Effect of p53 Status and STAT1 on Chemotherapy-Induced, Fas-Mediated Apoptosis in Colorectal Cancer

We investigated the role of p53 and the signal transducer and activator of transcription 1 (STAT1) in regulating Fas-mediated apoptosis in response to chemotherapies used to treat colorectal cancer. We found that 5-fluorouracil (5-FU) and oxaliplatin only sensitized p53 wild-type (WT) colorectal cancer cell lines to Fas-mediated apoptosis. In contrast, irinotecan (CPT-11) and tomudex sensitized p53 WT, mutant, and null cells to Fas-mediated cell death. Furthermore, CPT-11 and tomudex, but not 5-FU or oxaliplatin, up-regulated Fas cell surface expression in a p53-independent manner. In addition, increased Fas cell surface expression in p53 mutant and null cell lines in response to CPT-11 and tomudex was accompanied by only a slight increase in total Fas mRNA and protein expression, suggesting that these agents trigger p53-independent trafficking of Fas to the plasma membrane. Treatment with CPT-11 or tomudex induced STAT1 phosphorylation (Ser727) in the p53-null HCT116 cell line but not the p53 WT cell line. Furthermore, STAT1-targeted small interfering RNA (siRNA) inhibited up-regulation of Fas cell surface expression in response to CPT-11 and tomudex in these cells. However, we found no evidence of altered Fas gene expression following siRNA-mediated down-regulation of STAT1 in drug-treated cells. This suggests that STAT1 regulates expression of gene(s) involved in cell surface trafficking of Fas in response to CPT-11 or tomudex. We conclude that CPT-11 and tomudex may be more effective than 5-FU and oxaliplatin in the treatment of p53 mutant colorectal cancer tumors by sensitizing them to Fas-mediated apoptosis in a STAT1-dependent manner.

A review of the status and decline in abundance of the Irish Hare (Lepus timidus hibernicus) in Northern Ireland

The Northern Ireland Hare Survey documented the distribution of the Irish Hare (Lepus timidus hibernicus). Historical game bag records and other, more contemporary, records of hare distribution were examined. These data indicate how numbers of L t. hibernicus may have changed over the last 140 years. The results of the Northern Ireland Hare Survey suggested that L. t. hibernicus was widespread throughout Northern Ireland. Current average densities are no more than 0.65 hares/km(2). Game bag records indicate that hare densities may have been much higher in the past, with a maximum of 138 hares/km(2) recorded on Crom Estate, Co. Fermanagh, in 1864. Evidence from hare distribution recorded during the Northern Ireland Rabbit Survey indicates that hare numbers declined between 1984 and 1994. Evidence from all sources suggests that L. t. hibernicus has declined in abundance substantially, with present total population estimates for Northern Ireland ranging from 8250 to 21000 individuals. Flushing data indicate that rushes and hedgerows are important diurnal resting areas for hares. While the principal reason for the decline in numbers of L. t. hibernicus in Northern Ireland is not clear, more species-rich pasture and provision of areas of cover, such as rushes, may arrest further declines, or indeed promote numbers of hares, particularly in lowland areas.

Self-perception of dentofacial attractiveness among patients requiring orthognathic surgery

Objective: To test the hypothesis that the self-perception of dental and facial attractiveness among patients requiring orthognathic surgery is no different from that of control patients.

Materials and Methods: Happiness with dental and facial appearance was assessed using questionnaires completed by 162 patients who required orthognathic treatment and 157 control subjects. Visual analog scale, binary, and open response data were collected. Analysis was carried out using a general linear model, logistic regression, and chi-square tests.

Results: Orthognathic patients were less happy with their dental appearance than were controls. Class II patients and women had lower happiness scores for their dental appearance. Among orthognathic patients, the "shape" and "prominence" of their teeth were the most frequent causes of concern. Older subjects, women, and orthognathic patients were less happy with their facial appearance. Class III orthognathic patients, older subjects, and women were more likely to have looked at their own face in profile. A greater proportion of Class II subjects than Class III subjects wished to change their appearance.

Conclusions: The hypothesis is rejected. The findings indicate that women and patients requiring orthognathic surgery had lower levels of happiness with their dentofacial appearance. Although Class II patients exhibited the lowest levels of happiness with their dental appearance, there was some evidence that concerns and awareness about their facial profile were more pronounced among the Class III patients.

Country-wise differences in perception of health-related messages in cereal-based food products

The objective of the present study was to explore the impact of health-related messages on the perceived overall healthiness and consumers' likelihood to buy cereal-based products or non-cereal products containing beneficial compounds from grains, across four European countries. The data were collected from a sample of 2392 members of the public in Finland, Germany, Italy and the UK. The results from a conjoint task with a main effects additive model were reported. In general, the presence of a verbal health claim on foods had positive influence on respondents perception of healthiness and on likelihood to buy the products, whereas the pictorial health claims were found to have a weak influence on the two dependent variables. However, the findings showed that health-related information on food labels differently influenced the healthiness perception and the likelihood to buy the product across the four countries, suggesting that different cultures, traditions, and eating habits have to be taken into account before positioning cereal-based products containing beneficial compounds from grains on the market. (C) 2009 Elsevier Ltd. All rights reserved.

