Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.

Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer

The evolution of pellet size and shape during spheronisation of an extruded microcrystalline cellulose paste

The process by which cylindrical rods of soft solid paste extrudate are converted into round pellets on a spheroniser (Marumeriser™) plate was studied by interrupting spheronisation tests and measuring the size and shape of the pellets. Batches of 20 identical rods (20 mm long, 3 mm diameter) generated by ram extrusion of 47 wt% microcrystalline cellulose/water paste were spheronised at rotational speeds, ω, between 1200 rpm and 1800 rpm on a laboratory spheroniser. The time to complete spheronisation was found to scale with ω−3.6, which was close to the ω−3dependency predicted by a simple collision model. Breakage occupied the first 10% of the process duration: rounding off was the rate-determining step. The evolution of pellet shape was classified into five stages, the duration of which was found to scale with spheronisation time. Pellet shape, quantified by aspect ratio, circularity, shape and angularity factors presented by Sukumaran and Ashmawy (2001), showed similar behaviour for all ω studied. A phenomenological model is proposed which identifies different routes for small and large rod breakage products.This is the accepted manuscript of an article originally published in Chemical Engineering Research and Design. The final published version is available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0263876214000379

Creating, Connecting, and Communicating: A look at social support for postpartum women

The prevalence of postpartum depression underscores the critical need for support systems for new mothers. Virtual support groups, such as the Fourth Trimester Support Group described in this paper, represent a promising avenue for addressing these challenges and providing much-needed support. This article describes the formation, activities, and evaluation of an online support group that leverages technology to foster a sense of community for new mothers. Further, the details within the case study provide a basic model for starting a similar support group

Substantial Increases in Eastern Amazon and Cerrado Biomass Burning‐Sourced Tropospheric Ozone

The decline in Amazonian deforestation rates and biomass burning activity (2001–2012) has been shown to reduce air pollutant emissions (e.g., aerosols) and improve regional air quality. However, in the Cerrado region (savannah grasslands in northeastern Brazil), satellite observations reveal increases in fire activity and tropospheric column nitrogen dioxide (an ozone precursor) during the burning season (August‐October, 2005–2016), which have partially offset these air quality benefits. Simulations from a 3‐D global chemistry transport model (CTM) capture this increase in NO2 with a surface increase of ~1 ppbv per decade. As there are limited long‐term observational tropospheric ozone records, we utilize the well‐evaluated CTM to investigate changes in ozone. Here, the CTM suggests that Cerrado region surface ozone is increasing by ~10 ppbv per decade. If left unmitigated, these positive fire‐sourced ozone trends will substantially increase the regional health risks and impacts from expected future enhancements in South American biomass burning activity under climate change

Cooling interventions for athletes: An overview of effectiveness, physiological mechanisms, and practical considerations.

Exercise-induced increases in core body temperature could negative impact performance and may lead to development of heat-related illnesses. The use of cooling techniques prior (pre-cooling), during (per-cooling) or directly after (post-cooling) exercise may limit the increase in core body temperature and therefore improve exercise performance. The aim of the present review is to provide a comprehensive overview of current scientific knowledge in the field of pre-cooling, per-cooling and post-cooling. Based on existing studies, we will discuss 1) the effectiveness of cooling interventions, 2) the underlying physiological mechanisms and 3) practical considerations regarding the use of different cooling techniques. Furthermore, we tried to identify the optimal cooling technique and compared whether cooling-induced performance benefits are different between cool, moderate and hot ambient conditions. This article provides researchers, physicians, athletes and coaches with important information regarding the implementation of cooling techniques to maintain exercise performance and to successfully compete in thermally stressful conditions

Can programme theory be used as a 'translational tool’ to optimise health service delivery in a national early years’ initiative in Scotland: a case study

