Attentional bias towards interpersonal aggression in depression - an eye movement study

Depressed individuals exhibit an attentional bias towards mood-congruent stimuli, yet evidence for biased processing of threat-related information in human interaction remains scarce. Here, we tested whether an attentional bias towards interpersonally aggressive pictures over interpersonally neutral pictures could be observed to a greater extent in depressed participants than in control participants. Eye movements were recorded while the participants freely viewed visually matched interpersonally aggressive and neutral pictures, which were presented in pairs. Across the groups, participants spent more time looking at neutral pictures than at aggressive pictures, probably reflecting avoidance behavior. When the participants could anticipate the stimulus valence, depressed participants - but not controls - showed an early attentional bias towards interpersonally aggressive pictures, as indexed by their longer first fixation durations on aggressive pictures than on neutral pictures. Our results thus preliminarily suggest both an early attentional bias towards interpersonal aggression, which is present, in depressed participants, also when aggression contents are anticipated, and a later attentional avoidance of aggression. The early depression-related bias in information processing may have maladaptive effects on the way depressed individuals perceive and function in social interaction and can, therefore, maintain depressed mood

High frequency of TTK mutations in microsatellite-unstable colorectal cancer and evaluation of their effect on spindle assembly checkpoint

Frameshift mutations frequently accumulate in microsatellite-unstable colorectal cancers (MSI CRCs) typically leading to downregulation of the target genes due to nonsense-mediated messenger RNA decay. However, frameshift mutations that occur in the 3' end of the coding regions can escape decay, which has largely been ignored in previous works. In this study, we characterized nonsense-mediated decay-escaping frameshift mutations in MSI CRC in an unbiased, genome wide manner. Combining bioinformatic search with expression profiling, we identified genes that were predicted to escape decay after a deletion in a microsatellite repeat. These repeats, located in 258 genes, were initially sequenced in 30 MSI CRC samples. The mitotic checkpoint kinase TTK was found to harbor decay-escaping heterozygous mutations in exon 22 in 59% (105/179) of MSI CRCs, which is notably more than previously reported. Additional novel deletions were found in exon 5, raising the mutation frequency to 66%. The exon 22 of TTK contains an A(9)-G(4)-A(7) locus, in which the most common mutation was a mononucleotide deletion in the A(9) (c.2560delA). When compared with identical non-coding repeats, TTK was found to be mutated significantly more often than expected without selective advantage. Since TTK inhibition is known to induce override of the mitotic spindle assembly checkpoint (SAC), we challenged mutated cancer cells with the microtubule-stabilizing drug paclitaxel. No evidence of checkpoint weakening was observed. As a conclusion, heterozygous TTK mutations occur at a high frequency in MSI CRCs. Unexpectedly, the plausible selective advantage in tumourigenesis does not appear to be related to SAC

Apoptotic activity is increased in parallel with the metaplasia–dysplasia–carcinoma sequence of the bronchial epithelium

A high level of apoptotic activity and an independence of apoptosis from the expression of p53 and bcl-2 have been observed in non-small-cell lung carcinoma. We examined 44 samples of normal, metaplastic and premalignant (i.e. mild, moderate and severe dysplasias and carcinoma in situ) bronchial epithelia to evaluate whether differences in the apoptotic activity could already be seen in the stages preceding squamous cell carcinoma of the lung (SQCLC). Apoptotic cells and bodies were visualized by 3′ end labelling. The expression of p53 and members of the bcl-2 gene family, such as bcl-2, bax and mcl-1, were determined immunohistochemically with specific antibodies. The relative number of apoptotic cells and bodies [apoptotic index (AI%)] was already increased threefold as the normal bronchial epithelium changed to squamous metaplasia, and the AIs of the dysplastic lesions were about four times higher than those of the normal epithelium. Apoptosis was significantly associated with cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry. However, the extent of apoptosis did not correlate with the expression of p53, bcl-2, bax and mcl-1. We conclude that, in the metaplasia–dysplasia–carcinoma sequence in the lung, the elevation of the AI% is an early event associated with cell proliferation activity, but is independent of the expression of p53, bcl-2, mcl-1 and bax. © 1999 Cancer Research Campaig

Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided

Attentional bias towards interpersonal aggression in depression : an eye movement study

Depressed individuals exhibit an attentional bias towards mood-congruent stimuli, yet evidence for biased processing of threat-related information in human interaction remains scarce. Here, we tested whether an attentional bias towards interpersonally aggressive pictures over interpersonally neutral pictures could be observed to a greater extent in depressed participants than in control participants. Eye movements were recorded while the participants freely viewed visually matched interpersonally aggressive and neutral pictures, which were presented in pairs. Across the groups, participants spent more time looking at neutral pictures than at aggressive pictures, probably reflecting avoidance behaviour. When the participants could anticipate the stimulus valence, depressed participants – but not controls – showed an early attentional bias towards interpersonally aggressive pictures, as indexed by their longer first fixation durations on aggressive pictures than on neutral pictures. Our results thus preliminarily suggest both an early attentional bias towards interpersonal aggression, which is present, in depressed participants, also when aggression contents are anticipated, and a later attentional avoidance of aggression. The early depression-related bias in information processing may have maladaptive effects on the way depressed individuals perceive and function in social interaction and can therefore maintain depressed mood.peerReviewe