bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanisms of substrate-controlled ring dynamics and sub-stepping in a nucleic-acid dependent hexameric motor
Authors: Thomsen Nathan D. , Lawson Michael R. , Witkowsky Lea B. , Qu Song , Berger James M. 
Published: August 2016

ABSTRACTRing-shaped hexameric helicases and translocases support essential DNA, RNA, and protein-dependent transactions in all cells and many viruses. How such systems coordinate ATPase activity between multiple subunits to power conformational changes that drive the engagement and movement of client substrates is a fundamental question. Using theE. coliRho transcription termination factor as a model system, we have employed solution and crystallographic structural methods to delineate the range of conformational changes that accompany distinct substrate and nucleotide cofactor binding events. SAXS data show that Rho preferentially adopts an open-ring state in solution, and that RNA and ATP are both required to cooperatively promote ring closure. Multiple closed-ring structures with different RNA substrates and nucleotide occupancies capture distinct catalytic intermediates accessed during translocation. Our data reveal how RNA-induced ring closure templates a sequential ATP-hydrolysis mechanism, provide a molecular rationale for how the Rho ATPase domains distinguishes between distinct RNA sequences, and establish the first structural snapshots of substepping events in a hexameric helicase/translocase.SIGNIFICANCEHexameric, ring-shaped translocases are molecular motors that convert the chemical energy of ATP hydrolysis into the physical movement of protein and nucleic acid substrates. Structural studies of several distinct hexameric translocases have provided insights into how substrates are loaded and translocated; however, the range of structural changes required for coupling ATP turnover to a full cycle of substrate loading and translocation has not been visualized for any one system. Here, we combine low-and high-resolution structural studies of the Rho helicase, defining for the first time the ensemble of conformational transitions required both for substrate loading in solution and for substrate movement by a processive hexameric translocase.
Accurate eQTL prioritization with an ensemble-based framework
Authors: Zeng Haoyang , Edwards Matthew D. , Guo Yuchun , Gifford David K. 
Published: August 2016

AbstractExpression quantitative trait loci (eQTL) analysis links sequence variants with gene expression change and serves as a successful approach to fine-map variants causal for complex traits and understand their pathogenesis. In this work, we present an ensemble-based computational framework, EnsembleExpr, for eQTL prioritization. When trained on data from massively parallel reporter assays (MPRA), EnsembleExpr accurately predicts reporter expression levels from DNA sequence and identifies sequence variants that exhibit significant allele-specific reporter expression. This framework achieved the best performance in the “eQTL-causal SNPs” open challenge in the Fourth Critical Assessment of Genome Interpretation (CAGI 4). We envision EnsembleExpr to be a powerful resource for interpreting non-coding regulatory variants and prioritizing disease-associated mutations for downstream validation.
Ligand-induced and small molecule control of substrate loading in a hexameric helicase
Authors: Lawson Michael R. , Dyer Kevin , Berger James M. 
Published: August 2016

ABSTRACTProcessive, ring-shaped protein and nucleic acid protein translocases control essential biochemical processes throughout biology, and are considered high-prospect therapeutic targets. TheE. coliRho factor is an exemplar hexameric RNA translocase that terminates transcription in bacteria. Like many ring-shaped motor proteins, Rho activity is modulated by a variety of poorly understood mechanisms, including small molecule therapeutics, protein-protein interactions, and the sequence of its translocation substrate. Here, we establish the mechanism of action of two Rho effectors, the antibiotic bicyclomycin and nucleic acids that bind to Rho’s ‘primary’ mRNA recruitment site. Using SAXS and a novel reporter assay to monitor the ability of Rho to switch between open-ring (RNA loading) and closed-ring (RNA translocation) states, bicyclomycin is found to be a direct antagonist of ring closure. Reciprocally, the binding of nucleic acids to its N-terminal RNA recruitment domains is shown to promote the formation of a closed-ring Rho state, with increasing primary site occupancy providing additive stimulatory effects. This study establishes bicyclomycin as a conformational inhibitor of Rho ring dynamics, highlighting the utility of developing assays that read out protein conformation as a prospective screening tool for ring-ATPase inhibitors. Our findings further show that the RNA sequence specificity used for guiding Rho-dependent termination derives in part from an intrinsic ability of the motor to couple the recognition of pyrimidine patterns in nascent transcripts to RNA loading and activity.SIGNIFICANCEMany processive, ring-ATPase motor proteins rely on substrate-dependent conformational changes to assist with the loading of client substrates into the central pore of the enzyme and subsequent translocation. Using theE. coliRho transcription terminator as a model hexameric helicase, we show that two distinct ligands – the antibiotic bicyclomycin and pyrimidine-rich nucleic acids – alternatively repress or promote, respectively, the transition of Rho from an open, RNA-loading configuration to a closed-ring, active helicase. Our findings explain several mechanisms by which Rho activity is controlled, and provide a general illustration of how intrinsic and extrinsic factors can regulate ring-type ATPase dynamics through diverse mechanisms.
DEAR-O: Differential Expression Analysis based on RNA-seq data - Online
Authors: Zhang Zong-Hong , Wray Naomi R. , Zhao Qiong-Yi 
Published: August 2016

