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The proteasome is a large and complex protease formed by 66 polypeptides. The assembly of the proteasome is assisted by at least nine chaperones. One of these chaperones, Nas2/p27, binds to the C-terminal region of the AAA-ATPase Rpt5. We report here that the tail of Rpt5 provides two functions. First, it facilitates the previously reported interaction with the proteasome core particle (CP). Second, it is essential for the interaction with Nas2. Deletion of the C-terminal amino acid of Rpt5 disrupts the CP interaction, but not the binding to Nas2. The latter is surprising considering Nas2 contains a PDZ domain, which is often involved in binding to C termini. Interestingly, deletion of the last three amino acids interferes with both functions. The disruption of the Rpt5-CP interactions gave distinct phenotypes different from disruption of the Nas2-Rpt5 interaction. Additionally, proteasomes purified from a Saccharomyces cerevisiae rpt5-Δ3 strain show a strong enrichment of Ecm29. The function of Ecm29, a proteasome-associated protein, is not well understood. Our data show that Ecm29 can inhibit proteasomes, because our Ecm29-containing proteasomes have reduced suc-LLVY-AMC hydrolytic activity. Consistent with this apparent role as negative regulator, the deletion of ECM29 rescues the phenotypes of rpt5-Δ3 and nas2Δ in an hsm3Δ background. In sum, the interactions facilitated by the tail of Rpt5 act synergistically to minimize the formation of faulty proteasomes, thereby preventing recognition and inhibition by Ecm29.

Unlabelled: Activity patterns are believed to play an important role in the development and perpetuation of chronic pain. So far, 3 important activity patterns have been studied: avoidance behavior, persistence behavior, and pacing behavior. Yet, empirical evidence is limited and inconclusive about the relationships between these activity patterns and important outcomes. Therefore, the present study was aimed at identifying activity patterns by means of factor analyses and determining their relationship with disability and depressive symptomatology in participants with chronic pain (N = 132). Items across different measurement instruments pertaining to 1 particular activity pattern were aggregated, and submitted to factor analysis. Results from 3 separate factor analyses revealed 6 distinct activity patterns: pain avoidance, activity avoidance, task-contingent persistence, excessive persistence, pain-contingent persistence, and pacing. In line with our hypotheses, pain and activity avoidance, and excessive persistence, were related to higher levels of disability and depressive symptomatology. In contrast to hypotheses, pacing was associated with worse outcomes as well. Interestingly, task-contingent persistence was related to lower levels of disability and depressive symptomatology. When controlling for pain and the other activity patterns, excessive persistence and activity avoidance were the most detrimental in terms of relations with depressed mood or disability. Task-contingent persistence appeared to be the least detrimental., Perspective: Our findings suggest the existence of several activity patterns, which are differentially related to disability and depressive symptomatology, in participants with chronic pain. The present results are discussed in the light of previous findings, and may provide a new impetus for future studies on activity patterns in chronic pain research., (Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.)

In chronic low back pain (CLBP) research, the self-discrepancy model has been applied to explain dysfunctional avoidance and persistence behaviour. The main aim of this study was to evaluate whether specific self-discrepancies in patients with CLBP are associated with the abovementioned types of activity-related behaviour and whether changes in self-discrepancies over time are associated with changes in activity-related behaviour. Furthermore, the aim was to evaluate whether avoidance and persistence behaviour are associated with a higher level of disability and a diminished quality of life and whether changes over time in avoidance and persistence behaviour result in changes in disability and quality of life. A longitudinal cohort study in a sample of patients with CLBP (N=116), in which self-discrepancies, disability, quality of life, and objectively registered characteristics of activity-related behaviour were measured, was performed to evaluate the pathways in the aforementioned self-discrepancy model. Results indicate that patients with CLBP who feel closer to their ideal-other show more characteristics of persistence behaviour. Patients who move further away from their ideal-own also show more characteristics of persistence behaviour. Furthermore, in patients characterized as avoider, a decrease in a patient's daily uptime was associated with a decrease of mental health-related quality of life., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

The aim of the present study was to compare the subjectively reported and objectively assessed activity-related characteristics of patients with Chronic Low Back Pain (CLBP) who were classified according to their scores on the Patterns of Activity Measure-Pain (POAM-P) into avoiders, persisters, mixed performers (i.e. high scores on both avoidance and persistence behaviour) or functional performers (i.e. low scores on avoidance and persistence behaviour). Patients carried an electronic diary during 14 days to assess the self-reported activity and pain intensity levels in daily life. An accelerometer was used to objectively assess their activity level during the same time period. Results were available for 79 patients. Avoiders, persisters and mixed performers showed a higher level of self-reported disability than functional performers. Avoiders were characterized by a low level of self-reported habitual activities and persisters by long objectively measured daily uptime. The objectively assessed level of physical activity did not differ between the four groups. A further analysis tested the association between pain intensity levels and self-reported and objectively assessed daily life activity levels in avoiders and persisters. In persisters, a higher level of self-reported activities in daily life was related to increased pain. The objectively assessed activity level was not associated with pain intensity., (Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

This study examined associations between indices of the quality of attachment relationships of adolescents with parents and peers, rumination, and symptoms of depression. More specifically, a mediation model was investigated in which rumination was hypothesized to mediate the relation between quality of attachment relations and symptoms of depression. A total of 455 high school students completed a battery of questionnaires, including quality of attachment relations, rumination, and depression. Results showed that most indices of quality of attachment relations were significantly associated with rumination and symptoms of depression. When examining the relative contribution of these variables in explaining variance in depression symptoms, trust in parents, communication with peers, and alienation from peers accounted for a significant portion of the variance in depression scores. Finally, the relation between communication with peers and depressive symptoms was fully mediated by rumination, whereas partial mediation was found for the relations between parental trust and depressive symptoms, and between alienation from peers and depressive symptoms. Implications of the findings may be that the treatment of depression in adolescence should consist of both cognitive interventions aimed at targeting ruminative thinking as well as a focus on interpersonal relationships of the adolescent with parents and peers.

Background: Quality of attachment relations between adolescents and their parents and peers may be related to early maladaptive schemas as well as to symptoms of depression., Aims: The aim of the current study was to assess whether schema domains and maladaptive schemas mediate the relation between indices of quality of attachment relationships with parents and peers and symptoms of depression in non-clinical adolescents (N = 222)., Method: A battery of questionnaires was completed, including measures of quality of attachment relations, maladaptive schemas, and depression., Results: The schema domains of disconnection and rejection and other-directedness mediated the relation between quality of attachment relationships and symptoms of depression. More precisely, the schemas' mistrust/abuse and social isolation mediated the relation between trust in parents and depressive symptoms, whereas the schemas' social isolation and self-sacrifice mediated the relation between alienation from peers and symptoms of depression., Conclusions: The mediation analyses suggest that treatment of adolescent depression could be focused on both attachment bonds and on changing maladaptive schemas.

