Biology subjects

Gasse, C.

Publications and source records attributed to Gasse, C..

3 recordsLinked to original sources

bioRxiv2020

Stealth fluorescence labeling for live microscopy imaging of mRNA delivery

Methods for tracking of RNA molecules inside living cells are critical to probe their dynamics and biological functions, but also to monitor delivery of therapeutic RNA. We here describe a method for fluorescence labeling of RNAs of any length, via the enzymatic incorporation of the minimally perturbing and intrinsically fluorescent tricyclic cytosine analogue tCO. Using this approach, we demonstrate incorporation of tCO in up to 100% of all natural cytosine positions of a 1.2 kb mRNA encoding for the histone H2B fused to GFP (H2B:GFP). The resulting transcript is fully compatible with both in vitro transcription and subsequent in cell translation. Spectroscopic characterization of the in vitro transcribed mRNA, shows that the incorporation rate of tCO is on par with cytosine, facilitating efficient labeling and controlled tuning of labeling ratios for different applications. Using live cell confocal microscopy and flow cytometry, we show that the tCO-labeled mRNA is efficiently and correctly translated into H2B:GFP upon electroporation as well as lipid-mediated transfection of human Huh-7 cells; correct translation was further confirmed in cell-free systems. Importantly, the spectral properties of the tCO-modified transcripts and their translation product, in this case H2B:GFP, allow for their straightforward and simultaneous visualization in live cells.Competing Interest StatementAnders Dahlen is an employee of AstraZeneca and may hold shares in the company.View Full Text

biochemistry↗

bioRxiv2018

Schizophrenia polygenic risk scores, urbanicity and treatment-resistant schizophrenia

IntroductionTo investigate the impact of a polygenic risk score for schizophrenia (PRS-SZ) and urbanicity on the risk of treatment-resistant schizophrenia in people with a diagnosis of schizophrenia and to evaluate the association between PRS-SZ and TRS across areas of urbanicity.\n\nMethodsCohort study of people born after 1981 with a first time diagnosis of schizophrenia between 1996 and 2012 using Danish population registry data. Through linkage to genome-wide data, we calculated PRS-SZ based on a Psychiatric Genomics Consortium meta-analysis. We assessed urbanicity at birth (capital, provincial and rural areas). TRS was defined using prescription and hospital data. Performing Cox regression analysis, we calculated hazard rate ratios (HRs) and 95% confidence intervals (CI).\n\nResultsAmong 4,475 people with schizophrenia, we identified 593 (13.3%) with TRS during 17 558 person years of follow-up. The adjusted HR for TRS associated with 1 standard deviation (SD) increase in the PRS-SZ was 1.11 (95% CI: 1.00-1.24). The adjusted HRs for urbanicity and TRS were 1.20 (95% CI: 0.98-1.47) for provincial areas and 1.19 (95% CI 0.96-1.47) for rural areas compared with the capital area. Across strata of urbanicity, the adjusted HR for TRS was 1.39 (95% CI: 1.14-1.70) in the capital area with 1 SD increase in the PRS-SZ, 0.99 (95% CI 0.84-1.17) in provincial areas, and 1.03 (95% CI: 0.86-1.25) in rural areas.\n\nConclusionThe risk of TRS associated with genetic liability varied across urbanicity areas and was highest in people with schizophrenia who resided in the capital areas at birth.

epidemiology↗

bioRxiv2018

Statin treatment and the risk of depression

The effect of statin treatment on the risk of developing depression remains unclear. Therefore, we aimed to assess the association between statin treatment and depression in a nationwide register-based cohort study with up to 20 years of follow up. We identified all statin users among all individuals born in Denmark between 1920 and 1983. One non-user was matched to each statin user based on age, sex and a propensity score taking several potential confounders into account. Using Cox regression we investigated the association between statin use and: I) redemption of prescriptions for antidepressants, II) redemption of prescriptions for any other drug, III) depression diagnosed at psychiatric hospitals, IV) cardiovascular mortality and V) all-cause mortality. A total of 193,977 statin users and 193,977 non-users were followed for 2,621,282 person-years. Statin use was associated with I) increased risk of antidepressant use (hazard rate ratio (HRR)=1.33; 95% confidence interval (95%-CI)=1.31-1.36), II) increased risk of any other prescription drug use (HRR=1.33; 95%-CI=1.31-1.35), III) increased risk of receiving a depression diagnosis (HRR=1.22, 95%-CI=1.12-1.32) - but not after adjusting for antidepressant use (HRR=1.07, 95%-CI=0.99- 1.15), IV) reduced cardiovascular mortality (HRR=0.92, 95%-CI=0.87-0.97) and V) reduced all-cause mortality (HRR=0.90, 95%-CI=0.88-0.92). These results suggest that the association between statin treatment and antidepressant use was unspecific (equivalent association between statins and other drugs) and that the association between statin use and depression diagnoses was mediated by antidepressant use. Thus, statin users and non-users appear to be equally likely to develop depression, but the depression is more often detected/treated among statin users.

epidemiology↗