Factors associated with the 6-minute walk distance in patients with systemic sclerosis

Background

There is an ongoing debate regarding the relevance of the 6-minute walking distance (6MWD) in systemic sclerosis (SSc) assessment, widely used as a usual test in these patients as well as an outcome measure in clinical trials. In this work, we aimed to assess the associations between the 6MWD and various disease parameters in patients with SSc.

Methods

Consecutive patients followed in our SSc National Reference Centre were included in this cross-sectional study if they fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc. Data were systematically collected during a comprehensive standardized evaluation that included a 6-minute walk test, clinical assessment, biological results, pulmonary function tests, transthoracic echocardiography, composite scores (European Scleroderma Study Group Activity Index, Medsger severity score, Health Assessment Questionnaire–Disability Index (HAQ-DI)) and treatments.Associations of the 6MWD with various disease parameters were assessed by linear regression in univariate and multivariate analyses.

Results

The study population comprised 298 patients (females 81%; mean age 58.2?±?13.3 years; limited cutaneous SSc 82%; interstitial lung disease (ILD) 42%; pulmonary arterial hypertension (PAH) 6%). The 6MWD was significantly and independently associated with gender, age, body mass index, baseline heart rate (HR), HR variation during the test, PAH, history of arterial thrombosis and C-reactive protein levels, as well as with the HAQ-DI score in a sensitivity analysis. Muscle involvement, joint involvement and ILD were not independently associated with the 6MWD.

Conclusions

During SSc, the 6MWD is independently associated with initial HR and HR variation; with PAH but not ILD, suggesting that pulmonary vasculopathy may have a greater impact than parenchymal involvement on functional limitation; and with global markers of disease activity and patient disability. These results give clinicians further insight into how to interpret the 6MWD in the context of SSc.

     

Brassica juncea tested on urban soils moderately contaminated by lead: Origin of contamination and effect of chelates

Urban garden soils are a potential repository of heavy metal pollution, resulting from either anthropogenic or geogenic origin. The efficiency of phytoextraction was compared on two garden soils with the same texture and topsoil Pb concentration (170 mg kg^?1) but not the same origin: one geogenic, the other anthropogenic. Two varieties of Brassica juncea were tested with citric acid (25 mmol kg^?1) or ethylenediaminetetraacetic acid (EDTA, 2.5 mmol kg^?1). Geogenic Pb was shown to be two times less available than anthropogenic Pb, as a result of which the phytoextraction efficiency was reduced by 59%. Pb mobility in the soil was solely enhanced with EDTA, which increased the Pb concentration in shoots of B. juncea by between 14 and 26 times in comparison with the control. The highest Pb concentration in shoots still remained low, however (i.e., 45 mg kg^?1 dry weight). Regardless of the chelates introduced, B. juncea 426308 accumulated roughly twice as much lead as B. juncea 211000, but only for the anthropogenic contaminated soil. Under these conditions, the amount of Pb accumulated by B. juncea (even when assisted by EDTA) was not high enough to envision achieving soil clean-up within a reasonable time frame.     

Molecular mechanisms of invasion by cancer cells, leukocytes and microorganisms

Invasion is a phenotype common to cancer cells, leukocytes, parasites, bacteria and viruses, involving cell-cell adhesion, cell-matrix adhesion, proteolysis and motility. These activities are regulated by the cross talk between invaders and host. We discuss the invasion-related molecular interactions of E-cadherin, integrins, matrix metalloproteinases and the chemokine receptor RANTES.     

FisB relies on homo-oligomerization and lipid binding to catalyze membrane fission in bacteria

Little is known about mechanisms of membrane fission in bacteria despite their requirement for cytokinesis. The only known dedicated membrane fission machinery in bacteria, fission protein B (FisB), is expressed during sporulation in Bacillus subtilis and is required to release the developing spore into the mother cell cytoplasm. Here, we characterized the requirements for FisB-mediated membrane fission. FisB forms mobile clusters of approximately 12 molecules that give way to an immobile cluster at the engulfment pole containing approximately 40 proteins at the time of membrane fission. Analysis of FisB mutants revealed that binding to acidic lipids and homo-oligomerization are both critical for targeting FisB to the engulfment pole and membrane fission. Experiments using artificial membranes and filamentous cells suggest that FisB does not have an intrinsic ability to sense or induce membrane curvature but can bridge membranes. Finally, modeling suggests that homo-oligomerization and trans-interactions with membranes are sufficient to explain FisB accumulation at the membrane neck that connects the engulfment membrane to the rest of the mother cell membrane during late stages of engulfment. Together, our results show that FisB is a robust and unusual membrane fission protein that relies on homo-oligomerization, lipid binding, and the unique membrane topology generated during engulfment for localization and membrane scission, but surprisingly, not on lipid microdomains, negative-curvature lipids, or curvature sensing.

