Modelling the impact of tailored behavioural interventions on chlamydia transmission

Peer reviewe

Deciphering the folding kinetics of transmembrane helical proteins

Nearly a quarter of genomic sequences and almost half of all receptors that are likely to be targets for drug design are integral membrane proteins. Understanding the detailed mechanisms of the folding of membrane proteins is a largely unsolved, key problem in structural biology. Here, we introduce a general model and use computer simulations to study the equilibrium properties and the folding kinetics of a $C_{\alpha}$-based two helix bundle fragment (comprised of 66 amino-acids) of Bacteriorhodopsin. Various intermediates are identified and their free energy are calculated toghether with the free energy barrier between them. In 40% of folding trajectories, the folding rate is considerably increased by the presence of non-obligatory intermediates acting as traps. In all cases, a substantial portion of the helices is rapidly formed. This initial stage is followed by a long period of consolidation of the helices accompanied by their correct packing within the membrane. Our results provide the framework for understanding the variety of folding pathways of helical transmembrane proteins

The impact of STI test results and face-to-face consultations on subsequent behavior and psychological characteristics

Acknowledgments The authors would like to thank Maarten Schipper at the Biostatistics Department at the National Institute for Public Health and the Environment, who provided assistance with the statistical analyses. Furthermore, the authors are grateful to the staff at the SHC of Amsterdam, Kennemerland, Hollands Noorden, Twente (especially Karin Westra, Anne de Vries, and Karlijn Kampman) who were involved in the recruitment and data collection of participants at baseline and to Marlous Ratten and Klazien Visser from Soapoli-online, who coordinated the laboratory testing of the home-based test kits at six-month follow-up. The authors would also like to thank the staff at the STI department at the National Institute for Public Health and the Environment, especially Birgit van Benthem.Peer reviewe

Photocross-linking of nascent chains to the STT3 subunit of the oligosaccharyltransferase complex

In eukaryotic cells, polypeptides are N glycosylated after passing through the membrane of the ER into the ER lumen. This modification is effected cotranslationally by the multimeric oligosaccharyltransferase (OST) enzyme. Here, we report the first cross-linking of an OST subunit to a nascent chain that is undergoing translocation through, or integration into, the ER membrane. A photoreactive probe was incorporated into a nascent chain using a modified Lys-tRNA and was positioned in a cryptic glycosylation site (-Q-K-T- instead of -N-K-T-) in the nascent chain. When translocation intermediates with nascent chains of increasing length were irradiated, nascent chain photocross-linking to translocon components, Sec61α and TRAM, was replaced by efficient photocross-linking solely to a protein identified by immunoprecipitation as the STT3 subunit of the OST. No cross-linking was observed in the absence of a cryptic sequence or in the presence of a competitive peptide substrate of the OST. As no significant nascent chain photocross-linking to other OST subunits was detected in these fully assembled translocation and integration intermediates, our results strongly indicate that the nascent chain portion of the OST active site is located in STT3

Phosphatidylethanolamine mediates insertion of the catalytic domain of leader peptidase in membranes

AbstractLeader peptidase is an integral membrane protein of E. coli and it catalyses the removal of most signal peptides from translocated precursor proteins. In this study it is shown that when the transmembrane anchors are removed in vivo, the remaining catalytic domain can bind to inner and outer membranes of E. coli. Furthermore, the purified catalytic domain binds to inner membrane vesicles and vesicles composed of purified inner membrane lipids with comparable efficiency. It is shown that the interaction is caused by penetration of a part of the catalytic domain between the lipids. Penetration is mediated by phosphatidylethanolamine, the most abundant lipid in E. coli, and does not seem to depend on electrostatic interactions. A hydrophobic segment around the catalytically important residue serine 90 is required for the interaction with membranes

Identification of particles with Lorentz factor up to 10410^{4} with Transition Radiation Detectors based on micro-strip silicon detectors

This work is dedicated to the study of a technique for hadron identification in the TeV momentum range, based on the simultaneous measurement of the energies and of the emission angles of the Transition Radiation (TR) X-rays with respect to the radiating particles. A detector setup has been built and tested with particles in a wide range of Lorentz factors (from about $10^3$ to about $4 \times 10^4$ crossing different types of radiators. The measured double-differential (in energy and angle) spectra of the TR photons are in a reasonably good agreement with TR simulation predictions.Comment: 31 pages, 12 figures, paper published on Nuclear Instruments & Methods