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1.
Genet Epidemiol ; 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31544985

RESUMO

In genetic association studies, joint modeling of related traits/phenotypes can utilize the correlation between them and thereby provide more power and uncover additional information about genetic etiology. Moreover, detecting rare genetic variants are of current scientific interest as a key to missing heritability. Logistic Bayesian LASSO (LBL) has been proposed recently to detect rare haplotype variants using case-control data, that is, a single binary phenotype. As there is currently no haplotype association method that can handle multiple binary phenotypes, we extend LBL to fill this gap. We develop a bivariate model by using a latent variable to induce correlation between the two outcomes. We carry out extensive simulations to investigate the bivariate LBL and compare with the univariate LBL. The bivariate LBL performs better or similar to the univariate LBL in most settings. It has the highest gain in power when a haplotype is associated with both traits and it affects at least one trait in a direction opposite to the direction of the correlation between the traits. We analyze two data sets-Genetic Analysis Workshop 19 sequence data on systolic and diastolic blood pressures and a genome-wide association data set on lung cancer and smoking and detect several associated rare haplotypes.

2.
PLoS Pathog ; 15(8): e1007703, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31381590

RESUMO

Necrotrophic plant pathogens acquire nutrients from dead plant cells, which requires the disintegration of the plant cell wall and tissue structures by the pathogen. Infected plants lose tissue integrity and functional immunity as a result, exposing the nutrient rich, decayed tissues to the environment. One challenge for the necrotrophs to successfully cause secondary infection (infection spread from an initially infected plant to the nearby uninfected plants) is to effectively utilize nutrients released from hosts towards building up a large population before other saprophytes come. In this study, we observed that the necrotrophic pathogen Dickeya dadantii exhibited heterogeneity in bacterial cell length in an isogenic population during infection of potato tuber. While some cells were regular rod-shape (<10µm), the rest elongated into filamentous cells (>10µm). Short cells tended to occur at the interface of healthy and diseased tissues, during the early stage of infection when active attacking and killing is occurring, while filamentous cells tended to form at a later stage of infection. Short cells expressed all necessary virulence factors and motility, whereas filamentous cells did not engage in virulence, were non-mobile and more sensitive to environmental stress. However, compared to the short cells, the filamentous cells displayed upregulated metabolic genes and increased growth, which may benefit the pathogens to build up a large population necessary for the secondary infection. The segregation of the two subpopulations was dependent on differential production of the alarmone guanosine tetraphosphate (ppGpp). When exposed to fresh tuber tissues or freestanding water, filamentous cells quickly transformed to short virulent cells. The pathogen adaptation of cell length heterogeneity identified in this study presents a model for how some necrotrophs balance virulence and vegetative growth to maximize fitness during infection.

3.
Comput Methods Programs Biomed ; 178: 163-173, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31416545

RESUMO

BACKGROUND AND OBJECTIVE: Wheezing is a common symptom of patients caused by asthma and chronic obstructive pulmonary diseases. Wheezing detection identifies wheezing lung sounds and helps physicians in diagnosis, monitoring, and treatment of pulmonary diseases. Different from the traditional way to detect wheezing sounds using digital image process methods, automatic wheezing detection uses computerized tools or algorithms to objectively and accurately assess and evaluate lung sounds. We propose an innovative machine learning-based approach for wheezing detection. The phases of the respiratory sounds are separated automatically and the wheezing features are extracted accordingly to improve the classification accuracy. METHODS: To enhance the features of wheezing for classification, the Adaptive Multi-Level In-Exhale Segmentation (AMIE_SEG) is proposed to automatically and precisely segment the respiratory sounds into inspiratory and expiratory phases. Furthermore, the Enhanced Generalized S-Transform (EGST) is proposed to extract the wheezing features. The highlighted features of wheezing improve the accuracy of wheezing detection with machine learning-based classifiers. RESULTS: To evaluate the novelty and superiority of the proposed AMIE_SEG and EGST for wheezing detection, we employ three machine learning-based classifiers, Support Vector Machine (SVM), Extreme Learning Machine (ELM) and K-Nearest Neighbor (KNN), with public datasets at segment level and record level respectively. According to the experimental results, the proposed method performs the best using the KNN classifier at segment level, with the measured accuracy, sensitivity, specificity as 98.62%, 95.9% and 99.3% in average respectively. On the other aspect, at record level, the three classifiers perform excellent, with the accuracy, sensitivity, specificity up to 99.52%, 100% and 99.27% respectively. We validate the method with public respiratory sounds dataset. CONCLUSION: The comparison results indicate the very good performance of the proposed methods for long-term wheezing monitoring and telemedicine.

