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Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.
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This study investigated how gene expression is affected by dietary fatty acids (FA) by using pigs as a reliable model for studying human diseases that involve lipid metabolism. This includes changes in FA composition in the liver, blood serum parameters and overall metabolic pathways. RNA-Seq data from 32 pigs were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA). Our aim was to identify changes in blood serum parameters and gene expression between diets containing 3% soybean oil (SOY3.0) and a standard pig production diet containing 1.5% soybean oil (SOY1.5). Significantly, both the SOY1.5 and SOY3.0 groups showed significant modules, with a higher number of co-expressed modules identified in the SOY3.0 group. Correlated modules and specific features were identified, including enriched terms and pathways such as the histone acetyltransferase complex, type I diabetes mellitus pathway, cholesterol metabolism, and metabolic pathways in SOY1.5, and pathways related to neurodegeneration and Alzheimer's disease in SOY3.0. The variation in co-expression observed for HDL in the groups analyzed suggests different regulatory patterns in response to the higher concentration of soybean oil. Key genes co-expressed with metabolic processes indicative of diseases such as Alzheimer's was also identified, as well as genes related to lipid transport and energy metabolism, including CCL5, PNISR, DEGS1. These findings are important for understanding the genetic and metabolic responses to dietary variation and contribute to the development of more precise nutritional strategies.
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Oral film (OF) research has intensified due to the effortless administration and advantages related to absorption in systemic circulation. Chitosan is one of the polymers widely used in the production of OFs; however, studies evaluating the maintenance of the active principles' activity are incipient. Propolis has been widely used as an active compound due to its different actions. Printing techniques to incorporate propolis in OFs prove to be efficient. The objective of the present study is to develop and characterize oral films based on chitosan and propolis using printing techniques and to evaluate the main activities of the extract incorporated into the polymeric matrix. The OFs were characterized in relation to the structure using scanning and atomic force electron microscopy; the mechanical properties, disintegration time, wettability, and stability of antioxidant activity were evaluated. The ethanolic extract of green propolis (GPEE) concentration influenced the properties of the OFs. The stability (phenolic compounds and antioxidant activity) was reduced in the first 20 days, and after this period, it remained constant.
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Metagenomics has made it feasible to elucidate the intricacies of the ruminal microbiome and its role in the differentiation of animal production phenotypes of significance. The search for mobile genetic elements (MGEs) has taken on great importance, as they play a critical role in the transfer of genetic material between organisms. Furthermore, these elements serve a dual purpose by controlling populations through lytic bacteriophages, thereby maintaining ecological equilibrium and driving the evolutionary progress of host microorganisms. In this study, we aimed to identify the association between ruminal bacteria and their MGEs in Nellore cattle using physical chromosomal links through the Hi-C method. Shotgun metagenomic sequencing and the proximity ligation method ProxiMeta were used to analyze DNA, getting 1,713,111,307 bp, which gave rise to 107 metagenome-assembled genomes from rumen samples of four Nellore cows maintained on pasture. Taxonomic analysis revealed that most of the bacterial genomes belonged to the families Lachnospiraceae, Bacteroidaceae, Ruminococcaceae, Saccharofermentanaceae, and Treponemataceae and mostly encoded pathways for central carbon and other carbohydrate metabolisms. A total of 31 associations between host bacteria and MGE were identified, including 17 links to viruses and 14 links to plasmids. Additionally, we found 12 antibiotic resistance genes. To our knowledge, this is the first study in Brazilian cattle that connect MGEs with their microbial hosts. It identifies MGEs present in the rumen of pasture-raised Nellore cattle, offering insights that could advance biotechnology for food digestion and improve ruminant performance in production systems.
