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- Niska-Blakie, Joanna, et al.
(författare)
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Knockout of the non-essential gene SUGCT creates diet-linked, age-related microbiome disbalance with a diabetes-like metabolic syndrome phenotype
- 2019
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Ingår i: Cellular and Molecular Life Sciences. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071.
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Tidskriftsartikel (refereegranskat)abstract
- SUGCT (C7orf10) is a mitochondrial enzyme that synthesizes glutaryl-CoA from glutarate in tryptophan and lysine catabolism, but it has not been studied in vivo. Although mutations in Sugct lead to Glutaric Aciduria Type 3 disease in humans, patients remain largely asymptomatic despite high levels of glutarate in the urine. To study the disease mechanism, we generated SugctKO mice and uncovered imbalanced lipid and acylcarnitine metabolism in kidney in addition to changes in the gut microbiome. After SugctKO mice were treated with antibiotics, metabolites were comparable to WT, indicating that the microbiome affects metabolism in SugctKO mice. SUGCT loss of function contributes to gut microbiota dysbiosis, leading to age-dependent pathological changes in kidney, liver, and adipose tissue. This is associated with an obesity-related phenotype that is accompanied by lipid accumulation in kidney and liver, as well as “crown-like” structures in adipocytes. Furthermore, we show that the SugctKO kidney pathology is accelerated and exacerbated by a high-lysine diet. Our study highlights the importance of non-essential genes with no readily detectable early phenotype, but with substantial contributions to the development of age-related pathologies, which result from an interplay between genetic background, microbiome, and diet in the health of mammals.
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- Yeo, LLL, et al.
(författare)
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Posterior communicating and anterior communicating arteries on pre-thrombectomy computed tomography scans are associated with good outcomes irrespective of leptomeningeal collateral status
- 2019
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Ingår i: Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences. - : SAGE Publications. - 2385-2011. ; 25:4, s. 364-370
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Tidskriftsartikel (refereegranskat)abstract
- Collateral blood flow is known to be an important factor that sustains the penumbra during acute stroke. We looked at both the leptomeningeal collateral circulation and the presence of anterior and posterior communicating arteries to determine the factors associated with good outcomes and mortality. Methods We included all patients with acute ischaemic stroke in the anterior circulation, who underwent thrombectomy with the same thrombectomy device from 2013 to 2016. We assessed the leptomeningeal circulation by the Tan, Miteff and Maas validated scoring systems on pre-treatment computed tomographic angiography scans and looked at collateral flow through anterior and posterior communicating arteries. The results were good functional outcomes at 3 months (modified Rankin scale 0–2) and mortality. Results A total of 147 consecutive acute stroke patients treated with the Embotrap device were included with a median National Institutes of Health stroke scale of 15 (range 2–26). On multivariate analysis only younger age (odds ratio (OR) 0.96/year, 95% confidence interval (CI) 0.94–0.99, P = 0.026), lower National Institutes of Health stroke scale score (OR 0.87/point, 95% CI 0.80–0.93, P < 0.001), number of attempts (OR 0.80/attempt, 95% CI 0.65–0.99, P = 0.043) and the presence of a patent anterior communicating artery (OR 14.03, 95% CI 1.42–139.07, P = 0.024) were associated with good functional outcomes. The number of attempts (OR 1.66/attempt, 95% CI 1.21–2.29, P = 0.002) was significantly associated with mortality and the presence of a patent posterior communicating artery (OR 0.098, 95% CI 0.016–0.59, P = 0.011) was inversely associated with mortality. Conclusions Our study shows that the presence of anterior and posterior communicating arteries is significantly associated with good functional outcomes and reduced mortality, respectively, independent of the leptomeningeal circulation status.
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