Insulin potentiates cytokine-induced VCAM-1 expression in human endothelial cells

Hyperinsulinemia is an independent risk factor for cardiovascular events and may contribute to cardiovascular disease. Low-grade chronic inflammation has been implicated in the pathogenesis of atherosclerosis. We aimed at determining the impact of pathophysiologically high insulin concentrations on cytokine-induced endothelial activation in human umbilical vein endothelial cells (HUVEC). HUVEC were incubated with insulin (0-24 h)+/-tumor necrosis factor (TNF)-alpha or lipopolysaccharide (LPS). At pathophysiological/pharmacological concentrations (10(-9)-10(-7) mol/L), insulin selectively induced VCAM-1 expression and potentiated the effects of TNF-alpha andLPS, effects reverted by the proteasome inhibitor lactacystin. Compared with TNF-alpha alone, insulin+TNF-alpha doubled U937 cell adhesion. Insulin markedly increased TNF-alpha-induced NF-kappaB activation and induced phosphorylated IkappaB-alpha accumulation. Therefore, hyperinsulinemia enhances cytokine-induced VCAM-1 expression in endothelial cells, thus potentially contributing to detrimental effects of other inflammatory stimuli on atherogenesis.     

The Human Brain Maintains Contradictory and Redundant Auditory Sensory Predictions

Computational and experimental research has revealed that auditory sensory predictions are derived from regularities of the current environment by using internal generative models. However, so far, what has not been addressed is how the auditory system handles situations giving rise to redundant or even contradictory predictions derived from different sources of information. To this end, we measured error signals in the event-related brain potentials (ERPs) in response to violations of auditory predictions. Sounds could be predicted on the basis of overall probability, i.e., one sound was presented frequently and another sound rarely. Furthermore, each sound was predicted by an informative visual cue. Participants’ task was to use the cue and to discriminate the two sounds as fast as possible. Violations of the probability based prediction (i.e., a rare sound) as well as violations of the visual-auditory prediction (i.e., an incongruent sound) elicited error signals in the ERPs (Mismatch Negativity [MMN] and Incongruency Response [IR]). Particular error signals were observed even in case the overall probability and the visual symbol predicted different sounds. That is, the auditory system concurrently maintains and tests contradictory predictions. Moreover, if the same sound was predicted, we observed an additive error signal (scalp potential and primary current density) equaling the sum of the specific error signals. Thus, the auditory system maintains and tolerates functionally independently represented redundant and contradictory predictions. We argue that the auditory system exploits all currently active regularities in order to optimally prepare for future events.     

The Effects of Aging on Conflict Detection

Several cognitive changes characterize normal aging; one change regards inhibitory processing and includes both conflict monitoring and response suppression. We attempted to segregate these two aspects within a Go/No-go task, investigating three age categories. Accuracy, response times and event-related potentials (ERPs) were recorded. The ERP data were analyzed, and the Go and No-go trials were separated; in addition, the trials were organized in repeat trials (in which the subjects repeated the action delivered in the previous trial) and switch trials (in which the subjects produced a response opposite to the previous response). We assumed that the switch trials conveyed more conflict than the repeat trials. In general, the behavioral data and slower P3 latencies confirmed the well-known age-related speed/accuracy trade-off. The novel analyses of the repeat vs. switch trials indicated that the age-related P3 slowing was significant only for the high conflict condition; the switch-P3 amplitude increased only in the two older groups. The ‘aging switch effect’ on the P3 component suggests a failure in the conflict conditions and likely contributes to a generalized dysfunction. The absence of either a switch effect in the young group and the P3 slowing in middle-aged group indicate that switching was not particularly demanding for these participants. The N2 component was less sensitive to the repeat/switch manipulation; however, the subtractive waves also enhanced the age effects in this earlier time window. The topographic maps showed other notable age effects: the frontal No-go N2 was nearly undetectable in the elderly; in the identical time window, a large activity in the posterior and prefrontal scalp regions was observed. Moreover, the prefrontal activity showed a negative correlation with false alarms. These results suggest that the frontal involvement during action suppression becomes progressively dysfunctional with aging, and additional activity was required to reach a good level of accuracy.     

