Walls Mahmoud (trowelwax1)
Few proteins are more studied than the p53 tumour suppressor, but what have we learned from these studies and what do we really know about p53 that can benefit clinical practice? The DNA sequence encoding p53 is frequently mutated in cancers but the functional outcomes of single mutations, in respect to loss or gain of different activities, especially in relation to immune evasion, are not clear. This illustrates p53's complexity which even after 40 years keeps providing surprises, but also explains why it has not yet lived up to its potential to benefit cancer treatment. We have reassessed a few key experiments that shaped the p53 field and we take a closer look at the interpretations of these experiments what they have taught us, the resulting dogmas, and their potential clinical importance. One outcome is a more dynamic view of p53 in terms of its activity, its regulation, and downstream effectors, which will benefit the clinical application of p53 for diagnosis, prognosis, and therapy. Mutations and regulatory factors can have different effects on p53 activity depending on context, important but neglected aspects when interpreting p53 and its pathways in cancers. Even though p53 is undoubtedly unique as a multifunctional hub in different cellular pathways, the concept of a factor taking up different functions within a regulatory pathway during different conditions is not. selleck In this sense, p53 continues to lead the way for a better understanding of the cellular and molecular mechanisms underlying cancer development in vivo. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Intensive vegetable cropping systems rely heavily on nitrogen (N) inputs from multiple synthetic and organic fertilizer applications. The majority of applied N is lost to the environment through numerous pathways, including as nitrous oxide (N2 O). A field trial was conducted to examine the opportunities to reduce N input in an intensive vegetable system without compromising yield. Treatments applied were control (no N), manure (M, 408 kg N ha-1 from chicken manure), grower practice (GP, 408 kg N ha-1 from chicken manure + 195 kg N ha-1 from fertilizer), and 2/3 GP (two-thirds of the total N input in GP), all with and without 3,4-dimethylpyrazole phosphate (DMPP). Nitrogen recovery in the GP treatment was determined using 15 N-labeled fertilizer. Using only manure significantly lowered celery (Apium graveolens L.) yield and apparent N use efficiency (ANUE) compared with GP. Reducing N input by one-third did not affect yield or ANUE. Use of DMPP increased ANUE despite no yield improvement. More than 50% of the applied N in the GP treatment was lost to the environment, with almost 10 kg N ha-1 emitted as N2 O over the season, which was 67 times more than from the control. Reducing the N input by one-third or using manure only reduced N2 O emissions by more than 70% relative to GP. This study shows that there is a clear opportunity to reduce N input and N2 O emissions in high-fertilizer-input vegetable systems without compromising vegetable yield.Despite a lot of intensive research on cell-scaffold interaction, the focus is mainly on the capacity of construct scaffolds to regulate cell mobility, migration, and cytotoxicity. The effect of the scaffold's topographical and material properties on the expression of biologically active compounds from stem cells is not well understood. In this study, the influence of cellulose acetate (CA) on the electrospinnability of gelatin and the roles of gelatin-cellulose acetate (Ge-CA) on modulating the release of biologically active compounds from amniotic fluid stem cells (AFSCs) is emphasized. It was found that the presence of a small amount of CA could provide a better microenvironment that mimics AFSCs' niche. However, a large amount of CA exhibited no significant effect on AFSCs migration and infiltration. Further study on the effect of surface topography a