Immigrant women's diet challenges and strategies to achieve healthy eating behaviour for oneself and one's family - a qualitative story dialogue method study from Norwegian context.

Ubiquitination is a highly diverse and information-rich post-translational modification in eukaryotic biology. Its molecular complexity and context-dependent functions make it an attractive subject for machine learning–based investigation. Rather than acting as a simple binary modification, ubiquitination can occur as mono-ubiquitination, multiple mono-ubiquitination events, or polyubiquitin chains linked through different lysine residues or the N-terminal methionine of ubiquitin. Differences in linkage type, chain length, branching, topology, substrate-site selection, and editing by deubiquitinating enzymes together form a multidimensional ubiquitin code. [, ] This code is associated with diverse biological processes, including proteasomal degradation, signal transduction, DNA damage responses, vesicular trafficking, immune regulation, and subcellular relocalization. The functional outcome of ubiquitination is highly context-dependent. Similar ubiquitin architectures may produce different biological effects depending on protein conformation, binding partners, cellular state, and spatial organization. Therefore, models for decoding ubiquitination should consider both ubiquitin-chain features and their broader molecular and cellular context. The ubiquitin-proteasome system (UPS) is essential for controlling cellular signaling and preserving protein homeostasis. Numerous illnesses, including cancer, neurological diseases, immune dysfunction, and metabolic disorders, may result from this system’s disruption [, ]. Dysregulation of E3 ubiquitin ligases and DUBs can disturb substrate stability, ubiquitin-chain editing, and downstream signaling, thereby contributing to cancer, neurodegeneration, immune dysregulation, and other disease states. [, ] In particular, aberrant ubiquitination may result from changes in the quantity, activity, location, or substrate selectivity of these enzymes. Important regulatory proteins may be incorrectly stabilized or degraded as a result of these alterations. The UPS has long been regarded as an important therapeutic target because of its close association with human disease. Clinical experience with proteasome inhibitors, exemplified by bortezomib in relapsed and refractory multiple myeloma, provided early proof that pharmacological modulation of the UPS can produce therapeutic benefit. [] However, proteasome inhibition acts broadly on protein turnover rather than on individual substrates, and this lack of substrate selectivity contributes to dose-limiting toxicity. [] More recently, targeted protein degradation strategies, most notably proteolysis-targeting chimeras (PROTACs) [] and molecular glue degraders [], have shifted the field from global UPS inhibition toward induced, substrate-directed ubiquitination. These approaches exploit E3 ubiquitin ligases to promote the selective degradation of disease-associated proteins, thereby offering a more precise way to manipulate protein stability. [] In particular, these techniques preferentially bind E3 ligases to disease-related proteins in order to establish more precise control over protein degradation. However, the binary binding affinity is not the only factor that affects these techniques’ effectiveness. [] The choice of E3 ligase, the degradation signal’s accessibility to lysine sites, the ternary complex’s conformation, the effectiveness of ubiquitin transfer, and following cellular processes are some of the other variables that affect effective degradation. Our knowledge of ubiquitination is still lacking despite decades of biochemical and proteomic study []. Current maps of ubiquitination sites, ubiquitin chain features, and E3 ligase/DUB–substrate interactions remain incomplete and biased, with limited coverage and strong dependence on specific experimental conditions. Only a fraction of the actual biological processes can be captured by large-scale ubiquitin proteomics investigations. [, ] As a result, it is challenging to employ unobserved occurrences as trustworthy negative samples in studies. Ubiquitination is governed by multiple layers of complexity, including many-to-many regulatory relationships, transient protein assemblies, conformational heterogeneity, allosteric regulation, and strong dependence on cell type, developmental stage, stress state, and subcellular localization [, , ]. Because the ultimate functional consequences rely not only on molecular recognition but also on ubiquitin transfer kinetics, competition between binding partners, and the larger proteostasis environment, predicting degradation outcomes becomes much more difficult []. Collectively, ubiquitination is a multi-scale, partly visible, and highly dynamic regulatory system that cannot be adequately handled by reductionist frameworks or straightforward principles [].