Dynamic and regulated association of caveolin with lipid bodies: Modulation of lipid body motility and function by a dominant negative mutant

Caveolins are a crucial component of caveolae but have also been localized to the Golgi complex, and, under some experimental conditions, to lipid bodies (LBs). The physiological relevance and dynamics of LB association remain unclear. We now show that endogenous caveolin-1 and caveolin-2 redistribute to LBs in lipid loaded A431 and FRT cells. Association with LBs is regulated and reversible; removal of fatty acids causes caveolin to rapidly leave the lipid body. We also show by subcellular fractionation, light and electron microscopy that during the first hours of liver regeneration, caveolins show a dramatic redistribution from the cell surface to the newly formed LBs. At later stages of the regeneration process (when LBs are still abundant), the levels of caveolins in LBs decrease dramatically. As a model system to study association of caveolins with LBs we have used brefeldin A (BFA). BFA causes rapid redistribution of endogenous caveolins to LBs and this association was reversed upon BFA washout. Finally, we have used a dominant negative LB-associated caveolin mutant (cav(DGV)) to study LB formation and to examine its effect on LB function. We now show that the cav(DGV) mutant inhibits microtubule-dependent LB motility and blocks the reversal of lipid accumulation in LBs.

An integrated cognitive model of panic disorder: The role of positive and negative cognitions

One reason for the neglect of the role of positive factors in cognitive-behavioural therapy (CBT) may relate to a failure to develop cognitive models that integrate positive and negative cognitions. Bandura [Psychol. Rev. 84 (1977) 191; Anxiety Res. 1 (1988) 77] proposed that self-efficacy beliefs mediate a range of emotional and behavioural outcomes. However, in panic disorder, cognitively based research to date has largely focused on catastrophic misinterpretation of bodily sensations. Although a number of studies support each of the predictions associated with the account of panic disorder that is based on the role of negative cognitions, a review of the literature indicated that a cognitively based explanation of the disorder may be considerably strengthened by inclusion of positive cognitions that emphasize control or coping. Evidence to support an Integrated Cognitive Model (ICM) of panic disorder was examined and the theoretical implications of this model were discussed in terms of both schema change and compensatory skills accounts of change processes in CBT. (C) 2004 Elsevier Ltd. All rights reserved.

The positive impact of multiple sclerosis (MS) on carers: Associations between carer benefit finding and positive and negative adjustment domains

Purpose. This study examined benefit finding in MS carers including the dimensionality of benefit finding, relations between carer and care recipient benefit finding, and the effects of carer benefit finding on carer positive and negative adjustment domains. Method. A total of 267 carers and their care recipients completed questionnaires at Time 1 and 3 months later, Time 2 (n=155). Illness data were collected at Time 1, and number of problems, stress appraisal, benefit finding, negative (global distress, negative affect) and positive (life satisfaction, positive affect, dyadic adjustment) adjustment domains were measured at Time 2. Results. Qualitative data revealed seven benefit finding themes, two of which were adequately represented by the Benefit Finding Scale (BFS) [1] (Mohr et al. Health Psychology 1999; 18: 376). Factor analyses indicated two factors (Personal Growth, Family Relations Growth) which were psychometrically sound and showed differential relations with illness and adjustment domains. Although care recipients reported higher levels of benefit finding than carers, their benefit finding reports regarding personal growth were correlated. The carer BFS factors were positively related to carer and care recipient dyadic adjustment. Care recipient benefit finding was unrelated to carer adjustment domains. After controlling for the effects of demographics, care recipient characteristics, problems and appraisal, carer benefit finding was related to carer positive adjustment domains and unrelated to carer negative adjustment domains. Conclusion. Findings support the role of benefit finding in sustaining positive psychological states and the communal search for meaning within carer-care recipient dyads.

Relations between coping and positive and negative outcomes in carers of persons with multiple sclerosis (MS)

This study examined relations between stress and coping predictors and negative and positive outcomes in MS caregiving. A total of 222 carers and their care-recipients completed questionnaires at Time 1 and three months later, Time 2 ( n = 155). Predictors included care-recipient characteristics ( age, time since diagnosis, course and life satisfaction), and Times 1 and 2 carer problems, stress appraisal and coping. Dependent variables were Time 2 negative ( anxiety, depression) and positive outcomes ( life satisfaction, positive affect, benefits). Regressions indicated that, overall, the hypothesised direct effects of stress appraisal and coping strategies on positive and negative outcomes were supported. The hypothesised stress-buffering effects of positive reframing coping were also supported. All but one of the coping strategies were related to both positive and negative outcomes; specifically, practical assistance coping emerged as a unique predictor of distress. Of the model predictors, care-recipient life satisfaction emerged as the strongest and most consistent predictor of both positive and negative outcomes except benefit finding. Findings support the role of care-recipient characteristics and the carer's appraisal and coping processes in shaping both positive and negative outcomes. The guiding framework and findings have the potential to inform interventions designed to promote well-being in carers.

Benefit finding in multiple sclerosis, and associations with positive and negative outcomes

This study examined the direct and stress-buffering effects of benefit finding on positive and negative outcomes. A total of 502 people with multiple sclerosis completed a questionnaire at Time 1 and, 3 months later, at Time 2 (n = 404). Measures of illness were collected at Time 1, and number of problems, stress appraisal, benefit finding, subjective health, and negative (global distress, negative affect) and positive (life satisfaction, positive affect, dyadic adjustment) outcomes were measured at Time 2. Factor analyses showed the Benefit Finding scale to have 2 dimensions: Personal Growth and Family Relations Growth. Hierarchical regressions showed that after controlling for the effects of demographics, illness, problems, and appraisal, benefit finding showed strong direct effects on the positive outcomes. Benefit finding did not have a direct effect on distress, or subjective health but had a weak association with negative affect. Family Relations Growth had a stress-buffering effect on distress.

Chemoprevention of head and neck cancer with retinoids: a negative result

Objective: To determine whether isotretinoin (or 13-cis-retinoic acid) decreases the risk of second primary cancers in patients previously treated for cure of head and neck squamous cell carcinoma. Design: Randomized, double-blind, placebo-controlled trial. Setting: Two head and neck multidisciplinary cancer clinics in university teaching hospitals taking cases from 4 to 5 million people in Queensland, Australia, combined to,enter appropriate patients into this trial. Patients: One hundred fifty-one patients with their first head and neck squamous cell carcinoma treated with high expectation for cure and living close by. They were randomized into 3 arms to receive 3 years of treatment. Interventions: Patients took isotretinoin at a high dose (1.0 mg/kg per day) or a moderate dose (0.5 mg/kg per day) or placebo. Group 1 took the high dose for I year and then the moderate dose for 2 years. Group 2 took the moderate dose for 3 years. Group 3 took placebo for 3 years. Main Outcome Measures: The diagnosis of a second primary malignancy of the head and neck, lung, or bladder was regarded as the end point signifying failure of therapy. Issues of drug adverse effect profile and impact on survival were measured. Results: There was no significant difference in the occurrence of second primary disease (P=.90), the recurrence of primary disease (P=.70), or disease-free time (P=.80) between the treatment and nontreatment arms. Numbers were too small to find differences in survival. Conclusion: With evidence that retinoid treatment adversely affects survival of lung cancer and with this drug not significantly decreasing the incidence of second primary tumors of head and neck squamous cell carcinoma, the use of this drug in head and neck cancer patients for second cancer prophylaxis is not indicated.

Looking beyond the negatives: A time period analysis of positive cognitions, negative cognitions, and working alliance in cognitive-behavior therapy for panic disorder

Time period analysis was used in an international sample of clients ( N = 106) to demonstrate that cognitive - behavioral therapy (CBT) for panic disorder is associated with specific changes in both negative and positive cognitions during the treatment period. In the first 6 weeks of the treatment phase, working alliance failed to predict changes in panic severity, whereas changes in panic self-efficacy and catastrophic misinterpretation of bodily sensations predicted rapid symptom relief. In the last 6 weeks of treatment, higher doses of CBT were associated with further changes in positive and negative cognitions. The findings can be interpreted as suggesting that the role of the working alliance in CBT for panic disorder is to facilitate cognitive change.

Acquisition of negative valence and modified attentional processing by non fear relevant stimuli

The current research examined valence and attentional processing of a priori fear relevant stimuli and investigated the extent to which these characteristics can be acquired by non fear relevant stimuli across an aversive learning episode. The first experiment compared pictures of snakes and spiders with pictures of birds and fish using affective priming, visual search and detection of a dot probe. Snakes and spiders were more negative than birds and fish as indexed by affective priming, and were preferentially attended to in the visual search task. The second experiment exposed the non fear relevant animal pictures, birds and fish, in an aversive learning episode involving an aversive shock US. Skin conductance responding was measured during acquisition. After acquisition, conditioned non fear relevant animal stimuli, CS1, and non conditioned, non fear relevant animal stimuli, CS, were compared across affective priming, visual search and dot probe tasks. During acquisition, skin conductance responses were larger during CS1 than during CS across all three response intervals. After acquisition, CS1 non fear relevant animal pictures were more negative than CS non fear relevant animal pictures as indexed by affective priming, and were preferentially attended to in a dot probe task. These studies provide evidence that negative valence and modified attentional processing can be acquired in a brief aversive learning episode.

Mechanisms underlying the diminished sensitivity to prolactin negative feedback during lactation: Reduced STAT5 signaling and up-regulation of cytokine-inducible SH2 domain-containing protein (CIS) expression in tuberoinfundibular dopaminergic neurons

Hyperprolactinaemia during lactation is a consequence of the sucking stimulus and in part due to reduced prolactin (PRL) negative feedback. To date, the mechanisms involved in this diminished sensitivity to PRL feedback are unknown but may involve changes in PRL signal transduction within tuberoinfundibular dopaminergic (TIDA) neurons. Therefore, we investigated signal transducers and activators of transcription (STAT) 5 signaling in the TIDA neurons of lactating rats. Dual-label confocal immunofluorescence studies were used to determine the intracellular distribution of STAT5 within TIDA neurons in the dorsomedial arcuate nucleus. In lactating rats with pups removed for 16 h, injection of ovine PRL significantly (P < 0.05) increased the STAT5 nuclear/cytoplasmic ratio compared with vehicle-treated mothers. In contrast, ovine PRL injection did not increase the STAT5 nuclear/cytoplasmic ratio in lactating mothers with pups, demonstrating that PRL signal transduction through STAT5 is reduced in TIDA neurons in the presence of pups. To investigate possible mechanisms involved in reduced PRL signaling, we examined the expression of suppressors of cytokine signaling (SOCS) proteins. Northern analysis on whole hypothalamus showed that CIS (cytokine-inducible SH2 domain-containing protein), but not SOCS1 or SOCS3, mRNA expression was significantly (P < 0.01) up-regulated in suckled lactating rats. Semiquantitative RT-PCR on arcuate nucleus micropunches also showed up-regulation of CIS transcripts. Immunofluorescence studies demonstrated that CIS is expressed in all TIDA neurons in the dorsomedial arcuate nucleus, and the intensity of CIS staining in these neurons is significantly (P < 0.05) increased in lactating rats with sucking pups. Together, these results support the hypothesis that loss of sensitivity to PRL-negative feedback during lactation is a result of increased CIS expression in TIDA neurons.

