Spatially explicit modeling of pathogen adaptation to hosts with multiple resistance genes

One of the control strategies of fungal crop diseases is planting highly resistant varieties. However selection pressure on the pathogen, imposed by major resistance genes, leads to the development of new virulent races. In most cases breakdown of resistance has been reported for crop-pathogen systems with a genetically uniform crop distributed over large areas[2]. To derive strategies leading to durable resistance we focus on studying the role of recombination of pathogen genotypes and their spread in the process of succes-sive breakdowns of resistant hosts carrying different major resistance genes and their pyramids

Mechanical characterization and comparison of different NiTi/silicone rubber interfaces

International audienceThis paper investigates the effects of different surface treatments on the mechanical resistance of interface between wires of NiTi shape memory alloy and silicone rubber. Three different treatments were used; primer, plasma and combination of both. The wires deoxidation effects have also been studied. In order to characterize the interface properties in such composite material, pull-out tests were carried out by means of a home-made device. This test allows us to evaluate the mechanical resistance of the interface in terms of the maximum force reached during the test. First, results show that the debonding force is not higher after the wires deoxidation. This preparation is therefore not necessary. Second, using a primer PM820 and plasma separately leads to a significant improvment of the mechanical resistance. Third, the combination of these treatments (primer followed by plasma) and a longer time of exposure to the plasma alone get the debonding force higher. Consequently, NiTi/silicone rubber interface improved only by means of plasma offers a new way to obtain biocompatible interfaces in such composite material

αTAT1 controls longitudinal spreading of acetylation marks from open microtubules extremities OPEN

International audienceAcetylation of the lysine 40 of α-tubulin (K40) is a post-translational modification occurring in the lumen of microtubules (MTs) and is controlled by the α-tubulin acetyl-transferase αTAT1. How αTAT1 accesses the lumen and acetylates α-tubulin there has been an open question. Here, we report that acetylation starts at open ends of MTs and progressively spreads longitudinally from there. We observed acetylation marks at the open ends of in vivo MTs re-growing after a Nocodazole block, and acetylated segments growing in length with time. Bias for MTs extremities was even more pronounced when using non-dynamic MTs extracted from HeLa cells. In contrast, K40 acetylation was mostly uniform along the length of MTs reconstituted from purified tubulin in vitro. Quantitative modelling of luminal diffusion of αTAT1 suggested that the uniform acetylation pattern observed in vitro is consistent with defects in the MT lattice providing lateral access to the lumen. Indeed, we observed that in vitro MTs are permeable to macromolecules along their shaft while cellular MTs are not. Our results demonstrate αTAT1 enters the lumen from open extremities and spreads K40 acetylation marks longitudinally along cellular MTs. This mode of tip-directed microtubule acetylation may allow for selective acetylation of subsets of microtubules. Results and Discussion Microtubules (MTs) are dynamic polymers composed of α β-tubulin dimers that assembled into hollow tubes. In most eukaryotic cells, MTs can undergo post-translational modifications (PTMs) that modify their properties and functions 1. Acetylation of the lysine 40 of α-tubulin (K40) is a common PTM that is catalysed by the α-tubulin acetyl-transferase α TAT1 and is associated with stable, long-lived MTs 2-4. Remarkably, K40 acetylation occurs in the lumen of MTs 5,6 and is the only such PTM that we know of ref. 1. Supporting this, Szyk et al. recently used in vitro approaches to demonstrate that α TAT1 enters into and diffuses within the MT lumen 7. However, Szyk et al. also suggested that fast diffusivity of α TAT1 leads to stochastic acetylation that occurs uniformly along the length of MTs. This was in marked contrast with earlier in vivo observations of discrete acetylated segments along MTs 8-10 progressively elongating with time 11. More recently, several groups have reported that the acetylated segments were predominately associated with the ends of MTs in vivo 3,12. Thus, reported observations in vivo do not match the proposed model of uniformly distributed acetylated K40 marks based on experiments performed with in vitro MTs 7. To understand how acetylated K40 marks spreading occurs in vivo, we first analyzed acetylation dynamics in HeLa cells. In order to synchronize acetylation events, HeLa cells were subjected to complete MT depolymeri-sation by a prolonged treatment with Nocodazole before being allowed to reassemble MTs after washing out th

Fatigue of swollen elastomers

International audienceThe compatibility of the properties of elastomer with conventional diesel fuel has made it favourable in many engineering applications. However, due to global energy insecurity issues, there is an urgent need to find alternative renewable sources of energy as replacements to conventional diesel. In this respect, biodiesel appears to be a promising candidate. Hence, research into the compatibility and fatigue characteristics of elastomers exposed to biodiesel becomes essential. The present paper introduces the first attempt to investigate the effect of different solvents on the fatigue of swollen elastomers. The filled nitrile rubbers are immersed in the palm biodiesel and conventional diesel to obtain the same degree of swelling prior to the application of uniaxial fatigue loading. Field Emission Scanning Electron Microscopy (FESEM) analysis is carried out to observe the fracture surfaces. Stretch-N curves are plotted to illustrate the fatigue life duration. These curves showed that the fatigue lifetime of rubber is the longest for dry rubber and the least for rubber swollen in biodiesel. FESEM micrographs reveal that the loading conditions have no effect on the crack initiation and propagation patterns regardless of the swelling state

The Transcription Factor E4F1 Coordinates CHK1-Dependent Checkpoint and Mitochondrial Functions

Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells

Assembly mechanism and cryoEM structure of RecA recombination nucleofilaments from Streptococcus pneumoniae

