Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Filtros adicionais











País/Região como assunto
Intervalo de ano
1.
Talanta ; 205: 120133, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450408

RESUMO

Timely and effective detection of bacterial pathogens is of great importance to reduce morbidity rates from bacterial infections. Recently, enzyme-activated fluorogenic probes, which invoke enzymatic catalysis to trigger fluorescence emission, have been superior sensors for bacterial infections needed for accurate diagnoses. Here, a fluorescent sensor for nitroreductase (NTR) detection is described. It is based on a cyanine fluorophore and utilizes photoinduced electron transfer to generate a rapid 10-fold fluorescence response after being catalytically reduced by NTR. It has enabled selective and sensitive visualization of NTR activity in vitro and in living bacterial pathogens. Thus, the probe has great potential to provide a rapid, noninvasive tool to diagnose infections and guide antimicrobial selection.

2.
Cell Rep ; 28(1): 78-90.e6, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269452

RESUMO

RNA binding proteins, the key regulators in gene expression at the posttranscriptional level, remain largely uncharacterized with respect to aging and relevant cognitive deterioration. Here, we report that the levels of SFRS11 are substantially decreased in the prefrontal cortex (PFC) of aged brains. Notably, mice with SFRS11 deficiency in the PFC show impaired learning and memory. We demonstrate that SFRS11 directly binds to the 3' UTR of LRP8 mRNA, as well as to the third exon of apoE mRNA, resulting in stabilization of these mRNAs, eventually deactivating JNK signaling. Importantly, restoration of LRP8 and apoE reduces JNK signaling that is significantly enhanced in SFRS11-deficient cells. In addition, LRP8 and apoE rescue aging-like phenotypes induced by SFRS11 loss. Our findings demonstrate that age-dependent loss of SFRS11 in the PFC reduces levels of apoE and LRP8, leading to activation of the JNK pathway, ultimately influencing cognitive deficits.

3.
PLoS One ; 14(5): e0217463, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150453

RESUMO

Feature screening has become a real prerequisite for the analysis of high-dimensional genomic data, as it is effective in reducing dimensionality and removing redundant features. However, existing methods for feature screening have been mostly relying on the assumptions of linear effects and independence (or weak dependence) between features, which might be inappropriate in real practice. In this paper, we consider the problem of selecting continuous features for a categorical outcome from high-dimensional data. We propose a powerful statistical procedure that consists of two steps, a nonparametric significance test based on edge count and a multiple testing procedure with dependence adjustment for false discovery rate control. The new method presents two novelties. First, the edge-count test directly targets distributional difference between groups, therefore it is sensitive to nonlinear effects. Second, we relax the independence assumption and adapt Efron's procedure to adjust for the dependence between features. The performance of the proposed procedure, in terms of statistical power and false discovery rate, is illustrated by simulated data. We apply the new method to three genomic datasets to identify genes associated with colon, cervical and prostate cancers.

5.
Chem Commun (Camb) ; 55(35): 5064-5067, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-30896004
6.
J Am Chem Soc ; 141(12): 4861-4869, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30816046

RESUMO

Characterizing doping effects in a conductive polymer and physical diffusion in a passive polymer were performed using a remote-gate field-effect transistor (RG FET) detection system that was able to measure the electrical potential perturbation of a polymer film coupled to the gate of a silicon FET. Poly(3-hexylthiophene) (P3HT) film doped using various concentrations of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) solutions imposed additional positive potentials on the P3HT RG, resulting in a lower threshold voltage ( Vth) on the n-channel silicon FET. Changes in Vth were related to the induced hole concentrations and hole mobility in P3HT films by using our Vth shifting model for the RG FET. We discovered that the electron-donating P3HT and even inorganic materials, indium tin oxide and gold, showed similar electrical potential perturbations dependent on the concentration of F4TCNQ in overlying solutions as the dopant radical anions maximally covered the surfaces. This suggests that there are limited electroactive sites for F4TCNQ binding on electron donor surfaces which results in a similar number of positive charges in film materials forming dipoles with the F4TCNQ radical counteranions. The effect of electron acceptors such as 7,7,8,8-tetracyanoquinodimethane and tetracyanoethylene was compared to that of F4TCNQ in terms of Vth shift using our analytical tool, with differences attributed to acceptor size and reduction potential. Meanwhile, this FET analysis tool offered a means of monitoring the physical diffusion of small molecules, exemplified by F4TCNQ, in the passive polymer polystyrene, driven by concentration gradients. The technique allows for nondestructive, nonspectroscopic, ambient characterization of electron donor-acceptor interactions at surfaces.

