Cooperative report of #vBIB20 – the virtual conference of BIB and TIB about library topics (May 26-28 2020)

Nach der Covid-19-bedingten Absage des 109. Deutschen Bibliothekartags, der von 26. bis 29. Mai 2020 in Hannover stattfinden hätte sollen, wurde vom Berufsverband Information Bibliothek (BIB) und von TIB – Leibniz-Informationszentrum Technik und Naturwissenschaften und Universitätsbibliothek mit #vBIB20 zwischen 26. und 28. Mai 2020 kurzfristig eine virtuelle Konferenz rund um bibliothekarische Themen organisiert. Im vorliegenden kooperativen Bericht werden Vorträge zu den Themenbereichen Publikationswesen, Open Access, Forschungsdatenmanagement, Bibliothekstatistik und NS-Provenienzforschung vorgestellt.After the cancellation of the 109. Deutscher Bibiothekartag (109th German Librarian Day), which should have taken place in Hannover from Mai 26th to 29th 2020, the Berufsverband Infromation Bibliothek (BIB) and the TIB – Leibniz Information Centre for Science and Technology University Library – together with #vBIB20 organised at short notice a virtual conference about library topics from May 26th to 28th 2020. In this cooperative report lectures are presented about publication system, Open Access, research data management, library statistics and provenance research

XAB2 promotes Ku eviction from single-ended DNA double-strand breaks independently of the ATM kinase

Replication-associated single-ended DNA double-strand breaks (seDSBs) are repaired predominantly through RAD51-mediated homologous recombination (HR). Removal of the non-homologous end-joining (NHEJ) factor Ku from resected seDSB ends is crucial for HR. The coordinated actions of MRE11-CtIP nuclease activities orchestrated by ATM define one pathway for Ku eviction. Here, we identify the pre-mRNA splicing protein XAB2 as a factor required for resistance to seDSBs induced by the chemotherapeutic alkylator temozolomide. Moreover, we show that XAB2 prevents Ku retention and abortive HR at seDSBs induced by temozolomide and camptothecin, via a pathway that operates in parallel to the ATM-CtIP-MRE11 axis. Although XAB2 depletion preserved RAD51 focus formation, the resulting RAD51-ssDNA associations were unproductive, leading to increased NHEJ engagement in S/G2 and genetic instability. Overexpression of RAD51 or RAD52 rescued the XAB2 defects and XAB2 loss was synthetically lethal with RAD52 inhibition, providing potential perspectives in cancer therapy.publishedVersio

Identification of DNA damage response genes as targets for personalized treatment of Glioblastoma through RNA interference screens

Despite surgical resection and genotoxic treatment with ionizing radiation and the DNA alkylating agent temozolomide (TMZ), glioblastoma (GBM) remains one of the most lethal cancers, due in part to the action of DNA repair factors that drive resistance and lead to tumor relapse. Important features of these mechanisms include the inherent redundancy and complexity of the many DNA repair pathways activated as part of the DNA damage response (DDR). One important DDR factor is encoded by the O-6-methylguanine-DNA methyltransferase (MGMT) gene whose epigenetic silencing is a strong predictive marker for favorable outcome in GBM patients treated with TMZ. However, even patients displaying MGMT promoter methylation succumb to tumor relapse, indicating that other DNA repair mechanisms promote resistance to the treatment. The main aim of this work was to identify essential DDR factors that support GBM cell survival under TMZ treatment in order to provide novel targets and thus, novel insights into drug combinations that could overcome GBM chemoresistance. The strategy to achieve this goal was to use well-characterized GBM cell lines in focused loss of function shRNA screens performed under different conditions. Indeed, screens were designed to uncover DDR genes that are essential for GBM cells i) under normal conditions, ii) under TMZ treatment, iii) and under TMZ treatment in MGMT negative contexts. Pooled shRNAs targeting more than 500 DDR genes were introduced into GBM cells reflecting two clinically-relevant GBM contexts: a MGMT-positive context using MGMT-expressing cells and a negative one, using cell lines in which MGMT was depleted hrough pharmacological inhibition or RNA interference. Potential DDR targets that could sensitize GBM cells to TMZ have been identified and some of them validated. Surprisingly, some of these targets are not only involved in pathways that are commonly known to drive TMZ resistance (i.e. Double strand break repair, Direct repair), but also in repair pathways such as transcription-coupled nucleotide excision repair (TC-NER) or the early steps of the Fanconi Anemia pathway (FA). While components of the early FA pathway might be attractive targets especially in MGMT-negative contexts, it may be interesting to target factors involved in the early steps of the TC-NER to sensitize MGMTpositive cells to TMZ. So in addition to its predictive and prognostic value, MGMT might be a relevant stratification marker to treat patients in a personalized way. Supporting this hypothesis, the screen analyses revealed that the curative inhibition of some genes in combination with TMZ treatment might turn to be deleterious depending on MGMT expression level. One of the promising target will be further investigated in vitro as well as in vivo to elucidate the molecular mechanisms by which this gene operates to confer cellular resistance to TMZ. This study opens up new horizons for combinatorial therapies and hopefully, will be used to improve therapeutical approaches, particularly for MGMT-positive GBM patients, who currently do not benefit at all from chemotherapy

