Trypanosoma rangeli is phylogenetically closer to Old World trypanosomes than to Trypanosoma cruzi.

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Trypanosoma rangeli and Trypanosoma cruzi are generalist trypanosomes sharing a wide range of mammalian hosts; they are transmitted by triatomine bugs, and are the only trypanosomes infecting humans in the Neotropics. Their origins, phylogenetic relationships, and emergence as human parasites have long been subjects of interest. In the present study, taxon-rich analyses (20 trypanosome species from bats and terrestrial mammals) using ssrRNA, glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH), heat shock protein-70 (HSP70) and Spliced Leader RNA sequences, and multilocus phylogenetic analyses using 11 single copy genes from 15 selected trypanosomes, provide increased resolution of relationships between species and clades, strongly supporting two main sister lineages: lineage Schizotrypanum, comprising T. cruzi and bat-restricted trypanosomes, and Tra[Tve-Tco] formed by T. rangeli, Trypanosoma vespertilionis and Trypanosoma conorhini clades. Tve comprises European T. vespertilionis and African T. vespertilionis-like of bats and bat cimicids characterised in the present study and Trypanosoma sp. Hoch reported in monkeys and herein detected in bats. Tco included the triatomine-transmitted tropicopolitan T. conorhini from rats and the African NanDoum1 trypanosome of civet (carnivore). Consistent with their very close relationships, Tra[Tve-Tco] species shared highly similar Spliced Leader RNA structures that were highly divergent from those of Schizotrypanum. In a plausible evolutionary scenario, a bat trypanosome transmitted by cimicids gave origin to the deeply rooted Tra[Tve-Tco] and Schizotrypanum lineages, and bat trypanosomes of diverse genetic backgrounds jumped to new hosts. A long and independent evolutionary history of T. rangeli more related to Old World trypanosomes from bats, rats, monkeys and civets than to Schizotrypanum spp., and the adaptation of these distantly related trypanosomes to different niches of shared mammals and vectors, is consistent with the marked differences in transmission routes, life-cycles and host-parasite interactions, resulting in T. cruzi (but not T. rangeli) being pathogenic to humans.This study was supported by grants awarded to MMGT and EPC from CNPq (National Council for Scientific and Technological Development) PROAFRICA, PROSUL and UNIVERSAL programs, CAPES (Coordination for the Improvement of Higher Education Personnel) PNIPB, PNPD and PROTAX programs, and FAPESP (São Paulo Research Foundation; process 2016/07487-0). Genome sequencing was supported by the Assembling the Tree of Life (ATOL) Project of the National Science Foundation, USA (NSF DEB-0830056), and TCC-USP (Trypanosomatid Culture Collection of the University of São Paulo) projects. OEA received PhD fellowships from CNPq (PROTAX) and COLCIENCIAS (Administrative Department of Science, Technology and Innovation, Colombia); PAO is a postdoctoral fellow of CAPES (PNPD); LL and AGCM are supported by a postdoctoral fellowship from CAPES (PROTAX)

Sliding Wear Behavior of Al2O3-TiO2 Coatings Fabricated by the Suspension Plasma Spraying Technique

