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- 2019
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Tidskriftsartikel (refereegranskat)
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- Payer, Stefan E., et al.
(författare)
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Regioselective para-Carboxylation of Catechols with a Prenylated Flavin Dependent Decarboxylase
- 2017
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 56:44, s. 13893-13897
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Tidskriftsartikel (refereegranskat)abstract
- The utilization of CO2 as a carbon source for organic synthesis meets the urgent demand for more sustainability in the production of chemicals. Herein, we report on the enzyme-catalyzed para-carboxylation of catechols, employing 3,4-dihydroxybenzoic acid decarboxylases (AroY) that belong to the UbiD enzyme family. Crystal structures and accompanying solution data confirmed that AroY utilizes the recently discovered prenylated FMN (prFMN) cofactor, and requires oxidative maturation to form the catalytically competent prFMN(iminium) species. This study reports on the in vitro reconstitution and activation of a prFMN-dependent enzyme that is capable of directly carboxylating aromatic catechol substrates under ambient conditions. A reaction mechanism for the reversible decarboxylation involving an intermediate with a single covalent bond between a quinoid adduct and cofactor is proposed, which is distinct from the mechanism of prFMN-associated 1,3-dipolar cycloadditions in related enzymes.
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- Berberat, Jatta, et al.
(författare)
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Case Report : Cerebrospinal Fluid Dynamics in the Optic Nerve Subarachnoid Space and the Brain Applying Diffusion Weighted MRI in Patients With Idiopathic Intracranial Hypertension-A Pilot Study
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe aim of this study was to examine the cerebrospinal fluid (CSF) flow rates in the subarachnoid space (SAS) of the optic nerve (ON) and the brain in patients with idiopathic intracranial hypertension (IIH) and papilledema (PE) compared to healthy controls by applying non-invasive diffusion-weighted MRI. MethodsA retrospective analysis of diffusion-weighted MR images of 5 patients with IIH (10 ONs), mean age: 31 +/- 10 years (5 women), and 11 healthy controls (22 ONs, mean age: 60 +/- 13 years, 5 women) was performed. The flow velocity flow-range ratio (FRR) between the intracranial cavity and the SAS of the ON was calculated in both groups and then compared. ResultsThe mean FRR was 0.55 +/- 0.08 in patients with IIH and 0.63 +/- 0.05 in healthy controls. The difference between patients with IIH and healthy controls was statistically significant (p < 0.05). ConclusionsThe CSF flow velocity was decreased in patients with IIH with PE compared to healthy controls. The reduced CSF flow dynamics might be involved in the pathophysiology of PE in IIH and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON. Idiopathic intracranial hypertension is a neurological disease, where vision loss is the most feared complication of this disorder. The pathophysiology of IIH is not fully understood but is strongly linked to a reduced uptake of CSF into the central dural sinus veins. In this study, we examined the CSF flow rates in the SAS ON and the brain in patients with IIH and PE compared to healthy controls by applying non-invasive diffusion-weighted MRI. Knowing about the flow ratio of CSF may be of clinical relevance for the treatment decisions of IIH. If medical treatment fails, surgical options for lowering the ICP pressure need to be taken into consideration. As the primary goal of treatment is to prevent the loss of vision and visual field, it is important to know whether the communication of CSF between the intracranial CSF and the CSF in the perioptic space is intact. We showed that the CSF flow velocity was decreased in IIH patients with PE compared to healthy controls. The reduced CSF flow might be involved in the pathophysiology of PE in IIH, and diffusion-weighted MRI can be a useful non-invasive tool to study the CSF flow dynamics within the SAS ON.
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| 8. |
- Palmqvist, Richard, et al.
(författare)
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hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer
- 2005
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Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136 .- 1097-0215. ; 116:3, s. 395-400
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Tidskriftsartikel (refereegranskat)abstract
- In a majority of malignant human tumors telomerase activity can be detected, suggesting an immortal phenotype. Expression of the reverse transcriptase subunit, hTERT, in the human telomerase complex is required for telomerase activity. The regulation of hTERT, from gene level to a fully functional protein, is still a poorly understood process. Increased copy number of the hTERT gene has been demonstrated in a significant portion of established cell lines and tumors of different origin but its relevance for telomerase activity levels is unclear. In the present study, we examined the hTERT gene copy number using fluorescence in situ hybridization (FISH) in samples from 64 colorectal carcinomas and an increased copy number (≥ 3 hTERT gene copies/nucleus) was observed in 31 cases (48%). No statistical association existed between hTERT gene copy number and hTERT RNA expression or telomerase activity. However, a significant relationship was found between an increase in hTERT gene copy number and p53 protein accumulation (p = 0.002) and aneuploidy (p = 0.036). Only 4 tumors showed microsatellite instability, 3 of which had a normal hTERT gene copy number. The data indicated that the increased copy number of the hTERT gene in colorectal carcinoma was a result of genomic instability with no obvious consequence for telomerase activity levels.
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| 9. |
- Seyed Khoei, Nazlisadat, et al.
(författare)
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Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses
- 2020
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Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).CONCLUSIONS: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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