Premature birth and circadian preference in young adulthood: evidence from two birth cohorts

A preference for eveningness (being a “night owl”) and preterm birth (<37 weeks of gestation) are associated with similar adversities, such as elevated blood pressure, impaired glucose regulation, poorer physical fitness, and lower mood. Yet, it remains unclear if and how preterm birth is associated with circadian preference. The aim of this study was to assess this association across the whole gestation range, using both objective and subjective measurements of circadian preference.

Circadian preference was measured among 594 young adults (mean age 24.3 years, SD 1.3) from two cohorts: the ESTER study and the Arvo Ylppö Longitudinal Study. We compared 83 participants born early preterm (<34 weeks) and 165 late preterm (34 to <37 weeks) with those born at term (≥37 weeks, n = 346). We also compared very low birth weight (VLBW, <1500 g) participants with term-born controls. We obtained objective sleep data with actigraphs that were worn for a mean period of 6.8 (SD 1.4) nights. Our primary outcome was sleep midpoint during weekdays and weekend. The sleep midpoint is the half-way time between falling asleep and waking up, and it represents sleep timing. We also investigated subjective chronotype with the Morningness–Eveningness Questionnaire (MEQ) in 688 (n = 138/221/329) ESTER participants. The MEQ consists of 19 questions, which estimates the respondent to be of a “morning”, “evening,” or “intermediate” chronotype, based on the Morningness–Eveningness Score (MES). We analyzed the data from the actigraphs and the MES with three linear regression models, and analyzed distribution of the chronotype class with Pearson χ2.

There were no consistent differences across the study groups in sleep midpoint. As compared with those born at term, the mean differences in minutes:seconds and 95% confidence intervals for the sleep midpoint were: early preterm weekdays 11:47 (?8:34 to 32:08), early preterm weekend 4:14 (?19:45 to 28:13), late preterm weekdays ?10:28 (?26:16 to 5:21), and late preterm weekend ?1:29 (?20:36 to 17:37). There was no difference in sleep timing between VLBW-participants and controls either. The distribution of chronotype in the MEQ among all participants was 12.4% morningness, 65.4% intermediate, and 22.2% eveningness. The distribution of the subjective chronotype class did not differ between the three gestational age groups (p = 0.98). The linear regression models did not show any influence of gestational age group or VLBW status on the MES (all p > 0.5).

We found no consistent differences between adults born early or late preterm and those born at term in circadian preference. The earlier circadian preference previously observed in those born smallest is unlikely to extend across the whole range of preterm birth.     

The interplay between cytokinins and light during senescence in detached Arabidopsis leaves

Light and cytokinins are known to be the key players in the regulation of plant senescence. In detached leaves, the retarding effect of light on senescence is well described; however, it is not clear to what extent is this effect connected with changes in endogenous cytokinin levels. We have performed a detailed analysis of changes in endogenous content of 29 cytokinin forms in detached leaves of Arabidopsis thaliana (wild‐type and 3 cytokinin receptor double mutants). Leaves were kept under different light conditions, and changes in cytokinin content were correlated with changes in chlorophyll content, efficiency of photosystem II photochemistry, and lipid peroxidation. In leaves kept in darkness, we have observed decreased content of the most abundant cytokinin free bases and ribosides, but the content of cis‐zeatin increased, which indicates the role of this cytokinin in the maintenance of basal leaf viability. Our findings underscore the importance of light conditions on the content of specific cytokinins, especially N⁶‐(Δ²‐isopentenyl)adenine. On the basis of our results, we present a scheme summarizing the contribution of the main active forms of cytokinins, cytokinin receptors, and light to senescence regulation. We conclude that light can compensate the disrupted cytokinin signalling in detached leaves.