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Janz, S.

Publications and source records attributed to Janz, S..

4 recordsLinked to original sources

Three species, three labs, three experiments: testing the reproducibility of ecological studies on insect behaviour in a multi-laboratory setting

The reproducibility of studies involving insect species is an underexplored area in the broader discussion about poor reproducibility in science. Our study addresses this gap by conducting a systematic multi-laboratory investigation into the reproducibility of ecological studies on insect behaviour. We implemented a 3x3 experimental design, incorporating three study sites, and three independent experiments on three insect species from different orders: the turnip sawfly (Athalia rosae, Hymenoptera), the meadow grasshopper (Pseudochorthippus parallelus, Orthoptera) and the red flour beetle (Tribolium castaneum, Coleoptera). Using random-effect meta-analysis, we compared the consistency and accuracy of treatment effects on insect behavioural traits across replicate experiments. We successfully reproduced the overall statistical treatment effect in 83% of the replicate experiments, but overall effect size replication was achieved in only 66% of the replicates. Thus, though demonstrating sufficient reproducibility in some measures, this study also provides first experimental evidence for cases of poor reproducibility in insect experiments. Our findings further show that reasons causing poor reproducibility established in rodent research also hold for other study organisms and research questions. We believe that a rethinking of current best practices is required to face reproducibility issues in insect studies, but also across disciplines. Specifically, we advocate for adopting open research practices and the implementation of methodological strategies that reduce bias and problems arising from over-standardization. With respect to the latter, the introduction of systematic variation through multi-laboratory or heterogenized designs may contribute to improved reproducibility in studies involving any living organisms.

animal behavior and cognition↗

Inhibition of FOXM1 synergizes with BCL2 inhibitor Venetoclax in killing non-t(11;14) multiple myeloma cells via repressing MYC pathway

Despite significant improvements in the prognosis of Multiple Myeloma (MM), relapsed/refractory MM remains a major challenge. BCL2 inhibitor Venetoclax induced complete or very good partial responses in 6% of non-t(11;14) MM cases, compared to 27% in t(11;14) cases, when used as monotherapy in relapsed/refractory MM. Though Venetoclax was proposed to treat t(11;14) cases, the resistance became a concern. Furthermore, non-t(11;14) cases account for 80-85% of MM cases, which underscores the value of Venetoclax in non-t(11;14) MM. Here, we report a recently-invented small molecule inhibitor of FOXM1 NB73 synergizing with Venetoclax in killing MM cells. FOXM1, a critical forkhead box transcription factor in high-risk and relapsed/refractory MM, represents a promising therapeutic target of MM. We examined the mechanisms underlying the synergies of Venetoclax and NB73 using multi-omics and molecular and cellular biology tools in non-t(11;14) myeloma cell lines with high FOXM1 expression. NB73 induces immediate loss of FOXM1, decreases BCL2 expression, and increases Puma expression in myeloma cells. Venetoclax enhances NB73-induced FOXM1 ubiquitination and degradation. The NB73-Venetoclax combination abrogates the binding of FOXM1 to the promoters of genes in the MYC pathway, such as PLK1, MYC, CDC20, and CCNA2, leading to the repression of the transcription of these MYC pathway genes. The PLK1-specific inhibitor GSK461364 synergies with NB73 in suppressing myeloma cell growth. Therefore, NB73 synergizes with Venetoclax in killing myeloma cells. Conclusively, the NB73-Venetoclax combination abolishes FOXM1-mediated transcriptional activation of the MYC pathway, resulting in intensive apoptosis of myeloma cells without t(11;14) but with high FOXM1 expression. Statement of significanceThis study implicates that targeting FOXM1 will alleviate resistance to BCL2 inhibitor Venetoclax in non-t(11;14) myeloma cells expressing high FOXM1.

cancer biology↗

Orphan nuclear receptor NR2E3 and its small-molecule agonist induce cancer cell apoptosis through regulating p53, IFNα and MYC pathways

Orphan nuclear receptor NR2E3 activates p53 and induces cancer cell apoptosis. Further studies on p53-dependent and -independent functions of wild-type and mutated NR2E3 are needed. Herein, we showed that NR2E3 enhanced p53-DNA interactions in diverse cancer cells and up-regulated p53 and IFN pathways while down-regulating MYC pathway in cervical cancer cells. Studies of "All of Us" and TCGA databases showed NR2E3 nonsynonymous mutations associating with four cancers. We stratified NR2E3 SNVs for their cancer implications with the p53 reporter. A cancer-associated NR2E3R97Hmutation not only lost the wild-types tumor-suppressing functions but also prohibited the wild-type from enhancing p53 acetylation. These observations implicated the potential for pharmaceutically activating NR2E3 to suppress cancer. Indeed, NR2E3s small-molecule agonist 11a repressed 2-D and 3-D cultures of primary cells and cell lines of cervical cancer, in which screening FDA-approved anti-cancer drugs identified HDAC-1/2 inhibitor Romidepsin operating synergistically with 11a. The underlying molecular mechanisms included 11as down-regulating the transcription of Multidrug Resistance Protein ABCB1 that Romidepsin up-regulated. Transcriptomics studies revealed three synergy modes: (1) "sum-up" mode that the p53 pathway activated individually by 11a and Romidepsin got stronger by the combo; (2) "antagonism" mode that Romidepsin counteracted the activation of the Kras pathway by 11a; and (3) "de novo" mode that the combo instead of each individual drug repressed the MYC pathway. Conclusively, our experiments provide new data supporting tumor-suppressor like functions for wild-type NR2E3, reveal roles of mutated NR2E3 in cancer, and address values of NR2E3s agonist 11a in cancer therapy alone and combined.

cancer biology↗

Plant metabolites modulate animal social networks and lifespan

Social interactions influence disease spread, information flow, and resource allocation across species, yet heterogeneity in social interaction frequency and its fitness consequences remain poorly understood. Additionally, animals can utilize plant metabolites for purposes beyond nutrition, but whether that shapes social networks is unclear. Here, we investigated how non-nutritive plant metabolites impact social interactions and the lifespan of the turnip sawfly, Athalia rosae. Adult sawflies acquire neo-clerodane diterpenoids (clerodanoids) from non-food plants, showing intraspecific variation in natural populations and laboratory-reared individuals. Clerodanoids can also be transferred between conspecifics, leading to increased agonistic social interactions. Network analysis indicated increased social interactions in sawfly groups where some or all individuals had prior access to clerodanoids. Social interaction frequency varied with clerodanoid status, with fitness costs including reduced lifespan resulting from increased interactions. Our findings highlight the role of intraspecific variation in the acquisition of non-nutritional plant metabolites in shaping social networks, with fitness implications on individual social niches.

animal behavior and cognition↗