Analysis of the Basidiomycete Coprinopsis cinerea Reveals Conservation of the Core Meiotic Expression Program over Half a Billion Years of Evolution

Coprinopsis cinerea (also known as Coprinus cinereus) is a multicellular basidiomycete mushroom particularly suited to the study of meiosis due to its synchronous meiotic development and prolonged prophase. We examined the 15-hour meiotic transcriptional program of C. cinerea, encompassing time points prior to haploid nuclear fusion though tetrad formation, using a 70-mer oligonucleotide microarray. As with other organisms, a large proportion (∼20%) of genes are differentially regulated during this developmental process, with successive waves of transcription apparent in nine transcriptional clusters, including one enriched for meiotic functions. C. cinerea and the fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe diverged ∼500–900 million years ago, permitting a comparison of transcriptional programs across a broad evolutionary time scale. Previous studies of S. cerevisiae and S. pombe compared genes that were induced upon entry into meiosis; inclusion of C. cinerea data indicates that meiotic genes are more conserved in their patterns of induction across species than genes not known to be meiotic. In addition, we found that meiotic genes are significantly more conserved in their transcript profiles than genes not known to be meiotic, which indicates a remarkable conservation of the meiotic process across evolutionarily distant organisms. Overall, meiotic function genes are more conserved in both induction and transcript profile than genes not known to be meiotic. However, of 50 meiotic function genes that were co-induced in all three species, 41 transcript profiles were well-correlated in at least two of the three species, but only a single gene (rad50) exhibited coordinated induction and well-correlated transcript profiles in all three species, indicating that co-induction does not necessarily predict correlated expression or vice versa. Differences may reflect differences in meiotic mechanisms or new roles for paralogs. Similarities in induction, transcript profiles, or both, should contribute to gene discovery for orthologs without currently characterized meiotic roles

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

ANKHD1, ankyrin repeat and KH domain containing 1, is overexpressed in acute leukemias and is associated with SHP2 in K562 cells

In the present study, increased levels of ANKHD1 mRNA and protein expression in leukemia cell lines are reported, as compared with normal hematopoietic cells. Furthermore, a higher expression of ANKHD1 mRNA was detected in primary acute leukemia samples than in normal hematopoietic cells (P=0.002). ANKHD1 was detected in the cytosolic and membrane fraction of cells and was co-immumoprecipitated with SHP2 in protein extracts of K562 and LNCaP cell lines. These findings suggest a role for ANKHD1 as a scaffolding protein that may be associated with the abnormal phenotype of leukemia cells. (c) 2006 Elsevier B.V. All rights reserved.1762982883

Characterisation of a new splice variant of MASK-BP3(ARF) and MASK human genes, and their expression patterns during haematopoietic cell differentiation

In this study we report the characterisation of a new splice variant, here denominated splice variant 4 (accession number AF258557) of the human Multiple Ankyrin repeats Single KH domain (hMASK) (accession number AF521882) and the hMASK-4E-Binding Protein 3 Alternative Reading Frame (hMASK-BP3(ARF)) (accession number AF521883), containing a number of ANK-repeat motifs. Ankyrin (ANK) repeat-containing proteins carry out a wide variety of biological activities and are involved in processes, such as cell differentiation and transcriptional regulation. The present study reports the computer analysis of these splice variant cDNAs and their broad mRNA expression in different normal human tissues and cancer cell lines. An upregulation of the splice variant mRNAs expression was observed after HL-60 and erythroblast differentiation. The upregulation of splice variant 4 mRNA was considerably higher than those of the other variants, during erythroid differentiation. (c) 2005 Elsevier B.V. All rights reserved.36311312