterions versus ionic liquids: A comprehensive computational analysis to develop advanced separation processes

WILEY: "This is the peer reviewed version of the following article: ChemPhysChem 19.7 (2018): 801-815, which has been published in final form at http://doi.org/10.1002/cphc.201701093. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions." Este artículo apareció anteriormente con el siguiente título "Exploring molecular and thermodynamic properties of zwitterions vs ionic liquids: A comprehensive computational analysis to develop advanced separation processes"Zwitterion ionic liquids (ZIs) are compounds in which both counterions are covalently tethered, conferring them with unique characteristics; however, most of their properties are still unknown, representing a bottleneck to exploit their practical applications. Herein, the molecular and fluid properties of ZIs and their mixtures were explored by means of quantum chemical analysis based on the density functional theory (DFT) and COSMO-RS method, and compared against homologous ionic liquids (ILs) to provide a comprehensive overview of the effect of the distinct structures on their physicochemical and thermodynamic behavior. Overall, ZIs were revealed as compounds with higher polarity and stronger hydrogen-bonding capacity, implying higher density, viscosity, melting point, and even lower volatility than structurally similar ILs. The phase equilibrium of binary and ternary systems supports stronger attractive interactions between ZIs and polar compounds, whereas higher liquid–liquid immiscibility with nonpolar compounds may be expected. Ultimately, the performance of ZIs in the wider context of separation processes is illustrated, while providing molecular insights to allow their selection and design for relevant applicationsThe authors would like to acknowledge to Comunidad Autónoma de Madrid for the Project S2013/MAE-2800 and to Ministerio de Economía y Competitividad (MINECO) of Spain for financial support of Projects CTQ2014-52288-R. We are very grateful to Centro de Computación Científica de la Universidad Autónoma de Madrid for computational facilities. We all would like to acknowledge kind support in the framework of the COST Action EXIL-Exchange on Ionic Liquids (CM1206)

Characterization of mothers, mode of deliveries and newborns in Campinas, São Paulo, 2001 and 2005

OBJETIVO: Comparar dados pré-natais, dos partos e dos recém-nascidos de Campinas em 2001 e 2005. MÉTODOS: Estudo transversal que analisou 13.656 documentos do Sistema de Informações sobre Nascidos Vivos (Sinasc) de 2005, comparando-as aos resultados de 2001. Analisou-se o local de moradia e parto, idade materna, estado civil, escolaridade, ocupação, paridade, consultas de pré-natal, tipo de parto, duração da gestação e peso ao nascer. Para avaliar a associação entre as variáveis, utilizou-se o teste de qui-quadrado, sendo significante p<0,05. RESULTADOS: Os nascidos nos Distritos de Saúde (DS) com piores índices de condições de vida (ICV) diminuíram em relação a 2001. A taxa de adolescentes passou de 17,7% para 14,7%. Em 2001, 39,4% das mães trabalhavam e, em 2005, 42,9%. Quanto à presença de companheiro, 35,9 e 54,3% não o referiam em 2001 e 2005, respectivamente. A escolaridade passou de 37,8% de mães com até sete anos de estudo para 25,7%, com aumento das que estudaram entre oito e 11 anos e 12 anos ou mais. O comparecimento a mais de seis consultas no pré-natal passou de 74,4 para 86,6%. Houve aumento de cesáreas (54,9 para 60,3%) e de prematuridade (7,1 para 8,9%). Não houve alteração no perfil de peso ao nascimento. CONCLUSÕES: Verificou-se queda da paridade nos DS com piores ICV e no percentual de mães adolescentes. Elevou-se o número de trabalhadoras, mulheres sem companheiro, escolaridade e frequência ao pré-natal.OBJECTIVE: To compare data related to prenatal care, deliveries and newborns from Campinas, Brazil, in 2001 and 2005. METHODS: This cross-sectional study analyzed 13,656 Live Birth Certificates from 2005, comparing them to of 2001. The analyzed variables were: place of birth and dwelling, maternal age, marital status, schooling, number of births, number of prenatal consultations, mode of delivery, length of pregnancy and birthweight. Association between variables was evaluated by the chi-square test, being significant p<0.05. RESULTS: In 2005, there was a decrease in the number of newborns from Health Districts with worse living conditions in comparison to 2001. The rate of teenage pregnancies varied from 17.7% in 2001 to 14.7% in 2005. Working mothers were 42.9% of the sample in 2005 and 39.4% in 2001. In 2005, single mothers were 54.3% compared to 35.9% in 2001. Mothers with seven or less years of schooling were 37.8% in 2001, compared to 25.7% in 2005. In 2005, 86.6% of mothers had more than six prenatal visits compared to 74.4% in 2001. There was an increase in the rates of cesarean section (from 54.9% in 2001 to 60.3% in 2005) and prematurity (from 7.1% in 2001 to 8.9% in 2005). No significant changes in birthweight were observed. CONCLUSIONS: This study shows a decrease in the rate of births in the Health Districts with worse conditions of living and in teenage pregnancies. Rates of working mothers, single mothers, years of schooling, number of prenatal consultations increased

