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2.
EMBO Rep ; 20(12): e47964, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31680439

RESUMO

RNA-binding proteins (RBPs) participate in all steps of gene expression, underscoring their potential as regulators of RNA homeostasis. We structurally and functionally characterize Mip6, a four-RNA recognition motif (RRM)-containing RBP, as a functional and physical interactor of the export factor Mex67. Mip6-RRM4 directly interacts with the ubiquitin-associated (UBA) domain of Mex67 through a loop containing tryptophan 442. Mip6 shuttles between the nucleus and the cytoplasm in a Mex67-dependent manner and concentrates in cytoplasmic foci under stress. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation experiments show preferential binding of Mip6 to mRNAs regulated by the stress-response Msn2/4 transcription factors. Consistent with this binding, MIP6 deletion affects their export and expression levels. Additionally, Mip6 interacts physically and/or functionally with proteins with a role in mRNA metabolism and transcription such as Rrp6, Xrn1, Sgf73, and Rpb1. These results reveal a novel role for Mip6 in the homeostasis of Msn2/4-dependent transcripts through its direct interaction with the Mex67 UBA domain.

3.
PLoS Comput Biol ; 15(11): e1006555, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31682608

RESUMO

Rapid advances in single-cell assays have outpaced methods for analysis of those data types. Different single-cell assays show extensive variation in sensitivity and signal to noise levels. In particular, scATAC-seq generates extremely sparse and noisy datasets. Existing methods developed to analyze this data require cells amenable to pseudo-time analysis or require datasets with drastically different cell-types. We describe a novel approach using self-organizing maps (SOM) to link scATAC-seq regions with scRNA-seq genes that overcomes these challenges and can generate draft regulatory networks. Our SOMatic package generates chromatin and gene expression SOMs separately and combines them using a linking function. We applied SOMatic on a mouse pre-B cell differentiation time-course using controlled Ikaros over-expression to recover gene ontology enrichments, identify motifs in genomic regions showing similar single-cell profiles, and generate a gene regulatory network that both recovers known interactions and predicts new Ikaros targets during the differentiation process. The ability of linked SOMs to detect emergent properties from multiple types of highly-dimensional genomic data with very different signal properties opens new avenues for integrative analysis of heterogeneous data.

4.
Sci Data ; 6(1): 251, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672978
5.
Sci Data ; 6(1): 256, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672995

RESUMO

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.

6.
ACS Chem Neurosci ; 10(10): 4264-4279, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31464424

RESUMO

Exposure to low levels of environmental contaminants, including pesticides, induces neurodevelopmental toxicity. Environmental and food contaminants can reach the brain of the fetus, affecting brain development and leading to neurological dysfunction. The pesticide endosulfan is a persistent pollutant, and significant levels still remain detectable in the environment although its use is banned in some countries. In rats, endosulfan exposure during brain development alters motor activity, coordination, learning, and memory, even several months after uptake, and does so in a sex-dependent way. However, the molecular mechanisms driving these effects have not been studied in detail. In this work, we performed a multiomics study in cerebellum from rats exposed to endosulfan during embryonic development. Pregnant rats were orally exposed to a low dose (0.5 mg/kg) of endosulfan, daily, from gestational day 7 to postnatal day 21. The progeny was evaluated for cognitive and motor functions at adulthood. Expression of messenger RNA and microRNA genes, as well as protein and metabolite levels, were measured on cerebellar samples from males and females. An integrative analysis was conducted to identify altered processes under endosulfan effect. Effects between males and females were compared. Pathways significantly altered by endosulfan exposure included the phosphatidylinositol signaling system, calcium signaling, the cGMP-PKG pathway, the inflammatory and immune system, protein processing in the endoplasmic reticulum, and GABA and taurine metabolism. Sex-dependent effects of endosulfan in the omics results that matched sex differences in cognitive and motor tests were found. These results shed light on the molecular basis of impaired neurodevelopment and contribute to the identification of new biomarkers of neurotoxicity.

