Kunstfehler. Ärzterecht

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Allgemeine Pathologie und pathologische Anatomie

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Complex rearrangements are involved in <Emphasis Type="Italic">Cephalanthera</Emphasis> (Orchidaceae) chromosome evolution

The genus Cephalanthera is an excellent plant group for karyotype evolution studies because it exhibits a dysploid series and bimodal karyotypes. With the aim of understanding their chromosomal and phylogenetic relationships, rRNA genes and the Arabidopsis-type telomeric sequence were mapped by fluorescence in-situ hybridization (FISH), and the rDNA intergenic spacer (ITS) was sequenced for the first time in three European species: C. longifolia (2n = 4x = 32), C. damasonium (2n = 4x = 36) and C. rubra (2n = 4x = 44). One 45S and three 5S rDNA sites are observed in C. longifolia, one 45S and two 5S sites in C. damasonium, and two 45S and one 5S site in C. rubra. Telomeric signals were observed at every chromosome end in all three species and C. damasonium also displays interstitial signals on three chromosome pairs. In agreement with chromosome data, molecular analyses support C. longifolia and C. damasonium as closely related taxa, while C. rubra stands apart. Possible pathways of karyotype evolution are discussed in reference to a previous hypothesis. The results indicate that complex chromosomal rearrangements, possibly involving Robertsonian fusions and fissions, loss of telomeric repeats, gain or loss of rDNA sites and other heterochromatic sequences and inversions, may have contributed to generating the present-day karyotypes. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Sequence analysis, chromosomal distribution and long-range organization show that rapid turnover of new and old pBuM satellite DNA repeats leads to different patterns of variation in seven species of the Drosophila buzzatii cluster

We aimed to study patterns of variation and factors influencing the evolutionary dynamics of a satellite DNA, pBuM, in all seven Drosophila species from the buzzatii cluster (repleta group). We analyzed 117 alpha pBuM-1 (monomer length 190 bp) and 119 composite alpha/beta (370 bp) pBuM-2 repeats and determined the chromosome location and long-range organization on DNA fibers of major sequence variants. Such combined methodologies in the study of satDNAs have been used in very few organisms. In most species, concerted evolution is linked to high copy number of pBuM repeats. Species presenting low-abundance and scattered distributed pBuM repeats did not undergo concerted evolution and maintained part of the ancestral inter-repeat variability. The alpha and alpha/beta repeats colocalized in heterochromatic regions and were distributed on multiple chromosomes, with notable differences between species. High-resolution FISH revealed array sizes of a few kilobases to over 0.7 Mb and mutual arrangements of alpha and alpha/beta repeats along the same DNA fibers, but with considerable changes in the amount of each variant across species. From sequence, chromosomal and phylogenetic data, we could infer that homogenization and amplification events involved both new and ancestral pBuM variants. Altogether, the data on the structure and organization of the pBuM satDNA give insights into genome evolution including mechanisms that contribute to concerted evolution and diversification. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Capillary deposition of the complement fragment C4d in cardiac allograft biopsies is associated with allograft vasculopathy

Cardiac allograft vasculopathy (CAV) is a long-term threat in heart transplant recipients and its exact pathogenesis remains to be established. As complement activation contributes to early and late allograft dysfunction, we hypothesized that deposition of the complement fragment, C4d, in capillaries of cardiac allograft biopsies may be associated with CAV. A polyclonal anti-C4d antibody was used for immunohistochemistry on endomyocardial biopsies obtained from heart transplant recipients during the first year post-transplantation. CAV was assessed by intracoronary ultrasound performed at 1-year post-transplantation. We were able to show that CAV is highly associated with C4d deposition in capillaries of cardiac allografts and that serial C4d studies may predict development of CAV at 1-year post-transplantation.     

Reduced excitability in the dentate gyrus network of βIV‐spectrin mutant mice in vivo

The submembrane cytoskeletal meshwork of the axon contains the scaffolding protein βIV‐spectrin. It provides mechanical support for the axon and anchors membrane proteins. Quivering (qv^3j) mice lack functional βIV‐spectrin and have reduced voltage‐gated sodium channel (VGSC) immunoreactivity at the axon initial segment and nodes of Ranvier. Because VGSCs are critically involved in action potential generation and conduction, we hypothesized that qv^3j mice should also show functional deficits at the network level. To test this hypothesis, we investigated granule cell function in the dentate gyrus of anesthetized qv^3j mice after electrical stimulation of the perforant path in vivo. This revealed an impaired input‐output relationship between stimulus intensity and granule cell population spikes and an enhanced paired‐pulse inhibition of population spikes, indicating a reduced ability of granule cells to generate action potentials and decreased network excitability. In contrast, the input‐output curve for evoked field excitatory postsynaptic potentials (fEPSPs) and paired‐pulse facilitation of fEPSPs were unchanged, suggesting normal excitatory synaptic transmission at perforant path‐granule cell synapses in qv^3j mutants. To corroborate our findings, we analyzed the influence of VGSC density reduction on dentate network activity using an established computational model of the dentate gyrus network. This in silico approach confirmed that the loss of VGSCs is sufficient to explain the electrophysiological changes observed in qv^3j mice. Taken together, our findings demonstrate that βIV‐spectrin is required for normal granule cell firing and for physiological levels of network excitability in the mouse dentate gyrus in vivo. © 2009 Wiley‐Liss, Inc.