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1.
Genome Biol ; 21(1): 298, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33292397

RESUMO

STARR-seq technology has employed progressively more complex genomic libraries and increased sequencing depths. An issue with the increased complexity and depth is that the coverage in STARR-seq experiments is non-uniform, overdispersed, and often confounded by sequencing biases, such as GC content. Furthermore, STARR-seq readout is confounded by RNA secondary structure and thermodynamic stability. To address these potential confounders, we developed a negative binomial regression framework for uniformly processing STARR-seq data, called STARRPeaker. Moreover, to aid our effort, we generated whole-genome STARR-seq data from the HepG2 and K562 human cell lines and applied STARRPeaker to comprehensively and unbiasedly call enhancers in them.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33156795

RESUMO

An approximate logic neural model (ALNM) is a novel single-neuron model with plastic dendritic morphology. During the training process, the model can eliminate unnecessary synapses and useless branches of dendrites. It will produce a specific dendritic structure for a particular task. The simplified structure of ALNM can be substituted by a logic circuit classifier (LCC) without losing any essential information. The LCC merely consists of the comparator and logic \textscnot, and, and \textscor gates. Thus, it can be easily implemented in hardware. However, the architecture of ALNM affects the learning capacity, generalization capability, computing time and approximation of LCC. Thus, a Pareto-based multiobjective differential evolution (MODE) algorithm is proposed to simultaneously optimize ALNM's topology and weights. MODE can generate a concise and accurate LCC for every specific task from ALNM. To verify the effectiveness of MODE, extensive experiments are performed on eight benchmark classification problems. The statistical results demonstrate that MODE is superior to conventional learning methods, such as the backpropagation algorithm and single-objective evolutionary algorithms. In addition, compared against several commonly used classifiers, both ALNM and LCC are capable of obtaining promising and competitive classification performances on the benchmark problems. Besides, the experimental results also verify that the LCC obtains the faster classification speed than the other classifiers.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33129735

RESUMO

OBJECTIVES: This study sought to investigate nonculprit plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI) presenting with plaque erosion (PE) and plaque rupture (PR). Pancoronary vulnerability was considered at nonculprit sites: 1) the CLIMA study (NCT02883088) defined high-risk plaques with simultaneous presence of 4 optical coherence tomography (OCT) features (minimum lumen area <3.5 mm2; fibrous cap thickness [FCT] <75 µm; maximum lipid arc >180º; and macrophage accumulation); and 2) the presence of plaque ruptures or thin-cap fibroatheromas (TCFA). BACKGROUND: PE is a unique clinical entity associated with better outcomes than PR. There is limited evidence regarding pancoronary plaque characteristics of patients with culprit PE versus culprit PR. METHODS: Between October 2016 and September 2018, 523 patients treated by 3-vessel OCT at the time of primary percutaneous intervention were included with 152 patients excluded from final analysis. RESULTS: Overall, 458 nonculprit plaques were identified in 202 STEMI patients with culprit PE; and 1,027 nonculprit plaques were identified in 321 STEMI patients with culprit PR. At least 1 CLIMA-defined OCT nonculprit high-risk plaque was seen in 11.4% of patients with culprit PE, but twice as many patients were seen with culprit PR (25.2%; p < 0.001). This proportion was also seen when individual high-risk features were analyzed separately. When patients with PE were divided by a heterogeneous substrate (fibrous or lipid-rich plaque) underlying the culprit site, the prevalence of nonculprits with FCT <75 µm, macrophages, and TCFA showed a significant gradient from PE(Fibrous) to PElipid-rich plaque (LRP) to PR. Interestingly, nonculprit rupture was rarely found in patients with culprit PE(Fibrous) (1.9%), although it was exhibited with comparable prevalence in patients with culprit PE(LRP) (16.3%) versus PR (17.8%). Culprit PE predicted decreased pancoronary vulnerability independent of conventional risk factors. CONCLUSIONS: STEMI patients with culprit PE have a limited pancoronary vulnerability that may explain better outcomes in these patients than in STEMI patients with culprit PR.