7.
Histopathology ; 75(4): 496-507, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31025430

RESUMO

AIMS: To discern the differences in expression profiling of two histological subtypes of colorectal carcinoma (CRC) arising from the serrated route (serrated adenocarcinoma (SAC) and CRC showing histological and molecular features of a high level of microsatellite instability (hmMSI-H) both sharing common features (female gender, right-sided location, mucinous histology, and altered CpG methylation), but dramatically differing in terms of prognosis, development of an immune response, and treatment options. METHODS AND RESULTS: Molecular signatures of SAC and hmMSI-H were obtained by the use of transcriptomic arrays; quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to validate differentially expressed genes. An over-representation of innate immunity functions (granulomonocytic recruitment, chemokine production, Toll-like receptor signalling, and antigen processing and presentation) was obtained from this comparison, and intercellular cell adhesion molecule-1 (ICAM1) was more highly expressed in hmMSI-H, whereas two genes [those encoding calcitonin gene-related peptide-receptor component protein and C-X-C motif chemokine ligand 14 (CXCL14)] were more highly expressed in SAC. These array results were subsequently validated by qPCR, and by IHC for CXCL14 and ICAM1. Information retrieved from public databanks confirmed our findings. CONCLUSIONS: Our findings highlight specific functions and genes that provide a better understanding of the role of the immune response in the serrated pathological route and may be of help in identifying actionable molecules.

8.
PLoS Biol ; 17(4): e2006506, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30978178

RESUMO

The differentiation of self-renewing progenitor cells requires not only the regulation of lineage- and developmental stage-specific genes but also the coordinated adaptation of housekeeping functions from a metabolically active, proliferative state toward quiescence. How metabolic and cell-cycle states are coordinated with the regulation of cell type-specific genes is an important question, because dissociation between differentiation, cell cycle, and metabolic states is a hallmark of cancer. Here, we use a model system to systematically identify key transcriptional regulators of Ikaros-dependent B cell-progenitor differentiation. We find that the coordinated regulation of housekeeping functions and tissue-specific gene expression requires a feedforward circuit whereby Ikaros down-regulates the expression of Myc. Our findings show how coordination between differentiation and housekeeping states can be achieved by interconnected regulators. Similar principles likely coordinate differentiation and housekeeping functions during progenitor cell differentiation in other cell lineages.


Assuntos
Linfócitos B/citologia , Genes myc , Células Precursoras de Linfócitos B/citologia , Animais , Linfócitos B/metabolismo , Ciclo Celular/fisiologia , Diferenciação Celular/genética , Linhagem da Célula , Bases de Dados Genéticas , Regulação para Baixo , Regulação da Expressão Gênica , Genes Essenciais , Humanos , Fator de Transcrição Ikaros/metabolismo , Ativação Linfocitária , Camundongos , Células Precursoras de Linfócitos B/metabolismo , Fatores de Transcrição/metabolismo
9.
Biochim Biophys Acta Gen Subj ; 1863(6): 1040-1049, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30928490

RESUMO

BACKGROUND: The superfamily of adenylating enzymes is a large family of enzymes broadly distributed from bacteria to humans. Acetyl-CoA synthetase (Acs), member of this family, is a metabolic enzyme with an essential role in Escherichia coli (E. coli) acetate metabolism, whose catalytic activity is regulated by acetylation/deacetylation in vivo. METHODS: In this study, the kinetics and thermodynamic parameters of deacetylated and acetylated E. coli Acs were studied for the adenylating step. Moreover, the role of the T264, K270, D500 and K609 residues in catalysis and ATP-binding was also determined by Isothermal titration calorimetry. RESULTS: The results showed that native Acs enzyme binds ATP in an endothermic way. The dissociation constant has been determined and ATP-binding showed no significant differences between acetylated and deacetylated enzyme, although kcat was much higher for the deacetylated enzyme. However, K609 lysine mutation resulted in an increase in ATP-Acs-affinity and in a total loss of enzymatic activity, while T264 and D500 mutant proteins showed a total loss of ATP-binding ability and a decrease in catalytic activity. K609 site-specified acetylation induced a change in Acs conformation which resulted in an exothermic and more energetic ATP-binding. CONCLUSIONS: The differences in ATP-binding could explain the broadly conserved inactivation of Acs when K609 is acetylated. GENERAL SIGNIFICANCE: The results presented in this study demonstrate the importance of the selected residues in Acs ATP-binding and represent an advance in our understanding of the adenylation step of the superfamily of adenylating enzymes and of their acetylation/deacetylation regulation.


