Meeting report - shining light on septins

International audienceSeptins are enigmatic proteins; they bind GTP and assemble together like molecular Lego blocks to form intracellular structures of varied shapes such as filaments, rings and gauzes. To shine light on the biological mysteries of septin proteins, leading experts in the field came together for the European Molecular Biology Organization (EMBO) workshop held from 8–11 October 2017 in Berlin. Organized by Helge Ewers (Freie Universität, Berlin, Germany) and Serge Mostowy (Imperial College, London, UK), the workshop convened at the Harnack-Haus, a historic hub of scientific discourse run by the Max Planck Society

Prion-like proteins as epigenetic devices of stress adaptation.

Epigenetic modifications allow cells to quickly alter their gene expression and adapt to different stresses. In addition to direct chromatin modifications, prion-like proteins have recently emerged as a system that can sense and adapt the cellular response to stressful conditions. Interestingly, such responses are maintained through prions' self-templating conformations and transmitted to the progeny of the cell that established a prion trait. Alternatively, mnemons are prion-like proteins which conformational switch encodes memories of past events and yet does not propagate to daughter cells. In this review, we explore the biology of the recently described prions found in Saccharomyces cerevisiae including [ESI+], [SMAUG+], [GAR+], [MOT3+], [MOD+], [LSB+] as well as the Whi3 mnemon. The reversibility of the phenotypes they encode allows cells to remove traits which are no longer adaptive under stress relief and chaperones play a fundamental role in all steps of prion-like proteins functions. Thus, the interplay between chaperones and prion-like proteins provides a framework to establish responses to challenging environments

Protein Phase Separation during Stress Adaptation and Cellular Memory

Cells need to organise and regulate their biochemical processes both in space and time in order to adapt to their surrounding environment. Spatial organisation of cellular components is facilitated by a complex network of membrane bound organelles. Both the membrane composition and the intra-organellar content of these organelles can be specifically and temporally controlled by imposing gates, much like bouncers controlling entry into night-clubs. In addition, a new level of compartmentalisation has recently emerged as a fundamental principle of cellular organisation, the formation of membrane-less organelles. Many of these structures are dynamic, rapidly condensing or dissolving and are therefore ideally suited to be involved in emergency cellular adaptation to stresses. Remarkably, the same proteins have also the propensity to adopt self-perpetuating assemblies which properties fit the needs to encode cellular memory. Here, we review some of the principles of phase separation and the function of membrane-less organelles focusing particularly on their roles during stress response and cellular memory

Methodology for the adaptation of the excavation and support system of a tunnel based on the observational method

O presente artigo aborda uma nova aplicação do método observacional na engenharia de túneis para a adaptação em tempo real do método de escavação e suporte. O método observacional é utilizado há muitos anos, no entanto não existe uma metodologia consistente e estruturada para a incorporação dos dados da monitorização na adaptação do sistema de suporte em tempo real. A metodologia proposta possibilitará a otimização do sistema de suporte e do custo total da obra, tal como um aumento da segurança nos trabalhos de escavação. Primeiramente, são propostos critérios limite para os deslocamentos e tensões no maciço. Durante a fase de projecto são construídos gráficos de suporte de consulta rápida durante a fase de construção para a realização da adaptação referida. Caso não existam gráficos disponíveis para a situação específica em análise, é necessário o recurso a cálculos de retroanálise. A metodologia foi aplicada ao túnel de “Bois de Peu”, composto por dois túneis paralelos com um comprimento superior a 500 m. Este caso de estudo apresentava um elevado nível de incerteza relativa à heterogenidade do solo e consequentemente à definição dos parâmetros geomecânicos. A metodologia foi aplicada em 4 secções embora se apresentem os resultados para apenas duas. Foi possível confirmar o potencial da aplicação da metodologia na adaptação em tempo real do sistema de suporte, assim como a importância de existir um plano de monitorização específico e de qualidade no aperfeiçoamento dos processos de retroanálise.This paper presents a new application of the observational method in tunneling engineering for real time adaptation of the excavation method and support systems. The observational method has been used for many years, however, a gap exists when referring to a consistent and structured approach for the incorporation of monitoring data in the real time adaptation of the support system. The proposed methodology will enable the optimization of the support system and the total cost of the work, and also an increased safety in excavation works. In a first step limit criteria for displacements and stresses for the soil/rock formation are proposed. The methodology uses graphics that are constructed during the project stage based on parametric calculations to assist in the process and when these graphics are not available, since it is not possible to predict every possible scenario, inverse analysis calculations are carried out. The methodology is applied to the “Bois de Peu” tunnel which is composed by two tubes with over 500 m long. High uncertainty levels existed concerning the heterogeneity of the soil and consequently in the geomechanical design parameters. The methodology was applied in four sections and the results focus on two of them. It is shown that the methodology has potential to be applied in real cases contributing for a consistent approach of a real time adaptation of the support system and highlight the importance of the existence of good quality and specific monitoring data to improve the inverse analysis procedure

A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell.

