Velocity oscillations in actin-based motility

We present a simple and generic theoretical description of actin-based motility, where polymerization of filaments maintains propulsion. The dynamics is driven by polymerization kinetics at the filaments' free ends, crosslinking of the actin network, attachment and detachment of filaments to the obstacle interfaces and entropic forces. We show that spontaneous oscillations in the velocity emerge in a broad range of parameter values, and compare our findings with experiments.Comment: 5 pages, 6 figure

Convective Instability and Boundary Driven Oscillations in a Reaction-Diffusion-Advection Model

In a reaction-diffusion-advection system, with a convectively unstable regime, a perturbation creates a wave train that is advected downstream and eventually leaves the system. We show that the convective instability coexists with a local absolute instability when a fixed boundary condition upstream is imposed. This boundary induced instability acts as a continuous wave source, creating a local periodic excitation near the boundary, which initiates waves traveling both up and downstream. To confirm this, we performed analytical analysis and numerical simulations of a modified Martiel-Goldbeter reaction-diffusion model with the addition of an advection term. We provide a quantitative description of the wave packet appearing in the convectively unstable regime, which we found to be in excellent agreement with the numerical simulations. We characterize this new instability and show that in the limit of high advection speed, it is suppressed. This type of instability can be expected for reaction-diffusion systems that present both a convective instability and an excitable regime. In particular, it can be relevant to understand the signaling mechanism of the social amoeba Dictyostelium discoideum that may experience fluid flows in its natural habitat.Comment: 10 pages, 13 figures, published in Chaos: An Interdisciplinary Journal of Nonlinear Scienc

Spontaneous center formation in Dictyostelium discoideum

Dictyostelium discoideum (D.d.) is a widely studied amoeba due to its capabilities of development, survival, and self-organization. During aggregation it produces and relays a chemical signal (cAMP) which shows spirals and target centers. Nevertheless, the natural emergence of these structures is still not well understood. We present a mechanism for creation of centers and target waves of cAMP in D.d. by adding cell inhomogeneity to a well known reaction-diffusion model of cAMP waves and we characterize its properties. We show how stable activity centers appear spontaneously in areas of higher cell density with the oscillation frequency of these centers depending on their density. The cAMP waves have the characteristic dispersion relation of trigger waves and a velocity which increases with cell density. Chemotactically competent cells react to these waves and create aggregation streams even with very simple movement rules. Finally we argue in favor of the existence of bounded phosphodiesterase to maintain the wave properties once small cell clusters appear.Comment: Currently under review. 12 pages, 8 figures, 1 tabl

Actin-based motility

Spatially controlled polymerization of actin is at the origin of cell motility and is responsible for the formation of cellular protrusions like lamellipodia. The pathogens Listeria monocytogenes and Shigella flexneri, move inside the infected cells by riding on an actin tail. The actin tail is formed from highly crosslinked polymerizing actin filaments, which undergo cycles of attachment and detachment to and from the surface of bacteria. In this thesis, we formulated a simple theoretical model of actin-based motility. The physical mechanism for our model is based on the load-dependent detachment rate, the load-dependent polymerization velocity, the restoring force of attached filaments, the pushing force of detached filaments and finally on the cross-linkage and/or entanglement of the filament network. We showed that attachment and detachment of filaments to the obstacle, as well as polymerization and cross-linking of the filaments lead to spontaneous oscillations in obstacle velocity. The velocity spike amplitudes and periods given by our model are in good agreement with those observed experimentally in Listeria. In this model, elasticity and curvature of the obstacle is not included. Future modelling will yield insight into the role of curvature and elasticity in the actin-based motility. As an important prerequisite for this model, we used analytical calculations as well as extensive Monte Carlo (MC) simulations to investigate the pushing force of detached filaments. The analysis starts with calculations of the entropic force exerted by a grafted semiflexible polymer on a rigid wall. The pushing force, which is purely entropic in origin, depends on the polymer's contour length, persistence length, orientation and eventually on the distance of the grafting point from the rigid wall. We checked the validity range of our analytical results by performing extensive Monte Carlo simulations. This was done for stiff, semiflexible and flexible filaments. In this analysis, the obstacle is always assumed to be a rigid wall. In the real experimental situations, the obstacle (such as membrane) is not rigid and performs thermal fluctuations. Further analytical calculations and MC simulations are necessary to include the elasticity of the obstacl

The survey of pattern of abusing and causes of addiction tendency among women undergoing methadone maintenance treatment in Kashan city during 2017-2018

Background: The current prevalence rates indicate an increasing trend of substance abuse among women. This study aimed at determining the pattern of consumption and causative factors for tendency to drug abuse in woman referred to addiction treatment centers. Materials and Methods: In this descriptive cross-sectional study, the study population was all women referred to addiction treatment centers of Kashan during 2017-2018. The research instrument was a demographic information questionnaire, causes of drug abuse tendency and structured clinical interviews with the Diagnostic and Statistical Manual of Psychiatric Disorders (SCID) to assess the substance abuse disorder. Results: The mean age and onset age of drug abuse were 40±10.3 and 25±6.4 years, respectively. Opium was the most common abused drug (81) and smoking was the most cited method for drug abuse. Ten percent of the patients had a history of injection. The main causes of drug tendency from the perspective of the patients were addict family (77), easy access to drugs (64), as well as depression and disappointment (56). Conclusion: The pattern of drug abuse among women undergoing the method one maintenance treatment in Kashan is traditional on the basis of the opium derivatives. The addict family was the main cause of drug abuse. Therefore, it would be necessary to pay more attention to the family of the patients as vulnerable groups in planning and to provide training on the causes of drug abuse tendency and preventive measures