Assuntos
Acetilcoenzima A/química , Trifosfato de Adenosina/química , Proteínas de Escherichia coli/química , Escherichia coli/enzimologia , Acetilcoenzima A/metabolismo , Trifosfato de Adenosina/metabolismo , Cinética , Ligação Proteica
10.
Brief Bioinform ; 20(2): 471-481, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-29040385

RESUMO

Over the last few years, RNA-seq has been used to study alterations in alternative splicing related to several diseases. Bioinformatics workflows used to perform these studies can be divided into two groups, those finding changes in the absolute isoform expression and those studying differential splicing. Many computational methods for transcriptomics analysis have been developed, evaluated and compared; however, there are not enough reports of systematic and objective assessment of processing pipelines as a whole. Moreover, comparative studies have been performed considering separately the changes in absolute or relative isoform expression levels. Consequently, no consensus exists about the best practices and appropriate workflows to analyse alternative and differential splicing. To assist the adequate pipeline choice, we present here a benchmarking of nine commonly used workflows to detect differential isoform expression and splicing. We evaluated the workflows performance over different experimental scenarios where changes in absolute and relative isoform expression occurred simultaneously. In addition, the effect of the number of isoforms per gene, and the magnitude of the expression change over pipeline performances were also evaluated. Our results suggest that workflow performance is influenced by the number of replicates per condition and the conditions heterogeneity. In general, workflows based on DESeq2, DEXSeq, Limma and NOISeq performed well over a wide range of transcriptomics experiments. In particular, we suggest the use of workflows based on Limma when high precision is required, and DESeq2 and DEXseq pipelines to prioritize sensitivity. When several replicates per condition are available, NOISeq and Limma pipelines are indicated.


Assuntos
Processamento Alternativo , Benchmarking/métodos , Biologia Computacional/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Proteínas de Neoplasias/genética , Neoplasias da Próstata/genética , Análise de Sequência de RNA/métodos , Estudos de Casos e Controles , Perfilação da Expressão Gênica , Humanos , Masculino , Proteínas de Neoplasias/metabolismo , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Isoformas de Proteínas , Fluxo de Trabalho
11.
Mol Reprod Dev ; 86(1): 75-87, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30383328

RESUMO

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.


Assuntos
Estro/fisiologia , Metaboloma/fisiologia , Útero/metabolismo , Animais , Bovinos , Feminino , Fatores de Tempo
12.
NPJ Microgravity ; 4: 25, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588486

RESUMO

For long-duration space missions, it is critical to maintain health-associated homeostasis between astronauts and their microbiome. To achieve this goal it is important to more fully understand the host-symbiont relationship under the physiological stress conditions of spaceflight. To address this issue we examined the impact of a spaceflight analog, low-shear-modeled microgravity (LSMMG), on the transcriptome of the mutualistic bacterium Vibrio fischeri. Cultures of V. fischeri and a mutant defective in the global regulator Hfq (∆hfq) were exposed to either LSMMG or gravity conditions for 12 h (exponential growth) and 24 h (stationary phase growth). Comparative transcriptomic analysis revealed few to no significant differentially expressed genes between gravity and the LSMMG conditions in the wild type or mutant V. fischeri at exponential or stationary phase. There was, however, a pronounced change in transcriptomic profiles during the transition between exponential and stationary phase growth in both V. fischeri cultures including an overall decrease in gene expression associated with translational activity and an increase in stress response. There were also several upregulated stress genes specific to the LSMMG condition during the transition to stationary phase growth. The ∆hfq mutants exhibited a distinctive transcriptome profile with a significant increase in transcripts associated with flagellar synthesis and transcriptional regulators under LSMMG conditions compared to gravity controls. These results indicate the loss of Hfq significantly influences gene expression under LSMMG conditions in a bacterial symbiont. Together, these results improve our understanding of the mechanisms by which microgravity alters the physiology of beneficial host-associated microbes.