In many cell types, lateral diffusion barriers compartmentalize the plasma membrane and, at least in budding yeast, the endoplasmic reticulum (ER). However, the molecular nature of these barriers, their mode of action and their cellular functions are unclear. Here, we show that misfolded proteins of the ER remain confined into the mother compartment of budding yeast cells. Confinement required the formation of a lateral diffusion barrier in the form of a distinct domain of the ER-membrane at the bud neck, in a septin-, Bud1 GTPase- and sphingolipid-dependent manner. The sphingolipids, but not Bud1, also contributed to barrier formation in the outer membrane of the dividing nucleus. Barrier-dependent confinement of ER stress into the mother cell promoted aging. Together, our data clarify the physical nature of lateral diffusion barriers in the ER and establish the role of such barriers in the asymmetric segregation of proteotoxic misfolded proteins during cell division and aging.DOI: http://dx.doi.org/10.7554/eLife.01883.001

Numerical analysis of the venda nova II hydroelectrical complex main caverns and backanalysis of the geomechanical parameters

Neste trabalho é apresentado um modelo numérico 3D para as cavernas principais do complexo da Venda Nova II considerando as diferentes fases de escavação. Os parâmetros geomecânicos do maciço granítico, para os modelos, foram calculados utilizando o software GEOPAT. Este programa é um sistema baseado em conhecimento que permite obter os parâmetros geomecânicos para a modelação de obras subterrâneas em maciços graníticos. Os resultados do modelo são comparados com os deslocamentos observados por intermédio de extensómetros ao longo das várias fases construtivas. Nesta comparação são utilizadas diversas ferramentas estatísticas para a validação dos resultados obtidos. Finalmente, é realizada a retroanálise de parâmetros geomecânicos do maciço rochoso utilizando um algoritmo de optimização inovador. Os resultados obtidos permitiram concluir que a estimativa inicial dos parâmetros apresenta uma precisão bastante aceitável e que o algoritmo possui uma boa robustez e eficiência.In this work a 3D numerical model for the main caverns of the Venda Nova II complex which considers the different excavation stages is presented. The geomechanical parameters for the numerical models were computed using GEOPAT. This software is a knowledge based system which allows evaluating geomechanical parameters for the modelling of underground works built in granite rock masses. The results are compared with the observed displacements measured with extensometers along the different construction stages. In this comparison several statistical tools are used for the validation of the obtained results. Finally, the backanalysis of geomechanical parameters of the interested rock mass is performed using an innovative optimization algorithm. The results show that the initial evaluation of the parameters presents a very acceptable accuracy and that the algorithm posses good robustness and efficiency.Fundação para a Ciência e a Tecnologia (FCT) - Projecto POCI/ECM/57495/2004, intitulado Geotechnical Risk in Tunnels for High Speed Trains.Faculdade de Ciências e Tecnologia da Universidade de Coimbra (FCT-UC

Numerical analysis of the Venda Nova II powerhouse complex

In the North of Portugal a hydroelectric scheme called Venda Nova II was recently built in order to optimize the resources of the reservoirs created by Venda Nova and Salamonde dams. The scheme, almost fully composed by underground structures and built in a predominantly granite rock mass, include several tunnels with a total length of about 7.5km, inclined and vertical shafts with a total length of 750m and two caverns which compose the powerhouse complex. The complex consists of two caverns interconnected by two galleries at a dept of about 350m. For this complex, 2D and 3D numerical models were developed considering the different construction stages. The geomechanical parameters of the granite formation for the numerical models were obtained using GEOPAT. This software is a knowledge based system which allows obtaining geomechanical parameters for underground structures modelling in granite formations. The 2D model was developed in the Phases2 software while the 3D model in FLAC3D. In this paper results of these models are analysed. Some comparisons are carried out between the models results and the monitored data. The numerical results show in general a good agreement with the monitored ones.Fundação para a Ciência e a Tecnologia (FCT) - projecto POCI/ECM/57495/2004 - Geotechnical Risk in Tunnels for High Speed Trains

Inverse analysis on two geotechnical works : a tunnel and a cavern

One of the major difficulties for geotechnical engineers during project phase is to estimate in a reliable way the mechanical parameters values of the adopted constitutive model. In project phase, they can be evaluated by laboratory and in situ tests. But, these tests lead to uncertainties due to the soil reworking and to local character of the test which is not representative of the soil mass. Moreover for in situ tests interpretation difficulties exist due to the non homogeneous character of the strain and stress fields applied to the soil mass. In order to reduce these uncertainties, geotechnical engineers can use inverse analysis processes during construction. This article shows the application of two of these processes (a deterministic and a probabilistic method) on convergence leveling measurements realized during the excavation of the Bois de Peu tunnel (France). Moreover, these two processes are also applied on displacements measured by inclinometers during the excavation of the hydroelectric powerhouse cavern Venda Nova II (Portugal). The two inverse analysis methods are coupled with two geotechnical software (CESAR-LCPC and FLAC3D) to identify soil parameters. Numerical and experimental results are compared.(undefined

Random Field and Random Anisotropy Effects in Defect-Free Three-Dimensional XY Models

Monte Carlo simulations have been used to study a vortex-free XY ferromagnet with a random field or a random anisotropy on simple cubic lattices. In the random field case, which can be related to a charge-density wave pinned by random point defects, it is found that long-range order is destroyed even for weak randomness. In the random anisotropy case, which can be related to a randomly pinned spin-density wave, the long-range order is not destroyed and the correlation length is finite. In both cases there are many local minima of the free energy separated by high entropy barriers. Our results for the random field case are consistent with the existence of a Bragg glass phase of the type discussed by Emig, Bogner and Nattermann.Comment: 10 pages, including 2 figures, extensively revise

Erratum to: Comparative assessment of image quality for coronary CT angiography with iobitridol and two contrast agents with higher iodine concentrations: iopromide and iomeprol. A multicentre randomized double-blind trial

Unfortunately, there is amistake in the section Results, Clinical safety. While the text states that “no severe AEs were reported”, in fact one severe AE was reported in the iomeprol group (one severe injection site pain assessed as possibly related to contrast agent), as shown in Table 5. In addition, the name of the author Jean-François Paul was rendered incorrectly in the original publication but has since been corrected. The authors apologize for these mistakes