4.
Aging (Albany NY) ; 11(16): 6120-6133, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467256

RESUMO

MicroRNAs (miRNAs) have emerged as critical regulators in the pathology of Alzheimer's disease (AD). MiR-181a is associated with hippocampal memory formation and aberrantly expressed in patients with mild cognitive impairment (MCI), however, little is known about its role and underlying mechanism involved in AD. Here, we report that miR-181a expression declines in APP/PS1 mice, synchronous with the increase in amyloid ß (Aß) level, which suggests a reverse correlation between miR-181a level and AD development. Additionally, lentiviral overexpression of miR-181a via intrahippocampal injection ameliorates cognitive deficits and amyloid plaque deposition in APP/PS1 mice, indicating a beneficial role of miR-181a against AD progression. Moreover, miR-181a decelerates pericyte loss and blood-brain barrier breakdown in APP/PS1 mice. Furthermore, miR-181a protects against Aß accumulation-induced pericyte apoptosis in vitro, which is attributed to the negative regulation of FOXO1 by miR-181a, since FOXO1 restoration abolishes miR-181a protective role against pericyte apoptosis. Altogether, these results may identify miR-181a as a novel regulator of AD pathology, and also implicate that the protection of miR-181a in blood-brain barrier pericytes may underlie its ameliorating effect on APP/PS1 mice.

5.
J Interferon Cytokine Res ; 39(9): 564-571, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31264927

RESUMO

The aim of this study is to detect the dynamic expression of interleukin-23 (IL-23) in ApoE-/- mice at different ages and to further examine the effects of anti-IL-23 therapy on atherosclerosis development. The levels of IL-23 in the sera, aortas, and lymph nodes of ApoE-/- mice were significantly increased compared with those of age-matched controls at 8, 12, 16, 20, and 24 weeks of age. Then, 12-week-old ApoE-/- mice were intraperitoneally injected with anti-IL-23p19 neutralizing antibodies, isotype controls, and phosphate-buffered saline for 8 weeks. The proinflammatory and anti-inflammatory mediators in atherosclerotic aortas, plaque areas, plaque necrotic cores, and the contents of major inflammatory cells in plaques were subsequently determined. The results showed that anti-IL-23p19 treatment significantly decreased the expression of IL-17A, IL-6, and TNF-α in the aortas of ApoE-/- mice, but had no obvious effect on the plaque area, plaque necrotic core, or content of major inflammatory cells in atherosclerotic plaques. Although anti-IL-23p19 therapy reduces the expression of several proinflammatory cytokines, it does not significantly suppress the progression of atherosclerosis in ApoE-/- mice.

6.
Epigenomics ; 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31357869

RESUMO

Aim: Pericytes maintain homeostatic functions in the blood-brain barrier. N6-methyladenosine (m6A) is critical for various biological processes, but the role of mRNA m6A methylation in hypertension has not been fully elucidated. Methods: The m6A methylation levels of Wistar Kyoto rat pericytes and spontaneously hypertensive rat pericytes were detected via m6A high throughput sequencing. Results: The m6A methylations were more enriched in the coding sequence region, 3'UTR and 5'UTR of mRNAs, with the m6A motifs being relatively conserved across the different conditions investigated. The average m6A abundance of spontaneously hypertensive rat pericytes exhibited global reductions in the pericytes. Conclusion: This study revealed the m6A landscapes and identified an epitranscriptomic mechanism during the development of mammalian hypertension.

