Stochastic modeling of cargo transport by teams of molecular motors

Many different types of cellular cargos are transported bidirectionally along microtubules by teams of molecular motors. The motion of this cargo-motors system has been experimentally characterized in vivo as processive with rather persistent directionality. Different theoretical approaches have been suggested in order to explore the origin of this kind of motion. An effective theoretical approach, introduced by M\"uller et al., describes the cargo dynamics as a tug-of-war between different kinds of motors. An alternative approach has been suggested recently by Kunwar et al., who considered the coupling between motor and cargo in more detail. Based on this framework we introduce a model considering single motor positions which we propagate in continuous time. Furthermore, we analyze the possible influence of the discrete time update schemes used in previous publications on the system's dynamic.Comment: Cenference proceedings - Traffic and Granular Flow 1

Le manganèse dans l'eau - Elimination du manganèse dans l'eau par traitement biologique

Le manganèse est un élément minéral fréquemment rencontré dans différents types d'eau, surtout souterraines. Dans le cas des eaux de surface, le manganèse peut se trouver lors de pollutions accidentelles où lorsque la rivière reçoit des eaux d'un barrage réservoir en fin de vidange.Des essais de traitement d'une pollution par du manganèse par filtration lente ont été effectués sur un pilote.Les essais ont porté sur différentes concentrations de manganèse pendant des périodes de courte durée. La filtration lente semble très efficace pour l'élimination de ce composé, mais il faut noter que la nitrification biologique est altérée par la présence de fortes concentrations de manganèse.Manganese is a mineral element which is often found in differing types of water. The manganese content is rather consistent, especially in underground waters. In surface waters, manganese can only be found as a result of an occidental pollution or in rivers supplied with water from a dam whose tank has been sewed.This metal is not dangerous for humans but it can create problems in drinking water as it becomes progressively oxidized and thus precipitates in the water supply. This oxidation can produce direct effects like spots on linen or sanitary appliances, but also indirect effects, like important bacterial developments, as well as bacteria protection against biocides used as bactericidal or bacteriostatic agents.This study aims at :1) Underlining the possible effects of manganese in case of an accidental pollution.2) Underlining how much time the system takes to react to an increased manganese content, given that ferric salts which permanently incluse manganese (500 to 600 ppm in the 40 % commercial solution) are used in the coagulation phase.Amongst several methods to eliminate the manganese, the biological oxidation seems to be the most appropriate to this occasional pollution problem. Indeed, it filters are continually contaminated by manganese, the bacteria is likely to oxidize the divalent manganese, resulting in an immediate ceasing of the pollution, without human intervention. This is what the operation aims at.The existing data regarding the biological elimination of manganese in underground waters shows it to be consistent. There is no such data on manganese elimination by slow sand filtration, in surface waters, in case of a short accidental pollution. As far as slow sand filtration is concerned, the available results only represent waters with consistent manganese contents.This study has been carried out with a 50 m3/h pilote system, which was located in Paris surroundings. It was supplied with water from the Marne river and combined physicochemical and biological treatments. The physicochemical phase consisted of a coagulation-flocculation-decantation reaction in a pulsator, with ferric chloride including 500 to 600 ppm divalent manganese. Then, it was quickly filtered through sand, at a flow rate of 5 m/h. The water was subsequently poured into a storage tank in which it remained for around two hours. Then, it was filtered through slow sand filters, which biologically treated it. The filters contained 1 m high of sand and the filtration rate was 1 m/h, which allowed the development of a biological membrane on their surfaces.Simulated manganese pollution tests have been realised as follows :- water with two different manganese contents have been tested (0,5 and 1 mg/l),- ammonium Ions have been simultaneously added to show a possible inhibition of nitrification.Each test lasted around two weeks and time was spent as follows :- polluting agents were continuously added during 3 days (which is the maximum duration of an accidental pollution).These two tests gave the following results :1st test (0,5 manganese/l) :- 35 % of the manganese was eliminated during the coagulation-decantation-quick filtration phase.- 100 % of the manganese was held bock by the slow sand filtration.- An important amount of nitrites appeared in water at the end of the treatment, which suggested an inhibition of the nitrification, or a competition between manganese and ammoniacal oxidation.- After the manganese pollution was stopped, no release of manganese and no inhibition of the nitrification were noticed.2nd test (1 mg manganese/l) :- 25 % of the manganese was eliminated during the coagulation-decantation-quick filtration phase.- 97 % of the manganese was eliminated by slow sand filtration.- In this case, the ammonium and nitrites were eliminated by the biological filtration, which suggested a readaptation of the bacterial flora to this kind of pollution.The result showed chat the biological chain adapts itself very quickly to a rapid increase in water manganese content (no more than 2 hours). Indeed, the biological membrane, which was already contaminated by a permanent accumulation of manganese, reacted very quickly. The first test shows that nitrites appear and confirms the results that other searchers had already obtained before, in there is competition between nitrobacteria and the bacteria which oxidize manganese.A less efficient elimination of organic matter also shows competition during the biodegradation phase.In the second series of tests, a modification of the bacterial flora, due to the first manganese simulated pollution tests, is noticed.These encouraging results allowed us to propose an original system for water treatment, based on a physicochemical treatment and biological slow treatments and, afterwards, a refining phase with combined ozone and granular actiated carbon.In addition to its well-known properties, ozone allows to avoid the possible appearance of nitrites in water

