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The cow-calf industry’s sustainability and profitability depend on the reproductive success of the herd. Genomic information has provided insights into the quantitative trait loci (QTLs) underlying cow subfertility. Integrating functional information into the genomics regulatory layer can provide new markers for improving fertility. This study aims to identify gene expression regulatory polymorphisms in uterine luminal epithelial cells and investigate their effects on fertility-related genes. We retrieved RNA-Seq data from uterine epithelial cells (GSE171577) of recipient cows (n = 18 non-pregnant – NP and n = 25 pregnant – P) sampled on day four before embryo transfer. Raw data quality control was performed, and read mapping was carried out using the multi-sample 2-pass mapping procedure from STAR. Gene normalization was performed using the log2CPM function from edgeR. Variant detection was based on the uniquely mapped reads using the GATK software. After quality control, 43 samples, 203,404 SNPs, and 15,029 genes were used for eQTL analysis (expression quantitative trait loci). Using an additive linear model from the MatrixEQTL R-package, we identified 25,946 cis-eQTLs for 1,823 genes (FDR < 0.05). Chromosomes 18 and 19 harbored the greatest number of cis-eQTLs with 2,392 and 2,283, respectively. A total of 50 cis-eQTLs were previously reported as differentially expressed genes, including CD37, CXCL3, PILRA, and PPP6R1 genes. We also identified fertility-related genes such as PLOD3, HDHD3, and LY6G6E, which were modulated by 106, 86, and 65 SNPs, respectively. Functional analysis of cis-eQTLs retrieved immune-related biologic processes, including antigen processing and presentation of peptide antigen via MHC class Ib and defense response to Gram-positive bacterium (FDR < 0.05). Additionally, fatty acid degradation and metabolic pathways were among the over-represented KEGG pathways. Our findings show that eQTLs influence key biological pathways and genes affecting fertility. Additionally, it provides novel functional regulatory mechanisms that may lead to the identification of causative mutations.

Poster presented at the ISAG meeting - 2023

Additional file 4. Table S4. Composition of the experimental diets (as-fed basis). Table S5. Analyzed fatty acid profile of grower diets (as-fed basis). Table S6. Analyzed fatty acid profile of finisher diets (as-fed basis).

Female fertility significantly affects the efficiency of cow-calf production. Despite the collective efforts to understand the complex regulation of reproductive traits, causative genes and/or mutations have not been reported yet. Using omics technologies, such as gene expression, may unveil potential regulatory mechanisms and provide opportunities that link genotype to phenotype. Among them, expression quantitative trait loci (eQTL) are a powerful tool to identify biological mechanisms and potential markers for improving fertility. This study aimed to identify eQTLs underlying fertility-related traits and their co-localization with previously annotated QTLs. RNA-Seq from uterine epithelial cells (GSE171577) from crossbreed cows (n = 18 non-pregnant – NP and n = 25 pregnant – P) were used for gene expression analysis and SNP calling. Raw data quality control was performed, and read mapping was carried out using STAR. Genes were normalized to counts per million (CPM) and then the CPM values were log2 transformed using edgeR. Next, uniquely mapped reads were used for variant detection using the GATK software. Significant eQTLs were compared to the Animal Genome cattle database (QTLdb) to identify overlapping QTL regions. After quality control, 43 samples, 203,404 SNPs, and 15,029 genes were used for eQTL analysis. Using an additive linear model from the Matrix eQTL, we identified 3,989 cis- and 7,683 trans-eQTLs for 1,120 and 2,503 genes, respectively (FDR < 0.05). A total of 50 cis-eQTLs were previously reported as differentially expressed genes, including CD37, CXCL3, PILRA, and PPP6R1 genes. The QTLs from QTLdb overlapping with our eQTLs were associated with traits such as age at puberty, conception rate, fertility index, and luteal activity (FDR < 0.05). Additionally, QTLs for production traits, such as milk production and body weight gain, were over-represented by the eQTLs we have identified. Significant biological processes underlying cis-regulated genes retrieved from ShinyGO were related to antigen processing and presentation. Likewise, trans-eQTLs genes were involved with transcription cis-regulatory region binding and transcription regulator activity. Our study provides novel regulatory and potential causative genetic variants, biological pathways, and genes underlying fertility in cows. Annotation and co-localization of detected eQTLs retrieved genomic regions previously reported as QTLs for production and reproduction-related traits. Further investigation, however, is required to untangle the mechanisms modulating gene expression and its effects on fertility-related traits.

