The sensual human nature: a cognitive approach to religious poetry

Sensual experience has traditionally been admitted into religion as a means to convey mystic encounters with divinities. Even the strict Christian dogma gives its consent to the expression of sensual encounters, provided that they can be justified from a religious moral perspective. But the fact is that the use of sensual imagery with a communicative intention seems to have an experientialist base:Any kind of knowledge we have originates from our phenomenological apprehension of the world; and appealing to the motor-sensory domains seems to be the easiest and quickest way to guarantee understanding. Following a cognitive orientation, this paper explores into two samples of religious poetry (San Juan de la Cruz's "Noche Oscura" and G. Herbert's "Love") and shows evidence that meaning conveyance is possible thanks to the use of motor -sensory imagery, which at the same time allows for other more universal readings of the poems

The Challenges and Opportunities of lncRNAs in Ovarian Cancer Research and Clinical Use

[Abstract] Ovarian cancer is one of the most lethal gynecological malignancies worldwide because it tends to be detected late, when the disease has already spread, and prognosis is poor. In this review we aim to highlight the importance of long non-coding RNAs (lncRNAs) in diagnosis, prognosis and treatment choice, to make progress towards increasingly personalized medicine in this malignancy. We review the effects of lncRNAs associated with ovarian cancer in the context of cancer hallmarks. We also discuss the molecular mechanisms by which lncRNAs become involved in cellular physiology; the onset, development and progression of ovarian cancer; and lncRNAs’ regulatory mechanisms at the transcriptional, post-transcriptional and post-translational stages of gene expression. Finally, we compile a series of online resources useful for the study of lncRNAs, especially in the context of ovarian cancer. Future work required in the field is also discussed along with some concluding remarks.This work was funded by Plan Estatal I + D + I by the Instituto de Salud Carlos III (ISCIII, Spain) under grant agreement AES number PI18/01714, cofounded by Fondo Europeo de Desarrollo Regional-FEDER (The European Regional Development Fund-ERDF) “A way of Making Europe,” and by Xunta de Galicia (Consolidación Grupos Referencia Competitiva contract number ED431C 2016-012). M.S.M. was funded by a predoctoral fellowship from FPU-2018 (Spain)Xunta de Galicia; ED431C 2016-01

Saints and Birds: la renovación de una escena medieval en la poesía de Seamus Heaney

El poeta irlandés Seamus Heaney recupera la escena del ermitaño como motivo poético a fin de explorar la relación del hombre con la naturaleza y con el hecho religioso. En el presente artículo estudiaremos dos poemas de autoría heaneyana que comparten una es- tructura inicial basada en el motivo ermitaño: “Saint Francis and the Birds” (1966) y “Saint Kevin and the Blackbird” (1996). El análisis se llevará a cabo siguiendo una orientación poético cognitiva basada fundamentalmente en el modelo de los espacios mentales de Gilles Fauconnier y en la teoría de Eve Sweetser sobre percepción sensorial y conceptualización.Irish poet Seamus Heaney seems to use a traditionally Irish hermit situation as a poetic motif in order to explore man’s relation with nature and religion. Following a cognitive orientation, we will discuss two poems by Seamus Heaney which have a common initial structure based on the hermit motif: “Saint Francis and the Birds” (1966) and “Saint Kevin and the Blackbird” (1996). The poems will be approached through a cognitive poetics perspective mainly based on Gilles Fauconnier’s mental space model and Eve Sweetser’s findings on sensory perception and conceptualisation

Candidiasis by Candida glabrata, Candida nivariensis and Candida bracarensis in Galleria mellonella: Virulence and Therapeutic Responses to Echinocandins

Candida albicans is the major etiological agent of invasive candidiasis but the increasing prevalence of emerging species of Candida, such as Candida glabrata and phylogenetically closely related species, Candida nivariensis and Candida bracarensis, requires special attention. Differences in virulence among these species and their therapeutic responses using in vivo non-mammalian models are scarcely analysed. The aim of this study was analyse the survival of G. mellonella and host-pathogen interactions during infection by C. glabrata, C. nivariensis and C. bracarensis. Moreover, therapeutic responses to echinocandins were also assessed in the G. mellonella model of candidiasis. These three species produced lethal infection in G. mellonella; C. glabrata was the most virulent species and C. bracarensis the less. Haemocytes of G. mellonella phagocytised C. bracarensis cells more effectively than those of the other two species. Treatment with caspofungin and micafungin was most effective to protect larvae during C. glabrata and C. nivariensis infections while anidulafungin was during C. bracarensis infection. The model of candidiasis in G. mellonella is simple and appropriate to assess the virulence and therapeutic response of these emerging Candida species. Moreover, it successfully allows for detecting differences in the immune system of the host depending on the virulence of pathogens.This research was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2017-86188-P and PID2020-117983RB-I00] and from the Consejería de Educación, Universidades e Investigación of Gobierno Vasco-Eusko Jaurlaritza [GIC15/78 IT-990-16]. Ainara Hernando-Ortiz was funded by Ph.D. grants from the University of the Basque Country (PIF 16/39)

