The validity and reliability of the German version of the Somatoform Dissociation Questionnaire (SDQ-20).

The present study investigated the validity of the German version of the Somatoform Dissociation Questionnaire (SDQ-20), a scale designed to measure somatoform dissociative symptoms. Somatoform dissociation involves physical manifestations of a dissociation of the personality and is considered a unique entity in the phenomenological spectrum of dissociation. The validity and reliability of the German version of the SDQ-20 was examined using a sample of 225 patients with (n = 39) and without dissociative disorders who were recruited from several in- and outpatient psychiatric clinics. Patients were assessed using structured diagnostic interviews; diagnostic checklists; and self-rating scales for dissociation, and posttraumatic stress. Patients with dissociative disorders reported significantly more (p < .001) somatoform dissociative symptoms than patients without dissociative disorders (criterion validity). Significant correlations (p < .001) were found between scores of somatoform dissociation, psychoform dissociation, posttraumatic stress symptoms, and traumatic childhood experiences (construct validity). Reliability was corroborated by a Cronbach's alpha coefficient of .91 and a test-retest correlation of .89. A component factor analysis suggested unidimensionality of the SDQ-20. In conclusion, the psychometric properties and cross-cultural validity of the German version of the SDQ-20 are excellent. Our results form the basis for the further study of somatoform dissociation in German-speaking populations.

[Mental Disorder and Self-Rated Health Among Homeless People in Zurich - First Epidemiological Data from Switzerland]. / Psychische Krankheit und subjektive Gesundheit bei Wohnungslosen in Zürich.

Objective This study aims to assess psychiatric morbidity and self-rated health (SRH) of homeless people in Zurich, Switzerland. Methods Cross-sectional study of N = 338 homeless people, assessement of psychiatric disorders (ICD-10), level of functioning (GAF, HoNOS), self-rated health. Comparison of SRH among homeless people with a sample of Zurich (N = 956) and Swiss (N = 21 579) population. Results 96 % of the homeless people had at least one psychiatric disorder, most of them drug- (60.9 %) or alcohol-dependence (41.5 %). Homeless people had a far lower SRH than the Zurich population. Higher impairment in HoNOS was associated with lower levels of SRH. Low SRH was associated with help care seeking (OR = 1.9, p < 0.001) and medication (OR = 1.5, p = 0.006). Conclusions The prevalence of psychiatric disorders is far higher among homeless people compared to the general population in Zurich. Implications for providing help at the intersection of social and health care are discussed.

Identification and characterization of endogenous Langerin ligands in murine extracellular matrix.

Langerin is a C-type lectin that is expressed by Langerhans cells (LC) and related immune cells, and believed to play an important role in antigen recognition and uptake. To determine if Langerin has endogenous ligands, we generated S protein binding, bacterial recombinant, mouse soluble Langerin, and utilized it as a probe. Recombinant soluble Langerin did not bind to lymph node or spleen cells, or keratinocytes as assessed via flow cytometry. However, Langerin did bind to surfaces of primary skin fibroblasts and NIH3T3 cells. "Ligand blotting" of fibroblast membrane-enriched fractions with Langerin revealed reproducible binding to 140 and 240 kDa proteins resolved in reduced denaturing gels. Characterization of these proteins using mass spectrometry suggested types I and III procollagen and fibronectin as candidate ligands. Langerin bound to type I procollagen that was immunoprecipitated from fibroblast lysates, but did not bind to fibronectin that was immunoprecipitated from fibroblast-conditioned media or mouse plasma fibronectin. These results indicate that Langerin selectively interacts with at least one ligand in extracellular matrix (type I procollagen). Langerin may have an unanticipated role in cell-matrix interactions that modulate LC development, localization, or function.

Psychosocial functioning of individuals with schizophrenia in community housing facilities and the psychiatric hospital in Zurich.

Individuals with severe mental illness frequently have difficulties in obtaining and maintaining adequate accommodation. If they are not willing or able to adapt to requirements of traditional supported housing institutions they may live in sheltered and emergency accommodation. Adequate mental health services are rarely available in these facilities. The aim of the present study was to evaluate mental health, functional and social status of individuals living in community sheltered housing facilities. A cross-sectional survey of n=338 individuals in sheltered housing compared to a sample of patients at intake in acute inpatient psychiatry (n=619) concerning clinical and social variables was carried out in the catchment area of Zurich. Matched subsamples of individuals with schizophrenia (n=168) were compared concerning functioning and impairments on the Health of the Nation Outcome Scales (HoNOS). Individuals with schizophrenia in sheltered housing (25% of the residents) have significantly more problems concerning substance use, physical illness, psychopathological symptoms other than psychosis and depression, and relationships, daily activities and occupation than patients with schizophrenia at intake on an acute psychiatric ward. Community sheltered accommodation although conceptualized to prevent homelessness in the general population de facto serve as housing facilities for individuals with schizophrenia and other severe mental illness.