7.
Biochem Biophys Res Commun ; 514(3): 1023-1029, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31068251

RESUMO

It has been previously reported that the blockade of interleukin-7 receptor (IL-7R) promotes functional recovery following spinal cord injury (SCI), however, the direct function and molecular mechanism of IL-7 involved in this pathogenic process are unclear. Here, we report that, contrary to IL-7R blockade, the intraspinal administration of IL-7 limits functional recovery following SCI. In addition, IL-7 treatment promotes neuronal apoptosis in spinal cord lesions, which may be attributed to exacerbated focal inflammatory response, as shown by increased accumulation of activated microglia/macrophage and production of proinflammatory mediators. Moreover, IL-7 treatment activates JAK/STAT5 pathway following SCI. At last, more importantly, the pharmacological inhibition of STAT5 abrogates the effects of IL-7 treatment on functional recovery, neuronal apoptosis and focal inflammatory response, suggesting that the effects of IL-7 treatment following SCI are dependent on activating the JAK/STAT5 pathway. Overall, this study reveals the JAK/STAT5 pathway-dependent detrimental role of IL-7 following SCI, and also implies that targeting the IL-7/JAK/STAT5 axis may represent a potential therapeutic approach for SCI treatment.

8.
Environ Microbiol ; 21(8): 2755-2771, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30895662

RESUMO

Dickeya dadantii is a plant pathogen that causes soft rot disease on vegetable and potato crops. To successfully cause infection, this pathogen needs to coordinately modulate the expression of genes encoding several virulence determinants, including plant cell wall degrading enzymes (PCWDEs), type III secretion system (T3SS) and flagellar motility. Here, we uncover a novel feed-forward signalling circuit for controlling virulence. Global RNA chaperone Hfq interacts with an Hfq-dependent sRNA ArcZ and represses the translation of pecT, encoding a LysR-type transcriptional regulator. We demonstrate that the ability of ArcZ to be processed to a 50 nt 3'- end fragment is essential for its regulation of pecT. PecT down-regulates PCWDE and the T3SS by repressing the expression of a global post-transcriptional regulator- (RsmA-) associated sRNA encoding gene rsmB. In addition, we show that the protein levels of two cyclic di-GMP (c-di-GMP) diguanylate cyclases (DGCs), GcpA and GcpL, are repressed by Hfq. Further studies show that both DGCs are essential for the Hfq-mediated post-transcriptional regulation on RsmB. Overall, our report provides new insights into the interplays between ubiquitous signalling transduction systems that were most studied independently and sheds light on multitiered regulatory mechanisms for a precise disease regulation in bacteria.

9.
Life Sci ; 221: 47-55, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30738044

RESUMO

BACKGROUND: Spinal cord injury (SCI) disturbs the autonomic nervous system and induces dysfunction or failure of multiple organs. The systemic microcirculation disturbance that contributes to the complications associated with SCI remains to be clarified. METHODS: We used male mice (29-32 g) and modified weight-drop injury at T10 to evaluate the systemic microcirculation dysfunction during the first 2 weeks after SCI. We determined permeability and microvascular blood flow in several organs and evaluated their vasomotor function. We also measured circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), circulating pericyte progenitor cells (CPPCs), and serum proinflammatory cytokines. RESULTS: The endothelial permeability of almost all organs increased after SCI. Microvascular blood flow decreased in the bladder and kidney and increased in the spleen and was accompanied by endothelial vasomotor dysfunction. SCI also induced an increase in CECs, CEPCs, and CPPCs in peripheral blood. Finally, we confirmed changes in a systemic cytokine profile (interleukin [IL]-3, IL-6, IL-10, IL-13, granulocyte colony-stimulating factor, and regulated on activation normal T cell expressed and secreted) after SCI. CONCLUSIONS: These data indicate that a systemic microcirculation disturbance occurs after SCI. This information may play a key role in the development of effective therapeutic strategies for SCI.


