Search

Sigma non-opioid intracellular receptor 1 (Sigma-1R) is an intracellular chaperone protein residing on the endoplasmic reticulum at the mitochondrial-associated membrane (MAM) region. Sigma-1R is abundant in the brain and is involved in several physiological processes as well as in various disease states. The role of Sigma-1R at the blood–brain barrier (BBB) is incompletely characterized. In this study, the effect of Sigma-1R activation was investigated in vitro on rat brain microvascular endothelial cells (RBMVEC), an important component of the blood–brain barrier (BBB), and in vivo on BBB permeability in rats. The Sigma-1R agonist PRE-084 produced a dose-dependent increase in mitochondrial calcium, and mitochondrial and cytosolic reactive oxygen species (ROS) in RBMVEC. PRE-084 decreased the electrical resistance of the RBMVEC monolayer, measured with the electric cell-substrate impedance sensing (ECIS) method, indicating barrier disruption. These effects were reduced by pretreatment with Sigma-1R antagonists, BD 1047 and NE 100. In vivo assessment of BBB permeability in rats indicates that PRE-084 produced a dose-dependent increase in brain extravasation of Evans Blue and sodium fluorescein brain; the effect was reduced by the Sigma-1R antagonists. Immunocytochemistry studies indicate that PRE-084 produced a disruption of tight and adherens junctions and actin cytoskeleton. The brain microcirculation was directly visualized in vivo in the prefrontal cortex of awake rats with a miniature integrated fluorescence microscope (aka, miniscope; Doric Lenses Inc.). Miniscope studies indicate that PRE-084 increased sodium fluorescein extravasation in vivo. Taken together, these results indicate that Sigma-1R activation promoted oxidative stress and increased BBB permeability. [ABSTRACT FROM AUTHOR]

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have unique characteristics where they can both contribute to all three germ layers in vivo and self-renewal indefinitely in vitro. Post-translational modifications of proteins, particularly by the ubiquitin proteasome system (UPS), control cell pluripotency, self-renewal, and differentiation. A significant number of UPS members (mainly ubiquitin ligases) regulate pluripotency and influence ESC differentiation with key elements of the ESC pluripotency network (including the "master" regulators NANOG and OCT4) being controlled by ubiquitination. To further understand the role of the UPS in pluripotency, we performed an RNAi screen during induction of cellular reprogramming and have identified FBXO9 as a novel regulator of pluripotency associated protein DPPA5. Our findings indicate that FBXO9 silencing facilitates the induction of pluripotency through decreased proteasomal degradation of DPPA5. These findings identify FBXO9 as a key regulator of pluripotency. [ABSTRACT FROM AUTHOR]

Nitrous oxide (N2O) is a potent greenhouse gas and its reduction to dinitrogen gas by the N2O reductase (encoded by the nosZ gene) is the only known biological N2O sink. Within the nosZ phylogeny there are two major clades (I and II), which seem to have different ecological niches. However, physiological differences of nosZ I and nosZ II expression that may impact emissions of N2O are not well understood. Here, we evaluated the differential expression of nosZ I and nosZ II, both present in Thauera linaloolentis strain 47LolT, in response to N2O concentration and the presence of the competing electron acceptor nitrate (NO3−). Different N2O levels had a negligible effect on the expression of both nosZ clades. Interestingly, nosZ II expression was strongly upregulated in the absence of NO3−, while nosZ I expression remained constant across the conditions tested. Thus, NO3− possibly inhibited nosZ II expression, which suggests that N2O mitigation mediated by nosZ II can be restricted due to the presence of NO3− in the environment. This is the first study demonstrating differential expression of nosZ I and nosZ II genes under the same physiological conditions and their implications for N2O emission under varying environmental conditions in terms of NO3− availability. [ABSTRACT FROM AUTHOR]

