For this eBook, and the associated Research Topic in Frontiers in Genetics, entitled: ‘Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets’ we have selected 10 papers that each discusses important, yet distinct aspects of the response to DNA damage in normal cells and cancer cells. Using an evolutionary conserved signaling network called the ‘DNA damage response (DDR)’ cells maintain the integrity of their genome, and thus safeguard cellular functioning and the ability to create viably progeny. Initially, the DDR appeared to consist of few linear kinase-driven pathways. However, research over the past decades in model organisms, as well as in the human system has revealed that the DDR is a complex signaling network, wired by multiple parallel pathways and displaying extensive crosstalk. Besides phosphorylation, multiple other post-translational modifications, including ubiquitination and sumoylation, are involved to achieve chromatin remodeling and initiation of DNA repair. Also, rather than being a cell-intrinsic phenomenon, we increasingly appreciate that cell-cell communication is involved. The recognition and repair of DNA damage is essential to maintain normal physiology. Multiple pathological conditions have been attributed to defective DNA repair, most notably accelerated aging, neurodegeneration and cancer. In the context of cancer, through repair of DNA damage or elimination of irreparably damaged cells, the DDR clearly has a tumor-suppressive role. Indeed, many tumor cells show partially inactivated DDR signaling, which allows proliferation in the context of DNA damage-inducing oncogenes. Simultaneously, loss of specific DDR signaling nodes creates a specific dependence of tumor cells on their remaining DDR components, and thus creates therapeutic opportunities. Especially in the context of cancer treatment, numerous targeted agents are under investigation, either to potentiate the cytotoxic effects of chemo-radiotherapy, or to induce synthetic lethality with cancer-specific alterations, with the treatment of BRCA1/2 mutant cancers with PARP1 inhibitors as a prototype example. We have selected four review articles that provide insight into the key components and the wiring of the DDR and DNA repair. Torgovnick and Schumacher review the involvement of DNA repair in the initiation and treatment of cancer, Brinkmann et al., describe the involvement of ubiquitination in DNA damage signaling and Jaiswal and Lindqvist discuss how cell-extrinsic signaling participates in communication of DNA damage to neighboring cells. In addition, Shatneyeva and colleagues review the connection between the cellular response to DNA damage and escape from immune surveillance. Concerning the therapeutic application of targeting the DDR and DNA repair, three articles were included. Krajewska and van Vugt review the wiring of homologous recombination and how this offers therapeutic opportunities. Additionally, Knittel and colleagues describe how genetic loss of the central DDR component ATM in chronic lymphocytic leukemia can be exploited therapeutically by targeting certain parallel DNA repair pathways. Syljuasen and colleagues report on how targeting of the DDR can be used as a therapeutic strategy in lung cancer. Finally, three chapters describe newly identified regulators of the cellular response to DNA damage. Von Morgen et al. describe the R2TP complex, Lezzi and Fanciluuli review the involvement of Che-1/AATF in the DDR, and Ohms and co-authors describe how retrotransposons are at the basis of increased genomic instability. Altogether, these articles describe how defective responses to DNA damage underlie disease - and especially in the context of cancer -can be exploited to better treat disease.
Yeats’s Mask, Yeats Annual No. 19 is a special issue in this renowned research-level series. Fashionable in the age of Wilde, the Mask changes shape until it emerges as Mask in the system of A Vision. Chronologically tracing the concept through Yeats’s plays and those poems written as ‘texts for exposition’ of his occult thought which flowers in A Vision itself (1925 and 1937), the volume also spotlights ‘The Mask before The Mask’ numerous plays including Cathleen Ni-Houlihan, The King’s Threshold, Calvary, The Words upon the Window-pane, A Full Moon in March and The Death of Cuchulain. There are excurses into studies of Yeats’s friendship with the Oxford don and cleric, William Force Stead, his radio broadcasts, the Chinese contexts for his writing of ‘Lapis Lazuli’. His self-renewal after The Oxford Book of Modern Verse, and the key occult epistolary exchange ‘Leo Africanus’, edited from MSS by Steve L. Adams and George Mills Harper, is republished from the elusive Yeats Annual No. 1 (1982). The essays are by David Bradshaw, Michael Cade-Stewart, Aisling Carlin, Warwick Gould, Margaret Mills Harper, Pierre Longuenesse, Jerusha McCormack, Neil Mann, Emilie Morin, Elizabeth Müller and Alexandra Poulain, with shorter notes by Philip Bishop and Colin Smythe considering Yeats’s quatrain upon remaking himself and the pirate editions of The Land of Heart’s Desire. Ten reviews focus on various volumes of the Cornell Yeats MSS Series, his correspondence with George Yeats, and numerous critical studies. Yeats Annual is published by Open Book Publishers in association with the Institute of English Studies, University of London.
Robbery Under Arms is a novel by Thomas Alexander Browne, published under his pseudonym Rolf Boldrewood. It was first published in serialised form by The Sydney Mail between July 1882 and August 1883, then in three volumes in London in 1888. It was edited into a single volume in 1889 as part of Macmillan's Colonial Library series and has not been out of print since. It is considered a classic of Australian colonial literature, along with Marcus Clarke's For the Term of his Natural Life, and has inspired numerous adaptations in film, television and theatre. From Wikipedia (CC BY-SA).
Each time a border is crossed there are cultural, political and social issues to be considered. Applying the metaphor of the ‘border crossing’ from one temporal or spatial territory into another, this book examines the way classic Russian texts have been altered to suit new cinematic environments.In these essays, international scholars examine how political and economic circumstances – from a shifting Soviet political landscape to the perceived demands of American and European markets – have played a crucial role in dictating how filmmakers transpose their cinematic hypertext into a new environment. Rather than focus on the degree of accuracy or fidelity with which these films address their originating texts, this innovative collection explores the role of ideological, political and other cultural pressures that can affect the transformation of literary narratives into cinematic offerings.
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