Assuntos
Microcirculação/fisiologia , Traumatismos da Medula Espinal/sangue , Animais , Citocinas , Células Progenitoras Endoteliais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pericitos , Fluxo Sanguíneo Regional/fisiologia , Medula Espinal/irrigação sanguínea
10.
Mol Plant Microbe Interact ; 32(6): 729-739, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30589364

RESUMO

PdeR, a response regulator of the two-component system (TCS) with the cognate histidine kinase PdeK, has been shown to be an active phosphodiesterase (PDE) for intracellular cyclic dimeric guanosine monophosphate (c-di-GMP) turnover and positively regulates the virulence of Xanthomonas oryzae pv. oryzae, the causal pathogen of bacterial blight of rice. To further reveal the key components and pathways involved in the PdeR-mediated c-di-GMP regulation of virulence, 16 PdeR-interacting proteins were identified, using the yeast two-hybrid (Y2H) assay. Among them, PXO_04421 (named as TriP, a putative transcriptional regulator interacting with PdeR) was verified via Y2H and glutathione-S-transferase pull-down assays, and its regulatory functions in bacterial virulence and exopolysaccharide (EPS) production were assessed by biochemical and genetic analysis. The REC domain of TriP specifically interacted with the EAL domain of PdeR. TriP promoted the PDE activity of PdeR to degrade c-di-GMP in the presence of PdeK. In-frame deletion in triP abolished the polar localization of PdeR in the cell. Notably, the ∆triP mutant showed significantly reduced virulence on susceptible rice leaves and impaired EPS production compared with wild type, whereas the double mutant ∆triP∆pdeR, like ∆pdeR, caused shorter lesion lengths and produced less EPS than ∆triP. In addition, cross-complementation showed in trans expression of pdeR in ∆triP restored its EPS production to near wild-type levels but not vice versa. Taken together, our results suggest that TriP is a novel regulator that is epistatic to PdeR in positively regulating virulence expression in X. oryzae pv. oryzae.


Assuntos
Oryza , Virulência , Xanthomonas , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Oryza/microbiologia , Diester Fosfórico Hidrolases/metabolismo , Doenças das Plantas/microbiologia , Virulência/genética , Xanthomonas/enzimologia , Xanthomonas/genética , Xanthomonas/patogenicidade
11.
Medicine (Baltimore) ; 97(39): e12485, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30278536

RESUMO

In chronic heart failure (CHF), new-onset atrial fibrillation (AF) is associated with increased morbidity and mortality. We aimed to evaluate the influence of dyslipidemia on the incidence of new-onset AF in patients with CHF.In this single-center observational study, 308 patients with CHF and no history of AF were followed-up for 3 years. Of the 291 patients who attended the 1-year follow-up, 78 had developed AF (AF group; 10 deaths), while 213 had not (sinus rhythm [SR] group). Changes in lipid profile (ΔTC for total cholesterol and ΔLDLc for low-density lipoprotein cholesterol) were analyzed.The groups differed significantly regarding the decrease in lipid levels from baseline to the 1-year follow-up (AF vs SR: for ΔLDLc, 23.35 vs 7.80 mg/dL, P = .02; for ΔTC, 23.95 vs -2.76 mg/dL, P = .001). At the 3-year follow-up, new-onset AF was noted in 21 of the 188 living patients in the SR group. Cox proportional hazards analysis revealed ΔLDLc and ΔTC as independent risk factors for new-onset AF (hazard ratio, 1.018 and 1.013, respectively, per standard deviation increment), with higher incidence of new-onset AF for ΔTC > 9.65 mg/dL (P = .02) and for ΔLDLc > 9.73 mg/dL (P = .005).In CHF, pronounced decrease in LDLc and TC is associated with new-onset AF.


