Sharing of heteroplasmies between human liver lobes varies across the mtDNA genome

Mitochondrial DNA (mtDNA) heteroplasmy (intra-individual variation) varies among different human tissues and increases with age, suggesting that the majority of mtDNA heteroplasmies are acquired, rather than inherited. However, the extent to which heteroplasmic sites are shared across a tissue remains an open question. We therefore investigated heteroplasmy in two liver samples (one from each primary lobe) from 83 Europeans, sampled at autopsy. Minor allele frequencies (MAF) at heteroplasmic sites were significantly correlated between the two liver samples from an individual, with significantly more sharing of heteroplasmic sites in the control region than in the non-control region. We show that this increased sharing for the control region cannot be explained by recent mutations at just a few specific heteroplasmic sites or by the possible presence of 7S DNA. Moreover, we carried out simulations to show that there is significantly more sharing than would be predicted from random genetic drift from a common progenitor cell. We also observe a significant excess of non-synonymous vs. synonymous heteroplasmies in the protein-coding region, but significantly more sharing of synonymous heteroplasmies. These contrasting patterns for the control vs. the non-control region, and for non-synonymous vs. synonymous heteroplasmies, suggest that selection plays a role in heteroplasmy sharing

On the Mechanism of Time--Delayed Feedback Control

The Pyragas method for controlling chaos is investigated in detail from the experimental as well as theoretical point of view. We show by an analytical stability analysis that the revolution around an unstable periodic orbit governs the success of the control scheme. Our predictions concerning the transient behaviour of the control signal are confirmed by numerical simulations and an electronic circuit experiment.Comment: 4 pages, REVTeX, 4 eps-figures included Phys. Rev. Lett., in press also available at http://athene.fkp.physik.th-darmstadt.de/public/wolfram.htm

Restricted feedback control of one-dimensional maps

Dynamical control of biological systems is often restricted by the practical constraint of unidirectional parameter perturbations. We show that such a restriction introduces surprising complexity to the stability of one-dimensional map systems and can actually improve controllability. We present experimental cardiac control results that support these analyses. Finally, we develop new control algorithms that exploit the structure of the restricted-control stability zones to automatically adapt the control feedback parameter and thereby achieve improved robustness to noise and drifting system parameters.Comment: 29 pages, 9 embedded figure

Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections

The increasing incidence of aciclovir- (ACV) resistant strains in patients with ocular herpes simplex virus (HSV) infections is a major health problem in industrialized countries. In the present study, the humanized monoclonal antibody (mAb) hu2c targeting the HSV-1/2 glycoprotein B was examined for its efficacy towards ACV-resistant infections of the eye in the mouse model of acute retinal necrosis (ARN). BALB/c mice were infected by microinjection of an ACV-resistant clinical isolate into the anterior eye chamber to induce ARN and systemically treated with mAb hu2c at 24 h prior (pre-e

Quantification of protein mobility and associated reshuffling of cytoplasm during chemical fixation

Abstract To understand cellular functionalities, it is essential to unravel spatio-temporal patterns of molecular distributions and interactions within living cells. The technological progress in fluorescence microscopy now allows in principle to measure these patterns with sufficient spatial resolution. However, high resolution imaging comes with long acquisition times and high phototoxicity. Therefore, physiological live cell imaging is often unfeasible and chemical fixation is employed. Yet, fixation methods have not been rigorously investigated, in terms of pattern preservation, at the resolution at which cells can now be imaged. A key parameter for this is the time required until fixation is complete. During this time, cells are under unphysiological conditions and patterns decay. We demonstrate here that formaldehyde fixation takes more than one hour for cytosolic proteins in cultured cells. Other small aldehydes, glyoxal and acrolein, did not perform better. Associated with this, we found a distinct displacement of proteins and lipids, including their loss from cells. Fixations using glutaraldehyde were faster than four minutes and retained most cytoplasmic proteins. Surprisingly, autofluorescence produced by glutaraldehyde was almost completely absent with supplementary addition of formaldehyde without compromising fixation speed. These findings indicate, which cellular processes can actually be reliably imaged after a certain chemical fixation

Detection of enterovirus D68 in patients hospitalised in three tertiary university hospitals in Germany, 2013 to 2014

Enterovirus D68 (EV-D68) has been recognised as a worldwide emerging pathogen associated with severe respiratory symptoms since 2009. We here report EV-D68 detection in hospitalised patients with acute respiratory infection admitted to three tertiary hospitals in Germany between January 2013 and December 2014. From a total of 14,838 respiratory samples obtained during the study period, 246 (1.7%) tested enterovirus-positive and, among these, 39 (15.9%) were identified as EV-D68. Infection was observed in children and teenagers (0–19 years; n=31), the majority (n=22) being under five years-old, as well as in adults > 50 years of age (n=8). No significant difference in prevalence was observed between the 2013 and 2014 seasons. Phylogenetic analyses based on viral protein 1 (VP1) sequences showed co-circulation of different EV-D68 lineages in Germany. Sequence data encompassing the entire capsid region of the genome were analysed to gain information on amino acid changes possibly relevant for immunogenicity and revealed mutations in two recently described pleconaril binding sites

Approaching nonlinear dynamics by studying the motion of a pendulum I: Observing trajectories in state space

.-A phenomenological introduction into concepts of nonlinear dynamics is given. A driven pendulum is used as an appropriate model to demonstrate characteristic features of the dynamics of nonlinear systems. The mechanical and electronic setup of the pendulum is described and quantified in detail, and different techniques to visualize the motion in state space are discussed. Finally, a 'road map' in parameter space is calculated which provides a tool to find special scenarios by choosing appropriate driving amplitudes and frequencies. 1 Introduction Nonlinear systems have been a topic of general physics ever since, but progress in this field was slow, as in most cases analytical access is nearly impossible or is restricted to very special systems and parameter sets. Powerful mathematical tools such as the superposition principle can not be applied to these systems and so nonlinear systems have -- apart from some pioneering work of Poincar'e and others [Poincar'e, 1899]-- mainly been st..

Detection of influenza A(H1N1)v virus by real-time RT-PCR.

Influenza A(H1N1)v virus was first identified in April 2009. A novel real-time RT-PCR for influenza A(H1N1)v virus was set up ad hoc and validated following industry-standard criteria. The lower limit of detection of the assay was 384 copies of viral RNA per ml of viral transport medium (95% confidence interval: 273-876 RNA copies/ml). Specificity was 100% as assessed on a panel of reference samples including seasonal human influenza A virus H1N1 and H3N2, highly pathogenic avian influenza A virus H5N1 and porcine influenza A virus H1N1, H1N2 and H3N2 samples. The real-time RT-PCR assay for the influenza A matrix gene recommended in 2007 by the World Health Organization was modified to work under the same reaction conditions as the influenza A(H1N1)v virus-specific test. Both assays were equally sensitive. Clinical applicability of both assays was demonstrated by screening of almost 2,000 suspected influenza (H1N1)v specimens, which included samples from the first cases of pandemic H1N1 influenza imported to Germany. Measuring influenza A(H1N1)v virus concentrations in 144 laboratory-confirmed samples yielded a median of 4.6 log RNA copies/ml. The new methodology proved its principle and might assist public health laboratories in the upcoming influenza pandemic