Despite increasing understanding of the prognostic importance of vascular stiffening linked to perivascular fibrosis in hypertension, the molecular and cellular regulation of this process is poorly understood. OBJECTIVES: To study the functional role of microRNA-214 (miR-214) in the induction of perivascular fibrosis and endothelial dysfunction driving vascular stiffening. METHODS AND RESULTS: Out of 381 miRs screened in the perivascular tissues in response to Ang II (angiotensin II)-mediated hypertension, miR-214 showed the highest induction (8-fold, P=0.0001). MiR-214 induction was pronounced in perivascular and circulating T cells, but not in perivascular adipose tissue adipocytes. Global deletion of miR-214 −/− prevented Ang II-induced periaortic fibrosis, Col1a1, Col3a1, Col5a1, and Tgfb1 expression, hydroxyproline accumulation, and vascular stiffening, without difference in blood pressure. Mechanistic studies revealed that miR-214 −/− mice were protected against endothelial dysfunction, oxidative stress, and increased Nox2, all of which were induced by Ang II in WT mice. Ang IIinduced recruitment of T cells into perivascular adipose tissue was abolished in miR-214 −/− mice. Adoptive transfer of miR-214 −/− T cells into RAG1 −/− mice resulted in reduced perivascular fibrosis compared with the effect of WT T cells. Ang II induced hypertension caused significant change in the expression of 1380 T cell genes in WT, but only 51 in miR-214 −/−. T cell activation, proliferation and chemotaxis pathways were differentially affected. MiR-214 −/− prevented Ang II-induction of profibrotic T cell cytokines (IL-17, TNF-α, IL-9, and IFN-γ) and chemokine receptors (CCR1, CCR2, CCR4, CCR5, CCR6, and CXCR3). This manifested in reduced in vitro and in vivo T cell chemotaxis resulting in attenuation of profibrotic perivascular inflammation. Translationally, we show that miR-214 is increased in plasma of patients with hypertension and is directly correlated to pulse wave velocity as a measure of vascular stiffness. CONCLUSIONS: T-cell-derived miR-214 controls pathological perivascular fibrosis in hypertension mediated by T cell recruitment and local profibrotic cytokine release. VISUAL OVERVIEW: An online visual overview is available for this article.
Abstract:In this paper, we present a new questionnaire for the assessment of self-control as an individual trait. We describe the process of construction of this assessment tool. We also report the results of relevant validation studies. The questionnaire has two independent versions, one based on self-reports Tangney, Baumeister, and Boone's (2004) self-control scale. They also proved to be entirely independent of general intelligence. In conclusion, both versions can be regarded reliable and valid enough, and therefore suitable for the assessment of trait self-control for research purposes. and another one based on other-reports (NAS-40). The first version consists of five subscales (10 items each), called Initiative and Persistence (IP), Proactive Control (PC), Switching and Flexibility (SF), Inhibition and Adjournment (IA), and Goal Maintenance (GM). Seven samples of participants (N = 934 altogether) took part in the validation study. The second version has not been split into subscales. Both versions obtained satisfactory indices of internal consistency, assessed with Cronbach's alpha (for NAS-50 total score a = .861, for the subscales a between .726 and .867; for NAS-40 a = .844). The NAS-50 and NAS-40 scores were highly correlated with other measures of self-control, including
Vascular dysfunction is an important phenomenon in hypertension. We hypothesized that angiotensin II (AngII) affects transcriptome in the vasculature in a region-specific manner, which may help to identify genes related to vascular dysfunction in AngII-induced hypertension. Mesenteric artery and aortic transcriptome was profiled using Illumina WG-6v2.0 chip in control and AngII infused (490 ng/kg/min) hypertensive mice. Gene set enrichment and leading edge analyses identified Sphingosine kinase 1 (Sphk1) in the highest number of pathways affected by AngII. Sphk1 mRNA, protein and activity were up-regulated in the hypertensive vasculature. Chronic sphingosine-1-phosphate (S1P) infusion resulted in a development of significantly increased vasoconstriction and endothelial dysfunction. AngII-induced hypertension was blunted in Sphk1−/− mice (systolic BP 167 ± 4.2 vs. 180 ± 3.3 mmHg, p < 0.05), which was associated with decreased aortic and mesenteric vasoconstriction in hypertensive Sphk1−/− mice. Pharmacological inhibition of S1P synthesis reduced vasoconstriction of mesenteric arteries. While Sphk1 is important in mediating vasoconstriction in hypertension, Sphk1−/− mice were characterized by enhanced endothelial dysfunction, suggesting a local protective role of Sphk1 in the endothelium. S1P serum level in humans was correlated with endothelial function (arterial tonometry). Thus, vascular transcriptome analysis shows that S1P pathway is critical in the regulation of vascular function in AngII-induced hypertension, although Sphk1 may have opposing roles in the regulation of vasoconstriction and endothelium-dependent vasorelaxation.
