Pyridinic-N Coordination Effect on the Adsorption and Activation of CO2 by Single Vacancy Iron-Doped Graphene.

Graphene doped with different transition metals has been recently proposed to adsorb CO2 and help reduce the greenhouse effect. Iron-doped graphene is one of the most promising candidates for this task, but there is still a lack of full understanding of the adsorption mechanism. In this work, we analyze the electronic structure, geometry, and charge redistribution during adsorption of CO2 molecules by single vacancy iron-doped graphene by DFT calculations using the general gradient approximation of Perdew, Burke, and Ernzernhof functional (PBE) and the van der Waals density functional (vdW). To understand the impact of the pyridinic-N coordination of the iron atom, we gradually replaced the neighboring carbon atoms by nitrogen atoms. The analysis indicates that chemisorption and physisorption occur when the molecule is adsorbed in the side-on and end-on orientation, respectively. Adsorption is stronger when pyridinic-N coordination increases, and the vdW functional describes the chemical interactions and adsorption energy differently in relation to PBE without significant structural changes. The development of the chemical interactions with the change of coordination in the system is further investigated in this work with crystal overlap Hamilton population (COHP) analysis.

Reconstitution of human PDAC using primary cells reveals oncogenic transcriptomic features at tumor onset.

Animal studies have demonstrated the ability of pancreatic acinar cells to transform into pancreatic ductal adenocarcinoma (PDAC). However, the tumorigenic potential of human pancreatic acinar cells remains under debate. To address this gap in knowledge, we expand sorted human acinar cells as 3D organoids and genetically modify them through introduction of common PDAC mutations. The acinar organoids undergo dramatic transcriptional alterations but maintain a recognizable DNA methylation signature. The transcriptomes of acinar organoids are similar to those of disease-specific cell populations. Oncogenic KRAS alone do not transform acinar organoids. However, acinar organoids can form PDAC in vivo after acquiring the four most common driver mutations of this disease. Similarly, sorted ductal cells carrying these genetic mutations can also form PDAC, thus experimentally proving that PDACs can originate from both human acinar and ductal cells. RNA-seq analysis reveal the transcriptional shift from normal acinar cells towards PDACs with enhanced proliferation, metabolic rewiring, down-regulation of MHC molecules, and alterations in the coagulation and complement cascade. By comparing PDAC-like cells with normal pancreas and PDAC samples, we identify a group of genes with elevated expression during early transformation which represent potential early diagnostic biomarkers.

Enfermedad de Takayasu: serie de casos / Takayasu's disease: case series

Introducción: La arteritis de Takayasu se trata de una vasculitis de grandes vasos, crónica y granulomatosa caracterizada por la presencia de estenosis y aneurismas en la aorta y sus ramas principales. Se produce inflamación. vascular que causa dolor. Las pruebas de imagen como el PET-TC han ganado importancia en el diagnóstico. El tratamiento se realiza con inmunosupresores, pudiendo usar fármacos biológicos en casos refractarios. Material y métodos: Estudio descriptivo retrospectivo de 3 casos de enfermedad de Takayasu. Resultados: Presentamos 3 casos atípicos de vasculitis de Takayasu que fueron diagnosticados mediante PET-TC y que evolucionaron de forma diferente, requiriendo 2 de ellos tratamiento con fármacos biológicos. Conclusión: Pruebas de imagen como el PET-TC permiten un diagnóstico temprano y un seguimiento de la enfermedad. Con el uso de fármacos biológicos podemos controlar los casos refractarios. (AU)

Introduction: Takayasu's arteritis is a chronic granulomatous vasculitis of large vessels characterized by the presence of stenosis and aneurysms in the aorta and its mainbranches. Vascular inflammation occurs that causes pain. Imaging tests such as PET-CT have gained importance in diagnosis. The treatment is carried out with immunosuppressants, being able to use biological drugs in refractory cases. Material and methods: Retrospective descriptive study of 3 cases of Takayasu's disease. Results: We present 3 atypical cases of Takayasu vasculitis that were diagnosed by PET-CT and that evolved differently, requiring 2 of them treatment with biological drugs. Conclusion: Imaging tests such as PET-CT allow early diagnosis and monitoring of the disease. With the use of biological drugs we can control refractory cases. (AU)

Biogenic Photo-Catalyst TiO2 Nanoparticles for Remediation of Environment Pollutants.