Antimicrobial Peptides with Anti-Candida Activity

[EN] Mycoses are accountable for millions of infections yearly worldwide. Invasive candidiasis is the most usual, presenting a high morbidity and mortality. Candida albicans remains the prevalent etiologic agent, but the incidence of other species such as Candida parapsilosis, Candida glabrata and Candida auris keeps increasing. These pathogens frequently show a reduced susceptibility to commonly used antifungal drugs, including polyenes, triazoles and echinocandins, and the incidence of emerging multi-drug-resistant strains of these species continues to increase. Therefore, the need to search for new molecules that target these pathogenic species in a different manner is now more urgent than ever. Nature is an almost endless source of interesting new molecules that could meet this need. Among these molecules, antimicrobial peptides, present in different sources in nature, possess some advantages over conventional antifungal agents, even with their own drawbacks, and are considered as a promising pharmacological option against a wide range of microbial infections. In this review, we describe 20 antimicrobial peptides from different origins that possess an activity against Candida.This research was funded by the Spanish Ministry of Science and Innovation (PID2020-117983RB-I00) and by the Consejería de Educación, Universidades e Investigación of Gobierno Vasco-Eusko Jaurlaritza (IT1607-22). A.P.-R. was funded by a Ph.D. grant from the University of the Basque Country (PIF17/167)

In Vitro Interaction and Killing-Kinetics of Amphotericin B Combined with Anidulafungin or Caspofungin against Candida auris

Treatment of invasive infections caused by Candida auris is challenging due to the limited therapeutic options. The combination of antifungal drugs may be an interesting and feasible approach to be investigated. The aim of this study was to examine the in vitro activity of amphotericin B in combination with anidulafungin or caspofungin against C. auris. In vitro static time–kill curve experiments were conducted for 48 h with different combinations of amphotericin B with anidulafungin or caspofungin against six blood isolates of C. auris. The antifungal activity of 0.5 mg/L of amphotericin B was limited against the six isolates of C. auris. Similarly, echinocandins alone had a negligible effect, even at the highest tested concentrations. By contrast, 1 mg/L of amphotericin B showed fungistatic activity. Synergy was rapidly achieved (8 h) with 0.5 mg/L of amphotericin B plus 2 mg/L of anidulafungin or caspofungin. These combinations lead to a sustained fungistatic effect, and the fungicidal endpoint was reached against some C. auris isolates. Additionally, ≥0.5 mg/L of either of the two echinocandins with 1 mg/L of amphotericin B resulted in fungicidal effect against all C. auris isolates. In conclusion, combinations of amphotericin B with anidulafungin or caspofungin provided greater killing with a lower dose requirement for amphotericin B compared to monotherapy, with synergistic and/or fungicidal outcomes.This research was funded by Consejería de Educación, Universidades e Investigación of Gobierno Vasco-Eusko Jaurlaritza, GIC15/78 IT-990-16 and by FIS, Spain, PI17/01538. U.C. was funded by a Ph.D. grant from the University of the Basque Country, PIF 17/266

The HMGB1-2 Ovarian Cancer Interactome: the Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response

