“Out from Gens Romulum into the Weal-Kin”: Re-Locating Modernist Poetics in David Jones’ Anathémata and Basil Bunting’s Briggflatts

In the decades following its publication in 1922, T.S. Eliot\u27s Waste Land has become an epitome of the modernist sensibility and situation. This thesis challenges the poem\u27s dominance and dictate over the canon of modernist poetry persisting in the academic discourse and general cultural awareness. Focusing on two post-WWII sequences by Eliot\u27s younger contemporaries, David Jones\u27 s Anathemata (1952) and Basil Bunting\u27s Briggflatts (1966), this study explores alternative models and inspirative sources of the modernist poetic sequence. Through the constant comparison and contrast with Eliot\u27s earlier articulation of the modern historico-cultural circumstance, Jones\u27 and Bunting\u27s specific foci and methods emerge - while reflecting the elder poet\u27s heritage - as viable and vital transformations of the high modernist long poem. The surviving image of the modernist poetics, consecrated by The Waste Land, as most emphatically cosmopolitan, urban and exiled is confronted by the regional affiliation of Jones\u27 and Bunting\u27s sequences. The political/ poetic prestige of Eliot\u27s geo-cultural identification dramatically contrasts with the socio-historical marginality of the north-western territory captured and celebrated in The Anathemata and Briggflatts. This vibrant aesthetic dialectic is presented in a series of four dialogues. Following the initial reflection upon the precarious academic standing of the late modernist regional idiom, chapter 2 discusses Eliot\u27s controversial axiom of poetic impersonality in the light of Jones\u27 and Bunting\u27s geo-aesthetic stand. The following debate focuses on the formal experiment of the modernist sequence and the differing cultural motivation behind the fragmented structure of The Waste Land and Jones\u27 and Bunting\u27s poems. Chapter 4 explores how Eliot\u27s synchronic and cyclic vision of time and cultural history is revitalized in the region-bound poetic adventure of The Anathemata and Briggflatts. The final chapter, reflecting upon the troublesome heritage of Eliot\u27s self-exegesis, analyzes specific cultural impulses and textual strategies of Jones\u27 and Bunting\u27s annotation. This interactive exploration of Jones\u27 and Bunting\u27s aesthetics testifies that their sequences - contrary to many a critical opinion - live up to and beyond the daring of Eliot\u27s radical poetic statement

Landscape-use optimisation with regards to the groundwater resources protection in mountain hardrock areas, LOWRGREP

Synthesis of work performed during the European Project LOWRGREPThis report assesses the degree of interference of human activities with the hydrosphere in mountain-zones, all located in hard-rock areas of different countries in the European Union. Each of the test-regions has a specific degree of protection: from regions with very few inhabitants and very low human impact, to regions submitted to a strong anthropogenic impact. The investigations focused on the changes in water quality and on the simulation of various alternatives leading to optimum landscape-use from the point of view of water-management. The project's own Geographic Information System was used to fulfil the following objective: present all the obtained knowledge and analyse all the data in user-friendly form (maps of water vulnerability) and make this knowledge available for potential users with, for instance, the creation and use of a web site. A simulation tool has been developed which facilitates the assessment of the impact of landscape-use on the water budget of the catchment. In all the areas investigated chloride is present, only in winter and very close to roads. Another result of this work is the decreasing impact on water of sulphur and sulphuric compounds in Germany and in the Czech Republic, while the nitrogen impact is increasing. Recommendations concerning the landscape-use presented for all the regions in particular for good practices in agricultur

Amplified Cold Transduction in Native Nociceptors by M-Channel Inhibition

Topically applied camphor elicits a sensation of cool, but nothing is known about how it affects cold temperature sensing. We found that camphor sensitizes a subpopulation of menthol-sensitive native cutaneous nociceptors in the mouse to cold, but desensitizes and partially blocks heterologously expressed TRPM8(transient receptor potential cation channel subfamily M member 8). In contrast, camphor reduces potassium outward currents in cultured sensory neurons and, in cold nociceptors, the cold-sensitizing effects of camphor and menthol are additive. Using a membrane potential dye-based screening assay and heterologously expressed potassium channels, we found that the effects of camphor are mediated by inhibition of K(v)7.2/3 channels subtypes that generate the M-current in neurons. In line with this finding, the specific M-current blocker XE991 reproduced the cold-sensitizing effect of camphor in nociceptors. However, the M-channel blocking effects of XE991 and camphor are not sufficient to initiate cold transduction but require a cold-activated inward current generated by TRPM8. The cold-sensitizing effects of XE991 and camphor are largest in high-threshold cold nociceptors. Low-threshold corneal cold thermoreceptors that express high levels of TRPM8 and lack potassium channels are not affected by camphor. We also found that menthol-like camphor-potently inhibits K(v)7.2/3 channels. The apparent functional synergism arising from TRPM8 activation and M-current block can improve the effectiveness of topical coolants and cooling lotions, and may also enhance TRPM8-mediated analgesia

Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target

Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment. Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the tumor microenvironment and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that tumor microenvironment is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including anti-tumor agents with those targeting stromal cell metabolism, anti-angiogenic drugs and/or immunotherapy are being developed as promising therapeutics.Mª Carmen Ocaña is recipient of a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sport. Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Harmonizing Microstructures and Enhancing Mechanical Resilience: Novel Powder Metallurgy Approach for Zn-Mg Alloys

Zinc alloys are recognised for their excellent biocompatibility and favourable corrosion rates, making them suitable for bioabsorbable implants. However, their mechanical properties necessitate improvement to fulfil the rigorous requirements of biomedical applications. This research focuses on engineering pseudo-harmonic structures within zinc alloys through a comprehensive method combining mechanical alloying, spark plasma sintering, and hot extrusion techniques. This fabrication process results in a composite material characterised by a soft core surrounded by a continuous, three-dimensional, ultrafine-grained hard shell. The experiment involved blending pure zinc with Zn-1Mg alloy powder, leading to the formation of both ductile zinc and fine-grained Zn-1Mg regions. While the Mg2Zn11 intermetallic phase was found to enhance the alloy's mechanical strength, the presence of oxide shells adversely affected the material's properties. The elimination of these shells via hot extrusion markedly improved the alloy's tensile strength, reaching an average value of tensile strength of 333 MPa. This study provides significant insights into the material engineering of zinc-based alloys for biodegradable implant applications, demonstrating a viable approach to optimising their mechanical performance.Comment: paper preprin

Mitochondrial respiratory complex II is altered in renal carcinoma

Background: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. Methods: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. Results: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. Conclusions: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions

Groundwater dependent ecosystems. Part I: Hydroecological status and trends

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The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models

Recent research has shown that mtDNA-deficient cancer cells (ρ0 cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1KO) mice markedly delayed tumor formation after grafting ρ0 cancer cells. Miro1KO mice with fluorescently labeled mitochondria revealed that this delay was due to hindered mitochondrial transfer from the tumor stromal cells to grafted B16 ρ0 cells, which impeded recovery of mitochondrial respiration and tumor growth. Miro1KO led to the perinuclear accumulation of mitochondria and impaired mobility of the mitochondrial network. In vitro experiments revealed decreased association of mitochondria with microtubules, compromising mitochondrial transfer via tunneling nanotubes (TNTs) in mesenchymal stromal cells. Here we show the role of Miro1 in horizontal mitochondrial transfer in mouse melanoma models in vivo and its involvement with TNTs

The core domain as the force sensor of the yeast mechanosensitive TRP channel

Stretch-activated conductances are commonly encountered in careful electric recordings. Those of known proteins (TRP, MscL, MscS, K2p, Kv, etc.) all share a core, which houses the ion pathway and the gate, but no recognizable force-sensing domain. Like animal TRPs, the yeast TRPY1 is polymodal, activated by stretch force, Ca2+, etc. To test whether its S5–S6 core senses the stretch force, we tried to uncouple it from the peripheral domains by strategic peptide insertions to block the covalent core–periphery interactions. Insertion of long unstructured peptides should distort, if not disrupt, protein structures that transmit force. Such insertions between S6 and the C-terminal tail largely removed Ca2+ activation, showing their effectiveness. However, such insertions as well as those between S5 and the N-terminal region, which includes S1–S4, did not significantly alter mechanosensitivity. Even insertions at both locations flanking the S5–S6 core did not much alter mechanosensitivity. Tryptophan scanning mutations in S5 were also constructed to perturb possible noncovalent core–periphery contacts. The testable tryptophan mutations also have little or no effects on mechanosensitivity. Boltzmann fits of the wild-type force–response curves agree with a structural homology model for a stretch-induced core expansion of ∼2 nm2 upon opening. We hypothesize that membrane tension pulls on S5–S6, expanding the core and opening the TRPY1 gate. The core being the major force sensor offers the simplest, though not the only, explanation of why so many channels of disparate designs are mechanically sensitive. Compared with the bacterial MscL, TRPY1 is much less sensitive to force, befitting a polymodal channel that relies on multiple stimuli