Anodic and Cathodic Platinum Dissolution Processes Involve Different Oxide Species

The degradation of Pt-containing oxygen reduction catalysts for fuel cell applications is strongly linked to the electrochemical surface oxidation and reduction of Pt. Here, we study the surface restructuring and Pt dissolution mechanisms during oxidation/reduction for the case of Pt(100) in 0.1 M HClO4 by combining operando high-energy surface X-ray diffraction, online mass spectrometry, and density functional theory. Our atomic-scale structural studies reveal that anodic dissolution, detected during oxidation, and cathodic dissolution, observed during the subsequent reduction, are linked to two different oxide phases. Anodic dissolution occurs predominantly during nucleation and growth of the first, stripe-like oxide. Cathodic dissolution is linked to a second, amorphous Pt oxide phase that resembles bulk PtO2 and starts to grow when the coverage of the stripe-like oxide saturates. In addition, we find the amount of surface restructuring after an oxidation/reduction cycle to be potential-independent after the stripe-like oxide has reached its saturation coverage.Funding is acknowledged from Deutsche Forschungsgemeinschaft for OMM and SC (project number 418603497), for OMM by the German Federal Ministry of Education and Research (BMBF) via project 05K19FK3, and for DAH by the NSERC (grant RGPIN-2017-04045). FCV acknowledges that the grants PID2021-127957NB-I00 and TED2021-132550B-C21 were funded by MCIN/AEI/ 10.13039/501100011033 and by the European Union. The use of supercomputing facilities at SURFsara was sponsored by NWO Physical Sciences, with financial support by NWO. Open Access funding enabled and organized by Projekt DEAL

Genetic Deletion of Sost or Pharmacological Inhibition of Sclerostin Prevent Multiple Myeloma-induced Bone Disease without Affecting Tumor Growth

Multiple myeloma (MM) causes lytic bone lesions due to increased bone resorption and concomitant marked suppression of bone formation. Sclerostin (Scl) levels, an osteocyte-derived inhibitor of Wnt/β-catenin signaling, are elevated in MM patient sera and are increased in osteocytes in MM-bearing mice. We show here that genetic deletion of Sost, the gene encoding Scl, prevented MM-induced bone disease in an immune-deficient mouse model of early MM, and that administration of anti-Scl antibody (Scl-Ab) increased bone mass and decreases osteolysis in immune-competent mice with established MM. Sost/Scl inhibition increased osteoblast numbers, stimulated new bone formation and decreased osteoclast number in MM-colonized bone. Further, Sost/Scl inhibition did not affect tumor growth in vivo or anti-myeloma drug efficacy in vitro. These results identify the osteocyte as a major contributor to the deleterious effects of MM in bone and osteocyte-derived Scl as a promising target for the treatment of established MM-induced bone disease. Further, Scl did not interfere with efficacy of chemotherapy for MM suggesting that combined treatment with anti-myeloma drugs and Scl-Ab should effectively control MM growth and bone disease, providing new avenues to effectively control MM and bone disease in patients with active MM

Maternal resources, pregnancy concerns, and biological factors associated to birth weight and psychological health

Cognitive maternal adaptation during pregnancy may influence biological variables, maternal psychological, and neonatal health. We hypothesized that pregnant women with numerous general resources and less negative emotions would have a better coping with a positive influence on neonatal birth weight and maternal psychological health. The study included 131 healthy pregnant women. A blood sample was obtained in the first trimester to assess biological variables (polyphenols, hematological and biochemical parameters). Psychological variables (negative affect, anxiety, optimism, resilience, family–work conflicts, pregnancy concerns, general resources, and life satisfaction) were evaluated at several time points along gestation, and birth weight was recorded. Hierarchical linear regression models were used to associate the above parameters with maternal psychological outcome at the end of gestation (depression, resilience, and optimism) and neonatal outcome (birth weight). Maternal depression was associated with leukocytes (β = 0.08 ± 0.03, p-value = 0.003), cholesterol (β = 0.01 ± 0.002, p-value = 0.026), and pregnancy concerns (β = 0.31 ± 0.09, p-value = 0.001). Maternal resilience was associated with leukocytes (β = −0.14 ± 0.09, p-value = 0.010) and life satisfaction (β = 0.82 ± 0.08, p-value = 0.001), and maternal optimism was associated with polyphenol levels (β = 0.002 ± 0.001, p-value = 0.018) and life satisfaction (β = 0.49 ± 0.04, p-value = 0.001). Birth weight was associated with maternal resilience (β = 370.2 ± 97.0, p-value = 0.001), red blood cells (β = 480.3 ± 144.4, p-value = 0.001), and life satisfaction (β = 423.3 ± 32.6, p-value = 0.001). We found associations between maternal psychological, blood variables, and birth weight and maternal depression. This study reveals the relevance of psychological health during pregnancy for maternal and neonatal outcome, and it emphasizes the need to consider it in preventive policies in the obstetric fiel

