33 research outputs found
Effects of cold winters and roost site stability on population development of non-native Asian ring-necked parakeets (Alexandrinus manillensis) in temperate Central Europe – Results of a 16-year census
Asian ring-necked parakeets (Alexandrinus manillensis, formerly Psittacula krameri, hereafter RNP) first bred in Germany in 1969. Since then, RNP numbers increased in all three major German subpopulations (Rhineland, Rhine-Main, Rhine-Neckar) over the period 2003–2018. In the Rhine-Neckar region, the population increased to more than fivefold within only 15 years. Interestingly, there was no significant breeding range expansion of RNP in the period 2010–2018. In 2018, the total number of RNP in Germany amounted to >16,200 birds. Differences in RNP censuses between years were evident. Surprisingly, cold winters (extreme value, −13.7 °C) and cold weather conditions in the breeding season (coldest month average, −1.36 °C) were not able to explain between-year variation. This finding suggests that in general winter mortality is low – with exceptions for winters 2008/2009 and 2009/2010, and a population-relevant loss of broods is low in our study population. Surprisingly, the social behaviour in terms of spatio-temporal stability of roost sites could well explain positive and negative population trends. Years of spatially stable and regularly used roost sites seem to correlate with increasing population sizes. In contrast, known shifts of RNP among different roost sites or the formations of new roost sites by split are related to population stagnation or a decrease in numbers. Climate change may lead to further range expansion as cities not suitable yet for RNP may become so in the near future.
Activation of the Nrf2 response by intrinsic hepatotoxic drugs correlates with suppression of NF-κB activation and sensitizes toward TNFα-induced cytotoxicity
Uncovering the signaling landscape controlling breast cancer cell migration identifies novel metastasis driver genes
Ttriple-negative breast cancer (TNBC) is an aggressive and highly metastatic breast cancer subtype. Enhanced TNBC cell motility is a prerequisite of TNBC cell dissemination. Here, we apply an imaging-based RNAi phenotypic cell migration screen using two highly motile TNBC cell lines (Hs578T and MDA-MB-231) to provide a repository of signaling determinants that functionally drive TNBC cell motility. We have screened ~4,200 target genes individually and discovered 133 and 113 migratory modulators of Hs578T and MDA-MB-231, respectively, which are linked to signaling networks predictive for breast cancer progression. The splicing factors PRPF4B and BUD31 and the transcription factor BPTF are essential for cancer cell migration, amplified in human primary breast tumors and associated with metastasis-free survival. Depletion of PRPF4B, BUD31 and BPTF causes primarily down regulation of genes involved in focal adhesion and ECM-interaction pathways. PRPF4B is essential for TNBC metastasis formation in vivo, making PRPF4B a candidate for further drug development
Non-Standard Errors
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: Non-standard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for better reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants
Alternative signaling network activation through different insulin receptor family members caused by pro-mitogenic antidiabetic insulin analogues in human mammary epithelial cells
INTRODUCTION: Insulin analogues are designed to have improved pharmacokinetic parameters compared to regular human insulin. This provides a sustained control of blood glucose levels in diabetic patients. All novel insulin analogues are tested for their mitogenic side effects, however these assays do not take into account the molecular mode of action of different insulin analogues. Insulin analogues can bind the insulin receptor and the insulin-like growth factor 1 receptor with different affinities and consequently will activate different downstream signaling pathways. METHODS: Here we used a panel of MCF7 human breast cancer cell lines that selectively express either one of the isoforms of the INSR or the IGF1R. We applied a transcriptomics approach to assess the differential transcriptional programs activated in these cells by either insulin, IGF1 or X10 treatment. RESULTS: Based on the differentially expressed genes between insulin versus IGF1 and X10 treatment, we retrieved a mitogenic classifier gene set. Validation by RT-qPCR confirmed the robustness of this gene set. The translational potential of these mitogenic classifier genes was examined in primary human mammary cells and in mammary gland tissue of mice in an in vivo model. The predictive power of the classifier genes was evaluated by testing all commercial insulin analogues in the in vitro model and defined X10 and glargine as the most potent mitogenic insulin analogues. CONCLUSIONS: We propose that these mitogenic classifier genes can be used to test the mitogenic potential of novel insulin analogues as well as other alternative molecules with an anticipated affinity for the IGF1R. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0600-5) contains supplementary material, which is available to authorized users