7.
Org Lett ; 21(7): 2121-2125, 2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30860384

RESUMO

A range of γ-halide/pseudohalide-substituted cyanine-based photosensitizers with programmed levels of singlet oxygen generation capability have been developed as theranostic agents for photodynamic therapy of cancer and infectious diseases.

8.
J Org Chem ; 84(3): 1299-1309, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30589544

RESUMO

Enzyme-activated fluorogenic probes, which invoke enzymatic catalysis to trigger the generation of fluorescence, provide a versatile platform for monitoring biological processes. The development of fluorogenic probes that can readily penetrate the cell envelopes of bacteria are essential to examine intracellular targets of live bacterial cells. Herein, we present the design, synthesis, properties, and biological applications of two series of fluorogenic probes based on cyanine 5 for identification of bacterial nitroreductase (NTR). The selected fluorogenic probe 3 generates a rapid 10-fold fluorescence response after being catalytically reduced by NTR to the intermediate para-aminobenzyl substituted which then underwent a rearrangement elimination reaction. Moreover, probe 3 is cell permeable for both Gram-positive and Gram-negative bacterial cell envelopes and is selective for NTR over other biological analytes, thus minimizing the background signal and enabling the real-time intracellular imaging of NTR in live bacterial cells.

9.
Cell Res ; 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30514900

RESUMO

While N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, is linked to cell differentiation and tissue development, the biological significance of m6A modification in mammalian glial development remains unknown. Here, we identify a novel m6A reader, Prrc2a (Proline rich coiled-coil 2 A), which controls oligodendrocyte specification and myelination. Nestin-Cre-mediated knockout of Prrc2a induces significant hypomyelination, decreased lifespan, as well as locomotive and cognitive defects in a mouse model. Further analyses reveal that Prrc2a is involved in oligodendrocyte progenitor cells (OPCs) proliferation and oligodendrocyte fate determination. Accordingly, oligodendroglial-lineage specific deletion of Prrc2a causes a similar phenotype of Nestin-Cre-mediated deletion. Combining transcriptome-wide RNA-seq, m6A-RIP-seq and Prrc2a RIP-seq analysis, we find that Olig2 is a critical downstream target gene of Prrc2a in oligodendrocyte development. Furthermore, Prrc2a stabilizes Olig2 mRNA through binding to a consensus GGACU motif in the Olig2 CDS (coding sequence) in an m6A-dependent manner. Interestingly, we also find that the m6A demethylase, Fto, erases the m6A modification of Olig2 mRNA and promotes its degradation. Together, our results indicate that Prrc2a plays an important role in oligodendrocyte specification through functioning as a novel m6A reader. These findings suggest a new avenue for the development of therapeutic strategies for hypomyelination-related neurological diseases.

10.
BMC Syst Biol ; 12(1): 58, 2018 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-29769129

RESUMO

BACKGROUND: Differential co-expression analysis, as a complement of differential expression analysis, offers significant insights into the changes in molecular mechanism of different phenotypes. A prevailing approach to detecting differentially co-expressed genes is to compare Pearson's correlation coefficients in two phenotypes. However, due to the limitations of Pearson's correlation measure, this approach lacks the power to detect nonlinear changes in gene co-expression which is common in gene regulatory networks. RESULTS: In this work, a new nonparametric procedure is proposed to search differentially co-expressed gene pairs in different phenotypes from large-scale data. Our computational pipeline consisted of two main steps, a screening step and a testing step. The screening step is to reduce the search space by filtering out all the independent gene pairs using distance correlation measure. In the testing step, we compare the gene co-expression patterns in different phenotypes by a recently developed edge-count test. Both steps are distribution-free and targeting nonlinear relations. We illustrate the promise of the new approach by analyzing the Cancer Genome Atlas data and the METABRIC data for breast cancer subtypes. CONCLUSIONS: Compared with some existing methods, the new method is more powerful in detecting nonlinear type of differential co-expressions. The distance correlation screening can greatly improve computational efficiency, facilitating its application to large data sets.