The present study aimed to develop norms for the Tampa Scale for Kinesiophobia (TSK), a frequently used measure of fear of movement/(re)injury. Norms were assessed for the TSK total score as well as for scores on the previously proposed TSK activity avoidance and TSK somatic focus scales. Data from Dutch, Canadian, and Swedish pain samples were used (N=3082). Norms were established using multiple regression to obtain more valid and reliable norms than can be obtained by subgroup analyses based on age or gender. In the Dutch samples (N=2236), pain diagnosis was predictive of all TSK scales. More specifically, chronic low back pain displayed the highest scores on the TSK scores followed by upper extremity disorder, fibromyalgia, and osteoarthritis. Gender was predictive of TSK somatic focus scores and age of TSK activity avoidance scores, with male patients having somewhat higher scores than female patients and older patients having higher scores compared with younger patients. In the Canadian (N=510) and Swedish (N=336) samples, gender was predictive of all TSK scales, with male patients having somewhat higher scores than female patients. These norm data may assist the clinician and researcher in the process of decision making and treatment evaluation., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Prior research has shown that depressive symptoms are associated with an enhanced attention toward negative stimuli and difficulty of disengaging attention from negative stimuli. The current study was an extension of a 2005 study by Koster and colleagues. A different stimulus presentation time and word set were used. The whole range of depressive symptoms was included in this sample instead of creating dichotomized groups. The Exogenous Cueing Task with negative, positive, and neutral cues was administered to 85 female undergraduate university students. Participants completed the Beck's Depression Inventory-II-NL questionnaire to measure self-reported depression. Contrary to previous findings, depressive symptoms were related to a facilitated rather than impaired attentional disengagement from negative stimuli. An explanation for the discrepancy with findings from Koster, et al. may be the different stimulus presentation time (1000 msec. instead of 500 or 1500 msec.).

Chronic pain not only interferes with daily activities, it may also have a negative impact on the perceived integrity of one's self through self-discrepancies. Self-discrepancies are experienced distances between the actual self and self-guides that can exist from 2 perspectives (ie, own and other). Self-discrepancies are associated with negative mood states and incite self-regulatory behavior in order to reduce these discrepancies. The present study was aimed at replicating the emotional consequences of self-discrepancies in patients with chronic low back pain, and extending current knowledge of the behavioral consequences of self-discrepancies (ie, behavioral activity patterns such as avoidance and persistence). A cross-sectional design was employed with 83 patients who completed a number of self-report measures. We hypothesized that ideal and ought discrepancies, as well as feared congruencies were associated with depressed and anxious mood. On the behavioral level, a U-shaped relationship was hypothesized between ideal and ought self-discrepancies and persistence behavior, whereas feared self-discrepancies were hypothesized to be related to avoidance behavior. Results were partially in line with the hypotheses. With respect to the emotional consequences, feared (own and other) self-discrepancies were predictive of depressive and anxious mood. With regard to activity patterns, results showed a U-shaped relationship between ideal-other self-discrepancies and persistence behavior and a positive relationship between feared-own self-discrepancies and avoidance behavior. In contrast to expectations, none of the other self-discrepancies was related to activity patterns. Of interest was that avoidance, but not persistence behavior, was predictive of higher levels of disability and lower levels of quality of life. Support is provided for the role of self-discrepancies in the emotional well-being and behavioural patterns of patients with chronic low back pain., (Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

This study aimed to (a) assess relationships between the Children's Depression Inventory (CDI) and DSM-oriented depression and anxiety scales of the Youth Self Report, (b) develop reliable norms for the CDI, and (c) determine CDI cutoff scores for selecting youngsters at risk for depression and anxiety. A total of 3,073 nonclinical and 511 clinically referred children and adolescents from The Netherlands and Belgium were included. Results showed that CDI scores were significantly related to DSM-oriented symptoms of both depression and anxiety. CDI scores correlated highly with depression symptoms and moderately with anxiety symptoms. Norms for the CDI were determined by means of multiple regression analysis and depended on sex, age, and country. CDI cutoff scores for selecting individuals at risk for depression and anxiety as measured by the DSM-oriented depression and anxiety scales of the Youth Self Report were determined by means of multiple regression analysis and receiver operating characteristic analysis. A CDI score of 16 was found to have the most optimal balance between sensitivity and specificity for depression, whereas a score of 21 provided the best sensitivity and specificity for anxiety in a subsample of children. We conclude that the CDI is an effective instrument for screening depression and to a lesser extent anxiety in primary and secondary care centers, before applying further assessment of high-risk individuals.

Patients with social anxiety disorder (SAD) not only fear negative evaluation but are indeed less likeable than people without SAD. Previous research shows social performance to mediate this social anxiety-social rejection relationship. This study studied two pathways hypothesized to lead to poor social performance in social anxiety: increased self-focused attention and negative beliefs. State social anxiety was experimentally manipulated in high and low-blushing-fearful individuals by letting half of the participants believe that they blushed intensely during a 5 min getting-acquainted interaction with two confederates. Participants rated their state social anxiety, self-focused attention, and level of negative beliefs. Two confederates and two video-observers rated subsequently likeability (i.e., social rejection) and social performance of the participants. In both groups, the social anxiety-social rejection relationship was present. Although state social anxiety was related to heightened self-focused attention and negative beliefs, only negative beliefs were associated with relatively poor social performance. In contrast to current SAD models, self-focused attention did not play a key-role in poor social performance but seemed to function as a by-product of state social anxiety. Beliefs of being negatively evaluated seem to elicit changes in behavioral repertoire resulting in a poor social performance and subsequent rejection., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Objective: Little is known about depressed individuals' illness attributions and how these influence treatment assignment in clinical practice. The aim of the present study was to examine whether illness attribution across the domains of intraindividual, interpersonal and biological reasons was associated with treatment assignment in a naturalistic treatment setting., Method: Illness attribution was assessed with the Reasons for Depression Questionnaire in 221 depressed individuals. Participants were assigned to either cognitive-behavioural therapy (CBT), interpersonal therapy (IPT) or psychopharmacological treatment (PHT)., Results: Depressed individuals who strongly attributed their illness to intraindividual factors were more likely to be assigned to CBT, and depressed individuals attributing their depression to biological reasons were more likely to receive in PHT. In contrast, interpersonal illness attribution was not associated with treatment assignment., Conclusions: Illness attribution influences treatment assignment to CBT and PHT. However, factors other than illness attribution for depression affect a treatment choice of IPT. , (© 2009 John Wiley & Sons, Ltd.)

