Genetic relatedness and phenotypic characteristics of Treponema associated with human periodontal tissues and ruminant foot disease

Treponema have been implicated recently in the pathogenesis of digital dermatitis (DID) and contagious ovine digital dermatitis (CODD) that are infectious diseases of bovine and ovine foot tissues, respectively. Previous analyses of treponemal 16S rDNA sequences, PCR-amplified directly from DID or CODD lesions, have suggested relatedness of animal Treponema to some human oral Treponema species isolated from periodontal tissues. In this study a range of adhesion and virulence-related properties of three animal Treponema isolates have been compared with representative human oral strains of Treponema denticola and Treponema vincentii. In adhesion assays using biotinylated treponemal cells, T denticola cells bound in consistently higher numbers to fibronectin, laminin, collagen type 1, gelatin, keratin and lactoferrin than did T. vincentii or animal Treponema isolates. However, animal DID strains adhered to fibrinogen at equivalent or greater levels than T denticola. All Treponema strains bound to the amino-terminal heparin l/fibrin I domain of fibronectin. 16S rDNA sequence analyses placed ovine strain UB1090 and bovine strain UB1467 within a cluster that was phylogenetically related to T vincentii, while ovine strain UB1466 appeared more closely related to T denticola. These observations correlated with phenotypic properties. Thus, T denticola ATCC 35405, GM-1, and Treponema UB1466 had similar outer-membrane protein profiles, produced chymotrypsin-like protease (CTLP), trypsin-like protease and high levels of proline iminopeptidase, and co-aggregated with human oral bacteria Porphyromonas gingivalis and Streptococcus crista. Conversely, T vincentii ATCC 35580, D2A-2, and animal strains UB1090 and UB1467 did not express CTLP or trypsin-like protease and did not co-aggregate with P. gingivalis or S. crista. Taken collectively, these results suggest that human oral-related Treponema have broad host specificity and that similar control or preventive strategies might be developed for human and animal Treponema-associated infections.

The role of REST in transcriptional and epigenetic dysregulation in Huntington's disease

Huntington's disease (HD) is a devastating disorder that affects approximately 1 in 10,000 people and is accompanied by neuronal dysfunction and neurodegeneration. HD manifests as a progressive chorea, a decline in mental abilities accompanied by behavioural, emotional and psychiatric problems followed by, dementia, and ultimately, death. The molecular pathology of HD is complex but includes widespread transcriptional dysregulation. Although many transcriptional regulatory molecules have been implicated in the pathogenesis of HD, a growing body of evidence points to the pivotal role of RE1 Silencing Transcription Factor (REST). In HD, REST, translocates from the cytoplasm to the nucleus in neurons resulting in repression of key target genes such as BDNF. Since these original observations, several thousand direct target genes of REST have been identified, including numerous non-coding RNAs including both microRNAs and long non-coding RNAs, several of which are dysregulated in HD. More recently, evidence is emerging that hints at epigenetic abnormalities in HD brain. This in turn, promotes the notion that targeting the epigenetic machinery may be a useful strategy for treatment of some aspects of HD. REST also recruits a host of histone and chromatin modifying activities that can regulate the local epigenetic signature at REST target genes. Collectively, these observations present REST as a hub that coordinates transcriptional, posttranscriptional and epigenetic programmes, many of which are disrupted in HD. We identify several spokes emanating from this REST hub that may represent useful sites to redress REST dysfunction in HD.

The proteome of the infectious bronchitis virus Beau-R Virion

Infectious bronchitis is a highly contagious respiratory disease of poultry caused by the coronavirus IBV. It was thought that coronavirus virions were composed of three major viral structural proteins, until investigations of other coronaviruses showed that coronavirus virions also include viral non-structural and group specific proteins as well as host cell proteins. To study the proteome of IBV virions, virus was grown in embryonated chicken eggs and purified by sucrose gradient ultracentrifugation and analysed by mass spectrometry proteomic. Analysis of three preparations of purified IBV yielded the three expected structural proteins plus thirty-five additional virion-associated host proteins. Virion-associated host proteins had a diverse range of functional attributions, being involved in cytoskeleton formation, RNA binding and protein folding pathways. Some of these proteins were unique to this study, whilst others were found to be orthologous to proteins identified in SARS-CoV virions, and also virions from a number of other RNA and DNA viruses. Together these results demonstrate that coronaviruses have the capacity to incorporate a substantial variety of host protein, which may have implications for the disease process.