This article reports a benign environmentally friendly fabrication method of titanium dioxide (TDO) nanoparticles (named TDO NPs3, TDO NPs5, and TDO NPs8) using aqueous extract of durva herb waste. This synthesis process avoids use of harmful substances and persistent chemicals throughout the order and enables us to control the size of the nanomaterials. Characterization of TDO nanoparticles was analyzed by ultraviolet-visible spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The morphological nature of the TDO samples was inspected by transmission electron microscopy, which indicated that the TDO NPs3, TDO NPs5, and TDO NPs8 were spherical in shape, with average sizes of 5.14, 12.54, and 29.61 nm, respectively. The stability of TDO nanoparticles was assessed using thermogravimetric analysis and dynamic light scattering analysis. These samples could be used for degradation of polluting industrial textile dyes, such as methylene blue (MB) and rhodamine B (Rh-B). Remarkably, the TDO NPs3 sample (5.14 nm size) exhibits a noticeable degradation of the MB dye in a shorter time period (50 min) than the TDO NPs8 sample with a size of 29.61 nm (120 min). The TDO NPs3 sample was also tested for degradation of Rh-B dye, showing high degradation efficiency over a short period of time (60 min). In contrast, the TDO NPs8 sample showed degradation of the Rh-B dye in 120 min. The effect of the dye concentration and the catalyst dose to remove dye pollutants has also been investigated. The synthesized TDO NPs act as exceptional catalysts for the degradation of dyes, and they are promising materials for the degradation of industrial polluting dyes.

Green Biosynthesis of Tin Oxide Nanomaterials Mediated by Agro-Waste Cotton Boll Peel Extracts for the Remediation of Environmental Pollutant Dyes.

The sustainable synthesis of metal oxide materials provides an ecofriendly and more exciting approach in the domain of a clean environment. Besides, plant extracts to synthesize nanoparticles have been considered one of the more superior ecofriendly methods. This paper describes the biosynthetic preparation route of three different sizes of tetragonal structure SnO2 nanoparticles (SNPs) from the agro-waste cotton boll peel aqueous extract at 200, 500, and 800 °C for 3 h and represents a low-cost and alternative preparation method. The samples were characterized by X-ray diffraction, Fourier transform infrared spectrophotometry, ultraviolet-visible absorption spectroscopy, high-resolution transmission electron microscopy (HR-TEM), and energy-dispersive X-ray spectroscopy. Surface area and porosity size distribution were identified by nitrogen adsorption-desorption isotherms and Brunauer-Emmett-Teller analysis. The photocatalytic properties of the SNP samples were studied against methylene blue (MB) and methyl orange (MO), and the degradation was evaluated with three different size nanomaterials of 3.97, 8.48, and 13.43 nm. Photocatalytic activities were carried out under a multilamp (125 W Hg lamps) photoreactor. The smallest size sample exhibited the highest MB degradation efficiency within 30 min than the most significant size sample, which lasted 80 min. Similarly, in the case of MO, the smallest sample showed a more superior degradation efficiency with a shorter period (40 min) than the large-size samples (100 min). Therefore, our studies suggested that the developed SNP nanomaterials could be potential, promising photocatalysts against the degradation of industrial effluents.

Latent and active tuberculosis infections in migrants and travellers: A retrospective analysis from the Spanish +REDIVI collaborative network.

BACKGROUND: Tuberculosis (TB) is the leading cause of infectious disease mortality worldwide. We analysed active and latent TB infections (LTBI) from the Spanish Network for the Study of Imported Infectious Diseases by Travellers and Immigrants (+REDIVI). METHODS: Observational, retrospective, multicentre study of TB and LTBI registered in the +REDIVI network from October 2009 to December 2016. RESULTS: Of 1008 cases of LTBI, 884 (87.7%) were immigrants; 93 (4.5%), immigrants visiting friends and relatives (VFR); 2 (0.9%), VFR-travellers; and 29 (1.1%), travellers. Absolute (N = 157 vs. N = 75) and relative (12.5% vs. 5.9%) frequency decreased over the study period (p = 0.003). Median time to diagnosis was 24.6 months (females 50.3 vs males 11.9; p < 0.001). Of 448 TB cases, 405 (90.4%) were in immigrants; 30 (6.7%), VFR-immigrants; 6 (1.3%), VFR-travellers; and 7 (1.6%), travellers. Median time to diagnosis was 62.5 months (females 86.6 vs males 70.1; p = 0.0075). There were 8 multidrug resistant TB cases and 1 extensively drug resistant case of TB, all in immigrants. CONCLUSION: TB was frequently diagnosed more than 5 years after arrival in Spain. Screening programmes for TB and LTBI in immigrants should be considered beyond this time point. Women showed a higher diagnostic delay for both latent and active TB.