13.
Front Genet ; 9: 578, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555512

RESUMO

The Yeast Metabolic Cycle (YMC) is a model system in which levels of around 60% of the yeast transcripts cycle over time. The spatial and temporal resolution provided by the YMC has revealed that changes in the yeast metabolic landscape and chromatin status can be related to cycling gene expression. However, the interplay between histone modifications and transcription factor activity during the YMC is still poorly understood. Here we apply an innovative statistical approach to integrate chromatin state (ChIP-seq) and gene expression (RNA-seq) data to investigate the transcriptional control during the YMC. By using the multivariate regression models N-PLS (Partial Least Squares) and MORE (Multi-Omics REgulation) methodologies, we assessed the contribution of histone marks and transcription factors to the regulation of gene expression in the YMC. We found that H3K18ac and H3K9ac were the most important histone modifications, whereas Sfp1, Hfi1, Pip2, Mig2, and Yhp1 emerged as the most relevant transcription factors. A significant association in the co-regulation of gene expression was found between H3K18ac and the transcription factors Pip2 (involved in fatty acids metabolism), Xbp1 (cyclin implicated in the regulation of carbohydrate and amino acid metabolism), and Hfi1 (involved in the formation of the SAGA complex). These results evidence the crucial role of histone lysine acetylation levels in the regulation of gene expression in the YMC through the coordinated action of transcription factors and lysine acetyltransferases.

14.
Nat Commun ; 9(1): 4680, 2018 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-30409967

RESUMO

Drought represents a major threat to food security. Mechanistic data describing plant responses to drought have been studied extensively and genes conferring drought resistance have been introduced into crop plants. However, plants with enhanced drought resistance usually display lower growth, highlighting the need for strategies to uncouple drought resistance from growth. Here, we show that overexpression of BRL3, a vascular-enriched member of the brassinosteroid receptor family, can confer drought stress tolerance in Arabidopsis. Whereas loss-of-function mutations in the ubiquitously expressed BRI1 receptor leads to drought resistance at the expense of growth, overexpression of BRL3 receptor confers drought tolerance without penalizing overall growth. Systematic analyses reveal that upon drought stress, increased BRL3 triggers the accumulation of osmoprotectant metabolites including proline and sugars. Transcriptomic analysis suggests that this results from differential expression of genes in the vascular tissues. Altogether, this data suggests that manipulating BRL3 expression could be used to engineer drought tolerant crops.


Assuntos
Arabidopsis/fisiologia , Secas , Desenvolvimento Vegetal , Feixe Vascular de Plantas/metabolismo , Receptores de Superfície Celular/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Metaboloma , Mutação/genética , Pressão Osmótica , Desenvolvimento Vegetal/genética , Raízes de Plantas/genética , Raízes de Plantas/fisiologia , Plantas Geneticamente Modificadas , Estresse Fisiológico/genética , Transcrição Genética , Tropismo
15.
Clin Epigenetics ; 10(1): 141, 2018 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413173

RESUMO

BACKGROUND: Altered methylation patterns are driving forces in colorectal carcinogenesis. The serrated adenocarcinoma (SAC) and sporadic colorectal carcinoma showing histological and molecular features of microsatellite instability (hmMSI-H) are two endpoints of the so-called serrated pathological route sharing some characteristics but displaying a totally different immune response and clinical outcome. However, there are no studies comparing the methylome of these two subtypes of colorectal carcinomas. The methylation status of 450,000 CpG sites using the Infinium Human Methylation 450 BeadChip array was investigated in 48 colorectal specimens, including 39 SACs and 9 matched hmMSI-H. RESULTS: Microarray data comparing SAC and hmMSI-H showed an enrichment in functions related to morphogenesis, neurogenesis, cytoskeleton, metabolism, vesicle transport and immune response and also significant differential methylation of 1540 genes, including CD14 and HLA-DOA which were more methylated in hmMSI-H than in SAC and subsequently validated at the CpG, mRNA and protein level using pyrosequencing, quantitative polymerase chain reaction (qPCR) and immunohistochemistry. CONCLUSIONS: These results demonstrate particular epigenetic regulation patterns in SAC which may help to define key molecules responsible for the characteristic weak immune response of SAC and identify potential targets for treating SAC, which lacks molecular targeted therapy.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Metilação de DNA , Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Ilhas de CpG , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade
16.
Aliment Pharmacol Ther ; 48(8): 839-851, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30281832

RESUMO

BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Sistema de Registros , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doenças Transmissíveis/induzido quimicamente , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/epidemiologia , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Feminino , Seguimentos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Espanha/epidemiologia , Resultado do Tratamento
17.
Biomaterials ; 186: 8-21, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30278346

RESUMO

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.


