Targeted nasal vaccination provides antibody-independent protection against Staphylococcus aureus.

Despite showing promise in preclinical models, anti-Staphylococcus aureus vaccines have failed in clinical trials. To date, approaches have focused on neutralizing/opsonizing antibodies; however, vaccines exclusively inducing cellular immunity have not been studied to formally test whether a cellular-only response can protect against infection. We demonstrate that nasal vaccination with targeted nanoparticles loaded with Staphylococcus aureus antigen protects against acute systemic S. aureus infection in the absence of any antigen-specific antibodies. These findings can help inform future developments in staphylococcal vaccine development and studies into the requirements for protective immunity against S. aureus

Twenty-three unsolved problems in hydrology (UPH) – a community perspective

This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through on-line media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focussed on process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come

CD200 receptor restriction of myeloid cell responses antagonizes antiviral immunity and facilitates cytomegalovirus persistence within mucosal tissue

CD200 receptor (CD200R) negatively regulates peripheral and mucosal innate immune responses. Viruses, including herpesviruses, have acquired functional CD200 orthologs, implying that viral exploitation of this pathway is evolutionary advantageous. However, the role that CD200R signaling plays during herpesvirus infection in vivo requires clarification. Utilizing the murine cytomegalovirus (MCMV) model, we demonstrate that CD200R facilitates virus persistence within mucosal tissue. Specifically, MCMV infection of CD200R-deficient mice (CD200R-/-) elicited heightened mucosal virus-specific CD4 T cell responses that restricted virus persistence in the salivary glands. CD200R did not directly inhibit lymphocyte effector function. Instead, CD200R-/- mice exhibited enhanced APC accumulation that in the mucosa was a consequence of elevated cellular proliferation. Although MCMV does not encode an obvious CD200 homolog, productive replication in macrophages induced expression of cellular CD200. CD200 from hematopoietic and non-hematopoietic cells contributed independently to suppression of antiviral control in vivo. These results highlight the CD200-CD200R pathway as an important regulator of antiviral immunity during cytomegalovirus infection that is exploited by MCMV to establish chronicity within mucosal tissue

Suppression of antigen-specific T cell responses by the Kaposi's sarcoma-associated herpesvirus viral OX2 protein and its cellular orthologue, CD200.

Regulating appropriate activation of the immune response in the healthy host despite continual immune surveillance dictates that immune responses must be either self-limiting and therefore negatively regulated following their activation or prevented from developing inappropriately. In the case of antigen-specific T cells, their response is attenuated by several mechanisms, including ligation of CTLA-4 and PD-1. Through the study of the viral OX2 (vOX2) immunoregulator encoded by Kaposi's sarcoma-associated herpesvirus (KSHV), we have identified a T cell-attenuating role both for this protein and for CD200, a cellular orthologue of the viral vOX2 protein. In vitro, antigen-presenting cells (APC) expressing either native vOX2 or CD200 suppressed two functions of cognate antigen-specific T cell clones: gamma interferon (IFN-γ) production and mobilization of CD107a, a cytolytic granule component and measure of target cell killing ability. Mechanistically, vOX2 and CD200 expression on APC suppressed the phosphorylation of ERK1/2 mitogen-activated protein kinase in responding T cells. These data provide the first evidence for a role of both KSHV vOX2 and cellular CD200 in the negative regulation of antigen-specific T cell responses. They suggest that KSHV has evolved to harness the host CD200-based mechanism of attenuation of T cell responses to facilitate virus persistence and dissemination within the infected individual. Moreover, our studies define a new paradigm in immune modulation by viruses: the provision of a negative costimulatory signal to T cells by a virus-encoded orthologue of CD200

Quantification of In Situ Denitrification Rates in Groundwater Below an Arable and a Grassland System

peer-reviewedUnderstanding denitrification rates in groundwater ecosystems can help predict where agricultural reactive nitrogen (N) contributes to environmental degradation. In situ groundwater denitrification rates were determined in subsoil, at the bedrock-interface and in bedrock at two sites, grassland and arable, using an in situ ‘push-pull’ method with 15N labelled nitrate (NO3--N). Measured groundwater denitrification rates ranged from 1.3 to 469.5 µg N kg-1d-1. Exceptionally high denitrification rates observed at the bedrock-interface at grassland site (470±152µg N kg-1d-1; SE, standard error) suggest that deep groundwater can serve as substantial hotspots for NO3--N removal. However, denitrification rates at the other locations were low and may not substantially reduce NO3--N delivery to surface waters. Denitrification rates were negatively correlated with ambient dissolved oxygen (DO), redox potential (Eh), ks and NO3- (all p-values p<0.01) and positively correlated with SO42- (p<0.05). Higher mean N2O/(N2O+N2) ratios at arable (0.28) site than the grassland (0.10) revealed that arable site has higher potential to indirect N2O emissions. Identification of areas with high and low denitrification and related site parameters can be a tool to manage agricultural N to safeguard the environment.Department of Agriculture and Food, Ireland - Research Stimulus Fund Programme (Grant RSF 06383

Hydrology and the Water Framework Directive in Ireland

The Water Framework Directive has been the catalyst for a considerable amount of data collection, analysis and research covering a wide range of physical and biological characteristics and involving a wide range of scientific, social and management related disciplines. This paper starts with a short description of the discipline of hydrology and then identifies the main hydrological aspects of work for the WFD and notes their ecological significance. Some idea is given of the range of organisations and disciplines involved in the work and of the links between them. Of particular significance is the degree of cooperation between River Basin Districts in setting up working groups for special studies, avoiding overlaps in research.Other funderWater Framework DirectivePlease replace pdf with published version http://www.ria.ie/RIA/files/07/0764837f-7c6a-454f-a6da-454f5977c0af.pdf - AV 2/08/201