Genome-Wide Association Analyses Point to Candidate Genes for Electric Shock Avoidance in Drosophila melanogaster

Electric shock is a common stimulus for nociception-research and the most widely used reinforcement in aversive associative learning experiments. Yet, nothing is known about the mechanisms it recruits at the periphery. To help fill this gap, we undertook a genome-wide association analysis using 38 inbred Drosophila melanogaster strains, which avoided shock to varying extents. We identified 514 genes whose expression levels and/or sequences covaried with shock avoidance scores. We independently scrutinized 14 of these genes using mutants, validating the effect of 7 of them on shock avoidance. This emphasizes the value of our candidate gene list as a guide for follow-up research. In addition, by integrating our association results with external protein-protein interaction data we obtained a shock avoidance- associated network of 38 genes. Both this network and the original candidate list contained a substantial number of genes that affect mechanosensory bristles, which are hairlike organs distributed across the fly's body. These results may point to a potential role for mechanosensory bristles in shock sensation. Thus, we not only provide a first list of candidate genes for shock avoidance, but also point to an interesting new hypothesis on nociceptive mechanisms

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics

Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)

Memory decay and susceptibility to amnesia dissociate punishment- from relief-learning

Painful events shape future behaviour in two ways: stimuli associated with pain onset subsequently support learned avoidance (i.e. punishment-learning) because they signal future, upcoming pain. Stimuli associated with pain offset in turn signal relief and later on support learned approach (i.e. relief-learning). The relative strengths of such punishment- and relief-learning can be crucial for the adaptive organization of behaviour in the aftermath of painful events. Using Drosophila, we compare punishment- and relief-memories in terms of their temporal decay and sensitivity to retrograde amnesia. During the first 75 min following training, relief-memory is stable, whereas punishment-memory decays to half of the initial score. By 24 h after training, however, relief-memory is lost, whereas a third of punishment-memory scores still remain. In accordance with such rapid temporal decay from 75 min on, retrograde amnesia erases relief-memory but leaves a half of punishment-memory scores intact. These findings suggest differential mechanistic bases for punishment- and relief-memory, thus offering possibilities for separately interfering with either of them

Independent natural genetic variation of punishment- versus relief-memory

A painful event establishes two opponent memories: cues that are associated with pain onset are remembered negatively, whereas cues that coincide with the relief at pain offset acquire positive valence. Such punishment- versus relief-memories are conserved across species, including humans, and the balance between them is critical for adaptive behaviour with respect to pain and trauma. In the fruit fly, Drosophila melanogaster as a study case, we found that both punishment- and relief-memories display natural variation across wild-derived inbred strains, but they do not covary, suggesting a considerable level of dissociation in their genetic effectors. This provokes the question whether there may be heritable inter-individual differences in the balance between these opponent memories in man, with potential psycho-clinical implications

Post COVID - Just a matter of definition?

The prevalence of post-COVID syndrome (PCS) has not yet been conclusively clarified. The existing definitions primarily reflect temporal aspects, but disregard functional deficits as well as the objectification of symptoms. This leads to diagnostic as well as therapeutic ambiguities. Pubmed was searched for systematic reviews dealing with the impact of SARS-CoV-2 infection. The underlying definitions as well as temporal inclusion criteria were extracted. 16 systematic reviews were included, 11 of which included a definition of PCS. In 58 % of the individual studies analyzed, patients with symptomatology > 12 weeks and thus according to the definition of PCS were included. Conclusion: Further clarification of the definition of PCS is necessary to facilitate diagnosis and multimodal treatment and to use the scarce therapeutic resources accordingly