p53, a Novel Inhibitor of Apoptosis

p53 is a transcription factor known to induce apoptosis via transactivating the expression of pro-apoptotic proteins and by directly activating the mitochondria apoptotic pathway. p53 is also found to be mutated in 50% of human cancers with some of these tumours overexpressing both wild type (WT) and mutant p53. Overexpression of the p53 protein has been implicated with the more aggressive nature of these tumour cells, suggesting a possible gain-of-function of such mutants. In this study, the involvement of p53 in apoptosis via the caspase pathway was investigated. WT-p53 and three mutant p53 with mutations at the 1) N-terminus (D42Y), 2) central domain (R175H) and 3) C-terminus (R337H) were selected. The data collected demonstrated that p53 was able to inhibit the cleavage of caspases early in the apoptotic pathway. In vitro assays showed that addition of recombinant WT and the mutant p53 inhibited the cleavage of both caspase-9 and caspase-3 and subsequently PARP, while overexpression of p53 in mammalian cells yielded the same inhibition profile in vivo. Conversely, removal of p53 via siRNA and immunodepletetion showed accelerated caspase-9 activity and cleavage. Immunoprecipitation experiments and recombinant assay systems suggest that the inhibition by p53 is targeted at the active cleaved caspase-9. In addition, the presence of p53 (WT or mutant) in p53-null cells were able to confer a higher survival rate. These data therefore demonstrate that p53 may have an additional anti-apoptotic role via the inhibition of caspase-9, which is often masked by its pro-apoptotic functions. This anti-apoptotic role could manifest itself in a cancer background overexpressing mutant p53 which has lost its transcriptional activity and hence its ability to induce apoptosis via the induction of pro-apoptotic genes such as PUMA and NOXA. This newly discovered role of p53 could potentially explain the aggressive nature of cancers which overexpress p53

Chronic hepatitis B - New goals, new treatment

published_or_final_versio

Updates in the treatment of chronic hepatitis B

published_or_final_versio

Frequency and accuracy of weight comments by others, and the association with weight misperception among Hong Kong adolescents

*Purpose:* To assess the frequency and accuracy of weight comments received from different sources among Chinese adolescents and the relation of weight comments to weight misperception.

*Methods:* In the Hong Kong Student Obesity Surveillance (HKSOS) project 2006-07, 22612 form 1 to 7 students (41.5% boys) completed a questionnaire on obesity. Students were asked if they had received serious "too fat" or "too thin" comments over the past 30 days from family members, peers and professionals, and the accuracy of the comments was assessed against the actual weight status. Weight misperception was defined as discordance between the actual and perceived weight status. Logistic regression was used to calculate adjusted odd ratios (ORs) for weight misperception by weight comments received.

*Results:* One in three students received weight comments, most commonly from mother for both "too fat" and "too thin" comments. Health professional was the most accurate source of weight comments, yet less than half the comments were correct. Receiving incorrect weight comments was significantly associated with weight misperception in all sex-weight status sub-groups, particularly among obese girls. In contrast, student who received correct weight comments were less likely to have weight misperception.

*Conclusions:* Weight comments were commonly received by Chinese adolescents in Hong Kong, yet most of the comments were inaccurate, and such incorrect comments were associated with weight misperception. Family members, peers and professionals should realize the potential adverse effects of their weight comments and adolescents should be taught how to correctly assess their weight status to reduce misperceptions

Finite element analysis of concrete-encased steel composite columns with off-center steel section

[EN] Concrete encased steel composite columns have been widely used in high-rise buildings and top-down constructions owning to excellent load-carrying capacity and fire resistance. However, double symmetric composite section is rarely achieved due to the off-center eccentricity of steel kingpost, which is a common problem in top-down constructions. EN1994-1-1 (EC4) simplified method does not provide any explicit provisions for this kind of irregular composite columns, and many designers address this issue by reducing it into a symmetrical cross-section for ease of simple calculation. This paper presents a general method based on nonlinear finite element modelling software ABAQUS to analyze the ultimate strength behavior of concrete-encased composite columns with asymmetrically placed steel section. The accuracy of the FE model is verified against existing test results. Parametric study is performed to further investigate the influence of steel section eccentricity on ultimate strength of stub columns under different loading conditions. A simplified method based on modification of EC4 design approach is developed to construct the moment-axial force interaction diagram. Accuracy of the proposed method is assessed by comparing the analytically predicted results with the numerical results. It is found that the proposed method can be adopted as a useful tool to predict the cross-section resistance of non-symmetrical concrete-encased steel composite columns.The research is funded by the Building & Construction Authority of Singapore under project grant R-302-000-168-409.Lai, B.; Liew, JY.; Li, S. (2018). Finite element analysis of concrete-encased steel composite columns with off-center steel section. En Proceedings of the 12th International Conference on Advances in Steel-Concrete Composite Structures. ASCCS 2018. Editorial Universitat Politècnica de València. 297-303. https://doi.org/10.4995/ASCCS2018.2018.7005OCS29730