Universitätsbibliothek der Medizinischen Universität Wien - größte Medizinbibliothek Österreichs : Hybridbibliothek als Zukunftskonzept

The today's Medical University Library was established as Faculty Library of the Vienna University Library in 1986 and serves till now as the largest Medical Library in Austria. The Main Library is located in the Vienna General Hospital (University hospitals). During 1994 and 2003 it became the Austrian Central Library for Medicine. Since 2004 University Library of the newly founded Medical University of Vienna supplies literature and information for 8500 Students, 1800 scientists and 1600 doctors. The article describes the Library's participation on projects of the Austrian Library Consortium and the Austrian Cooperation for E-media. It specifies the offers and use of the digital library (professional databases, electronic journals, document delivery, e-books) but also the website and the "Van Swieten"-Blog which are the information and communication platforms of the University Library. The next part shows the supply of traditional library which consists of the Clinical Library, the Textbook Collection and the Students Reading Room. We report also on the Library for the History of Medicine, their precious medical historical holdings and their current activities connected with the digitalization of the card index. The library's activities to the "Medizin Curriculum Wien", trainings and tours are told in the chapter about the Teaching Library but also the Information Retrieval Service and the activities due to training, placement and projects of librarians. Another part speaks about the special activities in international projects like "subito", "E-books on demand" and a gateway for PDAs. The Medical University Library was the first Austrian library who used the LinkOut function of PubMed. The library works on a project of "Wiedergutmachung" (NS-Provenienzforschung) and a very ambitious Weblog for the remembrance of the displaced professors at the medical faculty of the University of Vienna in 1938. The last chapter presents a development plan of the prospective activities of the University Library. To complete the essay the characteristic factors, addresses and an extensive bibliography about the development of the library is added

DNA repair mechanisms and their clinical impact in glioblastoma.

peer reviewedDespite surgical resection and genotoxic treatment with ionizing radiation and the DNA alkylating agent temozolomide, glioblastoma remains one of the most lethal cancers, due in great part to the action of DNA repair mechanisms that drive resistance and tumor relapse. Understanding the molecular details of these mechanisms and identifying potential pharmacological targets have emerged as vital tasks to improve treatment. In this review, we introduce the various cellular systems and animal models that are used in studies of DNA repair in glioblastoma. We summarize recent progress in our knowledge of the pathways and factors involved in the removal of DNA lesions induced by ionizing radiation and temozolomide. We introduce the therapeutic strategies relying on DNA repair inhibitors that are currently being tested in vitro or in clinical trials, and present the challenges raised by drug delivery across the blood brain barrier as well as new opportunities in this field. Finally, we review the genetic and epigenetic alterations that help shape the DNA repair makeup of glioblastoma cells, and discuss their potential therapeutic impact and implications for personalized therapy

University Library of the Medical University Vienna - largest Medical Library of Austria: Hybrid Library as a concept for the future

