Genomic prediction in multi-environment trials in maize using statistical and machine learning methods.

In the context of multi-environment trials (MET), genomic prediction is proposed as a tool that allows the prediction of the phenotype of single cross hybrids that were not tested in field trials. This approach saves time and costs compared to traditional breeding methods. Thus, this study aimed to evaluate the genomic prediction of single cross maize hybrids not tested in MET, grain yield and female flowering time. We also aimed to propose an application of machine learning methodologies in MET in the prediction of hybrids and compare their performance with Genomic best linear unbiased prediction (GBLUP) with non-additive effects. Our results highlight that both methodologies are efficient and can be used in maize breeding programs to accurately predict the performance of hybrids in specific environments. The best methodology is case-dependent, specifically, to explore the potential of GBLUP, it is important to perform accurate modeling of the variance components to optimize the prediction of new hybrids. On the other hand, machine learning methodologies can capture non-additive effects without making any assumptions at the outset of the model. Overall, predicting the performance of new hybrids that were not evaluated in any field trials was more challenging than predicting hybrids in sparse test designs.

Using visual scores for genomic prediction of complex traits in breeding programs.

KEY MESSAGE: An approach for handling visual scores with potential errors and subjectivity in scores was evaluated in simulated and blueberry recurrent selection breeding schemes to assist breeders in their decision-making. Most genomic prediction methods are based on assumptions of normality due to their simplicity and ease of implementation. However, in plant and animal breeding, continuous traits are often visually scored as categorical traits and analyzed as a Gaussian variable, thus violating the normality assumption, which could affect the prediction of breeding values and the estimation of genetic parameters. In this study, we examined the main challenges of visual scores for genomic prediction and genetic parameter estimation using mixed models, Bayesian, and machine learning methods. We evaluated these approaches using simulated and real breeding data sets. Our contribution in this study is a five-fold demonstration: (i) collecting data using an intermediate number of categories (1-3 and 1-5) is the best strategy, even considering errors associated with visual scores; (ii) Linear Mixed Models and Bayesian Linear Regression are robust to the normality violation, but marginal gains can be achieved when using Bayesian Ordinal Regression Models (BORM) and Random Forest Classification; (iii) genetic parameters are better estimated using BORM; (iv) our conclusions using simulated data are also applicable to real data in autotetraploid blueberry; and (v) a comparison of continuous and categorical phenotypes found that investing in the evaluation of 600-1000 categorical data points with low error, when it is not feasible to collect continuous phenotypes, is a strategy for improving predictive abilities. Our findings suggest the best approaches for effectively using visual scores traits to explore genetic information in breeding programs and highlight the importance of investing in the training of evaluator teams and in high-quality phenotyping.

Physical exercise as a friend not a foe in acute kidney diseases through immune system modulation.

Regular and moderate exercise is being used for therapeutic purposes in treating several diseases, including cancer, cardiovascular diseases, arthritis, and even chronic kidney diseases (CKDs). Conversely, extenuating physical exercise has long been pointed out as one of the sources of acute kidney injury (AKI) due to its severe impact on the body's physiology. AKI development is associated with increased tubular necrosis, which initiates a cascade of inflammatory responses. The latter involves cytokine production, immune cell (macrophages, lymphocytes, and neutrophils, among others) activation, and increased oxidative stress. AKI can induce prolonged fibrosis stimulation, leading to CKD development. The need for therapeutic alternative treatments for AKI is still a relevant issue. In this context arises the question as to whether moderate, not extenuating, exercise could, on some level, prevent AKI. Several studies have shown that moderate exercise can help reduce tissue damage and increase the functional recovery of the kidneys after an acute injury. In particular, the immune system can be modulated by exercise, leading to a better recovery from different pathologies. In this review, we aimed to explore the role of exercise not as a trigger of AKI, but as a modulator of the inflammatory/immune system in the prevention or recovery from AKI in different scenarios. In AKI induced by ischemia and reperfusion, sepsis, diabetes, antibiotics, or chemotherapy, regular and/or moderate exercise could modulate the immune system toward a more regulatory immune response, presenting, in general, an anti-inflammatory profile. Exercise was shown to diminish oxidative stress, inflammatory markers (caspase-3, lactate dehydrogenase, and nitric oxide), inflammatory cytokines (interleukin (IL)-1b, IL-6, IL-8, and tumor necrosis factor-α (TNF-α)), modulate lymphocytes to an immune suppressive phenotype, and decrease tumor necrosis factor-ß (TGF-ß), a cytokine associated with fibrosis development. Thus, it creates an AKI recovery environment with less tissue damage, hypoxia, apoptosis, or fibrosis. In conclusion, the practice of regular moderate physical exercise has an impact on the immune system, favoring a regulatory and anti-inflammatory profile that prevents the occurrence of AKI and/or assists in the recovery from AKI. Moderate exercise should be considered for patients with AKI as a complementary therapy.

