Search Results (12)

This paper presents a conceptual and methodological framework for using Geographical Information Systems (GIS) to “deep map” cultural heritage sites along Ireland’s Wild Atlantic Way, with a focus on the 1588 Spanish Armada wrecks in County Kerry and archaeological landscapes in County Sligo’s “Yeats Country.” Drawing on interdisciplinary dialogues from the humanities, social sciences, and geospatial sciences, it illustrates how digital spatial technologies can excavate, preserve, and sustain intangible cultural knowledge embedded within such palimpsestic landscapes. Using MAXQDA 24 software to mine and code historical, literary, folkloric, and environmental texts, the study constructed bespoke GIS attribute tables and visualizations integrated with elevation models and open-source archaeological data. The result is a richly layered cartographic method that reveals the spectral and affective dimensions of heritage landscapes through climate, memory, literature, and spatial storytelling. By engaging with “deep mapping” and theories such as “Spectral Geography,” the research offers new avenues for sustainable heritage conservation, cultural tourism, and public education that are sensitive to both ecological and cultural resilience in the West of Ireland. Full article

Poetry and philosophy have had a close but uneasy relationship in the western tradition. Both share an eschewal of the discovery of novel facts, but are somewhat opposed in that discovery is a central aim of poetry, but not at all the aim of philosophy. Through a close reading of W.H. Auden’s ‘In Memory of W.B. Yeats’ and a versification of part of G.E. Moore’s ‘A Defence of Common Sense’, I argue that what poetry shows corresponds, in a broadly symbolist sense, to Wittgenstein’s understanding of the miraculous nature of the world. In this regard, poetry can offer philosophy clarity, in the form of its tonal architecture, value, and ethics, and may also constitute a perspicuous representation. Poetry remains in a perpetual mode of potential, as well as being possessed of a vatic autonomy. Full article

Chronic Lymphocytic Leukemia (CLL) is the most common B-cell malignancy in the Western world, characterized by frequent relapses despite temporary remissions. Our study integrated publicly available proteomic, transcriptomic, and patient survival datasets to identify key differences between healthy and CLL samples. We exposed approximately 1000 proteins that differentiate healthy from cancerous cells, with 608 upregulated and 415 downregulated in CLL cases. Notable upregulated proteins include YEATS2 (an epigenetic regulator), PIGR (Polymeric immunoglobulin receptor), and SNRPA (a splicing factor), which may serve as prognostic biomarkers for this disease. Key pathways implicated in CLL progression involve RNA processing, stress resistance, and immune response deficits. Furthermore, we identified three existing drugs—Bosutinib, Vorinostat, and Panobinostat—for potential further investigation in drug repurposing in CLL. We also found limited correlation between transcriptomic and proteomic data, emphasizing the importance of proteomics in understanding gene expression regulation mechanisms. This generally known disparity highlights once again that mRNA levels do not accurately predict protein abundance due to many regulatory factors, such as protein degradation, post-transcriptional modifications, and differing rates of translation. These results demonstrate the value of integrating omics data to uncover deregulated proteins and pathways in cancer and suggest new therapeutic avenues for CLL. Full article

Histone lysine methacrylation and crotonylation are epigenetic marks that play important roles in human gene regulation. Here, we explore the molecular recognition of histone H3 peptides possessing methacryllysine and crotonyllysine at positions 18 and 9 (H3K18 and H3K9) by the AF9 YEATS domain. Our binding studies demonstrate that the AF9 YEATS domain displays a higher binding affinity for histones possessing crotonyllysine than the isomeric methacryllysine, indicating that AF9 YEATS distinguishes between the two regioisomers. Molecular dynamics simulations reveal that the crotonyllysine/methacryllysine-mediated desolvation of the AF9 YEATS domain provides an important contribution to the recognition of both epigenetic marks. These results provide important knowledge for the development of AF9 YEATS inhibitors, an area of biomedical interest. Full article

