Localization of protein aggregation in Escherichia coli is governed by diffusion and nucleoid macromolecular crowding effect

Aggregates of misfolded proteins are a hallmark of many age-related diseases. Recently, they have been linked to aging of Escherichia coli (E. coli) where protein aggregates accumulate at the old pole region of the aging bacterium. Because of the potential of E. coli as a model organism, elucidating aging and protein aggregation in this bacterium may pave the way to significant advances in our global understanding of aging. A first obstacle along this path is to decipher the mechanisms by which protein aggregates are targeted to specific intercellular locations. Here, using an integrated approach based on individual-based modeling, time-lapse fluorescence microscopy and automated image analysis, we show that the movement of aging-related protein aggregates in E. coli is purely diffusive (Brownian). Using single-particle tracking of protein aggregates in live E. coli cells, we estimated the average size and diffusion constant of the aggregates. Our results evidence that the aggregates passively diffuse within the cell, with diffusion constants that depend on their size in agreement with the Stokes-Einstein law. However, the aggregate displacements along the cell long axis are confined to a region that roughly corresponds to the nucleoid-free space in the cell pole, thus confirming the importance of increased macromolecular crowding in the nucleoids. We thus used 3d individual-based modeling to show that these three ingredients (diffusion, aggregation and diffusion hindrance in the nucleoids) are sufficient and necessary to reproduce the available experimental data on aggregate localization in the cells. Taken together, our results strongly support the hypothesis that the localization of aging-related protein aggregates in the poles of E. coli results from the coupling of passive diffusion- aggregation with spatially non-homogeneous macromolecular crowding. They further support the importance of "soft" intracellular structuring (based on macromolecular crowding) in diffusion-based protein localization in E. coli.Comment: PLoS Computational Biology (2013

The 21-SPONGE HI Absorption Survey I: Techniques and Initial Results

We present methods and results from "21-cm Spectral Line Observations of Neutral Gas with the EVLA" (21-SPONGE), a large survey for Galactic neutral hydrogen (HI) absorption with the Karl G. Jansky Very Large Array (VLA). With the upgraded capabilities of the VLA, we reach median root-mean-square (RMS) noise in optical depth of $\sigma_{\tau}=9\times 10^{-4}$ per $0.42\rm\,km\,s^{-1}$ channel for the 31 sources presented here. Upon completion, 21-SPONGE will be the largest HI absorption survey with this high sensitivity. We discuss the observations and data reduction strategies, as well as line fitting techniques. We prove that the VLA bandpass is stable enough to detect broad, shallow lines associated with warm HI, and show that bandpass observations can be combined in time to reduce spectral noise. In combination with matching HI emission profiles from the Arecibo Observatory ($\sim3.5'$ angular resolution), we estimate excitation (or spin) temperatures ($\rm T_s$) and column densities for Gaussian components fitted to sightlines along which we detect HI absorption (30/31). We measure temperatures up to $\rm T_s\sim1500\rm\,K$ for individual lines, showing that we can probe the thermally unstable interstellar medium (ISM) directly. However, we detect fewer of these thermally unstable components than expected from previous observational studies. We probe a wide range in column density between $\sim10^{16}$ and $>10^{21}\rm\,cm^{-2}$ for individual HI clouds. In addition, we reproduce the trend between cold gas fraction and average $\rm T_s$ found by synthetic observations of a hydrodynamic ISM simulation by Kim et al. (2014). Finally, we investigate methods for estimating HI $\rm T_s$ and discuss their biases.Comment: Accepted for publication in ApJ; 24 pages, 14 figure

Independent Risk Factors for Fast-Track Failure Using a Predefined Fast-Track Protocol in Preselected Cardiac Surgery Patients

ObjectisvesThe purpose of this study was to identify the independent risk factors for fast-track failure (FTF) in cardiac surgery patients.DesignA retrospective analysis.SettingA university-affiliated heart center.ParticipantsIn a 2-year period, 1,704 consecutive preselected patients undergoing elective cardiac surgery were treated according to the local fast-track protocol in the postanesthetic care unit (PACU), bypassing the intensive care unit (ICU).Measurements and ResultsIndependent risk factors for FTF in the univariate regression analysis were tested in a multivariate regression analysis. FTF was defined as any transfer of the preselected patient to the ICU. FTF was primary when the patient was transferred directly from the postanesthetic care unit to the ICU and secondary when the patient was transferred from the intermediate care unit or ward to the ICU. FTF rate was 11.6% for primary and 5.6% for secondary FTF. In the multivariate regression analysis, age>70 years, female sex, prolonged surgery, and prolonged cross-clamp time could be defined as independent risk factors for FTF.ConclusionsIn a preselected patient population, fast-track treatment could be done with a low FTF rate. Independent risk factors for FTF are age, female sex, prolonged surgery, and prolonged cross-clamp time

Oscillations of neutrinos and mesons in quantum field theory

This report deals with the quantum field theory of particle oscillations in vacuum. We first review the various controversies regarding quantum-mechanical derivations of the oscillation formula, as well as the different field-theoretical approaches proposed to settle them. We then clear up the contradictions between the existing field-theoretical treatments by a thorough study of the external wave packet model. In particular, we show that the latter includes stationary models as a subcase. In addition, we explicitly compute decoherence terms, which destroy interferences, in order to prove that the coherence length can be increased without bound by more accurate energy measurements. We show that decoherence originates not only in the width and in the separation of wave packets, but also in their spreading through space-time. In this review, we neither assume the relativistic limit nor the stability of oscillating particles, so that the oscillation formula derived with field-theoretical methods can be applied not only to neutrinos but also to neutral K and B mesons. Finally, we discuss oscillations of correlated particles in the same framework.Comment: v2, 124 pages, 10 figures (7 more); updated review of the literature; complete derivation of the oscillation probability at short and large distance; more details on the influence of the spreading of the amplitude on decoherence; submitted to Physics Report

Active Brownian Particles. From Individual to Collective Stochastic Dynamics

We review theoretical models of individual motility as well as collective dynamics and pattern formation of active particles. We focus on simple models of active dynamics with a particular emphasis on nonlinear and stochastic dynamics of such self-propelled entities in the framework of statistical mechanics. Examples of such active units in complex physico-chemical and biological systems are chemically powered nano-rods, localized patterns in reaction-diffusion system, motile cells or macroscopic animals. Based on the description of individual motion of point-like active particles by stochastic differential equations, we discuss different velocity-dependent friction functions, the impact of various types of fluctuations and calculate characteristic observables such as stationary velocity distributions or diffusion coefficients. Finally, we consider not only the free and confined individual active dynamics but also different types of interaction between active particles. The resulting collective dynamical behavior of large assemblies and aggregates of active units is discussed and an overview over some recent results on spatiotemporal pattern formation in such systems is given.Comment: 161 pages, Review, Eur Phys J Special-Topics, accepte