Actin and dynamin2 dynamics and interplay during clathrin-mediated endocytosis.

Clathrin-mediated endocytosis (CME) involves the recruitment of numerous proteins to sites on the plasma membrane with prescribed timing to mediate specific stages of the process. However, how choreographed recruitment and function of specific proteins during CME is achieved remains unclear. Using genome editing to express fluorescent fusion proteins at native levels and live-cell imaging with single-molecule sensitivity, we explored dynamin2 stoichiometry, dynamics, and functional interdependency with actin. Our quantitative analyses revealed heterogeneity in the timing of the early phase of CME, with transient recruitment of 2-4 molecules of dynamin2. In contrast, considerable regularity characterized the final 20 s of CME, during which ∼26 molecules of dynamin2, sufficient to make one ring around the vesicle neck, were typically recruited. Actin assembly generally preceded dynamin2 recruitment during the late phases of CME, and promoted dynamin recruitment. Collectively, our results demonstrate precise temporal and quantitative regulation of the dynamin2 recruitment influenced by actin polymerization.

Targeted integration in rat and mouse embryos with zinc-finger nucleases.

Gene targeting is indispensible for reverse genetics and the generation of animal models of disease. The mouse has become the most commonly used animal model system owing to the success of embryonic stem cell-based targeting technology, whereas other mammalian species lack convenient tools for genome modification. Recently, microinjection of engineered zinc-finger nucleases (ZFNs) in embryos was used to generate gene knockouts in the rat and the mouse by introducing nonhomologous end joining (NHEJ)-mediated deletions or insertions at the target site. Here we use ZFN technology in embryos to introduce sequence-specific modifications (knock-ins) by means of homologous recombination in Sprague Dawley and Long-Evans hooded rats and FVB mice. This approach enables precise genome engineering to generate modifications such as point mutations, accurate insertions and deletions, and conditional knockouts and knock-ins. The same strategy can potentially be applied to many other species for which genetic engineering tools are needed.

Species differences in the carbohydrate binding preferences of surfactant protein D.

Interactions of surfactant protein D (SP-D) with micro-organisms and organic antigens involve binding to the trimeric neck plus carbohydrate recognition domain (neck+CRD). In these studies, we compared the ligand binding of homologous human, rat, and mouse trimeric neck+CRD fusion proteins, each with identical N-terminal tags remote from the ligand-binding surface. Although rat and mouse showed similar affinities for saccharide competitors, both differed markedly from the human protein. The human neck+CRD preferentially recognized N-acetyl-mannosamine, whereas the rat and mouse proteins showed greater affinity for myoinositol, maltose, and glucose. Although human neck+CRDs bound to maltosyl-agarose and fungal mannan, only rat and mouse neck+CRDs showed significant binding to maltosyl-Toyopearl beads, solid-phase maltosyl-albumin neo-glycoprotein, or the Phil82 strain of influenza A virus. Likewise, human SP-D dodecamers and trimeric subunits of full-length rat, but not full-length human SP-D trimers, bound to maltosyl-Toyopearl. Site-directed mutagenesis of the human neck+CRD demonstrated an important role of Asp324-Asp325 in the recognition of N-acetyl-mannosamine, and substitution of the corresponding murine sequence (Asn324-Asn325) conferred a capacity to interact with immobilized maltose. Thus, ligand recognition by human SP-D involves a complex interplay between saccharide presentation, the valency of trimeric subunits, and species-specific residues that flank the primary carbohydrate binding site.

Ligand specificity of human surfactant protein D: expression of a mutant trimeric collectin that shows enhanced interactions with influenza A virus.

Surfactant protein D is a pattern recognition molecule that plays diverse roles in immune regulation and anti-microbial host defense. Its interactions with known ligands are calcium-dependent and involve binding to the trimeric, C-type carbohydrate recognition domain. Surfactant protein D preferentially binds to glucose and related sugars. However, CL-43, a bovine serum lectin, which evolved through duplication of the surfactant protein D gene in ruminants, prefers mannose and mannose-rich polysaccharides. Surfactant protein D is characterized by two relatively conserved motifs at the binding face, along the edges of the shallow carbohydrate-binding groove. For CL-43, sequence alignments demonstrate a basic insertion, Arg-Ala-Lys (RAK), immediately N-terminal to the first motif. We hypothesized that this insertion contributes to the differences in saccharide selectivity and host defense function and compared the activities of recombinant trimeric neck + carbohydrate recognition domains of human surfactant protein D (NCRD) with CL-43 (RCL-43-NCRD) and selected NCRD mutants. Insertion of the CL-43 RAK sequence or a control Ala-Ala-Ala sequence (AAA) into the corresponding position in NCRD increased the efficiency of binding to mannan and changed the inhibitory potencies of competing saccharides to more closely resemble those of CL-43. In addition, RAK resembled CL-43 in its greater capacity to inhibit the infectivity of influenza A virus and to increase uptake of influenza by neutrophils.