Characterization of the D-amino acid oxidase interactome

Schizophrenia is a psychiatric disorder affecting about 1% of the world's population and manifests itself as positive symptoms (eg. hallucinations), negative symptoms (eg. social withdrawal) in conjunction with cognitive impairments (eg. working memory). Evidence suggests that schizophrenia is, in part, a heritable disease. Candidate susceptibility genes implicate the glutamatergic neurotransmitter system, reinforcing clinical observations of N-methyl-D-aspartate receptor (NMDAR) hypofunction in schizophrenia. One of those genes, D-amino acid oxidase (DAO), is genetically associated with schizophrenia and its function includes degradation of D-serine, the NMDAR co-agonist. DAO is a candidate gene of high interest due to schizophrenic patients' manifestation of reduced D-serine levels, increased DAO expression and increased DAO activity. Despite mounting evidence for DAO involvement in schizophrenia, its regulation is poorly understood. Characterization of DAO may lead to a more thorough understanding of its function and biology and ultimately to the identification of novel targets for this disorder. To this end, DAO-specific antibodies were utilized to identify DAO-interacting proteins through co-immunoprecipitation from rat cerebellum, where DAO expression is especially high. Subsequent mass spectroscopy analysis of associating proteins yielded twenty-four putative DAO interactors. The most abundant and interesting interactors include known presynaptic active zone members such as bassoon (BSN) and piccolo (PCLO). The DAO interaction with BSN was confirmed through co-immunoprecipitation and both proteins were shown to localize in the presynaptic junction. These data suggest that BSN is a novel DAO interactor and defines a previously unappreciated localization of DAO perhaps as a result of a physiologically important interaction with BSN. Furthermore, BSN was found to partially inhibit DAO enzymatic activity in transiently transfected human embryonic kidney (Hek293) cells. Collectively these novel findings suggest that synaptic D-serine concentration may be under tight regulation by BSN via proximally localized DAO. DAO may thus play a role in modulating the functions of the presynaptic active zone via its interaction with BSN

Are prisoners more psychopathic than non-forensic populations? Profiling psychopathic traits among prisoners, community adults, university students, and adolescents

The aim of this study was to compare prisoners (n = 772), community adults (n = 1201), university students (n = 2080), and adolescents (n = 472) on four sets of psychopathic traits (affective responsiveness, cognitive responsiveness, interpersonal manipulation, and egocentricity), using a psychopathy measure which does not index criminal/antisocial behaviour – the Psychopathic Personality Traits Scale. Another aim was to examine patterns of co-occurrence between psychopathic personality traits among offending and non-offending populations. ANOVA results indicated significant differences between the four groups on all PPTS dimensions. Adolescents demonstrated greater deficits in affective and cognitive responsiveness than the remaining groups of participants. Prisoners had elevated deficits in cognitive responsiveness, compared with university students and community adults. University students scored higher on interpersonal manipulation than adolescents and prisoners, and higher on egocentricity than community adults and prisoners. Latent profile analysis revealed four distinct classes of psychopathic traits among all samples, although not all classes were qualitatively equivalent across samples. Low psychopathy groups were identified for all samples. There were clear high psychopathy groups for prisoners and university students, with approximately 7% of prisoners and students belonging in the groups. This finding indicates that past research could have over-estimated the prevalence of psychopathy in forensic populations due to inclusion of criminal behaviour items in psychopathy assessment

Globally Distributed Drug Discovery of New Antibiotics: Design and Combinatorial Synthesis of Amino Acid Derivatives in the Organic Chemistry Laboratory

An experiment for the synthesis of N-acyl derivatives of natural amino acids has been developed as part of the Distributed Drug Discovery (D3) program. Students use solid-phase synthesis techniques to complete a three-step, combinatorial synthesis of six products, which are analyzed using LC–MS and NMR spectroscopy. This protocol is suitable for introductory organic laboratory students and has been successfully implemented at multiple academic sites internationally. Accompanying prelab activities introduce students to SciFinder and to medicinal chemistry design principles. Pairing of these activities with the laboratory work provides students an authentic and cohesive research project experience

Does true Gleason pattern 3 merit its cancer descriptor?

Nearly five decades following its conception, the Gleason grading system remains a cornerstone in the prognostication and management of patients with prostate cancer. In the past few years, a debate has been growing whether Gleason score 3 + 3 = 6 prostate cancer is a clinically significant disease. Clinical, molecular and genetic research is addressing the question whether well characterized Gleason score 3 + 3 = 6 disease has the ability to affect the morbidity and quality of life of an individual in whom it is diagnosed. The consequences of treatment of Gleason score 3 + 3 = 6 disease are considerable; few men get through their treatments without sustaining some harm. Further modification of the classification of prostate cancer and dropping the label cancer for Gleason score 3 + 3 = 6 disease might be warranted

Tasiemczyce w wojewodztwie dolnoslaskim w latach 1993-1997

This paper is the result of investigations of taeniosis in inhabitants of four former provinces of the Lower Silesia area in the 1993-1997 years. Analysis of frequency taneniosis (according to place of living and sex) confirmed clearly the decrease of tendency of this parasitosis