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Secuencias Repetitivas Esparcidas , Rumen , Animales , Bovinos , Rumen/microbiología , Secuencias Repetitivas Esparcidas/genética , Metagenómica/métodos , Metagenoma , Microbiota/genética , Microbioma Gastrointestinal/genética , Bacterias/genética , Bacterias/clasificación , Genoma Bacteriano , FilogeniaRESUMEN
The aim of this study was to describe epidemiological characteristics and perform SARS-CoV-2 genomic surveillance in the southeastern region of São Paulo State. During the first months of 2022, we compared weekly SARS-CoV-2 infection prevalence considering age, Ct value, and variants' lineages. An increase in the number of SARS-CoV-2-positive cases until the fourth epidemiological week of 2022 was observed. From the fourth epidemiological week onwards, the number of tests for SARS-CoV-2 diagnosis began to decrease, but the number of positive samples for SARS-CoV-2 remained high, reaching its most expressive level with a rate of 60% of infected individual cases. In this period, we observed a progressive increase in SARS-CoV-2 infection within the 0-10 age group throughout the epidemiological weeks, from 2.8% in the first epidemiological week to 9.2% in the eighth epidemiological week of 2022. We further observed significantly higher Ct values within younger patient samples compared to other older age groups. According to lineage assignment, SARS-CoV-2 (BA.1) was the most prevalent (74.5%) in the younger group, followed by BA.1.1 (23%), BA.2 (1.7%), and Delta (1%). Phylogenetic analysis showed that BA.2 sequences clustered together, indicating sustained transmission of this Omicron VOC sub-lineage by that time. Our results suggest the initial dissemination steps of the Omicron's sub-linage BA.2 into the younger group, due to specific genomic features of the detected sequences. These data provide interesting results related to the spread, emergence, and evolution of the Omicron variant in the southeast Brazilian population.
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Simple and complex carcinomas are the most common type of malignant Canine Mammary Tumors (CMTs), with simple carcinomas exhibiting aggressive behavior and poorer prognostic. Stemness is an ability associated with cancer initiation, malignancy, and therapeutic resistance, but is still few elucidated in canine mammary tumor subtypes. Here, we first validated, using CMT samples, a previously published canine one-class logistic regression machine learning algorithm (OCLR) to predict stemness (mRNAsi) in canine cancer cells. Then, using the canine mRNAsi, we observed that simple carcinomas exhibit higher stemness than complex carcinomas and other histological subtypes. Also, we confirmed that stemness is higher and associated with basal-like CMTs and with NMF2 metagene signature, a tumor-specific DNA-repair metagene signature. Using correlation analysis, we selected the top 50 genes correlated with higher stemness, and the top 50 genes correlated with lower stemness and further performed a gene set enrichment analysis to observe the biological processes enriched for these genes. Finally, we suggested two promise stemness-associated targets in CMTs, POLA2 and APEX1, especially in simple carcinomas. Thus, our work elucidates stemness as a potential mechanism behind the aggressiveness and development of canine mammary tumors, especially in simple carcinomas, describing evidence of a promising strategy to target this disease.
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Thermotolerance has become an essential factor in the prevention of the adverse effects of heat stress, but it varies among animals. Identifying genes related to heat adaptability traits is important for improving thermotolerance and for selecting more productive animals in hot environments. The primary objective of this research was to find candidate genes in the liver that play a crucial role in the heat stress response of Santa Ines sheep, which exhibit varying levels of heat tolerance. To achieve this goal, 80 sheep were selected based on their thermotolerance and placed in a climate chamber for 10 days, during which the average temperature was maintained at 36 °C from 10 a.m. to 4 p.m. and 28 °C from 4 p.m. to 10 a.m. A subset of 14 extreme animals, with seven thermotolerant and seven non-thermotolerant animals based on heat loss (rectal temperature), were selected for liver sampling. RNA sequencing and differential gene expression analysis were performed. Thermotolerant sheep showed higher expression of genes GPx3, RGS6, GPAT3, VLDLR, LOC101108817, and EVC. These genes were mainly related to the Hedgehog signaling pathway, glutathione metabolism, glycerolipid metabolism, and thyroid hormone synthesis. These enhanced pathways in thermotolerant animals could potentially mitigate the negative effects of heat stress, conferring greater heat resistance.
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Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.