11.
Genome Announc ; 6(16)2018 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-29674558

RESUMO

We present the genome sequence of Komagataeibacter maltaceti LMG 1529T, which is a vinegar-producing acetic acid bacterium. The draft genome sequence consists of 3.6 Mb and contains 3,225 predicted protein-encoding genes. In addition, 53 genes encoding potential oxidoreductases were identified.

12.
Anal Chem ; 90(3): 1934-1940, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29293308

RESUMO

Magnetic resonance imaging (MRI) is a powerful diagnostic technique that can penetrate deep into tissue providing excellent spatial resolution without the need for ionizing radiation or harmful radionuclides. However, diagnosing bacterial infections in vivo with clinical MRI is severely hampered by the lack of contrast agents with high relaxivity, targeting capabilities, and bacterial penetration and specificity. Here, we report the development of the first gadolinium (Gd)-based bacteria-specific targeting MRI contrast agent, probe 1, by conjugating neomycin, an aminoglycoside antibiotic, with Dotarem (Gd-DOTA, an FDA approved T1-weighted MRI contrast agent). The T1 relaxivity of probe 1 was found to be comparable to that of Gd-DOTA; additionally, probe 1-treated bacteria generated a significantly brighter T1-weighted MR signal than Gd-DOTA-treated bacteria. More importantly, in vitro cellular studies and preliminary in vivo MRI demonstrated probe 1 exhibits the ability to efficiently target bacteria over macrophage-like cells, indicating its great potential for high-resolution imaging of bacterial infections in vivo.

13.
Chem Commun (Camb) ; 53(81): 11177-11180, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-28953270

RESUMO

The identification of bacterial pathogens is the critical first step in conquering infection diseases. A novel turn-on fluorescent probe for the selective sensing of nitroreductase (NTR) activity and its initial applications in rapid, real-time detection and identification of ESKAPE pathogens have been reported.

14.
Org Lett ; 19(17): 4496-4499, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28819980

RESUMO

A series of novel fluorogenic dyes based on 3-indole-Malachite Green, MGs 5-7, have been developed that are dark in solution but highly fluorescent when bound to the cognate reporter, fluorogen-activating protein (FAP). Significantly, the new MGs 5-7 probes are superior to the traditional MG 1 with high fluorescent efficiency and low toxicity to cells while maintaining the large "pseudo-Stokes" shifts (Δλ = λex - λem) and the malachite green (MG)-like fluorescence OFF-ON switching mechanism in both live mammalian cells and bacterial cells when bound to FAP.


Assuntos
Corantes de Rosanilina/química , Animais , Corantes Fluorescentes , Indóis , Estrutura Molecular
15.
Cancer Inform ; 16: 1176935117702389, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28469391

RESUMO

Gaussian Bayesian networks have become a widely used framework to estimate directed associations between joint Gaussian variables, where the network structure encodes the decomposition of multivariate normal density into local terms. However, the resulting estimates can be inaccurate when the normality assumption is moderately or severely violated, making it unsuitable for dealing with recent genomic data such as the Cancer Genome Atlas data. In the present paper, we propose a mixture copula Bayesian network model which provides great flexibility in modeling non-Gaussian and multimodal data for causal inference. The parameters in mixture copula functions can be efficiently estimated by a routine expectation-maximization algorithm. A heuristic search algorithm based on Bayesian information criterion is developed to estimate the network structure, and prediction can be further improved by the best-scoring network out of multiple predictions from random initial values. Our method outperforms Gaussian Bayesian networks and regular copula Bayesian networks in terms of modeling flexibility and prediction accuracy, as demonstrated using a cell signaling data set. We apply the proposed methods to the Cancer Genome Atlas data to study the genetic and epigenetic pathways that underlie serous ovarian cancer.