Assuntos
Fibrilação Atrial/complicações , Dislipidemias/complicações , Insuficiência Cardíaca/fisiopatologia , Lipídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , China/epidemiologia , LDL-Colesterol/sangue , Doença Crônica , Feminino , Seguimentos , Insuficiência Cardíaca/classificação , Insuficiência Cardíaca/complicações , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco
12.
Am J Transl Res ; 10(8): 2372-2386, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30210677

RESUMO

BACKGROUND: Changes in the structure and function of micro-vessels is the pathogenic basis of organ damage in cardiovascular and cerebrovascular diseases. Microcirculation is primarily affected in hypertension, resulting in increased vascular resistance. Pericytes are contractile cells that are embedded in the basement membrane of capillaries, and regulate endothelial cell membrane maturation, capillary blood flow, cell debris removal, and stability of endothelial cells. However, the exact role of brain microvascular pericytes in the pathogenesis of hypertension has not been elucidated. METHODS: Brain microvascular pericytes were isolated from spontaneously hypertensive rats (SHR) and wild type Wistar Kyoto (WKY) rats. The transcriptomes of SHR and WKY pericytes were analyzed by RNA-Seq, and the differentially expressed genes (DEGs) were screened by Ballgown, and Student's t test was used to be used to compare differences between groups. DAVID was used for the GO-enrichment analysis and KEGG pathway analysis of the DEGs, and an interaction network between the significant signaling pathways and DEGs was constructed. RESULTS: A total of 1356 DEGs were identified between the WKY and the SHR group pericytes (P value < 0.05, Fold change > 1.5), of which 733 were upregulated and 623 downregulated. The genes with greatest betweenness centrality values were Itgb1, Vcam-1 and MMP-9. Based on KEGG analysis, 34 interacting signaling pathways and 43 interacting genes were screened, and MAPK, p53, Wnt, Jak-STAT, TGF-beta, VEGF and PPAR signaling pathways were the key nodes. CONCLUSIONS: Several DEGs and signaling pathways were identified in the brain microvascular pericytes of SHR rats compared to the WKY rats. Our findings will lay the foundation to study the role of brain microvascular pericytes in the development of spontaneous hypertension.

13.
Appl Environ Microbiol ; 84(22)2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30217836

RESUMO

In Xanthomonas oryzae pv. oryzae, the bacterial blight pathogen of rice, there are over 20 genes encoding GGDEF, EAL, and HD-GYP domains, which are potentially involved in the metabolism of second messenger c-di-GMP. In this study, we focused on the characterization of an EAL domain protein, EdpX1. Deletion of the edpX1 gene resulted in a 2-fold increase in the intracellular c-di-GMP levels, which were restored to the wild-type levels in the complemented ΔedpX1(pB-edpX1) strain, demonstrating that EdpX1 is an active phosphodiesterase (PDE) in X. oryzae pv. oryzae. In addition, colorimetric assays further confirmed the PDE activity of EdpX1 by showing that the E153A mutation at the EAL motif strongly reduced its activity. Virulence assays on the leaves of susceptible rice showed that the ΔedpX1 mutant was severely impaired in causing disease symptoms. In trans expression of wild-type edpX1, but not edpX1 E153A, was able to complement the weakened virulence phenotype. These results indicated that an active EAL domain is required for EdpX1 to regulate the virulence of X. oryzae pv. oryzae. We then demonstrated that the ΔedpX1 mutant was defective in secreting exopolysaccharide (EPS) and forming biofilms. The expression of edpX1 in the ΔedpX1 mutant, but not edpX1 E153A, restored the defective phenotypes to near-wild-type levels. In addition, we observed that EdpX1-green fluorescent protein (EdpX1-GFP) exhibited multiple subcellular localization foci, and this pattern was dependent on its transmembrane (TM) region, which did not seem to directly contribute to the regulatory function of EdpX1. Thus, we concluded that EdpX1 exhibits PDE activity to control c-di-GMP levels, and its EAL domain is necessary and sufficient for its regulation of virulence in X. oryzae pv. oryzae.IMPORTANCE Bacteria utilize c-di-GMP as a second messenger to regulate various biological functions. The synthesis and degradation of c-di-GMP are catalyzed by GGDEF domains and an EAL or HD-GYP domain, respectively. Multiple genes encoding these domains are often found in one bacterial strain. For example, in the genome of X. oryzae pv. oryzae PXO99A, 26 genes encoding proteins containing these domains were identified. Therefore, to fully appreciate the complexity and specificity of c-di-GMP signaling in X. oryzae pv. oryzae, the enzymatic activities and regulatory functions of each GGDEF, EAL, and HD-GYP domain protein need to be elucidated. In this study, we showed that the EAL domain protein EdpX1 is a major PDE to regulate diverse virulence phenotypes through the c-di-GMP signaling pathway.