In coastal sediments, excess nitrogen is removed primarily by denitrification. However, losses in habitat diversity may reduce the functional diversity of microbial communities that drive this important filter function. We examined how habitat type and habitat diversity affects denitrification and the abundance and diversity of denitrifying and N2O reducing communities in illuminated shallow-water sediments. In a mesocosm experiment, cores from four habitats were incubated in different combinations, representing ecosystems with different habitat diversities. We hypothesized that habitat diversity promotes the diversity of N2O reducing communities and genetic potential for denitrification, thereby influencing denitrification rates. We also hypothesized that this will depend on the identity of the habitats. Habitat diversity positively affected ecosystem-level diversity of clade II N2O reducing communities, however neither clade I nosZ communities nor denitrification activity were affected. The composition of N2O reducing communities was determined by habitat type, and functional gene abundances indicated that silty mud and sandy sediments had higher genetic potentials for denitrification and N2O reduction than cyanobacterial mat and Ruppia maritima meadow sediments. These results indicate that loss of habitat diversity and specific habitats could have negative impacts on denitrification and N2O reduction, which underpin the capacity for nitrogen removal in coastal ecosystems. [ABSTRACT FROM AUTHOR]

Background: Cognitive models of psychosis postulate an important role of Theory of mind (ToM) in the formation and maintenance of delusions, but research on this plausible conjecture has gathered conflicting findings. In addition, it is still an open question whether problems in emotion recognition (ER) are associated with delusions. We examined the association of problems in ToM and ER with different aspects of delusions in a large sample of patients with psychosis enrolled in a therapy trial. This also enabled us to explore the possible impact of ToM and ER on one part of patients' social life: the quality of their therapeutic relationship. Methods: Patients with psychotic disorders and delusions and/or hallucinations (n = 185) and healthy controls (n = 48) completed a ToM picture sequencing task and an ER task. Subsequently, patients were enrolled in a randomized-controlled Cognitive Behavior Therapy (CBT) trial (ISRCTN29242879). Patients and therapists rated the quality of the therapeutic relationship during the first five sessions of therapy. Results: In comparison to controls, patients were impaired in both ToM and ER. Patients with deficits in ER experienced more severe delusional distress, whereas ToM problems were not related to delusions. In addition, deficits in ER predicted a less favorable therapeutic relationship and interactional problems viewed by the therapist. Impaired ER also moderated (increased) the negative influence of delusions on the therapeutic relationship and interactional difficulties viewed by the therapist. Conclusions: Cognitive models on the formation and maintenance of delusions should consider ER as a potential candidate that might be related to the formation and maintenance of delusional distress, whereas problems in ToM might not be directly related to delusions and secondary dimensions of delusions. In addition, problems in ER in patients with psychosis might have an impact on the quality of the therapeutic relationship and patients with problems in ER are more likely to be viewed as problematic by their therapists. Nevertheless, training ER might be a way to improve the quality of the therapeutic relationship and potentially the effectiveness of CBT or other interventions for patients with psychosis. [ABSTRACT FROM AUTHOR]

Focuses on the heteroepitaxial growth of diamond films on silicon. Characterization of the diamond films; Indication of results; Improvement of the structural quality of the films; Consistency of the surface of the diamond films; Structural features of the films.

Summary: Nitrous oxide (N2O) reducing microorganisms may be key in the mitigation of N2O emissions from managed ecosystems. However, there is still no clear understanding of the physiological and bioenergetic implications of microorganisms possessing either of the two N2O reductase genes (nosZ), clade I and the more recently described clade II type nosZ. It has been suggested that organisms with nosZ clade II have higher growth yields and a lower affinity constant (Ks) for N2O. We compared N2O reducing communities with different nosZI/nosZII ratios selected in chemostat enrichment cultures, inoculated with activated sludge, fed with N2O as a sole electron acceptor and growth limiting factor and acetate as electron donor. From the sequencing of the 16S rRNA gene, FISH and quantitative PCR of nosZ and nir genes, we concluded that betaproteobacterial denitrifying organisms dominated the enrichments with members within the family Rhodocyclaceae being highly abundant. When comparing cultures with different nosZI/nosZII ratios, we did not find support for (i) a more energy conserving N2O respiration pathway in nosZ clade II systems, as reflected in the growth yield per mole of substrate, or (ii) a higher affinity for N2O, defined by μmax/Ks, in organisms with nosZ clade II. [ABSTRACT FROM AUTHOR]