Self-control (SC) is an individual trait defined as the ability to pursue long-distance goals in spite of the obstacles generated by current desires, innate or learned automatisms, and physiological needs of an organism. This trait is relatively stable across the life span and it predicts such important features as level of income, quality of social relationships, and proneness to addictions. It is widely believed that the cognitive substrate of SC involves the executive functions (EFs), such as inhibitory control, shifting of attention, and working memory updating. However, the empirical evidence concerning the relationships between trait SC and EFs is not convincing. The present study aims to address two questions: (1) what is the strength of relationships between trait SC and EFs, and (2) which aspects of SC are predicted by particular EFs, if at all. In order to answer these questions, we carried out a psychometric study with 296 participants (133 men and 163 women, mean age 23.31, SD 3.64), whom we investigated with three types of tools: (1) a battery SC scales and inventories, (2) a battery of EFs tasks, and (3) two general intelligence tests. Structural equation modeling approach was used to analyze the data. We found that the latent variables representing SC and the latent variable representing EFs did not show any relationship. The standardized path coefficient between EFs and general intelligence turned out rather strong. We conclude that the trait of SC, measured with questionnaires, does not depend on the strength of cognitive control, measured with EFs tasks.
Water shortage is a major environmental stress that causes the generation of reactive oxygen species (ROS). The increase in ROS production induces molecular responses, which are key factors in determining the level of plant tolerance to stresses, including drought. The aim of this study was to determine the expression levels of genes encoding MAPKs ( MAPK3 and MAPK6 ), antioxidant enzymes ( CAT , APX and GPX ) and enzymes involved in proline biosynthesis ( P5CS and P5CR ) in Triticum aestivum L. seedlings in response to short-term drought conditions. A series of wheat intervarietal substitution lines (ISCSLs) obtained by the substitution of single chromosomes from a drought-sensitive cultivar into the genetic background of a drought-tolerant cultivar was used. This source material allowed the chromosomal localization of the genetic elements involved in the response to the analyzed stress factor (drought). The results indicated that the initial plant response to drought stress resulted notably in changes in the expression of MAPK6 and CAT and both the P5CS and P5CR genes. Our results showed that the substitution of chromosomes 3B, 5A, 7B and 7D had the greatest impact on the expression level of all tested genes, which indicates that they contain genetic elements that have a significant function in controlling tolerance to water deficits in the wheat genome.
Infection of phyllosphere (stems, leaves, husks, and grains) by pathogenic fungi reduces the wheat yield and grain quality. Detection of the main wheat pathogenic fungi provides information about species composition and allows effective and targeted plant treatment. Since conventional procedures for the detection of these organisms are unreliable and time consuming, diagnostic DNA-based methods are required. Nucleic acid amplification technologies are independent of the morphological and biochemical characteristics of fungi. Microorganisms do not need to be cultured. Therefore, a number of PCR-based methodologies have been developed for the identification of key pathogenic fungi, such as Fusarium spp., Puccinia spp., Zymoseptoria tritici, Parastagonospora nodorum, Blumeria graminis f. sp. tritici, and Pyrenophora tritici-repentis. This article reviews frequently used DNA regions for fungus identification and discusses already known PCR assays for detection of the aforementioned wheat pathogens. We demonstrate that PCR-based wheat pathogen identification assays require further research. In particular, the number of diagnostic tests for Fusarium graminearum, Puccinia spp., and P. tritici-repentis are insufficient.
Background: Quantitative PCR (qPCR) is one of the most common and accurate methods of gene expression analysis. However, the biggest challenge for this kind of examinations is normalization of the results, which requires the application of dependable internal controls. The selection of appropriate reference genes (RGs) is one of the most crucial points in qPCR data analysis and for correct assessment of gene expression. Because of the fact that many reports indicate that the expression profiles of typically used RGs can be unstable in certain experimental conditions, species or tissues, reference genes with stable expression levels should be selected individually for each experiment. In this study, we analysed a set of ten candidate RGs for wheat seedlings under short-term drought stress. Our tests included five 'traditional' RGs (GAPDH, ACT, UBI, TUB, and TEF1) and five novel genes developed by the RefGenes tool from the Genevestigator database. Results: Expression stability was assessed using five different algorithms: geNorm, NormFinder, BestKeeper, Ref-Finder and the delta Ct method. In the final ranking, we identified three genes: CJ705892, ACT, and UBI, as the best candidates for housekeeping genes. However, our data indicated a slight variation between the different algorithms that were used. We revealed that the novel gene CJ705892, obtained by means of in silico analysis, showed the most stable expression in the experimental tissue and condition. Conclusions: Our results support the statement, that novel genes selected for certain experimental conditions have a more stable level of expression in comparison to routinely applied RGs, like genes encoding actin, tubulin or GAPDH. Selected CJ705892 gene can be used as a housekeeping gene in the expression analysis in wheat seedlings under short-term drought. The results of our study will be useful for subsequent analyses of gene expression in wheat tissues subjected to drought.
Fusarium populations were investigated on 53 samples of wheat grains and husks collected approximately three weeks before harvest in 53 wheat fields in southeastern Poland. A limited area of sample collection was chosen intentionally to avoid the effect of climate and weather variability. The study was conducted to assess the occurrence of 13 Fusarium species using species-specific PCR assays separately on grains and husks of winter wheat. The obtained data suggest that husks could take a protective role of wheat grain against Fusarium spp. The incidence of Fusarium species decreased in grains vs. husks from 29 to 100%. While Fusarium species were present in husks at 11.32% and less, they were absent in the grain. The presence of Fusarium species on husks is inversely proportional to the percentage reduction of Fusarium spp. in grain. There was a correlation of the presence of certain species of Fusarium in husks and in grains. The number of Fusarium species found on husks was about three times higher in comparison to wheat grain. In conclusion, the presented data indicate the importance of Fusarium populations analysis on wheat husk in seeds pathological studies.
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