The in silico macrophage: toward a better understanding of inflammatory disease

Macrophages function as sentinel, cell-regulatory hubs capable of initiating, perpetuating and contributing to the resolution of an inflammatory response, following their activation from a resting state. Highly complex and varied gene expression programs within the macrophage enable such functional diversity. To investigate how programs of gene expression relate to the phenotypic attributes of the macrophage, the development of in silico modeling methods is needed. Such models need to cover multiple scales, from molecular pathways in cell-autonomous immunity and intercellular communication pathways in tissue inflammation to whole organism response pathways in systemic disease. Here, we highlight the potential of in silico macrophage modeling as an amenable and important yet under-exploited tool in aiding in our understanding of the immune inflammatory response. We also discuss how in silico macrophage modeling can help in future therapeutic strategies for modulating both the acute protective effects of inflammation (such as host defense and tissue repair) and the harmful chronic effects (such as autoimmune diseases).Comment: 7 pages plus 1 figur

Management and pest management considerations on droughty soils: four year results

Four year survival of pines on droughty (Typic Quartzips~mments) soils was best for longleaf pine and Terr-Sorb -treated loblolly pine. Pest considerations include town ants and Nantucket pine tip moths on loblolly pine. Untreated loblolly pine had reduced leader and total height growth anH increased tip moth infestations, compared to Terra-Sorb and clay-slurry treated loblolly pine. Soil texture averaged less than eight percent silt and clay combined in the treatment areas

Therapeutic Treatment with the Anti-Inflammatory Drug Candidate MW151 May Partially Reduce Memory Impairment and Normalizes Hippocampal Metabolic Markers in a Mouse Model of Comorbid Amyloid and Vascular Pathology

Alzheimer\u27s disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop small molecule, anti-inflammatory therapeutics for neurological injury and disease, we have recently been exploring potentially promising treatments in preclinical multi-morbidity contexts. In the present study, we generated a mouse model of mixed amyloid and hyperhomocysteinemia (HHcy) pathology in which to test the efficacy of one of our anti-inflammatory compounds, MW151. HHcy can cause cerebrovascular damage and is an independent risk factor for both AD dementia and vascular contributions to cognitive impairment and dementia. We found that MW151 was able to partially rescue hippocampal-dependent spatial memory and learning deficits in this comorbidity context, and further, that the benefit is associated with a normalization of hippocampal metabolites detectable via magnetic resonance spectroscopy. These findings provide evidence that MW151 in particular, and potentially anti-inflammatory treatment more generally, may be beneficial in AD patients with comorbid vascular pathology

Growing Green: the emergent role of non-tilapia attributes in marketing tilapia

This paper is focussed upon the emergent emphasis of environmentally friendly (ENVF) attributes in fish with particular regard to tilapia in the UK. The focus is upon the technical production issues, marketing implications, public health and adoption responses from a 3 years multidisciplinary Research Councils UK project which examined the prospects for UK (agricultural) farmers to diversify into production of warmwater tilapia. The proposed production process and product characteristics abound with green credentials, consistent with emergent market demands. This combination might enable small scale producers to access growing UK niche markets for fresh fish and to compete through upmarket positions with expanding EU tilapia imports. Having ascertained the wider market characteristics, primary research was undertaken through consumer focus groups and in-depth interviews with organisational channel members. The results supported the initial premise of niche markets existing for tilapia produced from local, small-scale environmentally-friendly units. Three target groups in the UK were identified: ethnic consumers, green consumers and discrete segments (gastro-pubs and upscale fish restaurants) within foodservice. Having established favourable market prospects the propensity of farmers to diversify into this novel area of activity was explored. Investigation of farmer entrepreneurship, undertaken in 2006 and 2007, explored perceived challenges in the new aquaculture venture. In-depth face to face and telephone interviews with agricultural farmers identified a number of factors that both encouraged and dissuaded them from diversification into tilapia. Despite the ongoing interests of some, and other emergent adopters, the majority seem disinclined to commercialise their interest. The paper concludes that a more holistic support perspective will be required to promote a more favourable reaction and reviews the prognosis for the success of local fish production

A stabilized subunit vaccine for ebola virus

The ongoing Ebola epidemic in West Africa has claimed over eleven thousand lives and has highlighted our unpreparedness to counter emerging viral epidemics. While two recombinant vaccines have shown promising results in clinical trials, we have developed an alternate subunit vaccine candidate that could be called upon in the event that problems are encountered with regard to safety or protection efficacy. Our subunit vaccine candidate is based on a soluble version of the recombinant Ebola glycoprotein (GP) stabilized in its pre-fusion conformation. This protein is recognized by the neutralizing monoclonal antibody KZ52 and all three ZMapp antibodies (currently employed as a therapeutic for clinical treatment), indicating both GP1/2 and glycan cap domains are available and are presented in the desired conformation. Immunization via NanopatchTM (NP) microneedle delivery and intradermal injection were compared in C57 black mice. We assessed the antibody response elicited in immunized mice against Ebola virus (Zaire strain) using facilities at CSIRO’s Australian Animal Health Laboratories in Geelong (AAHL). Promising plaque reduction neutralization titers (PRNT50 = 1/80 sera dilution) were demonstrated. Furthermore, we have shown this vaccine is thermostable, retaining significant antigenicity after extended incubation at 37°C, indicating this vaccine strategy may not require cold chain delivery. In addition, the absence of any replicative elements ensures that it is likely to have a safer profile than live recombinant vaccines

Immersive Installation: “A Virtual St Kilda”

