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The molecular mechanisms of IBD have been the subject of intensive exploration. We, therefore, assembled the available information into a suite of causal biological network models, which offer comprehensive visualization of the processes underlying IBD. Scientific text was curated by using Biological Expression Language (BEL) and compiled with OpenBEL 3.0.0. Network properties were analysed by Cytoscape. Network perturbation amplitudes were computed to score the network models with transcriptomic data from public data repositories. The IBD network model suite consists of three independent models that represent signalling pathways that contribute to IBD. In the “intestinal permeability” model, programmed cell death factors were downregulated in CD and upregulated in UC. In the “inflammation” model, PPARG, IL6, and IFN-associated pathways were prominent regulatory factors in both diseases. In the “wound healing” model, factors promoting wound healing were upregulated in CD and downregulated in UC. Scoring of publicly available transcriptomic datasets onto these network models demonstrated that the IBD models capture the perturbation in each dataset accurately. The IBD network model suite can provide better mechanistic insights of the transcriptional changes in IBD and constitutes a valuable tool in personalized medicine to further understand individual drug responses in IBD.

Nonsense-mediated decay is well known by the lucid definition of being a RNA surveillance mechanism that ensures the speedy degradation of mRNAs containing premature translation termination codons. However, as we review here, NMD is far from being a simple quality control mechanism; it also regulates the stability of many wild-type transcripts. We summarise the abundance of research that has characterised each of the NMD factors and present a unified model for the recognition of NMD substrates. The contentious issue of how and where NMD occurs is also discussed, particularly with regard to P-bodies and SMG6-driven endonucleolytic degradation. In recent years, the discovery of additional functions played by several of the NMD factors has further complicated the picture. Therefore, we also review the reported roles of UPF1, SMG1 and SMG6 in other cellular processes.

Virtually any stressor that alters the cellular homeostatic state may result in an inflammatory response. As a critical component of innate immunity, inflammasomes play a prominent role in the inflammatory response. The information on inflammasome biology is rapidly growing, thus creating the need for structuring it into a model that can help visualize and enhance the understanding of underlying biological processes. Causal biological network (CBN) models provide predictive power for novel disease mechanisms and treatment outcomes. We assembled the available literature information on inflammasome activation into the CBN model and scored it with publicly available transcriptomic datasets that address viral infection of the lungs, osteo- and rheumatoid arthritis, psoriasis, and aging. The scoring inferred pathway activation leading to NLRP3 inflammasome activation in these diverse conditions, demonstrating that the CBN model provides a platform for interpreting transcriptomic data in the context of inflammasome activation.

Pten inactivation promotes cell survival in leukemia cells by activating glycolytic metabolism. We found that targeting ribosomal protein S6 kinase 1 (S6K1) in Pten-deficient cells suppressed glycolysis and induced apoptosis. S6K1 knockdown decreased expression of HIF-1α, and HIF-1α was sufficient to restore glycolysis and survival of cells lacking S6K1. In the Ptenfl/fl Mx1-Cre⁺ mouse model of leukemia, S6K1 deletion delayed the development of leukemia. Thus, S6K1 is a critical mediator of glycolytic metabolism, cell survival, and leukemogenesis in Pten-deficient cells.

‘Metal‐responsive transcription factor‐1’ (MTF‐1), a zinc finger protein, is conserved from mammals to insects. In the mouse, it activates metallothionein genes and other target genes in response to several cell stress conditions, notably heavy metal load. The knockout of MTF‐1 in the mouse has an embryonic lethal phenotype accompanied by liver degeneration. Here we describe the targeted disruption of the MTF‐1 gene in Drosophila by homologous recombination. Unlike the situation in the mouse, knockout of MTF‐1 in Drosophila is not lethal. Flies survive well under laboratory conditions but are sensitive to elevated concentrations of copper, cadmium and zinc. Basal and metal‐induced expression of Drosophila metallothionein genes MtnA ( Mtn ) and MtnB ( Mto ), and of two new metallothionein genes described here, MtnC and MtnD , is abolished in MTF‐1 mutants. Unexpectedly, MTF‐1 mutant larvae are sensitive not only to copper load but also to copper depletion. In MTF‐1 mutants, copper depletion prevents metamorphosis and dramatically extends larval development/lifespan from normally 4–5 days to as many as 32 days, possibly reflecting the effects of impaired oxygen metabolism. These findings expand the roles of MTF‐1 in the control of heavy metal homeostasis.

Identifying animal species used in osseous industry production is crucial for reconstructing human-animal interactions in ancient societies. However, bone artefact manufacture often involves intensive modifications to raw materials that hamper taxonomic identifications. Here, for the first time in central Eurasia, we taxonomically assess bone objects stored in museum collections, recovered from Late Neolithic to Iron Age contexts in Armenia, using a minimally invasive peptide mass fingerprinting technique, also known as Zooarchaeology by Mass Spectrometry (ZooMS). Our pilot study shows remarkable collagen preservation in the bone artefacts, demonstrating the rich potential of ZooMS for examining legacy collections. The successful ZooMS screening provided taxonomic identification for 86% of the artefacts, offering insights into species selection for bone manufacturing, as well as broader socioeconomic developments and interregional links. Our study underscores the utility of minimally invasive proteomic techniques, enabling the preservation of cultural and historical artefacts while addressing limitations of studying museum collections.

Dairy products are a key component of the diet in Armenia today, yet the origins of milk consumption, its historical development, and genetic adaptations related to milk digestion in the region remain understudied. Here, we investigate the co-evolution of dairying practices and lactase persistence in Armenia through combined palaeoproteomic and genetic analyses spanning from prehistory to the present. Our palaeoproteomic results provide direct evidence for milk consumption in prehistoric Armenia and, in conjunction with existing regional data, indicate that dairying was an established component of the South Caucasus subsistence economy from at least the late fourth millennium BCE. We found evidence of milk consumption from multiple species across archaeological periods, with cattle milk representing the earliest confirmed evidence from the Chalcolithic period. Notably, milk proteins were predominantly recovered from high-altitude sites, suggesting that dairy consumption served as an adaptive strategy for harsh highland environmental conditions. In contrast to the widespread evidence for milk consumption, our genetic findings indicate that the lactase persistence-associated variants never reached high frequencies throughout Armenian prehistory. This pattern suggests that the relatively low frequency of lactase persistence may reflect a predominant cultural adaptation to the fermentation of dairy products, which reduces lactose content and enables dairy use even in genetically lactose-intolerant populations.