Search bioRxiv⌕ Search

Biology subjects

Gottschick, C.

Publications and source records attributed to Gottschick, C..

3 recordsLinked to original sources

Exposure to childhood adversity and adult alcohol, nicotine, and illicit drug use in Germany: a cross-sectional analysis of the German National Cohort (NAKO)

Rationale: Exposure to adversity in childhood and adolescence (i.e., "early-life stress"; ELS) is a well-established risk factor for substance use. Objectives: The aim of this study was to investigate associations between ELS exposure and substance use across subtypes of ELS, different substance classes, and behavioral profiles of substance use. Methods: In this cross-sectional study, we examined associations between ELS exposure and substance use in a population-based sample of 172,173 adults aged 19-74 years from the German National Cohort (NAKO). ELS exposure was assessed using the Childhood Trauma Screener. Substance use included nicotine, alcohol, and illicit drug use. Associations were examined using regression models evaluating overall ELS exposure, cumulative trauma load, and ELS subtypes. Latent class analysis (LCA) was conducted to identify substance use profiles. Results: ELS exposure was associated with higher odds of smoking, greater smoking severity, heavier alcohol consumption among drinkers, and higher odds of lifetime illicit drug use. Overall, the strongest associations were observed for opioid and stimulant use. Dose-response analyses revealed higher risk with increasing numbers of ELS subtypes. Abuse-related subtypes, particularly exposure to physical and sexual abuse, consistently showed strongest independent associations across substances, whereas neglect exhibited weaker, more variable associations. LCA identified four substance use profiles, with ELS exposure predicting membership in more severe polysubstance classes. Conclusions: ELS emerged as a robust risk factor for adult substance use, underscoring the need for trauma-informed approaches in clinical practice, public health, and policy to mitigate the long-term consequences of early adversity.

neuroscience↗

Rapid hypermutation B cell trajectory recruits previously primed B cells upon third SARS-CoV-2 mRNA vaccination

High antibody affinity against the ancestral SARS-CoV-2 strain seems to be necessary (but not always sufficient) for the control of emerging immune-escape variants. Therefore, aiming at strong B cell somatic hypermutation - not only at high antibody titers - is a priority when utilizing vaccines that are not targeted at individual variants. Here, we developed a next-generation sequencing based SARS-CoV-2 B cell tracking protocol to rapidly determine the level of immunoglobulin somatic hypermutation at distinct points during the immunization period. The percentage of somatically hypermutated B cells in the SARS-CoV-2 specific repertoire was low after the primary vaccination series, evolved further over months and increased steeply after boosting. The third vaccination mobilized not only naive, but also antigen-experienced B cell clones into further rapid somatic hypermutation trajectories indicating increased affinity. Together, the strongly mutated post-booster repertoires and antibodies deriving from this may explain why the booster, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron B.1.1.529. Brief summaryPriming SARS-CoV-2 vaccinations generate antibodies from low-level matured B cells while the third vaccination strongly boosts somatic hypermutation potentially explaining different protection from immune-escape variants.

immunology↗

Metatranscriptome analysis of the vaginal microbiota reveals potential mechanisms for recurrence and protection against metronidazole in bacterial vaginosis

Bacterial vaginosis (BV) is a prevalent multifactorial disease of women in their reproductive years characterized by a shift from the Lactobacillus spp. dominated microbial community towards a taxonomically diverse anaerobic community. For unknown reasons, some women do not respond to therapy. In our recent clinical study, out of 37 women diagnosed with BV, 31 were successfully treated with metronidazole, while 6 still had BV after treatment. To discover possible reasons for the lack of response in those patients, we performed a metatranscriptome analysis of their vaginal microbiota, comparing them to patients who responded. Seven out of 8 Cas genes of Gardnerella vaginalis were highly up-regulated in non-responding patients. Cas genes, in addition to protecting against phages, might be involved in DNA repair thus mitigating the bactericidal effect of DNA damaging agents like metronidazole. In the second part of our study, we analyzed the vaginal metatranscriptomes of four patients over three months and showed high in vivo expression of genes for pore-forming toxins in L. iners and of genes encoding enzymes for the production of hydrogen peroxide and D-lactate in L. crispatus.

microbiology↗