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- Bellamy, Chyrell D., et al.
(author)
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Relevance of spirituality for people with mental illness attending consumer-centered services
- 2007
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In: Psychiatric rehabilitation journal. - : American Psychological Association (APA). - 1095-158X .- 1559-3126. ; 30:4, s. 287-294
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Journal article (peer-reviewed)abstract
- Spirituality has been cited in the literature as having a positive effect on mental health outcomes. This paper explores the relationship of spirituality to demographic, psychiatric illness history and psychological constructs for people with mental illness (N=1835) involved in consumer-centered services (CCS-Clubhouses and Consumer run drop-in centers). Descriptive statistics indicate that spirituality is important for at least two thirds of the members in the study. Members primarily indicated participation in public spiritual activities (i.e., church, bible study groups), followed by private activities (prayer, reading the bible, and meditation) (both of which were centered on belief in the transcendent). A logistic regression analysis was done to explore variables related to spirituality (i.e., demographics, psychiatric illness history, and psychological constructs). Results suggest that age, gender, having psychotic symptoms, having depressive symptoms, and having a higher global quality of life, hope and sense of community were all significant correlates of spirituality.
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- Singh, Vinayak, et al.
(author)
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Identification of aminopyrimidine-sulfonamides as potent modulators of Wag31-mediated cell elongation in mycobacteria.
- 2017
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In: Molecular Microbiology. - : Wiley. - 0950-382X .- 1365-2958. ; 103:1, s. 13-25
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Journal article (peer-reviewed)abstract
- There is an urgent need to discover new anti-tubercular agents with novel mechanisms of action in order to tackle the scourge of drug-resistant tuberculosis. Here, we report the identification of such a molecule - an AminoPYrimidine-Sulfonamide (APYS1) that has potent, bactericidal activity against M. tuberculosis. Mutations in APYS1-resistant M. tuberculosis mapped exclusively to wag31, a gene that encodes a scaffolding protein thought to orchestrate cell elongation. Recombineering confirmed that a Gln201Arg mutation in Wag31 was sufficient to cause resistance to APYS1, however, neither overexpression nor conditional depletion of wag31 impacted M. tuberculosis susceptibility to this compound. In contrast, expression of the wildtype allele of wag31 in APYS1-resistant M. tuberculosis was dominant and restored susceptibility to APYS1 to wildtype levels. Time-lapse imaging and scanning electron microscopy revealed that APYS1 caused gross malformation of the old pole of M. tuberculosis, with eventual lysis. These effects resembled the morphological changes observed following transcriptional silencing of wag31 in M. tuberculosis. These data show that Wag31 is likely not the direct target of APYS1, but the striking phenotypic similarity between APYS1 exposure and genetic depletion of Wag31 in M. tuberculosis suggests that APYS1 might indirectly affect Wag31 through an as yet unknown mechanism.
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- Nordqvist, Anneli, et al.
(author)
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Evaluation of the amino acid binding site of Mycobacterium tuberculosis glutamine synthetase for drug discovery
- 2008
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In: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 16:10, s. 5501-5513
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Journal article (peer-reviewed)abstract
- A combination of a literature survey, structure-based virtual screening and synthesis of a small library was performed to identify hits to the potential antimycobacterial drug target, glutamine synthetase. The best inhibitor identified from the literature survey was (2S,5R)-2,6-diamino-5-hydroxyhexanoic acid (4, IC(50) of 610+/-15microM). In the virtual screening 46,400 compounds were docked and subjected to a pharmacophore search. Of these compounds, 29 were purchased and tested in a biological assay, allowing three novel inhibitors containing an aromatic scaffold to be identified. Based on one of the hits from the virtual screening a small library of 15 analogues was synthesized producing four compounds that inhibited glutamine synthetase.
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