The current study sought to examine three forms of negative, repetitive thinking in non-clinical children and adolescents aged between 10 and 18. More specifically, this study addressed the degree to which stress-reactive rumination can be differentiated from other forms of repetitive thinking, such as emotion-focused rumination and worry, and the associations between the various indices of repetitive thinking and symptoms of anxiety and depression. Participants completed a battery of self-report questionnaires including measures of stress-reactive rumination, emotion-focused rumination, worry, and symptoms of anxiety and depression. Results showed that stress-reactive rumination, emotion-focused rumination and worry are related but distinct forms of repetitive negative thinking. Positive associations were found between all indices of repetitive thinking and symptoms of depression and anxiety, but the effects of emotion-focused rumination disappeared when controlling for the other forms of repetitive thinking. The findings are discussed in the light of current theories and previous research, and directions for future research are provided.

Recurrent pain not only has an impact on disability, but on the long term it may become a threat to one's sense of self. This paper presents a cross-sectional study of patients with work-related upper extremity pain and focuses on: (1) the role of self-discrepancies in this group, (2) the associations between self-discrepancies, pain, emotions and (3) the interaction between self-discrepancies and flexible-goal adjustment. Eighty-nine participants completed standardized self-report measures of pain intensity, pain duration, anxiety, depression and flexible-goal adjustment. A Selves Questionnaire was used to generate self-discrepancies. A series of hierarchical regression analyses showed relationships between actual-ought other, actual-ought self, actual-feared self-discrepancies and depression as well as a significant association between actual-ought other self-discrepancy and anxiety. Furthermore, significant interactions were found between actual-ought other self-discrepancies and flexibility, indicating that less flexible participants with large self-discrepancies score higher on depression. This study showed that self-discrepancies are related to negative emotions and that flexible-goal adjustment served as a moderator in this relationship. The view of self in pain and flexible-goal adjustment should be considered as important variables in the process of chronic pain., (Copyright (c) 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

Good detection of estrus is critically important in dairy husbandry. Incorrect detection of estrus is related to loss of profit due to extended calving intervals, milk loss, veterinary costs, etc. Detection of estrus remains a major problem despites enormous progress in the knowledge of reproductive physiology of the cow and in development of estrus detection aids. To achieve good estrus detection, many factors have to be taken into account. On one hand a cow has to express estrus and on the other hand the farmer has to detect it. Combined action of several hormones causes physiological changes that lead to ovulation and an environment in the uterus that allows sperm to fertilize the egg. Besides these internal actions, a number of external changes can be observed. When using visual observations, time of the day and time spend on observation have a great impact on detection rates. Many devices are available to aid in estrus detection, such as pedometers, mount devices, temperature, and hormone measurements. Expression of estrus can be influenced by many factors. Heritability, number of days postpartum, lactation number, milk production, and health are known to influence estrus expression. Environmental factors like nutrition, season, housing, herd size, etc. also play a role in estrus expression. To evaluate estrus detection, record keeping is very important; a number of formulas can be used to assess detection efficiency. Besides the farmer, the veterinarian and inseminator can play an important role in estrus confirmation and good insemination strategy. In the end, the time of ovulation and the age of the egg at sperm penetration is critical for conception. Therefore, emphasis in research needs to be on the timing of insemination relative to ovulation, and thus on the detection of ovulation., (Copyright 2010 Elsevier Inc. All rights reserved.)

The 26S proteasome is a large multiprotein complex involved in the regulated degradation of ubiquitinated proteins in the cell. The 26S proteasome has been shown to control an increasing number of essential biochemical mechanisms of the cellular lifecycle including DNA synthesis, repair, transcription, translation, and cell signal transduction. Concurrently, it is increasingly seen that malfunction of the ubiquitin proteasome system contributes to the pathogenesis of disease. The recent identification of four molecular chaperones, in addition to five previously identified chaperones, have provided mechanistic insight into how this cellular megastructure is assembled in the cell. These data, together with new insights into the structure and function of the proteasome, provide a much better understanding of this complex protease., (Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.)

Patients with chronic pain may have difficulties estimating their own physical activity level in daily life. Pain-related factors such as depression and pain intensity may affect a patients' ability to estimate their own daily life activity level. This study evaluates whether patients with Chronic Low Back Pain (CLBP) who are more depressed and/or report more pain indeed have a lower objectively assessed daily life activity level or whether they only perceive their activity level as lower. Patients with CLBP were included in a cross-sectional study. During 14days physical activity in daily life was measured, with both an electronic diary and an accelerometer. Multilevel analyses were performed to evaluate whether a higher level of depression and/or pain intensity was associated with a lower objectively assessed activity level or the discrepancy between the self-reported and objectively assessed daily life activity levels. Results, based on 66 patients with CLBP (mean RDQ score 11.8), showed that the objectively assessed daily life activity level is not associated with depression or pain intensity. There was a moderate association between the self-reported and objectively assessed activity levels (beta=0.39, p<0.01). The discrepancy between the two was significantly and negatively related to depression (beta=-0.19, p=0.01), indicating that patients who had higher levels of depression judged their own activity level to be relatively low compared to their objectively assessed activity level. Pain intensity was not associated with the perception of a patient's activity level (beta=0.12, ns)., (Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Patients with chronic pain are not only faced with disabilities but are also challenged to maintain a valued sense of self. This sense of self is in part determined by the extent to which patients can accomplish their identity-related goals. The present study explores the content of three domains of the self, namely the ideal, ought and feared self and examines how the content relates to disability and depression. The ideal, ought and feared attributes of 80 chronic low back pain patients were analyzed and categorized in eight general goal-domains: interpersonal attributes, personal abilities, physical, emotional and psychological well-being, close interpersonal relationships, self-expression abilities, achievement-related attributes, physical appearance, and religion. Results showed that most of the attributes that patients generated involved interpersonal attributes. Comparisons between the self-guides revealed that ideal attributes were more intrapersonally focused while ought and feared attributes were interpersonally focused. The content appeared to be related to disability but not to depression. More specifically, the more disabled patients were, the more they listed well-being related attributes as part of their ought self. None of the other goal-domains was related to disability or depression. The present study provides additional insight into the goals of patients with chronic pain at the level of identity and has shown that these are, at least in part, related to the level of functional disability. These results might be useful for future studies incorporating the role of identity in chronic pain, such as psychological interventions., (Copyright (c) 2009 European Federation of International Association for the Study of Pain Chapters. All rights reserved.)

The proteasome is the most complex protease known, with a molecular mass of approx. 3 MDa and 33 distinct subunits. Recent studies reported the discovery of four chaperones that promote the assembly of a 19-subunit subcomplex of the proteasome known as the regulatory particle, or RP. These and other findings define a new and highly unusual macromolecular assembly pathway. The RP mediates substrate selection by the proteasome and injects substrates into the CP (core particle) to be degraded. A heterohexameric ring of ATPases, the Rpt proteins, is critical for RP function. These ATPases abut the CP and their C-terminal tails help to stabilize the RP-CP interface. ATPase heterodimers bound to the chaperone proteins are early intermediates in assembly of the ATPase ring. The four chaperones have the common feature of binding the C-domains of Rpt proteins, apparently a remarkable example of convergent evolution; each chaperone binds a specific Rpt subunit. The C-domains are distinct from the C-terminal tails, but are proximal to them. Some, but probably not all, of the RP chaperones appear to compete with CP for binding of the Rpt proteins, as a result of the proximity of the tails to the C-domain. This competition may underlie the release mechanism for these chaperones. Genetic studies in yeast point to the importance of the interaction between the CP and the Rpt tails in assembly, and a recent biochemical study in mammals suggests that RP assembly takes place on pre-assembled CP. These results do not exclude a parallel CP-independent pathway of assembly. Ongoing work should soon clarify the roles of both the CP and the four chaperones in RP assembly.

A 46-year-old woman was referred for orthodontic surgery consultation because ofa retrognathic maxilla, unilateral cross bite and functional, aesthetic and speech problems. The maxilla was widened unilaterally by unilateral surgically assisted rapid maxillary expansion with a bone-borne transpalatal distractor. During post-operative orthodontic treatment, a temporary anchorage device was administered. With the help of composite veneers, crowns and a removable partial denture, a functionally and aesthetically satisfying result was achieved.

Patients with chronic low back pain (CLBP) often report a disabling decrease in their activity level due to pain. The nature of the association between disability, activity, and pain over time is however, unclear. An intriguing issue here is whether a high level of pain-related disability is associated with a low activity level or are changes in the level of activity over time pain provoking and thus more disabling? The objectives of this study were to investigate associations between disability, pain intensity, pain-related fear, and characteristics of physical activity in patients with CLBP. A total of 42 patients with CLBP were recruited from the Pain Clinic of the Maastricht University Hospital. Each pain patient carried an electronic diary for one week, in which questions about current pain intensity, and the level of physical activity were completed at 8 moments a day. Disability was scored by the Quebec Back Pain Disability Scale (QBPDS), Fear of movement by the Tampa Scale for Kinesiophobia (TSK). To explain the level of disability regression analyses were performed with disability as dependent variable and pain intensity, pain-related fear, and consecutively the level of physical activity in daily life and fluctuations in physical activity as independent variables. Results, based on 34 patients, showed that activity fluctuations (beta=0.373, p<0.05) rather than the mean activity level over time (beta=-0.052, ns) contributed significantly in explaining disability. The results are discussed in the light of current theories, previous research, and clinical implications.

This review examined evidence for some core predictions of the response styles theory (RST) concerning the relation between response styles and symptoms of depression and gender differences in the use of response styles in non-clinical children and adolescents. In summarizing the literature, effect sizes (pooled correlation coefficients) were calculated for cross-sectional and longitudinal studies. Stability of the obtained effect sizes was evaluated by means of a fail-safe N analysis. Results indicated that stable and significant effect sizes were found for rumination being associated with concurrent and future levels of depression. When controlling for baseline levels of depression, effect sizes for rumination and distraction were not stable, indicating that these findings should be interpreted with considerable caution. Finally, significant and stable effect sizes for gender differences in response styles were found only for rumination among adolescents. Taken together, the findings partly support the predictions of the response styles theory examined in this meta-analysis and may implicate that rumination is a cognitive vulnerability factor for depressive symptoms among adolescents.

The present study sought to test predictions of the response styles theory in a sample of children and adolescents. More specifically, a ratio approach to response styles was utilized to examine the effects on residual change scores in depression and anxiety. Participants completed a battery of questionnaires including measures of rumination, distraction, depression, and anxiety at baseline (Time 1) and 8-10 weeks follow-up (Time 2). Results showed that the ratio score of rumination and distraction was significantly associated with depressed and anxious symptoms over time. More specifically, individuals who have a greater tendency to ruminate compared to distracting themselves have increases in depression and anxiety scores over time, whereas those who have a greater tendency to engage in distraction compared to rumination have decreases in depression and anxiety symptoms over time. These findings indicate that a ratio approach can be used to examine the relation between response styles and symptoms of depression and anxiety in non-clinical children and adolescents. Implications of the results may be that engaging in distractive activities should be promoted and that ruminative thinking should be targeted in juvenile depression treatment.

The Dysfunctional Attitude Scale (DAS) was designed to measure the intensity of dysfunctional attitudes, a hallmark feature of depression. Various exploratory factor analytic studies of the DAS form A (DAS-A) yielded mixed results. The current study was set up to compare the fit of various factor models. We used a large community sample (N = 8,960) to test the previously proposed factor models of the DAS-A using confirmatory factor analysis. The retained model of the DAS-A was subjected to reliability and validity analyses. All models showed good fit to the data. Finally, a two-factor solution of the DAS-A was retained, consisting of 17 items. The factors demonstrated good reliability and convergent construct validity. Significant associations were found with depression. Norm-scores were presented. We advocate the use of a 17-item DAS-A, which proved to be useful in measuring dysfunctional beliefs. On the basis of previous psychometric studies, our study provides solid evidence for a two-factor model of the DAS-A, consisting of 'dependency' and 'perfectionism/performance evaluation'.

Substrates of the proteasome are recognized and unfolded by the regulatory particle, and then translocated into the core particle (CP) to be degraded. A hetero-hexameric ATPase ring, containing subunits Rpt1-6, is situated within the base subassembly of the regulatory particle. The ATPase ring sits atop the CP, with the Rpt carboxy termini inserted into pockets in the CP. Here we identify a previously unknown function of the Rpt proteins in proteasome biogenesis through deleting the C-terminal residue from each Rpt in the yeast Saccharomyces cerevisiae. Our results indicate that assembly of the hexameric ATPase ring is templated on the CP. We have also identified an apparent intermediate in base assembly, BP1, which contains Rpn1, three Rpts and Hsm3, a chaperone for base assembly. The Rpt proteins with the strongest assembly phenotypes, Rpt4 and Rpt6, were absent from BP1. We propose that Rpt4 and Rpt6 form a nucleating complex to initiate base assembly, and that this complex is subsequently joined by BP1 to complete the Rpt ring. Our studies show that assembly of the proteasome base is a rapid yet highly orchestrated process.

