GABA-modulating bacteria of the human gut microbiota.

The gut microbiota affects many important host functions, including the immune response and the nervous system1. However, while substantial progress has been made in growing diverse microorganisms of the microbiota2, 23-65% of species residing in the human gut remain uncultured3,4, which is an obstacle for understanding their biological roles. A likely reason for this unculturability is the absence in artificial media of key growth factors that are provided by neighbouring bacteria in situ5,6. In the present study, we used co-culture to isolate KLE1738, which required the presence of Bacteroides fragilis to grow. Bioassay-driven purification of B. fragilis supernatant led to the isolation of the growth factor, which, surprisingly, is the major inhibitory neurotransmitter GABA (γ-aminobutyric acid). GABA was the only tested nutrient that supported the growth of KLE1738, and a genome analysis supported a GABA-dependent metabolism mechanism. Using growth of KLE1738 as an indicator, we isolated a variety of GABA-producing bacteria, and found that Bacteroides ssp. produced large quantities of GABA. Genome-based metabolic modelling of the human gut microbiota revealed multiple genera with the predicted capability to produce or consume GABA. A transcriptome analysis of human stool samples from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides, Parabacteroides and Escherichia species. By coupling 16S ribosmal RNA sequencing with functional magentic resonance imaging in patients with major depressive disorder, a disease associated with an altered GABA-mediated response, we found that the relative abundance levels of faecal Bacteroides are negatively correlated with brain signatures associated with depression

Optimal search strategies for identifying moderators and predictors of treatment effects in PubMed

BACKGROUND: Treatment effects differ across patients. To guide selection of treatments for patients, it is essential to acknowledge these differences and identify moderators or predictors. Our aim was to generate optimal search strategies (commonly known as filters) for PubMed to retrieve papers identifying moderators and predictors of treatment effects. METHODS: Six journals were hand-searched for articles on moderators or predictors. Selected articles were randomly allocated to a development and validation set. Search terms were extracted from the development set and tested for their performance. Search filters were created from combinations of these terms and tested in the validation set. RESULTS: Of 4407 articles, 198 were considered to be relevant. The most sensitive filter in the development set '("Epidemiologic Methods" [MeSH] OR assign* OR control*[tiab] OR trial*[tiab]) AND therapy*[sh]' yielded in the validation set a sensitivity of 89% [88%-90%] and a specificity of 80% [79%-82%]. CONCLUSIONS: The search filters created in this study can help to efficiently retrieve evidence on moderators and predictors of treatment effect. Testing of the filters in multiple domains should reveal robustness across disciplines. These filters can facilitate the retrieval of evidence on moderators and predictors of treatment effects, helping the implementation of stratified or personalised health care

Analysis of variation in results of CD34 hematopoietic progenitor cell enumeration in a multicenter study

Analysis of variation in results of CD34+ hematopoietic progenitor cell enumeration in a multicenter study Gratama, J.W.; Kraan, J.; Levering, W.; van Bockstaele, D.R.; Rijkers, G.T.; van der Schoot, C.E. Published in: Cytometry DOI: 10.1002/(SICI) 1097-0320(19970615) Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible

Surface Affinity of the Hydronium Ion: The Effective Fragment Potential and Umbrella Sampling

The surface affinity of the hydronium ion in water is investigated with umbrella sampling and classical molecular dynamics simulations, in which the system is described with the effective fragment potential (EFP). The solvated hydronium ion is also explored using second order perturbation theory for the hydronium ion and the empirical TIP5P potential for the waters. Umbrella sampling is used to analyze the surface affinity of the hydronium ion, varying the number of solvent water molecules from 32 to 256. Umbrella sampling with the EFP method predicts the hydronium ion to most probably lie about halfway between the center and edge of the water cluster, independent of the cluster size. Umbrella sampling using MP2 for the hydronium ion and TIP5P for the solvating waters predicts that the solvated proton most probably lies about 0.5–2.0 Å from the edge of the water cluster independent of the cluster size

Management Ideologies and Organizational Spirituality: a Typology

The topic of spirituality is gaining an increasing visibility in organization studies. It is our contention that every theory of organization is a theory of organizational spirituality. Based on Barley and Kunda’s 1992 Administrative Science Quarterly article, we discuss the evolution of management theories as spirituality theories. From such analysis, we suggest that there may be both a meaningful/liberating and an instrumental/exploitative side in the relationship between organizations and spirituality. Such a possibility is illustrated with a typology that advances four possible types of organizations regarding spirituality: the soulful organization, the holistic organization, the ascetic organization, and the professional organization. The expression of spirituality in each of these forms is discussed with the aim of contributing to a theoretically-based analysis of organizational spirituality.N/

Viral Load Levels Measured at Set-Point Have Risen Over the Last Decade of the HIV Epidemic in the Netherlands

HIV-1 RNA plasma concentration at viral set-point is associated not only with disease outcome but also with the transmission dynamics of HIV-1. We investigated whether plasma HIV-1 RNA concentration and CD4 cell count at viral set-point have changed over time in the HIV epidemic in the Netherlands.We selected 906 therapy-naïve patients with at least one plasma HIV-1 RNA concentration measured 9 to 27 months after estimated seroconversion. Changes in HIV-1 RNA and CD4 cell count at viral set-point over time were analysed using linear regression models. The ATHENA national observational cohort contributed all patients who seroconverted in or after 1996; the Amsterdam Cohort Studies (ACS) contributed seroconverters before 1996. The mean of the first HIV-1 RNA concentration measured 9-27 months after seroconversion was 4.30 log(10) copies/ml (95% CI 4.17-4.42) for seroconverters from 1984 through 1995 (n = 163); 4.27 (4.16-4.37) for seroconverters 1996-2002 (n = 232), and 4.59 (4.52-4.66) for seroconverters 2003-2007 (n = 511). Compared to patients seroconverting between 2003-2007, the adjusted mean HIV-1 RNA concentration at set-point was 0.28 log(10) copies/ml (95% CI 0.16-0.40; p<0.0001) and 0.26 (0.11-0.41; p = 0.0006) lower for those seroconverting between 1996-2002 and 1984-1995, respectively. Results were robust regardless of type of HIV-1 RNA assay, HIV-1 subtype, and interval between measurement and seroconversion. CD4 cell count at viral set-point declined over calendar time at approximately 5 cells/mm(3)/year.The HIV-1 RNA plasma concentration at viral set-point has increased over the last decade of the HIV epidemic in the Netherlands. This is accompanied by a decreasing CD4 cell count over the period 1984-2007 and may have implications for both the course of the HIV infection and the epidemic