Objective The therapeutic alliance is intensively investigated in psychotherapy research. However, there is scarce research on the role of the specific diagnosis of the patient in the formation of the therapeutic alliance. Hence, the aim of this study was to address this research gap by comparing the alliance in different mental disorders. Design Our sample comprised 348 patients (mean age = 40 years; 68% female; 133 patients with depression, 122 patients with somatoform disorders, and 93 patients with eating disorders). Methods Patients completed the Working Alliance Inventory and measures of therapeutic outcome in early, middle, and late stages of inpatient psychotherapy. We applied multivariate multilevel models to address the nested data structure. Results All three disorder groups experienced positive alliances that increased across the course of therapy and showed similar alliance-outcome relations that were of comparable strengths as in current meta-analyses. However, we found perspective incongruence of alliance ratings from patient and therapist in the three disorder groups. Conclusions Our results generally indicate that the working alliance is of importance irrespective of the specific mental disorder. Perspective incongruence feedback of working alliance experiences could help to strengthen coordination between patient and therapist and thereby improve the therapeutic process. Further implications of these findings are discussed. Practitioner points We found no differences in the strengths of alliance ratings and alliance-outcome associations in depressive, somatoform, and eating disorder patients., This indicates that the working alliance is of general clinical importance irrespective of the disorder group and should be a central target in all therapies., We found perspective incongruence in alliance ratings between patient and therapist in all three disorder groups., Perspective incongruence feedback of working alliance experiences could help to strengthen coordination between patient and therapist and thereby improve the therapeutic process. [ABSTRACT FROM AUTHOR]

Presents a study which observed formation of defects during zinc diffusion into undoped and semi-insulating iron-doped indium phosphide single crystal using transmission electron microscopy for various diffusion conditions. Observation on the zinc concentration depth profiles after diffusion; Example of an agglomerate of defects with emanating planar arrays of precipitates at the diffusion front; comparison of results from diffused and non diffused sample regions.

Denitrification is of global significance for the marine nitrogen budget and the main process for nitrogen loss in coastal sediments. This facultative anaerobic respiratory pathway is modular in nature and the final step, the reduction of nitrous oxide (N2O), is performed by microorganisms with a complete denitrification pathway as well as those only capable of N2O reduction. Fluctuating oxygen availability is a significant driver of denitrification in sediments, but the effects on the overall N2O-reducing community that ultimately controls the emission of N2O from marine sediments is not well known. To investigate the effects of different oxygen regimes on N2O reducing communities, coastal marine surface sediment was incubated in microcosms under oxic, anoxic or oscillating oxygen conditions in the overlying water for 137 days. Quantification of the genetic potential for denitrification, anammox and respiratory ammonification indicated that denitrification supported nitrogen removal in these sediments. Furthermore, denitrifiers with a complete pathway were identified as the dominant community involved in N2O reduction, rather than organisms that are only N2O reducers. Specific lineages within each group were associated with different oxygen regimes suggesting that oxygen availability in the overlying water is associated with habitat partitioning of N2O reducers in coastal marine surface sediments. [ABSTRACT FROM AUTHOR]

There is a dearth of measures specifically designed to assess empirically validated mechanisms of therapeutic change. To fill in this research gap, the aim of the current study was to develop a measure that covers a large variety of empirically validated mechanisms of change with corresponding versions for the patient and therapist. To develop an instrument that is based on several important change process frameworks, we combined two established change mechanisms instruments: the Scale for the Multiperspective Assessment of General Change Mechanisms in Psychotherapy (SACiP) and the Scale of the Therapeutic Alliance-Revised (STA-R). In our study, 457 psychosomatic inpatients completed the SACiP and the STA-R and diverse outcome measures in early, middle and late stages of psychotherapy. Data analyses were conducted using factor analyses and multilevel modelling. The psychometric properties of the resulting Individual Therapy Process Questionnaire were generally good to excellent, as demonstrated by (a) exploratory factor analyses on both patient and therapist ratings, (b) CFA on later measuring times, (c) high internal consistencies and (d) significant outcome predictive effects. The parallel forms of the ITPQ deliver opportunities to compare the patient and therapist perspectives for a broader range of facets of change mechanisms than was hitherto possible. Consequently, the measure can be applied in future research to more specifically analyse different change mechanism profiles in session-to-session development and outcome prediction. Copyright © 2014 John Wiley & Sons, Ltd. Key Practitioner Message This article describes the development of an instrument that measures general mechanisms of change in psychotherapy from both the patient and therapist perspectives., Post-session item ratings from both the patient and therapist can be used as feedback to optimize therapeutic processes., We provide a detailed discussion of measures developed to evaluate therapeutic change mechanisms. [ABSTRACT FROM AUTHOR]

