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Sci Data ; 6(1): 256, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672995


Multi-omics approaches use a diversity of high-throughput technologies to profile the different molecular layers of living cells. Ideally, the integration of this information should result in comprehensive systems models of cellular physiology and regulation. However, most multi-omics projects still include a limited number of molecular assays and there have been very few multi-omic studies that evaluate dynamic processes such as cellular growth, development and adaptation. Hence, we lack formal analysis methods and comprehensive multi-omics datasets that can be leveraged to develop true multi-layered models for dynamic cellular systems. Here we present the STATegra multi-omics dataset that combines measurements from up to 10 different omics technologies applied to the same biological system, namely the well-studied mouse pre-B-cell differentiation. STATegra includes high-throughput measurements of chromatin structure, gene expression, proteomics and metabolomics, and it is complemented with single-cell data. To our knowledge, the STATegra collection is the most diverse multi-omics dataset describing a dynamic biological system.

Mol Reprod Dev ; 86(1): 75-87, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30383328


The uterine microenvironment during the first 7 days after ovulation accommodates and facilitates sperm transit to the oviduct and constitutes the sole source of nutrients required for the development of preimplantation embryos. Knowledge of the composition of uterine fluid is largely incomplete. Using untargeted mass spectrometry, we characterized the uterine metabolome during the first 7 days of the estrous cycle. Bovine uteri were collected on Days 0 (N = 4), 3 ( N = 4), 5 ( N = 3), and 7 ( N = 4) relative to ovulation and flushed with Dulbecco's phosphate-buffered saline. A total of 1,993 molecular features were detected of which 184 peaks with putative identification represent 147 unique metabolites, including amino acids, benzoic acids, lipid molecules, carbohydrates, purines, pyrimidines, vitamins, and other intermediate and secondary metabolites. Results revealed changes in the uterine metabolome as the cow transitions from ovulation to Day 7 of the estrous cycle. The majority of metabolites that changed with day reached maximum intensity on either Day 5 or 7 relative to ovulation. Moreover, several metabolites found in the uterine fluid have signaling capabilities and some have been shown to affect preimplantation embryonic development. In conclusion, the metabolome of the bovine uterus changes during early stages of the estrous cycle and is likely to participate in the regulation of preimplantation embryonic development. Data reported here will serve as the basis for future studies aiming to evaluate maternal regulation of preimplantation embryonic development and optimal conditions for the culture of embryos.

Estro/fisiologia , Metaboloma/fisiologia , Útero/metabolismo , Animais , Bovinos , Feminino , Fatores de Tempo
Biomaterials ; 186: 8-21, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30278346


The intrinsic characteristics of the tumor microenvironment (TME), including acidic pH and overexpression of hydrolytic enzymes, offer an exciting opportunity for the rational design of TME-drug delivery systems (DDS). We developed and characterized a pH-responsive biodegradable poly-L-glutamic acid (PGA)-based combination conjugate family with the aim of optimizing anticancer effects. We obtained combination conjugates bearing Doxorubicin (Dox) and aminoglutethimide (AGM) with two Dox loadings and two different hydrazone pH-sensitive linkers that promote the specific release of Dox from the polymeric backbone within the TME. Low Dox loading coupled with a short hydrazone linker yielded optimal effects on primary tumor growth, lung metastasis (∼90% reduction), and toxicological profile in a preclinical metastatic triple-negative breast cancer (TNBC) murine model. The use of transcriptomic analysis helped us to identify the molecular mechanisms responsible for such results including a differential immunomodulation and cell death pathways among the conjugates. This data highlights the advantages of targeting the TME, the therapeutic value of polymer-based combination approaches, and the utility of -omics-based analysis to accelerate anticancer DDS.

