How Fast Does a Signal Propagate through Proteins?

As the molecular basis of signal propagation in the cell, proteins are regulated by perturbations, such as mechanical forces or ligand binding. The question arises how fast such a signal propagates through the protein molecular scaffold. As a first step, we have investigated numerically the dynamics of force propagation through a single (Ala) protein following a sudden increase in the stretching forces applied to its end termini. The force propagates along the backbone into the center of the chain on the picosecond scale. Both conformational and tension dynamics are found in good agreement with a coarse-grained theory of force propagation through semiflexible polymers. The speed of force propagation of 50Å ps⁻¹ derived from these simulations is likely to determine an upper speed limit of mechanical signal transfer in allosteric proteins or molecular machines.     

Habitat selection by adult Golden Eagles Aquila chrysaetos during the breeding season and implications for wind farm establishment

Capsule: Global Positioning System (GPS)-tagged adult Golden Eagles Aquila chrysaetos breeding in forests in northern Sweden selected clear-cuts, coniferous forests with lichens and steep slopes during the breeding season but avoided wetlands and mixed forest.

Aims: To investigate the habitat selection patterns of tree-nesting Golden Eagles, and identify how potential conflicts with wind farm development could be minimized.

Methods: The study is based on GPS tracking data from 22 adult eagles. We estimated home range sizes using a biased random bridge approach and habitat selection patterns using resource selection functions following a use-availability design.

Results: Core home range size among adults was variable during the breeding season (5–30?km²). Individual movement extents were variable, but sexes did not significantly differ in their scale of movement. At the landscape scale, individuals selected for clear-cuts and coniferous forest with ground lichens, whereas wetland, water bodies and mixed forest were avoided. Steeper and south facing slopes were selected for, whereas, north facing slopes were avoided.

Conclusions: Potential conflicts between eagles and wind energy establishment can be reduced if wind farms are placed away from steep slopes, minimizing areas that are clear-cut during construction, and locating turbines within dense, young and other less favoured forest habitats.     

Arsenite oxidase,an ancient bioenergetic enzyme

Operons coding for the enzyme arsenite oxidase have been detected in the genomes from Archaea and Bacteria by Blast searches using the amino acid sequences of the respective enzyme characterized in two different beta-proteobacteria as templates. Sequence analyses show that in all these species, arsenite oxidase is transported over the cytoplasmic membrane via the tat system and most probably remains membrane attached by an N-terminal transmembrane helix of the Rieske subunit. The biochemical and biophysical data obtained for arsenite oxidase in the green filamentous bacterium Chloroflexus aurantiacus allow a structural model of the enzyme's membrane association to be proposed. Phylogenies for the two constituent subunits (i.e., the molybdopterin-containing and the Rieske subunit) of the heterodimeric enzyme and their respective homologs in DMSO-reductase, formate dehydrogenase, nitrate reductase, and the Rieske/cytb complexes were calculated from multiple sequence alignments. The obtained phylogenetic trees indicate an early origin of arsenite oxidase before the divergence of Archaea and Bacteria. Evolutionary implications of these phylogenies are discussed.     

Correction to: Dose–responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950–2003

Radiation and Environmental Biophysics - The article Dose–responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950–2003, written by Helmut...     

Clinical studies on the appearance of natural anterior teeth in young and old adults

Objectives: To evaluate the typical appearance of natural anterior teeth in young and elderly people and to develop guidelines for the natural appearance of dentures. Design: Clinical examination and photography. Inclusion criteria were a dental state with natural anterior teeth and no more than two crowns. Subjects: A study group (SG) consisting of 64 patients ranging in age from 60 to 86 years (67.3 ± 5.8) and a control group (CG) composed of 64 dental students aged 21–33 years (25.8 ± 2.4). Setting: Dental schools of the Johannes‐Gutenberg‐University Mainz and the University of Leipzig. Results: Most participants were content with the appearance of their own natural teeth. With relaxed lips a mean of 1.5 (±0.19) mm of upper incisors and 1.6 (±0.19) mm of lower incisors were visible in the SG compared with 2.5 (±0.16) and 0.4 (±0.07) mm in the CG, respectively. The subjects in the SG showed a greater diversity in position of teeth in the anterior arch and this was more often with incisors than with canines. Features such as stains, cracks and defects were much more noticeable in the SG. An inter‐dental ‘black triangle’ seemed to be a typical feature of an aged dental appearance. Conclusion: The majority of people older than 60 years who still have their own natural anterior teeth would not wish for a change in appearance if they needed a prosthodontic reconstruction. Thus techniques for customisation should be promoted to obtain a natural appearance in dentures.     

An environmentally relevant endocrine-disrupting antiandrogen, vinclozolin, affects calling behavior of male Xenopus laevis

Vinclozolin (VIN) is an antiandrogenic model substance as well as a common fungicide that can affect the endocrine system of vertebrates. The objective of this study was to investigate how VIN affects mate calling behavior of South African clawed frogs (Xenopus laevis) and whether it is effective at environmentally relevant concentrations. Male X. laevis were injected with human chorionic gonadotropin (hCG) to stimulate their androgen-controlled mate calling behavior and were treated with VIN at concentrations of 10⁻⁶, 10⁻⁸ and 10⁻¹⁰ M. VIN at 10⁻⁶ M reduced calling activity. Furthermore, the vocalization composition of VIN-treated X. laevis was altered. The call types advertisement calls and chirping are uttered by reproductively active males, whereas the call types growling, ticking, and rasping indicate a sexually unaroused state of a male. VIN at any of the tested concentrations led to a decrease in utterance of calls, which indicate a sexually aroused state of the males, and an increase in relative proportions of calls, indicating a sexually unaroused state of the males. Additionally, the mean duration of clicks and the number of accentuated clicks during the advertisement calls decreased at all concentrations of VIN. No significant differences were observed in any other temporal or spectral calling parameters between the treatments. This study illustrates that exposure to the antiandrogen VIN might result in a reduced reproductive success by altering mate calling behavior of X. laevis. Moreover, it suggests that the behavioral parameters examined in this study can be used as sensitive biomarkers for detecting antiandrogenic endocrine disrupting compounds in amphibians.     