Polyphenol composition and in vitro antiproliferative effect of corm, tepal and leaf from Crocus sativus L. on human colon adenocarcinoma cells (Caco-2)

25 Páginas, 3 Figuras, 3 TablasSaffron is cultivated for production of the saffron spice. Nevertheless, a huge amount of saffron by-products including corms, tepals and leaves with little or no commercial value are generated during the processing of the spice. This biomass contains bioactive compounds whose exploitation can increase the profitability and sustainability of this traditional crop. A significant amount of polyphenols, mainly glycosides of kaempferol, luteolin and quercetin, have been determined in tepals and leaves of saffron. Proliferation of Caco-2 cells was greatly inhibited by the tepal and leaf extracts (ED50 0.42 mg/ml), while the corm extract caused some signs of toxicity and completely abolished proliferation (ED50 0.05 mg/ml). To our knowledge, these are the first data reporting the inhibition of the proliferation of Caco-2 cells by extracts from tepals and leaves of saffron, and polyphenols could be responsible for this effect.This work has been supported by the grant RTA2013-00005-00-00 (INIA, Spain) and is part of a Short Term Scientific Mission (STSM) carried out in the Agricultural University of Athens (AUA) and supported by the grant COST ActionFA1101 (http://www.saffronomics.org). We are grateful to the European Social Fund, Fundación Parque Científico y Tecnológico de Castilla-La Mancha and Junta de Andalucía for additional financing.Peer reviewe

First trimester elevations of hematocrit, lipid peroxidation and nitrates in women with twin pregnancies who develop preeclampsia

Twin pregnancies are considered a risk factor for preeclampsia, an obstetric complication with high maternal and infant morbi-mortality. We hypothesize that alterations in maternal hematocrit, plasma lipid peroxidation and nitrates in the first trimester of pregnancy are associated with preeclampsia development in twin pregnancies. Blood samples were extracted from 102 healthy women with twin pregnancies at tenth week of gestation to assess hematological parameters and plasma levels of malondialdehyde and nitrates. Logistic regression model showed an association between red blood cells (OR = 38.8; p-value = 0.009), hematocrit (OR = 1.6; p-value = 0.017), malondialdehyde (OR = 1.5; p-value = 0.002), and nitrates (OR = 1.1; p-value = 0.045) and preeclampsia development. These parameters are potential biomarkers for early preeclampsia detection in twin pregnancies. Future research is needed to assess their value in predictive algorithmsThis work was supported by Multidisciplinary Research Project [CEMU, 2013-10], Universidad Autónoma de Madrid) and collaborative project Universidad Autónoma de Madrid-Khon Kaen University [KKU: 0514.7.I.12-1948

An unstable Th epitope of P. falciparum fosters central memory T cells and anti-CS antibody responses

Malaria is transmitted by Plasmodium-infected anopheles mosquitoes. Widespread resistance of mosquitoes to insecticides and resistance of parasites to drugs highlight the urgent need for malaria vaccines. The most advanced malaria vaccines target sporozoites, the infective form of the parasite. A major target of the antibody response to sporozoites are the repeat epitopes of the circumsporozoite (CS) protein, which span almost one half of the protein. Antibodies to these repeats can neutralize sporozoite infectivity. Generation of protective antibody responses to the CS protein (anti-CS Ab) requires help by CD4 T cells. A CD4 T cell epitope from the CS protein designated T* was previously identified by screening T cells from volunteers immunized with irradiated P. falciparum sporozoites. The T* sequence spans twenty amino acids that contains multiple T cell epitopes restricted by various HLA alleles. Subunit malaria vaccines including T* are highly immunogenic in rodents, non-human primates and humans. In this study we characterized a highly conserved HLA-DRbeta1*04:01 (DR4) restricted T cell epitope (QNT-5) located at the C-terminus of T*. We found that a peptide containing QNT-5 was able to elicit long-term anti-CS Ab responses and prime CD4 T cells in HLA-DR4 transgenic mice despite forming relatively unstable MHC-peptide complexes highly susceptible to HLA-DM editing. We attempted to improve the immunogenicity of QNT-5 by replacing the P1 anchor position with an optimal tyrosine residue. The modified peptide QNT-Y formed stable MHC-peptide complexes highly resistant to HLA-DM editing. Contrary to expectations, a linear peptide containing QNT-Y elicited almost 10-fold lower long-term antibody and IFN-gamma responses compared to the linear peptide containing the wild type QNT-5 sequence. Some possibilities regarding why QNT-5 is more effective than QNT-Y in inducing long-term T cell and anti-CS Ab when used as vaccine are discussed

Unregulated actin polymerization by WASp causes defects of mitosis and cytokinesis in X-linked neutropenia

