The Role of Damage-Associated Molecular Patterns in Human Diseases : Part I - Promoting inflammation and immunity

There is increasing interest by physicians in the impact of the innate immune system on human diseases. In particular, the role of the molecules that initiate and amplify innate immune pathways, namely damage associated molecular patterns (DAMPs), is of interest as these molecules are involved in the pathogenesis of many human disorders. The first part of this review identifies five classes of cell stress/tissue injury-induced DAMPs that are sensed by various recognition receptor-bearing cells of the innate immune system, thereby mounting inflammation, promoting apoptosis and shaping adaptive immune responses. The DAMPs activate and orchestrate several innate immune machineries, including inflammasomes and the unfolded protein response that synergistically operates to induce inflammatory, metabolic and adaptive immune pathologies. Two examples of autoimmune diseases are discussed as they represent a typical paradigm of the intimate interplay between innate and adaptive immune responses

The Innate Immune System: Its Rediscovery before Toll Was Described

In 1994, in a prospective control trial in cyclosporine-treated, kidneytransplant patients, we observed that treatment of a non-specificallograft injury (postischemic reperfusion injury) leads to asignificant reduction in the incidence of both specificalloimmune-mediated allograft rejection and chronic allograft failure. From these convincing clinical data, we concluded in terms of an‘argumentum e contrario’: it is the tissue injury that induces immunity. As from where we stand today in innate immunity research, these earlyclinical observations can be regarded as the discovery of the existence of a human innate immune system activated by tissue injury and precedingadaptive immunity

Posterior shoulder tightness; an intersession reliability study of 3 clinical tests.

Background Although posterior shoulder tightness (PST) has been associated with shoulder pathology and altered glenohumeral joint kinematics, uncertainty remains regarding its cause and definition. To understand the efficacy of treatments for PST, it must be possible to identify people with PST for the purposes of research and clinical decision-making. Clinical tests for PST must demonstrate acceptable levels of measurement reliability in order to identify the condition and to evaluate the response to intervention. There is currently a lack of research describing intersession reliability for measures of PST. The aim of this study was to quantify the inter-session reliability for three clinical tests used to identify PST over a 6–10 week interval. Methods A convenience sample of 26 asymptomatic adult participants (52 shoulders) were recruited from a university setting over a five-month duration. Participants attended the human movement laboratory for measurement of glenohumeral joint internal rotation, horizontal adduction and low flexion on two occasions separated by an interval of 6–10 weeks. Intra-class correlation coefficients were calculated from the mean square values derived from the within-subject, single factor (repeated measures) ANOVA. Test-retest measurement stability was evaluated by calculating the standard error of measurement and the minimum detectable change for each measurement. Results All 3 tests demonstrated good intersession intra-rater reliability (0.86–0.88), and the standard error of measurement (95%) were 7.3° for glenohumeral horizontal adduction, 9.4° for internal rotation, and 6.9° for low flexion. The minimum detectable change for glenohumeral horizontal adduction was 10.2°, internal rotation was 13.3°, and low flexion was 9.7°. Conclusion In this population of people without symptoms, the 3 measures of PST all demonstrated acceptable inter-session reliability. The standard error of measurement and minimum detectable change results can be used to determine if a change in measures of PST are due to measurement error or an actual change over time.Peer reviewe

The Evolution of Host Specialization in the Vertebrate Gut Symbiont Lactobacillus reuteri

Recent research has provided mechanistic insight into the important contributions of the gut microbiota to vertebrate biology, but questions remain about the evolutionary processes that have shaped this symbiosis. In the present study, we showed in experiments with gnotobiotic mice that the evolution of Lactobacillus reuteri with rodents resulted in the emergence of host specialization. To identify genomic events marking adaptations to the murine host, we compared the genome of the rodent isolate L. reuteri 100-23 with that of the human isolate L. reuteri F275, and we identified hundreds of genes that were specific to each strain. In order to differentiate true host-specific genome content from strain-level differences, comparative genome hybridizations were performed to query 57 L. reuteri strains originating from six different vertebrate hosts in combination with genome sequence comparisons of nine strains encompassing five phylogenetic lineages of the species. This approach revealed that rodent strains, although showing a high degree of genomic plasticity, possessed a specific genome inventory that was rare or absent in strains from other vertebrate hosts. The distinct genome content of L. reuteri lineages reflected the niche characteristics in the gastrointestinal tracts of their respective hosts, and inactivation of seven out of eight representative rodent-specific genes in L. reuteri 100-23 resulted in impaired ecological performance in the gut of mice. The comparative genomic analyses suggested fundamentally different trends of genome evolution in rodent and human L. reuteri populations, with the former possessing a large and adaptable pan-genome while the latter being subjected to a process of reductive evolution. In conclusion, this study provided experimental evidence and a molecular basis for the evolution of host specificity in a vertebrate gut symbiont, and it identified genomic events that have shaped this process

ASEAN's unchanged melody? The theory and practice of 'non-interference' in Southeast Asia

This is an Author's Accepted Manuscript of an article published as Jones, Lee. (2010). ASEAN's unchanged melody? The theory and practice of 'non-interference' in Southeast Asia. Pacific Review 23:4, 479-502 as published in PACIFIC REVIEW 2010 © Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/09512748.2010.49599

Towards an integrated model for breast cancer etiology: The lifelong interplay of genes, lifestyle, and hormones

While the association of a number of risk factors, such as family history and reproductive patterns, with breast cancer has been well established for many years, work in the past 10–15 years also has added substantially to our understanding of disease etiology. Contributions of particular note include the delineation of the role of endogenous and exogenous estrogens to breast cancer risk, and the discovery and quantification of risk associated with several gene mutations (e.g. BRCA1). Although it is difficult to integrate all epidemiologic data into a single biologic model, it is clear that several important components or pathways exist. Early life events probably determine both the number of susceptible breast cells at risk and whether mutations occur in these cells. High endogenous estrogens are well established as an important cause of breast cancer, and many known risk factors appear to operate through this pathway. Estrogens (and probably other growth factors) appear to accelerate the development of breast cancer at many points along the progression from early mutation to tumor metastasis, and appear to be influential at many points in a woman's life. These data now provide a basis for a number of strategies that can reduce risk of breast cancer, although some strategies represent complex decision-making. Together, the modification of nutritional and lifestyle risk factors and the judicious use of chemopreventive agents could have a major impact on breast cancer incidence. Further research is needed in many areas, but a few specific arenas are given particular mention

The Magnitude of Global Marine Species Diversity

Background: The question of how many marine species exist is important because it provides a metric for how much we do and do not know about life in the oceans. We have compiled the first register of the marine species of the world and used this baseline to estimate how many more species, partitioned among all major eukaryotic groups, may be discovered. Results: There are ∼226,000 eukaryotic marine species described. More species were described in the past decade (∼20,000) than in any previous one. The number of authors describing new species has been increasing at a faster rate than the number of new species described in the past six decades. We report that there are ∼170,000 synonyms, that 58,000–72,000 species are collected but not yet described, and that 482,000–741,000 more species have yet to be sampled. Molecular methods may add tens of thousands of cryptic species. Thus, there may be 0.7–1.0 million marine species. Past rates of description of new species indicate there may be 0.5 ± 0.2 million marine species. On average 37% (median 31%) of species in over 100 recent field studies around the world might be new to science. Conclusions: Currently, between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely. More species than ever before are being described annually by an increasing number of authors. If the current trend continues, most species will be discovered this century