Morphological and Transcriptomic Analysis of a Beetle Chemosensory System Reveals a Gnathal Olfactory Center

OR gene tissue expression and their chromosomal localization. a Venn diagram showing the number of ORs expressed (RPKM ≥ 0.5) in the different body parts: antennae, legs, mouthparts (as piece of the head capsule anterior of the antennae), heads (the whole head capsule including mouthparts but excluding the antennae), and bodies (excluding head and legs). b Venn diagram comparing our results (yellow, green) with data from Engsontia et al. [115] (blue, red). Number of expressed ORs, defined by RPKM ≥ 0.5 (yellow), by RT-PCR (blue), not expressed RPKM < 0.5 (green), or with no RT-PCR amplicon (red). ORs of the brown group were not previously tested by Engsontia et al. c Chromosomal localization of T. castaneum ORs. Based on the Georgia GA-2 strain genome assembly 3.0 [81], only chromosomal linkage groups containing an IR or SNMP are depicted. Gene clusters are indicated by a number referring to the chromosome and a letter conveys the relative position on the chromosome. The number of genes within this cluster is indicated in the square brackets. (PDF 277 kb

Does the antidiabetic drug metformin affect embryo development and the health of brown trout (Salmo trutta f. fario)?

Abstract Background Due to the rising number of type 2 diabetes patients, the antidiabetic drug, metformin is currently among those pharmaceuticals with the highest consumption rates worldwide. Via sewage-treatment plants, metformin enters surface waters where it is frequently detected in low concentrations (µg/L). Since possible adverse effects of this substance in aquatic organisms have been insufficiently explored to date, the aim of this study was to investigate the impact of metformin on health and development in brown trout (Salmo trutta f. fario) and its microbiome. Results Brown trout embryos were exposed to 0, 1, 10, 100 and 1000 µg/L metformin over a period from 48 days post fertilisation (dpf) until 8 weeks post-yolk sac consumption at 7 °C (156 dpf) and 11 °C (143 dpf). Chemical analyses in tissues of exposed fish showed the concentration-dependent presence of metformin in the larvae. Mortality, embryonic development, body length, liver tissue integrity, stress protein levels and swimming behaviour were not influenced. However, compared to the controls, the amount of hepatic glycogen was higher in larvae exposed to metformin, especially in fish exposed to the lowest metformin concentration of 1 µg/L, which is environmentally relevant. At higher metformin concentrations, the glycogen content in the liver showed a high variability, especially for larvae exposed to 1000 µg/L metformin. Furthermore, the body weight of fish exposed to 10 and 100 µg/L metformin at 7 °C and to 1 µg/L metformin at 11 °C was decreased compared with the respective controls. The results of the microbiome analyses indicated a shift in the bacteria distribution in fish exposed to 1 and 10 µg/L metformin at 7 °C and to 100 µg/L metformin at 11 °C, leading to an increase of Proteobacteria and a reduction of Firmicutes and Actinobacteria. Conclusions Overall, weight reduction and the increased glycogen content belong to the described pharmaceutical effects of the drug in humans, but this study showed that they also occur in brown trout larvae. The impact of a shift in the intestinal microbiome caused by metformin on the immune system and vitality of the host organism should be the subject of further research before assessing the environmental relevance of the pharmaceutical

Zeit für sich selbst : Muße, Langeweile und die Nutzung digitaler Medien im Alltag ; Zwei Forschungsberichte

