244 research outputs found

    Decreased expression of breast cancer resistance protein in the duodenum in patients with obstructive cholestasis

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    Background/Aims: The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Since the drug efflux transporter breast cancer resistance protein (BCRP) is known to transport bile acids, we investigated whether duodenal BCRP expression could be altered during cholestasis. Methods: Using real-time RT-PCR analysis we determined mRNA expression levels in duodenal tissue of 19 cholestatic patients. Expression levels were compared to 14 healthy subjects. BCRP protein staining was determined in biopsies of 6 cholestatic and 6 healthy subjects by immunohistochemistry. Results: We found that in patients with obstructive cholestasis mean duodenal BCRP mRNA levels were significantly reduced to 53% and mean protein staining was reduced to 57%. Conclusions: BCRP, a transporter for bile acids and numerous drugs, appears to be down-regulated in the human duodenum during cholestasis. The clinical impact of these results has to be investigated in further studies. Copyright (c) 2006 S. Karger AG, Basel

    Having a lot of a good thing: multiple important group memberships as a source of self-esteem.

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    Copyright: © 2015 Jetten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedMembership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem.This study was supported by 1. Australian Research Council Future Fellowship (FT110100238) awarded to Jolanda Jetten (see http://www.arc.gov.au) 2. Australian Research Council Linkage Grant (LP110200437) to Jolanda Jetten and Genevieve Dingle (see http://www.arc.gov.au) 3. support from the Canadian Institute for Advanced Research Social Interactions, Identity and Well-Being Program to Nyla Branscombe, S. Alexander Haslam, and Catherine Haslam (see http://www.cifar.ca)

    Does an extensive diagnostic workup for upfront resectable pancreatic cancer result in a delay which affects survival? Results from an international multicentre study

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    Backgrounds/Aims: Pancreatoduodenectomy (PD) is recommended in fit patients with a carcinoma (PDAC) of the pancreatic head, and a delayed resection may affect survival. This study aimed to correlate the time from staging to PD with long-term survival, and study the impact of preoperative investigations (if any) on the timing of surgery. // Methods: Data were extracted from the Recurrence After Whipple’s (RAW) study, a multicentre retrospective study of PD outcomes. Only PDAC patients who underwent an upfront resection were included. Patients who received neoadjuvant chemo-/radiotherapy were excluded. Group A (PD within 28 days of most recent preoperative computed tomography [CT]) was compared to group B (> 28 days). // Results: A total of 595 patents were included. Compared to group A (median CT-PD time: 12.5 days, interquartile range: 6–21), group B (49 days, 39–64.5) had similar one-year survival (73% vs. 75%, p = 0.6), five-year survival (23% vs. 21%, p = 0.6) and median time-todeath (17 vs. 18 months, p = 0.8). Staging laparoscopy (43 vs. 29.5 days, p = 0.009) and preoperative biliary stenting (39 vs. 20 days, p 0.99) and endoscopic ultrasonography (28 vs. 32 days, p > 0.99) were not. // Conclusions: Although a treatment delay may give rise to patient anxiety, our findings would suggest this does not correlate with worse survival. A delay may be necessary to obtain further information and minimize the number of PD patients diagnosed with early disease recurrence

    Development of aggression subtypes from childhood to adolescence:a group-based multi-trajectory modelling perspective

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    The persistence of elevated subtypes of aggression beginning in childhood have been associated with long-term maladaptive outcomes. Yet it remains unclear to what extent there are clusters of individuals following similar developmental trajectories across forms (i.e., physical and indirect) and functions (i.e., proactive and reactive) of aggression. We aimed to identify groups of children with distinct profiles of the joint development of forms and functions of aggression and to identify risk factors for group membership. A sample of 787 children was followed from birth to adolescence. Parent and teacher reports, and standardised assessments were used to measure two forms and two functions of aggressive behaviour, between six and 13 years of age along with preceding child, maternal, and family-level risk-factors. Analyses were conducted using a group-based multi-trajectory modelling approach. Five trajectory groups emerged: non-aggressors, low-stable, moderate-engagers, high-desisting, and high-chronic. Coercive parenting increased membership risk in the moderate-engagers and high-chronic groups. Lower maternal IQ increased membership risk in both high-desisting and high-chronic groups, whereas maternal depression increased membership risk in the high-desisting group only. Never being breastfed increased membership risk in the moderate-engagers group. Boys were at greater risk for belonging to groups displaying elevated aggression. Individuals with chronic aggression problems use all subtypes of aggression. Risk factors suggest that prevention programs should start early in life and target mothers with lower IQ. Strategies to deal with maternal depression and enhance positive parenting while replacing coercive parenting tactics should be highlighted in programming efforts

    The Integrative Effects of Cognitive Reappraisal on Negative Affect: Associated Changes in Secretory Immunoglobulin A, Unpleasantness and ERP Activity

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    Although the regulatory role of cognitive reappraisal in negative emotional responses is widely recognized, this reappraisal's effect on acute saliva secretory immunoglobulin A (SIgA), as well as the relationships among affective, immunological, and event-related potential (ERP) changes, remains unclear. In this study, we selected only people with low positive coping scores (PCSs) as measured by the Trait Coping Style Questionnaire to avoid confounding by intrinsic coping styles. First, we found that the acute stress of viewing unpleasant pictures consistently decreased SIgA concentration and secretion rate, increased perceptions of unpleasantness and amplitude of late positive potentials (LPPs) between 200–300 ms and 400–1000 ms. After participants used cognitive reappraisal, their SIgA concentration and secretion rate significantly increased and their unpleasantness and LPP amplitudes significantly decreased compared with a control condition. Second, we found a significantly positive correlation between the increases in SIgA and the decreases in unpleasantness and a significantly negative correlation between the increases in SIgA and the increases in LPP across the two groups. This study is the first to demonstrate that cognitive reappraisal reverses the decrease of SIgA. In addition, it revealed strong correlations among affective, SIgA and electrophysiological changes with convergent multilevel evidence

    Conserved BK Channel-Protein Interactions Reveal Signals Relevant to Cell Death and Survival

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    The large-conductance Ca2+-activated K+ (BK) channel and its β-subunit underlie tuning in non-mammalian sensory or hair cells, whereas in mammals its function is less clear. To gain insights into species differences and to reveal putative BK functions, we undertook a systems analysis of BK and BK-Associated Proteins (BKAPS) in the chicken cochlea and compared these results to other species. We identified 110 putative partners from cytoplasmic and membrane/cytoskeletal fractions, using a combination of coimmunoprecipitation, 2-D gel, and LC-MS/MS. Partners included 14-3-3γ, valosin-containing protein (VCP), stathmin (STMN), cortactin (CTTN), and prohibitin (PHB), of which 16 partners were verified by reciprocal coimmunoprecipitation. Bioinformatics revealed binary partners, the resultant interactome, subcellular localization, and cellular processes. The interactome contained 193 proteins involved in 190 binary interactions in subcellular compartments such as the ER, mitochondria, and nucleus. Comparisons with mice showed shared hub proteins that included N-methyl-D-aspartate receptor (NMDAR) and ATP-synthase. Ortholog analyses across six species revealed conserved interactions involving apoptosis, Ca2+ binding, and trafficking, in chicks, mice, and humans. Functional studies using recombinant BK and RNAi in a heterologous expression system revealed that proteins important to cell death/survival, such as annexinA5, γ-actin, lamin, superoxide dismutase, and VCP, caused a decrease in BK expression. This revelation led to an examination of specific kinases and their effectors relevant to cell viability. Sequence analyses of the BK C-terminus across 10 species showed putative binding sites for 14-3-3, RAC-α serine/threonine-protein kinase 1 (Akt), glycogen synthase kinase-3β (GSK3β) and phosphoinositide-dependent kinase-1 (PDK1). Knockdown of 14-3-3 and Akt caused an increase in BK expression, whereas silencing of GSK3β and PDK1 had the opposite effect. This comparative systems approach suggests conservation in BK function across different species in addition to novel functions that may include the initiation of signals relevant to cell death/survival

    The Human Affectome

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    Over the last decades, the interdisciplinary field of the affective sciences has seen proliferation rather than integration of theoretical perspectives. This is due to differences in metaphysical and mechanistic assumptions about human affective phenomena (what they are and how they work) which, shaped by academic motivations and values, have determined the affective constructs and operationalizations. An assumption on the purpose of affective phenomena can be used as a teleological principle to guide the construction of a common set of metaphysical and mechanistic assumptions—a framework for human affective research. In this capstone paper for the special issue “Towards an Integrated Understanding of the Human Affectome”, we gather the tiered purpose of human affective phenomena to synthesize assumptions that account for human affective phenomena collectively. This teleologically-grounded framework offers a principled agenda and launchpad for both organizing existing perspectives and generating new ones. Ultimately, we hope Human Affectome brings us a step closer to not only an integrated understanding of human affective phenomena, but an integrated field for affective research
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