4.
EuroIntervention ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33164894

RESUMO

AIMS: To test whether a non-stenting anti-thrombotic strategy was still effective at 4-year follow-up in patients enrolled in the EROSION study and to explore potential predictors of long-term prognosis. METHODS AND RESULTS: Out of 55 patients who completed 1-month follow-up, 52 patients finished 4-year follow-up. The median duration was 4.8 years (4.2 - 5.8 years). The majority of patients remained free from events, and all patients were free from hard endpoints (death, myocardial infarction, stroke, bypass surgery, or heart failure). Only 1 patient had gastrointestinal bleeding, and 11 patients underwent elective target lesion revascularization (TLR). Patients in the non-TLR group had more optical coherence tomography (OCT) thrombus reduction from baseline to 1 month; 95% patients in the non-TLR group versus 45% in the TLR group (p=0.001) met the primary endpoint (thrombus volume reduction >50%). Consistent with the OCT findings, angiographic results showed that the TLR group had less improvement in diameter stenosis (p=0.014) at 1 month compared with non-TLR group. CONCLUSIONS: Four-year follow-up findings reconfirmed the safety of an anti-thrombotic therapy without stenting for erosion-caused acute coronary syndrome. Patients with better response to anti-thrombotic therapy in the first month were less likely to require stent implantation during the next four years.

5.
Cancer Res ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33093168

RESUMO

T cell exhaustion was initially identified in chronic infection in mice and was subsequently described in humans with cancer. Although the distinct signature of exhausted T cells in cancer has been well investigated, the molecular mechanism of T cell exhaustion in cancer is not fully understood. Using single-cell RNA sequencing, we report here that exhausted T cells in esophageal cancer were more heterogeneous than previously clarified. SPRY1 was notably enriched in two subsets of exhausted CD8+ T cells. When overexpressed, SPRY1 impaired T cell activation by interacting with CBL, a negative regulator of ZAP-70 tyrosine phosphorylation. Data from the Tumor Immune Estimation Resource revealed a strong correlation between FGF2 and SPRY1 expression in esophageal cancer. High expression of FGF2 was evident in fibroblasts from esophageal cancer tissue and correlated with poor overall survival. In vitro administration of FGF2 significantly upregulated expression of SPRY1 in CD8+ T cells and attenuated TCR-triggered CD8+ T cell activation. A mouse tumor model confirmed that overexpression of FGF2 in fibroblasts significantly upregulated SPRY1 expression in exhausted T cells, impaired T cell cytotoxic activity, and promoted tumor growth. Thus, these findings identify FGF2 as an important regulator of SPRY1 expression involved in establishing the dysfunctional state of CD8+ T cells in esophageal cancer.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32989612

RESUMO

Local factors of plaque rupture (e.g. lipid burden) are related to preprocedural thrombolysis in myocardial infarction (TIMI) flow grade during primary percutaneous coronary intervention (PCI). However, the pathological mechanism differs between plaque erosion and rupture. We aimed to identify the factors associated with reduced TIMI flow in plaque erosion. A total of 329 ST-segment elevation myocardial infarction (STEMI) patients with optical coherence tomography (OCT) identified plaque erosion were divided into 2 groups by preprocedural TIMI flow grade [TIMI 0-1 group (n = 219) and TIMI 2-3 group (n = 110)]. Patients in TIMI 0-1 group were older (age > 50 years, 68.5% vs. 51.8%, P = 0.003), and had more diabetes mellitus (18.3% vs. 8.2%, P = 0.015). Plaque erosion with TIMI flow 0-1 was less frequently located in the left anterior descending artery (LAD, 58.4% vs. 72.7%, P = 0.011), but more frequently located in the right coronary artery (RCA, 34.2% vs. 7.3%, P = 0.001) than those with TIMI flow 2-3. TIMI 0-1 group had more lipid plaques (53.9% vs. 41.8%, P = 0.039), macrophage accumulation (59.8% vs. 41.8%, P = 0.002), and calcification (34.2% vs. 21.8%, P = 0.020). In the multivariable analysis, age > 50 years, diabetes mellitus, RCA location, and macrophage accumulation were the independent predictors of reduced TIMI flow grade in STEMI patients with plaque erosion. Systemic factors (older age and diabetes mellitus) and local factors (RCA location and macrophage accumulation) were independently associated with reduced coronary flow in STEMI patients with plaque erosion. CLINICAL TRIAL REGISTRATION : ClinicalTrials.gov NCT03084991 May 17, 2017 (retrospectively registered).