Population size in QTL detection using quantile regression in genome-wide association studies.

The aim of this study was to evaluate the performance of Quantile Regression (QR) in Genome-Wide Association Studies (GWAS) regarding the ability to detect QTLs (Quantitative Trait Locus) associated with phenotypic traits of interest, considering different population sizes. For this, simulated data was used, with traits of different levels of heritability (0.30 and 0.50), and controlled by 3 and 100 QTLs. Populations of 1,000 to 200 individuals were defined, with a random reduction of 100 individuals for each population. The power of detection of QTLs and the false positive rate were obtained by means of QR considering three different quantiles (0.10, 0.50 and 0.90) and also by means of the General Linear Model (GLM). In general, it was observed that the QR models showed greater power of detection of QTLs in all scenarios evaluated and a relatively low false positive rate in scenarios with a greater number of individuals. The models with the highest detection power of true QTLs at the extreme quantils (0.10 and 0.90) were the ones with the highest detection power of true QTLs. In contrast, the analysis based on the GLM detected few (scenarios with larger population size) or no QTLs in the evaluated scenarios. In the scenarios with low heritability, QR obtained a high detection power. Thus, it was verified that the use of QR in GWAS is effective, allowing the detection of QTLs associated with traits of interest even in scenarios with few genotyped and phenotyped individuals.

Efeito da intervenção educativa sobre o nível de conhecimento de acadêmicos de medicina, participantes de uma equipe do Serviço de Atendimento Móvel de Urgência (SAMU), em relação a avulsão de dentes permanentes / Effect of educational intervention on the level of knowledge of participants in a mobile emergency care team (SAMU) in cases of avulsion of permanent teeth

Objetivo: Avaliar o efeito de uma intervenção educativa, sobre avulsão de dentes permanentes, no nível de conhecimento de participantes de uma equipe do SAMU. Métodos: Participaram acadêmicos de Medicina que compunham a equipe do SAMU de Juiz de Fora (MG). A intervenção educativa foi realizada por meio de uma palestra com duração de 15 minutos. Para coleta dos dados foi utilizado um questionário, contendo 13 perguntas sobre avulsão dentária, aplicado em três etapas: antes da palestra (T0), imediatamente após a palestra (T1) e quinze dias após a palestra (T2). Foi realizada análise descritiva e teste McNemar para análise estatística (p < 0,05). Resultados:A amostra foi composta por 36 indivíduos. Nenhum participante relatou ter prestado atendimento a um caso de avulsão dentária. Trinta e quatro acadêmicos informaram não ter recebido orientações anteriores sobre o que fazer diante desse episódio e 35 afirmaram que esse conhecimento é necessário para o médico do SAMU. Houve aumento na porcentagem de acertos após os acadêmicos assistirem a palestra educativa (T1), para sete questões avaliadas. As mesmas questões também apresentaram maior percentual de acertos quinze dias após a palestra educativa (T2). Não houve diferença na capacidade dos acadêmicos reimplantarem um dente avulsionado tanto imediatamente após a palestra educativa (T1), quanto quinze dias após as orientações (T2) (T0-T1: p = 0,999; T0-T2: p = 0,999). Conclusão:A palestra educativa influenciou de forma significativa à melhora do conhecimento sobre avulsão dentária dos acadêmicos de Medicina que fazem parte da equipe do SAMU-JF.

Aim: To evaluate the effect of an educational intervention concerning the avulsion of permanent teeth upon the level of knowledge of members of a SAMU (Ambulance) team. Methods:Medical students who were members of the SAMU team in Juiz de Fora (MG) participated in this study. The educational intervention on the theme was carried out by means of a 15-minute lecture. Data collection was conducted using a structured questionnaire containing 13 objective questions on tooth avulsion, applied to the medical students in three stages: before the lecture (T0), immediately after the lecture (T1), and fifteen days after the lecture (T2). Descriptive analysis and the McNemar test were performed (p < 0.05). Results: The sample consisted of 36 individuals. All participants reported never having attended a dental avulsion case. Thirty-four students reported that they had not received previous guidance on what to do when faced with this type of episode, and 35 stated that information about dental avulsion is necessary for SAMU doctors. For seven of the evaluated questions, an increase was identified in the percentage of correct answers after the students attended the educational lecture (T1). The same questions also showed a higher percentage of correct answers fifteen days after the educational lecture (T2). No difference was found in the students' ability to reimplant an avulsed tooth either immediately after the educational lecture (T1) or fifteen days after receiving guidance on the subject (T2) (T0-T1: p = 0.999; T0-T2: p = 0.999). Conclusion: The educational lecture significantly influenced the improvement of knowledge about dental avulsion among medical students who are members of the SAMU-JF team.

Fatores associados a qualidade de vida no trabalho de profissionais da saúde da atenção primária à saúde / Factors associated with the quality of life at work of health professionals in primary health care / Factores asociados a la calidad de vida en el trabajo de los profesionales de la salud en la atención primaria de salud

Objetivo: analisar os principais fatores que estão associados a qualidade de vida no trabalho de profissionais da saúde da atenção primária à saúde. Método: Estudo transversal de abordagem quantitativa, realizada com 163 trabalhadores, os quais respon- deram ao questionário Total Quality of Work Life-42 e a um outro sobre características sociodemográficas e laborais. Resultados: Dos respondentes 84% sexo feminino; 47,9% pardos; 55,2% casados; 55,8% com grau de escolaridade médio, 23,9% graduados e 15,5% possuíam pós-graduação. A renda foi observada correlação positiva entre renda e qualidade de vida, além de fatores pessoais como ser do sexo masculino, solteiro, tempo de trabalho no município (anos). Verificou-se que profissionais do sexo feminino apre- sentaram menores escores de qualidade de vida no aspecto econômico e político quando comparados aos do sexo masculino. Conclusão: Medidas devem ser tomadas para pro- mover um ambiente laboral que mantenha a qualidade de vida no trabalho e, por sua vez, favorecer a saúde física e mental dos profissionais de atenção primária à saúde.

Objective: to analyze the main factors that are associated with the quality of life at work of health professionals in primary health care. Method: Cross-sectional study with a quantitative approach, carried out with 163 workers, who answered the Total Quality of Work Life-42 questionnaire and another on sociodemographic and labor characteristics. Results: Of the respondents, 84% were female; 47.9% brown; 55.2% married; 55.8% had a high school education, 23.9% graduated and 15.5% had a postgraduate degree. Income was observed to have a positive correlation between income and quality of life, in addition to personal factors such as being male, single, working time in the municipality (years). It was found that female professionals had lower quality of life scores in the economic and political aspects when compared to males. Conclusion: Measures must be taken to promote a work environment that maintains the quality of life at work and, in turn, favors the physical and mental health of primary health care professionals.

Objetivo: analizar los principales factores que se asocian a la calidad de vida en el trabajo de los profesionales de la salud en la atención primaria de salud. Método: Estudio transversal con enfoque cuantitativo, realizado con 163 trabajadores, quienes respondieron el cuestionario de Total Quality of Work Life-42 y otro sobre características sociodemográficas y laborales. Resultados: De los encuestados, el 84% eran mujeres; 47,9% marrón; 55,2% casados; El 55,8% tenía educación secundaria, el 23,9% se graduó y el 15,5% tenía posgrado. Ingreso, se observó una correlación positiva entre ingreso y calidad de vida, además de factores personales como ser hombre, soltero, tiempo de trabajo en la ciudad (años). Se constató que las mujeres profesionales tenían puntajes de calidad de vida más bajos en los aspectos económico y político en comparación con los hombres. Conclusión: Se deben tomar medidas para promover un ambiente de trabajo que mantenga la calidad de vida en el trabajo y, a su vez, favorezca la salud física y mental de los profesionales de la atención primaria de salud.

Factor analysis applied in genomic selection studies in the breeding of Coffea canephora.

Brazil stands out worldwide in the production of coffee. The observed increases in its productivity and morpho agronomic traits are the results of the improvement of several methodologies applied in obtaining improved cultivars, among which the predictive methods of genetic value stand out. These contribute significantly to the selection of higher genotypes, increasing the genetic gain per unit time. In this context, genomic-wide selection (GWS) is a tool that stands out, since it allows predicting the future phenotype of an individual based only on molecular information. Performing joint selection of traits is the interest of most breeding programs, and factor analysis (FA) has been used to assist in this end. The aim of this study was to evaluate the use of FA in the context of GWS, in genotypes of Coffea canephora. It was found that FA was efficient to elucidate the relationships between the traits and generate new variables. The factors formed can assist in the selection, as in addition to allowing joint interpretations, they present good estimates of predictive capacity, heritability and accuracy. Furthermore, high agreement was observed between the individuals selected based on the factors and those selected considering the individual traits. Additionally, it was observed agreement between the top 10% individuals selected based on the "vigor factor" and each variable individually. However, the selection based on "vigor factor" presented individuals with more suitable size from the phytotechnical point of view.

Marker effects and heritability estimates using additive-dominance genomic architectures via artificial neural networks in Coffea canephora.