The proteasome is a protease that controls diverse processes in eukaryotic cells. Its regulatory particle (RP) initiates the degradation of ubiquitin-protein conjugates by unfolding the substrate and translocating it into the proteasome core particle (CP) to be degraded. The RP has 19 subunits, and their pathway of assembly is not understood. Here we show that in the yeast Saccharomyces cerevisiae three proteins are found associated with RP but not with the RP-CP holoenzyme: Nas6, Rpn14 and Hsm3. Mutations in the corresponding genes confer proteasome loss-of-function phenotypes, despite their virtual absence from the holoenzyme. These effects result from deficient RP assembly. Thus, Nas6, Rpn14 and Hsm3 are RP chaperones. The RP contains six ATPases-the Rpt proteins-and each RP chaperone binds to the carboxy-terminal domain of a specific Rpt. We show in an accompanying study that RP assembly is templated through the Rpt C termini, apparently by their insertion into binding pockets in the CP. Thus, RP chaperones may regulate proteasome assembly by directly restricting the accessibility of Rpt C termini to the CP. In addition, competition between the RP chaperones and the CP for Rpt engagement may explain the release of RP chaperones as proteasomes mature.

Rumination and worrying are considered possible mediating variables that may explain the relation between neuroticism and symptoms of depression and anxiety. The current study sought to examine the mediational effects of rumination and worry in the relationships between neuroticism and symptoms of depression and anxiety in a sample of clinically depressed individuals (N=198). All patients completed a battery of questionnaires including measures of neuroticism, rumination, worrying, depression, and anxiety. Results showed that in subsequent analyses, rumination and worrying both mediated the relation between neuroticism and depression and anxiety. When rumination and worrying were simultaneously entered in the mediation analysis, only rumination was found to mediate the relation between neuroticism and symptoms of anxiety and depression. Two components of rumination (i.e., brooding and reflection) were also analyzed in the mediational analysis. Both reflection and brooding were significant mediators with respect to depressive symptoms, whereas brooding was the only significant mediator in relation to anxiety symptoms. The results are discussed in the light of current theories, previous research, and recent treatment developments. Clinical implications and suggestions for future research are provided.

Objectives: Patients with social anxiety disorder (SAD) not only fear social rejection, but accumulating evidence also shows that they are indeed less liked than their non-anxious counterparts. Three factors are hypothesized to play a role in this social anxiety-social rejection relationship: (1) social performance; (2) elicited negative emotions, and (3) perceived similarity., Method: Patients with SAD (N=63) and control participants (N=27) were observed during a 5 minutes 'getting acquainted' conversation with a male and female confederate who rated their social performance. Video-observers rated their own negative emotions and perceived similarity with the patients, while other video-observers rated their wish to engage in future contact with them (a measure of social rejection)., Results: Analysed by way of structural equation modelling (SEM), the results supported the social anxiety-social rejection relationship. More specifically, poor social performance was associated with perceived dissimilarity ratings and mediated by evoked negative emotions, both of which were in turn associated with social rejection., Conclusion: These results suggest that a sequence of events links social anxiety to social rejection. Treatment should aim to improve social performance and perceived similarity to reverse SAD's vicious, negative interpersonal cycle.

The 26S proteasome holoenzyme is formed by the association of a 20S core particle (CP) with a 19S regulatory particle (RP). The CP-RP interaction is labile and subject to regulation in vivo, but the factors controlling this association are poorly understood. Here we describe an in vitro proteasome reconstitution assay and a high-resolution, two-dimensional gel electrophoresis system. Using these techniques, we find that a yeast CP-RP complex can contain a substoichiometric amount of tightly bound, essentially non-exchangeable ATP. However, this nucleotide is dispensable for gating of the CP channel, provided that the CP-RP complex is preserved by the Ecm29 protein. Unexpectedly, proteasome inhibitors are potent in stabilizing proteasomes against the dissociation of CP-RP. These data indicate that active sites of the CP communicate with bound RP, despite their spatial separation. We propose that ongoing protein degradation may suppress proteasome disassembly, thereby enhancing the processivity of proteolysis.

The aims of the current study were twofold. First, the factor structure, reliability (i.e., internal consistency), and validity (i.e., concurrent criterion validity) of the Tampa Scale for Kinesiophobia (TSK), a measure of fear of movement and (re)injury, were investigated in a Dutch sample of patients with work-related upper extremity disorders (study 1). More specifically, examination of the factor structure involved a test of three competitive models: the one-factor model of all 17 TSK items, a one-factor model of the TSK (Woby SR, Roach NK, Urmston M, Watson P. Psychometric properties of the TSK-11: a shortened version of the Tampa Scale for Kinesiophobia. Pain 2005;117:137-44.), and a two-factor model of the TSK-11. Second, invariance of the aforementioned TSK models was examined in patients with chronic musculoskeletal pain conditions (i.e., work-related upper extremity disorders, chronic low back pain, fibromyalgia, osteoarthritis) from The Netherlands, Sweden, and Canada was assessed (study 2). Results from study 1 showed that the two-factor model of the TSK-11 consisting of 'somatic focus' (TSK-SF) and 'activity avoidance' (TSK-AA) had the best fit. The TSK factors showed reasonable internal consistency, and were modestly but significantly related to disability, supporting the concurrent criterion validity of the TSK scales. Results from study 2 showed that the two-factor model of the TSK-11 was invariant across pain diagnoses and Dutch, Swedish, and Canadian samples. Altogether, we consider the TSK-11 and its two subscales a psychometrically sound instrument of fear of movement and (re)injury and recommend to use this measure in future research as well as in clinical settings.

Background: People with depression often experience interpersonal problems. Family therapy for depression is a widely used intervention, but it is unclear whether this is an effective therapy for the treatment of depression., Objectives: To assess the efficacy of family therapy for depression., Search Strategy: The following electronic databases were searched using a specific search strategy: CCDANCTR-Studies and CCDANCTR-References searched on 21/10/2005, The Cochrane Central Register of Controlled Trials, Medline (1966 to January 2005), EMBASE (1980 to January 2005), Psycinfo (1974 to January 2005). Reference lists of articles were also searched. Handsearches of relevant journals and bibliographies were conducted and first authors of included studies and experts in the field were contacted for further information., Selection Criteria: Included studies were randomised controlled and controlled clinical trials comparing family therapy with no intervention or an alternative intervention in which depression symptomatology was a main outcome measure., Data Collection and Analysis: Methodological quality was independently assessed by two review authors using the Maastricht-Amsterdam Criteria List. The qualitative and quantitative characteristics of the selected trials were independently extracted by three review authors using a standardised data extraction form. Levels of evidence were used to determine the strength of the evidence available. It was not possible to perform meta-analyses because of the heterogeneity of the selected studies., Main Results: Three high-quality and three low-quality studies, involving 519 people with depression, were identified. The studies were very heterogeneous in terms of interventions, participants, and measuring instruments. Despite fairly good methodological quality and positive findings of some studies, evidence for the effectiveness of family therapy for depression did not exceed level 3 (limited or conflicting evidence), except for moderate evidence (level 2), based on the non-combined findings from three studies, indicating that family therapy is more effective than no treatment or waiting list condition on decreasing depression, and on increasing family functioning., Authors' Conclusions: The current evidence base is too heterogeneous and sparse to draw conclusions on the overall effectiveness of family therapy in the treatment of depression. At this point, use of psychological interventions for the treatment of depression for which there is already an evidence-base would seem to be preferable to family therapy. Further high quality trials examining the effectiveness and comparative effectiveness of explicitly defined forms of family therapy are required.