The kinase ZAKα acts as the proximal sensor of translational impairment and ribotoxic stress, which results in the activation of the MAP kinases p38 and JNK. Despite recent insights into the functions and binding partners of individual protein domains in ZAKα, the mechanisms by which ZAKα binds ribosomes and becomes activated have remained elusive. Here, we highlight a short, thrice-repeated, and positively charged peptide motif as critical for the ribotoxic stress-sensing function of the Sensor (S) domain of ZAKα. We use this insight to demonstrate that the mutation of the SAM domain uncouples ZAKα activity from ribosome binding. Finally, we use 3D structural comparison to identify and functionally characterize an additional folded domain in ZAKα with structural homology to YEATS domains. These insights allow us to formulate a model for ribosome-templated ZAKα activation based on the re-organization of interactions between modular protein domains. In sum, our work both advances our understanding of the protein domains and 3D architecture of the ZAKα kinase and furthers our understanding of how the ribotoxic stress response is activated. Full article

Hepatocellular carcinoma (HCC) is one of the most common cancers and the fourth leading cause of death in men. YEATS domain containing 2 (YEATS2) gene encodes a scaffolding subunit of the ATAC complex. We found that YEATS2 was upregulated in HCC tissues and was associated with a poor prognosis. However, the role of YEATS2 in HCC remains unclear. The purpose of this study was to investigate the effect of YEATS2 on the progression of HCC and to elucidate its related mechanisms. We found that overexpression of YEATS2 promoted tumor cell proliferation, migration, and invasion through the PI3K/AKT signaling pathway and regulation of extracellular matrix. These findings help to understand the role of YEATS2 in HCC, and YEATS2 may become a new target for HCC therapy. Full article

Traditional fermented foods and beverages play an important role in a range of human diets, and several experimental studies have shown their potential positive effects on human health. Studies from different continents have revealed strong associations between the microorganisms present in certain fermented foods (e.g., agave fructans, kefir, yeats, kombucha, chungkookjang, cheeses and vegetables, among others) and weight maintenance, reductions in the risk of cardiovascular disease, antidiabetic and constipation benefits, improvement of glucose and lipids levels, stimulation of the immunological system, anticarcinogenic effects and, most importantly, reduced mortality. Accordingly, the aim of this review is to corroborate information reported in experimental studies that comprised interventions involving the consumption of traditional fermented foods or beverages and their association with human health. This work focuses on studies that used fermented food from 2014 to the present. In conclusion, traditional fermented foods or beverages could be important in the promotion of human health. Further studies are needed to understand the mechanisms involved in inflammatory, immune, chronic and gastrointestinal diseases and the roles of fermented traditional foods and beverages in terms of preventing or managing those diseases. Full article

YEATS (YAF9, ENL, AF9, TAF14, SAS5) family proteins recognize acylated histones and in turn regulate chromatin structure, gene transcription, and stress signaling. The chromosomal translocations of ENL and mixed lineage leukemia are considered oncogenic drivers in acute myeloid leukemia and acute lymphoid leukemia. However, known ENL YEATS domain inhibitors have failed to suppress the proliferation of 60 tested cancer cell lines. Herein, we identified four hits from the NMR fragment-based screening against the AF9 YEATS domain. Ten inhibitors of new chemotypes were then designed and synthesized guided by two complex structures and affinity assays. The complex structures revealed that these inhibitors formed an extra hydrogen bond to AF9, with respect to known ENL inhibitors. Furthermore, these inhibitors demonstrated antiproliferation activities in AF9-sensitive HGC-27 cells, which recapitulated the phenotype of the CRISPR studies against AF9. Our work will provide the basis for further structured-based optimization and reignite the campaign for potent AF9 YEATS inhibitors as a precise treatment for AF9-sensitive cancers. Full article