AbstractSummaryDifferential expression analysis using high-throughput RNA sequencing (RNA-seq) data is widely applied in transcriptomic studies and many software tools have been developed for this purpose. Active development of existing popular tools, together with emergence of new tools means that studies comparing the performance of differential expression analysis methods become rapidly out-of-date. In order to enable researchers to evaluate new and updated software in a timely manner, we developed DEAR-O, a user-friendly platform for performance evaluation of differential expression analysis based on RNA-seq data. The platform currently includes four of the most popular tools: DESeq, DESeq2, edgeR and Cuffdiff2. Based on the DEAR-O platform, researchers can evaluate the performance of different tools, or the same tool with different versions, with a customised number of biological replicates using already curated RNA-seq datasets. We also initiated an online forum for discussion of RNA-seq differential expression analysis. Through this forum, new useful tools and benchmarking datasets can be introduced. Our platform will be actively maintained to ensure new major versions of existing tools and new popular tools are included. DEAR-O will serve the community by providing timely evaluations of tools, versions and number of replicates for RNA-seq differential expression analysis.Availability and implementationThe DEAR-O platform is available athttp://cnsgenomics.com/software/dear-o; the online discussion forum ishttps://groups.google.com/d/forum/dear-oContactz.zhang5@uq.edu.auandq.zhao@uq.edu.au
The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation
Authors: Schwartz John C. , Gibson Mark S. , Heimeier Dorothea , Koren Sergey , Phillippy Adam M. , Bickhart Derek M. , Smith Timothy P. L. , Medrano Juan F. , Hammond John A. 
Published: August 2016

ABSTRACTNatural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK gene complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high quality draft genome assemblies for cattle and goat, re-annotated sheep, pig and horse genome assemblies and the published human, rat and mouse lemur NKC. The major NKC genes are largely in syntenic positions in all eight species, with significant independent expansions and deletions between species, allowing us to present a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a secondKLRClocus flanked byKLRAandKLRJand a novelKLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between these NKC genes concentrated in the predicted extracellular ligand binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination.
Entering the accounting profession: the operationalization of ethnicity-based discrimination
Authors: Huang Guozhen , Fowler Carolyn J. , Baskerville Rachel F. 
Published: August 2016

PurposeThe purpose of this paper is to offer a Bourdieu-oriented study that investigates race discrimination when graduates of diverse ethnicities aspire to enter the accounting profession. This study illustrates the benefits of a careful and fine-grained operationalization of ethnicity for such a research project.Design/methodology/approachThe cohort interviewed comprises 45 participants of 20 different ethnicities.FindingsFrom this interview data, it appears that employers mostly favour “Pakeha” New Zealanders (the non-Maori ethnic majority group, mostly of British origin); those who migrated from China and East Asia are the most disfavoured; between them are those of ethnic minorities brought up in New Zealand and those who migrated from the Indian subcontinent and South Asia. Underneath the experience of discrimination is the operationalization of ten subtle factors, and a range of strategies adopted to overcome such factors, as further described in this study.Research limitations/implicationsThe findings may permit stakeholders, including professional bodies, employers, aspirant accountants, vocational counsellors, and those who have interests in promoting equality and meritocracy in the accounting profession, to formulate effective rules and structures to combat discrimination. It may also inform those in other professions seeking to lessen ethnic discrimination, and wider society.Originality/valueThe study fills a gap in the accounting literature by elaborating on the mechanisms of how ethnic minorities are discriminated against. It confirms that discrimination is suffered not only by the most salient ethnic groups, but by graduates of “Western” universities, of many and diverse ethnicities, all of whom suffer being perceived as “outsiders”.
E-lending in digital libraries: a systematic review
Authors: Alipour-Hafezi Mehdi , Khedmatgozar Hamid Reza 
Published: August 2016

Purpose
The purpose of this paper is to systematically review e-lending research studies in the digital library domain to identify their subjects, existing research gap and their research methods.

Design/methodology/approach
This is a systematic review. Through several stages of searching in related databases, 30 research works including journal and conference research papers, theses and dissertations, research and technical reports were identified and reviewed based on the guidelines of systematic review protocols.

Findings
It was found that research in e-lending domain is growing, and the subject will receive greater attention in the near future. Studies were in the following four categories: e-books (specifications, creation and software and viewpoints), business models, e-book status in libraries and copyright issues, e-book lending and inter-library loan. Some research gaps were identified including e-lending domain, business models and legislation. Little has been done with qualitative and mixed approaches in terms of research methods. Moreover, findings showed that this area has received less attention in developing countries.

Originality/value
This is the first review of the e-lending domain in digital libraries. It identifies the key works related to e-lending, categorizes them, provides an overview and identifies emerging research issues.
Institutions, capital control, and liquidity creation
Authors: Baradwaj Babu G. , Shao Yingying , Dewally Michaël 
Published: August 2016

Purpose
The purpose of this study is to conduct an empirical investigation on how country-specific characteristics such as the quality of the institutional environment and the restrictiveness of capital control policy affect domestic financial sector’s ability to provide liquidity to the economy.

Design/methodology/approach
This study uses panel regressions on international banking data across 102 countries from Bankscope.

Findings
The results show that strong institutions and looser capital control in a country enhance the banks’ role as the liquidity provider to the economy. The study also finds that institutional quality and capital control have a dynamic effect that influences the creation of liquidity. Better institutions benefit the creation of liquidity in either under normal economic conditions or during economic downturn. Loosened capital control, as a result of financial openness, facilitates liquidity creation under normal economic conditions.

Originality/value
This study complements the research on the role of country-level institutions in financial and economic development and suggests a liquidity channel through which a country’s institutions can further economic growth. The study also provides evidence on the impact of a country’s control of capital flows on the role of banking sector in domestic economy.
Encouraging the positive use of technology through community engagement
Authors: Lester Leanne , Cross Donna , Terrelinck Debbie , Falconer Sarah , Thomas Laura 
Published: August 2016

Purpose
The purpose of this paper is to describe a seven stage community engagement process to develop and disseminate community uptake strategies which encouraged cybersafety as part of a positive transition from primary to secondary school among Australian young people.

Design/methodology/approach
The combined principles from socio-ecological models, community development models and student participation models formed the foundation for the strategies. Resources were developed for all members of the community – students, parents, teachers and the broader community. The methods included: the formation of a steering committee and a Youth Advisory Board; review of the current literature; development of online resources; a youth resource development activity; development of youth resources; translation of resources into health promotion initiatives; and the dissemination of resources at community events and facilities such as schools, libraries and recreation centres and through print and social media.

Findings
Community engagement strategies – in particular a partnership between a Western Australian university and local government body, the steering committee consisting of local organisations, and the student advisory board – were used to successfully design and promote resources developed by young people for young people.

Originality/value
This study utilises a community-level approach to develop resources to encourage cybersafety and a positive transition from primary to secondary school.
Optimizing confirmation of invasive species eradication with rapid eradication assessment
Authors: Russell James C. , Binnie Hannah R. , Oh Jimmy , Anderson Dean P. , Samaniego‐Herrera Araceli 
Published: August 2016

Summary

Confirmation of invasive species eradication following management programmes is typically determined by waiting an arbitrary period of time before determining success or failure based upon the then obvious presence or absence of the target species. Rapid eradication assessment could be achieved more expediently by applying statistical models of the probability of detecting survivors and their offspring, using a grid of detection devices, for a given set of biological and monitoring parameters.

We simulate estimation of the probability of eradication for invasive rodents on islands across a range of monitoring parameters in order to provide guidance to managers on the optimal values, diminishing returns and trade‐offs in monitoring to achieve a given level of confidence in successful eradication.