False-positive results of a rapid K39-based strip test and Chagas disease

Background: The definitive diagnosis of visceral. leishmaniasis (VL) requires invasive procedures with demonstration of amastigotes in tissue or promastigotes in culture. Unfortunately, these approaches require laboratory materials not available in poor countries where the disease is endemic. The correct diagnosis of VL is important, and made more difficult by the fact that several common tropical diseases such as malaria, disseminated tuberculosis, and enteric fever share the same clinical presentation. Serological tests have been developed to replace parasitological diagnosis in the field. A commercially available K39-based strip test for VL has been developed for this purpose. The endemic area of leishmaniasis in Brazil overlaps the endemic area of Chagas disease, a disease that can cause false-positive serological test results. The aim of this study was to evaluate the incidence of false-positive exams using a rapid test for VL in patients with Chagas disease. Methods: A rapid test based on the recombinant K39 antigen of Leishmania was used in: (1) 30 patients with confirmed Chagas disease, (2) 30 patients with a serological diagnosis of Chagas disease by ELISA, indirect immunofluorescence, indirect hemagglutination, and chemiluminescence, (3) 30 healthy patients from a non-endemic area as the control group, (4) 30 patients with confirmed VL, and (5) 20 patients with proved cutaneous leishmaniasis. Results: The sensitivity and specificity of the rapid strip test were 100% when compared with healthy volunteers and those with confirmed Chagas disease. One false-positive result occurred in the group with Chagas disease diagnosed by serological tests (specificity of 96%). Conclusion: The rapid test based on recombinant K39 is a useful diagnostic assay, and a false-positive result rarely occurs in patients with a serological diagnosis of Chagas disease. (C) 2008 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Emerging health issues: the widening challenge for population health promotion

The spectrum of tasks for health promotion has widened since the Ottawa Charter was signed. In 1986, infectious diseases still seemed in retreat, the potential extent of HIV/AIDS was unrecognized, the Green Revolution was at its height and global poverty appeared less intractable. Global climate change had not yet emerged as a major threat to development and health. Most economists forecast continuous improvement, and chronic diseases were broadly anticipated as the next major health issue. Today, although many broadly averaged measures of population health have improved, many of the determinants of global health have faltered. Many infectious diseases have emerged; others have unexpectedly reappeared. Reasons include urban crowding, environmental changes, altered sexual relations, intensified food production and increased mobility and trade. Foremost, however, is the persistence of poverty and the exacerbation of regional and global inequality. Life expectancy has unexpectedly declined in several countries. Rather than being a faint echo from an earlier time of hardship, these declines could signify the future. Relatedly, the demographic and epidemiological   transitions have faltered. In some regions, declining fertility has overshot that needed for optimal age structure, whereas elsewhere mortality increases have reduced population growth rates, despite continuing high fertility. Few, if any, Millennium Development Goals (MDG), including those for health and sustainability, seem achievable. Policy-makers generally misunderstand the link between environmental sustainability (MDG #7) and health. Many health workers also fail to realize that social cohesion and sustainability—maintenance of the Earth’s ecological and geophysical systems—is a necessary basis for health. In sum, these issues present an enormous challenge to health. Health promotion must address population health influences that transcend national boundaries and generations and engage with the development, human rights and environmental movements. The big task is to promote sustainable environmental and social conditions that bring enduring and equitable health gains.

Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions

Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in Schistosoma mansoni infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis,  apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining  coordinated gene expression profiles but are also highly effective for molecularly “fingerprinting” diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious  disease pathogenesis.

