Architects at the bacterial surface - sortases and the assembly of pili with isopeptide bonds

The cell wall envelope of Gram-positive bacteria can be thought of as a surface organelle for the assembly of macromolecular structures that enable the unique lifestyle of each microorganism. Sortases - enzymes that cleave the sorting signals of secreted proteins to form isopeptide (amide) bonds between the secreted proteins and peptidoglycan or polypeptides - function as the principal architects of the bacterial surface. Acting alone or with other sortase enzymes, sortase construction leads to the anchoring of surface proteins at specific sites in the envelope or to the assembly of pili, which are fibrous structures formed from many protein subunits. The catalysis of intermolecular isopeptide bonds between pilin subunits is intertwined with the assembly of intramolecular isopeptide bonds within pilin subunits. Together, these isopeptide bonds endow these sortase products with adhesive properties and resistance to host proteases.     

The Architects of the Evolutionary Synthesis in National Socialist Germany: Science and Politics

The Synthetic Theory of Evolution (SyntheticDarwinism) was forged between 1925 and 1950.Several historians of science have pointed outthat this synthesis was a joint venture ofSoviet, German, American and Britishbiologists: A fascinating example of scientificcooperation, considering the fact that theevolutionary synthesis emerged during thedecades in which these countries were engagedin fierce political, military and ideologicalconflicts. The ideological background of itsAnglo-American representatives has beenanalyzed in the literature. We have examinedthe scientific work and ideological commitmentsof the German Darwinians during the ThirdReich. We based our analysis on four criteria:1) General attitude towards the Third Reich. 2) Membership in the NSDAP and other nationalsocialist organizations. Endorsement anddisapproval of the state ideology in 3) scientific and 4) other publications. We willmainly discuss the various authors that havecontributed to Die Evolution derOrganismen (1943), a collection thatrepresented the evolutionary synthesis inGermany. Most of the authors promoted eugenicideas, but not all of them adopted the racistinterpretation of the Third Reich. Anotherfinding is that there existed no directconnection between party membership andpromotion of the state ideology.     

Is the Y chromosome of Drosophila an evolved supernumerary chromosome?

The Y chromosomes of most Drosophila species are necessary for male fertility but they are not involved in sex determination. They have many puzzling properties that resemble the effects caused by B chromosomes. Classical genetic and molecular studies reveal substantial affinities between Y and B chromosomes and suggest that the Y chromosomes of Drosophila are not degenerated homologues of the X chromosomes, but rather that their Y chromosomes evolved as specialized supernumeraries similar to classical B chromosomes.     

Detection of microdeletions in the short arm of the X chromosome by chromosome stretching

The present study was focused on the resolution of "chromosome stretching". In order to determine if this method can be used for the detection of microdeletions, the p-arms of 13 normal X chromosomes were stretched as well as of those with three different deletions of known size within the DMD/BMD region in Xp21 (case A: 0.42-0.45 Mb, case B: 2.3-2.9 Mb and case C: 3.0-3.5 Mb). The process of band splitting was recorded on a video-tape and the resulting banding pattern analyzed. Stretching of the normal Xp-arms led to a splitting on a maximum band level of 1400 and showed in all cases an identical banding pattern with 13 Giemsa-dark subbands. All new Giemsa-dark and -light subbands were derived from the three initial Giemsa-dark bands at the 400 band level according to ISCN (1995): five subbands from Xp21, four subbands from Xp11.3 and Xp22.2, respectively. The origin of these subbands is partly in contrast to the high resolution ISCN (1995) ideograms: subband Xp11.22 does not originate from the Giemsa-light band Xp11.2, but from the Giemsa-dark band Xp11.3; Xp22.12 originates from Xp21; Xp22.32 from Xp22.2. Stretching of the chromosomes containing deletions showed in cases A and B no differences in banding patterns and splitting order compared to normal X chromosomes. Only in patient C was a significant difference with the normal pattern visible due to the absence of one dark subband. In this case only four Giemsa-dark subbands derived from band Xp21. Thus, at least in the DMD/BMD region, the minimal size of a deletion detected by chromosome-stretching-generated high-resolution ideograms is about 3.0-3.5 Mb.     

Architects of assembly: roles of Flaviviridae non-structural proteins in virion morphogenesis

Viruses of the Flaviviridae family, including hepatitis C, dengue and bovine viral diarrhoea, are responsible for considerable morbidity and mortality worldwide. Recent advances in our understanding of virion assembly have uncovered commonalities among distantly related members of this family. We discuss the emerging hypothesis that physical virion components are not alone in forming the infectious particle, but that non-structural proteins are intimately involved in orchestrating morphogenesis. Pinpointing the roles of Flaviviridae proteins in virion production could reveal new avenues for antiviral therapeutics.     

Tandem duplication chromosome 21 in the offspring of a ring chromosome 21 carrier

A direct tandem duplication chromosome 21 was found in a boy with Down's syndrome. The proband's mother and grandmother both carried a ring chromosome 21. The observed duplication chromosome in the child may be explained either by recombination between the maternal ring and the mother's normal chromosome 21 or by break of a double-sized ring chromosome 21.     

Fragile X chromosome and chromosome condensation

The effect of chromosome condensation on the frequency of expression of the fragile X chromosome was examined. Chromosome decondensation substances were tested for their ability to elicit expression or improve frequencies of expression of the fragile X chromosome in five patients. The substances tested included the AT specific DNA ligands ethidium bromide, Hoechst 33258, and netropsin, and the GC specific substances actinomycin D and olivomycin. Under culture conditions appropriate for eliciting fragile X expression none of the decondensation compounds studied significantly altered frequencies of expression, nor did any of the substances elicit fragile X expression under conditions that normally suppress fragile X expression. The fragile X was found to be more frequently evident in less condensed chromosome preparations from fibroblasts. The implications of these findings with respect to the nature of fragile sites are discussed.     

Large-scale mapping and chromosome jumping in the q27 region of the human X chromosome

We have used pulsed field gel electrophoresis for further physical mapping studies in the q27 region of the human X chromosome. We show that the DXS 102 locus and the F9 gene are separated by only 300 kb despite a genetic distance of 1.4 cM; this linkage orients our large-scale map and shows that the mcf.2 transforming sequence is telomeric to F9. A BssHII complete-digest jumping library was used to jump toward the DXS 105 locus; a 130-kb jump was achieved and the corresponding "linking clone" was obtained.