Biology subjects

Johansen, J. S.

Publications and source records attributed to Johansen, J. S..

3 recordsLinked to original sources

bioRxiv2024

Technical and biological variations in the purification of extrachromosomal circular DNA (eccDNA) and the finding of more eccDNA in the plasma of lung adenocarcinoma patients compared with healthy donors

Human plasma DNA originates from all tissues and organs, holding the potential as a versatile marker for diseases such as cancer, as fragments of cancer-specific alleles can be found circulating in the blood. While linear DNA has been studied intensely as a liquid biomarker, the role of circular circulating DNA in cancer is more unknown due, in part, to a lack of comprehensive testing methods. Our developed method profiles extrachromosomal circular DNA (eccDNA) in plasma, integrating Solid-Phase Reversible Immobilization (SPRI) bead purification, the removal of linear DNA and mitochondrial DNA, and DNA sequencing. As an initial assessment, we examined the method, biological variations, and technical variations using plasma samples from four patients with lung adenocarcinoma and four healthy and physically fit individuals. Despite the small sample group, we observed a significant eccDNA increase in cancer patients in two independent laboratories and that eccDNA covered up to 0.4 % of the genome/mL plasma. We found a subset of eccDNA from recurrent genes present in cancer samples but not in every control. In conclusion, our data reflect the large variation found in eccDNA sequence content and show that the variability observed among replicates in eccDNA stems from a biological source and can cause inconclusive findings for biomarkers. This suggests the need to explore other biological markers, such as epigenetic features on eccDNA.

molecular biology↗

bioRxiv2021

Effects of Perinatal Fluoxetine Exposure on Novelty-induced Social and Non-Social Investigation Behaviors in a Seminatural Environment

Selective serotonin reuptake inhibitors (SSRIs) are increasingly prescribed as medication for various affective disorders during pregnancy. SSRIs cross the placenta and affect serotonergic neurotransmission in the fetus, but the neurobehavioral consequences for the offspring remain largely unclear. Recent rodent research has linked perinatal SSRI exposure to alterations in both social and non-social aspects of behavior. However, this research has mainly focused on behavior within simplified environments. The current study investigates the effects of perinatal SSRI exposure on social and non-social investigation behaviors of adult rat offspring upon introduction to a novel seminatural environment with unknown conspecifics. During the perinatal period (gestational day 1 until postnatal day 21), rat dams received daily treatment with either an SSRI (fluoxetine, 10 mg/kg) or vehicle. Adult male and female offspring were observed within the first hour after introduction to a seminatural environment. The results showed that perinatal fluoxetine exposure altered aspects of non-social investigation behaviors, while not altering social investigation behaviors. More specifically both fluoxetine exposed males and females spent more total time on locomotor activity than controls. Furthermore, fluoxetine exposed females spent less time exploring objects and specific elements in the environment. The data suggest that perinatal exposure to SSRIs leads to a quicker, less detailed investigation strategy in novel environments, and that the alteration is mostly pronounced in females.

animal behavior and cognition↗

bioRxiv2018

Biomarker de-Mendelization: principles, potentials and limitations of a strategy to improve biomarker prediction by reducing the component of variance explained by genotype

In observational studies, the Mendelian randomization approach can be used to circumvent confounding, bias and reverse causation, and to assess a potential causal association between a biomarker and risk of disease. If, on the other hand, a substantial component of variance of a non-causal biomarker is explained by genotype, then genotype could potentially attenuate the observational association and the strength of the prediction. In order to reduce the component of variance explained by genotype, an approach that can be seen as the inverse of Mendelian randomization - biomarker de-Mendelization - appears plausible.Plasma YKL-40 is a good candidate for demonstrating principles of biomarker de-Mendelization because it is a non-causal biomarker with a substantial component of variance explained by genotype. This approach is an attempt to improve the observational association and the strength of a predictive biomarker; it is explicitly not aimed at detection of causal effects.\n\nWe studied 21 161 individuals form the Danish general population with measurements of YKL-40 concentration and rs4950928 genotype. Four different methods for biomarker de-Mendelization are explored for alcoholic liver cirrhosis and lung cancer.\n\nDe-Mendelization methods only improved predictive ability slighly. We observed an interaction between genotype and markers of developing disease with respect to YKL-40 concentration.\n\nEven when genotype explains 14% of the variance in a non-causal biomarker, we found no useful empirical improvement in risk prediction by biomarker de-Mendelization. This could reflect the predictive interaction between genotype and disease development being removed which counterbalanced any beneficial properties of the method in this situation.

epidemiology↗