Little is known about how membrane fission occurs in bacteria; this study suggests that the membrane fission protein FisB exploits the unique cellular geometry encountered during sporulation to enable its localization to the fission site through a novel mechanism, where it catalyzes membrane scission.     

Effect of organic amendment on soil fertility and plant nutrients in a post-fire Mediterranean ecosystem

Backgrounds and aims

In Mediterranean frequently burnt areas, the decrease of soil fertility leads to regressive vegetation dynamics. Organic amendments could help to accelerate post-fire ecosystem resilience, by improving soil properties and plant nutrition. This study was conducted to assess the potential of a composted biosolid to restore an early post-fire shrubland.

Methods

About 50 Mg.ha^?1 of fresh co-composted sewage sludge and green wastes were surface applied 7 months after fire on a silty-clayey soil. We monitored over a 2-year period organic matter and nutrient transfers to soil, nutrient responses of dominant plant species, and ecosystem contamination by potentially toxic trace elements.

Results

Over the experimental survey, compost rapidly and durably improved soil P₂O₅, MgO and K₂O content, and temporarily increased N-(NO₃ ^? + NO₂ ^?) content. Plant nutrition was improved more or less durably depending species. The most positive compost effect was on plant and soil phosphorus content. Plant nutrient storage was not improved 2 years after amendment, suggesting luxury consumption. No contamination by trace elements was detected in soil and plant.

Conclusions

The use of compost after fire could help for rapidly restoring soil fertility and improving plant nutrition. The increase of soil nutrient pools after amendment emphazised the diversity of plant nutritional traits. Eutrophication risk could occur from high compost and soil P₂O₅ content.     

Root Architecture Responses: In Search of Phosphate

Soil phosphate represents the only source of phosphorus for plants and, consequently, is its entry into the trophic chain. This major component of nucleic acids, phospholipids, and energy currency of the cell (ATP) can limit plant growth because of its low mobility in soil. As a result, root responses to low phosphate favor the exploration of the shallower part of the soil, where phosphate tends to be more abundant, a strategy described as topsoil foraging. We will review the diverse developmental strategies that can be observed among plants by detailing the effect of phosphate deficiency on primary and lateral roots. We also discuss the formation of cluster roots: an advanced adaptive strategy to cope with low phosphate availability observed in a limited number of species. Finally, we will put this work into perspective for future research directions.Plant embryogenesis generates a very primitive developmental blueprint with two apical meristems (shoot and root) that, unlike in animals, do not reflect the anatomy of the adult organism. The ability to form new organs is maintained throughout their lifecycle because of the sustained activity of these meristems as well as the presence of dedicated cells that dedifferentiate and generate new meristems. The continuous nature of plant development associated with their sessile lifestyle results in a strong dependency on their immediate environment. As a result, the study of plant development must not only focus on the fundamental molecular and cellular mechanisms but also, integrate their ability to perceive and respond to the environment. In this regard, plant root systems represent a good model, because they have a high level of developmental plasticity in response to water, nutrients, gravity, and mechanical characteristics of the soil as well as biotic interactions.Among the essential nutrients for plant growth and development, phosphorus is a key component of nucleic acids and phospholipids and present in soil in the form of either inorganic phosphate (Pi) or organophosphates. The former strongly interacts with divalent and trivalent cations. The latter has to be hydrolyzed to release phosphate for root uptake. The high sorption capacity of phosphate to soil particles results in a very low mobility and availability for uptake by plants. Therefore, the capacity of plants to find an adequate phosphate supply is directly correlated with their ability to explore the soil. Correspondingly, phosphorus deficiency induces changes in root system architecture as a key adaptive mechanism. A general strategy has been described under the term topsoil foraging that favors a shallower root system to explore the upper part of the soil, where phosphate tends to be more available because of the presence of organic matter and animal excrements. Although this term was first introduced to describe root system adaptation in bean (Phaseolus vulgaris; Lynch and Brown, 2001), the set of responses behind the topsoil foraging strategy has now been described in many other species (Panigrahy et al., 2009; Péret et al., 2011; Li et al., 2012; Shi et al., 2013). We will give an up-to-date overview of recent publications on developmental adaptations to low phosphate observed in diverse monocot and dicot species by focusing on the responses of the primary root (PR) and lateral roots. Finally, we will describe the evolutionarily advanced developmental adaptation to low phosphorus that has been found in several plant families’ (i.e. cluster or proteoid) root formation.     