The present study aimed to test the central components of Papageorgiou and Wells' (2003) non-clinical metacognitive model of rumination and depression that is grounded on the Self-Regulatory Executive Function (S-REF) model of emotional disorders [Wells, A., & Matthews, G. (1994). Attention and emotion: A clinical perspective. Hove, UK: Lawrence Erlbaum.]. A second aim of this study was to extend the non-clinical model with the concept of self-discrepancy in line with the S-REF model. Data of the current study were collected in a large sample of non-clinical Dutch undergraduates (N=196), who completed a battery of questionnaires including measures of rumination, positive and negative metacognitions, depressive symptoms, and self-discrepancy (i.e., actual-ideal, actual-ought, and actual-feared discrepancies). Hypothesized relationships among these variables were tested by means of structural equation modelling. Following some theoretically consistent modifications, the model was an adequate fit to the data. With respect to the second aim of the study, self-discrepancies were directly linked to symptoms of depression as well as indirectly via the cognitive processes involved in the metacognitive model of rumination and depression. Evidence was found for positive beliefs about rumination to partially mediate the relation between self-discrepancy and rumination. Clinical implications of the findings, including implementation of a metacognitive-focused cognitive therapy of depression, and suggestions for future research are discussed.

Rumination is considered a specific cognitive vulnerability factor that is thought to play a prominent role in the maintenance of depressive symptoms. The present study investigated the psychometric properties of two measures of rumination, the ruminative response scale (RRS) and the rumination on sadness scale (RSS) in undergraduates (N=331). A joint factor analysis yielded three factors, 'rumination on causes of sadness', 'symptom-based rumination', and 'rumination on sadness'. The internal consistency of the rumination factors was good and the test-retest stability over a 6-month period of time was moderate. Support was also found for the construct validity of the rumination factors. Finally, the 'rumination on the causes of sadness' factor was found to moderate the relation between depression measured at baseline and at 6-month follow-up. More specifically, baseline depression was a strong predictor of future depression but this was particularly true for high ruminating individuals. Implications of the results and directions for future research are provided.

Objective: The present study examined the effects of a manipulation of attention to pain (i.e. attentional focusing vs. distraction) on pain intensity in daily life of patients with chronic low back pain. It was hypothesized that attentional focusing would lead to decreased pain intensity in high pain fearful individuals, whereas distraction from pain would be associated with decreased pain intensity in low pain fearful individuals., Design: An experience sampling methodology was used to examine the effects of a manipulation of attention to pain on pain intensity in daily life of pain patients., Methods: A total number of 38 patients with chronic low back pain participated in this study and carried a palmtop computer for 2 weeks. During this period, patients were 'beeped' 8 times a day to complete diary questions. On certain days, instructions to either attend to or distract from pain were given., Results: Multi-level analyses showed that attentional focusing was not associated with decreased pain intensity in high pain fearful individuals and that distraction did not lead to decreased pain intensity in low pain fearful individuals. The manipulations in isolation neither influenced pain intensity. The manipulation check was generally weak., Conclusion: A manipulation of attention to pain in daily life of patients with chronic low back pain proved difficult to accomplish. As the manipulation check was generally unsuccessful, no clear inferences about the underlying theory can be made. Future research within the field of pain treatments (e.g. in vivo exposure) might benefit greatly from electronic diary assessments studies.

Three fundamental fears - anxiety sensitivity (AS), injury/illness sensitivity (IS) and fear of negative evaluation (FNE) - have been proposed to underlie common fears and psychopathological conditions. In pain research, the relation between AS and (chronic) pain processes was the subject of several studies, whereas the possible role of IS has been ignored. The current research examines the role of IS with respect to various pain-related variables in two studies. In the first study, 192 healthy college students completed the Sensitivity Index (SI; a composite measure assessing the three fundamental fears) and various pain-related questionnaires. In a second study, 60 students out of the original sample took part in a pain induction procedure and completed the SI as well. We first examined the properties of the SI. Factor analysis on the SI replicated the proposed factor structure [Taylor S. The structure of fundamental fears, J Behav Ther Exp Psychiat 1993;24:289-99]. However, some items of the ASI did show problematic loadings and were therefore excluded in subsequent analyses. The main hypothesis of the current study states that IS is a stronger predictor than AS of pain catastrophizing and fear of pain as assessed by self-report measures, and of pain tolerance and anticipatory fear of pain as assessed in a pain induction study. This hypothesis could be confirmed for all variables, except for pain tolerance, which was not predicted by any of the three fundamental fears. The current study can be considered as an impetus for devoting attention to IS in future pain research.

Study Design: Prospective inception cohort study., Objective: To investigate prospectively whether pain-related fear predicts future perceived disability and participation in patients with acute low back pain (LBP)., Summary of Background Data: There are indications that fear of movement/(re)injury, as measured by the Tampa Scale for Kinesiophobia, is present early in an episode of LBP, and that it might be a predictor of future perceived disability and participation., Methods: A cohort of 555 patients with acute LBP included by general practitioners and physical therapists in primary care settings was followed for 6 months., Results: Results indicate that baseline fear of movement/(re)injury was predictive of future perceived disability and, to a lesser extent (and together with duration and radiation), of participation., Conclusions: The results suggest that interventions aimed at reducing pain-related fear in the acute stage of LBP might prevent restrictions of activity and participation because of pain, and might be a way of preventing the transition from acute to chronic LBP.