Many methodologies are used to predict the genetic merit in animals and plants, but some of them require priori assumptions that may increase the complexity of the model. Artificial neural network (ANN) has advantage to not require priori assumptions about the relationships between inputs and the output allowing great flexibility to handle different types of complex non-additive effects, such as dominance and epistasis. Despite this advantage, the biological interpretability of ANNs is still limited. The aim of this research was to estimate the heritability and markers effects for two traits in Coffea canephora using an additive-dominance architecture ANN and to compare it with genomic best linear unbiased prediction (GBLUP). The data used consists of 51 clones of C. canephora varietal Conilon, 32 of varietal group Robusta and 82 intervarietal hybrids. From this, 165 phenotyped individuals were genotyped for 14,387 SNPs. Due to the high computational cost of ANNs, we used Bagging decision tree to reduce the dimensionality of the data, selecting the markers that accumulated 70% of the total importance. An ANN with three hidden layers was run, each varying from 1 to 40 neurons summing 64,000 neural networks. The network architectures with the best predictive ability were selected. The best architectures were composed by 4, 15, and 33 neurons in the first, second and third hidden layers, respectively, for yield, and by 13, 20, and 24 neurons, respectively for rust resistance. The predictive ability was greater when using ANN with three hidden layers than using one hidden layer and GBLUP, with 0.72 and 0.88 for yield and coffee leaf rust resistance, respectively. The concordance rate (CR) of the 10% larger markers effects among the methods varied between 10% and 13.8%, for additive effects and between 5.4% and 11.9% for dominance effects. The narrow-sense ([Formula: see text]) and dominance-only ([Formula: see text]) heritability estimates were 0.25 and 0.06, respectively, for yield, and 0.67 and 0.03, respectively for rust resistance. The ANN was able to estimate the heritabilities from an additive-dominance genomic architectures and the ANN with three hidden layers obtained best predictive ability when compared with those obtained from GBLUP and ANN with one hidden layer.

Pacientes Trans e Cuidado Multiprofissional em Centros de Atendimento Psicossocial

Considerando a discriminação social contra pessoas trans como um determinante para o sofrimento psíquico, este trabalho objetiva analisar a assistência à saúde mental da população trans em dois Centros de Atenção Psicossocial (CAPS) de uma capital brasileira. Entrevistas com nove trabalhadores da equipe multiprofissional possibilitaram identificar práticas, crenças e percepções que permeiam este cuidado. A interpretação dos relatos foi pautada pela análise hermenêutico-dialética. Identifica-se que, mesmo as equipes compreendendo as demandas de saúde mental de pacientes trans como atreladas à discriminação, à violência e à marginalização, são remanescentes compreensões arraigadas em estereótipos, tal como a de que equidade para pacientes trans implicaria privilégio. Consoante à literatura sobre acesso de pessoas trans à saúde pública, o nome social também se afirmou como prática de acolhimento fundamental, porém, insuficiente quando dissociada do maior preparo das equipes nas etapas subsequentes ao atendimento. Sugere-se que a efetividade do cuidado trilha pela garantia do processo terapêutico humanizado, considerando iniquidades sociais enfrentadas (como preconiza o Sistema Único de Saúde) por pacientes trans.

Quantile regression in genomic selection for oligogenic traits in autogamous plants: A simulation study.

This study assessed the efficiency of Genomic selection (GS) or genome-wide selection (GWS), based on Regularized Quantile Regression (RQR), in the selection of genotypes to breed autogamous plant populations with oligogenic traits. To this end, simulated data of an F2 population were used, with traits with different heritability levels (0.10, 0.20 and 0.40), controlled by four genes. The generations were advanced (up to F6) at two selection intensities (10% and 20%). The genomic genetic value was computed by RQR for different quantiles (0.10, 0.50 and 0.90), and by the traditional GWS methods, specifically RR-BLUP and BLASSO. A second objective was to find the statistical methodology that allows the fastest fixation of favorable alleles. In general, the results of the RQR model were better than or equal to those of traditional GWS methodologies, achieving the fixation of favorable alleles in most of the evaluated scenarios. At a heritability level of 0.40 and a selection intensity of 10%, RQR (0.50) was the only methodology that fixed the alleles quickly, i.e., in the fourth generation. Thus, it was concluded that the application of RQR in plant breeding, to simulated autogamous plant populations with oligogenic traits, could reduce time and consequently costs, due to the reduction of selfing generations to fix alleles in the evaluated scenarios.

α-Synuclein Overexpression Induces Lysosomal Dysfunction and Autophagy Impairment in Human Neuroblastoma SH-SY5Y.