On-line cleanup for 2-aminobenzamide-labeled oligosaccharides

Analysis of 2-aminobenzamide-labeled oligosaccharides requires removal of excess labeling reagents before chromatography. Manual cleanup is time-consuming and not optimal for routine analysis, so an on-line solid-phase extraction was developed. Labeled oligosaccharides are trapped on an amide phase in a small guard column, the excess reagents are washed away, and then the sample is transferred to the analytical column for analysis. The on-line protocol shortened the sample preparation time and has been applied for the analysis of oligosaccharides and N-glycans released from glycoproteins.     

TOX4 and its binding partners recognize DNA adducts generated by platinum anticancer drugs

Platinating agents are commonly prescribed anticancer drugs damaging DNA. Induced lesions are recognized by a wide range of proteins. These are involved in cellular mechanisms such as DNA repair, mediation of cytotoxicity or chromatin remodeling. They therefore constitute crucial actors to understand pharmacology of these drugs. To expand our knowledge about this subproteome, we developed a ligand fishing trap coupled to high throughput proteomic tools. This trap is made of damaged plasmids attached to magnetic beads, and was exposed to cell nuclear extracts. Retained proteins were identified by nanoHPLC coupled to tandem mass spectrometry. This approach allowed us to establish a list of 38 proteins interacting with DNA adducts generated by cisplatin, oxaliplatin and satraplatin. Some of them were already known interactome members like high mobility group protein 1 (HMGB1) or the human upstream binding factor (hUBF), but we also succeeded in identifying unexpected proteins such as TOX HMG box family member 4 (TOX4), phosphatase 1 nuclear targeting subunit (PNUTS), and WD repeat-containing protein 82 (WDR82), members of a recently discovered complex. Interaction between TOX4 and platinated DNA was subsequently validated by surface plasmon resonance imaging (SPRi). These interactions highlight new cellular responses to DNA damage induced by chemotherapeutic agents.     

Nature of sterols affects plasma membrane behavior and yeast survival during dehydration

The plasma membrane (PM) is a main site of injury during osmotic perturbation. Sterols, major lipids of the PM structure in eukaryotes, are thought to play a role in ensuring the stability of the lipid bilayer during physicochemical perturbations. Here, we investigated the relationship between the nature of PM sterols and resistance of the yeast Saccharomyces cerevisiae to hyperosmotic treatment. We compared the responses to osmotic dehydration (viability, sterol quantification, ultrastructure, cell volume, and membrane permeability) in the wild-type (WT) strain and the ergosterol mutant erg6Δ strain. Our main results suggest that the nature of membrane sterols governs the mechanical behavior of the PM during hyperosmotic perturbation. The mutant strain, which accumulates ergosterol precursors, was more sensitive to osmotic fluctuations than the WT, which accumulates ergosterol. The hypersensitivity of erg6Δ was linked to modifications of the membrane properties, such as stretching resistance and deformation, which led to PM permeabilization during the volume variation during the dehydration-rehydration cycles. Anaerobic growth of erg6Δ strain with ergosterol supplementation restored resistance to osmotic treatment. These results suggest a relationship between hydric stress resistance and the nature of PM sterols. We discuss this relationship in the context of the evolution of the ergosterol biosynthetic pathway.     

Genetic diversity, geographical range and origin of Bemisia tabaci (Hemiptera: Aleyrodidae) Indian Ocean Ms

The whitefly Bemisia tabaci is a pest vector of begomoviruses on crops worldwide. Bemisia tabaci is composed of a complex of cryptic species which barely interbreed. An exception is the Ms from the South West Indian Ocean (SWIO), which crosses in low proportions with the exotic B. The Ms, together with B and Q is part of the same phylogenetic clad. To infer the genetic structure, the geographical range and putative origin of this putative species, microsatellite data and mitochondrial DNA (cytochrome oxydase I) sequences were analysed on an extensive sample set, including all the islands of the region and samples from mainland Africa. Only B and Ms populations were detected across these islands. The exotic B was found only on the islands of Réunion and Mauritius, whereas the Ms is found on all the SWIO islands. Very high isolation by distance was found for the Ms populations between islands of the SWIO, suggesting a long period of presence in this region. Ms populations from mainland Africa had a higher COI diversity than the Ms of the SWIO islands. This diversity is correlated with size and geological ages of the SWIO islands. The population genetic data obtained are in accordance with an origin of Ms in Africa, followed by its expansion and evolution across the SWIO islands prior to human arrival, confirming the status of Ms as indigenous in the SWIO islands.