Objectives: Fear-avoidance beliefs have been shown to be associated with disability and work status in patients with low back pain. Especially in acute low back pain, much research is needed to increase the knowledge concerning the role of fear-avoidance beliefs and its associated avoidance behavior in the influence on disability and the participation in daily and social life activities. The Fear-Avoidance Beliefs Questionnaire is developed to measure such beliefs and has become increasingly popular for use in primary care practice. The aim of the current study was: 1) to investigate the factor structure of the Fear-Avoidance Beliefs Questionnaire in a population of patients with acute low back pain by means of confirmatory factor analysis; 2) to examine the relationship between fear-avoidance beliefs and perceived disability, as well as participation in daily and social life; and 3) to investigate whether perceived disability mediates the association between pain and participation and between fear-avoidance beliefs and participation., Methods: The study has a cross-sectional design and was performed on a sample of 615 patients with acute low back pain in primary care settings in The Netherlands. Patients completed a visual analogue scale for pain, the Roland Disability Questionnaire, the Fear-Avoidance Beliefs Questionnaire, a sociodemographic questionnaire, and 5 participation items., Results: Confirmatory factor analysis corroborated the 2-factor structure of the Fear-Avoidance Beliefs Questionnaire as found by Waddell et al. Investigation of the association between fear-avoidance beliefs and perceived disability or participation was performed for workers and non-workers separately. The 2 subscales of the Fear-Avoidance Beliefs Questionnaire were significantly associated with perceived disability and participation, although there were differences between the samples. Perceived disability was significantly predicted by pain intensity and fear-avoidance beliefs. Perceived disability significantly predicted participation, and finally, the mediational role of perceived disability was supported., Discussion: In the early stage of low back pain, the reduction of pain and fear-avoidance beliefs might increase the level of activity, which might foster increased participation in daily and social life activities.

Pain-related fear and pain catastrophizing are associated with disability and actual performance in chronic pain patients. In acute low back pain (LBP), little is known about the prediction of actual performance or perceived disability by pain-related fear and pain catastrophizing. This experimental, cross-sectional study aimed at examining whether pain-related fear and pain catastrophizing were associated with actual performance and perceived disability. Ninety six individuals with an episode of acute LBP performed a dynamic lifting task to measure actual performance. Total lifting time was used as outcome measure. The results show that pain-related fear, as measured with the Tampa Scale for Kinesiophobia, was the strongest predictor of this physical task. Using the Roland Disability Questionnaire as a measure of perceived disability, both pain-related fear and pain catastrophizing, as measured with the Pain Catastrophizing Scale, were significantly predictive of perceived disability and more strongly than pain intensity was. The results of the current study suggest that pain-related fear is an important factor influencing daily activities in individuals suffering an episode of acute LBP. The study results have important clinical implications, especially in the development of preventive strategies for chronic LBP.

The present study sought to examine psychometric properties of the Fear of Pain Questionnaire (FPQ), a measure of pain-related fear, in a sample of undergraduates. Confirmatory factor analysis confirmed the previously reported three-factor model of the FPQ (e.g. severe pain, minor pain, medical pain), but some items may be redundant. With respect to the reliability of the FPQ, both the FPQ and the subscales showed good internal consistency and test-retest stability was moderate to good. Convergent and predictive validity of the FPQ (and the subscales) were partly supported by moderate correlations with related constructs and with self-reported fear associated with three experimental pain tests. Discriminant validity of the FPQ (and the subscales) was partly supported by low correlations with unrelated self-report measures. Moreover, modest correlation coefficients were found between the FPQ and other pain-related measures. Finally, the minor pain subscale of the FPQ accounted for pain intensity scores on the ischemic pain test and the remaining subscales and the FPQ total scores accounted for pain tolerance on the electrical stimulation test and the thermal pain test. Results are discussed and directions for future research are provided.

The present study examined the role of personal relevance of sensory pain-related words in selective attentional processing measured with a modified Stroop task administered to 30 patients with chronic low back pain. A related aim of this study was to introduce the application of multilevel analysis to test the influence of personal relevance on selective attentional processing in this sample. Patients completed the modified Stroop task, as well as a set of self-report measures aimed to assess Fear of Pain, Trait Anxiety, Catastrophizing, Pain Vigilance, and Pain Intensity. The modified Stroop task comprised 33 sensory pain-related words for which the personal relevance towards current concerns was rated afterwards by each participant on a 7-point Likert-type scale. The multilevel analyses did not support the hypothesis that personal relevance of sensory pain-related words interacted with Fear of Pain scores of patients in accounting for reaction times in naming the color of sensory pain-related words. None of the other self-report measures accounted for reaction times in isolation or in interaction with personal relevance. The modified Stroop task does not appear to be a robust measure of selective attentional processing in patients with chronic low back pain. The usefulness of other paradigms, such as the visual dot-probe task, should be explored in examining selective attentional processing in this population.

Unlabelled: The present study sought to investigate to what extent patients with chronic low back pain and pain-free control subjects selectively attend to pain-related stimuli as measured with 2 dot-probe tasks with word stimuli and pictorial stimuli. Selective attentional processing was measured by means of 3 indices: the bias index, a congruency effect, and an incongruency effect. Pain-related fear as a trait measure (Tampa Scale for Kinesiophobia [TSK]) was expected to be positively associated with all indices of selective attentional processing of pain stimuli. Results were analyzed with repeated-measures analysis of variance. An incongruency effect was found for patients and to a significantly less degree for pain-free control subjects on the dot-probe task with pictorial stimuli, indicating that pain patients have difficulty disengaging from threat pictures. Pain-related fear as a trait measure (TSK) was not associated with selective attentional processing of word and pictorial stimuli in either pain patients or control subjects. Results from the present study are discussed, and directions for future research are provided., Perspective: Demonstrating difficulty to disengage from threat might be clinically relevant because patients might pay less attention to fear-disconfirming information and remain engaged in avoidance, which might eventually lead to prolonged anxiety states.

Dictyostelium contains two guanylyl cyclases, GCA, a 12-transmembrane enzyme, and sGC, a homologue of mammalian soluble adenylyl cyclase. sGC provides nearly all chemoattractant-stimulated cGMP formation and is essential for efficient chemotaxis toward cAMP. We show that in resting cells the major fraction of the sGC-GFP fusion protein localizes to the cytosol, and a small fraction is associated to the cell cortex. With the artificial substrate Mn2+/GTP, sGC activity and protein exhibit a similar distribution between soluble and particulate fraction of cell lysates. However, with the physiological substrate Mg2+/GTP, sGC in the cytosol is nearly inactive, whereas the particulate enzyme shows high enzyme activity. Reconstitution experiments reveal that inactive cytosolic sGC acquires catalytic activity with Mg2+/GTP upon association to the membrane. Stimulation of cells with cAMP results in a twofold increase of membrane-localized sGC-GFP, which is accompanied by an increase of the membrane-associated guanylyl cyclase activity. In a cAMP gradient, sGC-GFP localizes to the anterior cell cortex, suggesting that in chemotacting cells, sGC is activated at the leading edge of the cell.