[EN] The friction and dry sliding wear behavior of alumina and alumina-titania near-nanometric coatings were examined. Coatings were obtained by the suspension plasma spraying technique. Dry sliding wear tests were performed on a ball-on-disk tribometer, with an Al2O3 ball as counterpart material, a normal load of 2 N, a sliding distance of 1200 m and a sliding speed of 0.1 m/s. The effect of including TiO2 in the fabricated coatings on friction coefficient behavior, wear rates and wear damage patterns was determined. The addition of TiO2 to the coatings was found to greatly increase wear resistance by, for example, 2.6-fold for 40 wt% of TiO2. The analysis of the wear surface was correlated with microstructural parameters, mechanical properties and wear rates.The authors wish to thank for the Spanish Ministry of Economy and Competitiveness (MAT2012-38364-C03) and the Autonomous Government of Valencia for funding for the stay in SPCTS-UMR CNRS (France), and the French FCENANOSURF consortium funded by the French Ministry and Industry and local governments of Region Centre and Region Limousin.Klyatskina, E.; Espinosa Fernández, L.; Darut, G.; Segovia López, EF.; Salvador Moya, MD.; Montavon, G.; Agorges, H. (2015). Sliding Wear Behavior of Al2O3-TiO2 Coatings Fabricated by the Suspension Plasma Spraying Technique. Tribology Letters. 59(1):1-9. https://doi.org/10.1007/s11249-015-0530-5S19591Pawlowski, L.: The Science and Engineering of Thermal Spray Coatings. Wiley: Hoboken (2008)Lampe, Th, Eisenberg, S., Cabeo, E.R.: Plasma surface engineering in the automotive industry—trends and future prospective. Surf. Coat. Technol. 174–175, 1–7 (2003)Wang, Y., Jiang, S., Wang, M., Wang, S., Xiao, T.D., Strutt, P.R.: Abrasive wear characteristics of plasma sprayed nanostructured alumina/titania coatings. Wear 237, 176–185 (2000)Kabacoff, L.T.: Nanoceramic coatings exhibit much higher toughness and wear resistance than conventional coatings. AMPITAC Newslett. 6(1), 37–42 (2002)Wang, M., Shaw, L.L.: Effects of the powder manufacturing method on microstructure and wear performance of plasma sprayed alumina–titania coatings. Surf. Coat. Technol. 202, 34–44 (2007)Shaw, L.L., Goberman, D., Ren, R., Gell, M., Jing, S., Wang, Y., Xiao, T.D., Strutt, P.R.: The dependency of microstructure and properties of nanostructured coatings on plasma spray conditions. Surf. Coat. Technol. 130, 1–8 (2000)Dahotre, N.B., Nayak, S.: Nanocoatings for engine application. Surf. Coat. Technol. 194(1), 58–67 (2005)Sathish, S., Geetha, M., Aruna, S.T., Balaji, N., Rajam, K.S., Asokamani, R.: Sliding wear behavior of plasma sprayed nanoceramic coatings for biomedical applications. Wear 271, 934–941 (2011)Pawlowski, L.: Finely grained nanometric and submicrometric coatings by thermal sparing: a review. Surf. Coat. Technol. 202, 4318–4328 (2008)Xiao, D., Wang, Y., Strutt, P.: Fabrication and evaluation of plasma sprayed nanostructured alumina–titania coatings with superior properties. Mater. Sci. Eng. 301, 80–89 (2001)Tjong, S.C., Chen, H.: Nanocrystalline materials and coatings. Mater. Sci. Eng. 45, 1–88 (2004)Fauchais, P., Montavon, G., Bertrand, G.: From powders to thermally sprayed coatings. J. Therm. Spray Technol. 19, 56–80 (2010)Lima, R.S., Marple, B.R.: Thermal spray coatings engineered from nanostructured ceramic agglomerated powders for structural, thermal barrier and biomedical applications: a review. J. Therm. Spray Technol. 16, 40–63 (2007)Fauchais, P., Etchart-Salas, R., Delbos, C., Tognonvi, M., Rat, V., Coudert, J.F., Chartier, T.: Suspension and solution plasma spraying of finely structured layers: potential application to SOFCs. J. Phys. D Appl. Phys. 40, 2394–2406 (2007)Ramachandran, K., Selvajaran, V., Ananthapadmanabhan, P.V., Sreekumar, K.P.: Microstructure, adhesion, micro hardness, abrasive wear resistance and electrical resistivity of the plasma sprayed alumina and alumina–titania coatings. Thin Solid Films 315, 144–152 (1998)Lee, S.W., Morillo, C., Lira-Olivares, J., Kim, S.H., Sekino, T., Niihara, K., Hockey, B.J.: Tribological and microstructural analysis of Al2O3/13TiO2 nanocomposites to use in femoral head of hip replacement. Wear 225, 1040–1044 (2003)Dejang, N., Watcharapasorn, A., Wirojupatump, S., Niranatlumpong, P., Jiansirisomboon, S.: Fabrication and properties of plasma-sprayed Al2O3/TiO2 composite coatings: a role of nano-sized TiO2 addition. Surf. Coat. Technol. 204, 1651–1657 (2010)Yimaz, S.: An evaluation of plasma sprayed coatings based on Al2O3 and Al2O3–13wt% TiO2 with bond coat on pure titanium substrate. Ceram. Int. 35, 2017–2022 (2009)Fervel, V., Normand, B., Coddet, C.: Tribological behavior of plasma sprayed Al2O3-based cermet coatings. Wear 230(1), 70–77 (1999)Vargas, F., Ageorges, H., Fauchais, P., López, M.E.: Mechanical and a tribological performance of Al2O3 coatings elaborated by flame and plasma spraying. Surf. Coat. Technol. 205, 1132–1136 (2010)Bacciochini, A., Ilavsky, J., Montavon, G., Denoirjean, A., Ben-ettouil, F., Valette, S., Fauchais, P., Wittmann-teneze, K.: Quantification of void network architectures of suspension plasma-sprayed (SPS) yttria-stabilized zirconia (YSZ) coatings using ultra-small-angle X-ray scattering (USAXS). Mater. Sci. Eng. 528, 91–102 (2010)ASTM International: ASTM G99-03: Standard test method for wear testing with a pin-on-disc apparatus. ASTM annual book of standards. ASTM International: West Conshohocken (2003)Lancaster, K.: The influence of substrate hardness on the formation and endurance of molybdenum disulphide films. Wear 10, 103–107 (1967)Fauchais, P., Rat, V., Delbos, C., Fazilleau, J., Coudert, J.F., Chartier, T., Bianchi, L.: Understanding of suspension plasma spraying of finely structured coatings for SOFC. IEEE Plasma Sci. 33(2), 920–930 (2005)Bannier, E., Vicent, M., Rayón, E., Benavente, R., Salvador, M.D., Sánchez, E.: Effect of TiO2 addition on the microstructure and nanomechanical properties of Al2O3 suspension plasma sprayed coatings. Appl. Surf. Sci. 316, 141–146 (2014)Darut, G., Klyatskina, E., Valette, S., Carles, P., Denoirjean, A., Montavon, G., Ageorges, H., Segovia, F., Salvador, M.D.: Architecture and phases composition of suspension plasma sprayed alumina–titania sub-micrometer-sized coatings. Mater. Lett. 67, 241–244 (2012)Fauchais, P., Montavon, G.: Latest developments in suspension and liquid precursor thermal spraying. J. Therm. Spray Technol. 19(1–2), 226–239 (2010)Darut, G., Ben-Ettouli, F., Denoirjean, A., Montavon, G., Ageourges, H., Fauchais, P.: Dry sliding behavior of sub-micrometer-sized suspension plasma sprayed ceramic oxide coatings. J. Therm. Spray Technol. 19, 275–285 (2010)Tingaud, O., Bacciochini, A., Montavon, G., Denoirjean, A., Fauchais, P.: Suspension DC plasma spraying of thick finely-structured ceramic coatings: process manufacturing mechanisms. Surf. Coat. Technol. 203, 2157–2161 (2009)Guesama, S., Bounazef, M., Nardin, P., Sahraoui, T.: Wear behavior of alumina–titania coatings: analysis of process and parameters. Ceram. Int. 32, 13–19 (2006)Espinosa-Fernández, L., Borrell, A., Salvador, M.D., Gutierrez-Gonzalez, C.F.: Sliding wear behavior of WC–Co–Cr3C2–VC composites fabricated by conventional and non-conventional techniques. Wear 307, 60–67 (2013)Zhang, J., Moslehy, F.A., Rice, S.L.: A model for friction in quasi-steady-state. Part I. Derivation. Wear 149, 1–12 (1991)Zhang, J., Moslehy, F.A., Rice, S.L.: A model for friction in quasi-steady-state sliding Part II. Numerical results and discussion. Wear 149, 13–25 (1991)Bolelli, G., Cannilo, V., Lusvarghi, L., Manfredini, T.: Wear behaviour of thermally sprayed ceramic oxide coatings. Wear 261, 1298–1315 (2006)Normand, B., Fervel, V., Coddet, C., Nikitine, V.: Tribological properties of plasma sprayed alumina–titania coatings: next term role and control of the microstructure. Surf. Coat. Technol. 123, 278–287 (2000)Hutchings, I.: Tribology: friction and wear of engineering materials. Mater. Des. 13, 187 (1992)Ahn, J., Hwang, B., Song, E.P., Lee, S., Kim, N.J.: Correlation of microstructure and wear resistance of Al2O3–TiO2 coatings plasma sprayed with nanopowders. Metall. Mater. Trans. A 37, 1851–1860 (2006)Erickson, L.C., Hawthorne, H.M., Troczynski, T.: Correlations between microstructural parameters, micromechanical properties and wear resistance of plasma sprayed ceramic coatings. Wear 250, 569–575 (2001)Song, E.P., Ahn, J., Lee, S., Kim, N.J.: Microstructure and wear resistance of nanostructured Al2O3–8 wt%TiO2 coatings plasma-sprayed with nanopowders. Surf. Coat. Technol. 201, 1309–1315 (2006)Tucker Jr., R.C.: ASM Handbook Volume 5A: Thermal Spray Technology. ASM International, Materials Park (2013)Stachowiack, G.W., Batchelor, A.: Engineering Tribology Handbook. Elsevier-Butterworth-Heineman: Oxford (2005)Fischer, T.E., Zhu, Z., Kim, H., Shin, D.S.: Genesis and role of wear debris in sliding wear of ceramics. Wear 245, 53–60 (2000)Lima, R.S., Moureau, C., Marple, B.R.: HVOF-sprayed coatings engineered from mixtures of nanostructured and submicron Al2O3–TiO2 powders: an enhanced wear performance. J. Therm. Spray Technol. 16, 866 (2007