14.
ACS Chem Neurosci ; 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30168706

RESUMO

It is time-consuming and costly to bring new drugs to market, making it necessary and urgent to exploit existing drugs for new uses. Recently, fenoprofen was demonstrated as an allosteric modulator at melanocortin receptors (MCRs), although the exact mode of action has not been clarified. MCRs regulate multiple functions, including pigmentation, adrenal steroidogenesis, inflammation, energy homeostasis, and exocrine gland secretion. In this study, we showed that fenoprofen failed to displace the orthosteric agonist Nle4-d-Phe7-α-melanocyte stimulating hormone from binding to MC3-5R while possessing positive allosteric modulator activities at these receptors. In addition, fenoprofen induced biased signaling at MC3-5R, as it selectively activated ERK1/2 cascade but not the canonical cAMP signaling. Notably, fenoprofen stimulated biased signaling at MC3-5R, but not at MC1R, hence acting selectively among this highly conserved family of receptors. Moreover, PAM activity and biased signaling induced by fenoprofen were observed not only at wild-type but also at naturally occurring mutant MC3Rs, suggesting that this biased allosteric enhancer action might constitute as novel therapeutic opportunity for obese patients harboring these mutations. Our study might guide novel therapeutic applications for repurposing current drugs or designing new drugs combining allosteric and biased properties.

15.
Front Microbiol ; 9: 1429, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30002651

RESUMO

Dickeya dadantii is a bacterial plant pathogen that causes soft rot disease on a wide range of host plants. The type III secretion system (T3SS) is an important virulence factor in D. dadantii. Expression of the T3SS is induced in the plant apoplast or in hrp-inducing minimal medium (hrp-MM), and is repressed in nutrient-rich media. Despite the understanding of induction conditions, how individual cells in a clonal bacterial population respond to these conditions and modulate T3SS expression is not well understood. In our previous study, we reported that in a clonal population, only a small proportion of bacteria highly expressed T3SS genes while the majority of the population did not express T3SS genes under hrp-MM condition. In this study, we developed a method that enabled in situ observation and quantification of gene expression in single bacterial cells in planta. Using this technique, we observed that the expression of the T3SS genes hrpA and hrpN is restricted to a small proportion of D. dadantii cells during the infection of potato. We also report that the expression of T3SS genes is higher at early stages of infection compared to later stages. This expression modulation is achieved through adjusting the ratio of T3SS ON and T3SS OFF cells and the expression intensity of T3SS ON cells. Our findings not only shed light into how bacteria use a bi-stable gene expression manner to modulate an important virulence factor, but also provide a useful tool to study gene expression in individual bacterial cells in planta.