16.
Chem Commun (Camb) ; 53(8): 1366-1369, 2017 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-27935615
17.
Cell Discov ; 2: 15046, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27462443

RESUMO

Specialized chromatin structures such as nucleosomes with specific histone modifications decorate exons in eukaryotic genomes, suggesting a functional connection between chromatin organization and the regulation of pre-mRNA splicing. Through profiling the functional location of Poly (ADP) ribose polymerase, we observed that it is associated with the nucleosomes at exon/intron boundaries of specific genes, suggestive of a role for this enzyme in alternative splicing. Poly (ADP) ribose polymerase has previously been implicated in the PARylation of splicing factors as well as regulation of the histone modification H3K4me3, a mark critical for co-transcriptional splicing. In light of these studies, we hypothesized that interaction of the chromatin-modifying factor, Poly (ADP) ribose polymerase with nucleosomal structures at exon-intron boundaries, might regulate pre-mRNA splicing. Using genome-wide approaches validated by gene-specific assays, we show that depletion of PARP1 or inhibition of its PARylation activity results in changes in alternative splicing of a specific subset of genes. Furthermore, we observed that PARP1 bound to RNA, splicing factors and chromatin, suggesting that Poly (ADP) ribose polymerase serves as a gene regulatory hub to facilitate co-transcriptional splicing. These studies add another function to the multi-functional protein, Poly (ADP) ribose polymerase, and provide a platform for further investigation of this protein's function in organizing chromatin during gene regulatory processes.

18.
Biomarkers ; 21(7): 578-88, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27133288

RESUMO

Bladder cancer (BC) is latent in its early stage and lethal in its late stage. Therefore, early diagnosis and intervention are essential for successful BC treatment. Considering the limitations of current diagnostic tools, noninvasive biomarkers that are both highly sensitive and specific are needed to improve the overall survival and quality of life of patients. With the advent of systems biology, "-omics" technologies have been developed over the past few decades. As a promising member, global metabolomics has increasingly been found to have clear potential for biomarker discovery. However, urinary metabolomics studies related to BC have lagged behind those of other urinary cancers, and major findings have not been systematically reported. The objective of this review is to comprehensively list the currently identified potential urinary metabolite biomarkers for BC.


Assuntos
Biomarcadores Tumorais , Metabolômica/métodos , Neoplasias da Bexiga Urinária/diagnóstico , Humanos , Masculino , Metaboloma , Sensibilidade e Especificidade
19.
Gynecol Endocrinol ; 32(7): 553-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26850117

RESUMO

OBJECTIVE: The aim of the present study was to analyze the genetic association between the three estrogen receptor 1 (ESR1) single nucleotide polymorphisms (SNPs; rs1062577, rs2881766, and rs9479118) and breast cancer risk in Han Chinese women. METHODS/MATERIALS: To investigate the possible association of genetic polymorphisms of any of the three ESR1 SNPs in breast cancer patients (n = 198) and healthy controls (n = 218) collected from the college hospital, peripheral blood mononuclear cells samples were analyzed by high-resolution melt-polymerase chain reaction. Odds ratios and 95% confidence intervals were used to evaluate the association between the ESR1 SNPs and breast cancer. RESULTS: Patients genotyped AA for ESR1 rs1062577 showed increased breast cancer risk (p = 0.005). In the menarche at ≤ 13-year-old group, there were significant differences in alleles A versus T at rs1062577 and alleles G versus T at rs2881766 between the breast cancer group and the control group. In the > 13-year-old group, the AA genotype at rs1062577, the GG genotype at rs2881766, and the CC genotype at rs9479118 increased breast cancer susceptibility. CONCLUSIONS: These results showed that the ESR1 rs1062577 polymorphism increased breast cancer risk in Han Chinese women, which might be used as a new SNP marker.


Assuntos
Neoplasias da Mama/genética , Receptor alfa de Estrogênio/genética , Menarca/genética , Adulto , China , Feminino , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
20.
Analyst ; 140(16): 5627-33, 2015 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-26134063

RESUMO

We herein report an ultralow background substrate for protein microarrays. Conventional protein microarray substrates often suffer from non-specific protein adsorption and inhomogeneous spot morphology. Consequently, surface treatment and a suitable printing solution are required to improve the microarray performance. In the current work, we improved the situation by developing a new microarray substrate based on a fluorinated ethylene propylene (FEP) membrane. A polydopamine microspot array was fabricated on the FEP membrane, with proteins conjugated to the FEP surface through polydopamine. Uniform microspots were obtained on FEP without the application of a special printing solution. The modified FEP membrane demonstrated ultralow background signal and was applied in protein and peptide microarray analysis.


Assuntos
Politetrafluoretileno/análogos & derivados , Análise Serial de Proteínas/métodos , Ensaio de Imunoadsorção Enzimática , Membranas Artificiais , Politetrafluoretileno/química , Análise Serial de Proteínas/tendências
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA