Mechanistic insights into RAD51-associated protein 1 (RAD51AP1) action in homologous DNA repair

Homologous recombination catalyzed by the RAD51 recombinase is essential for maintaining genome integrity upon the induction of DNA double strand breaks and other DNA lesions. By enhancing the recombinase activity of RAD51, RAD51AP1 (RAD51-associated protein 1) serves a key role in homologous recombination-mediated chromosome damage repair. We show here that RAD51AP1 harbors two distinct DNA binding domains that are both needed for maximal protein activity under physiological conditions. We have finely mapped the two DNA binding domains in RAD51AP1 and generated mutant variants that are impaired in either or both of the DNA binding domains. Examination of these mutants reveals that both domains are indispensable for RAD51AP1 function in cells. These and other results illuminate the mechanistic basis of RAD51AP1 action in homologous DNA repair.

Indonesian LIS professionals’ understanding of Library 2.0 : a pilot study

The literature around Library 2.0 remains largely theoretical with few empirically studies and is particularly limited in developing countries such as Indonesia. This study addresses this gap and aims to provide information about the current state of knowledge on Indonesian LIS professionals’ understanding of Library 2.0. The researchers used qualitative and quantitative approaches for this study, asking thirteen closed- and open-ended questions in an online survey. The researchers used descriptive and in vivo coding to analyze the responses. Through their analysis, they identified three themes: technology, interactivity, and awareness of Library 2.0. Respondents demonstrated awareness of Library 2.0 and a basic understanding of the roles of interactivity and technology in libraries. However, overreliance on technology used in libraries to conceptualize Library 2.0 without an emphasis on its core characteristics and principles could lead to the misalignment of limited resources. The study results will potentially strengthen the research base for Library 2.0 practice, as well as inform LIS curriculum in Indonesia so as to develop practitioners who are able to adapt to users’ changing needs and expectations. It is expected that the preliminary data of this study could be used to design a much larger and more complex future research project in this area.

Human single-stranded DNA binding protein 1 (hSSB1/NABP2) is required for the stability and repair of stalled replication forks

Aberrant DNA replication is a primary cause of mutations that are associated with pathological disorders including cancer. During DNA metabolism, the primary causes of replication fork stalling include secondary DNA structures, highly transcribed regions and damaged DNA. The restart of stalled replication forks is critical for the timely progression of the cell cycle and ultimately for the maintenance of genomic stability. Our previous work has implicated the single-stranded DNA binding protein, hSSB1/NABP2, in the repair of DNA double-strand breaks via homologous recombination. Here, we demonstrate that hSSB1 relocates to hydroxyurea (HU)-damaged replication forks where it is required for ATR and Chk1 activation and recruitment of Mre11 and Rad51. Consequently, hSSB1-depleted cells fail to repair and restart stalled replication forks. hSSB1 deficiency causes accumulation of DNA strand breaks and results in chromosome aberrations observed in mitosis, ultimately resulting in hSSB1 being required for survival to HU and camptothecin. Overall, our findings demonstrate the importance of hSSB1 in maintaining and repairing DNA replication forks and for overall genomic stability.

Chemotherapeutic compounds targeting the DNA double-strand break repair pathways : the good, the bad, and the promising

The repair of DNA double-strand breaks (DSBs) is a critical cellular mechanism that exists to ensure genomic stability. DNA DSBs are the most deleterious type of insult to a cell’s genetic material and can lead to genomic instability, apoptosis, or senescence. Incorrectly repaired DNA DSBs have the potential to produce chromosomal translocations and genomic instability, potentially leading to cancer. The prevalence of DNA DSBs in cancer due to unregulated growth and errors in repair opens up a potential therapeutic window in the treatment of cancers. The cellular response to DNA DSBs is comprised of two pathways to ensure DNA breaks are repaired: homologous recombination and non-homologous end joining. Identifying chemotherapeutic compounds targeting proteins involved in these DNA repair pathways has shown promise as a cancer therapy for patients, either as a monotherapy or in combination with genotoxic drugs. From the beginning, there have been a number of chemotherapeutic compounds that have yielded successful responses in the clinic, a number that have failed (CGK-733 and iniparib), and a number of promising targets for future studies identified. This review looks in detail at how the cell responds to these DNA DSBs and investigates the chemotherapeutic avenues that have been and are currently being explored to target this repair process.