Background Theory-based evaluation (TBE) approaches are heralded as supporting formative evaluation by facilitating increased use of evaluative findings to guide programme improvement. It is essential that learning from programme implementation is better used to improve delivery and to inform other initiatives, if interventions are to be as effective as they have the potential to be. Nonetheless, few studies describe formative feedback methods, or report direct instrumental use of findings resulting from TBE. This paper uses the case of Scotland’s, National Health Service, early years’, oral health improvement initiative (Childsmile) to describe the use of TBE as a framework for providing feedback on delivery to programme staff and to assess its impact on programmatic action.<p></p> Methods In-depth, semi-structured interviews and focus groups with key stakeholders explored perceived deviations between the Childsmile programme 'as delivered’ and its Programme Theory (PT). The data was thematically analysed using constant comparative methods. Findings were shared with key programme stakeholders and discussions around likely impact and necessary actions were facilitated by the authors. Documentary review and ongoing observations of programme meetings were undertaken to assess the extent to which learning was acted upon.<p></p> Results On the whole, the activities documented in Childsmile’s PT were implemented as intended. This paper purposefully focuses on those activities where variation in delivery was evident. Differences resulted from the stage of roll-out reached and the flexibility given to individual NHS boards to tailor local implementation. Some adaptations were thought to have diverged from the central features of Childsmile’s PT, to the extent that there was a risk to achieving outcomes. The methods employed prompted national service improvement action, and proposals for local action by individual NHS boards to address this.<p></p> Conclusions The TBE approach provided a platform, to direct attention to areas of risk within a national health initiative, and to agree which intervention components were 'core’ to its hypothesised success. The study demonstrates that PT can be used as a 'translational tool’ to facilitate instrumental use of evaluative findings to optimise implementation within a complex health improvement programme.<p></p&gt

Glycerine derived from biodiesel production as a feedstuff for broiler diets

The performance, carcass traits, and litter humidity of broilers fed increasing levels of glycerine derived from biodiesel production were evaluated. In this experiment, 1,575 broilers were distributed according to a completely randomized experimental design into five treatments with seven replicates of 45 birds each. Treatments consisted of a control diet and four diets containing 2.5, 5.0, 7.5, or 10% glycerine. The experimental diets contained equal nutritional levels and were based on corn, soybean meal and soybean oil. The glycerine included in the diets contained 83.4% glycerol, 1.18% sodium, and 208 ppm methanol, and a calculated energy value of 3,422 kcal AMEn/kg. Performance parameters (weight gain, feed intake, feed conversion ratio, live weight, and livability) were monitored when broilers were 7, 21, and 42 days of age. On day 43, litter humidity was determined in each pen, and 14 birds/treatment were sacrificed for the evaluation of carcass traits. During the period of 1 to 7 days, there was a positive linear effect of the treatments on weight gain, feed intake, and live weight gain. Livability linearly decreased during the period of 1 to 21 days. During the entire experimental period, no significant effects were observed on performance parameters or carcass traits, but there was a linear increase in litter humidity. Therefore, the inclusion of up to 5% glycerine in the diet did not affect broiler performance during the total rearing period

Fear and Courage in Children: Two Sides of the Same Coin?

This study further investigated the construct of courage in children. Children aged 8–13 years (n = 51) were interviewed about the most courageous action that they had ever performed during their life, and to retrospectively rate their level of fear and courage experienced during that event. On a separate occasion, children also completed the Courage Measure for Children (CM-C) as an index of children’s general level of personal courage, as well as scales for assessing anxiety symptoms and sensation seeking. Results indicated that almost all children (i.e., 94%) indicated that they had carried out a courageous action at some point during their life, although the levels of fear and courage associated with these acts varied considerably. Further, there was no relation between fear and courage reported for the courageous action, but these variables were significantly correlated with respectively anxiety symptoms and personal courage as indexed by the CM-C. Finally, a significant positive correlation was observed between sensation seeking and personal courage, indicating that children who are more thrill and adventure seeking are generally also more courageous. It is concluded that fear and courage in children are largely unrelated and not just two sides of the same coin. The implications of these results for the etiology and treatment of childhood anxiety problems are discussed