Specific mutations in the human gene encoding the Wiskott-Aldrich syndrome protein (WASp) that compromise normal auto-inhibition of WASp result in unregulated activation of the actin-related protein 2/3 complex and increased actin polymerizing activity. These activating mutations are associated with an X-linked form of neutropenia with an intrinsic failure of myelopoiesis and an increase in the incidence of cytogenetic abnormalities. To study the underlying mechanisms, active mutant WASpI294T was expressed by gene transfer. This caused enhanced and delocalized actin polymerization throughout the cell, decreased proliferation, and increased apoptosis. Cells became binucleated, suggesting a failure of cytokinesis, and micronuclei were formed, indicative of genomic instability. Live cell imaging demonstrated a delay in mitosis from prometaphase to anaphase and confirmed that multinucleation was a result of aborted cytokinesis. During mitosis, filamentous actin was abnormally localized around the spindle and chromosomes throughout their alignment and separation, and it accumulated within the cleavage furrow around the spindle midzone. These findings reveal a novel mechanism for inhibition of myelopoiesis through defective mitosis and cytokinesis due to hyperactivation and mislocalization of actin polymerization

Variante morfológica de adultos hembras de Anopheles benarrochi (Diptera: Culicidae) en Putumayo, Colombia

A survey of Anopheles mosquitoes was undertaken in Putumayo, southern Colombia, to clarify the identity of specimens classified as Anopheles (N) evansae in the region. Female anophelines were captured on human bait; then blood fed on small mammals to obtain eggs for progeny broods. Morphological characteristics of the eggs. larvae, pupae and adults of both sexes, including male genitalia were examined. Eggs were obtained from 247 females provisionally identified as A. (N.) evansae Morphology of associated life stages of the progeny broods was compared among 27 families. The morphology of al1 stages corresponded to the published descriptions of Anopheles (N.) benarrochi. However, morphologically variable adult females were noted. In hind tarsomere 2, the dark portion ranged from 0.17 to 0.33 of the tarsomere length; this is less than previously reported for A. (N) benarrochi and overlaps the ranges described for A. (N,) oswaldoi and A. (N) evansae This variable character probably has led to incorrect identifications of adult A. (N.) benarrochifemales as A. (N.) evansae or A. (N.) oswaldoi in specimens from southern Colombia. As a consequence, A. (N) benarrochi has not been previously recognized in Putumayo, and probably has been misidentified in other areas of northwestern South America.Con el propósito de ampliar el conocimiento sobre las especies de Anopheles presentes en el Putumayo, sur de Colombia, y para esclarecer la identidad de los ejemplares clasificados como Anopheles (Nyssorhynchus) evansae en esta región, se recolectaron mosquitos hembra en cebo humano, se alimentaron en pequeños mamíferos y se mantuvieron vivos para la cría de isofamilias. Se realizaron observaciones de las características morfológicas de los huevos, larvas, pupas y adultos de ambos sexos, incluidas las genitalias masculinas. Se obtuvieron 247 posturas de madres identificadas preliminarmente como A. (N) evansae A 27 de estas familias se les estudió la morfología de los estadios asociados. Todos los especimenes fueron subsecuentemente identificados como Anopheles (N) benarrochi por la morfología de los huevos, larvas, pupas y genitalias masculinas, lo cual coincidió con las descripciones publicadas para esta especie. Sin embargo, los adultos hembra de Putumayo presentaron la proporción oscura en el tarsómero posterior 2, entre 0.17 y 0.33 de su longitud, inferior a lo informado para esta especie, lo cual se superpone con los rangos de Anopheles (N.) oswaldoi y A. (N.) evansae. Como resultado de la superposición en este carácter, es probable que hembras adultas de A. (N.) benarrochi hayan sido incorrectamente identificadas como A. (N) evansae y A. (N.) oswaldoi en el sur de Colombia. La presencia de esta variante morfológica ha dificultado la identificación de A. (N.) benarrochi en Putumayo y, probablemente, en otras regiones de Colombia y paises vecinos

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

Refractory Materials for Flame Deflector Protection System Corrosion Control: Similar Industries and/or Launch Facilities Survey

A trade study and litera ture survey of refractory materials (fi rebrick. refractory concrete. and si licone and epoxy ablatives) were conducted to identify candidate replacement materials for Launch Complexes 39A and 398 at Kennedy Space Center (KSC). In addition, site vis its and in terviews with industry expens and vendors of refractory materials were conducted. As a result of the si te visits and interviews, several products were identified for launch applications. Firebrick is costly to procure and install and was not used in the si tes studied. Refractory concrete is gunnable. adheres well. and costs less 10 install. Martyte. a ceramic fi lled epoxy. can protect structural stccl but is costly. difficullto apply. and incompatible with silicone ablatives. Havanex, a phenolic ablative material, is easy to apply but is costly and requires frequent replacement. Silicone ablatives are ineJ[pensive, easy to apply. and perl'onn well outside of direct rocket impingement areas. but refractory concrete and epoxy ablatives provide better protection against direcl rocket exhaust. None of the prodUCIS in this trade study can be considered a panacea for these KSC launch complexes. but the refractory products. individually or in combination, may be considered for use provided the appropriate testing requirements and specifications are met