Description of the topographical changes associated to the different stages of the DsbA catalytic cycle.

This paper provides a description of the surface topography of DsbA, the bacterial disulfide-bond forming enzyme, in the different phases of its catalytic cycle. Three representative states, that is, oxidized and reduced protein and a covalent complex mimicking the DsbA-substrate disulfide intermediate, have been investigated by a combination of limited proteolysis experiments and mass spectrometry methodologies. Protease-accessible sites are largely distributed in the oxidized form with a small predominance inside the thioredoxin domain. Proteolysis occurs even in secondary structure elements, revealing a significant mobility of the protein. Many cleavage sites disappear in the reduced form and most of the remaining ones appear with strongly reduced kinetics. The protein within the complex shows an intermediate behavior. This variation of flexibility in DsbA is probably the determining factor for the course of its catalytic cycle. In particular, the great mobility of the oxidized protein might facilitate the accommodation of its various substrates, whereas the increasing rigidity from the complexed to the reduced form could help the release of oxidized products. The formation of the complex between PID peptide and DsbA does not significantly protect the enzyme against proteolysis, reinforcing the results previously obtained by calorimetry concerning the weakness of their interaction. The few cleavage sites observed, however, are in favor of the presence of the peptide in the binding site postulated from crystallographic studies. As for the peptide itself, the proteolytic pattern and the protection effect exerted by DsbA could be explained by a preferential orientation within the binding site

Field demonstration of a tunable WDM-PON system with novel SFP+ modules and centralized wavelength control

We report on a demonstration of a novel tunable WDM-PON system over 25km of field deployed fiber. We show error-free operation at 1 GbE with sensitivity better than -30dBm and centralized control of the ONU wavelengths.This work has been supported by the EU ERA-NET+ projects PIANO+ IMPACT and PIANO+ TUCAN co-funded by the German BMBF, the UK Technology Strategy Board and the Austrian FFG. Also support from the UK EPSRC INTERNET project is acknowledged.This is the author accepted manuscript. The final version is available from OAS Publishing via http://dx.doi.org/10.1364/OFC.2015.M2A.

Abnormal T-cell phenotype in episodic angioedema with hypereosinophilia (Gleich's syndrome): frequency, clinical implication and prognosis

BACKGROUND: Episodic Angioedema with eosinophilia (EAE, Gleich\u27s syndrome) is a rare disorder consisting of recurrent episodes of angioedema, hypereosinophilia and frequent elevated serum Immunoglobin M. METHODS: We conducted a retrospective multicenter nationwide study regarding the clinical spectrum and therapeutic management of patients with EAE in France. RESULTS: Thirty patients were included with a median age at diagnosis of 41 years [5-84]. The median duration of each crisis was 5.5 days [1-90] with swelling affecting mainly the face and the upper limbs. Total serum IgM levels were increased in 20 patients (67%). Abnormal T-cell immunophenotypes were detected in 12 patients (40%) among which 5 (17%) showed evidence of clonal TCR γ gene rearrangement. Median follow-up duration was 53 months [31-99]. The presence of an abnormal T-cell population was the sole factor associated with a shorter time to flare (hazard ratio 4.15 [CI 95% 1.18-14.66; p=0.02). At last follow-up, 3 patients (10%) were able to withdraw all treatments and 11 (37%) were in clinical and biological remission with less than 10 mg of daily prednisone. CONCLUSION: EAE is a heterogeneous condition that encompasses several disease forms. Although patients usually respond well to glucocorticoids, those with evidence of abnormal T-cell phenotype have a shorter time to flare

Effects of Heavy Metals and Arbuscular Mycorrhiza on the Leaf Proteome of a Selected Poplar Clone: A Time Course Analysis

Arbuscular mycorrhizal (AM) fungi establish a mutualistic symbiosis with the roots of most plant species. While receiving photosynthates, they improve the mineral nutrition of the plant and can also increase its tolerance towards some pollutants, like heavy metals. Although the fungal symbionts exclusively colonize the plant roots, some plant responses can be systemic. Therefore, in this work a clone of Populus alba L., previously selected for its tolerance to copper and zinc, was used to investigate the effects of the symbiosis with the AM fungus Glomus intraradices on the leaf protein expression. Poplar leaf samples were collected from plants maintained in a glasshouse on polluted (copper and zinc contaminated) or unpolluted soil, after four, six and sixteen months of growth. For each harvest, about 450 proteins were reproducibly separated on 2DE maps. At the first harvest the most relevant effect on protein modulation was exerted by the AM fungi, at the second one by the metals, and at the last one by both treatments. This work demonstrates how importantly the time of sampling affects the proteome responses in perennial plants. In addition, it underlines the ability of a proteomic approach, targeted on protein identification, to depict changes in a specific pattern of protein expression, while being still far from elucidating the biological function of each protein

Discerning natural and anthropogenic organic matter inputs to salt marsh sediments of Ria Formosa lagoon (South Portugal)

Sedimentary organic matter (OM) origin and molecular composition provide useful information to understand carbon cycling in coastal wetlands. Core sediments from threors' Contributionse transects along Ria Formosa lagoon intertidal zone were analysed using analytical pyrolysis (Py-GC/MS) to determine composition, distribution and origin of sedimentary OM. The distribution of alkyl compounds (alkanes, alkanoic acids and alkan-2-ones), polycyclic aromatic hydrocarbons (PAHs), lignin-derived methoxyphenols, linear alkylbenzenes (LABs), steranes and hopanes indicated OM inputs to the intertidal environment from natural-autochthonous and allochthonous-as well as anthropogenic. Several n-alkane geochemical indices used to assess the distribution of main OM sources (terrestrial and marine) in the sediments indicate that algal and aquatic macrophyte derived OM inputs dominated over terrigenous plant sources. The lignin-derived methoxyphenol assemblage, dominated by vinylguaiacol and vinylsyringol derivatives in all sediments, points to large OM contribution from higher plants. The spatial distributions of PAHs (polyaromatic hydrocarbons) showed that most pollution sources were mixed sources including both pyrogenic and petrogenic. Low carbon preference indexes (CPI > 1) for n-alkanes, the presence of UCM (unresolved complex mixture) and the distribution of hopanes (C-29-C-36) and steranes (C-27-C-29) suggested localized petroleum-derived hydrocarbon inputs to the core sediments. Series of LABs were found in most sediment samples also pointing to domestic sewage anthropogenic contributions to the sediment OM.EU Erasmus Mundus Joint Doctorate fellowship (FUECA, University of Cadiz, Spain)EUEuropean Commission [FP7-ENV-2011, 282845, FP7-534 ENV-2012, 308392]MINECO project INTERCARBON [CGL2016-78937-R]info:eu-repo/semantics/publishedVersio

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Experimental characterization of liposomes stabilized by polyelectrolytes and mechanism of interaction involved

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