Cloning and expression analysis of an endo-1,3-ß-D-glucosidase from Phytophthora cinnamomi.

Phytophthora is considered one of the most destructive genus for many agricultural plant species worldwide, with a strong environmental and economic impact. Phytophthora cinnamomi is a highly aggressive Phytophthora species associated with the forest decline and responsible for the ink disease in chestnut trees (Castanea sativa Miller), a culture which is extremely important in Europe. This pathogenicity occurs due to the action of several enzymes like the hydrolysis of 1,3-ß-glucans at specific sites by the enzyme endo-1,3-ß-D-glucosidase. The aim of this work to analyze the heterologous expression in two microorganisms, Escherichia coli and Pichia pastoris, of an endo-1,3-ß-D-glucosidase encoded by the gene ENDO1 (AM259651) from P. cinnamomi. Different plasmids were used to clone the gene on each organism and the real-time quantitative polymerase chain reaction was used to determine its level of expression. Homologous expression was also analyzed during growth in different carbon sources (glucose, cellulose, and sawdust) and time-course experiments were used for endo-1,3-ß-D-glucosidase production. The highest expression of the endo-1,3-ß-D-glucosidase gene occurred in glucose after 8 h of induction. In vivo infection of C. sativa by P. cinnamomi revealed an increase in endo-1,3-ß-D-glucosidase expression after 12 h. At 24 h its expression decreased and at 48 h there was again a slight increase in expression, and more experiments in order to further explain this fact are underway.

Levan-Capped Silver Nanoparticles for Bactericidal Formulations: Release and Activity Modelling.

An environmentally friendly technique was used to produce levan-capped silver nanoparticles of about 30 nm (with a loading of 30%) that showed bactericide effect, for E. coli and B. subtilis. That effect was mathematically studied with a dose-response model (lethal dose of 12.4 ppm and 6.8 ppm respectively). These silver nanoparticles were subsequently introduced in a gel to create a silver release system with bacteria inhibition activity. Silver release from the gel and its bactericidal activity was theoretically studied to develop a unique model that is able to predict accurately both silver release and lethal dose for any type of bacteria. This model will be useful for performing predictions for future silver in gel applications.

Paraqueratosis pustulosa / Parakeratosis pustulosa

La paraqueratosis pustulosa es una entidad poco frecuente, cuenta tan solo con una decena de publicaciones. Las lesiones se limitan a uno o dos dedos de las manos, y es más frecuente en niñas durante la primera infancia. Dado que, en ocasiones, su aparición puede simular el debut de otras enfermedades dermatológicas como psoriasis, es importante completar una adecuada anamnesis dirigida a descartar estos antecedentes familiares, así como otros diagnósticos diferenciales como acrodermatitis continua de Hallopeau, micosis y dermatitis atópica o de contacto. La evolución suele ser favorable, precisando tratamientos tópicos con emolientes y, en casos refractarios, con corticoides tópicos. Se presenta un caso de esta entidad

Pustular parakeratosis is a rare entity with few cases published nowadays. The lesions are limited to one or two fingers of the hands, being more frequent in girls during early childhood. Given that its appearance can sometimes simulate the first stages of others dermatological diseases such as psoriasis, it is important to complete an adequate anamnesis with the family history, as well as ruling out other differential diagnoses such as Hallopeau's continuous acrodermatitis, mycosis, atopic dermatitis or contact dermatitis. The evolution is usually favourable, requiring topical treatments with emollients and, in refractory cases, topical corticosteroids. We present a case of this entity

Identification and characterization of a cell wall porin from Gordonia jacobaea.

Gordonia jacobaea is a bacterium belonging to the mycolata group characterized by its ability to produce carotenoids. Mycolic acids in the cell wall contribute to reducing the permeability of their envelopes requiring the presence of channel-forming proteins to allow the exchange of hydrophilic molecules with the surrounding medium. Identification and purification of the channel-forming proteins was accomplished by SDS-PAGE, Mass spectrometry and Mass peptide fingerprinting and the channel-forming activity was studied by reconstitution in lipid bilayers. Here, we describe for the first time the presence of a cell-wall protein from G. jacobaea with channel-forming activity. Our results suggest that this protein bears a low similarity to other hypothetical proteins from the genus Gordonia of uncharacterized functions. The channel has an average single-channel conductance of 800 pS in 1 M KCl, is moderately anion-selective, and does not show any voltage dependence for voltages between +100 and -100 mV. The channel characteristics suggest that this protein could be of relevance in the import and export of negatively charged molecules across the cell wall. This could contribute to design treatments for mycobacterial infections, as well as being of interest in biotechnology applications.