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A safe and effective vaccine with long-term protection against SARS-CoV-2 variants of concern (VOCs) is a global health priority. Here, we develop lipid nanoparticles (LNPs) to provide safe and effective delivery of plasmid DNA (pDNA) and show protection against VOCs in female small animal models. Using a library of LNPs encapsulating unique barcoded DNA (b-DNA), we screen for b-DNA delivery after intramuscular administration. The top-performing LNPs are further tested for their capacity of pDNA uptake in antigen-presenting cells in vitro. The lead LNP is used to encapsulate pDNA encoding the HexaPro version of SARS-CoV-2 spike (LNP-HPS) and immunogenicity and protection is tested in vivo. LNP-HPS elicit a robust protective effect against SARS-CoV-2 Gamma (P.1), correlating with reduced lethality, decreased viral load in the lungs and reduced lung damage. LNP-HPS induce potent humoral and T cell responses against P.1, and generate high levels of neutralizing antibodies against P.1 and Omicron (B.1.1.529). Our findings indicate that the protective efficacy and immunogenicity elicited by LNP-HPS are comparable to those achieved by the approved COVID-19 vaccine from Biontech/Pfizer in animal models. Together, these findings suggest that LNP-HPS hold great promise as a vaccine candidate against VOCs.
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COVID-19 , ADN Forma B , Vacunas de ADN , Femenino , Animales , Humanos , SARS-CoV-2/genética , Vacunas de ADN/genética , Nanovacunas , Vacunas contra la COVID-19 , COVID-19/prevención & control , ADN , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
The skin plays an important role in thermoregulation. Identification of genes on the skin that contribute to increased heat tolerance can be used to select animals with the best performance in warm environments. Our objective was to identify candidate genes associated with the heat stress response in the skin of Santa Ines sheep. A group of 80 sheep assessed for thermotolerance was kept in a climatic chamber for 8 days at a stress level temperature of 36 °C (10 am to 04 pm) and a maintenance temperature of 28 °C (04 pm to 10 am). Two divergent groups, with seven animals each, were formed after ranking them by thermotolerance using rectal temperature. From skin biopsy samples, total RNA was extracted, quantified, and used for RNA-seq analysis. 15,989 genes were expressed in sheep skin samples, of which 4 genes were differentially expressed (DE; FDR < 0.05) and 11 DE (FDR 0.05-0.177) between the two divergent groups. These genes are involved in cellular protection against stress (HSPA1A and HSPA6), ribosome assembly (28S, 18S, and 5S ribosomal RNA), and immune response (IGHG4, GNLY, CXCL1, CAPN14, and SAA-4). The candidate genes and main pathways related to heat tolerance in Santa Ines sheep require further investigation to understand their response to heat stress in different climatic conditions and under solar radiation. It is essential to verify whether these genes and pathways are present in different breeds and to understand the relationship between heat stress and other genes identified in this study.
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Termotolerancia , Ovinos/genética , Animales , Termotolerancia/genética , Piel , Regulación de la Temperatura Corporal/genética , Respuesta al Choque Térmico/genética , Perfilación de la Expresión GénicaRESUMEN
Replacement of bone defects with bone graft or implant is an important therapeutic strategy that has been used in routine practice. However, the identification of biomaterials that can mimic natural bone properties and serve as bone substitutes remains a major challenge. In this context, alumina-zirconia (Al2O3/ZrO2) nanocomposites emerge as potential alternatives for biomedical applications, owing to their high mechanical strength, wear resistance, and biocompatibility. In this sense, in this study, we prepared porous Al2O3/ZrO2 nanocomposites (scaffolds) using the gelcasting method and biomimetically coated them with calcium phosphate (CaP). We evaluated the biocompatibility of the scaffolds using the quantitative MTT cytotoxicity test in L929 cells. Moreover, rabbit adipose-derived mesenchymal stem cells (rADMSCs) were seeded with CaP-containing and CaP-free porous samples to evaluate cell proliferation and cell-scaffold interaction in vitro. Our results showed that the Al2O3/ZrO2 scaffolds were non-cytotoxic, and there were no significant differences between CaP-containing and CaP-free scaffolds in terms of cell growth and adhesion. In contrast, when co-cultured with rADMSCs, the scaffolds enhanced cell proliferation and cell adhesion. The rADMSCs adhered and migrated through the pores of the scaffold and anchored to different poles with differentiated elongated structures. These results suggest osteogenic differentiation of rADMSCs in response to mechanical loading of Al2O3/ZrO2 scaffolds. Therefore, we conclude that Al2O3/ZrO2 scaffolds have demonstrated significant implications in bone tissue engineering and are valuable biomaterials for bone replacement.
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(1) Background: Mammary neoplasms in female dogs share many similarities with the same tumor class in humans, rendering these animals a valuable preclinical model for studying novel therapies against breast cancer. The intricate role of extracellular vesicles (EVs), particularly exosomes, in breast carcinogenesis, by transferring specific proteins to recipient cells within the tumor microenvironment, underscores their significance. Melatonin, a hormone recognized for its antitumor effects, adds another layer of intrigue. (2) Methods: EVs obtained from the plasma of dogs diagnosed with mammary tumors were co cultivated with the benign epithelial lineage E-20 using DMEM. The experiment comprised four 24 h treatment groups: control, EVs, melatonin, and EVs + melatonin. A series of assays were conducted, including colony formation, proliferation, and cellular migration assessments. Furthermore, we conducted colony formation, proliferation, and cellular migration assays. We performed immunohistochemistry for proteins of the mTOR pathway, including mTOR and AKT. (3) Results: Exosomes alone significantly increased proliferation, migration, and colony formation rates and, upregulated the expression of mTOR and AKT proteins. However, when melatonin was added, a protective effect was observed. (4) Conclusions: These findings contributed to the use of melatonin to modulate EV-mediated signaling in the clinical veterinary oncology of mammary tumors.
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Hemangiosarcoma is a mesenchymal neoplasm originating in the endothelial cells of blood vessels; they can be classified as non-visceral and visceral types. Non-visceral hemangiosarcomas can affect the skin, subcutaneous tissues, and muscle tissues; visceral hemangiosarcomas can affect the spleen, liver, heart, lungs, kidneys, oral cavity, bones, bladder, uterus, tongue, and retroperitoneum. Among domestic species, dogs are most affected by cutaneous HSA. Cutaneous HSA represents approximately 14% of all HSA diagnosed in this species and less than 5% of dermal tumors, according to North American studies. However, Brazilian epidemiological data demonstrate a higher prevalence, which may represent 27 to 80% of all canine HSAs and 13.9% of all skin neoplasms diagnosed in this species. Cutaneous HSA most commonly affects middle-aged to elderly dogs (between 8 and 15 years old), with no gender predisposition for either the actinic or non-actinic forms. The higher prevalence of cutaneous HSA in some canine breeds is related to lower protection from solar radiation, as low skin pigmentation and hair coverage lead to greater sun exposure. Actinic changes, such as solar dermatosis, are frequent in these patients, confirming the influence of solar radiation on the development of this neoplasm. There are multiple clinical manifestations of hemangiosarcoma in canines. The diagnostic approach and staging classification of cutaneous HSAs are similar between the different subtypes. The definitive diagnosis is obtained through histopathological analysis of incisional or excisional biopsies. Cytology can be used as a presurgical screening test; however, it has little diagnostic utility in cases of HSA because there is a high risk of blood contamination and sample hemodilution. Surgery is generally the treatment of choice for dogs with localized non-visceral HSA without evidence of metastatic disease. Recently, electrochemotherapy (ECT) has emerged as an alternative therapy for the local ablative treatment of different neoplastic types; the use of radiotherapy for the treatment of dogs with cutaneous HSA is uncommon. There is greater consensus in the literature regarding the indications for adjuvant chemotherapy in subcutaneous and muscular HSA; doxorubicin is the most frequently used antineoplastic agent for subcutaneous and muscular subtypes and can be administered alone or in combination with other drugs. Other therapies include antiangiogenic therapy, photodynamic therapy, the association of chemotherapy with the metronomic dose, targeted therapies, and natural products. The benefits of these therapies are presented and discussed. In general, the prognosis of splenic and cardiac HSA is unfavorable. As a challenging neoplasm, studies of new protocols and treatment modalities are necessary to control this aggressive disease.
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BACKGROUND: The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs' brain tissue. RESULTS: Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from - 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change - 1.489), CALB1 (log2 fold change - 3.431) and CAST (log2 fold change + 0.421) genes. A "calcium transport" network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. CONCLUSION: The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.