The today's Medical University Library was established as Faculty Library of the Vienna University Library in 1986 and serves till now as the largest Medical Library in Austria. The Main Library is located in the Vienna General Hospital (University hospitals). During 1994 and 2003 it became the Austrian Central Library for Medicine. Since 2004 University Library of the newly founded Medical University of Vienna supplies literature and information for 8500 Students, 1800 scientists and 1600 doctors. The article describes the Library's participation on projects of the Austrian Library Consortium and the Austrian Cooperation for E-media. It specifies the offers and use of the digital library (professional databases, electronic journals, document delivery, e-books) but also the website and the "Van Swieten"-Blog which are the information and communication platforms of the University Library. The next part shows the supply of traditional library which consists of the Clinical Library, the Textbook Collection and the Students Reading Room. We report also on the Library for the History of Medicine, their precious medical historical holdings and their current activities connected with the digitalization of the card index. The library's activities to the "Medizin Curriculum Wien", trainings and tours are told in the chapter about the Teaching Library but also the Information Retrieval Service and the activities due to training, placement and projects of librarians. Another part speaks about the special activities in international projects like "subito", "E-books on demand" and a gateway for PDAs. The Medical University Library was the first Austrian library who used the LinkOut function of PubMed. The library works on a project of "Wiedergutmachung" (NS-Provenienzforschung) and a very ambitious Weblog for the remembrance of the displaced professors at the medical faculty of the University of Vienna in 1938. The last chapter presents a development plan of the prospective activities of the University Library. To complete the essay the characteristic factors, addresses and an extensive bibliography about the development of the library is added.Die heutige Universitätsbibliothek der Medizinischen Universität Wien wurde 1986 als Fakultätsbibliothek der Universität Wien gegründet und fungiert seit damals als größte Medizinbibliothek Österreichs. Die Hauptbibliothek befindet sich im Allgemeinen Krankenhaus der Stadt Wien (Universitätskliniken). Zwischen 1994 und 2003 wurde sie die Österreichische Zentralbibliothek für Medizin. Seit 2004 ist sie als Universitätsbibliothek der neu gegründeten Medizinischen Universität Wien für die Literatur- und Informationsversorgung von 8500 Studierenden, 1800 Forschern und 1600 Ärzten zuständig. Im Beitrag wird zunächst die Teilnahme der Universitätsbibliothek an Projekten des Österreichischen Bibliothekenverbundes und an der Kooperation E-Medien Österreich dargestellt. Beschrieben werden auch Angebote und Nutzung der Digitalen Bibliothek (Fachdatenbanken, elektronische Zeitschriften, Dokumentenlieferdienst, elektronische Bücher), sowie Website und Van Swieten Blog als Informations- und Kommunikationsinstrumente der Universitätsbibliothek. Es folgt die Vorstellung der Angebote der traditionellen Bibliothek, bestehend aus der Klinischen Bibliothek, einer Lehrbuchsammlung und einem Studentenlesesaal. Informiert wird über die an der Zweigbibliothek für Geschichte der Medizin untergebrachten wertvollen medizinhistorischen Altbestände und über die aktuellen Maßnahmen zur Digitalisierung der vorhandenen Zettelkataloge. Die Beiträge der Universitätsbibliothek zum Medizin Curriculum Wien, das Angebot an Schulungen und Führungen, die Informationsvermittlungsstelle und die Maßnahmen zur Ausbildung, für Praktika und Projekte werden im Abschnitt über die Teaching Library beschrieben. Vorgestellt werden auch die Spezifika der Universitätsbibliothek. Sie beteiligt sich aktiv an den internationalen Projekten subito und E-Books on Demand, betreibt ein PDA-Portal und nutzt als erste Bibliothek in Österreich die LinkOut-Funktion von PubMed. Die Universitätsbibliothek betreibt seit 2007 ein Projekt zur Wiedergutmachung (NS-Provenienzforschung) und ein ambitioniertes Weblog-Projekt zur Erinnerung an die 1938 von der damaligen Medizinischen Fakultät der Universität Wien vertriebenen Professoren. Im letzten Abschnitt werden jene Abschnitte aus dem aktuellen Entwicklungsplan der Medizinischen Universität Wien vorgestellt, in denen die zukünftige Entwicklung der Universitätsbibliothek skizziert wird. Vervollständigt wird der Beitrag um Kennzahlen, Kontaktadressen und eine ausführliche Bibliographie zur Entwicklung der Bibliothek

RNAi/CRISPR Screens: from a Pool to a Valid Hit

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