The present study investigated the relationships between pain-related fear, attention to pain, and pain intensity in daily life in patients with chronic low back pain. An experience sampling methodology was used in which electronic diary data were collected by means of palmtop computers from 40 chronic low back pain patients who were followed for one week. Attention to pain was hypothesized to mediate the relation between pain-related fear and pain intensity. Further, pain-related fear as a trait characteristic was expected to moderate the relation between attention to pain and pain intensity. Multi-level analysis was used for all analyses. Although the tested mediation models yielded statistically significant mediation effects, the sizes of these effects were relatively small and clinically irrelevant. Instead, results suggested that pain-related fear and attention to pain independently predicted pain intensity. No evidence for moderation of the relation between attention to pain and pain intensity by pain-related fear as a trait characteristic was found. Implications of the results from this study are discussed and suggestions for future research are provided.

The present study attempted to replicate the robustness of a two-factor model of the Tampa Scale for Kinesiophobia (TSK) in chronic low back pain (CLBP) patients and fibromyalgia patients, by means of confirmatory factor analysis. Construct and predictive validity of the TSK subscales were also examined. Results clearly indicated that a two-factor model fitted best in both pain samples. These two factors were labelled somatic focus, which reflects the belief in underlying and serious medical problems, and activity avoidance, which reflects the belief that activity may result in (re)injury or increased pain. Construct validity of the TSK and its subscales was supported by moderate correlation coefficients with self-report measures of pain-related fear, pain catastrophising, and disability, predominantly in patients with CLBP. Predictive validity was supported by moderate correlation coefficients with performance on physical performance tests (i.e., lifting tasks, bicycle task) mainly in CLBP patients. Implications of the results are discussed and directions for future research are provided.

There is growing evidence supporting the relationship between pain-related fear and functional disability in chronic musculoskeletal pain conditions. In osteoarthritis (OA) patients the role of pain-related fear and avoidance has received little research attention so far. The present study investigates the degree to which pain-related fear, measured with the Tampa Scale for Kinesiophobia (TSK), influences daily functioning in OA patients. The purpose of the present paper was twofold: (1) to investigate the factor structure of the TSK in a sample of OA patients by means of confirmatory factor analysis; and (2) to investigate the role of pain-related fear in OA compared to other factors, such as radiological findings and level of pain intensity. The results show that TSK consists of two factors, called 'activity avoidance' and 'somatic focus', which is in line with other studies in low back pain and fibromyalgia. Furthermore, pain-related fear occurred to a considerable extent in this sample of osteoarthritis patients and was negatively associated with daily functioning. Level of pain and level of pain-related fear were significantly associated with functional limitations. Radiological findings were not significant predictors and when compared to pain-related fear they were not significant. These findings underscore the importance of pain-related fear in daily functioning of OA patients. Therefore, treatment strategies aiming at reduction of pain-related fear in OA patients need to be developed and investigated.

The leading edge of Dictyostelium cells in chemoattractant gradients can be visualized using green fluorescent protein (GFP) tagged to the pleckstrin-homology (PH) domain of cytosolic regulator of adenylyl cyclase (CRAC), which presumable binds phosphatidylinositol-(3,4,5)triphosphate [PtdIns(3,4,5)P(3)]. Uniform cyclic AMP (cAMP) concentrations induce persistent translocation of PH(Crac)-GFP from the cytosol to multiple patches, which are similar to the single patch of PH(Crac)-GFP at the leading edge in a cAMP gradient. We show that cAMP determines the probability of patch formation (half-maximal effect at 0.5 nM cAMP) but not the size, lifetime or intensity of patches, indicating that patches are self-organizing structures. A pseudopod is extended from the area of the cell with a PH(Crac)-GFP patch at about 10 seconds after patch formation. Cells treated with the F-actin inhibitor latrunculin A are round without pseudopodia; uniform cAMP still induces localized patches of PH(Crac)-GFP. Inhibition of phosphoinositide-3-kinase (PI3K) activity with LY294002 inhibits PH(Crac)-GFP patches and inhibits chemotaxis towards nanomolar cAMP but has no effect at higher cAMP concentrations. Thus, very low cAMP concentrations induce self-organizing PH(Crac)-GFP patches that serve as a spatial cue for pseudopod formation, which enhances the sensitivity and amplitude of chemotactic movement.

Unlabelled: The present study investigated the influence of sensory focusing and distraction on pain tolerance and self-reported pain intensity in healthy female university students ranking high or low in pain-related fear. Pain was induced experimentally by means of a cold pressor test. Results showed that individuals high in pain-related fear groups had greater pain intensity ratings than those low in pain-related fear groups. A planned comparison analysis showed that distraction produced reduced pain ratings only in low fearful individuals, whereas sensory focusing led to reduced pain ratings only in high fearful individuals. Self-report measures of anxiety sensitivity, pain vigilance, and pain catastrophizing were positively associated with pain intensity, but, except for pain vigilance, no meaningful association was found between these measures and pain tolerance. Implications of the results and directions for future research are provided., Perspective: In the management of chronic pain, distraction might be especially useful in low fearful individuals. Learning to focus on the sensory aspects (ie, monitoring) of the pain experience might be beneficial for high fearful individuals.

Background and Aims: The pathogenesis of asymptomatic diverticular disease (ADD) and symptomatic uncomplicated diverticular disease (SUDD) has not been elucidated. The aim of our study was to assess whether altered visceral perception or abnormal compliance of the colorectal wall play a role in these clinical entities., Methods: Ten ADD patients, 11 SUDD patients, and nine healthy controls were studied. Using a dual barostat device, sensations were scored and compliance curves obtained using stepwise intermittent isobaric distensions of the rectum and sigmoid, before and after a liquid meal. In addition, the colonic response to eating was assessed by monitoring the volumes of both barostat bags at operating pressure before and after the meal., Results: In the rectum, perception was increased in the SUDD group compared with controls (p = 0.010) and the ADD group (p = 0.030). Rectal compliance curves were not different between the groups. In the sigmoid colon, perception in the pre- and postprandial periods was increased in SUDD compared with controls (p = 0.018) but not when compared with ADD. Sigmoid volume-pressure curves had comparable slopes (compliance) in all groups but were shifted downwards in SUDD compared with ADD in the preprandial period (p = 0.026). The colonic response to eating (decrease in intrabag volume) was similar in all three groups, both in the rectum and sigmoid., Conclusion: Symptomatic but not asymptomatic uncomplicated diverticular disease is associated with heightened perception of distension, not only in the diverticula bearing sigmoid, but also in the unaffected rectum. This hyperperception is not due to altered wall compliance.