Although the etiology of Parkinson's disease (PD) is multifactorial, it has been linked to abnormal accumulation of α-synuclein (α-syn) in dopaminergic neurons, which could lead to dysfunctions on intracellular organelles, with potential neurodegeneration. Patients with familial early-onset PD frequently present mutation in the α-syn gene (SNCA), which encodes mutant α-syn forms, such as A30P and A53T, which potentially regulate Ca2+ unbalance. Here we investigated the effects of overexpression of wild-type α-syn (WT) and the mutant forms A30P and A53T, on modulation of lysosomal Ca2+ stores and further autophagy activation. We found that in α-syn-overexpressing cells, there was a decrease in Ca2+ released from endoplasmic reticulum (ER) which is related to the increase in lysosomal Ca2+ release, coupled to lysosomal pH alkalization. Interestingly, α-syn-overexpressing cells showed lower LAMP1 levels, and a disruption of lysosomal morphology and distribution, affecting autophagy. Interestingly, all these effects were more evident with A53T mutant isoform when compared to A30P and WT α-syn types, indicating that the pathogenic phenotype for PD is potentially related to impairment of α-syn degradation. Taken together, these events directly impact PD-related dysfunctions, being considered possible molecular targets for neuroprotection.

When tongue strength exercises reflect in the cervical region. / Quando exercícios de fortalecimento da língua refletem na região cervical.

PURPOSE: To compare the impact of isokinetic exercise (tongue suction on the palate) in the cervical region of Class I and Class II / 2nd Division participants, considering the average and the symmetry of Root Means Square (RMS) of suprahyoid and suboccipital muscles and cervical sensory reports. METHOD: 11 participants Class I and 19 Class II / 2nd Division, both genders, mean age 33.4 ± 14.1 years. For the analysis of RMS average and symmetry, electromyography was performed in the suboccipital and suprahyoid muscles, bilaterally, at rest and suction of water in the initial, intermediate and final phases. The cervical sensation was evaluated qualitatively during the exercises. RESULTS: the mean RMS did not differ between Classes (p=0.7), but showed an increase in the intermediate phase in the suboccipital musculature (p=0.0001) and decrease in the suprahyoid musculature. In symmetry, the suprahyoid musculature showed a significant difference between classes (p=0.0001) during the intermediate phase. In the Class I participant the symmetry was reestablished in the final phase, a fact that did not occur in Class II / 2nd Division. Regarding the cervical sensation, only the Class II / 2nd Division had expressive complaints. CONCLUSION: The Isokinetic suctioning exercise of the tongue against the palate, had an expressive repercussion with reports of discomfort and neck pain in the Class II / 2nd Division participants. On average RMS, there was no difference between the classes, but in the intermediate phase, the suboccipital muscles showed a significant increase in the activity. Symmetry in the suprahyoid musculature had a significant difference between the classes and asymmetry in the intermediate phase.

Quando exercícios de fortalecimento da língua refletem na região cervical / When tongue strength exercises reflect in the cervical region

RESUMO Objetivo: Comparar o impacto do exercício isocinético "sucção da língua contra o palato" na região cervical em participantes Classe I e Classe II/2.ª Divisão, considerando a média e a simetria do Root Means Square (RMS) dos músculos supra-hióideos e suboccipitais, e relatos sensoriais cervicais. Método: Onze participantes Classe I e 19 Classe II/2.ª Divisão, ambos os gêneros, média de idade 33,4 ±14,1 anos. Para análise da média do RMS e da simetria, realizou-se eletromiografia dos músculos suboccipitais e supra-hióideos, bilateralmente, no repouso e na sucção de água nas fases inicial, intermediária e final. A sensação cervical foi avaliada qualitativamente durante os exercícios. Resultados: A média do RMS não apresentou diferença entre Classes (p=0,7), mas revelou, na fase intermediária, elevação na musculatura suboccipital (p=0,0001) e diminuição na musculatura supra-hióidea. Na simetria, a musculatura supra-hióidea mostrou diferença significativa entre classes (p=0,0001) durante a fase intermediária. No participante Classe I, foi restabelecida a simetria na fase final, fato que não ocorreu na Classe II/2.ª Divisão. Em relação à sensação cervical, somente os Classe II/2.ª Divisão apresentaram queixas expressivas. Conclusão: O exercício isocinético de sucção da língua contra o palato repercutiu de forma expressiva com relatos de desconforto e dor cervical nos participantes Classe II/2.ª Divisão. Na média do RMS, não houve diferença entre as classes, mas, na fase intermediária, a musculatura suboccipital apresentou elevação de atividade significativa. A simetria na musculatura supra-hióidea teve diferença significativa entre as classes e assimetria na fase intermediária.