Conceptualising the learning organisation : creating a maturity framework to develop a shared understanding of the library's role in literacy and learning

Although they sit outside the formal education sector, libraries are intrinsically centres of learning where people can engage with knowledge and ideas and acquire the literacy skills that are essential for active participation in an increasingly digital society. In Australia, National and State Libraries Australasia (NSLA) has acknowledged the need to not only better understand the general concept of the library as a learning institution, but also to help the individual NSLA libraries specifically identify their capabilities in this arena. The NSLA Literacy and Learning project aimed to improve the members' organisational comprehension and practice as learning institutions and to help them conceptualise their ability to deliver literacy and learning programmes that will benefit their staff and their communities. The NSLA concept of learning institution encompassed two discrete lenses: the internal lens of the library's own organisational understanding and practice, and the external lens of the clients who engage in the literacy and learning programmes delivered by the library. The ultimate goal was to develop a matrix which could enable libraries to assess their perceived levels of maturity as learning institutions along a continuum of emerging to active capabilities. The matrix should also serve as a tool for shared understanding about the NSLA's own strategic directions in the literacy and learning space. This case study documents the evolving process of developing a learning institution maturity framework for libraries that considers individual, team and organisational learning, as well as clients' interactions with the organisation, with the goal of producing a framework that has the potential to measure the value of learning and growth in both the library's staff and the library's communities

The role of interpersonal influence in budget decision making: The Canadian public library experience

This study determined factors which influenced Canadian provincial (state) politicians when making funding decisions for public libraries. Using the case study methodology, Canadian provincial/state-level funding for public libraries in the 2009-2010 fiscal year was examined. The data were analyzed to determine whether Cialdini’s theory of influence and specifically any of the six tactics of influence (i.e., commitment and consistency, authority, liking, social proof, scarcity, and reciprocity) were instrumental in these budgetary decision-making processes. Findings show the principles of “authority,” “consistency and commitment,” and “liking” were relevant, and that “liking” was especially important to these decisions.

Integrated analysis of epigenomic and genomic changes by DNA methylation dependent mechanisms provides potential novel biomarkers for prostate cancer

Epigenetic silencing mediated by CpG methylation is a common feature of many cancers. Characterizing aberrant DNA methylation changes associated with tumor progression may identify potential prognostic markers for prostate cancer (PCa). We treated two PCa cell lines, 22Rv1 and DU-145 with the demethylating agent 5-Aza 2’–deoxycitidine (DAC) and global methylation status was analyzed by performing methylation-sensitive restriction enzyme based differential methylation hybridization strategy followed by genome-wide CpG methylation array profiling. In addition, we examined gene expression changes using a custom microarray. Gene Set Enrichment Analysis (GSEA) identified the most significantly dysregulated pathways. In addition, we assessed methylation status of candidate genes that showed reduced CpG methylation and increased gene expression after DAC treatment, in Gleason score (GS) 8 vs. GS6 patients using three independent cohorts of patients; the publically available The Cancer Genome Atlas (TCGA) dataset, and two separate patient cohorts. Our analysis, by integrating methylation and gene expression in PCa cell lines, combined with patient tumor data, identified novel potential biomarkers for PCa patients. These markers may help elucidate the pathogenesis of PCa and represent potential prognostic markers for PCa patients.

Untangling the evidence : introducing an empirical model for evidence-based library and information practice

Introduction This research is the first to investigate the experiences of teacher-librarians as evidence-based practice. An empirically derived model is presented in this paper. Method This qualitative study utilised the expanded critical incident approach, and investigated the real-life experiences of fifteen Australian teacher-librarians, through semi-structured interviews and inductive data analysis. Data collection utilised semi-structured interviews, on-site observations, journaling and the rubric for contextual information. These approaches allowed each of the interviewees to tell their own story and provided richness to the data. Analysis The analysis involved two types of data categorisation: binary and thematic. Binary classification was used to identify factual details. Thematic analysis involved categorising the emerging themes. Results An empirically derived model for evidence-based practice was devised and associated critical findings identified. The results demonstrate that evidence-based practice for teacher-librarians is a holistic practice. It is not a linear, step-by-step process. Conclusions This study is significant for teacher-librarians and library and information professionals as it provides new understanding of evidence-based practice.

A participatory library model for university libraries

This research investigated the ways academic libraries are using social media and adopting participatory principles in their programs and services. Using the Grounded Theory method the research developed an empirically derived model for participatory libraries. The research revealed three core categories representing the participatory library: community, empowerment, and experience. The research provides library professionals, researchers and the library community, with a fresh perspective and holistic picture of the contemporary library. The findings can be used to guide the development of participatory libraries in Australia and internationally.