Genomic approaches for understanding dengue: insights from the virus, vector, and host.

The incidence and geographic range of dengue have increased dramatically in recent decades. Climate change, rapid urbanization and increased global travel have facilitated the spread of both efficient mosquito vectors and the four dengue virus serotypes between population centers. At the same time, significant advances in genomics approaches have provided insights into host-pathogen interactions, immunogenetics, and viral evolution in both humans and mosquitoes. Here, we review these advances and the innovative treatment and control strategies that they are inspiring

Genome-wide association studies are coming for human infectious diseases

A genetic contribution to infectious disease in human populations has long been suspected and is now supported by more than 50 years of epidemiological evidence showing, for example, infection rates to be much higher than disease rates. In successful family studies of high-penetrance effects, single gene mutations have been identified that reveal a molecular mechanism leading to increased risk of a specific infectious disease. However, in population-based studies, genetic variants conferring host susceptibility to various infectious diseases have been difficult to uncover. Although mutations such as that in the CCR5 gene, which confers protection against HIV infection, have been reliably discovered, polymorphisms affecting larger proportions of a population have been hard to prove definitively. The recent arrival of the genome-wide association study format, currently being applied to Kawasaki disease, tuberculosis, malaria, HIV, dengue and others, gives us hope that these challenges can finally be met, with implications for population-based treatment and prognosis strategies

Genetics and Genomics of Infectious Diseases: advancing our understanding of host/pathogens and their interactions

A report on the Genetics and Genomics of Infectious Diseases conference, Singapore, 21-24 March 2009

Shared pathways to infectious disease susceptibility?

The recent advent of genomic approaches for association testing is starting to enable a more comprehensive understanding of the role of human immune response in determining infectious disease outcomes. Progressing from traditional linkage approaches using microsatellite markers to high-resolution genome-wide association scans, these new approaches are leading to the robust discovery of a large number of disease susceptibility genes and the beginnings of an appreciation of their connections. In this commentary, we discuss how this technology development has led to increasingly complex and common infectious diseases being unraveled, and how this is starting to dissect pathogen-specific human responses. Intriguingly, these still preliminary findings suggest that pathogen innate detection mechanisms may not be as shared among diseases as immune response mechanisms

Genome wide expression profiling reveals suppression of host defence responses during colonisation by Neisseria meningitides but not N. lactamica.

Both Neisseria meningitidis and the closely related bacterium Neisseria lactamica colonise human nasopharyngeal mucosal surface, but only N. meningitidis invades the bloodstream to cause potentially life-threatening meningitis and septicaemia. We have hypothesised that the two neisserial species differentially modulate host respiratory epithelial cell gene expression reflecting their disease potential. Confluent monolayers of 16HBE14 human bronchial epithelial cells were exposed to live and/or dead N. meningitidis (including capsule and pili mutants) and N. lactamica, and their transcriptomes were compared using whole genome microarrays. Changes in expression of selected genes were subsequently validated using Q-RT-PCR and ELISAs. Live N. meningitidis and N. lactamica induced genes involved in host energy production processes suggesting that both bacterial species utilise host resources. N. meningitidis infection was associated with down-regulation of host defence genes. N. lactamica, relative to N. meningitidis, initiates up-regulation of proinflammatory genes. Bacterial secreted proteins alone induced some of the changes observed. The results suggest N. meningitidis and N. lactamica differentially regulate host respiratory epithelial cell gene expression through colonisation and/or protein secretion, and that this may contribute to subsequent clinical outcomes associated with these bacteria

The Design of Haptic Gas Pedal Feedback to Support Eco-Driving

Previous literature suggests that haptic gas pedals can assist the driver in search of maximum fuel economy. This study investigated three haptic pedal designs, each with high and low intensities of feedback, in a rapid prototyping, paired comparison design. Twenty drivers took part, experiencing the systems in a high-fidelity driving simulator. Results suggested that drivers were best guided towards an “idealized” (most fuel efficient) gas pedal position by force feedback (where a driver feels a step change in gas pedal force) as opposed to stiffness feedback (where a driver feels a changing gas pedal firmness). In either case, high levels of force/stiffness feedback were preferred. Objective performance measures mirrored the subjective results. Whilst the short-term nature (brief system exposure) of this study led to difficulties in drawing longer-term conclusions, it would appear that force feedback haptics are better suited than stiffness feedback to augment an effective driver interface supporting “green” driving

Environmental monitoring of Mycobacterium bovis in badger feces and badger sett soil by real-time PCR, as confirmed by immunofluorescence, immunocapture, and cultivation

Real-time PCR was used to detect and quantify Mycobacterium bovis cells in naturally infected soil and badger faeces. Immunomagnetic capture, immunofluorescence and selective culture confirmed species identification and cell viability. These techniques will prove useful for monitoring M. bovis in the environment and for elucidating transmission routes between wildlife and cattle

The Effects of an Eco-Driving Interface on Driver Safety and Fuel Efficiency

Real-time, in-vehicle guidance on eco-driving is likely to produce substantial improvements in vehicle fuel economy. However, the benefits of such in-vehicle systems should be achieved without impairing driver safety. A simulator study evaluated both visual and haptic eco-driving feedback systems, which provided advice on gas pedal usage. Hill driving scenarios with variable traffic density were used to test drivers’ prioritization of safe and fuel-efficient driving. A visual, second-order display and a haptic force feedback gas pedal created the smallest errors in gas pedal usage and so maximized fuel efficiency. The visual display increased time spent looking away from the road, implying reduced driver safety. Participants were worse at eco-driving in more demanding, high traffic conditions. Drivers appeared to prioritize safety over eco-driving, however safety margins were shorter in the high density traffic condition, despite the degradation in eco-driving performance. The findings suggest which modality could be most appropriate for presenting in-vehicle eco-driving guidance, and hint that these systems should advise drivers based on the prevailing traffic conditions