ABSTRACT Purpose: To compare the impact of isokinetic exercise (tongue suction on the palate) in the cervical region of Class I and Class II / 2nd Division participants, considering the average and the symmetry of Root Means Square (RMS) of suprahyoid and suboccipital muscles and cervical sensory reports. Method: 11 participants Class I and 19 Class II / 2nd Division, both genders, mean age 33.4 ± 14.1 years. For the analysis of RMS average and symmetry, electromyography was performed in the suboccipital and suprahyoid muscles, bilaterally, at rest and suction of water in the initial, intermediate and final phases. The cervical sensation was evaluated qualitatively during the exercises. Results: the mean RMS did not differ between Classes (p=0.7), but showed an increase in the intermediate phase in the suboccipital musculature (p=0.0001) and decrease in the suprahyoid musculature. In symmetry, the suprahyoid musculature showed a significant difference between classes (p=0.0001) during the intermediate phase. In the Class I participant the symmetry was reestablished in the final phase, a fact that did not occur in Class II / 2nd Division. Regarding the cervical sensation, only the Class II / 2nd Division had expressive complaints. Conclusion: The Isokinetic suctioning exercise of the tongue against the palate, had an expressive repercussion with reports of discomfort and neck pain in the Class II / 2nd Division participants. On average RMS, there was no difference between the classes, but in the intermediate phase, the suboccipital muscles showed a significant increase in the activity. Symmetry in the suprahyoid musculature had a significant difference between the classes and asymmetry in the intermediate phase.

Nonlinear quantile regression to describe the dry matter accumulation of garlic plants / Regressão quantílica não linear para descrever o acúmulo de matéria seca de alho

ABSTRACT: The objective of this study was to adjust nonlinear quantile regression models for the study of dry matter accumulation in garlic plants over time, and to compare them to models fitted by the ordinary least squares method. The total dry matter of nine garlic accessions belonging to the Vegetable Germplasm Bank of Universidade Federal de Viçosa (BGH/UFV) was measured in four stages (60, 90, 120 and 150 days after planting), and those values were used for the nonlinear regression models fitting. For each accession, there was an adjustment of one model of quantile regression (τ=0.5) and one based on the least squares method. The nonlinear regression model fitted was the Logistic. The Akaike Information Criterion was used to evaluate the goodness of fit of the models. Accessions were grouped using the UPGMA algorithm, with the estimates of the parameters with biological interpretation as variables. The nonlinear quantile regression is efficient for the adjustment of models for dry matter accumulation in garlic plants over time. The estimated parameters are more uniform and robust in the presence of asymmetry in the distribution of the data, heterogeneous variances, and outliers.

RESUMO: Este trabalho teve como objetivo ajustar modelos de regressão quantílica não linear para o estudo do acúmulo de matéria seca total em plantas de alho ao longo do tempo, e compará-los com modelos ajustados pelo método dos mínimos quadrados. A matéria seca total de nove acessos de alho pertencentes ao Banco de Germoplasma de Hortaliças da Universidade Federal de Viçosa (BGH/UFV) foi avaliada em quatro períodos (60, 90, 120 e 150 dias após plantio), e estes valores foram utilizados para o ajuste de modelos de regressão - não linear - logística. Para cada acesso, foram ajustados um modelo de regressão quantílica (τ=0,5) e um modelo pela metodologia dos mínimos quadrados. Para avaliar a qualidade de ajuste dos modelos foi utilizado o Critério de Informação de Akaike. Os acessos foram agrupados pelo algoritmo UPGMA, utilizando as estimativas dos parâmetros com interpretação biológica como variáveis. A regressão quantílica não linear foi eficiente no ajuste de modelos para descrição do acúmulo de matéria seca ao longo do tempo. As estimativas de parâmetros foram mais uniformes e robustas na presença de dados assimétricos, variâncias heterogêneas e de valores discrepantes.

The Interplay between Ca2+ Signaling Pathways and Neurodegeneration.

Calcium (Ca2+) homeostasis is essential for cell maintenance since this ion participates in many physiological processes. For example, the spatial and temporal organization of Ca2+ signaling in the central nervous system is fundamental for neurotransmission, where local changes in cytosolic Ca2+ concentration are needed to transmit information from neuron to neuron, between neurons and glia, and even regulating local blood flow according to the required activity. However, under pathological conditions, Ca2+ homeostasis is altered, with increased cytoplasmic Ca2+ concentrations leading to the activation of proteases, lipases, and nucleases. This review aimed to highlight the role of Ca2+ signaling in neurodegenerative disease-related apoptosis, where the regulation of intracellular Ca2+ homeostasis depends on coordinated interactions between the endoplasmic reticulum, mitochondria, and lysosomes, as well as specific transport mechanisms. In neurodegenerative diseases, alterations-increased oxidative stress, energy metabolism alterations, and protein aggregation have been identified. The aggregation of α-synuclein, ß-amyloid peptide (Aß), and huntingtin all adversely affect Ca2+ homeostasis. Due to the mounting evidence for the relevance of Ca2+ signaling in neuroprotection, we would focus on the expression and function of Ca2+ signaling-related proteins, in terms of the effects on autophagy regulation and the onset and progression of neurodegenerative diseases.

Multi-trait multi-environment models in the genetic selection of segregating soybean progeny.

At present, single-trait best linear unbiased prediction (BLUP) is the standard method for genetic selection in soybean. However, when genetic selection is performed based on two or more genetically correlated traits and these are analyzed individually, selection bias may arise. Under these conditions, considering the correlation structure between the evaluated traits may provide more-accurate genetic estimates for the evaluated parameters, even under environmental influences. The present study was thus developed to examine the efficiency and applicability of multi-trait multi-environment (MTME) models by the residual maximum likelihood (REML/BLUP) and Bayesian approaches in the genetic selection of segregating soybean progeny. The study involved data pertaining to 203 soybean F2:4 progeny assessed in two environments for the following traits: number of days to maturity (DM), 100-seed weight (SW), and average seed yield per plot (SY). Variance components and genetic and non-genetic parameters were estimated via the REML/BLUP and Bayesian methods. The variance components estimated and the breeding values and genetic gains predicted with selection through the Bayesian procedure were similar to those obtained by REML/BLUP. The frequentist and Bayesian MTME models provided higher estimates of broad-sense heritability per plot (or heritability of total effects of progeny; [Formula: see text]) and mean accuracy of progeny than their respective single-trait versions. Bayesian analysis provided the credibility intervals for the estimates of [Formula: see text]. Therefore, MTME led to greater predicted gains from selection. On this basis, this procedure can be efficiently applied in the genetic selection of segregating soybean progeny.

Analysis of the adaptability of black bean cultivars by means of quantile regression / Análise da adaptabilidade de cultivares de feijão preto por meio de regressão quantílica

ABSTRACT: The aim of this study was to use quantile regression (QR) to characterize the effect of the adaptability parameter throughout the distribution of the productivity variable on black bean cultivars launched by different national research institutes (research centers) over the last 50 years. For this purpose, 40 cultivars developed by Brazilian genetic improvement programs between 1959 and 2013 were used. Initially, QR models were adjusted considering three quantiles (τ = 0.2, 0.5 and 0.8). Subsequently, with the confidence intervals, quantile models τ = 0.2 and 0.8 (QR0.2 and QR0.8) showed differences regarding the parameter of adaptability and average productivity. Finally, by grouping the cultivars into one of the two groups defined from QR0.2 and QR0.8, it was reported that the younger cultivars were associated to the quantile τ = 0.8, i.e., those with higher yields and more responsive conditions indicating that genetic improvement over the last 50 years resulted in an increase in both the productivity and the adaptability of cultivars.

RESUMO: Neste estudo objetivou-se utilizar a regressão quantílica (RQ) para caracterizar o efeito do parâmetro de adaptabilidade ao longo de toda a distribuição da variável produtividade em cultivares de feijão preto lançadas por diferentes instituições nacionais de pesquisa nos últimos 50 anos. Para tanto utilizou-se 40 cultivares desenvolvidas pelos programas brasileiros de melhoramento genético entre os anos de 1959 a 2013. Inicialmente foram ajustados modelos de RQ considerando três quantis (τ=0,2, 0,5, 0,8). Posteriormente, com os intervalos de confiança verificou-se que os modelos quantílicos τ=0,2 e 0,8 (RQ0,2 e RQ0,8) apresentaram diferenças quanto ao parâmetro de adaptabilidade e produtividade média. Finalmente, por meio do agrupamento das cultivares em um dos dois grupos definidos a partir de RQ0,2 e RQ0,8, constatou-se que as cultivares mais novas foram associadas ao quantil τ = 0,8, ou seja, aquelas com maiores produtividades e mais responsivas as condições ambientais indicando que o melhoramento ao longo dos últimos 50 anos possibilitou o incremento tanto na produtividade quanto na adaptabilidade das cultivares.

Autophagy and intermittent fasting: the connection for cancer therapy?