The role of microtubule movement in bidirectional organelle transport

We study the role of microtubule movement in bidirectional organelle transport in Drosophila S2 cells and show that EGFP-tagged peroxisomes in cells serve as sensitive probes of motor induced, noisy cytoskeletal motions. Multiple peroxisomes move in unison over large time windows and show correlations with microtubule tip positions, indicating rapid microtubule fluctuations in the longitudinal direction. We report the first high-resolution measurement of longitudinal microtubule fluctuations performed by tracing such pairs of co-moving peroxisomes. The resulting picture shows that motor-dependent longitudinal microtubule oscillations contribute significantly to cargo movement along microtubules. Thus, contrary to the conventional view, organelle transport cannot be described solely in terms of cargo movement along stationary microtubule tracks, but instead includes a strong contribution from the movement of the tracks.Comment: 24 pages, 5 figure

PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores.

The PAT family of lipid droplet proteins includes 5 members in mammals: perilipin, adipose differentiation-related protein (ADRP), tail-interacting protein of 47 kDa (TIP47), S3-12, and OXPAT. Members of this family are also present in evolutionarily distant organisms, including insects, slime molds and fungi. All PAT proteins share sequence similarity and the ability to bind intracellular lipid droplets, either constitutively or in response to metabolic stimuli, such as increased lipid flux into or out of lipid droplets. Positioned at the lipid droplet surface, PAT proteins manage access of other proteins (lipases) to the lipid esters within the lipid droplet core and can interact with cellular machinery important for lipid droplet biogenesis. Genetic variations in the gene for the best-characterized of the mammalian PAT proteins, perilipin, have been associated with metabolic phenotypes, including type 2 diabetes mellitus and obesity. In this review, we discuss how the PAT proteins regulate cellular lipid metabolism both in mammals and in model organisms

Action du sulfite de sodium sur la concentration en composés organohalogénés et sur l'activité mutagène de solutions chlorées de substances humiques