Peridontal disease : the overlooked diabetes complication

Periodontal diseases are infectious processes that occur in the presence of bacteria, which trigger an inflammatory response. Periodontal disease is associated with many medical conditions, including diabetes mellitus and its complications (such as kidney disease). It has been described as the "sixth diabetes complication" but is often overlooked in routine diabetes management and complication screening processes. Proactive, preventative dental and diabetes self care, as well as regular dental and diabetes assessment, are important management strategies because periodontal disease contributes to the progression of impaired glucose tolerance to diabetes mellitus and to hyperglycemia in individuals with established diabetes.

Development and evaluation of an ELISA for the detection and 3D antibodies to foot and mouth disease virus

A group specific ELISA (enzyme-linked immunosorbent assay) was developed to detect virus infection associated antibodies in the serum of animals infected with any serotype of foot and mouth disease virus. The assay was developed from non-infectious sources, and is therefore suitable for use in countries where FMDV is exotic.

Oxidative stress : emerging mitochondrial and cellular themes and variations in neuronal injury

Oxidative stress plays a central role in neuronal injury and cell death in acute and chronic pathological conditions. The cellular responses to oxidative stress embrace changes in mitochondria and other organelles, notably endoplasmic reticulum, and can lead to a number of cell death paradigms, which cover a spectrum from apoptosis to necrosis and include autophagy. In Alzheimer's disease, and other pathologies including Parkinson's disease, protein aggregation provides further cellular stresses that can initiate or feed into the pathways to cell death engendered by oxidative stress. Specific attention is paid here to mitochondrial dysfunction and programmed cell death, and the diverse modes of cell death mediated by mitochondria under oxidative stress. Novel insights into cellular responses to neuronal oxidative stress from a range of different stressors can be gained by detailed transcriptomics analyses. Such studies at the cellular level provide the key for understanding the molecular and cellular pathways whereby neurons respond to oxidative stress and undergo injury and death. These considerations underpin the development of detailed knowledge in more complex integrated systems, up to the intact human bearing the neuropathology, facilitating therapeutic advances.

Drought-rainfall cycles as potential environmental drivers of fowl plague and Newcastle disease uutbreaks in Australian poultry

Climatic conditions in Australia are erratic and characterised by periods of intense rainfall followed by periods of intense drought. This has considerable impact on the population dynamics and ecology of many Australian species of waterfowl, which are thought to form the reservoir of avian influenza viruses (AIV) but may also be important carriers (and possibly reservoirs) of other diseases (e.g. bursal disease, Newcastle disease). During the wet, waterfowl numbers increase with many serologically naive juveniles entering the population. During the subsequent period of drought, bird densities increase in the few remaining wetlands. We hypothesise that it is during this period of increasing densities of naive birds that the population’s viral prevalence of some infectious diseases may increase dramatically. Indeed, there exists a remarkable and suggestive coincidence between outbreaks of fowl plaque and Newcastle disease in Australian poultry farms and the periods of drought following a very wet period. In other words, we suspect a link between increased risk for disease outbreaks in poultry farms and the hypothesised high in the prevalences of the viruses causing these diseases in waterfowl. Given that poultry farms may provide ideal conditions for development of high-pathogenic strains, there is also a reciprocal risk for wildlife involved during these periods.

Building equity in chronic disease management in Thailand : a whole-system provincial trial of systematic, pro-active chronic illness care

Thailand has a history of implementing innovative and proactive policies to address the health needs of its population. Since 1962 Thailand has implemented initiatives that led to it having a health system characterized by a primary care focus, decentralization and mechanisms to maximize equity and universal access to basic care at the local level. Thai health structures initially evolved to meet challenges including infectious and developmental diseases and later HIV. Early in the 21st century chronic illness rapidly became the greatest cause of morbidity and mortality and the question has arisen how Thailand can adapt its strong health system to deal with the new epidemics. This article describes an effort to reorient provincial health services to meet the needs of the increasing number of people with diabetes and heart disease. It describes measures taken to build on the equity-promoting elements of the Thai health system. The project included; a situational analysis, development and implementation of a chronic disease self-management intervention implemented by nurses and alignment of provincial health services. The self-management intervention is currently being evaluated within a clustered randomized control trial. The evaluation has been developed to fit with the focus on equity in relation to both selection criteria and the outcomes that are being assessed.