16.
Clin Exp Hypertens ; : 1-11, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29939761

RESUMO

This work was aimed to study skin blood perfusion, vasomotion and vascular responses of the Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in different stages of age using spectral. Laser-Doppler flowmetry (LDF) was used to examine the ears and limbs of WKY (12 and 48 weeks old) and SHR (12 and 48 weeks old). The skin blood flow oscillations (SBFOs) were studied by wavelet spectral analysis of LDF tracings. Then, we observed that old groups showed decreased perfusion and SBFO in the ears of both SHR and WKY. The SHR showed obviously lower postocclusive reactive hypera (PORH) ratio at the same age. A decreased peak-time occurred in the SHR of old age group. After PORH test, a statistically significant increase was observed within all subintervals in the absolute amplitude of 12-week WKY and only within IV and III subintervals in the absolute amplitude of 12-week SHR. But, the absolute amplitude of 48-week WKY and SHR showed no statistically significant increase within all subintervals. Results indicated that local regulating function of peripheral vascular was impaired in rat with hypertension and aging. Abbreviations LDF: Laser-Doppler flowmetry; SBF: Skin blood flow; SBFO: Skin blood flow oscillation; PORH: Postocclusive reactive hyperemia; SHR: Spontaneously hypertensive rats; WKY: Wistar-Kyoto rats; LDF: Laser-Doppler flowmetry; LDI: Laser Doppler Imaging; BP: Blood pressure.

17.
Sci Rep ; 8(1): 6934, 2018 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-29720695

RESUMO

Although previous studies have indicated importance of taste receptors in food habits formation in mammals, little is known about those in fish. Grass carp is an excellent model for studying vegetarian adaptation, as it shows food habit transition from carnivore to herbivore. In the present study, pseudogenization or frameshift mutations of the umami receptors that hypothesized related to dietary switch in vertebrates, were not found in grass carp, suggesting other mechanisms for vegetarian adaptation in grass carp. T1R1 and T1R3 strongly responded to L-Arg and L-Lys, differing from those of zebrafish and medaka, contributing to high species specificity in amino acid preferences and diet selection of grass carp. After food habit transition of grass carp, DNA methylation levels were higher in CPG1 and CPG3 islands of upstream control region of T1R1 gene. Luciferase activity assay of upstream regulatory region of T1R1 (-2500-0 bp) without CPG1 or CPG3 indicated that CPG1 and CPG3 might be involved in transcriptional regulation of T1R1 gene. Subsequently, high DNA methylation decreased expression of T1R1 in intestinal tract. It could be a new mechanism to explain, at least partially, the vegetarian adaptation of grass carp by regulation of expression of umami receptor via epigenetic modification.

18.
Biosens Bioelectron ; 110: 16-22, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29579645

RESUMO

Contamination of surface and drinking water due to the presence of Escherichia coli bacteria is a major cause of water-borne disease outbreak. To address unmet challenges for practical pathogen detection in contaminated samples, we report fabrication of thermally reduced graphene oxide-based field-effect transistor (rGO FET) passivated with an ultrathin layer of Al2O3 for real-time detection of E. coli bacteria. The sensor could detect a single E. coli cell within 50 s in a 1 µL sample volume. The ultrathin layer of Al2O3 acted as a barrier between rGO and potential interferents present in the sample. E. coli specific antibodies anchored on gold nanoparticles acted as probes for selective capture of E. coli. The high density of negative charge on the surface of E. coli cells strongly modulates the concentration of majority charge carriers in the rGO monolayer, thereby allowing real-time monitoring of E. coli concentration in a given sample. With a low detection limit of single cell, the FET sensor had a linear range of 1-100 CFU in 1 µL volume of sample (i.e., 103 to 105 CFU/ mL). The biosensor with good selectivity and rapid detection was further successfully demonstrated for E. coli sensing in river water. The rGO-based FET sensor provides a low cost and label-free approach, and can be mass produced for detection of a broad spectrum of pathogens in water or other liquid media.


