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Biomedical subjects

K Wollenberg

Publications and source records attributed to K Wollenberg.

8 recordsLinked to original sources

Evolution of proteasomal ATPases.

In eukaryotic cells, the majority of proteins are degraded via the ATP-dependent ubiquitin/26S proteasome pathway. The proteasome is the proteolytic component of the pathway. It is a very large complex with a mass of around 2.5 MDa, consisting of at least 62 proteins encoded by 31 genes. The eukaryotic proteasome has evolved from a simpler archaebacterial form, similar in structure but containing only three different peptides. One of these peptides is an ATPase belonging to the AAA (Triple-A) family of ATPASES: Gene duplication and diversification has resulted in six paralogous ATPases being present in the eukaryotic proteasome. While sequence analysis studies clearly show that the six eukaryotic proteasomal ATPases have evolved from the single archaebacterial proteasomal ATPase, the deep node structures of the phylogenetic constructions lack resolution. Incorporating physical data to provide support for alternative phylogenetic hypotheses, we have constructed a model of a possible evolutionary history of the proteasomal ATPASES:

Adenosine Triphosphatases↗

Phylogenetic analyses of amino acid variation in the serpin proteins.

Phylogenetic analyses of 110 serpin protein sequences revealed clades consistent with independent phylogenetic analyses based on exon-intron structure and diagnostic amino acid sites. Trees were estimated by maximum likelihood, neighbor joining, and partial split decomposition using both the BLOSUM 62 and Jones-Taylor-Thornton substitution matrices. Neighbor-joining trees gave results closest to those based on independent analyses using genomic and chromosomal data. The maximum-likelihood trees derived using the quartet puzzling algorithm were very conservative, producing many small clades that separated groups of proteins that other results suggest were related. Independent analyses based on exon-intron structure suggested that a neighbor-joining tree was more accurate than maximum-likelihood trees obtained using the quartet puzzling algorithm.

Amino Acids↗

Careful clinical monitoring in comparison to sequential Doppler sonography for the detection of acute rejection in the early phase after renal transplantation.

Acute rejection is the most frequent cause of early graft failure. There is unanimity that Doppler sonography is a helpful method for the detection of complications after kidney transplantation. In the past, the indication for renal biopsy relied mainly on clinical assessment, although this assessment has not been standardised. Therefore, we conducted this prospective study to compare the value of sequential Doppler measurements with a standardised clinical rejection score, based on renal function, weight gain, graft swelling and tenderness. Fifty-eight patients (37 males, 21 females, mean age 46 +/- 12 years) after kidney transplantation were consecutively enrolled into the study. Doppler investigations were obtained within the first 24 h after transplantation, followed by an interval of 48-72 h. At the same time, a clinical examination was scored by a transplant physician blinded to the Doppler results. Clinical score and Doppler results, both were referred to the histological results of renal biopsy. In 24 out of 58 patients 25 acute rejections occurred. In seven patients, acute rejection was superimposed on primary graft failure. The cut-off levels for rejection were set at RI > or = 0.80 and PI > or = 1.70 based on receiver-operator curves using data from 663 Doppler examinations. Sensitivity and specificity was 72% for RI, and 72% and 74% for PI, respectively. The calculation of the intraindividual increase (deltaRI > or = 3%, deltaPI > or = 10%) did not improve these values. The clinical score revealed a sensitivity and specificity of 82% and 87%, respectively. The combined analysis of Doppler indices and clinical score showed a sensitivity of 96% with a specificity of 66%. Careful clinical monitoring alone using a clinical score is an appropriate procedure with which to decide about renal biopsy. Our data show that Doppler sonography should be performed within the first 24 h after transplantation to evaluate graft perfusion and baseline values. Afterwards, it should be used when clinical signs of rejection occur to underline the decision for renal biopsy even in borderline cases.

Acute Disease↗

Phylogenetics and the origin of species.

A recent criticism that the biological species concept (BSC) unduly neglects phylogeny is examined under a novel modification of coalescent theory that considers multiple, sex-defined genealogical pathways through sexual organismal pedigrees. A competing phylogenetic species concept (PSC) also is evaluated from this vantage. Two analytical approaches are employed to capture the composite phylogenetic information contained within the braided assemblages of hereditary pathways of a pedigree: (i) consensus phylogenetic trees across allelic transmission routes and (ii) composite phenograms from quantitative values of organismal coancestry. Outcomes from both approaches demonstrate that the supposed sharp distinction between biological and phylogenetic species concepts is illusory. Historical descent and reproductive ties are related aspects of phylogeny and jointly illuminate biotic discontinuity.

Models, Genetic↗

Recognizing the forest for the trees: testing temporal patterns of cladogenesis using a null model of stochastic diversification.

Computer simulations are developed and employed to examine the expected temporal distributions of nodes under a null model of stochastic lineage bifurcation and extinction. These Markovian models of phylogenetic process were constructed so as to permit direct comparisons against empirical phylogenetic trees generated from molecular or other information available solely from extant species. For replicate simulated phylads with n extant species, cumulative distribution functions (cdf's) of branching times were calculated, and compared (using the Kolmogorov-Smirnov test statistic D) to those from three published empirical trees. Molecular phylogenies for columbine plants and avian cranes showed statistically significant departures from the null expectations, in directions indicating recent and ancient species' radiations, respectively, whereas a molecular phylogeny for the Drosophila virilis species group showed no apparent historical clustering of branching events. Effects of outgroup choice and phylogenetic frame of reference were investigated for the columbines and found to have a predictable influence on the types of conclusions to be drawn from such analyses. To enable other investigators to statistically test for nonrandomness in temporal cladogenetic pattern in empirical trees generated from data on extant species, we present tables of mean cdf's and associated probabilities under the null model for expected branching times in phylads of varying size. The approaches developed in this report complement and extend those of other recent methods for employing null models to assess the statistical significance of pattern in evolutionary trees.

Animals↗