(1) Background: Clinical decision support (CDS) is a vitally important adjunct to the implementation of pharmacogenomic-guided prescribing in clinical practice. A novel CDS was sought for the APOL1, NAT2, and YEATS4 genes to guide optimal selection of antihypertensive medications among the African American population cared for at multiple participating institutions in a clinical trial. (2) Methods: The CDS committee, made up of clinical content and CDS experts, developed a framework and contributed to the creation of the CDS using the following guiding principles: 1. medical algorithm consensus; 2. actionability; 3. context-sensitive triggers; 4. workflow integration; 5. feasibility; 6. interpretability; 7. portability; and 8. discrete reporting of lab results. (3) Results: Utilizing the principle of discrete patient laboratory and vital information, a novel CDS for APOL1, NAT2, and YEATS4 was created for use in a multi-institutional trial based on a medical algorithm consensus. The alerts are actionable and easily interpretable, clearly displaying the purpose and recommendations with pertinent laboratory results, vitals and links to ordersets with suggested antihypertensive dosages. Alerts were either triggered immediately once a provider starts to order relevant antihypertensive agents or strategically placed in workflow-appropriate general CDS sections in the electronic health record (EHR). Detailed implementation instructions were shared across institutions to achieve maximum portability. (4) Conclusions: Using sound principles, the created genetic algorithms were applied across multiple institutions. The framework outlined in this study should apply to other disease-gene and pharmacogenomic projects employing CDS. Full article

After Evans and colleagues identified the lipomatous tumor with a well-differentiated liposarcoma in a subcutaneous location or within a muscle layer, namely, atypical lipomatous tumor (ALT), this malignancy has been investigated to clarify the characteristics of clinical behavior and genomic changes. As one of the important issues for clinicians, it is a hot topic of how to distinguish ALT from benign lipoma in the clinical aspect. Recent studies revealed novel findings to clarify the risk factor for the diagnosis of ALT and molecular targets for the treatment of ALT. Clinical characteristics of superficial-type ALT well reflect the subcutaneous location of the tumor and are slightly different compared to deep-type ALT, such as tumor size. In addition, there has been a recent discovery of novel findings in ALT-related genes, namely, HMG2A (high mobility group protein 2a), YEATS4 (YEATS domain containing 4), and CPM (Carboxypeptidase M). Recent updates on treatment for advanced ALT are well developed including immunotherapy and conducting clinical trials. Finally, this review introduces one of the hot topics of ALT research focused on epigenetic changes: their attention in recent updates on clinical characteristics and the novel discovery of related genes, treatment, and epigenetic modifications in atypical lipomatous tumors. Full article

This essay addresses the ideas and schemas of reincarnation as used in the poetry and prose of William Butler Yeats, with particular focus on the two editions of A Vision. It contrasts the metaphysical system as given in A Vision (1937) with a number of inconsistencies found in Yeats’s poetic corpus, with an emphasis on how one might interpolate an escape from the cycle of lives, in at least one possibility while still maintaining corporality. The justification for this last comes from an analysis of complex cabalistic metaphors and teachings that Yeats learned as a member of MacGregor Mathers’ Hermetic Order of the Golden Dawn. Full article

Through close readings of the work of two major poets of the twentieth century—W.B. Yeats and Fernando Pessoa—this paper identifies and attempts to make sense of an important shift in European modernism away from a broadly Romantic aesthetic toward what might be called “post-Romanticism.” Taking its cue from W.H. Auden’s “In Memory of W.B. Yeats,” where having stated that “poetry makes nothing happen” he asserts that it survives as “a way of happening,” and drawing on the philosophy of Heidegger and Jean-Luc Nancy, this paper argues that this shift from Romanticism to post-Romanticism hinges on a deep metaphysical reconceptualization of poetry understood as poiesis. In light of this reassessment of the aesthetics and philosophical affinities of poetic modernism, it is argued that post-Romanticism should be understood as offering a modest, salutary, phenomenological re-acquaintance with our involvement with the everyday world, in sharp contrast to the transcendental ambitions of the Romantic aesthetic that preceded it. Full article