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- Coleman, Jonathan R I, et al.
(författare)
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The Genetics of the Mood Disorder Spectrum: Genome-wide Association Analyses of More Than 185,000 Cases and 439,000 Controls.
- 2020
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Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 88:2, s. 169-184
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Tidskriftsartikel (refereegranskat)abstract
- Mood disorders (including major depressive disorder and bipolar disorder) affect 10% to 20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of risk factors across mood disorders despite their diagnostic distinction.To clarify the shared molecular genetic basis of major depressive disorder and bipolar disorder and to highlight disorder-specific associations, we meta-analyzed data from the latest Psychiatric Genomics Consortium genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; nonoverlapping N = 609,424).Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More loci from the Psychiatric Genomics Consortium analysis of major depression than from that for bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single-episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment-the relationship is positive in bipolar disorder but negative in major depressive disorder.The mood disorders share several genetic associations, and genetic studies of major depressive disorder and bipolar disorder can be combined effectively to enable the discovery of variants not identified by studying either disorder alone. However, we demonstrate several differences between these disorders. Analyzing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum.
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| 2. |
- Mbuayama, Kabuzi R., et al.
(författare)
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Antifungal activity and mode of action of synthetic peptides derived from the tick OsDef2 defensin
- 2022
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Ingår i: Journal of Peptide Science. - : John Wiley & Sons. - 1075-2617 .- 1099-1387. ; 28:5
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Tidskriftsartikel (refereegranskat)abstract
- Candida albicans is the principal opportunistic fungal pathogen in nosocomial settings and resistance to antifungal drugs is on the rise. Antimicrobial peptides from natural sources are promising novel therapeutics against C. albicans. OsDef2 defensin was previously found to be active against only Gram-positive bacteria, whereas derived fragments Os and its cysteine-free analogue, Os-C, are active against Gram-positive and Gram-negative bacteria at low micromolar concentrations. In this study, OsDef2-derived analogues and fragments were screened for anticandidal activity with the aim to identify peptides with antifungal activity and in so doing obtain a better understanding of the structural requirements for activity and modes of action. Os, Os-C and Os(11-22)NH2 , a Os-truncated carboxy-terminal-amidated fragment, had the most significant antifungal activities, with minimum fungicidal concentrations (MFCs) in the micromolar range (6-28 μM). C. albicans killing was rapid and occurred within 30-60 min. Further investigations showed all three peptides interacted with cell wall derived polysaccharides while both Os and Os(11-22)NH2 permeabilized fungal liposomes. Confocal laser scanning microscopy confirmed that Os-C and Os(11-22)NH2 could enter the cytosol of live cells and subsequent findings suggest that the uptake of Os and Os-C, in contrast to Os(11-22)NH2 , is energy dependent. Although Os, Os-C and Os(11-22)NH2 induced the production of reactive oxygen species (ROS), co-incubation with ascorbic acid revealed that only ROS generated by Os-C and to a lesser extent Os(11-22)NH2 resulted in cell death. Overall, Os, Os-C and Os(11-22)NH2 are promising candidacidal agents.
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