Neutrophil responses to Aspergillosis : new roles for old players

Neutrophils are professional phagocytic cells that play a crucial role in innate immunity. Through an assortment of antifungal effector mechanisms, neutrophils are essential in controlling the early stages of fungal infection. These mechanisms range from the production of reactive oxygen intermediates and release of antimicrobial enzymes to the formation of complex extracellular traps that aid in the elimination of the fungus. Their importance in antifungal immunity is supported by the extreme susceptibility to infection of patients with primary (e.g., chronic granulomatous disease) or acquired (e.g., undergoing immunosuppressive therapy) neutrophil deficiency. More recently, common genetic variants affecting neutrophil antifungal capacity have also been disclosed as major risk factors for aspergillosis in conditions of generalized immune deficiency. The present review revisits the role of neutrophils in the host response against Aspergillus and highlights the consequences of their deficiency in susceptibility to aspergillosis.This work was supported by a Research Grant from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Cristina Cunha was supported by the Fundacao para a Ciencia e Tecnologia, Portugal (contract SFRH/BPD/96176/2013)

Mapping the Conformational Dynamics and Pathways of Spontaneous Steric Zipper Peptide Oligomerization

The process of protein misfolding and self-assembly into various, polymorphic aggregates is associated with a number of important neurodegenerative diseases. Only recently, crystal structures of several short peptides have provided detailed structural insights into -sheet rich aggregates, known as amyloid fibrils. Knowledge about early events of the formation and interconversion of small oligomeric states, an inevitable step in the cascade of peptide self-assembly, however, remains still limited

Characterisation of DOG-1 expression in salivary gland tumours and comparison with myoepithelial markers

DOG1 is an established diagnostic marker for gastrointestinal stromal tumours (GIST), but has been reported in salivary gland tumours (SGT) as an acinar and intercalated duct marker. However, its specificity and distribution is not well established. The aim of this study was to evaluate the diagnostic utility of DOG-1 expression in SGT in addition to comparing it with myoepithelial markers. Normal salivary tissue and SGT (n = 184) were examined for expression of DOG1 and a range of myoepithelial markers. SGT included: acinic cell carcinoma (ACC, n = 15), secretory carcinoma (SC, n = 9), pleomorphic adenoma (PA, n = 49), carcinoma ex-PA (Ca ex-PA, n = 11), adenoid cystic carcinoma (AdCC, n = 20), polymorphous adenocarcinoma (PAC, n = 6), myoepithelioma (n = 6), myoepithelial carcinoma (MC, n = 2), basal cell adenoma (BCA, n = 14), canalicular adenoma (CA, n = 19), mucoepidermoid carcinoma (MEC, n = 11), oncocytoma (n = 2), adenocarcinoma NOS (AdNOS, n = 4), basal cell adenocarcinoma (BCAC, n = 2), salivary duct carcinoma (SDC, n = 3) and papillary cystadenocarcinoma (PCAC, n = 1). Normal acini and ACC (14/15) showed strong luminal DOG1 staining; SC were largely negative with only focal expression in 3/9 cases. Luminal staining was seen in PA (14/49), PAC (4/6), Ca ex-PA (4/11) and AdCC (6/20). 8/11 MEC showed luminal and/or mucous cell staining. No staining was seen in myoepithelioma, MC, CA, adNOS and BCAC. BCA showed strong staining of myoepithelial cells in some cases (5/14). Variable myoepithelial DOG1 staining was seen in PA, Ca ex PA, BCA, SDC and PCAC which was not as consistent as myoepithelial markers such as calponin, p63 and αSMA. Absence of DOG1 can differentiate ACC from SC, but staining is variable in PA, PLGA and Ca ex-PA. Myoepithelial staining in some tumours but not in normal gland suggests a wider distribution in SGT than originally envisaged

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

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion