An 11.7‐Å‐resolution cryo‐EM map of the yeast 80S·eEF2 complex in the presence of the antibiotic sordarin was interpreted in molecular terms, revealing large conformational changes within eEF2 and ...the 80S ribosome, including a rearrangement of the functionally important ribosomal intersubunit bridges. Sordarin positions domain III of eEF2 so that it can interact with the sarcin–ricin loop of 25S rRNA and protein rpS23 (S12p). This particular conformation explains the inhibitory action of sordarin and suggests that eEF2 is stalled on the 80S ribosome in a conformation that has similarities with the GTPase activation state. A ratchet‐like subunit rearrangement (RSR) occurs in the 80S·eEF2·sordarin complex that, in contrast to Escherichia coli 70S ribosomes, is also present in vacant 80S ribosomes. A model is suggested, according to which the RSR is part of a mechanism for moving the tRNAs during the translocation reaction.
The objectives of this study were to gain further insight on
genotype distribution and percentage of clustered isolates between hospitals and to identify potential clusters involving different ...hospitals and cities. We aim to genotype
spp. isolates causing candidemia in patients admitted to 16 hospitals in Spain, Italy, Denmark, and Brazil. Eight hundred and eighty-four isolates (
= 534;
= 282; and
= 68) were genotyped using species-specific microsatellite markers. CDC3, EF3, HIS3, CAI, CAIII, and CAVI were used for
, Ctrm1, Ctrm10, Ctrm12, Ctrm21, Ctrm24, and Ctrm28 for
, and CP1, CP4a, CP6, and B for
. Genotypes were classified as singletons (genotype only found once) or clusters (same genotype infecting two or more patients). Clusters were defined as intra-hospital (involving patients admitted to a single hospital), intra-ward (involving patients admitted to the same hospital ward) or widespread (involving patients admitted to different hospitals). The percentage of clusters and the proportion of patients involved in clusters among species, genotypic diversity and distribution of genetic diversity were assessed. Seven hundred and twenty-three genotypes were detected, 78 (11%) being clusters, most of which (57.7%;
= 45/78) were intra-hospital clusters including intra-ward ones (42.2%;
= 19/45). The proportion of clusters was not statistically different between species, but the percentage of patients in clusters varied among hospitals. A number of genotypes (7.2%; 52/723) were widespread (found at different hospitals), comprising 66.7% (52/78) of clusters, and involved patients at hospitals in the same city (
= 21) or in different cities (
= 31). Only one
cluster was a widespread genotype found in all four countries. Around 11% of
and
isolates causing candidemia are clusters that may result from patient-to-patient transmission, widespread genotypes commonly found in unrelated patients, or insufficient microsatellite typing genetic discrimination.
AbstractMicrobially induced calcite precipitation (MICP) is a ground improvement technique that uses ureolytic bacteria to biocement soils by precipitating calcium carbonate on soil contacts and ...surfaces. In this study, five 3.7-m long horizontal columns, each containing 0.15 m3 of natural sand, were treated to address current knowledge gaps regarding the application of MICP at field-scale including investigating treatment extent, improvement of spatial uniformity, stimulation strategies, and posttreatment removal of ammonium by-products. Two stimulated columns containing poorly graded alluvial sand were treated to achieve high and low ureolytic rates to investigate differences in treatment uniformity and extent. An additional column with the same sand was augmented with Sporosarcina pasteurii targeting a high ureolytic rate similar to the high rate stimulated column. Two additional stimulated columns, containing poorly graded alluvial and marine sands, were treated to achieve a low ureolytic rate to evaluate the effect of soil mineralogy. Treatments were first applied to establish either indigenous or augmented microorganisms, after which all columns received nine cementation treatments. Following cementation, produced ammonium by-products were removed using a rinse solution injection and soil samples were obtained and analyzed for calcite content. During all treatments, solution urea and ammonium concentrations as well as soil hydraulic conductivities and shear wave velocities were monitored. In all columns, insignificant changes in permeability were observed during treatments despite Vs increases up to 1,325 m/s. Results suggest that improvements in the spatial uniformity and extent of biocementation can be achieved through the use of lower ureolytic rates that minimize reactions during injections.
A wide variety of carbon materials (ordered mesoporous carbons, carbon blacks, activated carbon, carbon nanotubes, coke and graphite) have been investigated as catalysts for hydrogen production by ...methane decomposition, with the aims of identifying the carbon properties which control in a greater extension the catalytic activity and determine the nature of the active sites involved in the reaction.
The catalytic activity of the different carbon materials was determined and compared using temperature-programmed experiments in a thermobalance. The initial activity was followed through the threshold temperature, defined as the temperature at which hydrogen production starts being detected, whereas the average reaction rate was also calculated and compared. The lowest threshold temperature was observed with ordered mesoporous carbons (CMK materials), followed by activated carbon and carbon blacks. On the other hand, at long reaction times activated carbon was quickly deactivated yielding a relatively low average reaction rate. The deactivation process seems to be greatly linked to the presence of micropores while the long-term activity is retained in those materials with ordered mesoporosity (CMKs) or formed by nanoparticles (carbon blacks), which make them more resistant to deactivation by the formation of carbonaceous deposits.
Whereas no clear dependence is observed between the threshold temperature and the surface area neither with the presence of polar groups in the carbon catalysts, characterization of these materials by XPS shows that a direct relationship exists with the amount of defects present on the graphene layers. This fact strongly supports that these defects are the main active sites for methane decomposition over carbon catalysts.
Artificial smokes focusing on macroscopic or fluid properties of smoke have been available for a long time. This paper presents a simple method to generate fully customizable smoke-like atmospheres ...at microscopic scale (i.e. considering their constituent particles as discrete elements) using a different approach. Synthetic, reproducible media can be generated combining monodisperse microspheres with known geometrical and optical properties conveniently parameterized. The method is presented as a proof-of-concept, highlighting the design decisions along with their implications. Practical issues such as aerosol nebulization, particle carrier selection or the features of the medium chamber where the smoke-like atmosphere is to be tested are analyzed. A comparison between methanol and ethanol as carriers for polystyrene microsphere nebulization is also made. The method could be the seed for the obtention of standard reference media for calibration or standardized characterization of not only smoke detectors and exhaust smoke sensors but also other instruments relying on optical properties of dispersive media (dust in PV panels, public lighting, etc.).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mutations in mitochondrial DNA as well as nuclear-encoded mitochondrial proteins have been reported to cause tubulointerstitial kidney diseases and focal segmental glomerulosclerosis (FSGS). ...Recently, genes and pathways affecting mitochondrial turnover and permeability have been implicated in adult-onset FSGS. Furthermore, dysfunctioning mitochondria may be capable of engaging intracellular innate immune-sensing pathways. To determine the impact of mitochondrial dysfunction in FSGS and secondary innate immune responses, we generated Cre/loxP transgenic mice to generate a loss-of-function deletion mutation of the complex IV assembly cofactor heme A:farnesyltransferase (COX10) restricted to cells of the developing nephrons. These mice develop severe, early-onset FSGS with innate immune activation and die prematurely with kidney failure. Mutant kidneys showed loss of glomerular and tubular epithelial function, epithelial apoptosis, and, in addition, a marked interferon response. In vitro modeling of Cox10 deletion in primary kidney epithelium compromises oxygen consumption, ATP generation, and induces oxidative stress. In addition, loss of Cox10 triggers a selective interferon response, which may be caused by the leak of mitochondrial DNA into the cytosol activating the intracellular DNA sensor, stimulator of interferon genes. This new animal model provides a mechanism to study mitochondrial dysfunction in vivo and demonstrates a direct link between mitochondrial dysfunction and intracellular innate immune response.