Cancer is a leading cause of death worldwide, and its incidence is continually increasing. Although anticancer therapy has improved significantly, it still has limited efficacy for tumor eradication and is highly toxic to healthy cells. Thus, novel therapeutic strategies to improve chemotherapy, radiotherapy and targeted therapy are an important goal in cancer research. Macroautophagy (herein referred to as autophagy) is a conserved lysosomal degradation pathway for the intracellular recycling of macromolecules and clearance of damaged organelles and misfolded proteins to ensure cellular homeostasis. Dysfunctional autophagy contributes to many diseases, including cancer. Autophagy can suppress or promote tumors depending on the developmental stage and tumor type, and modulating autophagy for cancer treatment is an interesting therapeutic approach currently under intense investigation. Nutritional restriction is a promising protocol to modulate autophagy and enhance the efficacy of anticancer therapies while protecting normal cells. Here, the description and role of autophagy in tumorigenesis will be summarized. Moreover, the possibility of using fasting as an adjuvant therapy for cancer treatment, as well as the molecular mechanisms underlying this approach, will be presented.

Portuguese adaptation of Shulman's test of pragmatic skills. / Adaptação para o português do teste de habilidades pragmáticas de Shulman.

PURPOSE: The purpose of this study was to apply the Test of Pragmatic Skills in Brazilian children with normal development. METHODS: Participants of this study were 60 children 3:00 to 8:11 years old, equally divided between genders. The examiners had prior contact with the group of children and applied the TOPS - a traditional test that proposes four sets of simple activities, with the common material, applicable in a short period of time - according to the procedure proposed by the author. RESULTS: The results showed a large variability in performance, illustrating that the linguistic and pragmatic skills develop according to the age. It was also observed that the subjects performed all the categories of communicative intentions required by Shulman, indicating that it is not the presence or absence of a specific intent that influences the score in this test, but the quality of the answers provided, which evolves with age. CONCLUSION: Thus, we can conclude that the TOPS proved to be an important instrument that allows answers in informal conversation contexts, verifying that the test is effective in assessing the pragmatic skills of typically developing children and can be an important tool to be used in the assessment of communicative intentions in Brazilian children.

OBJETIVO: A proposta do presente estudo foi aplicar o Test of Pragmatic Skills em crianças brasileiras com desenvolvimento típico. MÉTODO: Foram participantes desta pesquisa 60 crianças de 3:00 a 8:11 anos, divididas igualmente entre os gêneros. As examinadoras tiveram contato prévio com o grupo de crianças e aplicaram o TOPS ­ um teste tradicional composto por quatro conjuntos de atividades simples, com material comum, aplicáveis em um curto período de tempo ­ segundo o proposto pelo autor. RESULTADOS: Nos resultados, observamos bastante variabilidade no desempenho, exemplificando que as habilidades linguísticas e pragmáticas vão se desenvolvendo de acordo com a idade. Foi possível observar, ainda, que os participantes apresentaram as categorias de intenções comunicativas pretendidas por Shulman, indicando que não é a presença ou ausência de alguma intenção específica que influencia a pontuação nesse teste, mas a qualidade das respostas fornecidas, que evolui com a idade. CONCLUSÃO: Desta forma, podemos concluir que o TOPS mostrou-se importante por permitir respostas em contextos informais de conversação, verificando-se que o teste é eficaz para avaliar as habilidades pragmáticas de crianças de desenvolvimento típico e pode ser um instrumento relevante a ser empregado na avaliação das intenções comunicativas de crianças brasileiras.

Quantile regression for genome-wide association study of flowering time-related traits in common bean.

Flowering is an important agronomic trait. Quantile regression (QR) can be used to fit models for all portions of a probability distribution. In Genome-wide association studies (GWAS), QR can estimate SNP (Single Nucleotide Polymorphism) effects on each quantile of interest. The objectives of this study were to estimate genetic parameters and to use QR to identify genomic regions for phenological traits (Days to first flower-DFF; Days for flowering-DTF; Days to end of flowering-DEF) in common bean. A total of 80 genotypes of common beans, with 3 replicates were raised at 4 locations and seasons. Plants were genotyped for 384 SNPs. Traditional single-SNP and 9 QR models, ranging from equally spaced quantiles (τ) 0.1 to 0.9, were used to associate SNPs to phenotype. Heritabilities were moderate high, ranging from 0.32 to 0.58. Genetic and phenotypic correlations were all high, averaging 0.66 and 0.98, respectively. Traditional single-SNP GWAS model was not able to find any SNP-trait association. On the other hand, when using QR methodology considering one extreme quantile (τ = 0.1) we found, respectively 1 and 7, significant SNPs associated for DFF and DTF. Significant SNPs were found on Pv01, Pv02, Pv03, Pv07, Pv10 and Pv11 chromosomes. We investigated potential candidate genes in the region around these significant SNPs. Three genes involved in the flowering pathways were identified, including Phvul.001G214500, Phvul.007G229300 and Phvul.010G142900.1 on Pv01, Pv07 and Pv10, respectively. These results indicate that GWAS-based QR was able to enhance the understanding on genetic architecture of phenological traits (DFF and DTF) in common bean.