Health equity and quantifying the patient experience: A case study

The COVID-19 pandemic has invigorated efforts to address health inequities disproportionately burdened by racial/ethnic groups and individuals of low socioeconomic status. Measuring and monitoring patient experience is crucial to understanding why the gaps exist and identifying mechanisms necessary to close them. Electronic health records and digital health tools hold much promise in this regard and can lead to change. We present a case study describing the innovative efforts undertaken at Sutter Health, a large integrated health network in Northern California, to quantify gaps in health equity using electronic platforms and visualization modalities. More work is needed to identify and address barriers rooted in social context and structural inequities and ultimately impact health equity. Experience Framework This article is associated with the Policy & Measurement lens of The Beryl Institute Experience Framework. (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens

Improved linkage analysis of Quantitative Trait Loci using bulk segregants unveils a novel determinant of high ethanol tolerance in yeast

Background: Bulk segregant analysis (BSA) coupled to high throughput sequencing is a powerful method to map genomic regions related with phenotypes of interest. It relies on crossing two parents, one inferior and one superior for a trait of interest. Segregants displaying the trait of the superior parent are pooled, the DNA extracted and sequenced. Genomic regions linked to the trait of interest are identified by searching the pool for overrepresented alleles that normally originate from the superior parent. BSA data analysis is non-trivial due to sequencing, alignment and screening errors. Results: To increase the power of the BSA technology and obtain a better distinction between spuriously and truly linked regions, we developed EXPLoRA (EXtraction of over-rePresented aLleles in BSA), an algorithm for BSA data analysis that explicitly models the dependency between neighboring marker sites by exploiting the properties of linkage disequilibrium through a Hidden Markov Model (HMM). Reanalyzing a BSA dataset for high ethanol tolerance in yeast allowed reliably identifying QTLs linked to this phenotype that could not be identified with statistical significance in the original study. Experimental validation of one of the least pronounced linked regions, by identifying its causative gene VPS70, confirmed the potential of our method. Conclusions: EXPLoRA has a performance at least as good as the state-of-the-art and it is robust even at low signal to noise ratio's i.e. when the true linkage signal is diluted by sampling, screening errors or when few segregants are available

A Fast Goal Recognition Technique Based on Interaction Estimates

Goal Recognition is the task of inferring an actor's goals given some or all of the actor's observed actions. There is considerable interest in Goal Recognition for use in intelligent personal assistants, smart environments, intelligent tutoring systems, and monitoring user's needs. In much of this work, the actor's observed actions are compared against a generated library of plans. Recent work by Ramirez and Geffner makes use of AI planning to determine how closely a sequence of observed actions matches plans for each possible goal. For each goal, this is done by comparing the cost of a plan for that goal with the cost of a plan for that goal that includes the observed actions. This approach yields useful rankings, but is impractical for real-time goal recognition in large domains because of the computational expense of constructing plans for each possible goal. In this paper, we introduce an approach that propagates cost and interaction information in a plan graph, and uses this information to estimate goal probabilities. We show that this approach is much faster, but still yields high quality results