Transcriptomics as a tool to discover new antibacterial targets.

The emergence of antibiotic-resistant pathogens, multiple drug-resistance, and extremely drug-resistant strains demonstrates the need for improved strategies to discover new drug-based compounds. The development of transcriptomics, proteomics, and metabolomics has provided new tools for global studies of living organisms. However, the compendium of expression profiles produced by these methods has introduced new scientific challenges into antimicrobial research. In this review, we discuss the practical value of transcriptomic techniques as well as their difficulties and pitfalls. We advocate the construction of new databases of transcriptomic data, using standardized formats in addition to standardized models of bacterial and yeast similar to those used in systems biology. The inclusion of proteomic and metabolomic data is also essential, as the resulting networks can provide a landscape to rationally predict and exploit new drug targets and to understand drug synergies.

Clinical features and short-term outcomes of cancer patients with suspected and unsuspected pulmonary embolism: the EPIPHANY study.

The study aimed to identify predictors of overall 30-day mortality in cancer patients with pulmonary embolism including suspected pulmonary embolism (SPE) and unsuspected pulmonary embolism (UPE) events. Secondary outcomes included 30- and 90-day major bleeding and venous thromboembolism (VTE) recurrence.The study cohort included 1033 consecutive patients with pulmonary embolism from the multicentre observational ambispective EPIPHANY study (March 2006-October 2014). A subgroup of 497 patients prospectively assessed for the study were subclassified into three work-up scenarios (SPE, truly asymptomatic UPE and UPE with symptoms) to assess outcomes.The overall 30-day mortality rate was 14%. The following variables were associated with the overall 30-day mortality on multivariate analysis: VTE history, upper gastrointestinal cancers, metastatic disease, cancer progression, performance status, arterial hypotension <100 mmHg, heart rate >110 beats·min-1, basal oxygen saturation <90% and SPE (versus overall UPE).The overall 30-day mortality was significantly lower in patients with truly asymptomatic UPE events (3%) compared with those with UPE-S (20%) and SPE (21%) (p<0.0001). Thirty- and 90-day VTE recurrence and major bleeding rates were similar in all the groups.In conclusion, variables associated with the severity of cancer and pulmonary embolism were associated with short-term mortality. Our findings may help to develop pulmonary embolism risk-assessment models in this setting.

Prognostic value of computed tomography pulmonary angiography indices in patients with cancer-related pulmonary embolism: Data from a multicenter cohort study.

OBJECTIVE: To analyze the prognostic value of pulmonary artery obstruction versus right-ventricle (RV) dysfunction radiologic indices in cancer-related pulmonary embolism (PE). METHODS: We enrolled 303 consecutive patients with paraneoplastic PE, evaluated by computed tomography pulmonary angiography (CTPA) between 2013 and 2014. The primary outcome measure was serious complications at 15days. Multivariate analyses were conducted by using binary logistic and robust regressions. Radiological features such as the Qanadli index (QI) and RV dysfunction signs were analyzed with Spearman's partial rank correlations. RESULTS: RV diameter was the only radiological variable associated with an adverse outcome. Subjects with enlarged RV (diameter>45mm) had more 15-day complications (58% versus 40%, p=0.001). The QI correlated with the RV diameter (r=0.28, p<0.001), left ventricle diameter (r=-0.19, p<0.001), right ventricular-to-left ventricular diameter ratio (r=0.39, p<0.001), pulmonary artery diameter (r=0.22, p<0.001), and pulmonary artery/ascending aorta ratio (r=0.27, p<0.001). A QI≥50% was only associated with 15-day complications in subjects with enlarged RV, inverted intraventricular septum, or chronic cardiopulmonary diseases. The central or peripheral PE location did not affect the correlations among radiological variables and was not associated with clinical outcomes. CONCLUSIONS: Right ventricular dysfunction signs in CTPA are more useful than QI in predicting cancer-related PE outcome.

Null mutants of Candida albicans for cell-wall-related genes form fragile biofilms that display an almost identical extracellular matrix proteome.

By two-dimensional gel electrophoresis (2-DE) and mass spectrometry, we have characterized the polypeptide species present in extracts obtained by 60% ethanol treatment of whole mature (48 h) biofilms formed by a reference strain (CAI4-URA3) and four Candida albicans null mutants for cell-wall-related genes (ALG5, CSA1, MNN9 and PGA10) Null mutants form fragile biofilms that appeared partially split and weakly attached to the substratum contrary to those produced by the reference strain. An almost identical, electrophoretic profile consisting of about 276 spots was visualized in all extracts examined. Proteomic analysis led to the identification of 131 polypeptides, corresponding to 86 different protein species, being the rest isoforms-83 displayed negative hydropathic indexes and 82 lack signal peptide. The majority of proteins appeared at pI between 4 and 6, and molecular mass between 10 and 94 kDa. The proteins identified belonged to the following Gene Ontology categories: 21.9% unknown molecular function, 16.2% oxidoreductase activity, 13.3% hydrolase activity and 41.8% distributed between other different GO categories. Strong defects in biofilm formation appreciated in the cell-wall mutant strains could be attributed to defects in aggregation due to abnormal cell wall formation rather than to differences in the biofilm extracellular matrix composition.

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication.

Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi [3-6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes.

The UmGcn5 gene encoding histone acetyltransferase from Ustilago maydis is involved in dimorphism and virulence.

We isolated a gene encoding a histone acetyltransferase from Ustilago maydis (DC.) Cda., which is orthologous to the Saccharomyces cerevisiae GCN5 gene. The gene was isolated from genomic clones identified by their specific hybridization to a gene fragment obtained by the polymerase chain reaction (PCR). This gene (Umgcn5; um05168) contains an open reading frame (ORF) of 1421bp that encodes a putative protein of 473 amino acids with a Mr. of 52.6kDa. The protein exhibits a high degree of homology with histone acetyltransferases from different organisms. Null a2b2 ΔUmgcn5 mutants were constructed by substitution of the region encoding the catalytic site with a hygromycin B resistance cassette. Null a1b1 ΔUmgcn5 mutants were isolated from genetic crosses of a2b2 ΔUmgcn5 and a1b1 wild-type strains in maize. Mutants displayed a slight reduction in growth rate under different conditions, and were more sensitive than the wild type to stress conditions, but more important, they grew as long mycelial cells, and formed fuzz-like colonies under all conditions where wild-type strains grew in the yeast-like morphology and formed smooth colonies. This phenotype was not reverted by cAMP addition. Mutants were not virulent to maize plants, and were unable to form teliospores. These phenotypic alterations of the mutants were reverted by their transformation with the wild-type gene.

Simultaneous determination of cocaine and opiates in dried blood spots by electrospray ionization tandem mass spectrometry.

A sample pre-treatment method based on blood spot collection filter cards was optimized as a means of using small volume samples for the screening and confirmation of cocaine and opiates abuse. Dried blood spots (DBSs) were prepared by dispersing 20 µL of whole blood specimens previously mixed with the internal standards (deuterated analogs of each target), and subjecting the whole DBS to extraction with 5 mL of methanol under orbital-horizontal shaking (180 rpm) for 10 min. Determinations were based on direct electrospray ionization tandem mass spectrometry (ESI-MS/MS) by injecting the re-dissolved methanol extract with the delivery solution (acetonitrile-water-formic acid, 80:19.875:0.125) at a flow rate of 60 µL min(-1), and using multiple reaction monitoring (MRM) mode with the m/z (precursor ion)→m/z (product ion) transitions for acquisition. Matrix effect has been found to be statistically significant (Multiple Range Test) when assessing cocaine, BZE, codeine and morphine, and the use of the standard addition method (dispersion of whole blood previously mixed with standards onto the filter papers) was needed for accurate determinations. The developed DBS-ESI-MS/MS procedure offered good intra-day and inter-day precisions (lower than 10% and 12%, respectively), as well as good intra-day and inter-day accuracies (inter-day absolute recoveries, expressed as the mean analytical recovery over three target concentration levels, of 103%, 100%, 101%, 98% and 100% for cocaine, BZE, codeine, morphine and 6-MAM, respectively). The high sensitivity inherent to MS/MS determinations combined with the minimal dilution of sample allowed low limits of quantification for all targets, and the developed method results therefore adequate for cocaine and opiates screening and confirmation purposes. The procedure was finally applied to DBSs prepared from whole blood from polydrug abusers, and results were compared with those obtained after a conventional sample pretreatment method based on solid phase extraction for plasma specimens and gas chromatography-mass spectrometry.