Theoretical models postulate an important role of attributional style (AS) in the formation and maintenance of persecutory delusions and other positive symptoms of schizophrenia. However, current research has gathered conflicting findings. In a cross-sectional design, patients with persistent positive symptoms of schizophrenia (n = 258) and healthy controls (n = 51) completed a revised version of the Internal, Personal and Situational Attributions Questionnaire (IPSAQ-R) and assessments of psychopathology. In comparison to controls, neither patients with schizophrenia in general nor patients with persecutory delusions (n = 142) in particular presented an externalizing and personalizing AS. Rather, both groups showed a “self-blaming” AS and attributed negative events more toward themselves. Persecutory delusions were independently predicted by a personalizing bias for negative events (beta = 0.197, P = .001) and by depression (beta = 0.152, P = .013), but only 5% of the variance in persecutory delusions could be explained. Cluster analysis of IPSAQ-R scores identified a “personalizing” (n = 70) and a “self-blaming” subgroup (n = 188), with the former showing slightly more pronounced persecutory delusions (P = .021). Results indicate that patients with schizophrenia and patients with persecutory delusions both mostly blamed themselves for negative events. Nevertheless, still a subgroup of patients could be identified who presented a more pronounced personalizing bias and more severe persecutory delusions. Thus, AS in patients with schizophrenia might be less stable but more determined by individual and situational characteristics that need further elucidation. [ABSTRACT FROM PUBLISHER]

Copyright of Psychotherapy Research is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction. The knowledge of the specificity of cognitive biases in psychiatric disorders is important in order to develop disorder-specific cognitive models and therapies. This cross-sectional study aimed to investigate the specificity of jumping to conclusions (JTC) and attributional biases (AB) for patients with schizophrenia. Methods. Twenty patients with paranoid schizophrenia were compared with patients with depression (n=20) and with anorexia nervosa (n=15) and nonclinical controls (n=55). All participants were administered a modified version of the beads task (JTC), a revised German version of the Internal, Personal, and Situational Attributions Questionnaire (AB), and several symptom and neurocognitive measures. Results. The proportion of patients with JTC bias in the schizophrenia group was, at the descriptive level, higher than in the depression and the anorexia groups. Regarding AB, the schizophrenia group showed a significantly stronger externalising but not personalising bias than the clinical control groups. Neither JTC nor attributional biases were significantly associated with delusions in general or persecutory delusion. Conclusions. We found evidence for the specificity of an externalising bias for paranoid schizophrenia. Concerning JTC bias the evidence was less clear. Whether the modification of those biases through psychological interventions would have an effect on psychopathology should be investigated in the context of clinical trials. [ABSTRACT FROM AUTHOR]