How multisite phosphorylation impacts the conformations of intrinsically disordered proteins

Phosphorylation of intrinsically disordered proteins (IDPs) can produce changes in structural and dynamical properties and thereby mediate critical biological functions. How phosphorylation effects intrinsically disordered proteins has been studied for an increasing number of IDPs, but a systematic understanding is still lacking. Here, we compare the collapse propensity of four disordered proteins, Ash1, the C-terminal domain of RNA polymerase (CTD2’), the cytosolic domain of E-Cadherin, and a fragment of the p130Cas, in unphosphorylated and phosphorylated forms using extensive all-atom molecular dynamics (MD) simulations. We find all proteins to show V-shape changes in their collapse propensity upon multi-site phosphorylation according to their initial net charge: phosphorylation expands neutral or overall negatively charged IDPs and shrinks positively charged IDPs. However, force fields including those tailored towards and commonly used for IDPs overestimate these changes. We find quantitative agreement of MD results with SAXS and NMR data for Ash1 and CTD2’ only when attenuating protein electrostatic interactions by using a higher salt concentration (e.g. 350 mM), highlighting the overstabilization of salt bridges in current force fields. We show that phosphorylation of IDPs also has a strong impact on the solvation of the protein, a factor that in addition to the actual collapse or expansion of the IDP should be considered when analyzing SAXS data. Compared to the overall mild change in global IDP dimension, the exposure of active sites can change significantly upon phosphorylation, underlining the large susceptibility of IDP ensembles to regulation through post-translational modifications.     

Apolipoprotein E Codetermines Tissue Tropism of Hepatitis C Virus and Is Crucial for Viral Cell-to-Cell Transmission by Contributing to a Postenvelopment Step of Assembly

Hepatitis C virus (HCV) predominantly infects human hepatocytes, although extrahepatic virus reservoirs are being discussed. Infection of cells is initiated via cell-free and direct cell-to-cell transmission routes. Cell type-specific determinants of HCV entry and RNA replication have been reported. Moreover, several host factors required for synthesis and secretion of lipoproteins from liver cells, in part expressed in tissue-specific fashion, have been implicated in HCV assembly. However, the minimal cell type-specific requirements for HCV assembly have remained elusive. Here we report that production of HCV trans-complemented particles (HCV_TCP) from nonliver cells depends on ectopic expression of apolipoprotein E (ApoE). For efficient virus production by full-length HCV genomes, microRNA 122 (miR-122)-mediated enhancement of RNA replication is additionally required. Typical properties of cell culture-grown HCV (HCVcc) particles from ApoE-expressing nonliver cells are comparable to those of virions derived from human hepatoma cells, although specific infectivity of virions is modestly reduced. Thus, apolipoprotein B (ApoB), microsomal triglyceride transfer protein (MTTP), and apolipoprotein C1 (ApoC1), previously implicated in HCV assembly, are dispensable for production of infectious HCV. In the absence of ApoE, release of core protein from infected cells is reduced, and production of extracellular as well as intracellular infectivity is ablated. Since envelopment of capsids was not impaired, we conclude that ApoE acts after capsid envelopment but prior to secretion of infectious HCV. Remarkably, the lack of ApoE also abrogated direct HCV cell-to-cell transmission. These findings highlight ApoE as a host factor codetermining HCV tissue tropism due to its involvement in a late assembly step and viral cell-to-cell transmission.     

Application of sterilised human amnion for reconstruction of the ocular surface

BACKGROUND: Despite improved surgical techniques and the use of new medication, healing of corneal and conjunctival defects cannot always be achieved. In this connection the clinical use of human amnion, produced by different techniques, has represented a successful alternative for the past ten years. The purpose of the present investigation was the development of a clinically secure, therapeutically efficient, and easy-to-handle (transport, storage, application) allogenic amnion transplant. PATIENTS AND METHODS: A new method for an amnion preparation, which contains a sterilisation process in peracetic acid and a drying process in a laminar flow cabinet, was developed as an alternative to previous techniques described in the literature. Amnion transplantation was used to treat 41 patients, 36 of them with corneal ulcer. Further indications for amnion transplantation were symblepharon, descemetocele, as well as dehiscence of conjunctiva after cerclage. RESULTS: Seventy-three percent of cases showed postoperative improvement evidenced by constant vision, while 15 percent showed decreased vision. CONCLUSIONS: The study confirms the observations of previous investigators who consider amnion transplantation an efficient therapeutic method for a multitude of eye diseases. The new method described in this report, guarantees patients' safety by using a validated new sterilisation process against infections that can be transmitted by human tissue. At present this method constitutes the only process available in Germany, and is approved by the Federal Institute for Drugs and Medical Products (BfArM) for the manufacture of human amnion transplants as a finished medical product.