This paper discusses a Virtual Histories project, which developed a digital reconstruction of St Kilda. St Kilda is the most remote and western part of the United Kingdom. It was evacuated in the 1930s and lay empty for several decades. It is a world heritage site for both built and natural environment . The Virtual St Kilda acted as a focus for the collection and presentation of tangible and intangible cultural heritage. It was on show as an exhibition in the Taigh Chearsabah museum (Figure 5) located in North Uist Scotland. The exhibition is built around the OpenSimulator Open VirtualWorld server using commodity hardware. The simulation covers some 4 square km of virtual space, and models both tangible and intangible culture. It is integrated into an exhibition and articulates an interpretation of the St Kilda legacy through the prism of contemporary North Uist life.Postprin

Towards integration of environmental and health impact assessments for wild capture fishing and farmed fish with particular reference to public health and occupational health dimensions

The paper offers a review and commentary, with particular reference to the production of fish from wild capture fisheries and aquaculture, on neglected aspects of health impact assessments which are viewed by a range of international and national health bodies and development agencies as valuable and necessary project tools. Assessments sometimes include environmental health impact assessments but rarely include specific occupational health and safety impact assessments especially integrated into a wider public health assessment. This is in contrast to the extensive application of environmental impact assessments to fishing and the comparatively large body of research now generated on the public health effects of eating fish. The value of expanding and applying the broader assessments would be considerable because in 2004 the United Nations Food and Agriculture Organization reports there were 41,408,000 people in the total ‘fishing’ sector including 11,289,000 in aquaculture. The paper explores some of the complex interactions that occur with regard to fishing activities and proposes the wider adoption of health impact assessment tools in these neglected sectors through an integrated public health impact assessment tool

A Cost Benefit Analysis from Instructor, Community Partner, and Student Perspectives: Cabrini College CBR Courses Merge Service, Education, and Research

Two community-based research (CBR) courses—Watershed Citizenship and Watershed Ecology—were piloted at Cabrini College in southeastern Pennsylvania. The courses connected service, education, and research using a local Pennsylvania stream, Crabby Creek, as the focal point, while working with several community partners. Course feedback using a qualitative student focus group regarding attitudes about environmental awareness, interdisciplinary thinking, and community-based, undergraduate research experiences showed that students gained a better understanding of how different disciplines can collaborate to address a problem in an integrative manner. Students also valued the faculty interdisciplinary team-teaching approach of the courses. We offer a model for designing and conducting an interdisciplinary team-taught CBR course employing instructors with different disciplinary backgrounds and areas of expertise. In this paper we present a case study in which we discuss the benefits and costs of these types of courses offered through the eyes of course instructors, community partners, and students and emphasize lessons learned that should prove helpful for others considering developing similar courses

Multiple AMPK activators inhibit L-Carnitine uptake in C2C12 skeletal muscle myotubes

Mutations in the gene that encodes the principal L-Carnitine transporter, OCTN2, can lead to a reduced intracellular L-Carnitine pool and the disease Primary Carnitine Deficiency. L-Carnitine supplementation is used therapeutically to increase intracellular L-Carnitine. As AMPK and insulin regulate fat metabolism and substrate uptake we hypothesised that AMPK activating compounds and insulin would increase L-Carnitine uptake in C2C12myotubes. The cells express all three OCTN transporters at the mRNA level and immunohistochemistry confirmed expression at the protein level. Contrary to our hypothesis, despite significant activation of PKB and 2DG uptake, insulin did not increase L-Carnitine uptake at 100nM. However, L-Carnitine uptake was modestly increased at a dose of 150nM insulin. A range of AMPK activators that increase intracellular calcium content [caffeine (10mM, 5mM, 1mM, 0.5mM), A23187 (10μM)], inhibit mitochondrial function [Sodium Azide (75μM), Rotenone (1μM), Berberine (100μM), DNP (500μM)] or directly activate AMPK [AICAR (250μM)] were assessed for their ability to regulate L-Carnitine uptake. All compounds tested significantly inhibited L-Carnitine uptake. Inhibition by caffeine was not dantrolene (10μM) sensitive. Saturation curve analysis suggested that caffeine did not competitively inhibit L-Carnitine transport. However, the AMPK inhibitor Compound C (10μM) partially rescued the effect of caffeine suggesting that AMPK may play a role in the inhibitory effects of caffeine. However, caffeine likely inhibits L-Carnitine uptake by alternative mechanisms independently of calcium release. PKA activation or direct interference with transporter function may play a role

Multidisciplinary Perspectives on an Emergent Fish Product: The Tank of British Tilapia

This paper presents the interim results of an ongoing research project funded by the 'Research Councils UK' Rural Economy Land Use programme. The project has a multi-disciplinary perspective on the potential production and marketing of tilapia as a niche product under a diversification strategy for UK arable and dairy farmers; in addition to marketing and production issues the implications for sustainability and public health are considered. The tripartite disciplinary research focus: marketing, aquaculture and public health, along with entrepreneurship and commercial partners, aims to develop technical guidelines for sustainable tilapia production along with market and social analysis throughout the value chain. Concomitant health impact assessments add to the appraisal of the direct and indirect impacts of UK tilapia culture. The paper establishes current knowledge and perceptions of industry and consumers of this novel tilapia farming process and product, including sustainability, health benefits and food safety. This background established, the paper presents the interim marketing findings. The UK is shown to be a latecomer to the tilapia table, yet it is contended that there is significant niche market potential. Ethnic, green and other consumer segments are identified within the at-home market along with components of the foodservice sector. Secondary data analysis is supplemented with primary data from consumer focus groups and in-depth interviews with organisational channel members. Preliminary consumer research results provide a clearer insight into understanding of perceptions and attitudes towards sustainable aquatic food production, health concerns with fish, organic aquatic food products and tilapia. It appears that whilst there is significant emergent interest in the concept of a greener farmed product, delivering a competitive product advantage still presents a number of challenges to prospective producers