Propagation of melting cooperativity along the phosphodiester backbone of DNA

The role of the DNA phosphodiester backbone in the transfer of melting cooperativity between two helical domains was experimentally addressed with a helix-bulge-helix DNA model, in which the bulge consisted of a varying number of either conformationally flexible propanediol or conformationally constrained bicyclic anucleosidic phosphodiester backbone units. We found that structural communication between two double helical domains is transferred along the DNA backbone over the equivalent of ca. 12-20 backbone units, depending on whether there is a symmetric or asymmetric distribution of the anucleosidic units on both strands. We observed that extension of anucleosidic units on one strand only suffices to disrupt cooperativity transfer in a similar way as if extension occurs on both strands, indicating that the length of the longest anucleosidic inset determines cooperativity transfer. Furthermore, conformational rigidity of the sugar unit increases the distance of coopertivity transfer along the phosphodiester backbone. This is especially the case when the units are asymmetrically distributed in both strands

European guidelines on management of restless legs syndrome: report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society

Since the publication of the first European Federation of Neurological Societies (EFNS) guidelines in 2005 on the management of restless legs syndrome (RLS; also known as Willis-Ekbom disease), there have been major therapeutic advances in the field. Furthermore, the management of RLS is now a part of routine neurological practice in Europe. New drugs have also become available, and further randomized controlled trials have been undertaken. These guidelines were undertaken by the EFNS in collaboration with the European Neurological Society and the European Sleep Research Society.

The Good Society. A Comparative Study of Denmark and Switzerland

Denmark and Switzerland are small and successful countries with exceptionally content populations. However, they have very different political institutions and economic models. They have followed the general tendency in the West toward economic convergence, but both countries have managed to stay on top. They both have a strong liberal tradition, but otherwise their economic strategies are a welfare state model for Denmark and a safe haven model for Switzerland. The Danish welfare state is tax-based, while the expenditures for social welfare are insurance-based in Switzerland. The political institutions are a multiparty unicameral system in Denmark, and a permanent coalition system with many referenda and strong local government in Switzerland. Both approaches have managed to ensure smoothly working political power-sharing and economic systems that allocate resources in a fairly efficient way. To date, they have also managed to adapt the economies to changes in the external environment with a combination of stability and flexibility.

Impaired genome encapsidation restricts the in vitro propagation of human parvovirus B19.

The lack of a permissive cell culture system hampers the study of human parvovirus B19 (B19V). UT7/Epo is one of the few established cell lines that can be infected with B19V but generates none or few infectious progeny. Recently, hypoxic conditions or the use of primary CD36+ erythroid progenitor cells (CD36+ EPCs) have been shown to improve the infection. These novel approaches were evaluated in infection and transfection experiments. Hypoxic conditions or the use of CD36+ EPCs resulted in a significant acceleration of the infection/transfection and a modest increase in the yield of capsid progeny. However, under all tested conditions, genome encapsidation was impaired seriously. Further analysis of the cell culture virus progeny revealed that differently to the wild-type virus, the VP1 unique region (VP1u) was exposed partially and was unable to become further externalized upon heat treatment. The fivefold axes pore, which is used for VP1u externalization and genome encapsidation, might be constricted by the atypical VP1u conformation explaining the packaging failure. Although CD36+ EPCs and hypoxia facilitate B19V infection, large quantities of infectious progeny cannot be generated due to a failure in genome encapsidation, which arises as a major limiting factor for the in vitro propagation of B19V.

Isolation and propagation of Trypanosoma brucei gambiense from sleeping sickness patients in south Sudan

This study aimed at isolating Trypanosoma brucei gambiense from human African trypanosomiasis (HAT) patients from south Sudan. Fifty HAT patients identified during active screening surveys were recruited, most of whom (49/50) were in second-stage disease. Blood and cerebrospinal fluid samples collected from the patients were cryopreserved using Triladyl as the cryomedium. The samples were stored at -150 degrees C in liquid nitrogen vapour in a dry shipper. Eighteen patient stabilates could be propagated in immunosuppressed Mastomys natalensis and/or SCID mice. Parasitaemia was highest in SCID mice. Further subpassages in M. natalensis increased the virulence of the trypanosomes and all 18 isolates recovered from M. natalensis or SCID mice became infective to other immunosuppressed mouse breeds. A comparison of immunosuppressed M. natalensis and Swiss White, C57/BL and BALB/c mice demonstrated that all rodent breeds were susceptible after the second subpassage and developed a parasitaemia >10(6)/ml by Day 5 post infection. The highest parasitaemias were achieved in C57/BL and BALB/c mice. These results indicate that propagation of T. b. gambiense isolates after initial isolation in immunosuppressed M. natalensis or SCID mice can be done in a range of immunosuppressed rodents.

Propagation of Behavioral Variations with Delegation Proxies

Scoping behavioral variations to dynamic extents is useful to support non-functional concerns that otherwise result in cross-cutting code. Unfortunately, such forms of scoping are difficult to obtain with traditional reflection or aspects. We propose delegation proxies, a dynamic proxy model that supports behavioral intercession through the interception of various interpretation operations. Delegation proxies permit different behavioral variations to be easily composed together. We show how delegation proxies enable behavioral variations that can propagate to dynamic extents. We demonstrate our approach with examples of behavioral variations scoped to dynamic extents that help simplify code related to safety, reliability, and monitoring.