Dimerization of Translationally Controlled Tumor Protein Is Essential For Its Cytokine-Like Activity

BACKGROUND:Translationally Controlled Tumor Protein (TCTP) found in nasal lavage fluids of allergic patients was named IgE-dependent histamine-releasing factor (HRF). Human recombinant HRF (HrHRF) has been recently reported to be much less effective than HRF produced from activated mononuclear cells (HRFmn). METHODS AND FINDINGS:We found that only NH(2)-terminal truncated, but not C-terminal truncated, TCTP shows cytokine releasing activity compared to full-length TCTP. Interestingly, only NH(2)-terminal truncated TCTP, unlike full-length TCTP, forms dimers through intermolecular disulfide bonds. We tested the activity of dimerized full-length TCTP generated by fusing it to rabbit Fc region. The untruncated-full length protein (Fc-HrTCTP) was more active than HrTCTP in BEAS-2B cells, suggesting that dimerization of TCTP, rather than truncation, is essential for the activation of TCTP in allergic responses. We used confocal microscopy to evaluate the affinity of TCTPs to its putative receptor. We detected stronger fluorescence in the plasma membrane of BEAS-2B cells incubated with Del-N11TCTP than those incubated with rat recombinant TCTP (RrTCTP). Allergenic activity of Del-N11TCTP prompted us to see whether the NH(2)-terminal truncated TCTP can induce allergic airway inflammation in vivo. While RrTCTP had no influence on airway inflammation, Del-N11TCTP increased goblet cell hyperplasia in both lung and rhinal cavity. The dimerized protein was found in sera from allergic patients, and bronchoalveolar lavage fluids from airway inflamed mice. CONCLUSIONS:Dimerization of TCTP seems to be essential for its cytokine-like activity. Our study has potential to enhance the understanding of pathogenesis of allergic disease and provide a target for allergic drug development

Money matters: exploiting the data from outcomes research for quality improvement initiatives

In recent years, there has been an increase in studies that have sought to identify predictors of treatment outcome and to examine the efficacy of surgical and non-surgical treatments. In addition to the scientific advancement associated with these studies per se, the hospitals and clinics where the studies are conducted may gain indirect financial benefit from participating in such projects as a result of the prestige derived from corporate social responsibility, a reputational lever used to reward such institutions. It is known that there is a positive association between corporate social performance and corporate financial performance. However, in addition to this, the research findings and the research staff can constitute resources from which the provider can reap a more direct benefit, by means of their contribution to quality control and improvement. Poor quality is costly. Patient satisfaction increases the chances that the patient will be a promoter of the provider to friends and colleagues. As such, involvement of the research staff in the improvement of the quality of care can ultimately result in economic revenue for the provider. The most advanced methodologies for continuous quality improvement (e.g., six-sigma) are data-driven and use statistical tools similar to those utilized in the traditional research setting. Given that these methods rely on the application of the scientific process to quality improvement, researchers have the adequate skills and mind-set to embrace them and thereby contribute effectively to the quality team. The aim of this article is to demonstrate by means of real-life examples how to utilize the findings of outcome studies for quality management in a manner similar to that used in the business community. It also aims to stimulate research groups to better understand that, by adopting a different perspective, their studies can be an additional resource for the healthcare provider. The change in perspective should stimulate researchers to go beyond the traditional studies examining predictors of treatment outcome and to see things instead in terms of the “bigger picture”, i.e., the improvement of the process outcome, the quality of the service

An Integrated View of the Use of Quality Cost Information, the Improvement of the Quality Management System and Effects on Performance: a Study in Portuguese Companies

The literature focusing on quality costs has placed great importance on issues related to identifying, measuring and reporting quality cost information. Less attention has been paid to how this information is used in the management process and how it can enhance internal capabilities and thereby improve company performance. In addition to addressing this question, we analyse how the extensive use of quality costs can boost organisational learning and innovation in organisations' internal processes, thus leading to an overall improvement in the quality management system that is reflected in financial and non-financial performance. The conceptual model developed involves these relationships and has been tested using the structural equation modelling technique. To this end, a questionnaire survey was conducted in Portuguese companies with the ISO 9000 certification. The results shed light on the causal links between the variables, and thus validate the conceptual model indicating that the use of quality cost information has a positive effect on both the development of quality management systems and performanc

Effects of salinity acclimation on the expression and activity of Phase I enzymes (CYP450 and FMOs) in coho salmon (Oncorhynchus kisutch)

Phase I biotransformation enzymes are critically important in the disposition of xenobiotics within biota and are regulated by multiple environmental cues, particularly in anadromous fish species. Given the importance of these enzyme systems in xenobiotic/endogenous chemical bioactivation and detoxification, the current study was designed to better characterize the expression of Phase I biotransformation enzymes in coho salmon (Oncorhynchus kisutch) and the effects of salinity acclimation on those enzymes. Livers, gills and olfactory tissues were collected from coho salmon (Oncorhynchus kisutch) after they had undergone acclimation from freshwater to various salinity regimes of seawater (8, 16 and 32 g/L). Using immunoblot techniques coupled with testosterone hydroxylase catalytic activities, 4 orthologs of cytochrome P450 (CYP1A, CYP2K1, CYP2M1 and CYP3A27) were measured in each tissue. Also the expression of 2 transcripts of flavin-containing monooxygenases (FMO A and B) and associated activities were measured. With the exception of CYP1A, which was down-regulated in liver, protein expression of the other 3 enzymes was induced at higher salinity, with the greatest increase observed in CYP2M1 from olfactory tissues. In liver and gills, 6 - and 16 -hydroxylation of testosterone was also significantly increased after hypersaline acclimation. Similarly, FMO A was up-regulated in all 3 tissues in a salinity-dependent pattern, whereas FMO B mRNA was down-regulated. FMO-catalyzed benzydamine N-oxygenase and methyl p-tolyl sulfoxidation were significantly induced in liver and gills by hypersalinity, but was either unchanged or not detected in olfactory tissues. These data demonstrate thatenvironmental conditions may significantly alter the toxicity of environmental chemicals in salmon during freshwater/saltwater acclimation

Widespread patterns of sexually dimorphic gene expression in an avian hypothalamic–pituitary–gonadal (HPG) axis

The hypothalamic-pituitary-gonadal (HPG) axis is a key biological system required for reproduction and associated sexual behaviors to occur. In the avian reproductive model of the rock dove (Columba livia), we characterized the transcript community of each tissue of the HPG axis in both sexes, thereby significantly expanding our mechanistic insight into HPG activity. We report greater sex-biased differential expression in the pituitary as compared to the hypothalamus, with multiple genes more highly expressed in the male pituitary being related to secretory function, and multiple genes more highly expressed in the female pituitary being related to reproduction, growth, and development. We report tissue-specific and sex-biased expression in genes commonly investigated when studying reproduction, highlighting the need for sex parity in future studies. In addition, we uncover new targets of investigation in both sexes, which could potentially change our understanding of HPG function