We found that monitoring an island for survivors over 15–20 nights is optimal and that waiting longer than a year before commencing monitoring has a negligible impact on the estimated probability of success. The spacing between detection devices has a considerable influence on estimated probability of success but only when it is <60 m.

Intrinsic biological parameters of the target species have a substantial impact on confirming the probability of success, but validated field data are lacking to reliably incorporate these in current rapid eradication assessment models.

We present case studies demonstrating cost savings of at least 5% to managers when applying rapid eradication assessment to the eradication of house mice Mus musculus from Isla Pájaros and Isla Muertos in Arrecife Alacranes (Scorpion Reef) Mexico, and implement the rapid eradication assessment model in an HTML GUI interface for eradication managers (www.rea.is).

Synthesis and applications. Rapid eradication assessment (REA) is a powerful tool for managers to design optimal invasive species eradication monitoring programmes. We recommend island eradication managers routinely implement REA on small islands for the demonstrated cost savings and to accelerate eradication confirmation, ultimately facilitating island restoration.
Francesco Saverio (Father), Marcello Cesare Augusto (Son): Finding Useful Histories in Fascist Rome?
Authors: BOSWORTH R. J. B. 
Published: August 2016

AbstractThe choice by different regimes as to what matters in the past and what does not is always a telling factor in their character. Mussolini's dictatorship in Italy made major play with romanità through its representation of the dictator as a new Caesar and its claim to be ‘restoring’ the Roman empire. The centro storico of Rome is still full of such Fascist messaging. The regime was also the first to call itself totalitarian and, since the 1980s, a standard interpretation has developed accepting that Mussolini did indeed push his people far along the road to having their minds and actions fascistized. This interpretation, however, with its focus on culture above other issues, underestimates the extensive sectors of Italian life where rival ideas and behaviour survived and flourished. So, too, romanità could signal Catholic, Vatican, class, family and national allegiances as well as ones favoured by the regime. The real message of inter‐war Rome was therefore as much about an Italian dictatorship as a Fascist one.
Jung's views of Nazi Germany: the first year and Jung's transition
Authors: Schoenl William , Schoenl Linda 
Published: August 2016

AbstractThis article first considers Jung's response to the coming to power of the Nazis in Germany. It brings forth evidence that, besides wanting to preserve psychotherapy in Germany and maintain the international connection between the German and other communities of psychotherapists, he wanted to advance Jungian psychology – his psychology – in Germany. It also presents evidence that, although he occasionally made some anti‐Semitic statements during this early period, he was not anti‐Semitic in the way the Nazis were. The paper then argues that after Gustav Bally's criticisms in the Neue Zuercher Zeitung in February 1934, Jung entered into a transitional period that spring during which he became warier both of the Nazis and of making any statements that could be construed as being anti‐Semitic. Schoenl and Peck (2012) have shown how Jung's views of Nazi Germany changed from 1933 to March 1936. This present article demonstrates very significant changes in Jung's views during the important early part of this period, that is from January 1933 – when Hitler became Chancellor of Germany – through to the spring of 1934. It draws on evidence from archival and other primary sources.
Working with chronic and relentless self‐hatred, self‐harm, and existential shame: a clinical study and reflections (Paper 2 of 2)
Authors: Austin Sue 
Published: August 2016

AbstractThis second of two papers focuses on the shame which emerged in the first 14 years of analysis of a woman who was bulimic, self‐harmed, and repeatedly described herself as ‘feeling like a piece of shit’. To explore this intense and pervasive shame I draw on Jung's and Laplanche's emphasis on experiences of unresolvable, non‐pathological ‘foreignness’ or ‘otherness’ at the heart of the psyche. Images, metaphors, elements of clinical experience, and working hypotheses from a number of analytic traditions are used to flesh out this exploration. These include Kilborne's use of Pirandello's image of shame as like a ‘hole in the paper sky’ which, I suggest, points to a crack in subjectivity, and reveals our belief in the efficacy of the self to be illusory. Hultberg's observations on shame as having an existential mode (function) are also explored, as is the nature of analytic truth. Using these ideas I describe my patient's process of finding some small but freeing space in relation to her shame and self‐hatred. Through enduring and learning from her shame in analysis she realized that it was part of a desperate unconscious attempt to draw close to her troubled father and so to ‘love him better’.