BMP signaling modulates hedgehog-induced secondary heart field proliferation

AbstractSonic hedgehog signaling in the secondary heart field has a clear role in cardiac arterial pole development. In the absence of hedgehog signaling, proliferation is reduced in secondary heart field progenitors, and embryos predominantly develop pulmonary atresia. While it is expected that proliferation in the secondary heart field would be increased with elevated hedgehog signaling, this idea has never been tested. We hypothesized that up-regulating hedgehog signaling would increase secondary heart field proliferation, which would lead to arterial pole defects. In culture, secondary heart field explants proliferated up to 6-fold more in response to the hedgehog signaling agonist SAG, while myocardial differentiation and migration were unaffected. Treatment of chick embryos with SAG at HH14, just before the peak in secondary heart field proliferation, resulted unexpectedly in stenosis of both the aortic and pulmonary outlets. We examined proliferation in the secondary heart field and found that SAG-treated embryos exhibited a much milder increase in proliferation than was indicated by the in vitro experiments. To determine the source of other signaling factors that could modulate increased hedgehog signaling, we co-cultured secondary heart field explants with isolated pharyngeal endoderm or outflow tract and found that outflow tract co-cultures prevented SAG-induced proliferation. BMP2 is made and secreted by the outflow tract myocardium. To determine whether BMP signaling could prevent SAG-induced proliferation, we treated explants with SAG and BMP2 and found that BMP2 inhibited SAG-induced proliferation. In vivo, SAG-treated embryos showed up-regulated BMP2 expression and signaling. Together, these results indicate that BMP signaling from the outflow tract modulates hedgehog-induced proliferation in the secondary heart field

Uncertainty in three dimensions: the challenges of communicating probabilistic flood forecast maps

Real-time operational flood forecasting most often concentrates on issuing streamflow predictions at specific points along the rivers of a watershed. However, we are now witnessing an increasing number of studies aimed at also including flood mapping as part of the forecasting system. While this additional new information (flood extent, depth, velocity, etc.) can potentially be useful for decision-makers, it could also be overwhelming. This is especially true for probabilistic and ensemble forecasting systems. While ensemble streamflow forecasts for a given point in space can be visualized relatively easily, the visualization and communication of probabilistic forecasts for water depth and extent pose additional challenges. Confusion typically arises from too much information, counterintuitive interpretation, or simply too much complexity in the representation of the forecast. The communication and visualization of probabilistic streamflow forecasts has been studied in the past, but this is not the case for the probabilistic flood forecast map, which is still an emerging product. In this paper, we synthesize the results of a large-scale survey (28 government representatives, 52 municipalities, 9 organizations, and 38 citizens and farmers, for a total of 140 people) regarding the users' preferences in terms of visualizing probabilistic flood forecasts over an entire river reach. The survey was performed through interviews, during which the interviewees were asked about their needs in terms of hydrological forecasting. We also presented the interviewees with four prototypes representing alternative visualizations of the same probabilistic forecast in order to understand their preferences in terms of colour maps, wording, and the representation of uncertainty. Our results highlight several issues related to the understanding of probabilities in the specific context of visualizing forecasted flood maps. We propose several suggestions for visualizing probabilistic flood maps and also describe potential adaptations for different categories of end users. This study is the first to investigate the visualization of probabilistic flood maps, which are gaining popularity. Given that the interview questions were not tied to a specific geographical location, our findings are applicable outside of the study area and, therefore, to other operational centres interested in providing probabilistic flood forecast maps to decision-making organizations and citizens.</p

Twenty-four-hour time-use composition and cognitive function in older adults: cross-sectional findings of the ACTIVate study

IntroductionPhysical activity, sedentary behaviour and sleep are associated with cognitive function in older adults. However, these behaviours are not independent, but instead make up exclusive and exhaustive components of the 24-h day. Few studies have investigated associations between 24-h time-use composition and cognitive function in older adults. Of these, none have considered how the quality of sleep, or the context of physical activity and sedentary behaviour may impact these relationships. This study aims to understand how 24-h time-use composition is associated with cognitive function across a range of domains in healthy older adults, and whether the level of recreational physical activity, amount of television (TV) watching, or the quality of sleep impact these potential associations.Methods384 healthy older adults (age 65.5 ± 3.0 years, 68% female, 63% non-smokers, mean education = 16.5 ± 3.2 years) participated in this study across two Australian sites (Adelaide, n = 207; Newcastle, n = 177). Twenty-four-hour time-use composition was captured using triaxial accelerometry, measured continuously across 7 days. Total time spent watching TV per day was used to capture the context of sedentary behaviours, whilst total time spent in recreational physical activity was used to capture the context of physical activity (i.e., recreational accumulation of physical activity vs. other contexts). Sleep quality was measured using a single item extracted from the Pittsburgh Sleep Quality Index. Cognitive function was measured using a global cognition index (Addenbrooke’s Cognitive Examination III) and four cognitive domain composite scores (derived from five tests of the Cambridge Neuropsychological Test Automated Battery: Paired Associates Learning; One Touch Stockings of Cambridge; Multitasking; Reaction Time; Verbal Recognition Memory). Pairwise correlations were used to describe independent relationships between time use variables and cognitive outcomes. Then, compositional data analysis regression methods were used to quantify associations between cognition and 24-h time-use composition.ResultsAfter adjusting for covariates and false discovery rate there were no significant associations between time-use composition and global cognition, long-term memory, short-term memory, executive function, or processing speed outcomes, and no significant interactions between TV watching time, recreational physical activity engagement or sleep quality and time-use composition for any cognitive outcomes.DiscussionThe findings highlight the importance of considering all activities across the 24-h day against cognitive function in older adults. Future studies should consider investigating these relationships longitudinally to uncover temporal effects