Entropic forces generated by grafted semiflexible polymers

The entropic force exerted by the Brownian fluctuations of a grafted semiflexible polymer upon a rigid smooth wall are calculated both analytically and by Monte Carlo simulations. Such forces are thought to play an important role for several cellular phenomena, in particular, the physics of actin-polymerization-driven cell motility and movement of bacteria like Listeria. In the stiff limit, where the persistence length of the polymer is larger than its contour length, we find that the entropic force shows scaling behavior. We identify the characteristic length scales and the explicit form of the scaling functions. In certain asymptotic regimes we give simple analytical expressions which describe the full results to a very high numerical accuracy. Depending on the constraints imposed on the transverse fluctuations of the filament there are characteristic differences in the functional form of the entropic forces; in a two-dimensional geometry the entropic force exhibits a marked peak.Comment: 21 pages, 18 figures, minor misprints correcte

Antimicrobial Efficacy and Cytocompatibility of Calcium Hypochlorite Solution as a Root Canal Irrigant: An in Vitro Investigation

Introduction: The purpose of this study was to compare the antimicrobial efficacy of sodium hypochlorite (SH) and calcium hypochlorite (CH) against Enterococcus faecalis (E. faecalis) using quantitative real-time polymerase chain reaction (qPCR) analysis and also to compare their cytocompatibility on L929 murine fibroblasts using Mossman’s tetrazolium toxicity (MTT) assay. Methods and Materials: A broth micro-dilution susceptibility test was used to determine the minimum inhibitory concentration (MIC) of each irrigant against E. faecalis. Then, the root canals of 50 mature extracted human mandibular premolars were contaminated with E. faecalis and were randomly divided into three groups according to the irrigant used (n=20). Canals were irrigated with SH in group I (n=20) and CH in group II (n=20) at their obtained MIC. In group III (n=10), sterile saline was used. Microbial sampling was performed before and after biomechanical preparation. Quantitative PCR was used to quantify E. faecalis in the root canal samples. For cytocompatibility assessment, L929 murine fibroblasts were exposed to various concentrations of the irrigants. Results: Irrigation with test materials resulted in significant reduction in colony forming units (CFU) in post-instrumentation samples (with the MIC values of SH and CH against E. faecalis being 0.5% and 5%, respectively). However, the reduction in the normal saline group was not significant (P=0.203). In addition, 5% CH was more effective than 0.5% SH (P=0.006) in eliminating E. faecalis. Among the different concentrations of tested irrigants, 0.5% CH and 5% SH showed the least and the most cytotoxicity, respectively (P<0.001). The cytotoxicity of 5% CH and 0.5% SH was similar (P=0.99), and lower than 2.5% SH (P<0.001). Conclusion: CH at an MIC of 5% was effective in eliminating E. faecalis in planktonic state and also its biofilm and exhibited comparable cytocompatibility to that of 0.5% SH.Keywords: Calcium Hypochlorite; Enterococcus faecalis; Polymerase Chain Reaction; Root Canal Irrigant; Sodium Hypochlorit

Light-Powered Reactivation of Flagella and Contraction of Microtubule Networks: Toward Building an Artificial Cell

Artificial systems capable of self-sustained movement with self-sufficient energy are of high interest with respect to the development of many challenging applications, including medical treatments, but also technical applications. The bottom-up assembly of such systems in the context of synthetic biology is still a challenging task. In this work, we demonstrate the biocompatibility and efficiency of an artificial light-driven energy module and a motility functional unit by integrating light-switchable photosynthetic vesicles with demembranated flagella. The flagellar propulsion is coupled to the beating frequency, and dynamic ATP synthesis in response to illumination allows us to control beating frequency of flagella in a light-dependent manner. In addition, we verified the functionality of light-powered synthetic vesicles in in vitro motility assays by encapsulating microtubules assembled with force-generating kinesin-1 motors and the energy module to investigate the dynamics of a contractile filamentous network in cell-like compartments by optical stimulation. Integration of this photosynthetic system with various biological building blocks such as cytoskeletal filaments and molecular motors may contribute to the bottom-up synthesis of artificial cells that are able to undergo motor-driven morphological deformations and exhibit directional motion in a light-controllable fashion.R.A., V.N., E.B., I.G., and A.G. acknowledge support from the European Union’s Horizon 2020 research and innovation programme under grant agreement MAMI No. 766007. C.K., A.B., E.B., K.S., I.G., T.V.K., and A.G. thank MaxSynBio Consortium, which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Societ

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries