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Biomedical subjects

T Papenbrock

Publications and source records attributed to T Papenbrock.

13 recordsLinked to original sources
PubMed2002

Experimental test of a trace formula for a chaotic three-dimensional microwave cavity.

We have measured resonance spectra in a superconducting microwave cavity with the shape of a three-dimensional generalized Bunimovich stadium billiard and analyzed their spectral fluctuation properties. The experimental length spectrum exhibits contributions from periodic orbits of nongeneric modes and from unstable periodic orbits of the underlying classical system. It is well reproduced by our theoretical calculations based on the trace formula derived by Balian and Duplantier for chaotic electromagnetic cavities.

Journal Article↗
PubMed2001

Overexpression of Hoxc13 in differentiating keratinocytes results in downregulation of a novel hair keratin gene cluster and alopecia.

Studying the roles of Hox genes in normal and pathological development of skin and hair requires identification of downstream target genes in genetically defined animal models. We show that transgenic mice overexpressing Hoxc13 in differentiating keratinocytes of hair follicles develop alopecia, accompanied by a progressive pathological skin condition that resembles ichthyosis. Large-scale analysis of differential gene expression in postnatal skin of these mice identified 16 previously unknown and 13 known genes as presumptive Hoxc13 targets. The majority of these targets are downregulated and belong to a subgroup of genes that encode hair-specific keratin-associated proteins (KAPs). Genomic mapping using a mouse hamster radiation hybrid panel showed these genes to reside in a novel KAP gene cluster on mouse chromosome 16 in a region of conserved linkage with human chromosome 21q22.11. Furthermore, data obtained by Hoxc13/lacZ reporter gene analysis in mice that overexpress Hoxc13 suggest negative autoregulatory feedback control of Hoxc13 expression levels, thus providing an entry point for elucidating currently unknown mechanisms that are required for regulating quantitative levels of Hox gene expression. Combined, these results provide a framework for understanding molecular mechanisms of Hoxc13 function in hair growth and development.

Alopecia↗
PubMed2000

Wave function structure in two-body random matrix ensembles

We study the structure of eigenstates in two-body interaction random matrix ensembles and find significant deviations from random matrix theory expectations. The deviations are most prominent in the tails of the spectral density and indicate localization of the eigenstates in Fock space. Using ideas related to scar theory we derive an analytical formula that relates fluctuations in wave function intensities to fluctuations of the two-body interaction matrix elements. Numerical results for many-body fermion systems agree well with the theoretical predictions.

Journal Article↗
PubMed2000

Quantization of a billiard model for interacting particles

We consider a billiard model of a self-bound, interacting three-body system in two spatial dimensions. Numerical studies show that the classical dynamics is chaotic. The corresponding quantum system displays spectral fluctuations that exhibit small deviations from random matrix theory predictions. These can be understood in terms of a new type of scarring caused by a one-parameter family of orbits inside the collinear manifold.

Journal Article↗
PubMed2000

Assembly of tight junctions during early vertebrate development.

Tight junction formation during development is critical for embryonic patterning and organization. We consider mechanisms of junction biogenesis in cleaving mouse and Xenopus eggs. Junction assembly follows the establishment of cell polarity at 8-cell (mouse) or 2-cell (Xenopus) stages, characterized by sequential membrane delivery of constituents, coordinated by embryonic (mouse) or maternal (Xenopus) expression programmes. Cadherin adhesion is permissive for tight junction construction only in the mouse. Occludin post-translational modification and membrane delivery, mediated by delayed ZO-1 alpha(+)isoform expression in the mouse, provides a mechanism for completion of tight junction biogenesis and sealing, regulating the timing of blastocoel cavitation.

Animals↗
PubMed2000

Loss of fibula in mice overexpressing Hoxc11.

This study demonstrates severe malformations of the appendicular skeleton in mice overexpressing Hoxc11. Consistent with the endogenous expression pattern, the most conspicuous defect in Hoxc11 overexpressing neonates is aplasia/hypoplasia of the fibula. This is preceded at day 15.5 of embryonic development by marked reduction of chondrocyte proliferation, lack of PTHR expressing prehypertrophic cells, and the absence of hypertrophic and calcifying chondrocytes. Combined with the lack of an overt phenotype in the majority of Hoxc11 overexpressing embryos at day 13.5, the data suggest inhibition of chondrocyte differentiation during the elongation phase of the fibula bone as a primary effect of elevated Hoxc11 expression. This interpretation is further corroborated by Hoxc11 reporter gene expression in the joint areas at embryonic day 15.5, suggesting an involvement of the periarticular perichondrium in generating the mutant phenotype.

Animals↗
PubMed2000

Lyapunov exponents and kolmogorov-sinai entropy for a high-dimensional convex billiard

We compute the Lyapunov exponents and the Kolmogorov-Sinai (KS) entropy for a self-bound N-body system that is realized as a convex billiard. This system exhibits truly high-dimensional chaos, and 2N-4 Lyapunov exponents are found to be positive. The KS entropy increases linearly with the numbers of particles. We examine the chaos generating defocusing mechanism and investigate how high-dimensional chaos develops in this system with no dispersing elements.

