Proliferation status defines functional properties of endothelial cells

Homeostasis of solid tissue is characterized by a low proliferative activity of differentiated cells while special conditions like tissue damage induce regeneration and proliferation. For some cell types it has been shown that various tissue-specific functions are missing in the proliferating state, raising the possibility that their proliferation is not compatible with a fully differentiated state. While endothelial cells are important players in regenerating tissue as well as in the vascularization of tumors, the impact of proliferation on their features remains elusive. To examine cell features in dependence of proliferation, we established human endothelial cell lines in which proliferation is tightly controlled by a doxycycline-dependent, synthetic regulatory unit. We observed that uptake of macromolecules and establishment of cell–cell contacts was more pronounced in the growth-arrested state. Tube-like structures were formed in vitro in both proliferating and non-proliferating conditions. However, functional vessel formation upon transplantation into immune-compromised mice was restricted to the proliferative state. Kaposi’s sarcoma-associated herpes virus (KSHV) infection resulted in reduced expression of endothelial markers. Upon transplantation of infected cells, drastic differences were observed: proliferation arrested cells acquired a high migratory activity while the proliferating counterparts established a tumor-like phenotype, similar to Kaposi Sarcoma lesions. The study gives evidence that proliferation governs endothelial functions. This suggests that several endothelial functions are differentially expressed during angiogenesis. Moreover, since proliferation defines the functional properties of cells upon infection with KSHV, this process crucially affects the fate of virus-infected cells.     

Chemical investigation of hassium (element 108)

The periodic table provides a classification of the chemical properties of the elements. But for the heaviest elements, the transactinides, this role of the periodic table reaches its limits because increasingly strong relativistic effects on the valence electron shells can induce deviations from known trends in chemical properties. In the case of the first two transactinides, elements 104 and 105, relativistic effects do indeed influence their chemical properties, whereas elements 106 and 107 both behave as expected from their position within the periodic table. Here we report the chemical separation and characterization of only seven detected atoms of element 108 (hassium, Hs), which were generated as isotopes (269)Hs (refs 8, 9) and (270)Hs (ref. 10) in the fusion reaction between (26)Mg and (248)Cm. The hassium atoms are immediately oxidized to a highly volatile oxide, presumably HsO(4), for which we determine an enthalpy of adsorption on our detector surface that is comparable to the adsorption enthalpy determined under identical conditions for the osmium oxide OsO(4). These results provide evidence that the chemical properties of hassium and its lighter homologue osmium are similar, thus confirming that hassium exhibits properties as expected from its position in group 8 of the periodic table.     

Genetic evidence against panmixia in the European eel

The panmixia hypothesis--that all European eel (Anguilla anguilla) migrate to the Sargasso Sea for reproduction and comprise a single, randomly mating population--is widely accepted. If true, then this peculiar life history strategy would directly impact the population genetics of this species, and eels from European and north African rivers should belong to the same breeding population through the random dispersal of larvae. To date, the panmixia hypothesis has remained unchallenged: genetic studies realized on eel's mitochondrial DNA failed to detect any genetic structure; and a similar lack of structure was found using allozymes, with the exception of clinal variation imposed by selection. Here we have used highly polymorphic genetic markers that provide better resolution to investigate genetic structure in European eel. Analysis of seven microsatellite loci among 13 samples from the north Atlantic, the Baltic Sea and the Mediterranean Sea basins reveals that there is global genetic differentiation. Moreover, pairwise Cavalli-Sforza and Edwards chord distances correlate significantly with coastal geographical distance. This pattern of genetic structure implies non-random mating and restricted gene flow among eels from different sampled locations, which therefore refute the hypothesis of panmixia. Consequently, the reproductive biology of European eel must be reconsidered.     

Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity

Plague is a pandemic human invasive disease caused by the bacterial agent Yersinia pestis. We here report a comparison of 17 whole genomes of Y. pestis isolates from global sources. We also screened a global collection of 286 Y. pestis isolates for 933 SNPs using Sequenom MassArray SNP typing. We conducted phylogenetic analyses on this sequence variation dataset, assigned isolates to populations based on maximum parsimony and, from these results, made inferences regarding historical transmission routes. Our phylogenetic analysis suggests that Y. pestis evolved in or near China and spread through multiple radiations to Europe, South America, Africa and Southeast Asia, leading to country-specific lineages that can be traced by lineage-specific SNPs. All 626 current isolates from the United States reflect one radiation, and 82 isolates from Madagascar represent a second radiation. Subsequent local microevolution of Y. pestis is marked by sequential, geographically specific SNPs.     

A revision of the Nearctic species of Clinohelea Kieffer (Diptera: Ceratopogonidae)

The seven species of Clinohelea known to inhabit North America are described and illustrated, and a key is provided for identification. Two species groups are recognized: the unimaculata group and the bimaculata group. Clinohelea longitheca and C. pseudonubifera are new. Clino - helea nebulosa (Malloch) is a synonym of C. curriei (Coquillett) NEW SYNONOMY.     

Stable expression of the bacterial neor gene in Leishmania enriettii

Molecular genetic studies in parasitic protozoa have been hindered by the lack of methods for the introduction and expression of modified or foreign genes in these organisms. Two recent reports described the transient expression of the bacterial chloramphenicol acetyl transferase (CAT) gene under the control of parasite-specific sequences. We now describe the stable expression of a selectable marker, the gene for neomycin resistance (neor) in Leishmania enriettii. A chimaeric gene containing the neor gene inserted between two alpha-tubulin intergenic sequences was introduced into the cells and drug-resistant L. enriettii were observed which stably expressed the neor gene. One goal of this work was to analyse the sequences necessary for trans-splicing of messenger RNA, as trypanosomatids have a novel process of RNA trans-splicing, described initially in Trypanosome brucei and subsequently in several other trypanosomatids, including L. enriettii. Many trypanosomatid genes are arranged in tandem arrays and the intergenic sequences contain both the splice acceptor site for the addition of the spliced leader sequence and a putative polyadenylation site. Messenger RNA isolated from several different neor L. enrietti lines contained the spliced leader sequence joined to the neor gene at the position of the splice acceptor site in the alpha-tubulin intergenic sequence. The neor mRNA was also polyadenylated. Plasmid DNA is present within the drug-resistant organisms and appears to be extrachromosomal. The development of these methods allows the functional analysis of sequences necessary for trans-splicing.     

Constituents ofCannabis sativa L. XXI: Estrogenic activity of a non-cannabinoid constituent

Summary A non-cannabinoid phenol (4,4,dihydroxy-5-methoxybibenzyl) increased uterine weight in prepubescent female rats, suggesting non-cannabinoids contribute to the estrogenic effects ofCannabis.Acknowledgments. This research was supported by Contract 271-78-3527 from the National Institute on Drug Abuse and by the Research Institute of Pharmaceutical Sciences, University of Mississippi. The authors are grateful to Karen S. Tomaszewski for technical assistance.     

A genome-wide map of diversity in Plasmodium falciparum

Genetic variation allows the malaria parasite Plasmodium falciparum to overcome chemotherapeutic agents, vaccines and vector control strategies and remain a leading cause of global morbidity and mortality. Here we describe an initial survey of genetic variation across the P. falciparum genome. We performed extensive sequencing of 16 geographically diverse parasites and identified 46,937 SNPs, demonstrating rich diversity among P. falciparum parasites (pi = 1.16 x 10(-3)) and strong correlation with gene function. We identified multiple regions with signatures of selective sweeps in drug-resistant parasites, including a previously unidentified 160-kb region with extremely low polymorphism in pyrimethamine-resistant parasites. We further characterized 54 worldwide isolates by genotyping SNPs across 20 genomic regions. These data begin to define population structure among African, Asian and American groups and illustrate the degree of linkage disequilibrium, which extends over relatively short distances in African parasites but over longer distances in Asian parasites. We provide an initial map of genetic diversity in P. falciparum and demonstrate its potential utility in identifying genes subject to recent natural selection and in understanding the population genetics of this parasite.