The Chlamydia psittaci Genome: A Comparative Analysis of Intracellular Pathogens

Chlamydiaceae are a family of obligate intracellular pathogens causing a wide range of diseases in animals and humans, and facing unique evolutionary constraints not encountered by free-living prokaryotes. To investigate genomic aspects of infection, virulence and host preference we have sequenced Chlamydia psittaci, the pathogenic agent of ornithosis.A comparison of the genome of the avian Chlamydia psittaci isolate 6BC with the genomes of other chlamydial species, C. trachomatis, C. muridarum, C. pneumoniae, C. abortus, C. felis and C. caviae, revealed a high level of sequence conservation and synteny across taxa, with the major exception of the human pathogen C. trachomatis. Important differences manifest in the polymorphic membrane protein family specific for the Chlamydiae and in the highly variable chlamydial plasticity zone. We identified a number of psittaci-specific polymorphic membrane proteins of the G family that may be related to differences in host-range and/or virulence as compared to closely related Chlamydiaceae. We calculated non-synonymous to synonymous substitution rate ratios for pairs of orthologous genes to identify putative targets of adaptive evolution and predicted type III secreted effector proteins.This study is the first detailed analysis of the Chlamydia psittaci genome sequence. It provides insights in the genome architecture of C. psittaci and proposes a number of novel candidate genes mostly of yet unknown function that may be important for pathogen-host interactions

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Testing a Life-Cycle Theory of Cooperative Interorganizational Relationships: Movement Across Stages and Performance

This research examines the evolution of cooperative interorganizational relationships and provides an empirical test of four propositions from the DSO (Dwyer et al. 1987) life-cycle theory, and one proposition from the RV (Ring and Van de Ven 1994) theory of relationship development. Using primary data from over 1,500 resellers in a channel of distribution, we find that the mature phase is not the pinnacle of the relationship lifecycle; relationship properties (e.g., relationship harmony, overall dependence, and the reseller's trust in the manufacturer) in this stage are no different than in the build-up phase. However, relationship properties that support relationship expansion (e.g., goal congruence and information exchange norms) reach their zenith in the build-up phase and afterwards fade into the background. All of the various relationship properties hit their nadir in the decline phase. We also examine the development of relationships over a five-year period and consider whether movement across the stages in accordance with DSO's theory has the same association to overall performance evaluations as movement through regressive patterns. We find that a negative history extracts a price: Movement through regressive patterns is negatively related to performance, and these relationships do not enjoy a fresh start. Instead, these movements can last for an extended period of time and are negatively related to performance outcomes during the decline phase. Thus, the development path taken appears to be related to the results achieved. Finally, we also find evidence of the critical role that individual sales representatives play in creating successful interorganizational relationships.interorganizational relationships, cooperative relationships, life-cycle theory, path dependence, performance, relationship decline