Peroxisome proliferator-activated receptor /␦ (PPAR-) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily that regulates the transcription of many target genes. More recently, acute, nongenomic effects of PPAR- agonists have also been described. In the present study, we hypothesized that PPAR- agonists might exert acute nongenomic effects on vascular tone. Here, we report that the structurally unrelated PPAR- ligands [4-[3-(4-acetyl- sulfonyl]-2-thiophenecarboxylic acid methyl ester (GSK0660) also partially inhibited these relaxant responses, although PPAR-␥ blockade with 2-chloro-5-nitro-N-phenylbenzamide (GW9662) had no effect. In human umbilical vein endothelial cells, L-165041 and GW0742 increased nitric oxide (NO) production and Akt and endothelial NOS (eNOS) phosphorylation, which were sensitive to PI3K inhibition and PPAR- blockade. In conclusion, the PPAR- agonists acutely caused vasodilatation, which was partially dependent on endothelial-derived NO. The eNOS activation is calciumindependent and seems to be related to activation of the PI3K-Akt-eNOS pathway.
We present here emoFinder ( http://usc.es/pcc/emofinder ), a Web-based search engine for Spanish word properties taken from different normative databases. The tool incorporates several subjective word properties for 16,375 distinct words. Although it focuses particularly on normative ratings for emotional dimensions (e.g., valence and arousal) and discrete emotional categories (fear, disgust, anger, happiness, and sadness), it also makes available ratings for other word properties that are known to affect word processing (e.g., concreteness, familiarity, contextual availability, and age of acquisition). The tool provides two main functionalities: Users can search for words matched on specific criteria with regard to the selected properties, or users can obtain the properties for a set of words. The output from emoFinder is highly customizable and can be accessed online or exported to a computer. The tool architecture is easily scalable, so that it can be updated to include word properties from new Spanish normative databases as they become available.
This study presents semantic ambiguity norms for 530 Spanish words. Two subjective measures of semantic ambiguity and two subjective measures of relatedness of ambiguous word meanings were collected. In addition, two objective measures of semantic ambiguity were included. Furthermore, subjective ratings were obtained for some relevant lexicosemantic variables, such as concreteness, familiarity, emotional valence, arousal, and age of acquisition. In sum, the database overcomes some of the limitations of the published databases of Spanish ambiguous words; in particular, the scarcity of measures of ambiguity, the lack of relatedness of ambiguous word meanings measures, and the absence of a set of unambiguous words. Thus, it will be very helpful for researchers interested in exploring semantic ambiguity as well as for those using semantic ambiguous words to study language processing in clinical populations.
The cognate facilitation effect (i.e., a processing advantage for cognates compared to non-cognates) is an evidence of language non-selectivity in bilingual lexical access. Several studies using behavioral or electrophysiological measures have demonstrated that this effect is modulated by the degree of formal overlap between translations. However, it has never been tested with a psychophysiological measure such as pupillometry. In the present study we replicate the cognate facilitation effect by examining reaction times and pupil responses. Our results endorse pupillometry as a promising tool for bilingual research, and confirm the modulation of the cognate effect by the degree of formal similarity.
Background and Purpose
PPARβ enhances insulin sensitivity in adipocytes and skeletal muscle cells, but its effects on insulin signalling in endothelial cells are not known. We analysed the effects of the PPARβ/δ (PPARβ) agonists, GW0742 and L165041, on impaired insulin signalling induced by high glucose in HUVECs and aortic and mesenteric arteries from diabetic rats.
Experimental Approach
Insulin‐stimulated NO production, Akt‐Ser473 and eNOS‐Ser1177 phosphorylation, and reactive oxygen species (ROS) production were studied in HUVECs incubated in low‐ or high‐glucose medium. Insulin‐stimulated relaxations and protein phosphorylation in vessels from streptozotocin (STZ)‐induced diabetic rats were also analysed.
Key Results
HUVECs incubated in high‐glucose medium showed a significant reduction in insulin‐stimulated production of NO. High glucose also reduced insulin‐induced Akt‐Ser473 and eNOS‐Ser1177 phosphorylation, increased IRS‐1‐Ser636 and ERK1/2‐Thr183‐Tyr185 phosphorylation and increased ROS production. The co‐incubation with the PPARβ agonists GW0742 or L165041 prevented all these effects induced by high glucose. In turn, the effects induced by the agonists were suppressed when HUVEC were also incubated with the PPARβ antagonist GSK0660, the pyruvate dehydrogenase kinase (PDK)4 inhibitor dichloroacetate or after knockdown of both PPARβ and PDK4 with siRNA. The ERK1/2 inhibitor PD98059, ROS scavenger catalase, inhibitor of complex II thenoyltrifluoroacetone or uncoupler of oxidative phosphorylation, carbonyl cyanide m‐chlorophenylhydrazone, also prevented glucose‐induced insulin resistance. In STZ diabetic rats, oral GW0742 also improved insulin signalling and the impaired NO‐mediated vascular relaxation.
Conclusion and Implications
PPARβ activation in vitro and in vivo restores the endothelial function, preserving the insulin‐Akt‐eNOS pathway impaired by high glucose, at least in part, through PDK4 activation.
1. Urinary excretion of digoxin-like immunoreactive factor and arginine-vasopressin and other parameters related to salt and water metabolism were studied in hyper- and hypo-thyroid rats after different tests.
2. Urinary excretion of arginine-vasopressin was increased in hyperthyroid and reduced in hypothyroid rats with respect to controls, in response to water deprivation or a hypertonic saline load.
3. Control and hypothyroid rats showed the highest urinary excretion of digoxin-like immunoreactive factor after a hypertonic saline load. However, hyperthyroid rats had the highest urinary levels of digoxin-like immunoreactive factor under normal conditions.
4. From these results it is suggested that: (a) hyper- and hypo-thyroid rats exhibit hyper- and hypo-responsiveness of arginine-vasopressin secretion to osmotic stimuli, respectively; (b) an unidentified digoxin-like immunoreactive factor measured in unextracted rat urine may be related to diuresis and natriuresis in control and hypothyroid rats; however, dissociation between this factor and natriuresis is observed in hyperthyroid rats.
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