Screening Approaches for Targeting Ribonucleoprotein Complexes: A New Dimension for Drug Discovery.

RNA-binding proteins (RBPs) are pleiotropic factors that control the processing and functional compartmentalization of transcripts by binding primarily to mRNA untranslated regions (UTRs). The competitive and/or cooperative interplay between RBPs and an array of coding and noncoding RNAs (ncRNAs) determines the posttranscriptional control of gene expression, influencing protein production. Recently, a variety of well-recognized and noncanonical RBP domains have been revealed by modern system-wide analyses, underlying an evolving classification of ribonucleoproteins (RNPs) and their importance in governing physiological RNA metabolism. The possibility of targeting selected RNA-protein interactions with small molecules is now expanding the concept of protein "druggability," with new implications for medicinal chemistry and for a deeper characterization of the mechanism of action of bioactive compounds. Here, taking SF3B1, HuR, LIN28, and Musashi proteins as paradigmatic case studies, we review the strategies applied for targeting RBPs, with emphasis on the technological advancements to study protein-RNA interactions and on the requirements of appropriate validation strategies to parallel high-throughput screening (HTS) efforts

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033

Bioethics through Literature: Margaret Atwood's Cautionary Tales

Literature has been warning us for a long time about the dangers of uncontrolled techno-science, shedding cautionary light on bioethical issues. In Bioethics Through Literature, Valentina Adami underlines the importance of literature for contemporary bioethical reflection by analyzing Margaret Atwood\u2019s dystopias The Handmaid\u2019s Tale (1985), Oryx and Crake (2003) and The Year of the Flood (2009). In particular, The Handmaid\u2019s Tale provides a framework for discussion on biopower, the female body and the ethics of ARTs (Assisted Reproduction Technologies), while Oryx and Crake and The Year of the Flood offer interesting insights into other bioethical concerns such as ecology and the ethics of genetic engineering

Between Bioethics and Literature: Representations of (post-) human identities in Margaret Atwood's Oryx and Crake and The Year of The Flood

Literature can contribute to bioethical debate in several ways: by enabling us to see cases as embedded in specific human contexts, by enhancing our sensitivity to the narratives of others, and by developing a broader outlook to human identity. Both literature and bioethics are interested in the future of humanity and call attention to the dangers of uncontrolled scientific progress, looking for a balance between the excesses of technophobia on the one hand and technophilia on the other. In a context in which scientists face increasingly difficult ethical choices, novels such as Margaret Atwood\u2019s Oryx and Crake and The Year of the Flood can help us understand what it means to be human, which after all is the ultimate goal of all scientific as well as humanistic endeavors

Bioethical Issues in Margaret Atwood's Narrative

Fin dalla sua nascita, la bioetica ha rappresentato un approccio interdisciplinare in cui filosofia, teologia, diritto, medicina, scienze sociali e umane si fondono per riflettere sulle complesse interazioni tra vita umana e tecno-scienza. L\u2019obiettivo di questo lavoro \ue8 evidenziare il ruolo centrale della letteratura per la riflessione bioetica contemporanea attraverso l\u2019analisi di alcuni romanzi di Margaret Atwood: The Handmaid\u2019s Tale (1985), Oryx and Crake (2003) and The Year of the Flood (2009). In particolare, The Handmaid\u2019s Tale offre numerosi spunti per la discussione di fondamentali temi bioetici quali il biopotere, il corpo femminile e l\u2019etica della riproduzione assistita, mentre Oryx and Crake e The Year of the Flood permettono di analizzare altre questioni bioetiche come l\u2019ecologia e l\u2019etica dell\u2019ingegneria genetica.Since its birth, bioethics has been an interdisciplinary inquiry blending philosophy, theology, law, medicine, the social sciences and the humanities to reflect on the complex interactions of human life and techno-science. The present work aims to underline the central role of literature for contemporary bioethical reflection by analyzing Margaret Atwood\u2019s cautionary novels The Handmaid\u2019s Tale (1985), Oryx and Crake (2003) and The Year of the Flood (2009). In particular, The Handmaid\u2019s Tale provides a framework for discussion on biopower, the female body and the ethics of ARTs (Assisted Reproduction Technologies), while Oryx and Crake and The Year of the Flood allow us to analyze other bioethical concerns, namely ecology and the ethics of genetic engineering

The Role of the Reader in Peter Carey\u2019s and Frank Moorhouse\u2019s 1970s\u2019 Short Stories

This article examines the role of the reader in interpreting Peter Carey's and Frank Moorhouse's 1970s short stories

Culture, Language and Environmental Rights: The Anthropocentrism of English

Through the methodological perspective of ecolinguistics, this paper criticizes the unecological and anthropocentric features of English in order to reveal the manipulation forces at work within language and to create awareness of the relationship between language and the environment. Through examples from United Nations documents, the author underlines how the unecological ideologies entrenched in the structures of the English language influence cultural and legal approaches to environmental rights, which are always seen from a human rights perspective rather than from a \u201cnature rights\u201d perspective

Etica e diritto delle medicine alternative in The Spare Room di Helen Garner

Attraverso l'analisi del romanzo The Spare Room di Helen Garner, il presente saggio esamina il rapporto tra medicina alternativa e convenzionale, le possibili cause e conseguenze dell\u2019incremento nell\u2019uso delle medicine alternative, nonch\ue9 il ruolo e le responsabilit\ue0 dei medici nei confronti dei pazienti che scelgono di utilizzare terapie non convenzional