7.
Circ Cardiovasc Interv ; 13(10): e009125, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32957793

RESUMO

BACKGROUND: Subclinical atherothrombosis and plaque healing may lead to rapid plaque progression. The histopathologic healed plaque has a layered appearance when imaged using optical coherence tomography. We assessed the frequency, predictors, distribution, and morphological characteristics of optical coherence tomography layered culprit and nonculprit plaques in patients with acute myocardial infarction. METHODS: A prospective series of 325 patients with acute myocardial infarction underwent optical coherence tomography imaging of all 3 native coronary arteries. Layered plaque phenotype had heterogeneous signal-rich layered tissue located close to the luminal surface that was clearly demarcated from the underlying plaque. RESULTS: Layered plaques were detected in 74.5% of patients with acute myocardial infarction. Patients with layered culprit plaques had more layered nonculprit plaques; and they more often had preinfarction angina, ST-segment-elevation myocardial infarction, higher low-density lipoprotein cholesterol, and absence of antiplatelet therapy. Layered plaques tended to cluster in the proximal segment of the left anterior descending artery and left circumflex artery but were more uniformly distributed in the right coronary artery. As compared with nonlayered plaques, layered plaques had greater optical coherence tomography lumen area stenosis at both culprit and nonculprit sites. The frequency of layered plaque phenotype (P=0.038) and maximum area of layered tissue (P<0.001) increased from nonculprit thin-cap fibroatheromas to nonculprit ruptures to culprit ruptures. CONCLUSIONS: Layered plaques were identified in 3-quarters of patients with acute myocardial infarction, especially in the culprit plaques of patients with ST-segment-elevation myocardial infarction. Layered plaques had a limited, focal distribution in the left anterior descending artery, and left circumflex artery but were more evenly distributed in the right coronary artery and were characterized by greater lumen narrowing at both culprit and nonculprit sites. Graphic Abstract: A graphic abstract is available for this article.

8.
Nat Commun ; 11(1): 3696, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728046

RESUMO

ENCODE comprises thousands of functional genomics datasets, and the encyclopedia covers hundreds of cell types, providing a universal annotation for genome interpretation. However, for particular applications, it may be advantageous to use a customized annotation. Here, we develop such a custom annotation by leveraging advanced assays, such as eCLIP, Hi-C, and whole-genome STARR-seq on a number of data-rich ENCODE cell types. A key aspect of this annotation is comprehensive and experimentally derived networks of both transcription factors and RNA-binding proteins (TFs and RBPs). Cancer, a disease of system-wide dysregulation, is an ideal application for such a network-based annotation. Specifically, for cancer-associated cell types, we put regulators into hierarchies and measure their network change (rewiring) during oncogenesis. We also extensively survey TF-RBP crosstalk, highlighting how SUB1, a previously uncharacterized RBP, drives aberrant tumor expression and amplifies the effect of MYC, a well-known oncogenic TF. Furthermore, we show how our annotation allows us to place oncogenic transformations in the context of a broad cell space; here, many normal-to-tumor transitions move towards a stem-like state, while oncogene knockdowns show an opposing trend. Finally, we organize the resource into a coherent workflow to prioritize key elements and variants, in addition to regulators. We showcase the application of this prioritization to somatic burdening, cancer differential expression and GWAS. Targeted validations of the prioritized regulators, elements and variants using siRNA knockdowns, CRISPR-based editing, and luciferase assays demonstrate the value of the ENCODE resource.


Assuntos
Bases de Dados Genéticas , Genômica , Neoplasias/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Redes Reguladoras de Genes , Humanos , Mutação/genética , Reprodutibilidade dos Testes , Fatores de Transcrição/metabolismo
9.
Genome Biol ; 21(1): 136, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513233

RESUMO

CRISPR-based genome perturbation provides a new avenue to conveniently change DNA sequences, transcription, and epigenetic modifications in genetic screens. However, it remains challenging to assay the complex molecular readouts after perturbation at high resolution and at scale. By introducing an A/G mixed capture sequence into the gRNA scaffold, we demonstrate that gRNA transcripts could be directly reverse transcribed by poly (dT) primer together with the endogenous mRNA, followed by high-content molecular phenotyping in scRNA-seq (Direct-seq). With this method, the CRISPR perturbation and its transcriptional readouts can be profiled together in a streamlined workflow.