Assuntos
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
18.
Data Brief ; 20: 1500-1509, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30258954

RESUMO

Benzo(a)pyrene (BaP), the prototype of polycyclic aromatic hydrocarbons, is known to exhibits genotoxic and carcinogenic effects promoting molecular impacts. The dataset presented here is associated with the research article paper entitled "Transcriptome Analysis Reveals Novel Insights Into the Response of Low-dose Benzo(a)pyrene Exposure in Male Tilapia". In this article, we presented a transcriptomic characterization of male tilapia exposure to BaP in the short term. This data provides an extended analysis of changes in the gene expression and identification of pathways in the liver and testis of male tilapia exposure to BaP. We used gene set enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) to identify gene networks and pathways associated with molecular adverse effects of BaP exposure. The data indicates that target pathways related to promoting carcinogenesis such as DNA repair and DNA replication were affected as well as other crucial biological processes. Moreover, to determine whether some of the key reported genes of DNA damage are affected by BaP exposure, Quantitative PCR (qPCR) was performed. Gene set categories and sub-networks are provided and the corresponding signature differences from BaP exposure are listed. The information in these datasets may contribute to understanding the potential carcinogenesis mechanism of action from low BaP exposure.

19.
Genome Biol ; 19(1): 110, 2018 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-30097058

RESUMO

Single-cell RNAseq and alternative splicing studies have recently become two of the most prominent applications of RNAseq. However, the combination of both is still challenging, and few research efforts have been dedicated to the intersection between them. Cell-level insight on isoform expression is required to fully understand the biology of alternative splicing, but it is still an open question to what extent isoform expression analysis at the single-cell level is actually feasible. Here, we establish a set of four conditions that are required for a successful single-cell-level isoform study and evaluate how these conditions are met by these technologies in published research.


Assuntos
Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , Artefatos , Contagem de Células , Biologia Computacional , Simulação por Computador , Isoformas de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
Front Microbiol ; 9: 1359, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29988640

RESUMO

Stromatolites are organosedimentary build-ups that have formed as a result of the sediment trapping, binding and precipitating activities of microbes. Today, extant systems provide an ideal platform for understanding the structure, composition, and interactions between stromatolite-forming microbial communities and their respective environments. In this study, we compared the metagenomes of three prevalent stromatolite-forming microbial mat types in the Spaven Province of Hamelin Pool, Shark Bay located in Western Australia. These stromatolite-forming mat types included an intertidal pustular mat as well as a smooth and colloform mat types located in the subtidal zone. Additionally, the metagenomes of an adjacent, non-lithifying mat located in the upper intertidal zone were also sequenced for comparative purposes. Taxonomic and functional gene analyses revealed distinctive differences between the lithifying and non-lithifying mat types, which strongly correlated with water depth. Three distinct populations emerged including the upper intertidal non-lithifying mats, the intertidal pustular mats associated with unlaminated carbonate build-ups, and the subtidal colloform and smooth mat types associated with laminated structures. Functional analysis of metagenomes revealed that amongst stromatolite-forming mats there was an enrichment of photosynthesis pathways in the pustular stromatolite-forming mats. In the colloform and smooth stromatolite-forming mats, however, there was an increase in the abundance of genes associated with those heterotrophic metabolisms typically associated with carbonate mineralization, such as sulfate reduction. The comparative metagenomic analyses suggest that stromatolites of Hamelin Pool may form by two distinctive processes that are highly dependent on water depth. These results provide key insight into the potential adaptive strategies and synergistic interactions between microbes and their environments that may lead to stromatolite formation and accretion.

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