Emerging engineered magnetic nanoparticulate probes for molecular MRI of atherosclerosis : how far have we come?

Atherosclerosis is a chronic, progressive, immunoinflammatory disease of the large and medium-sized arteries, and a major cause of cardiovascular diseases. Atherosclerosis often progresses silently for decades until the occurrence of a major catastrophic clinical event such as myocardial infarction, cardiac arrest and stroke. The main challenge in the diagnosis and management of atherosclerosis is to develop a safe, noninvasive technique that is accurate and reproducible, which can detect the biologically active high-risk vulnerable plaques (with ongoing active inflammation, angiogenesis and apoptosis) before the occurrence of an acute clinical event. This Journal Article reviews the events involved in the pathogenesis of atherosclerosis in light of recently advanced understanding of the molecular pathogenesis of the disease. Next, we elaborate on the interesting developments in molecular MRI, by describing the recently engineered magnetic nanoparticulate probes targeting clinically promising molecular and cellular players/processes, involved in early atherosclerotic lesion formation to plaque rupture and erosion.

More rapid and severe disease outbreaks for aquaculture at the tropics : implications for food security

1. Aquaculture is replacing capture fisheries in supplying the world with dietary protein. Although disease is a major threat to aquaculture production, the underlying global epidemiological patterns are unknown. 2. We analysed disease outbreak severity across different latitudes in a diverse range of aquaculture systems. 3. Disease at lower latitudes progresses more rapidly and results in higher cumulative mortality, in particular at early stages of development and in shellfish. 4. Tropical countries suffer proportionally greater losses in aquaculture during disease outbreaks and have less time to mitigate losses. 5. Synthesis and applications. Disease can present a major problem for food production and security in equatorial regions where fish and shellfish provide a major source of dietary protein. As the incidences of some infectious diseases may increase with climate change, adaptation strategies must consider global patterns in disease vulnerability of aquaculture and develop options to minimize impacts on food production.

Nano-lactoferrin in diagnostic, imaging and targeted delivery for cancer and infectious diseases

Lactoferrin (Lf) is a natural occurring iron binding protein present in many mammalian excretions and involved in various physiological processes. Lf is used in the transport of iron along with other molecules and ions from the digestive system. However its the modulatory functions exhibited by Lf in connection to immune response, disease regression and diagnosis that has made this protein an attractive therapeutic against chronic diseases. Further, the exciting potentials of employing nanotechnology in advancing drug delivery systems, active disease targeting and prognosis have also shown some encouraging outcomes. This review focuses on the role of Lf in diagnosing infection, cancer, neurological and inflammatory diseases and the recent nanotechnology based strategies.

Identification of natural killer cell receptor genes in the genome of the marsupial Tasmanian devil (Sarcophilus harrisii)

Within the mammalian immune system, natural killer (NK) cells contribute to the first line of defence against infectious agents and tumours. Their activity is regulated, in part, by cell surface NK cell receptors. NK receptors can be divided into two unrelated, but functionally analogous superfamilies based on the structure of their extracellular ligand-binding domains. Receptors belonging to the C-type lectin superfamily are predominantly encoded in the natural killer complex (NKC), while receptors belonging to the immunoglobulin superfamily are predominantly encoded in the leukocyte receptor complex (LRC). Natural killer cell receptors are emerging as a rapidly evolving gene family which can display significant intra- and interspecific variation. To date, most studies have focused on eutherian mammals, with significantly less known about the evolution of these receptors in marsupials. Here, we describe the identification of 43 immunoglobulin domain-containing LRC genes in the genome of the Tasmanian devil (Sarcophilus harrisii), the largest remaining marsupial carnivore and only the second marsupial species to be studied. We also identify orthologs of NKC genesKLRK1, CD69, CLEC4E, CLEC1B, CLEC1A and an ortholog of an opossum NKC receptor. Characterisation of these regions in a second, distantly related marsupial provides new insights into the dynamic evolutionary histories of these receptors in mammals. Understanding the functional role of these genes is also important for the development of therapeutic agents against Devil Facial Tumour Disease, a contagious cancer that threatens the Tasmanian devil with extinction.