Die erste Studie ("Langweilen wir uns noch? Nutzung von digitalen Medien zur unbewussten Prävention von Langeweile") beschäftigt sich mit der Nutzung digitaler Medien als Prävention von Langeweile. Dabei wird hinterfragt, ob die Mediennutzung die Langeweile tatsächlich verhindern kann oder ob dieser Erfolg ausbleibt. Zunächst wird ermittelt, auf welche Weise mit Langeweile umgegangen wird. Darauf aufbauend werden Motive herausgearbeitet, die hinter der digitalen Mediennutzung stehen. Aus dieser Kombination von Mediennutzung und Langeweile leitet sich die Frage nach der bewussten oder unbewussten präemptiven Nutzung von Medien zur Vermeidung von Langweile ab. Zur Beantwortung der Forschungsfragen dient eine qualitativ durchgeführte Gruppendiskussion. - Die zweite Studie ("Langeweile oder Muße: Gründe der Selbstdarstellung in den sozialen Medien") thematisiert potentielle Gründe der Selbstdarstellung in den sozialen Medien vor dem Hintergrund der modernen digitalen Gesellschaft. Dabei werden vorranging die Konstrukte der Muße und der Langeweile sowie deren Zusammenhänge als Gründe für das Posting selbstdarstellerischer Inhalte in Social Media theoretisch betrachtet und methodisch analysiert. Im Rahmen der Forschungsarbeit wird dabei Instagram als beispielhaftes Medium zum Gegenstandsbereich der Untersuchung gewählt. Zur Beantwortung der Forschungsfrage wird die Methode der narrativen Medienforschung angewandt. Basierend auf den Erkenntnissen von fünf qualitativ und narrativ durchgeführten Tiefeninterviews erfolgt mittels einer Inhaltsanalyse eine deduktive sowie induktive Kategorienbildung, die potentielle Gründe der Selbstdarstellung aufzeigt

Comparing the value of mono- vs coculture for high-throughput compound screening in hematological malignancies

Large-scale compound screens are a powerful model system for understanding variability of treatment response and discovering druggable tumor vulnerabilities of hematological malignancies. However, as mostly performed in a monoculture of tumor cells, these assays disregard modulatory effects of the in vivo microenvironment. It is an open question whether and to what extent coculture with bone marrow stromal cells could improve the biological relevance of drug testing assays over monoculture. Here, we established a high-throughput platform to measure ex vivo sensitivity of 108 primary blood cancer samples to 50 drugs in monoculture and coculture with bone marrow stromal cells. Stromal coculture conferred resistance to 52% of compounds in chronic lymphocytic leukemia (CLL) and 36% of compounds in acute myeloid leukemia (AML), including chemotherapeutics, B-cell receptor inhibitors, proteasome inhibitors, and Bromodomain and extraterminal domain inhibitors. Only the JAK inhibitors ruxolitinib and tofacitinib exhibited increased efficacy in AML and CLL stromal coculture. We further confirmed the importance of JAK-STAT signaling for stroma-mediated resistance by showing that stromal cells induce phosphorylation of STAT3 in CLL cells. We genetically characterized the 108 cancer samples and found that drug-gene associations strongly correlated between monoculture and coculture. However, effect sizes were lower in coculture, with more drug-gene associations detected in monoculture than in coculture. Our results justify a 2-step strategy for drug perturbation testing, with large-scale screening performed in monoculture, followed by focused evaluation of potential stroma-mediated resistances in coculture

Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial

Ex vivo drug response profiling is a powerful tool to study genotype-drug response associations and is being explored as a tool set for precision medicine in cancer. Here we conducted a prospective non-interventional trial to investigate feasibility of ex vivo drug response profiling for treatment guidance in hematologic malignancies (SMARTrial, NCT03488641 ). The primary endpoint to provide drug response profiling reports within 7 d was met in 91% of all study participants (N = 80). Secondary endpoint analysis revealed that ex vivo resistance to chemotherapeutic drugs predicted chemotherapy treatment failure in vivo. We confirmed the predictive value of ex vivo response to chemotherapy in a validation cohort of 95 individuals with acute myeloid leukemia treated with daunorubicin and cytarabine. Ex vivo drug response profiles improved ELN-22 risk stratification in individuals with adverse risk. We conclude that ex vivo drug response profiling is clinically feasible and has the potential to predict chemotherapy response in individuals with hematologic malignancies beyond clinically established genetic markers

DNA DOUBLE STRAND BREAK REPAIR DURING HEAD-DOWN-TILT BEDREST: AGBRESA MEETS RADIATION

BACKGROUND Radiation and reduced gravity impose a major burden on health and performance during human spaceflight. While radiation increases cancer risk and limits tissue regeneration, reduced gravity predisposes to musculoskeletal and cardiovascular deconditioning. Deconditioning could conceivably limit the recovery from radiation damage. Our aim was to develop a terrestrial ex vivo model that could be utilized to study the effect of simulated reduced gravity using head-down-tilt bed-rest on repair of ionizing-radiation-induced DNA damage