While infection of the respiratory tract with herpes simplex virus type 1 (HSV-1) can have severe clinical complications, little is known of the immune mechanisms that control both the replication and spread of HSV-1 in this site. To better understand the contribution of innate immunity and in particular natural killer (NK) cells to the control of infection at this site, we have utilized a mouse model of intranasal HSV-1 infection. NK cell numbers increased in the lung following intranasal infection and they produced IFN-c and acquired an enhanced cytotoxic capacity. While depletion of NK cells resulted in increased HSV-1 titres in the lung, the time taken to clear the virus was unaffected. Interestingly, HSV-1 was also effectively cleared from the lungs of RAG-1 -/-mice that lack both B and T cells. However, RAG-1 -/-mice could not control the spread of virus to the central nervous system and its subsequent replication in the brain. Together, these data demonstrate that NK cells are recruited, activated and contribute to early protection of the lung during acute HSV-1 infection of the respiratory tract, but in the absence of adaptive immunity are unable to control the replication and spread of virus in the nervous system.

Natural killer (NK) cells play a crucial role in the initial response to viral infections but the mechanisms controlling their activation are unclear. We show a rapid and transient activation of NK cells that results in the production of IFN-γ immediately following infection with herpes simplex virus type 1 (HSV-1). Activation of NK cells leading to synthesis of IFN-γ was not mediated by a direct interaction with virus but required the presence of additional cell types and was largely dependent on the cytokine IL-18, but not IL-12. HSV-1-induced IFN-γ expression by NK cells in vitro was impaired in spleen cultures depleted of CD11c+ cells. Conversely, coculture of NK cells with virus-exposed conventional DC or plasmacytoid (p)DC restored the production of IFN-γ, indicating that multiple DC subsets could mediate NK cell activation. While conventional DC populations stimulated NK cells independently of IL-18, they were less effective than pDC in promoting NK cell IFN-γ expression. In contrast, the potent stimulation of NK cells by pDC was dependent on IL-18 as pDC from IL-18-deficient mice only activated a similar proportion of NK cells as conventional DC. These data identify IL-18 as a crucial factor for pDC-mediated NK cell regulation.

Infection of the respiratory tract with HSV type 1 (HSV-1) can have severe clinical complications, yet little is known of the immune mechanisms that control the replication and spread of HSV-1 in this site. The present study investigated the protective role of IL-12 and IL-18 in host defense against intranasal HSV-1 infection. Both IL-12 and IL-18 were detected in lung fluids following intranasal infection of C57BL/6 (B6) mice. IL-18-deficient (B6.IL-18−/−) mice were more susceptible to HSV-1 infection than wild-type B6 mice as evidenced by exacerbated weight loss and enhanced virus growth in the lung. IL-12-deficient (B6.IL-12−/−) mice behaved similarly to B6 controls. Enhanced susceptibility of B6.IL-18−/− mice to HSV-1 infection correlated with a profound impairment in the ability of NK cells recovered from the lungs to produce IFN-γ or to mediate cytotoxic activity ex vivo. The weak cytotoxic capacity of NK cells from the lungs of B6.IL-18−/− mice correlated with reduced expression of the cytolytic effector molecule granzyme B. Moreover, depletion of NK cells from B6 or B6.IL-12−/− mice led to enhanced viral growth in lungs by day 3 postinfection; however, this treatment had no effect on viral titers in lungs of B6.IL-18−/− mice. Together these studies demonstrate that IL-18, but not IL-12, plays a key role in the rapid activation of NK cells and therefore in control of early HSV-1 replication in the lung.

Data management plans (DMPs) have increasingly been encouraged as a key component of institutional and funding body policy. Although DMPs necessarily place administrative burden on researchers, proponents claim that DMPs have myriad benefits, including enhanced research data quality, increased rates of data sharing, and institutional planning and compliance benefits.

. The World Conferences were established as global forums for discussion of ideas, policies and empirical findings related to the responsible conduct of research. The Conferences aim to galvanise the global effort to strengthen the trustworthiness and reliability of research and encourage researchers worldwide to be accountable for their findings. Earlier conferences were held in Lisbon (2007), Singapore (2010) and Montréal (2010). The Rio conference attracted over 470 delegates from 42 countries, including leaders of research institutions and funding agencies, policy makers, editors and publishers, legal experts, researchers and graduate students. The theme of the conference was Research Rewards and Integrity: Improving Systems to Promote Responsible Research. These Proceedings contain the abstracts of the presentations given at the 4th World Conference in concurrent sessions, partner symposia, and poster sessions. Also included are summaries of the discussions in three focus tracks, which allowed delegates to consider and work on questions about the roles of funders, institutions, and countries in improving research systems and strengthening research integrity. Videos of the plenary presentations are available at the conference website (www.wcri2015.org). The 5 th World Conference will be held in Amsterdam, The Netherlands, May 28-31, 2017 (www.wcri2017.org). The University of Queensland (UQ) is one of the leading research-intensive universities in Australia. UQ first developed formal policy and procedure relating to responsible conduct of research in 2011. The ongoing practical application of the first iteration of these policies identified lack of clarity in procedure with challenges arising from unintended consequences. A significant case of research misconduct in 2013 was a catalyst to commission a comprehensive external review of policy, procedure and practice relevant to research integrity, ethics and compliance in line with the Australian Code for Responsible Conduct of Research (2007). This presentation will describe the comprehensive strategy arising from this review to improve our policies, our resources, our systems and to ensure the practice of responsible conduct of research sits at the heart of UQ. Additional funds have enabled us to increase the number and seniority of staff in the Research Integrity Office, to purchase a purpose built complaints management system and the Epigeum online Research Integrity training tool. With a team of experienced research leaders and other key staff we are revising our responsible research policies and developing an education and communication plan to ensure senior staff such as Executive Deans and Heads of Schools are confident in working collaboratively with the Research Integrity Office and that all staff understand their responsibilities under the Australian Code and university policy. We have appointed a team of 16 senior researchers to the roles of Research Integrity Advisors embedded within each Faculty and Institute as a first triage point for people wi...

Data management plans (DMPs) have increasingly been encouraged as a key component of institutional and funding body policy. Although DMPs necessarily place administrative burden on researchers, proponents claim that DMPs have myriad benefits, including enhanced research data quality, increased rates of data sharing, and institutional planning and compliance benefits. In this article, we explore the international history of DMPs and describe institutional and funding body DMP policy. We find that economic and societal benefits from presumed increased rates of data sharing was the original driver of mandating DMPs by funding bodies. Today, 86% of UK Research Councils and 63% of US funding bodies require submission of a DMP with funding applications. Given that no major Australian funding bodies require DMP submission, it is of note that 37% of Australian universities have taken the initiative to internally mandate DMPs. Institutions both within Australia and internationally frequently promote the professional benefits of DMP use, and endorse DMPs as ‘best practice’. We analyse one such typical DMP implementation at a major Australian institution, finding that DMPs have low levels of apparent translational value. Indeed, an extensive literature review suggests there is very limited published systematic evidence that DMP use has any tangible benefit for researchers, institutions or funding bodies. We are therefore led to question why DMPs have become the go-to tool for research data professionals and advocates of good data practice. By delineating multiple use-cases and highlighting the need for DMPs to be fit for intended purpose, we question the view that a good DMP is necessarily that which encompasses the entire data lifecycle of a project. Finally, we summarise recent developments in the DMP landscape, and note a positive shift towards evidence-based research management through more researcher-centric, educative, and integrated DMP services.

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In 2017, the University of Hong Kong and the University of California San Diego co-hosted the first Asian meeting of the recently formed Asia Pacific Research Integrity (APRI) network in Hong Kong. Aligned with planning meetings in 2015 and 2016 funded in part by the US Office of Research Integrity (ORI), the Hong Kong meeting was designed by a multi-national planning committee to address pressing challenges in research integrity: improving multi-national communication; exchanging information on managing misconduct investigations; and sharing best practices to promote research integrity. To create a sustainable, robust international partnership to promote research integrity in the region, the purpose of this 2017 meeting was to foster multinational awareness, understanding, and opportunities for collaboration. The meeting was defined by four objectives that emerged from the previous meetings: (1) Articulate differences as well as