Electrophysiological correlates of anticipatory task-switching processes

Abstract Recent studies show a differential switch-related positivity emerging before a switch trial and reflecting anticipatory task-set reconfiguration processes. In this study, the switch-related positivity was examined in a cued task-switching paradigm. Cue-stimulus and response-stimulus intervals were independently manipulated to dissociate between the effects of anticipatory preparation and passive dissipation of task-set interference. Reaction time switch cost declined with increasing cue-stimulus and response-stimulus intervals, suggesting a contribution from both active preparation and passive interference processes. In cue-related difference waveforms, a switch positivity peaked around 350-400 ms and is interpreted as reflecting differential activation of task-set reconfiguration. In stimulus-related difference waveforms, a switch-related negativity is believed to indicate the role of S-R priming and response interference in task-switching

HISTOLOGICAL AND IMMUNOHISTOCHEMICAL EVALUATION OF NEW EPITHELIUM AFTER REMOVAL OF ORAL LEUKOPLAKIA WITH ND:YAG LASER TREATMENT

Laser excision has been used with increasing success to treat oral leukoplakia. The aim of the present study was to evaluate whether clinical healing of a leukoplakia after laser surgery is associated with a normal functional status of the new epithelium and whether pathological alterations in these parameters are related to the risk of local recurrence. The study population consisted of 13 consecutive patients with oral leukoplakia in which clinical healing was achieved after laser therapy using an Nd:YAG laser (Model 6000, Laser Sonics, Cooper Laser Sonics). At the end of the therapy, all patients underwent a second biopsy of the clinically healthy tissue. Epithelial cell turnover was evaluated before and after laser surgery by Ki67 protein expression, and positive staining of more than 20% was considered abnormal. All patients were followed on a monthly basis. Eight patients had abnormally high Ki67 values before laser therapy (mean 27.4 \ub1 6.2%), but the levels decreased significantly after treatment (17.6 \ub1 8.5%; t = 2.6, p &lt; 0.05). High Ki67 values persisted in three patients, and local recurrences in the new epithelium was observed in two of these patients. Kaplan-Meier statistics showed that the between-group difference was statistically significant (Chi square 7.3; p &lt; 0.01). In conclusion, this is the first prospective study to show that clinical healing of leukoplakia treated by laser surgery may be accompanied by altered cell turnover in 20% of the cases. Ki67, as a marker of proliferative status, may be a prognostic indicator in the mucosa replacing the lesion

Early detection of microstructural white matter changes associated with arterial pulsatility

Increased cerebral blood flow pulsatility is common in vascular dementia and is associated with macrostructural damage to cerebral white matter or leukoaraiosis (LA). In this study, we examine whether cerebral blood flow pulsatility is associated with macrostructural and microstructural changes in cerebral white matter in older adults with no or mild leukoaraiosis and no evidence of dementia. Diffusion Tensor Imaging was used to measure fractional anisotropy (FA), an index of the microstructural integrity of white matter, and radial diffusivity (RaD), a measure sensitive to the integrity of myelin. When controlling for age, increased arterial pulsation was associated with deterioration in both measures of white matter microstructure but not LA severity. A stepwise multiple linear regression model revealed that arterial pulsatility index was the strongest predictor of FA (R = .483, adjusted R2 = .220), followed by LA severity, but not age. These findings suggest that arterial pulsatility may provide insight into age-related reduction in white matter FA. Specifically, increased arterial pulsatility may increase perivascular shear stress and lead to accumulation of damage to perivascular oligodendrocytes, resulting in microstructural changes in white matter and contributing to proliferation of LA over time. Changes in cerebral blood flow pulsatility may therefore provide a sensitive index of white matter health that could facilitate the early detection of risk for perivascular white matter damage and the assessment of the effectiveness of preventative treatment targeted at reducing pulsatility

Use of LDH- chromate adsorption co-product as an air purification photocatalyst

Embargado hasta 01/01/2024This work deals with the use of layered double hydroxides for a double environmental remediation. The residue obtained in the use of these materials as a chromate sorbent in water, was subsequently studied as a photocatalyst for the removal of NOx gases. With this aim, MgAl–CO3 layered double hydroxides were synthesized by the coprecipitation method with a divalent/trivalent metal ratio of 3. After its calcination at 500 °C, the mixed oxide was obtained and MgAl–CrO4 were synthesized by the reconstruction method. A complete chemical, morphological and photochemical study of the samples was carried out with techniques such as XRD, FT-IR, TGA, XRF, PL, DRIFTS and UV–Vis spectroscopy. Results showed that LDH materials presented no significant changes in their structure after their use as a sorbent. Photocatalytic tests of the samples showed a very good NO removal efficiency, as well as a high selectivity (low NO2 emissions) through complete oxidation of these oxides to nitrate. The incorporation of chromate into the LDH structure improved the absorption of light in the visible region of the spectra, producing an improvement of 20% in the NO elimination compared with the LDH without chromate