Journal Article↗
PubMed2000

Numerical study of a three-dimensional generalized stadium billiard

We study a generalized three-dimensional stadium billiard and present strong numerical evidence that this system is completely chaotic. In this convex billiard chaos is generated by the defocusing mechanism. The construction of this billiard uses cylindrical components as the focusing elements and thereby differs from the recent approach pioneered by Bunimovich and Rehacek [Commun. Math. Phys. 189, 729 (1997)]. We investigate the stability of lower-dimensional invariant manifolds and discuss bouncing ball modes.

Journal Article↗
PubMed2000

Genomic instability-based transgenic models of prostate cancer.

To develop animal models that represent the broad spectrum of human prostate cancer, we created transgenic mice with targeted prostate-specific expression of two genes (ECO:RI and c-fos) implicated in the induction of genomic instability. Expression of the transgenes was restricted to prostate epithelial cells by coupling them to the tissue-specific, hormonally regulated probasin promoter (PB). The effects of transgene expression were examined histologically in prostate sections at time points taken from 4 to 24 months of age. The progressive presence of regions of mild-to-severe hyperplasia, low- and high-grade prostatic intra-epithelial neoplasia, and well-differentiated adenocarcinoma was observed in both PBECO:RI lines but no significant pathology was detected in the PBfos line. Prostate tissue of PBECO:RI mice was examined for expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 at multiple time points. Although p53 does not appear to be mutated, levels of PCNA and Ki67 are elevated and correlate with the severity of the prostatic lesions. Overall, pre-neoplastic and neoplastic stages represented in the PBECO:RI model showed similarity to corresponding early stages of the human disease. This genomic instability-based model will be used to study the mechanisms involved in the early stages of prostate carcinogenesis and to investigate the nature of subsequent events necessary for the progression to advanced disease.

Animals↗
PubMed1998

Murine Hoxc-9 gene contains a structurally and functionally conserved enhancer.

Reporter gene analysis of the Hoxc-9 genomic region in transgenic mice allowed us to identify a positional enhancer in the Hoxc-9 intron that drives expression in the posterior neural tube of midgestation mouse embryos in a Hoxc-9-related manner. Sequence comparison to the chicken Choxc-9 intron revealed the existence of two highly conserved sequence elements (CSEs) in a similar spatial arrangement. These structural similarities in the mammalian and avian lineage are mirrored by conserved function of the chicken Choxc-9 intron in transgenic mice. Deletion analysis of the two introns suggests that full activity of both enhancers depends on cooperation between the two CSEs located close to the respective 5' and 3' splice sites. Following the paradigm of phylogenetically conserved developmental control mechanisms, the Hoxc-9 intragenic enhancer was tested in Drosophila. Our data show that the mouse Hoxc-9 enhancer acts in a conserved fashion in transgenic flies, conferring posteriorly restricted reporter gene expression to the developing central nervous system in third instar larvae. This finding indicates that the Hoxc-9 intragenic enhancer is involved in transcriptional regulatory circuits conserved between vertebrates and arthropods.

Animals↗
PubMed1994

The murine Hoxc cluster contains five neighboring AbdB-related Hox genes that show unique spatially coordinated expression in posterior embryonic subregions.

A common feature of the murine Abdominal B (AbdB) -related Hox genes, located in the 5' regions of the four Hox clusters, appears to be a function in patterning the developing limb. As a prerequisite for studying the role of the AbdB-related Hoxc genes during limb development, we have isolated and mapped the three predicted AbdB-related Hoxc-11, -12, and -13 loci, thus defining the 5' end of the Hoxc cluster. Sequence comparisons based on the homeobox sequences of presumably all murine AbdB-related Hox genes strongly support the concept of a two step process in their evolution. As expected, Hoxc-11, -12 and -13 exhibit nested and extremely posteriorly restricted expression domains, whose anterior boundaries reflect their map positions, in accordance with the colinearity rule. A limited comparison of the primary expression domains of all five AbdB-related Hoxc genes in the developing hindlimb revealed nested and increasingly restricted domains of expression in the mesenchyme for only Hoxc-9, -10 and -11. However, separate localized expression was detected for Hoxc-9, -10, -11, -12 and possibly -13 in distal epidermal regions of the developing hind- and forelimb, whereas no expression of any of the five genes was observed in mesenchymal tissues of the developing forelimb. These data suggest a specific role for the AbdB-related Hoxc genes in patterning the hindlimb and pelvic girdle, which is separate from a second role relevant for both hind- and forelimb development.

Amino Acid Sequence↗
PubMed1987

A highly abundant transcript in adult murine cerebellar granule cells contains repetitive sequences homologous to L1.

Cloned cDNA from adult mouse cerebellum composed of subsequences homologous to the L1Md consensus sequence (long interspersed repetitive element "LINE" family of the mouse) hybridizes specifically with large nuclear poly(A)+RNAs that are highly concentrated in the murine and rat cerebellum. These homogeneous L1-related transcripts were localized in the mouse CNS by in situ hybridization with 3H- and biotin-labeled DNA probes. They were found to hybridize to cerebellar granule cells specifically.

Animals↗