Somatic diversification of variable lymphocyte receptors in the agnathan sea lamprey

Although jawless vertebrates are apparently capable of adaptive immune responses, they have not been found to possess the recombinatorial antigen receptors shared by all jawed vertebrates. Our search for the phylogenetic roots of adaptive immunity in the lamprey has instead identified a new type of variable lymphocyte receptors (VLRs) composed of highly diverse leucine-rich repeats (LRR) sandwiched between amino- and carboxy-terminal LRRs. An invariant stalk region tethers the VLRs to the cell surface by means of a glycosyl-phosphatidyl-inositol anchor. To generate rearranged VLR genes of the diversity necessary for an anticipatory immune system, the single lamprey VLR locus contains a large bank of diverse LRR cassettes, available for insertion into an incomplete germline VLR gene. Individual lymphocytes express a uniquely rearranged VLR gene in monoallelic fashion. Different evolutionary strategies were thus used to generate highly diverse lymphocyte receptors through rearrangement of LRR modules in agnathans ( jawless fish) and of immunoglobulin gene segments in gnathostomes ( jawed vertebrates).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62870/1/nature02740.pd

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

Allozyme variation in relation to ecotypic differentiation and population size in marginal populations of Silene nutans

In Belgium, at the north-western margin of its geographical range, Silene nutans is a rare species, which has evolved a silicicolous (Si) and a calcicolous (Ca) ecotype, with contrasting morphometric traits. Genetic diversity and population genetic structure were examined for seven allozyme loci in 16 Si and 18 Ca populations (a total of 567 individuals). High genetic variation was found at both the ecotypic and population level, and no significant correlation was found between population size and any measure of genetic variation. The maintenance of high levels of genetic diversity in small, marginal populations might be explained by the perennial, long-lived life form and the outcrossing breeding system of the species. Additionally, low F(ST)-values suggested that efficient gene flow was occurring within both ecotypes. Genetic distance measures and cluster analysis using UPGMA on the distance matrix revealed that the populations were differentiated according to their ecotypic property in two distinct gene pools. It is argued that the congruence of allozymic and morphometric differentiation between edaphic races is unusual for an outcrossing species. This finding, together with previous observations of isolating mechanisms between ecotypes, strongly suggests that incipient speciation is occurring within Silene nutans at the margin of its geographical range.SCOPUS: ar.jSCOPUS: ar.jinfo:eu-repo/semantics/publishe