Calcineurin expression and activity is regulated by the intracellular redox status and under hypertension in human neutrophils

Calcineurin (protein phosphatase 2B) (CN) comprises a family of serine/threonine phosphatases that play a pivotal role in signal transduction cascades in a variety of cells, including neutrophils. Angiotensin II (Ang II) increases both activity and de novo synthesis of CN in human neutrophils. This study focuses on the role that intracellular redox status plays in the induction of CN activity by Ang II. Both de novo synthesis of CN and activity increase promoted by Ang II were downregulated when cells were treated with l-buthionine-(S,R)-sulfoximine, an inhibitor of synthesis of the antioxidant glutathione. We have also investigated the effect of pyrrolidine dithiocarbamate and phenazine methosulfate, which are antioxidant and oxidant compounds, respectively, and concluded that the intracellular redox status of neutrophils is highly critical for Ang II-induced increase of CN expression and activity. Results obtained in neutrophils from hypertensive patients were very similar to those obtained in these cells on treatment with Ang II. We have also addressed the possible functional implication of CN activation in the development of hypertension. Present findings indicate that downregulation of hemoxygenase-1 expression in neutrophils from hypertensive subjects is likely mediated by CN, which acts by hindering translocation to the nucleus of the transcription factor NRF2. These data support and extend our previous results and those from other authors on modulation of CN expression and activity levels by the intracellular redox status.

First molar size and wear within and among modern hunter-gatherers and agricultural populations

Apart from reflecting modern human dental variation, differences in dental size among populations provide a means for studying continuous evolutionary processes and their mechanisms. Dental wear, on the other hand, has been widely used to infer dietary adaptations and variability among or within diverse ancient human populations. Few such studies have focused on modern foragers and farmers, however, and diverse methods have been used. This research aimed to apply a single, standardized, and systematic quantitative procedure to measure dental size and dentin exposure in order to analyze differences among several hunter-gatherer and agricultural populations from various environments and geographic origins. In particular, we focused on sexual dimorphism and intergroup differences in the upper and lower first molars. Results indicated no sexual dimorphism in molar size and wear within the studied populations. Despite the great ethnographic variation in subsistence strategies among these populations, our findings suggest that differences in sexual division of labor do not affect dietary wear patterns.

The Big BIM battle: BIM adoption in the UK for large and small companies

As BIM adoption continues, the goal of a totally collaborative model with multiple contributors is attainable. Many initiatives such as the 2016 UK government level 2 BIM deadline are putting pressure on the construction industry to speed up the changeover. Clients and collaborators have higher expectations of using digital 3D models to communicate design ideas and solve practical problems. Contractors and clients are benefitting from cost saving scheduling and clash detection offered by BIM. Effective collaboration on the project will also give speed and efficiency gains. Despite this, many businesses of varying sizes are still having problems. The cost of the software and the training provides an obvious barrier for micro-enterprises and could explain a delay in adoption. Many studies have looked at these problems faced by SME and micro-enterprises. Larger companies have different problems. The efforts made by government to encourage them are quite comprehensive, but is anything being done to help smaller sectors and keep the industry cohesive? This limited study examines several companies of varying size and varying project type: architectural design businesses, main contractor, structural engineer and building consultancy. The study examines the barriers to a truly collaborative BIM workflow facing different specialities on a larger project and a contrasting small/medium project. The findings will establish that different barriers for each sector are actually pushing further apart, thus potentially creating a BIM-only construction elite, leaving the small companies remaining on 2D based drawing.