Rhamnolipids (RMLs) have more effectiveness for specific uses according to their homologue proportions. Thus, the novelty of this work was to compare mono‐RMLs and di‐RMLs physicochemical properties ...on microbial enhanced oil recovery (MEOR) applications. For this, RML produced by three strains of Pseudomonas aeruginosa containing different homologues proportion were used: a mainly mono‐RMLs producer (mono‐RMLs); a mainly di‐RMLs producer (di‐RMLs), and the other one that produces relatively balanced amounts of mono‐RML and di‐RML homologues (mono/di‐RML). For mono‐RML, the most abundant molecules were Rha‐C10C10 (m/z 503.3), for di‐RML were RhaRha‐C10C10 (m/z 649.4) and for Mono/di‐RML were Rha‐C10C10 (m/z 503.3) and RhaRha‐C10C10 (m/z 649.4). All RMLs types presented robustness under high temperature and variation of salinity and pH, and high ability for oil displacement, foam stability, wettability reversal and were classified as safe for environment according to the European Union Directive No. 67/548/EEC. For all these properties, it was observed a highlight for mono‐RML. Mono‐RML presented the lowest surface tension (26.40 mN/m), interfacial tension (1.14 mN/m), and critical micellar concentration (CMC 27.04 mg/L), the highest emulsification index (EI24 100%) and the best wettability reversal (100% with 25 ppm). In addition, mono‐RML showed the best acute toxicity value (454 mg/L), making its application potential even more attractive. Based on the results, it was concluded that all RMLs homologues studied have potential for MEOR applications. However, results showed that mono‐RML stood out and have the best mechanism of oil incorporation in micelles due their most effective surface‐active physicochemical features.
Summary
In order to reset the immune system to baseline function, autologous hematopoietic stem cell transplantation (HSCT) has been performed in patients with multiple sclerosis (MS). After June ...2015, 617 new consecutive patients with MS were autografted in our center with non‐frozen peripheral blood stem cells. The autografts were performed on an out‐patient basis, after conditioning with cyclophosphamide and rituximab. The aim of the study was the assessment of both safety and efficacy of the method. The study’s primary co‐end‐points were recovery of granulocyte and platelet counts and transplant‐related mortality. Secondary end‐points were overall survival and clinical response (improvement or stabilization of the self‐reported expanded disability status scale score). The protocol was registered in ClinicalTrials.gov identifier NCT02674217.0. We included 401 females and 216 males, with a median age of 46 years. A total of 259 patients had relapsing–remitting MS (RRMS), 228 had secondary progressive (SPMS) and 130 had primary progressive (PPMS) multiple sclerosis. All procedures were initially performed on an out‐patient basis and only 32 individuals (5%) required hospitalization. One to three aphereses (median 1) were required to harvest at least 1 × 106/kg viable CD34+ cells. The total number of viable CD34+ infused cells ranged between 1 and 37·83 × 106/kg (median 5·68). Patients recovered more than 0·5 × 109/l absolute granulocytes by day 8 (median, range = 2–14), and platelet values were above 20 × 109/l by day 4 (median, range = 0–11). Eleven individuals required red blood cells and six needed platelet transfusions. To date, there have been no deaths attributable to the transplant, yielding a 30‐month overall survival of 100%. Patients have been followed for 3–42 months (median = 12). The overall response rate (decrease or stabilization of the self‐reported EDSS score) at 12 months was 78% for all patients (83% in RRMS, 78% in PPMS and 73% in SPMS), while the disability progression‐free survival was 82% for all patients (86% in RRMS, 78·5% in SPMS and 78% in SPMS). Changes in the self‐reported EDSS score in parallel with neurological improvement were observed in people with all types of MS after HSCT, employing the ‘Mexican method’.
Changes in the self‐reported EDSS score accordant with neurological improvement, were observed in peoples with all types of MS after HSCT, employing the ‘Mexican method’.
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