10.
J Clin Invest ; 130(6): 3005-3020, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32364535

RESUMO

Transcriptional reactivation of telomerase catalytic subunit (TERT) is a frequent hallmark of cancer, occurring in 90% of human malignancies. However, specific mechanisms driving TERT reactivation remain obscure for many tumor types and in particular gastric cancer (GC), a leading cause of global cancer mortality. Here, through comprehensive genomic and epigenomic analysis of primary GCs and GC cell lines, we identified the transcription factor early B cell factor 1 (EBF1) as a TERT transcriptional repressor and inactivation of EBF1 function as a major cause of TERT upregulation. Abolishment of EBF1 function occurs through 3 distinct (epi)genomic mechanisms. First, EBF1 is epigenetically silenced via DNA methyltransferase, polycomb-repressive complex 2 (PRC2), and histone deacetylase activity in GCs. Second, recurrent, somatic, and heterozygous EBF1 DNA-binding domain mutations result in the production of dominant-negative EBF1 isoforms. Third, more rarely, genomic deletions and rearrangements proximal to the TERT promoter remobilize or abolish EBF1-binding sites, derepressing TERT and leading to high TERT expression. EBF1 is also functionally required for various malignant phenotypes in vitro and in vivo, highlighting its importance for GC development. These results indicate that multimodal genomic and epigenomic alterations underpin TERT reactivation in GC, converging on transcriptional repressors such as EBF1.

11.
Nat Chem Biol ; 16(8): 887-895, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32341503

RESUMO

Transcriptome-wide mapping of N6-methyladenosine (m6A) at base resolution remains an issue, impeding our understanding of m6A roles at the nucleotide level. Here, we report a metabolic labeling method to detect mRNA m6A transcriptome-wide at base resolution, called 'm6A-label-seq'. Human and mouse cells could be fed with a methionine analog, Se-allyl-L-selenohomocysteine, which substitutes the methyl group on the enzyme cofactor SAM with the allyl. Cellular RNAs could therefore be metabolically modified with N6-allyladenosine (a6A) at supposed m6A-generating adenosine sites. We pinpointed the mRNA a6A locations based on iodination-induced misincorporation at the opposite site in complementary DNA during reverse transcription. We identified a few thousand mRNA m6A sites in human HeLa, HEK293T and mouse H2.35 cells, carried out a parallel comparison of m6A-label-seq with available m6A sequencing methods, and validated selected sites by an orthogonal method. This method offers advantages in detecting clustered m6A sites and holds promise to locate nuclear nascent RNA m6A modifications.


Assuntos
Adenosina/análogos & derivados , Perfilação da Expressão Gênica/métodos , Adenosina/análise , Animais , Linhagem Celular , Células HEK293 , Células HeLa , Humanos , Metilação , Camundongos , RNA/genética , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , Transcriptoma/genética
12.
Artigo em Inglês | MEDLINE | ID: mdl-32305933

RESUMO

The global alignment of biological networks (GABN) aims to find an optimal alignment between proteins across species, such that both the biological structures and the topological structures of the proteins are maximally conserved. The research on GABN has attracted great attention due to its applications on species evolution, orthology detection and genetic analyses. Most of the existing methods for GABN are difficult to obtain a good tradeoff between the conservation of the biological structures and topological structures. In this paper, we propose a multi-neighborhood learning method for solving GABN (called as CLMNA). CLMNA first models GABN as an optimization of a weighted similarity which evaluates the conserved biological and topological similarities of an alignment, and then it combines a first-proximity, second-proximity and individual-aware proximity learning algorithm to solve the modeled problem. Finally, systematic experiments on 10 pairs of biological networks across 5 species show the superiority of CLMNA over the state-of-the-art network alignment algorithms. They also validate the effectiveness of CLMNA as a refinement method on improving the performance of the compared algorithms.

13.
IEEE Trans Cybern ; 50(10): 4430-4443, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31581105

RESUMO

The robust controllability (RC) of a complex system tries to select a set of dominating entities for the functional control of this entire system without uncertain disturbances, and the research on RC will help to understand the system's underlying functions. In this article, we introduce the control cost in signed networks and present a cost-aware robust control (CRC) problem in this scenario. The aim of CRC is to minimize the cost to control a set of dominating nodes and transform a set of unbalanced links into balanced ones, such that the signed network can be robustly controlled without uncertain unbalanced factors (like nodes and links). To solve this problem, we first model CRC as a constrained combination optimization problem, and then present a memetic algorithm with some problem-specific knowledge (like the neighbors of nodes, the constraints of CRC, and the fast computation of the cost under each optimization) to solve this problem on signed networks. The extensive experiments on both real social and biological networks assess that our algorithm outperforms several state-of-the-art RC algorithms.