Influence of the Graphical Levels of Detail of a Virtual Thrower on the Perception of the Movement

Virtual reality has a number of advantages for analyzing sports interactions such as the standardization of experimental conditions, stereoscopic vision, and complete control of animated humanoid movement. Nevertheless, in order to be useful for sports applications, accurate perception of simulated movement in the virtual sports environment is essential. This perception depends on parameters of the synthetic character such as the number of degrees of freedom of its skeleton or the levels of detail (LOD) of its graphical representation. This study focuses on the influence of this latter parameter on the perception of the movement. In order to evaluate it, this study analyzes the judgments of immersed handball goalkeepers that play against a graphically modified virtual thrower. Five graphical representations of the throwing action were defined: a textured reference level (L0), a nontextured level (L1), a wire-frame level (L2), a moving point light display (MLD) level with a normal-sized ball (L3), and a MLD level where the ball is represented by a point of light (L4). The results show that judgments made by goalkeepers in the L4 condition are significantly less accurate than in all the other conditions (p

Influence of social status on the welfare of sows in static and dynamic groups

Forty-eight Large White x Landrace multiparous sows were mixed into twelve groups of four animals after their piglets were weaned. These groups were defined as static, with no animals being added to or removed from the groups after their formation. Aggressive and submissive behaviours were recorded continuously for 9 h after the sows were mixed, and the sows were assigned high or low social status on the basis of their relative aggressiveness and success in aggressive interactions. After five weeks, each static group was mixed into a dynamic group of 40+/-2 sows for an 11-week period. Three static groups (ie 12 animals) at a time were added to the dynamic group at three-week intervals; the same number of animals was removed at these time-points in order to maintain the group number at 40+/-2. Injury levels increased significantly with the transition from static groups to the dynamic group (P

‘A planet of confusion and debate’: children's and young people's response to the news coverage of Pluto's loss of planetary status

Despite calls that the school science curriculum should develop among students an ability to understand and respond critically to science-related media reports, very little research has been directed toward an important matter relevant to that aim, namely, how children and young people, untutored, react to science in the news. This study sought, in the context of media coverage of the debate surrounding the planetary status of Pluto, to explore this issue. A questionnaire, completed by 350 students aged between eight and 18, showed just over half of the children and young people were able to write relevantly about the subject though it was the gist not the detail of the story they recounted. There was evidence, nonetheless, that this media-acquired information functioned as active rather than passive knowledge. Students demonstrated relatively few misconceptions and those presented were predominately pre-existing rather than media-derived. As with the wider public, many of the children and young people held strong opinions on Pluto's loss of planethood. Such responses diminished with age, however, with older students expressing a degree of indifference. The paper concludes with a discussion of some implications of the research findings for science instruction.

Perception of emotion: towards a realistic understanding of the task

A decade ago, perceiving emotion was generally equated with taking a sample (a still photograph or a few seconds of speech) that unquestionably signified an archetypal emotional state, and attaching the appropriate label. Computational research has shifted that paradigm in multiple ways. Concern with realism is key. Emotion generally colours ongoing action and interaction: describing that colouring is a different problem from categorizing brief episodes of relatively pure emotion. Multiple challenges flow from that. Describing emotional colouring is a challenge in itself. One approach is to use everyday categories describing states that are partly emotional and partly cognitive. Another approach is to use dimensions. Both approaches need ways to deal with gradual changes over time and mixed emotions. Attaching target descriptions to a sample poses problems of both procedure and validation. Cues are likely to be distributed both in time and across modalities, and key decisions may depend heavily on context. The usefulness of acted data is limited because it tends not to reproduce these features. By engaging with these challenging issues, research is not only achieving impressive results, but also offering a much deeper understanding of the problem.

The RET mutation E768D confers a late-onset Familial medullary thyroid carcinoma - only phenotype with incomplete penetrance: Implications for screening and management of carrier status

Objective: We describe a 4-generation family with familial medullary thyroid carcinoma (FMTC) - a variant of multiple endocrine neoplasia type 2 (MEN 2) without extra-thyroid features. RET mutation analysis confirmed an E768D mutation in exon 13 in 8 family members, 3 affected with medullary thyroid cancer alone while the other 5 were detected to be mutation carriers. This mutation has been described in very few families worldwide and the spectrum of disease and natural history is unclear. Results: Three affected members had medullary thyroid cancer (MTC) confirmed histologically at ages 25, 50 and 56 years, respectively. The E768D mutation appears to have a less aggressive clinical course compared to other high risk RET mutations with no evidence of clinical recurrence up to I I years after initial therapy. Of five gene carriers identified, two are asymptomatic at the age of 70 and 61, and three had raised calcitonin levels at 46, 39, and 45 years. Following total thyroidectomy, one gene carrier had a histologically normal thyroid at age 46, following a mildly elevated calcitonin, one had C-cell hyperplasia at the age of 39, and one had a frank focus of carcinoma in the left thyroid lobe at the age of 45. No members had evidence of phaeochromocytoma or parathyroid disease on screening. Conclusion: The RET E768D mutation is associated with MTC with a later age at presentation, incomplete penetrance and less aggressive course compared with other high risk RET mutations. To date in this family the E768D mutation has not been associated with either phaeochromocytoma or hyperparathyroidism. The appropriate screening strategy for and management of E768D carriers is difficult reflecting the phenotypic heterogeneity.