Abstract RecA-mediated Homologous Recombination (HR) is a key mechanism for genome maintenance and plasticity in bacteria. It proceeds through RecA assembly into a dynamic filament on ssDNA, the presynaptic filament, which mediates DNA homology search and ordered DNA strand exchange. Here, we combined structural, single molecule and biochemical approaches to characterize the ATP-dependent assembly mechanism of the presynaptic filament of RecA from Streptococcus pneumoniae ( Sp RecA), in comparison to the Escherichia coli RecA ( Ec RecA) paradigm. Ec RecA polymerization on ssDNA is assisted by the Single-Stranded DNA Binding (SSB) protein, which unwinds ssDNA secondary structures that block Ec RecA nucleofilament growth. We report that neither of the two paralogous pneumococcal SSBs could assist Sp RecA polymerization on ssDNA. Instead, we found that the conserved RadA helicase promotes this Sp RecA nucleofilamentation in an ATP-dependent manner. This allowed us to solve the atomic structure of such a long native Sp RecA nucleopolymer by cryoEM stabilized with ATPγS. It was found to be equivalent to the crystal structure of the Ec RecA filament with a marked difference in how RecA mediates nucleotide orientation in the stretched ssDNA. Then, our results show that Sp RecA and Ec RecA HR activities are different, in correlation with their distinct ATP-dependent ssDNA binding modes

Rain-Use-Efficiency: What it Tells us about the Conflicting Sahel Greening and Sahelian Paradox

Rain Use Efficiency (RUE), defined as Aboveground Net Primary Production (ANPP) divided by rainfall, is increasingly used to diagnose land degradation. Yet, the outcome of RUE monitoring has been much debated since opposite results were found about land degradation in the Sahel region. The debate is fueled by methodological issues, especially when using satellite remote sensing data to estimate ANPP, and by differences in the ecological interpretation. An alternative method which solves part of these issues relies on the residuals of ANPP regressed against rainfall (“ANPP residuals”). In this paper, we use long-term field observations of herbaceous vegetation mass collected in the Gourma region in Mali together with remote sensing data (GIMMS-3g Normalized Difference Vegetation Index) to estimate ANPP, RUE, and the ANPP residuals, over the period 1984–2010. The residuals as well as RUE do not reveal any trend over time over the Gourma region, implying that vegetation is resilient over that period, when data are aggregated at the Gourma scale. We find no conflict between field-derived and satellite-derived results in terms of trends. The nature (linearity) of the ANPP/rainfall relationship is investigated and is found to have no impact on the RUE and residuals interpretation. However, at odds with a stable RUE, an increased run-off coefficient has been observed in the area over the same period, pointing towards land degradation. The divergence of these two indicators of ecosystem resilience (stable RUE) and land degradation (increasing run-off coefficient) is referred to as the “second Sahelian paradox”. When shallow soils and deep soils are examined separately, high resilience is diagnosed on the deep soil sites. However, some of the shallow soils show signs of degradation, being characterized by decreasing vegetation cover and increasing run-off coefficient. Such results show that contrasted changes may co-exist within a region where a strong overall re-greening pattern is observed, highlighting that both the scale of observations and the scale of the processes have to be considered when performing assessments of vegetation changes and land degradation

Nucleosome Chiral Transition under Positive Torsional Stress in Single Chromatin Fibers

Using magnetic tweezers to investigate the mechanical response of single chromatin fibers, we show that fibers submitted to large positive torsion transiently trap positive turns, at a rate of one turn per nucleosome. A comparison with the response of fibers of tetrasomes (the (H3-H4)2 tetramer bound with ~50 bp of DNA) obtained by depletion of H2A-H2B dimers, suggests that the trapping reflects a nucleosome chiral transition to a metastable form built on the previously documented righthanded tetrasome. In view of its low energy, <8 kT, we propose this transition is physiologically relevant and serves to break the docking of the dimers on the tetramer which in the absence of other factors exerts a strong block against elongation of transcription by the main RNA polymerase.Comment: 33 pages (double spacing), 7 figure

HIV-1 Protease and Reverse Transcriptase Control the Architecture of Their Nucleocapsid Partner

The HIV-1 nucleocapsid is formed during protease (PR)-directed viral maturation, and is transformed into pre-integration complexes following reverse transcription in the cytoplasm of the infected cell. Here, we report a detailed transmission electron microscopy analysis of the impact of HIV-1 PR and reverse transcriptase (RT) on nucleocapsid plasticity, using in vitro reconstitutions. After binding to nucleic acids, NCp15, a proteolytic intermediate of nucleocapsid protein (NC), was processed at its C-terminus by PR, yielding premature NC (NCp9) followed by mature NC (NCp7), through the consecutive removal of p6 and p1. This allowed NC co-aggregation with its single-stranded nucleic-acid substrate. Examination of these co-aggregates for the ability of RT to catalyse reverse transcription showed an effective synthesis of double-stranded DNA that, remarkably, escaped from the aggregates more efficiently with NCp7 than with NCp9. These data offer a compelling explanation for results from previous virological studies that focused on i) Gag processing leading to nucleocapsid condensation, and ii) the disappearance of NCp7 from the HIV-1 pre-integration complexes. We propose that HIV-1 PR and RT, by controlling the nucleocapsid architecture during the steps of condensation and dismantling, engage in a successive nucleoprotein-remodelling process that spatiotemporally coordinates the pre-integration steps of HIV-1. Finally we suggest that nucleoprotein remodelling mechanisms are common features developed by mobile genetic elements to ensure successful replication