Laccaria bicolor MiSSP8 is a small-secreted protein decisive for the establishment of the ectomycorrhizal symbiosis

The ectomycorrhizal symbiosis is a predominant tree–microbe interaction in forest ecosystems sustaining tree growth and health. Its establishment and functioning implies a long-term and intimate relationship between the soil-borne fungi and the roots of trees. Mycorrhiza-induced Small-Secreted Proteins (MiSSPs) are hypothesized as keystone symbiotic proteins, required to set up the symbiosis by modifying the host metabolism and/or building the symbiotic interfaces. L. bicolor MiSSP8 is the third most highly induced MiSSPs in symbiotic tissues and it is also expressed in fruiting bodies. The MiSSP8-RNAi knockdown mutants are strongly impaired in their mycorrhization ability with Populus, with the lack of fungal mantle and Hartig net development due to the lack of hyphal aggregation. MiSSP8 C-terminus displays a repetitive motif containing a kexin cleavage site, recognized by KEX2 in vitro. This suggests MiSSP8 protein might be cleaved into small peptides. Moreover, the MiSSP8 repetitive motif is found in other proteins predicted secreted by both saprotrophic and ectomycorrhizal fungi. Thus, our data indicate that MiSSP8 is a small-secreted protein involved at early stages of ectomycorrhizal symbiosis, likely by regulating hyphal aggregation and pseudoparenchyma formation.     

Mental Health Outcomes of Psychosocial Intervention Among Traditional Health Practitioner Depressed Patients in Kenya

Task-shifting in mental health such as engaging Traditional Health Practitioners (THPs) in appropriate management of mental disorders is crucial in reducing global mental health challenges. This study aims to determine the outcomes of using evidence-based mental health Global Action Programme Intervention guide (mhGAP-IG) to provide psychosocial interventions among depressed patients seeking care from THPs. THPs were trained to deliver psychosocial interventions to their patients screening positive for mild to severe depression on Beck’s Depression Inventory (BDI). Assessments were conducted at 0, 6 and 12 weeks and Analysis of Variance (ANOVA) performed to determine the change in depression scores over the three time period. BDI mean score was 26.52 before intervention and reduced significantly at 6 (13%) and 12 (35%) weeks after intervention. 58 and 78% of patients showed reduction in symptoms of depression at 6 and 12 weeks. It is therefore crucial to engage THPs in the care of patients with depression and the need for inclusion of training packages; and other mental disorders in order to establish and maintain collaboration between THPs and conventional health workers and promote evidence-based care among marginalized populations. Moreover, further research on randomized control trials of mhGAP-IG intervention versus usual care is required.     

A Cluster-Randomized Controlled Intervention Study to Assess the Effect of a Contact Intervention in Reducing Leprosy-Related Stigma in Indonesia

Background

Can deliberate interaction between the public and persons affected by leprosy reduce stigmatization? The study described in this paper hypothesises that it can and assesses the effectiveness of a ‘contact intervention’.

Methods/Principal Findings

This cluster-randomized controlled intervention study is part of the Stigma Assessment and Reduction of Impact (SARI) project conducted in Cirebon District, Indonesia. Testimonies, participatory videos and comics given or made by people affected by leprosy were used as methods to facilitate a dialogue during so-called ‘contact events’. A mix of seven quantitative and qualitative methods, including two scales to assess aspects of stigma named the SDS and EMIC-CSS, were used to establish a baseline regarding stigma and knowledge of leprosy, monitor the implementation and assess the impact of the contact events. The study sample were community members selected using different sampling methods. The baseline shows a lack of knowledge about leprosy, a high level of stigma and contrasting examples of support. In total, 91 contact events were organised in 62 villages, directly reaching 4,443 community members (mean 49 per event). The interview data showed that knowledge about leprosy increased and that negative attitudes reduced. The adjusted mean total score of the EMIC-CSS reduced by 4.95 points among respondents who had attended a contact event (n = 58; p <0.001, effect size = 0.75) compared to the score at baseline (n = 213); for the SDS this was 3.56 (p <0.001, effect size = 0.81). About 75% of those attending a contact event said they shared the information with others (median 10 persons).

Conclusions/Significance

The contact intervention was effective in increasing knowledge and improving public attitudes regarding leprosy. It is relatively easy to replicate elsewhere and does not require expensive technology. More research is needed to improve scalability. The effectiveness of a contact intervention to reduce stigma against other neglected tropical diseases and conditions should be evaluated.     

CXCL4 and CXCL4L1 Differentially Affect Monocyte Survival and Dendritic Cell Differentiation and Phagocytosis

Upon inflammation, circulating monocytes leave the bloodstream and migrate into the tissues, where they differentiate after exposure to various growth factors, cytokines or infectious agents. The best defined macrophage polarization types are M1 and M2. However, the platelet-derived CXC chemokine CXCL4 induces the polarization of macrophages into a unique phenotype. In this study, we compared the effect of CXCL4 and its variant CXCL4L1 on the differentiation of monocytes into macrophages and into immature monocyte-derived dendritic cells (iMDDC). Differently to M-CSF and CXCL4, CXCL4L1 is not a survival factor for monocytes. Moreover, the expression of the chemokine receptors CCR2, CCR5 and CXCR3 was significantly higher on CXCL4L1-treated monocytes compared to M-CSF- and CXCL4-stimulated monocytes. IL-1 receptor antagonist (IL-1RN) expression was upregulated by CXCL4 and downregulated by CXCL4L1, respectively, whereas both chemokines reduced the expression of the mannose receptor (MRC). Furthermore, through activation of CXCR3, CXCL4L1-stimulated monocytes released significantly higher amounts of CCL2 and CXCL8 compared to CXCL4-treated monocytes, indicating more pronounced inflammatory traits for CXCL4L1. In contrast, in CXCL4L1-treated monocytes, the production of CCL22 was lower. Compared to iMDDC generated in the presence of CXCL4L1, CXCL4-treated iMDDC showed an enhanced phagocytic capacity and downregulation of expression of certain surface markers (e.g. CD1a) and specific enzymes (e.g. MMP-9 and MMP-12). CXCL4 and CXCL4L1 did not affect the chemokine receptor expression on iMDDC and cytokine production (CCL2, CCL18, CCL22, CXCL8, IL-10) by CXCL4- or CXCL4L1-differentiated iMDDC was similar. We can conclude that both CXCL4 and CXCL4L1 exert a direct effect on monocytes and iMDDC. However, the resulting phenotypes are different, which suggests a unique role for the two CXCL4 variants in physiology and/or pathology.     

The Cultural Validation of Two Scales to Assess Social Stigma in Leprosy

Background

Stigma plays in an important role in the lives of persons affected by neglected tropical diseases, and assessment of stigma is important to document this. The aim of this study is to test the cross-cultural validity of the Community Stigma Scale (EMIC-CSS) and the Social Distance Scale (SDS) in the field of leprosy in Cirebon District, Indonesia.

Methodology/principle findings

Cultural equivalence was tested by assessing the conceptual, item, semantic, operational and measurement equivalence of these instruments. A qualitative exploratory study was conducted to increase our understanding of the concept of stigma in Cirebon District. A process of translation, discussions, trainings and a pilot study followed. A sample of 259 community members was selected through convenience sampling and 67 repeated measures were obtained to assess the psychometric measurement properties. The aspects and items in the SDS and EMIC-CSS seem equally relevant and important in the target culture. The response scales were adapted to ensure that meaning is transferred accurately and no changes to the scale format (e.g. lay out, statements or questions) of both scales were made. A positive correlation was found between the EMIC-CSS and the SDS total scores (r = 0.41). Cronbach''s alphas of 0.83 and 0.87 were found for the EMIC-CSS and SDS. The exploratory factor analysis indicated for both scales an adequate fit as unidimensional scale. A standard error of measurement of 2.38 was found in the EMIC-CSS and of 1.78 in the SDS. The test-retest reliability coefficient was respectively, 0.84 and 0.75. No floor or ceiling effects were found.

Conclusions/significance

According to current international standards, our findings indicate that the EMIC-CSS and the SDS have adequate cultural validity to assess social stigma in leprosy in the Bahasa Indonesia-speaking population of Cirebon District. We believe the scales can be further improved, for instance, by adding, changing and rephrasing certain items. Finally, we provide suggestions for use with other neglected tropical diseases.     

The cellular redox state as a modulator in cadmium and copper responses in Arabidopsis thaliana seedlings

The cellular redox state is an important determinant of metal phytotoxicity. In this study we investigated the influence of cadmium (Cd) and copper (Cu) stress on the cellular redox balance in relation to oxidative signalling and damage in Arabidopsis thaliana. Both metals were easily taken up by the roots, but the translocation to the aboveground parts was restricted to Cd stress. In the roots, Cu directly induced an oxidative burst, whereas enzymatic ROS (reactive oxygen species) production via NADPH oxidases seems important in oxidative stress caused by Cd. Furthermore, in the roots, the glutathione metabolism plays a crucial role in controlling the gene regulation of the antioxidative defence mechanism under Cd stress. Metal-specific alterations were also noticed with regard to the microRNA regulation of CuZnSOD gene expression in both roots and leaves. The appearance of lipid peroxidation is dual: it can be an indication of oxidative damage as well as an indication of oxidative signalling as lipoxygenases are induced after metal exposure and are initial enzymes in oxylipin biosynthesis.In conclusion, the metal-induced cellular redox imbalance is strongly dependent on the chemical properties of the metal and the plant organ considered. The stress intensity determines its involvement in downstream responses in relation to oxidative damage or signalling.     

Immunoglobulin Deposition in Liver of Patients with Active Chronic Hepatitis and Antibody against Smooth Muscle

Liver biopsies from 33 patients with miscellaneous liver diseases were studied by direct immunofluorescence. Three patients with active chronic hepatitis possessed a distinctive pattern of staining with anti-IgG conjugate. They were relatively young women and all three possessed the anti-smooth-muscle antibody. In addition, all three were untreated at the time of study. It is suggested that direct immunofluorescence on liver biopsies may help in the investigation of liver disease and that humoral immunity may participate in the pathogenesis of active chronic hepatitis.