15.
Atherosclerosis ; 289: 94-100, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31487565

RESUMO

BACKGROUND AND AIMS: About 20% of patients with ST-segment elevated myocardial infarction (STEMI) are young adults. Morphological characteristics of culprit lesion in young STEMI patients have not been systematically evaluated in vivo. The present study aimed to investigate culprit lesion characteristics in young patients versus older patients using optical coherence tomography (OCT). METHODS: 1442 STEMI patients who underwent OCT examination of culprit lesion were included and divided into young group (age ≤50 years, n = 400) and older group (age >50 years, n = 1042). Clinical characteristics, angiography and OCT findings were compared between the two groups. RESULTS: Culprit lesions in STEMI patients aged ≤50 years had more plaque erosion (32.0% vs. 21.1%, p < 0.001) and larger minimal lumen area (2.3 ±â€¯1.7 mm2vs. 1.9 ±â€¯1.1 mm2, p < 0.001) than in those aged >50 years. As compared with older patients, lipid rich plaque (80.5% vs. 87.2%, p = 0.001), thin cap fibroatheroma (TCFA, 59.5% vs. 69.5%, p < 0.001), calcification (31.3% vs. 48.7%, p < 0.001), spotty calcification (25.3% vs. 36.1%, p < 0.001) and cholesterol crystals (26.3% vs. 38.4%, p < 0.001) were less frequently observed in young patients. A gradient increase in typical plaque vulnerability was observed from age ≤50 years to 50-70 years to >70 years. In multivariate regression analysis, age ≤50 years was independently associated with less frequency of plaque rupture, TCFA, spotty calcification, cholesterol crystals and smaller lumen area stenosis. CONCLUSIONS: Morphological characteristics of culprit lesion in young STEMI patients were different from those in older patients. Patients aged ≤50 years had more plaque erosion and less vulnerable plaque features.


Assuntos
Angiografia Coronária , Coração/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Tomografia de Coerência Óptica , Adulto , Idoso , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nitroglicerina/farmacologia , Estudos Prospectivos , Fatores de Risco
16.
Nat Commun ; 10(1): 1898, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015515

RESUMO

N6-methyladenosine (m6A) modification plays important roles in various cellular responses by regulating mRNA biology. However, how m6A modification is involved in innate immunity via affecting the translation of immune transcripts remains to be further investigated. Here we report that RNA methyltransferase Mettl3-mediated mRNA m6A methylation promotes dendritic cell (DC) activation and function. Specific depletion of Mettl3 in DC resulted in impaired phenotypic and functional maturation of DC, with decreased expression of co-stimulatory molecules CD40, CD80 and cytokine IL-12, and reduced ability to stimulate T cell responses both in vitro and in vivo. Mechanistically, Mettl3-mediated m6A of CD40, CD80 and TLR4 signaling adaptor Tirap transcripts enhanced their translation in DC for stimulating T cell activation, and strengthening TLR4/NF-κB signaling-induced cytokine production. Our findings identify a new role for Mettl3-mediated m6A modification in increasing translation of certain immune transcripts for physiological promotion of DC activation and DC-based T cell response.


Assuntos
Adenosina/análogos & derivados , Células Dendríticas/imunologia , Epigênese Genética , Metiltransferases/genética , RNA Mensageiro/genética , Linfócitos T/imunologia , Adenosina/imunologia , Adenosina/metabolismo , Sequência de Aminoácidos , Animais , Antígenos/imunologia , Antígenos/farmacologia , Antígeno B7-1/genética , Antígeno B7-1/imunologia , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Antígenos CD40/genética , Antígenos CD40/imunologia , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Interleucina-12/genética , Interleucina-12/imunologia , Ativação Linfocitária , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Metilação , Metiltransferases/imunologia , Camundongos , Camundongos Transgênicos , NF-kappa B/genética , NF-kappa B/imunologia , Peptídeos/imunologia , Peptídeos/farmacologia , Cultura Primária de Células , Biossíntese de Proteínas , RNA Mensageiro/imunologia , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/imunologia , Transdução de Sinais , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia
17.
Front Neurosci ; 13: 1408, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31992969

RESUMO

Different from conventional single-task optimization, the recently proposed multitasking optimization (MTO) simultaneously deals with multiple optimization tasks with different types of decision variables. MTO explores the underlying similarity and complementarity among the component tasks to improve the optimization process. The well-known multifactorial evolutionary algorithm (MFEA) has been successfully introduced to solve MTO problems based on transfer learning. However, it uses a simple and random inter-task transfer learning strategy, thereby resulting in slow convergence. To deal with this issue, this paper presents a two-level transfer learning (TLTL) algorithm, in which the upper-level implements inter-task transfer learning via chromosome crossover and elite individual learning, and the lower-level introduces intra-task transfer learning based on information transfer of decision variables for an across-dimension optimization. The proposed algorithm fully uses the correlation and similarity among the component tasks to improve the efficiency and effectiveness of MTO. Experimental studies demonstrate the proposed algorithm has outstanding ability of global search and fast convergence rate.

18.
Methods ; 156: 85-90, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30471344

RESUMO

The post-transcriptional modification 2'-O-Methyl (2'OMe) could be present on the ribose of all four ribonucleosides, and is highly prevalent in a wide variety of RNA species, including the 5' RNA cap of viruses and higher eukaryotes, as well as internally in transfer RNA and ribosomal RNA. Recent studies have suggested that 2'OMe is also located internally in low-abundance RNA species such as viral RNA and mRNA. To profile 2'OMe on different RNA species, we have developed Nm-seq, which could identify 2'OMe sites at single base resolution. Nm-seq is particularly useful for identifying 2'OMe sites located at the 3' terminal ends of small RNAs. Here, we present an optimized protocol for Nm-seq and a protocol for applying Nm-seq to identify 2'OMe sites on small RNA 3' terminal ends.


Assuntos
MicroRNAs/genética , Anotação de Sequência Molecular/métodos , Poli A/genética , RNA Mensageiro/genética , Região 3'-Flanqueadora , Arabidopsis/genética , Arabidopsis/metabolismo , Sequência de Bases , Biblioteca Gênica , Humanos , Hidrólise , Metilação , MicroRNAs/metabolismo , Oxirredução , Fosforilação , Poli A/metabolismo , RNA Mensageiro/metabolismo , Ribose/metabolismo , Plântula/genética , Plântula/metabolismo
19.
IEEE Trans Cybern ; 49(9): 3347-3361, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30176616

RESUMO

Complex systems are often characterized by complex networks with links and entities. However, in many complex systems such as protein-protein interaction networks, recommender systems, and online communities, their links are hard to reveal directly, but they can be inaccurately observed by multiple data collection platforms or by a data collection platform at different times. Then, the links of the systems are inferred by the integration of the collected observations. As those data collection platforms are usually distributed over a large area and in different fields, their observations are unreliable and sensitive to the potential structures of the systems. In this paper, we consider the link inference problem in network data with community structures, in which the reliability of data collection platforms is unknown a priori and the link errors and reliability of platforms' observations are heterogeneous to the underlying community structures of the systems. We propose an expectation maximization algorithm for link inference in a network system with community structures (EMLIC). The EMLIC algorithm is also used to infer the link errors and reliability of platforms' observations in different communities. Experimental results on both synthetic data and eight real-world network data demonstrate that our algorithm is able to achieve lower link errors than the existing reliable link inference algorithms when the network data have community structures.

20.
Biochem Biophys Res Commun ; 505(1): 242-248, 2018 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-30243718

RESUMO

In diabetic cardiomyopathy, mitochondrial fatty acid oxidation dominates over mitochondrial glucose oxidation, leading to metabolic disturbances. Fibroblast growth factor 19 (FGF19) acts as a metabolic regulator and may have a cardioprotective role on diabetic cardiomyopathy. In this study, we investigated the effects of FGF19 on energy metabolism. FGF19 treatment of diabetic hearts exhibited higher glucose uptake and lower lipid profiles, suggesting changes in energy metabolism. The protective effects of FGF19 prevented ventricular dysfunction in diabetic hearts and improved mitochondrial function by the upregulation of PGC-1α expression. On the other side, knockdown of PGC-1α by siRNA attenuated the effects of FGF19 on the enhancement of mitochondrial function and energy efficiency. Taken together, these results show that FGF19 exhibited improved mitochondrial efficiency, which might be associated with higher cardiac contractility in diabetic hearts. It is also of note that modulation of PGC-1α, which is responsible for the activation by FGF19, may be a therapeutic target for diabetic cardiomyopathy.


Assuntos
Cardiomiopatias Diabéticas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/farmacologia , Coração/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Animais , Células Cultivadas , Cardiomiopatias Diabéticas/fisiopatologia , Fatores de Crescimento de Fibroblastos/administração & dosagem , Coração/fisiopatologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Interferência de RNA , Ratos Sprague-Dawley
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