Nuclear Segmentation, Condensation and Bilateral Symmetry in Polymorphonuclear Leukocytes Reflect Genomic Order and Favor Immunologic Function

Segmentation, condensation and bilateral symmetry of the nuclei ofpolymorphonuclear leukocytes seem related to their function.Segmentation of the nuclei into two or more lobes and their condensationfacilitate their passage (diapedesis) through the endothelial layer ofblood vessels to the extravasal space and subsequent locomotion throughthe interstitial compartment of different tissues. Bilateral symmetry ofthese nuclei along with their association to the cytoskeletal fiberscontribute to their efficiency in locomotion by alignment of the axis ofnuclear symmetry to the axis of cellular polarity, which orients towardsthe direction of locomotion in response to cytokines and other stimuli.Observations of the cytogenetic facets of intranuclear order supportthese assumptions

Nuclear Segmentation, Condensation and Bilateral Symmetry in Polymorphonuclear Leukocytes Reflect Genomic Order and Favor Immunologic Function

Segmentation, condensation and bilateral symmetry of the nuclei ofpolymorphonuclear leukocytes seem related to their function.Segmentation of the nuclei into two or more lobes and their condensationfacilitate their passage (diapedesis) through the endothelial layer ofblood vessels to the extravasal space and subsequent locomotion throughthe interstitial compartment of different tissues. Bilateral symmetry ofthese nuclei along with their association to the cytoskeletal fiberscontribute to their efficiency in locomotion by alignment of the axis ofnuclear symmetry to the axis of cellular polarity, which orients towardsthe direction of locomotion in response to cytokines and other stimuli.Observations of the cytogenetic facets of intranuclear order supportthese assumptions

Detection and characterization of 3D-signature phosphorylation site motifs and their contribution towards improved phosphorylation site prediction in proteins

<p>Abstract</p> <p>Background</p> <p>Phosphorylation of proteins plays a crucial role in the regulation and activation of metabolic and signaling pathways and constitutes an important target for pharmaceutical intervention. Central to the phosphorylation process is the recognition of specific target sites by protein kinases followed by the covalent attachment of phosphate groups to the amino acids serine, threonine, or tyrosine. The experimental identification as well as computational prediction of phosphorylation sites (P-sites) has proved to be a challenging problem. Computational methods have focused primarily on extracting predictive features from the local, one-dimensional sequence information surrounding phosphorylation sites.</p> <p>Results</p> <p>We characterized the spatial context of phosphorylation sites and assessed its usability for improved phosphorylation site predictions. We identified 750 non-redundant, experimentally verified sites with three-dimensional (3D) structural information available in the protein data bank (PDB) and grouped them according to their respective kinase family. We studied the spatial distribution of amino acids around phosphorserines, phosphothreonines, and phosphotyrosines to extract signature 3D-profiles. Characteristic spatial distributions of amino acid residue types around phosphorylation sites were indeed discernable, especially when kinase-family-specific target sites were analyzed. To test the added value of using spatial information for the computational prediction of phosphorylation sites, Support Vector Machines were applied using both sequence as well as structural information. When compared to sequence-only based prediction methods, a small but consistent performance improvement was obtained when the prediction was informed by 3D-context information.</p> <p>Conclusion</p> <p>While local one-dimensional amino acid sequence information was observed to harbor most of the discriminatory power, spatial context information was identified as relevant for the recognition of kinases and their cognate target sites and can be used for an improved prediction of phosphorylation sites. A web-based service (Phos3D) implementing the developed structure-based P-site prediction method has been made available at <url>http://phos3d.mpimp-golm.mpg.de</url>.</p