Cette étude a eu pour but de déterminer l'effet d'un traitement par le sulfite de sodium sur la concentration en composés organohalogénés totaux (TOX) et sur l'activité mutagène de solutions chlorées de substances humiques d'origine aquatique (SHA), après avoir cherché à préciser l'influence du pH et du temps sur la concentration en TOX.Les résultats obtenus à partir d'échantillons chlorés de SHA en absence de chlore résiduel ont permis de mettre en évidence une diminution de la concentration en composés organohalogénés totaux, soit par stockage en milieu neutre ou basique, soit par addition de sulfite de sodium. L'intensité de cette réduction de la concentration en TOX augmente avec le pH, le temps de réaction et la dose de sulfite de sodium introduite.Les résultats obtenus à partir d'échantillons contenant du chlore libre indiquent que seule une déchloration totale avec un excès de sulfite de sodium peut conduire, en milieu neutre, à une diminution de l'activité mutagène et de la concentration en TOX des solutions diluées de SHA. La comparaison des pourcentages d'abattement obtenus sur le paramètre TOX et sur l'activité mutagène indique que la diminution de la génotoxicité par déchloration totale est due à l'action du sulfite sur des composés mutagènes non chlorés ou sur des composés chlorés fortement mutagènes et ne représentant qu'une très faible fraction du TOX.If is a well known tact that mimerous organohalogenated compounds are formed during the chlorination (preoxidation or final disinfection) of drinking water. Some of these compounds have been shown to be mutagenic. Recent studies have suggested that a treatment with oxygenated derivatives of SIV (SO2, NaHSO3 and Na2SO3) could reduce the genotoxicity of chlorinated drinking water.The general aim of Ibis study was to determine the effect of dechlorination treatments on the mutagenic activity of chlorinated drinking water. The following experiments were carried out in order to point out the effect of a treatment with sodium sulfite on the concentration of total organohalogenated compounds (TOX) and on the mutagenic activity of chlorinated dilute solutions of Aquatic Humic Substances (AHS).At first, the affects of pH, sodium sulfite dose and contact time on TOX concentration were investigated. Then, the importance of the dechlorination rate (partial or complete) on TOX concentration and also on the mutagenic activity could be studied.ExperimentalAquatic Humic Substances (natural mixture of fulvic and humic acids) were dissolved in phosphate-buffered ultra-pure water at 5 and 15 mg l-1 concentrations (pH 6.1 and 6.9 respectively). Stock solutions of chlorine were prepared in the laboratory and titrated by iodometry. Chlorination and dechlorination treatments were carried out in headspace-free baffles, at 20± 1 °C in the dark. Residual chlorine was determined by spectrophotometric measurements at 510 nm, following the calorimetric method using N,N-diethylphenylene-1,4-diamine (DPD). To avoid the slow oxidation of Slv into Svl by dissolved oxygen, the sodium sulfite solutions were prepared freshly before use. TOX concentrations were measured using a DOHRMAN DX-20 TOX analyser equipped with a MC-1 microcoulometric cell and with an AD-2 adsorption module. Before analysis, the residual chlorine was neutralized with sodium thiosulfate and samples were acidified to pH 1.4.The mutagenic activity was determined using acetone-dichloromethane extracts (AMBERLITE XAD-8 and XAD-2 resins) of the aqueous samples of chlorinated and dechlorinated solutions of AHS, acidified to pH 2.0 before extraction. The mutagenicity tests were carried out on TA 98 and TA 100 tester strains, following the method described by MARON and AMES (1983).Results-Effect of pH, addition of sodium sulfite and storage time on the TOX concentrationThe experiments carried out with dilute solutions of AHS ([AHS] = 5 mg 1-1; DOC = 2.5 mg Cl-1; pH = 6.1) showed a linear relationship between TOX production and chlorine consumption in the range 0-2.0 mg Cl2 l-1 (fig. 2).15 % of the chlorine demand was incorporated as organic chlorine in molecules.Experiments performed on solutions containing no residual free chlorine showed that organohatogenated compounds could be partially destroyed upon storage at neutral or basic pH (table 1). Reductions in TOX concentrations of 10 % at pH 6.1-8.5 in 24 hours and of 20 % at pH 11.5 in 2 hours were observed. This was enhanced by increasing the storage time.The addition of sodium sulfite (100 µmol l-1) in solutions containing no residual free chlorine significantly reduced the TOX concentration (10 % in 2 hours at pH 6.1-8.5; table 1). This reduction was enhanced by increasing sulfite dose and storage time and by increasing pH (30 % in 2 hours at pH 11.5). Furthermore, at a given pH value and for a reaction time of 2 hours, the decrease in TOX concentration was larger in presence of sulfite.- Effect of a dechlorination treatment on the TOX concentrationAs shown in figure 3, a dechlorination treatment (reduction of the residual free chlorine concentration) with sodium sulfite could significantly reduce the TOX concentration of the dilute solutions of AHS at pH 6.1 only if an excess of the dechlorinating agent was added. This effect was enhanced by increasing the excess of sulfite but nevertheless seemed to be limited (less than 15 % of reduction for the highest doses used; table 2).The free chlorine residuals measured after a 2 hours partial dechlorination confirmed the stoichiometric factor of 1 mole/mole for the reaction between chlorine and sodium sulfite.- Effect of a dechlorination treatment on the mutagenic activity and on the TOX concentrationThe dechlorination treatments were carried out on chlorinated dilute solutions of AHS ([AHS] = 15 mg l-1; DOC 7.5 mg C l-1; pH = 6.9). The TOX concentrations were measured on aqueous solutions and mutagenicity tests were performed on the corresponding acetone-dichloromethane extracts following a solvent exchange (dimethylsulfoxide). The results obtained showed again that only a total dechlorination treatment could reduce the TOX concentration of the aqueous chlorinated solutions and was able to destroy a significant part of the mutagenic activity of the extracts (table 3 and fig. 4).Although the effect of sulfite on TOX concentration seemed limited (less than 7 % reduction for the highest sulfite dose tested), the reduction in the genotoxicity was more important when the excess of sulfite was increased. No correlation between the TOX concentration and the mutagenic activity could be established. The mutagenic compounds destroyed by sodium sulfite do not appear to be organohalogenated ones. If they are, they are present at trace levels and thus are extremely patent and account for a very little part of the TOX concentration

Tuberculosis in a South African prison - a transmission modelling analysis

Background. Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A. recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a mathematical model was developed to explore the interactions between incarceration conditions and TB control measures. Methods. Cell dimensions, cell occupancy, lock-up time, TB incidence and treatment delays were derived from court evidence and judicial reports. Using the Wells-Riley equation and probability analyses of contact between prisoners, we estimated the current TB transmission probability within prison cells, and estimated transmission probabilities of improved levels of case finding in combination with implementation of national and international minimum standards for incarceration. Results. Levels of overcrowding (230%) in communal cells and Poor TB case finding result in annual TB transmission risks of 90% per annum. Implementing current national or international cell occupancy recommendations would reduce TB transmission probabilities by 30% and 50%, respectively. Improved passive case finding, modest ventilation increase or decreased lock-up time would minimally impact on transmission if introduced individually. However, active case finding together with implementation of minimum national and international standards of incarceration could reduce transmission by 50% and 94%, respectively. Conclusions. Current conditions of detention for awaiting-trial prisoners are highly conducive for spread of drug-sensitive and drug-resistant TB. Combinations of simple well-established scientific control measures should be implemented urgently

Reverse methanogenesis and respiration in methanotrophic archaea

Anaerobic oxidation of methane (AOM) is catalyzed by anaerobic methane-oxidizing archaea (ANME) via a reverse and modified methanogenesis pathway. Methanogens can also reverse the methanogenesis pathway to oxidize methane, but only during net methane production (i.e., "trace methane oxidation"). In turn, ANME can produce methane, but only during net methane oxidation (i.e., enzymatic back flux). Net AOM is exergonic when coupled to an external electron acceptor such as sulfate (ANME-1, ANME-2abc, and ANME-3), nitrate (ANME-2d), or metal (oxides). In this review, the reversibility of the methanogenesis pathway and essential differences between ANME and methanogens are described by combining published information with domain based (meta)genome comparison of archaeal methanotrophs and selected archaea. These differences include abundances and special structure of methyl coenzyme M reductase and of multiheme cytochromes and the presence of menaquinones or methanophenazines. ANME-2a and ANME-2d can use electron acceptors other than sulfate or nitrate for AOM, respectively. Environmental studies suggest that ANME-2d are also involved in sulfate-dependent AOM. ANME-1 seem to use a different mechanism for disposal of electrons and possibly are less versatile in electron acceptors use than ANME-2. Future research will shed light on the molecular basis of reversal of the methanogenic pathway and electron transfer in different ANME types.The authors thank Stefanie Berger (RU,Nijmegen) for critical reading of the manuscript. This research is supported by the Soehngen Institute of Anaerobic Microbiology (SIAM) Gravitation Grant (024.002.002) of the Netherlands Ministry of Education, Culture and Science and the Netherlands Organisation for Scientific Research (NWO). Mike S. M. Jetten was further supported by ERC AG 339880 Eco-MoM and Alfons J. M. Stams was supported by ERC AG 323009 Novel Anaerobes.info:eu-repo/semantics/publishedVersio

Risk factors for COPD spirometrically defined from the lower limit of normal in the BOLD project.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and disability worldwide by 2020. The prevalence of COPD defined by the lower limit of normal was estimated using high-quality spirometry in surveys of 14 populations aged ≥ 40 yrs. The strength and consistency of associations were assessed using random effects meta-analysis. Pack-years of smoking were associated with risk of COPD at each site. After adjusting for this effect, we still observed significant associations of COPD risk with age (OR 1.52 for a 10 yr age difference, 95% CI 1.35-1.71), body mass index in obese compared with normal weight (OR 0.50, 95% CI 0.37-0.67), level of education completed (OR 0.76, 95% CI 0.67-0.87), hospitalisation with a respiratory problem before age 10 yrs (OR 2.35, 95% CI 1.42-3.91), passive cigarette smoke exposure (OR 1.24, 95% CI 1.05-1.47), tuberculosis (OR 1.78, 95%CI 1.17-2.72) and a family history of COPD (OR 1.50, 95% CI 1.19-1.90). Although smoking is the most important risk factor for COPD, other risk factors are also important. More research is required to elucidate relevant risk factors in low- and middle-income countries where the greatest impact of COPD will occur.ALTANA Aventis AstraZeneca Boehringer-Ingelheim Chiesi GlaxoSmithKline Merck Novartis Pfizer Schering-Plough Sepracor University of Kentucky Boehringer Ingelheim China (Guangzhou, China) Turkish Thoracic Society Pfizer (Adana, Turkey) Merck Sharpe Dohme Salzburger Gebietskrankenkasse Salzburg Local Government (Salzburg, Austria) Research for International Tobacco Control International Development Research Centre South African Medical Research Council South African Thoracic Society GlaxoSmithKline University of Cape Town Lung Institute (Cape Town, South Africa) Landspitali-University Hospital GlaxoSmithKline Iceland AstraZeneca Iceland (Reykjavik, Iceland) GlaxoSmithKline Pharmaceuticals Polpharma Ivax Pharma Poland AstraZeneca Pharma Poland ZF Altana Pharma Pliva Krakow Linde Gaz Polska Novartis Poland Lek Polska Farmaceutyczne Polfa Starostwo Proszowice Skanska Zasada Agencja Mienia Wojskowego w Krakowie Telekomunikacja Polska Biernacki Amplus Bucki Skrzydlewski Sotwin Agroplon (Krakow, Poland) Pfizer Germany (Hanover, Germany) Norwegian Ministry of Health's Foundation for Clinical Research Haukeland University Hospital's Medical Research Foundation for Thoracic Medicine (Bergen, Norway) GlaxoSmithKline (Vancouver, Canada) Marty Driesler Cancer Project (Lexington, KY, USA) Philippine College of Chest Physicians Boehringer Ingelheim (Phil) Philippine College of Physicians United Laboratories (Phil) (Manila, Philippines) Air Liquide Healthcare P/L AstraZeneca P/L Boehringer Ingelheim P/L GlaxoSmithKline Australia P/L Pfizer Australia P/L (Sydney, Australia) UK Department of Health's Policy (London, UK) Swedish Heart-Lung Foundation Swedish Heart and Lung Association GlaxoSmithKline (Uppsala, Sweden) Adamed Lek Polska Biogra

A three dimensional model of the photosynthetic membranes of Ectothiorhodospira halochloris

The three dimensional organization of the complete photosynthetic apparatus of the extremely halophilic, bacteriochlorophyll b containing Ectothiorhodospira halochloris has been elaborated by several techniques of electron microscopy. Essentially all thylakoidal sacs are disc shaped and connected to the cytoplasmic membrane by small membraneous ldquobridgesrdquo. In sum, the lumina of all thylakoids (intrathylakoidal space) form one common periplasmic space. Thin sections confirm a paracrystalline arrangement of the photosynthetic complexes in situ. The ontogenic development of the photosynthetic apparatus is discussed based on a structural model derived from serial thin sections