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Aceite de Soja , Transcriptoma , Animales , Masculino , Encéfalo , Calcio , Dieta/veterinaria , Ácidos Grasos , Aceite de Soja/farmacología , PorcinosRESUMEN
Pork is of great importance in world trade and represents the largest source of fatty acids in the human diet. Lipid sources such as soybean oil (SOY), canola (CO), and fish oil (FO) are used in pig diets and influence blood parameters and the ratio of deposited fatty acids. In this study, the main objective was to evaluate changes in gene expression in porcine skeletal muscle tissue resulting from the dietary oil sources and to identify metabolic pathways and biological process networks through RNA-Seq. The addition of FO in the diet of pigs led to intramuscular lipid with a higher FA profile composition of C20:5 n-3, C22:6 n-3, and SFA (C16:0 and C18:0). Blood parameters for the FO group showed lower cholesterol and HDL content compared with CO and SOY groups. Skeletal muscle transcriptome analyses revealed 65 differentially expressed genes (DEG, FDR 10%) between CO vs SOY, and 32 DEG for CO vs FO, and 531 DEG for SOY vs FO comparison. Several genes, including AZGP1, PDE3B, APOE, PLIN1, and LIPS, were found to be down-regulated in the diet of the SOY group compared to the FO group. The enrichment analysis revealed DEG involved in lipid metabolism, metabolic diseases, and inflammation between the oil groups, with specific gene functions in each group and altered blood parameters. The results provide mechanisms to help us understand the behavior of genes according to fatty acids.
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Perfilación de la Expresión Génica , Transcriptoma , Humanos , Animales , Masculino , Porcinos , Ácidos Grasos , Inflamación , Músculo Esquelético , Aceite de SojaRESUMEN
Pigs (Sus scrofa) are an animal model for metabolic diseases in humans. Pork is an important source of fatty acids (FAs) in the human diet, as it is one of the most consumed meats worldwide. The effects of dietary inclusion of oils such as canola, fish, and soybean oils on pig gene expression are mostly unknown. Our objective was to evaluate FA composition, identify changes in gene expression in the liver of male pigs fed diets enriched with different FA profiles, and identify impacted metabolic pathways and gene networks to enlighten the biological mechanisms' variation. Large White male pigs were randomly allocated to one of three diets with 18 pigs in each; all diets comprised a base of corn and soybean meal to which either 3% of soybean oil (SOY), 3% canola oil (CO), or 3% fish oil (FO) was added for a 98-day trial during the growing and finishing phases. RNA sequencing was performed on the liver samples of each animal by Illumina technology for differential gene expression analyses, using the R package DESeq2. The diets modified the FA profile, mainly in relation to polyunsaturated and saturated FAs. Comparing SOY vs. FO, 143 differentially expressed genes (DEGs) were identified as being associated with metabolism, metabolic and neurodegenerative disease pathways, inflammatory processes, and immune response networks. Comparing CO vs. SOY, 148 DEGs were identified, with pathways related to FA oxidation, regulation of lipid metabolism, and metabolic and neurodegenerative diseases. Our results help explain the behavior of genes with differential expression in metabolic pathways resulting from feeding different types of oils in pig diets.
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São Paulo is the financial center of Brazil, with a population of over 12 million, that receives travelers from all over the world for business and tourism. It was the first city in Brazil to report a case of COVID-19 that rapidly spread across the city despite the implementation of the restriction measures. Despite many reports, much is still unknown regarding the genomic diversity and transmission dynamics of this virus in the city of São Paulo. Thus, in this study, we provide a retrospective overview of the COVID-19 epidemic in São Paulo City, Southeastern, Brazil, by generating a total of 9995 near-complete genome sequences from all the city's different macro-regions (North, West, Central, East, South, and Southeast). Our analysis revealed that multiple independent introduction events of different variants (mainly Gamma, Delta, and Omicron) occurred throughout time. Additionally, our estimates of viral movement within the different macro-regions further suggested that the East and the Southeast regions were the largest contributors to the Gamma and Delta viral exchanges to other regions. Meanwhile, the North region had a higher contribution to the dispersion of the Omicron variant. Together, our results reinforce the importance of increasing SARS-CoV-2 genomic monitoring within the city and the country to track the real-time evolution of the virus and to detect earlier any eventual emergency of new variants of concern that could undermine the fight against COVID-19 in Brazil and worldwide.
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COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2/genética , Brasil/epidemiología , América Latina , Estudios RetrospectivosRESUMEN
BACKGROUND: Potential functional variants (PFVs) can be defined as genetic variants responsible for a given phenotype. Ultimately, these are the best DNA markers for animal breeding and selection, especially for polygenic and complex phenotypes. Herein, we described the identification of PFVs for complex phenotypes (in this case, Feed Efficiency in beef cattle) using a systems-biology driven approach based on RNA-seq data from physiologically relevant organs. RESULTS: The systems-biology coupled with deep molecular phenotyping by RNA-seq of liver, muscle, hypothalamus, pituitary, and adrenal glands of animals with high and low feed efficiency (FE) measured by residual feed intake (RFI) identified 2,000,936 uniquely variants. Among them, 9986 variants were significantly associated with FE and only 78 had a high impact on protein expression and were considered as PFVs. A set of 169 significant uniquely variants were expressed in all five organs, however, only 27 variants had a moderate impact and none of them a had high impact on protein expression. These results provide evidence of tissue-specific effects of high-impact PFVs. The PFVs were enriched (FDR < 0.05) for processing and presentation of MHC Class I and II mediated antigens, which are an important part of the adaptive immune response. The experimental validation of these PFVs was demonstrated by the increased prediction accuracy for RFI using the weighted G matrix (ssGBLUP+wG; Acc = 0.10 and b = 0.48) obtained in the ssGWAS in comparison to the unweighted G matrix (ssGBLUP; Acc = 0.29 and b = 1.10). CONCLUSION: Here we identified PFVs for FE in beef cattle using a strategy based on systems-biology and deep molecular phenotyping. This approach has great potential to be used in genetic prediction programs, especially for polygenic phenotypes.
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Alimentación Animal , Ingestión de Alimentos , Animales , Bovinos/genética , Ingestión de Alimentos/genética , Biología de Sistemas , Marcadores Genéticos , FenotipoRESUMEN
Despite advances in diagnostic and therapeutic approaches for lung cancer, new therapies targeting metastasis by the specific regulation of cancer genes are needed. In this study, we screened a small library of epigenetic inhibitors in non-small-cell lung cancer (NSCLC) cell lines and evaluated 38 epigenetic targets for their potential role in metastatic NSCLC. The potential candidates were ranked by a streamlined approach using in silico and in vitro experiments based on publicly available databases and evaluated by real-time qPCR target gene expression, cell viability and invasion assays, and transcriptomic analysis. The survival rate of patients with lung adenocarcinoma is inversely correlated with the gene expression of eight epigenetic targets, and a systematic review of the literature confirmed that four of them have already been identified as targets for the treatment of NSCLC. Using nontoxic doses of the remaining inhibitors, KDM6B and PADI4 were identified as potential targets affecting the invasion and migration of metastatic lung cancer cell lines. Transcriptomic analysis of KDM6B and PADI4 treated cells showed altered expression of important genes related to the metastatic process. In conclusion, we showed that KDM6B and PADI4 are promising targets for inhibiting the metastasis of lung adenocarcinoma cancer cells.
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Adenocarcinoma del Pulmón , Carcinoma de Pulmón de Células no Pequeñas , Histona Demetilasas con Dominio de Jumonji , Neoplasias Pulmonares , Arginina Deiminasa Proteína-Tipo 4 , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Detección Precoz del Cáncer , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Humanos , Histona Demetilasas con Dominio de Jumonji/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Arginina Deiminasa Proteína-Tipo 4/genéticaRESUMEN
The authors hereby request the inclusion of two authors (Olivia Teixeira and Maria Cristina Nonato) in the recently published article in Viruses entitled "Nucleocapsid (N) gene mutations of SARS-CoV-2 can affect real-time RT-PCR diagnostic and impact false-negative results" [...].