Additional file 1. Supplementary Figures S1–S9.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) The mineral concentration of the bovine muscle does not only depend on the balance between the ingestion and excretion of minerals, but also the environment, breed and genetic factors. In addition, mineral content can affect biological processes related to meat quality, acting in chemical reactions related to tenderness in postmortem as well as in the maintanance of muscular cells throught its action in methabolism, as enzimatic co-factors and in the regulation of cell replication and differentiation. Since detecting genetic elements involved with mineral homeostasis is of interest to the meat industry, we present analyzes performed for this purpose. Differential gene expression tests were performed in muscle Longissiumus thoracis of groups of Nelore steers contrasting separately to the concentration of the minerals calcium, copper, potassium, magnesium, sodium, phosphorus, sulfur, selenium and zinc. The iron mineral was not included in these analyses because the differentially expressed genes related to iron concentration in the same population in study were already published by our research group. A functional enrichment of the differentially expressed genes was made, also verifying protein-protein interactions known among them, in search of biological processes related to each mineral. Then, also including iron concentration data, two new approaches were developed to use the PCIT (Partial Correlation Coefficient with Information Theory) and RIF algorithms (Regulatory Impact Factor). The new applications for using these algorithms allowed the direct identification of genetic elements correlated to the mineral concentration continuously in our population and the quantification of the regulatory impact of the genes and miRNAs correlated to a mineral on the concentration of this mineral. The regulation of the pathways related to adipogenesis was significant and the genes indicated here may explain the antagonistic effect known between Cu and Zn in the biosynthesis of fatty acids. With the new applications to use the PCIT and RIF algorithms, genes known to be linked to mineral homeostasis with high regulatory impact were identified and previously indicated as regulatory in our population for being transcription factors, eQTLs or miRNAs. The PLCB2 gene is correlated with Fe and S, the latter correlates to the other minerals. The NOX1 gene possessed significant RIF and is correlated to Se. In humans, the concentration of zinc regulates NOX1. We conclude that the core of genetic regulation for all minerals studied seems to be in the interactions between the components of the extracellular matrix. We can infer that the integration of the proposed techniques in our work may include a new level of information about the regulatory elements involved in mineral homeostasis. A concentração mineral do músculo bovino não depende somente do equilíbrio entre a ingestão e a excreção de minerais, mas também do ambiente, da raça, do estado fisológico e de fatores genéticos. Além disso, o conteúdo mineral pode afetar processos biológicos relacionados à qualidade da carne, atuando em reações químicas relacionadas à maciez no post mortem e, na manutenção das células musculares, através de sua ação no metabolismo, como co-fatores enzimáticos e na regulação da replicação e diferenciação celular. Visto que detectar elementos genéticos envolvidos com a homeostase mineral é de interesse da indústria de produção da carne, apresentamos análises executadas para este fim. Testes de expressão gênica diferencial foram realizados em músculo Longissimus thoracis de grupos de novilhos Nelore contrastantes separadamente para a concentração dos minerais cálcio, cobre, potássio, magnésio, sódio, fósforo, enxofre, selênio e zinco. O mineral ferro não foi incluído nessas análises pois os genes diferencialmente expressos relacionados à concentração de ferro na mesma população em estudo já foram previamente publicados por nosso grupo de pesquisa. Um enriquecimento funcional dos genes diferencialmente expressos foi feito, verificando também interações proteína-proteína conhecidas entre eles, em busca de processos biológicos relacionados a cada mineral. Em seguida, incluindo-se também dados de concentração de ferro, desenvolveram-se duas novas abordagens de utilização dos algoritmos PCIT (Partial Correlation Coefficient with Information Theory) e RIF (Regulatory Impact Factor). Essas abordagens permitiram a identificação direta de elementos genéticos correlacionados à concentração de minerais, de forma contínua, em nossa população e a quantificação do impacto regulatório dos genes e miRNAs correlacionados a um mineral sobre a concentração deste mineral. A regulação das vias relacionadas à adipogênese foi significativa e genes apontados aqui podem explicar o efeito antagônico conhecido entre Cu e Zn na biossíntese de ácidos graxos. Com as novas abordagens de utilização dos algoritmos PCIT e RIF, foram identificados genes sabidamente ligados à homeostase mineral, com alto impacto regulatório e previamente apontados como regulatórios em nossa população por serem fatores de transcrição, eQTLs ou miRNAs. O gene PLCB2 é correlacionado com Fe e S, sendo esse gene a provável conexão entre Fe e os demais minerais. O gene NOX1 possuiu impacto regulatório significativo sobre a concentração de Se e Zn. Em humanos, a concentração de zinco regula NOX1. Concluímos que o cerne da regulação genética da concentração tecidual para todos os minerais estudados parece estar nas interações entre os componentes da matriz extracelular. Podemos inferir que a integração das técnicas realizadas em nosso trabalho pode incluir um novo nível de informação acerca dos elementos regulatórios envolvidos na homeostase mineral. CAPES: Código de Financiamento 001

Orientador: Prof. Dr. José Luiz Parré. Tese (doutorado em Ciências Econômicas) - Universidade Estadual de Maringá, 2017. A importância da agricultura para o crescimento econômico tende a ser desigual nas diferentes regiões brasileiras, decorrente das especificidades de solo, clima e dispersão do espaço rural, que interferem na adaptação de culturas e sua viabilidade técnica e econômica. No entanto, as inovações tecnológicas ocorridas no setor, frutos dos investimentos em pesquisa e qualificação da mão-de-obra, tendem a reduzir esta desigualdade, visto que gera ganhos de produtividade e viabiliza a adaptação de culturas entre as regiões. Isto em conjunto com os investimentos em infraestrutura de armazenamento que melhora o fluxo de mercadorias dentro da cadeia produtiva e do crédito rural, que viabiliza os investimentos em insumos modernos, tende a reduzir as desigualdades regionais do setor agrícola e sua contribuição para o desenvolvimento econômico. Neste sentido esta pesquisa buscou analisar o comportamento da Produtividade Total dos Fatores (PTF) nos estados brasileiros para o período de 1990 a 2014, avaliando se sua evolução tende a uma convergência no longo prazo e a influencia dos investimentos em pesquisa, infraestrutura de armazenamento, capital humano e crédito rural para aceleração deste processo. Para isso foi utilizado um modelo econométrico de efeitos fixos, controlando-se os efeitos espaciais, ou seja, a dependência espacial e a heterogeneidade espacial. O resultado da pesquisa, além de comprovar a hipótese de convergência absoluta e condicional da PTF agropecuária, revelou que a taxa média de crescimento da PTF foi afetada por variáveis como Crédito Rural, Capital Humano e Infraestrutura de Armazenamento e externalidades espaciais, gerando uma aceleração no processo de convergência. Pelos critérios de informação de Akaike (AIC) e Schwarz (SC) verificou-se que o modelo de Durbin Espacial (SDM) e o modelo Regressivo Cruzado Espacial (SLX) são os mais adequados para explicar o processo de convergência absoluta e condicional da PTF. O primeiro apresentando uma velocidade de convergência de 0,52% ao ano e o segundo de 0,66% ao ano, sendo o tempo necessário para se completar a metade do processo de transição da PTF da agropecuária entre os estados brasileiros de 134 e 105 anos, evidenciando um processo de convergência lento. The importance of agriculture for economic growth tends to be unequal in the different Brazilian regions, due to the specificities of soil, climate and dispersion of the rural space, which interfere in the adaptation of crops and their technical and economic viability. However, technological innovations in the sector, as a result of investment in research and labor qualification, tend to reduce this inequality, since it generates productivity gains and allows the adaptation of crops between regions. This, together with investments in storage infrastructure that improves the flow of goods within the production chain and rural credit, which enables investments in modern inputs, tends to reduce the regional inequalities of the agricultural sector and their contribution to economic development. In this sense, this research sought to analyze the behavior of TFP in the Brazilian states for the period from 1990 to 2014, evaluating if its evolution tends to a convergence and the influence of investments in research, storage infrastructure, human capital and rural credit to accelerate this process . For this, an econometric model of fixed effects was used, controlling the spatial effects, that is, spatial dependence and spatial heterogeneity. The result of the research, besides confirming the hypothesis of absolute and conditional convergence of agricultural TFP, showed that the average rate of TFP growth was affected by variables such as Rural Credit, Human Capital and Storage Infrastructure and spatial externalities, generating an acceleration in the Convergence process. According to the Akaike (AIC) and Schwarz (SC) information criteria, the Spatial Durbin Model (SDM) and the Regressive Spatial Crusade model (SLX) are the most adequate to explain the process of absolute and conditional convergence of TFP. The first one presented a convergence rate of 0.52% per year and the second one of 0.66% per year, the time required to complete half of the transition process of agricultural TFP between the Brazilian states of 134 and 105 A process of slow convergence. 256 f. : il. color., figs., tabs., maps.

Objective: To characterise and compare the in vitro transport properties of respiratory mucoid secretion in individuals with no lung disease and in stable patients with chronic obstructive pulmonary disease (COPD) and bronchiectasis.Methodology: Samples of mucus were collected, from 21 volunteers presenting no lung disease who had undergone surgery, from 10 patients presenting chronic COPD, and from 16 patients with bronchiectasis. Mucociliary transport (MCT), transport by cough (SCM), and contact angle (CAM) were evaluated.Results: MCT was found to be greater in healthy individuals (1.0 +/- 0.19) than in COPD (0.91 +/- 0.17) and bronchiectasis (0.76 +/- 0.23) patients (p < 0.05), whereas SCM was greater in COPD patients (16.31 +/- 7.35 cm) than in patients with bronchiectasis (12.16 +/- 6.64 cm) and healthy individuals (10.50 +/- 25.8 cm) (p < 0.05). No significant differences were observed between the groups regarding CAM.Conclusion: Mucus from healthy individuals allows better mucociliary transport compared to that from patients with lung diseases. However, the mucus from COPD patients allows a better transport by coughing, demonstrating that these individuals have adapted to a defence mechanism compared to patients with bronchiectasis, who have impairment in their ciliary and cough transport mechanisms. (c) 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier Espana, S.L. All rights reserved. Ctr Univ Tridngulo, Dept Fisioterapia, Uberlandia, MG, Brazil Fac Med Ribeirao Preto, Dept Fisioterapia, Ribeirao Preto, Brazil Universidade Federal de São Paulo, Dept Pneumol, São Paulo, Brazil Fac Med Ribeirao Preto, Dept Pneumol, Ribeirao Preto, Brazil Universidade Federal de São Paulo, Dept Pneumol, São Paulo, Brazil Web of Science