Binding partners for the COOH-Terminal appendage domains of the GGAs and gamma-adaptin

The adaptor appendage domains are believed to act as binding platforms for coated vesicle accessory proteins. Using glutathione S-transferase pulldowns from pig brain cytosol, we find three proteins that can bind to the appendage domains of both the AP-1 gamma subunit and the GGAs: gamma-synergin and two novel proteins, p56 and p200. p56 elicited better antibodies than p200 and was generally more tractable. Although p56 and gamma-synergin bind to both GGA and gamma appendages in vitro, immunofluorescence labeling of nocodazole-treated cells shows that p56 colocalizes with GGAs on TGN46-positive membranes, whereas gamma-synergin colocalizes with AP-1 primarily on a different membrane compartment. Furthermore, in AP-1-deficient cells, p56 remains membrane-associated whereas gamma-synergin becomes cytosolic. Thus, p56 and gamma-synergin show very strong preferences for GGAs and AP-1, respectively, in vivo. However, the GGA and gamma appendages share the same fold as determined by x-ray crystallography, and mutagenesis reveals that the same amino acids contribute to their binding sites. By overexpressing wild-type GGA and gamma appendage domains in cells, we can drive p56 and gamma-synergin, respectively, into the cytosol, suggesting a possible mechanism for selectively disrupting the two pathways

A Brief Mindfulness-Based Family Psychoeducation Intervention for Chinese Young Adults With First Episode Psychosis: A Study Protocol

Family psychoeducation (FPE) has been recommended as a major component in the treatment of psychosis. Many previous studies have implemented an intensive program design that often only emphasized improvements in patients’ illness outcomes but the benefits for caregivers were limited. There have been calls for a time-limited but cost-effective FPE program to mitigate the looming reality of the suffering of people with psychosis and their families. A Brief Mindfulness-Based Family Psychoeducation for psychosis program is developed to reduce caregivers’ burden and promote young adult’s recovery. A randomized controlled trial will be conducted to compare this intervention with an ordinary FPE intervention. Both arms will involve six sessions, with a total contact time of 12 h. 300 caregivers of young adults who have experienced first episode psychosis within last 3 years will be recruited. Program effectiveness will be assessed by comparing outcomes measuring the caregivers’ burden, mental health symptoms, positive well-being, and the young adult’s mental health symptoms during the study and at 9-month post-randomization. The role of expressed emotions, interpersonal mindfulness, and non-attachment in mediating these outcomes will be explored. An additional qualitative approach Photovoice is selected to explore the complex family experiences and the benefits of mindfulness from the caregivers’ personal perspectives.Trial Registration: The trial is registered with the United States Clinical Trials Registry (ClinicalTrials.gov): NCT03688009

Psychological distress among adolescents in Chengdu, Sichuan at one month after the 2008 Sichuan Earthquake

A devastating earthquake occurred on May 12, 2008 in Sichuan, China. This study investigated the prevalence and factors in association with psychological problems among secondary school students living in Chengdu (90 km away from the disaster epicenter) in June 2008. In a cross-sectional survey, 3,324 secondary students self-administered a structured questionnaire in classroom setting. Validated scales were used in this study. Among all respondents, 22.3% reported post-traumatic stress disorder (PTSD); 22.6% were probable depression cases; 10.6% reported suicidal ideation; and 14.1% would like to receive psychological counseling. No gender differences were found. While social/emotional support from teachers or peers (OR from 0.40 to 0.78) and exposure to positive news reports (OR from 0.59 to 0.62) were found protective, prior experience of severe mental distress (OR from 1.60 to 2.68) and corporal punishment (OR from 1.31 to 1.58), worry about future aftershocks (OR from 1.64 to 3.11), absence from school when it was not closed (OR from 1.38 to 1.48), exposures to scary or sorrowful disaster media coverage (OR from 1.39 to 2.07), post-disaster visits to affected sites (OR from 1.51 to 1.59), separation from parents (OR = 1.61), etc., were risk factors predictive of some of the aforementioned psychological problems. Negative mental health impacts were prevalent among the respondents. Teachers, parents, and the mass media are all important in maintaining good mental health among adolescents that are indirectly affected by the severe earthquake. The results have important implications for earthquake preparedness and relief work in the future

Validation of the Chinese version of the Children's Revised Impact of Event Scale (CRIES) among Chinese adolescents in the aftermath of the Sichuan Earthquake in 2008

Objective: This study examined the psychometric properties of the 13-item Chinese version of the revised Impact of Event Scale for Children (CRIES) among 3160 high school students in Chengdu, China, 1 month after the Sichuan Earthquake in 2008.</p

Posttraumatic growth and reduced suicidal ideation among adolescents at month 1 after the Sichuan Earthquake

Background: This study investigated posttraumatic growth (PTG) and reduced suicidal ideation among Chinese adolescents at one month after the occurrence of the Sichuan Earthquake

HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis

<div><p>Background</p><p>We aimed to study the pathogenic roles of High-Mobility Group Box 1 (HMGB1) / Receptor-for-Advanced-Glycation-End-products (RAGE) signaling and pro-inflammatory cytokines in patients with active pulmonary tuberculosis (PTB).</p><p>Methods</p><p>A prospective study was conducted among non-HIV adults newly-diagnosed with active PTB at two acute-care hospitals (n = 80); age-and-sex matched asymptomatic individuals (tested for latent TB) were used for comparison (n = 45). Plasma concentrations of 8 cytokines/chemokines, HMGB1, soluble-RAGE, and transmembrane-RAGE expressed on monocytes/dendritic cells, were measured. Gene expression (mRNA) of HMGB1, RAGE, and inflammasome-NALP3 was quantified. Patients’ PBMCs were stimulated with recombinant-HMGB1 and MTB-antigen (lipoarabinomannan) for cytokine induction e<i>x vivo</i>.</p><p>Results</p><p>In active PTB, plasma IL-8/CXCL8 [median(IQR), 6.0(3.6–15.1) <i>vs</i> 3.6(3.6–3.6) pg/ml, P<0.001] and IL-6 were elevated, which significantly correlated with mycobacterial load, extent of lung consolidation (<b><i>r</i></b>_{<b><i>s</i></b>} +0.509, P<0.001), severity-score (<b><i>r</i></b>_{<b><i>s</i></b>} +0.317, P = 0.004), and fever and hospitalization durations (<b><i>r</i></b>_{<b><i>s</i></b>} +0.407, P<0.001). IL-18 and sTNFR1 also increased. Plasma IL-8/CXCL8 (adjusted OR 1.12, 95%CI 1.02–1.23 per unit increase, P = 0.021) and HMGB1 (adjusted OR 1.42 per unit increase, 95%CI 1.08–1.87, P = 0.012) concentrations were independent predictors for respiratory failure, as well as for ICU admission/death. Gene expression of HMGB1, RAGE, and inflammasome-NALP3 were upregulated (1.2−2.8 fold). Transmembrane-RAGE was increased, whereas the decoy soluble-RAGE was significantly depleted. RAGE and HMGB1 gene expressions positively correlated with cytokine levels (IL-8/CXCL8, IL-6, sTNFR1) and clinico-/radiographical severity (e.g. extent of consolidation <i>r</i>_s +0.240, P = 0.034). <i>Ex vivo</i>, recombinant-HMGB1 potentiated cytokine release (e.g. TNF-α) when combined with lipoarabinomannan.</p><p>Conclusion</p><p>In patients with active PTB, HMGB1/RAGE signaling and pro-inflammatory cytokines may play important roles in pathogenesis and disease manifestations. Our clinico-immunological data can provide basis for the development of new strategies for disease monitoring, management and control.</p></div