Antineoplásicos/administração & dosagem , Portadores de Fármacos/química , Ácido Poliglutâmico/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Microambiente Tumoral , Aminoglutetimida/administração & dosagem , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/administração & dosagem , Liberação Controlada de Fármacos , Feminino , Xenoenxertos , Humanos , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Neoplasias de Mama Triplo Negativas/patologia
Nucleic Acids Res ; 46(W1): W503-W509, 2018 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-29800320


The increasing availability of multi-omic platforms poses new challenges to data analysis. Joint visualization of multi-omics data is instrumental in better understanding interconnections across molecular layers and in fully utilizing the multi-omic resources available to make biological discoveries. We present here PaintOmics 3, a web-based resource for the integrated visualization of multiple omic data types onto KEGG pathway diagrams. PaintOmics 3 combines server-end capabilities for data analysis with the potential of modern web resources for data visualization, providing researchers with a powerful framework for interactive exploration of their multi-omics information. Unlike other visualization tools, PaintOmics 3 covers a comprehensive pathway analysis workflow, including automatic feature name/identifier conversion, multi-layered feature matching, pathway enrichment, network analysis, interactive heatmaps, trend charts, and more. It accepts a wide variety of omic types, including transcriptomics, proteomics and metabolomics, as well as region-based approaches such as ATAC-seq or ChIP-seq data. The tool is freely available at

Regulação da Expressão Gênica , Redes e Vias Metabólicas/genética , Transdução de Sinais/genética , Software , Transcriptoma , Linhagem Celular Transformada , Reprogramação Celular , Gráficos por Computador , Fibroblastos/citologia , Fibroblastos/metabolismo , Genômica/métodos , Humanos , Internet , Metabolômica/métodos , Anotação de Sequência Molecular , Proteômica/métodos
Vet Parasitol Reg Stud Reports ; 13: 205-211, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-31014875


The infectivity and virulence of seven Trypanosoma evansi and Trypanosoma equiperdum Venezuelan strains isolated from horses, donkeys and capybaras were compared in a mouse model up to 41 days, for parasitemia, animal weight, survival rates, packed cell volume, haemoglobin and erythrocyte count. Two T. equiperdum strains and three of the T. evansi strains resulted in 100% mice mortality, while the two T. evansi donkey strains exhibited lower infectivity and mortality. T. equiperdum strains had shorter pre-patent periods (4 days) than the T. evansi strains (4-12 days). In terms of pathogenicity, only the T. evansi horse strain and the two capybara strains produced a significant decrease of the packed cell volume, in haemoglobin concentration and in red blood cell count. In contrast, the T. evansi donkey strains did not show any changes in the hematological parameters. From the seven variables studied, only pre-patent period, day of maximum parasitemia, day of first parasitemia peak and number of parasitemia peaks were statistically significant. Weight decrease was only observed in mice infected with the T. evansi horse strain. T. equiperdum strains showed the highest mice lethality (7% survival by day 8 post-infection) with no change in the hematological parameters. The three T. evansi horse and capybara strains showed 80%, 87% and 97% survival rates, respectively by day 12 post-infection. However, by day 20 post-inoculation all the mice infected with the T. evansi horse strain died, while 53% and 27% capybara strains infected survived. Whereas by day 40 post-infection, 53 and 73% of the mice infected with the T. evansi donkey strains had survived. These results demonstrate striking infectivity and virulence differences between Venezuelan T. evansi and T. equiperdum strains in NMRI mice and open new possibilities to characterize inter and intra-species variations that may contribute to the pathogenicity of these two species.

Trypanosoma/patogenicidade , Tripanossomíase/veterinária , Anemia/etiologia , Animais , Modelos Animais de Doenças , Equidae/parasitologia , Cavalos/parasitologia , Camundongos , Roedores/parasitologia , Tripanossomíase/mortalidade , Virulência
PLoS Negl Trop Dis ; 9(2): e0003512, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25647069


RATIONALE: Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. OBJECTIVE: The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. METHODS AND RESULTS: We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. CONCLUSIONS: These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients.

Bradicardia/parasitologia , Cardiomiopatia Chagásica/fisiopatologia , Coração/fisiopatologia , Proteínas de Protozoários/imunologia , Animais , Western Blotting , Bradicardia/fisiopatologia , Cardiomiopatia Chagásica/parasitologia , Feminino , Insuficiência Cardíaca/parasitologia , Insuficiência Cardíaca/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Protozoários/metabolismo , Ratos , Ratos Sprague-Dawley , Trypanosoma cruzi/patogenicidade , Células Vero