Biphasic Chromatin Structure and FISH Signals Reflect Intranuclear Order

Background and Aim: One of the two parental allelic genes may selectively be expressed, regulated by imprinting, X-inactivation or by other less known mechanisms. This study aims to reflect on such genetic mechanisms. Materials and Methods: Slides from short term cultures or direct smears of blood, bone marrow and amniotic fluids were hybridized with FISH probes singly, combined or sequentially. Two to three hundred cells were examined from each preparation. Results and Aignificance: A small number of cells (up to about 5%), more frequent in leukemia cases, showed the twin features: (1) nuclei with biphasic chromatin, one part decondensed and the other condensed; and (2) homologous FISH signals distributed equitably in those two regions. The biphasic chromatin structure with equitable distribution of the homologous FISH signals may correspond to the two sets of chromosomes, supporting observations on ploidywise intranuclear order. The decondensed chromatin may relate to enhanced transcriptions or advanced replications. Conclusions: Transcriptions of only one of the two parental genomes cause allelic exclusion. Genomes may switch with alternating monoallelic expression of biallelic genes as an efficient genetic mechanism. If genomes fail to switch, allelic exclusion may lead to malignancy. Similarly, a genome-wide monoallelic replication may tilt the balance of heterozygosity resulting in aneusomy, initiating early events in malignant transformation and in predicting cancer mortality

Chromosomes in a genome-wise order: evidence for metaphase architecture

Background: One fundamental finding of the last decade is that, besides the primary DNA sequence information there are several epigenetic "information-layers" like DNA-and histone modifications, chromatin packaging and, last but not least, the position of genes in the nucleus. Results: We postulate that the functional genomic architecture is not restricted to the interphase of the cell cycle but can also be observed in the metaphase stage, when chromosomes are most condensed and microscopically visible. If so, it offers the unique opportunity to directly analyze the functional aspects of genomic architecture in different cells, species and diseases. Another aspect not directly accessible by molecular techniques is the genome merged from two different haploid parental genomes represented by the homologous chromosome sets. Our results show that there is not only a well-known and defined nuclear architecture in interphase but also in metaphase leading to a bilateral organization of the two haploid sets of chromosomes. Moreover, evidence is provided for the parental origin of the haploid grouping. Conclusions: From our findings we postulate an additional epigenetic information layer within the genome including the organization of homologous chromosomes and their parental origin which may now substantially change the landscape of genetics

Sacred Objects in Arts and Crafts of Rudolf II. Types and Iconography

When Emperor Rudolf II. moved to Prague with his court, city became one of the most important centers in Europe. The cultural aspirations of the new Emperor led to organizing a large collection with the great things from categories artificialia, naturalia, scientifica and to invitation of extraordinary craftsmen from the whole Europe. Masters of art and crafts were also invited on special decrees. Masters of art and crafts made very specific types in sacred way. Firstly there were small home altars with original commessi made by family of Castrucci and Miseroni in combination with other materials and cooperation with the other craftsmen. Further there were portrait medals by family of Abondio, gems - first of all by Ottavio Miseroni and Alessandro Masnago with assemblys by Jan Vermeyen and Andreas Osenbruck, commessi di pietre dure with sacred themes in fantastic and real landscapes by Castrucci family, plaquettes by Paulus von Vianen, statues by Ottavio Miseroni, chalices, crucifixes and monstrances. There were also very important handstones (handstein) with the sculpture solution of origin material with sacred themes. Further Emperor very appreciated original mosaics from various kinds of exotic birds with sacred themes from Mexico. This type of work has iris effect. There were also very important..

Additional file 5: Figure S4. of Chromosomes in a genome-wise order: evidence for metaphase architecture

Metaphases from ten different primate species (see also Additional file 4: Table S1) demonstrating a genome-wise sorting of the haploid chromosome sets after M-FISH showing chromosome grouping and the closer location of homologous chromosomes next to the symmetry line. (TIF 727 kb

Additional file 7: Figure S6. of Chromosomes in a genome-wise order: evidence for metaphase architecture

Round shaped metaphase spread from Silvery Langur (TCR, Trachypithecus cristata). Measurement of DNA content by DAPI per area resulted in ~20 % independent if the whole area is counted or a pie slice reflecting a symmetric/round shaped distribution of DNA in the metaphase state of the cell cycle. (TIF 255 kb