Nach der empirischen Absicherung der Wirksamkeit Kognitiver Verhaltenstherapie (KVT) bei schizophrenen Psychosen stellt sich zunehmend die Frage nach den Wirkmechanismen. In diesem Zusammenhang spielt die supportive Therapie (ST) eine bedeutsame Rolle als unspezifische Kontrollbedingung. Die vorliegende Arbeit stellt den derzeitigen Stand der Forschung zur ST bei schizophrenen Störungen dar. Heterogene Definitionen von ST führen dabei zu schwer vergleichbaren Ergebnissen. Eine Theorie möglicher Wirkmechanismen von ST wird erläutert und die Moderator- oder Mediatorfunktion der therapeutischen Beziehung diskutiert. Aufbauend auf der Darstellung der Wirkmechanismen werden eine eigene Konzeption der ST sowie erste Ergebnisse zur Rolle der therapeutischen Allianz aus einer laufenden Studie zu Psychotherapie bei psychotischen Symptomen vorgestellt. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Klingberg S, Wittorf A, Fischer A, Jakob-Deters K, Buchkremer G, Wiedemann G. Evaluation of a cognitive behaviourally oriented service for relapse prevention in schizophrenia. Objective: There is little work demonstrating the effectiveness of cognitive behaviourally oriented interventions in routine service settings. This pragmatic trial is designed to test the impact of a group treatment service on relapse rates under the conditions of routine health care. Method: A total of 169 schizophrenia patients were randomly allocated either to a comprehensive cognitive behaviourally oriented service (CBOS) or to treatment as usual (TAU). The primary outcome is the time until the first relapse after discharge from hospital. Relapse was defined as an increase in positive or negative symptoms as assessed with the Positive and Negative Syndrome Scale. Survival analysis has been conducted up to the 6-month assessment. Results: The mean time to relapse after discharge from hospital in the CBOS group was significantly longer than in the TAU group (log rank test, P = 0.033). This was due to less exacerbations regarding negative symptoms in the CBOS condition (log rank test, P = 0.014). The number of social contacts was improved in the CBOS group only. Conclusion: The CBOS intervention appears to be beneficial in reducing early negative symptom exacerbations. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that cognitive behavioural therapy (CBT) has a moderate effect on symptom reduction and on general well being of patients suffering from psychosis. However, questions regarding the specific efficacy of CBT, the treatment safety, the cost-effectiveness, and the moderators and mediators of treatment effects are still a major issue. The major objective of this trial is to investigate whether CBT is specifically efficacious in reducing positive symptoms when compared with non-specific supportive therapy (ST) which does not implement CBT-techniques but provides comparable therapeutic attention. Methods/Design: The POSITIVE study is a multicenter, prospective, single-blind, parallel group, randomised clinical trial, comparing CBT and ST with respect to the efficacy in reducing positive symptoms in psychotic disorders. CBT as well as ST consist of 20 sessions altogether, 165 participants receiving CBT and 165 participants receiving ST. Major methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, analysis by intention to treat, data management using remote data entry, measures of quality assurance (e.g. on-site monitoring with source data verification, regular query process), advanced statistical analysis, manualized treatment, checks of adherence and competence of therapists. Research relating the psychotherapy process with outcome, neurobiological research addressing basic questions of delusion formation using fMRI and neuropsychological assessment and treatment research investigating adaptations of CBT for adolescents is combined in this network. Problems of transfer into routine clinical care will be identified and addressed by a project focusing on cost efficiency. Discussion: This clinical trial is part of efforts to intensify psychotherapy research in the field of psychosis in Germany, to contribute to the international discussion on psychotherapy in psychotic disorders, and to help implement psychotherapy in routine care. Furthermore, the study will allow drawing conclusions about the mediators of treatment effects of CBT of psychotic disorders. Trial Registration: Current Controlled Trials ISRCTN29242879 [ABSTRACT FROM AUTHOR]

Currently, there are no convincing treatment strategies for negative symptoms of schizophrenia. On this background, we are conducting the treatment of negative symptoms (TONES) study which addresses the question whether cognitive behavioural therapy (CBT) is efficacious for the reduction of negative symptoms in schizophrenia. The present paper aims at presenting the design of the clinical trial of the study as well as the treatment concept. Further, we investigate the feasibility and the safety of our study treatment. The TONES study is a multicentric, prospective, single-blind, randomised, and controlled trial (RCT). The clinical trial compares CBT (test condition) and cognitive remediation (CR; control condition) with respect to the efficacy in reducing negative symptoms. In order to systematically assess aspects of adherence and feasibility therapists filled in session reports after each session. The safety analysis is performed using the sequential method of Whitehead (The design and analysis of sequential clinical trials, Ellis Horwood, Chichester, 1983). We were able to conduct a systematic recruitment and to include a sample of N = 198 patients which is characterised by negative symptoms of medium severity. The majority of patients accepted the format of a 50-min treatment session. The manualised treatment content seemed to be adequate and the cooperation between patients and therapists was excellent or adequate in approximately 80% of the treatment sessions. Of the 15 severe adverse events 10 occurred in the CBT and 5 in the CR. This difference between the groups was not significant. The study presented here is presumably the first high quality RCT which evaluates CBT with negative symptoms as primary endpoint. On the background of the data presented we conclude that CBT for the reduction of negative symptoms is feasible and can be conducted safely. [ABSTRACT FROM AUTHOR]