Modelling predicts positive and negative interactions between three Australian tropical tree species in monoculture and binary mixture

Computer modelling promises to. be an important tool for analysing and predicting interactions between trees within mixed species forest plantations. This study explored the use of an individual-based mechanistic model as a predictive tool for designing mixed species plantations of Australian tropical trees. The 'spatially explicit individually based-forest simulator' (SeXI-FS) modelling system was used to describe the spatial interaction of individual tree crowns within a binary mixed-species experiment. The three-dimensional model was developed and verified with field data from three forest tree species grown in tropical Australia. The model predicted the interactions within monocultures and binary mixtures of Flindersia brayleyana, Eucalyptus pellita and Elaeocarpus grandis, accounting for an average of 42% of the growth variation exhibited by species in different treatments. The model requires only structural dimensions and shade tolerance as species parameters. By modelling interactions in existing tree mixtures, the model predicted both increases and reductions in the growth of mixtures (up to +/- 50% of stem volume at 7 years) compared to monocultures. This modelling approach may be useful for designing mixed tree plantations. (c) 2006 Published by Elsevier B.V.

Negative second virial coefficients as predictors of protein crystal growth: Evidence from sedimentation equilibrium studies that refutes the designation of those light scattering parameters as osmotic virial coefficients

The effects of ammonium sulphate concentration on the osmotic second virial coefficient (B-AA/M-A) for equine serum albumin (pH 5.6, 20 degrees C) have been examined by sedimentation equilibrium. After an initial steep decrease with increasing ammonium sulphate concentration, B-AA/M-A assumes an essentially concentration-independent magnitude of 8-9 ml/g. Such behaviour conforms with the statistical-mechanical prediction that a sufficient increase in ionic strength should effectively eliminate the contributions of charge interactions to B-AA/M-A but have no effect on the covolume contribution (8.4 ml/g for serum albumin). A similar situation is shown to apply to published sedimentation equilibrium data for lysozyme (pH 4.5). Although termed osmotic second virial coefficients and designated as such (B-22), the negative values obtained in published light scattering studies of both systems have been described incorrectly because of the concomitant inclusion of the protein-salt contribution to thermodynamic nonideality of the protein. Those negative values are still valid predictors of conditions conducive to crystal growth inasmuch as they do reflect situations in which there is net attraction between protein molecules. However, the source of attraction responsible for the negative virial coefficient stems from the protein-salt rather than the protein-protein contribution, which is necessarily positive. (c) 2005 Elsevier B.V. All rights reserved.

Relations between social support, appraisal and coping and both positive and negative outcomes for children of a parent with multiple sclerosis and comparisons with children of healthy parents

Objective: To examine adjustment in children of a parent with multiple sclerosis within a stress and coping framework and compare them with those who have 'healthy' parents. Subjects: A total of 193 participants between 10 and 25 years completed questionnaires; 48 youngsters who had a parent with multiple sclerosis and 145 youngsters who reported that they did not have a parent with an illness or disability. Method: A questionnaire survey methodology was used. Variable sets included caregiving context (e.g. additional parental illness, family responsibilities, parental functional impairment, choice in helping), social support (network size, satisfaction), stress appraisal, coping (problem solving, seeking support, acceptance, wishful thinking, denial), and positive (life satisfaction, positive affect, benefits) and negative (distress, health) adjustment outcomes. Results: Caregiving context variables significantly correlated with poorer adjustment in children of a parent with multiple sclerosis included additional parental illness, higher family responsibilities, parental functional impairment and unpredictability of the parent's multiple sclerosis, and less choice in helping. As predicted, better adjustment in children of a parent with multiple sclerosis was related to higher levels of social support, lower stress appraisals, greater reliance on approach coping strategies (problem solving, seeking support and acceptance) and less reliance on avoidant coping (wishful thinking and denial). Compared with children of 'healthy' parents, children of a parent with multiple sclerosis reported greater family responsibilities, less reliance on problem solving and seeking social support coping, higher somatization and lower life satisfaction and positive affect. Conclusions: Findings delineate the key impacts of young caregiving and support a stress and coping model of adjustment in children of a parent with multiple sclerosis.