[Abstract] High mobility group box B (HMGB) proteins are overexpressed in different types of cancers such as epithelial ovarian cancers (EOC). We have determined the first interactome of HMGB1 and HMGB2 in epithelial ovarian cancer (the EOC-HMGB interactome). Libraries from the SKOV-3 cell line and a primary transitional cell carcinoma (TCC) ovarian tumor were tested by the Yeast Two Hybrid (Y2H) approach. The interactome reveals proteins that are related to cancer hallmarks and their expression is altered in EOC. Moreover, some of these proteins have been associated to survival and prognosis of patients. The interaction of MIEN1 and NOP53 with HMGB2 has been validated by co-immunoprecipitation in SKOV-3 and PEO1 cell lines. SKOV-3 cells were treated with different anti-tumoral drugs to evaluate changes in HMGB1, HMGB2, MIEN1 and NOP53 gene expression. Results show that combined treatment of paclitaxel and carboplatin induces a stronger down-regulation of these genes in comparison to individual treatments. Individual treatment with paclitaxel or olaparib up-regulates NOP53, which is expressed at lower levels in EOC than in non-cancerous cells. On the other hand, bevacizumab diminishes the expression of HMGB2 and NOP53. This study also shows that silencing of these genes affects cell-viability after drug exposure. HMGB1 silencing causes loss of response to paclitaxel, whereas silencing of HMGB2 slightly increases sensitivity to olaparib. Silencing of either HMGB1 or HMGB2 increases sensitivity to carboplatin. Lastly, a moderate loss of response to bevacizumab is observed when NOP53 is silenced.This work has been funded by the Projects Nº PI14/01031 and PI18/01714, integrated in the National Plan for Scientific Research, Development and Technological Innovation 2013–2016 of the ISCIII- General Subdirection of Assesment and Promotion of the Research – European Regional Development Fund (FEDER) “A way of making Europe”. Funding is also acknowledged from Xunta de Galicia (Consolidación Grupos Referencia Competitiva Contract no. ED431C 2016–012). Aida Barreiro-Alonso was funded by a predoctoral fellowship from Xunta de Galicia-2013 (Spain) cofinanced by FEDERXunta de Galicia; ED431C 2016–01

Postantifungal Effect of Antifungal Drugs against Candida: What Do We Know and How Can We Apply This Knowledge in the Clinical Setting?

The study of the pharmacological properties of an antifungal agent integrates the drug pharmacokinetics, the fungal growth inhibition, the fungicidal effect and the postantifungal activity, laying the basis to guide optimal dosing regimen selection. The current manuscript reviews concepts regarding the postantifungal effect (PAFE) of the main classes of drugs used to treat Candida infections or candidiasis. The existence of PAFE and its magnitude are highly dependent on both the fungal species and the class of the antifungal agent. Therefore, the aim of this article was to compile the information described in the literature concerning the PAFE of polyenes, azoles and echinocandins against the Candida species of medical interest. In addition, the mechanisms involved in these phenomena, methods of study, and finally, the clinical applicability of these studies relating to the design of dosing regimens were reviewed and discussed. Additionally, different factors that could determine the variability in the PAFE were described. Most PAFE studies were conducted in vitro, and a scarcity of PAFE studies in animal models was observed. It can be stated that the echinocandins cause the most prolonged PAFE, followed by polyenes and azoles. In the case of the triazoles, it is worth noting the inconsistency found between in vitro and in vivo studiesThe research group was funded by the Consejería de Educación, Universidades e Investigación of Gobierno Vasco-Eusko Jaurlaritza (GIC15/78 IT-990-16/IT1607-22) and by the Spanish Ministry of Science and Innovation (PID2020-117983RB-I00)

In Vitro Pharmacokinetic/Pharmacodynamic Modelling and Simulation of Amphotericin B against Candida auris

The aims of this study were to characterize the antifungal activity of amphotericin B against Candida auris in a static in vitro system and to evaluate different dosing schedules and MIC scenarios by means of semi-mechanistic pharmacokinetic/pharmacodynamic (PK/PD) modelling and simulation. A two-compartment model consisting of a drug-susceptible and a drug-resistant subpopulation successfully characterized the time-kill data and a modified Emax sigmoidal model best described the effect of the drug. The model incorporated growth rate constants for both subpopulations, a death rate constant and a transfer constant between both compartments. Additionally, the model included a parameter to account for the delay in growth in the absence or presence of the drug. Amphotericin B displayed a concentration-dependent fungicidal activity. The developed PK/PD model was able to characterize properly the antifungal activity of amphotericin B against C. auris. Finally, simulation analysis revealed that none of the simulated standard dosing scenarios of 0.6, 1 and 1.5 mg/kg/day over a week treatment showed successful activity against C. auris infection. Simulations also pointed out that an MIC of 1 mg/L would be linked to treatment failure for C. auris invasive infections and therefore, the resistance rate to amphotericin B may be higher than previously reported.This research was funded by Consejería de Educación, Universidades e Investigación of Gobierno Vasco-Eusko Jaurlaritza, GIC15/78 IT-990-16 and by FIS, Spain, PI17/01538. U.C. was funded by a Ph.D. grant from the University of the Basque Country, PIF 17/266