Abstract: The present study aimed to assess the neurocognitive effects of atypical and conventional antipsychotic drugs on neurocognition under naturalistic treatment conditions. Eighty-two patients with schizophrenia underwent a comprehensive neuropsychological assessment both at baseline during inpatient treatment and 6 months after discharge from hospital (follow-up). From this sample, we selected two subgroups of patients, which had either a continuous atypical (n =33) or conventional (n =16) antipsychotic medication. Twenty-seven out of 40 healthy controls were also retested to control for practice effects. Both patient groups showed a moderate and significant improvement in global cognitive functioning. The repeated measurement ANOVAs revealed no differential treatment effects for all neuropsychological domains. These results remained after controlling for potential confounders between groups. Administering antipsychotic medications in an individually optimized manner seems to have the potential to improve some aspects of neurocognition in schizophrenia, regardless of the kind of antipsychotic medication. [Copyright &y& Elsevier]

This longitudinal study aimed at identifying predictors of community outcome from a broad range of neuropsychological, clinical psychopathologic, sociodemographic, and treatment related factors. N = 96 schizophrenia patients were assessed both at baseline during inpatient treatment and 1 year after discharge from hospital (follow-up). At follow-up functional outcome was measured by the Global Assessment of Functioning Scale (GAF) and the Social Adjustment Scale II (SAS II). Data were analyzed in an explorative way by means of multiple linear regression analyses. Three out of the five functional outcome measures were predicted by the negative syndrome and measures of cognitive functioning. However, the positive syndrome also consistently predicted psychosocial functioning. Altogether, the regression models explained between 20% and 35% of the variance in our outcome measures. The findings not only reemphasize that negative symptoms and cognitive dysfunctions are key determinants of community outcome but also point to a potential predictive relevance of positive symptoms. [ABSTRACT FROM AUTHOR]

Cognitive deficits are increasingly considered as essential in schizophrenic disorders. Positive symptoms and cognitive deficits have been found to be independent, whereas negative symptoms show only weak correlations to cognitive impairment. However, the relationship to a third symptom dimension, disorganization, is yet unclear. In a sample of n = 151 schizophrenia inpatients (DSM-IV/SCID) we assessed cognitive impairment using a comprehensive neuropsychological test battery and symptoms of schizophrenia applying the Positive and Negative Syndrome Scale (PANSS). Factor analyses resulted in three neuropsychological (attention, memory, abstraction) and five symptom factor scores (negative, impulsiveness, positive, disorganization, depression). The disorganization factor did not correlate significantly with any of the neuropsychological factor scores. Even after controlling for different demographic and clinical variables partial correlation coefficients did not reach a significant level. Thus, we could not confirm the previously reported associations between disorganization and measures of cognitive impairment. Despite a considerable conceptual overlap between interview based symptom ratings and classic neuropsychological tests the empirical association is limited. Our results suggest that disorganization and cognitive impairment represent different symptom dimensions. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is characterized by cognitive decline and loss of neurons in specific brain regions. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. To our knowledge, the present pilot study assessed for the first time BDNF serum and CSF concentrations in 30 patients with different stages of AD in comparison to 10 age-matched non-demendet controls. AD patients were divided in two groups according to their MMSE score: Group 1 (n = 15) in early stages with MMSE scores ≥21 (mean of 25.5) and Group 2 (n = 15) with more severe stages of dementia with MMSE scores <21 (mean of 13.3). As main results, we found in patients with early stages of probable AD significantly increased BDNF serum concentrations as compared to more severe stages of AD (p < 0.0001) and age-matched healthy controls (p = 0.028). BDNF serum values in all AD patients correlated significantly with MMSE scores (r = 0.486; p < 0.0001). Levels of BDNF were below the detection limit of the assay in unconcentrated CSF samples of AD patients and non-demendet controls. In summary, BDNF serum values are increased in early stages of Alzheimer’s disease, which may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of beta-amyloid (Abeta). During the course of the disease, BDNF is decreasing, which correlates with the severity of dementia. The decrease of BDNF may constitute a lack of trophic support with an increase of Abeta accumulation and thus contribute to progressive degeneration of specific regions in the AD-affected brain. BDNF should be further evaluated as a candidate marker for clinical diagnosis and therapeutic monitoring in Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Estimates source contributions to PM2.5 aerosol measured at Chilliwack and Pitt Meadows in the Lower Fraser Valley, British Columbia during the REgional Visibility Experimental Assessment study. Use of chemical mass balance receptor modeling; Motor vehicles accounting for the largest share; Low accountability of geological materials at both sites for PM2.5.