Assuntos
Técnicas Biossensoriais/instrumentação , Infecções por Escherichia coli/microbiologia , Escherichia coli/isolamento & purificação , Grafite/química , Rios/microbiologia , Transistores Eletrônicos , Técnicas Biossensoriais/economia , Desenho de Equipamento , Humanos , Limite de Detecção , Óxidos/química , Fatores de Tempo
19.
Mol Plant Pathol ; 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29390166

RESUMO

Dickeya dadantii 3937 secretes pectate lyases (Pels) to degrade plant cell walls. Previously, we have demonstrated that EGcpB and EcpC function as bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP)-specific phosphodiesterases (PDEs) to positively regulate Pel production. However, the diguanylate cyclase (DGC) responsible for the synthesis of c-di-GMP and the dichotomous regulation of Pel has remained a mystery. Here, we identified GcpA as the dominant DGC to negatively regulate Pel production by the specific repression of pelD gene expression. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays revealed that the expression levels of histone-like, nucleoid-structuring protein encoding gene hns and post-transcriptional regulator encoding genes rsmA and rsmB were significantly affected by GcpA. Deletion of hns or rsmB in the gcpAD418A site-directed mutant restored its Pel production and pelD expression, demonstrating that H-NS and RsmB contribute to the GcpA-dependent regulation of Pel in D. dadantii. In addition, RsmB expression was subject to positive regulation by H-NS. Thus, we propose a novel pathway consisting of GcpA-H-NS-RsmB-RsmA-pelD that controls Pel production in D. dadantii. Furthermore, we showed that H-NS and RsmB are responsible for the GcpA-dependent regulation of motility and type III secretion system (T3SS) gene expression, respectively. Of the two PDEs involved in the regulation of Pels, only EGcpB regulates pelD expression through the same pathway as GcpA.

20.
Mol Plant Pathol ; 19(3): 579-592, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28213905

RESUMO

Flagellin glycosylation plays a crucial role in flagellar assembly, motility and virulence in several pathogenic bacteria. However, little is known about the genetic determinants and biological functions of flagellin glycosylation in Xanthomonas oryzae pv. oryzae (Xoo), the causal pathogen of bacterial blight of rice. Here, the structure, regulation and functions of a ten-gene cluster gigX (glycosylation island genes of Xoo), which was embedded in a flagellar regulon, were characterized. gigX1 to gigX10 encoded putative enzymes or proteins involved in glycan biosynthesis and transfer, including a nucleotide sugar transaminase, an acyl-carrier protein (ACP), a 3-oxoacyl-ACP synthase, a 3-oxoacyl-ACP reductase, a dehydrogenase, an acetyltransferase, a ring hydroxylating dioxygenase, a hypothetical protein, a methyltransferanse and a glycosyltransferase, respectively. The gigX genes were co-transcribed in an operon and up-regulated by the upstream σ54 factor RpoN2 and transcriptional activator FleQ. In-frame deletion of each gigX gene affected flagellin glycosylation modification, meaning that the unglycosylated flagellin of the mutants was smaller than the glycosylated flagellin of the wild-type. No significant changes in flagellar filament and motility were observed in the ΔgigX mutants, among which only ΔgigX6 displayed increased swimming ability. Importantly, all mutants, except ΔgigX9, showed significantly increased virulence and bacterial growth in the susceptible rice cultivar IR24, and ΔgigX1 and ΔgigX10 showed enhanced type III secretion system (T3SS)-related gene expression. Moreover, the glycosylated flagellin of the wild-type induced higher H2 O2 levels in rice leaves than did the unglycosylated flagellins of ΔgigX1 or ΔgigX10. Taken together, this study reveals that the gigX cluster determines flagellin glycosylation, and implicates the regulatory role of post-translational modification with the glycosylation, acetylation and methylation of flagellin in the regulation of motility and virulence of Xoo.


Assuntos
Flagelina/metabolismo , Ilhas Genômicas/genética , Oryza/microbiologia , Virulência/fisiologia , Xanthomonas/patogenicidade , Regulação Bacteriana da Expressão Gênica , Glicosilação , Oryza/genética , Sistemas de Secreção Tipo III/metabolismo , Virulência/genética , Xanthomonas/genética
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