The process for outsourcing photocopying includes developing a clear Request for Proposal, monitoring and responding to vendor performance and ensuring quality controls are used. Outsourcing photocopying, done carefully, can help the library husband precious resources while outsourcing activities not traditionally associated with librarianship. [ABSTRACT FROM AUTHOR]

A kinetic investigation of the behavior of apopyruvate decarboxylase from Saccharomyces carlsbergensis with thiamine pyrophosphate analogues gave the values of 23 µM as the Km for thiamine pyrophosphate and 20 µM as the Km for 2'-ethylthiamine pyrophosphate. The V for the latter compound was 25% that of thane pyrophosphate. Inhibitor constants, Ki, were determined for the following competitive inhibitors of thiamine pyrophosphate with the apoenzyme, (the values are for the pyrophosphate esters): tetrahydrothiamine, 6.5µM; t X oxythiamine, 20 µM; 2'-n-butylthiamine, 45 µM; 2-methoxy thiamme, 70 µM; pyruthiamine, 78 µM; 2'-demethylthiamine, 220 µM; 2'-hydroxythiamine, 380 µM. None of the inhibitors exhibited coenzyme activity. A hydrophobic interaction of the 2'-methyl group of thiamine pyrophosphate with the apoenzyme has been proposed and a model for the coenzyme binding site of pyruvate decarboxytase, consisting of a pyrophosphate and a pyrimidine binding region, is discussed. [ABSTRACT FROM AUTHOR]

The formation of a fluorescent complex between apopyruvate decarboxylase of Saccharomyces carlsbergensis and thiochromc pyrophosphate, a competitive inhibitor with thiamine pyrophosphate, and Mg(II) ions is reported. A similar complex between thiochrome and the apoenzyme could not be detected, demonstrating the importance of the pyrophosphate group of the coenzyme in binding to the protein. Complex formation between the apoenzyme and thiochrome pyrophosphate in the absence of Mg(II) could also not be demonstrated. The role of magnesium in coenzyme binding is discussed, especially in reference to interaction with the pyrophosphate moiety. The apparent Km for Mg(II) ions, after correction for residual apoenzyme activity, is reported to µM. The shift in the fluorescence emission spectrum of thiochrome pyrophosphate of 23-24 nm toward lower wavelengths, upon complex formation, coincided with the behavior of thiochrome in solvents of lower polarity than water. A hydrophobic region at the coenzyme binding site of pyruvate decarboxylase is proposed. Enhancement of thiochrome fluorescence occurred concomitantly with the blue shift in the emission spectrurn upon complex formation. The excitation wavelength of 290 nm employed to demonstrate complex formation suggested energy transfer from the tryptophan to the thiochrome chromophore. Quenching of fluorescence in the 340-350 nm region, however, occurred not only in the protein emission spectrum upon complex formation, but also when free tryptophan and thiochrome interacted with each other. The quenching of the protein fluorescence appears to be independent of hydrophobic interaction at the coenzyme binding site. It is suggested ghat protein tryptophan residues relatively exposed to solvent interact individually with the thiochrome molecule by an energy transfer mechanism to produce the quenching in pyruvate decarboxylase. [ABSTRACT FROM AUTHOR]

Background: The jumping to conclusions bias (JTC) is considered to be an important causal factor in theoretical models for the formation and maintenance of delusions. However, recent meta-analytic findings show a rather equivocal pattern of results regarding associations between JTC and delusions. Thus, the present study aims to investigate in a large sample whether the JTC-bias is more pronounced in patients with psychotic disorders in comparison to controls and whether the JTC bias is associated with a more severe delusional conviction, persecutory delusions, and positive symptoms in general. Methods: Patients with psychotic disorders (n = 300) enrolled in a therapy trial and healthy controls (n = 51) conducted a variant of the beads task (fish task) as a measure for the JTC-bias at the start of the trial. Further, clinical interviews were used to assess patients' delusional severity and delusional conviction. Results: There were no statistically significant differences between patients with psychotic disorders (with 53% displaying the JTC-bias) and controls (41%). Furthermore, there were no statistically significant correlations between JTC measures and persecutory delusions, delusional conviction, and positive symptoms. Conclusions: We found no differences in JTC between patients with psychotic disorders and healthy controls, which is in part in line with meta-analytic findings using a wide range of JTC task variants. Interestingly, patients with psychotic disorders displayed JTC rates commonly found in the literature, while healthy control subjects showed an unexpectedly high level of JTC. The task variant we used in the present study (fish task) is discussed as a potential reason for our results, as it may induce a more deliberative reasoning style in controls as compared to the traditional beads task. Furthermore, possible implications for the measurement of the JTC-bias, in general, are discussed. Trial Registration: ISRCTN29242879 (isrctn.com), date of registration: April 12th 2006, retrospectively registered. [ABSTRACT FROM AUTHOR]

The hematopoietic system is maintained throughout life by stem cells that are capable of differentiating into all hematopoietic lineages. An intimate balance between self-renewal, differentiation, and quiescence is required to maintain hematopoiesis and disruption of this balance can result in malignant transformation. FBXO9, the substrate recognition component from the SCF E3 ubiquitin ligase family, is downregulated in patients with acute myeloid leukemia (AML) compared to healthy bone marrow, and this downregulation is particularly evident in patients with inv(16) AML. To study FBXO9 in malignant hematopoiesis, we generated a conditional knockout mouse model using a novel CRISPR/Cas9 strategy. Deletion of Fbxo9 in the murine hematopoietic system showed no adverse effects on stem and progenitor cell function but in AML lead to markedly accelerated and aggressive leukemia development in mice with inv(16). Not only did Fbxo9 play a role in leukemia initiation but it also functioned to maintain AML activity and promote disease progression. Quantitative mass spectrometry from primary tumors reveals tumors lacking Fbxo9 highly express proteins associated with metastasis and invasion as well as components of the ubiquitin proteasome system. We confirmed that the loss of FBXO9 leads to increased proteasome activity and tumors cells were more sensitive to in vitro proteasome inhibition with bortezomib, suggesting that FBXO9 expression may predict patients' response to bortezomib. [ABSTRACT FROM AUTHOR]

The detection of NO-forming nitrite reductase genes (nir) has become the standard when studying denitrifying communities in the environment, despite well-known amplification biases in available primers. We review the performance of 35 published and 121 newly designed primers targeting the nirS and nirK genes, against sequences from complete genomes and 47 metagenomes from three major habitats where denitrification is important. There were no optimal universal primer pairs for either gene, although published primers targeting nirS displayed up to 75% coverage. The alternative is clade-specific primers, which show a trade-off between coverage and specificity. The test against metagenomic datasets showed a distinct performance of primers across habitats. The implications of clade-specific nir primers choice and their performance for ecological inference when used for quantitative estimates and in sequenced-based community ecology studies are discussed and our phylogenomic primer evaluation can be used as a reference along with their environmental specificity as a guide for primer selection. Based on our results, we also propose a general framework for primer evaluation that emphasizes the testing of coverage and phylogenetic range using full-length sequences from complete genomes, as well as accounting for environmental range using metagenomes. This framework serves as a guideline to simplify primer performance comparisons while explicitly addressing the limitations and biases of the primers evaluated. [ABSTRACT FROM AUTHOR]