Reduced graphene oxides as carbocatalysts in acceptorless dehydrogenation of N-heterocycles

The catalytic properties of graphene-derived materials are evaluated in acceptorless dehydrogenation of N-heterocycles. Among them, reduced graphene oxides (rGOs) are active (quantitative yields in 23 h) under mild conditions (130 °C) and act as efficient heterogeneous carbocatalysts. rGO exhibits reusability and stability at least during eight consecutive runs. Mechanistic investigations supported by experimental evidence (i.e., organic molecules as model compounds, purposely addition of metal impurities and selective functional group masking experiments) suggest a preferential contribution of ketone carbonyl groups as active sites for this transformation.

Benzbromarone, quercetin, and folic acid inhibit amylin aggregation

Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic ß-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of ß-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce ß-cell damage. Interestingly, three of the compounds analyzed—benzbromarone, quercetin, and folic acid—are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma ß cells by modulating the aggregation propensity of amylin

Management of risk factors associated with chronic oral lesions in sheep

Oral disorders constitute a significant cause of weight loss in sheep. In a study of disorders of the oral cavity of 36, 033 sheep from 60 meat sheep flocks in Spain, we looked for management risk factors associated with chronic oral lesions. Mandibular and maxillary disorders were assessed as an external manifestation of oral lesions by palpation, searching for tissue swellings, fistulae, or open wounds. The prevalence of flocks containing sheep with jaw disorders was 98.3%, with an average individual prevalence of 5.5%. The majority of lesions were located in in the mid-region of the mandible, and the most relevant risk factor was increasing age. Use of acidic diets based on silage and inclusion of hard foods, such as maize straw or hay, was associated with the occurrence of jaw inflammation. It was concluded that hard diets containing plant material with edges and sharp areas, plus acidic foods including silage, are more likely to cause lesions of the gingiva, enabling entry of pathogens to the oral mucosa that eventually establish locally in bony tissues, usually as mandibular osteomyelitis. It was also observed that mineral supplementation appears to prevent the occurrence of these lesions

Design, synthesis and structure-activity evaluation of novel 2-pyridone-based inhibitors of a-synuclein aggregation with potentially improved BBB permeability

The treatment of Parkinson''s disease (PD), the second most common neurodegenerative human disorder, continues to be symptomatic. Development of drugs able to stop or at least slowdown PD progression would benefit several million people worldwide. SynuClean-D is a low molecular weight 2-pyridone-based promising drug candidate that inhibits the aggregation of a-synuclein in human cultured cells and prevents degeneration of dopaminergic neurons in a Caenorhabditis elegans model of PD. Improving SynuClean-D pharmacokinetic/pharmacodynamic properties, performing structure/activity studies and testing its efficacy in mammalian models of PD requires the use of gr-amounts of the compound. However, not enough compound is on sale, and no synthetic route has been reported until now, which hampers the molecule progress towards clinical trials. To circumvent those problems, we describe here an efficient and economical route that enables the synthesis of SynuClean-D with good yields as well as the synthesis of SynuClean-D derivatives. Structure-activity comparison of the new compounds with SynuClean-D reveals the functional groups of the molecule that can be disposed of without activity loss and those that are crucial to interfere with a-synuclein aggregation. Several of the derivatives obtained retain the parent''s compound excellent in vitro anti-aggregative activity, without compromising its low toxicity. Computational predictions and preliminary testing indicate that the blood brain barrier (BBB) permeability of SynuClean-D is low. Importantly, several of the newly designed and obtained active derivatives are predicted to display good BBB permeability. The synthetic route developed here will facilitate their synthesis for BBB permeability determination and for efficacy testing in mammalian models of PD. © 2021 The Author

Effects of rapid gravity load changes on immunophenotyping and leukocyte function of human peripheral blood after parabolic flight

One of the biological systems that suffers a physiological de-conditioning in space is the immune system. It is in charge of defending the body against pathogens and other aggressions. The aim of this work is to assess if there are any relevant changes in the aggregation of erythrocytes, cell count, immunophenotyping and functionality after parabolic flight. This effect has been assessed ex vivo using human peripheral blood, which was drawn from the radial vein (n=6 healthy volunteers) and anticoagulated with heparin and EDTA. Blood samples were split into two aliquots and maintained in two identical thermally isolated boxes; one stayed on the ground whereas the other one was subjected to parabolic flight. The parabolic flight consisted of 15 parabolas performed with a Mudry CAP-10B acrobatic aircraft. Each parabola consists of 8 seconds of hypogravity preceded and followed by 2 seconds of hypergravity. Any of the biological parameters measured showed no statistically significant differences. Altered gravity could increase aggregation of red blood cells, as demonstrated by a decrease in the number of single cells after parabolic flight exposure. No counting changes in haemoglobin concentration were observed when comparing the two different groups. Furthermore, potential functional alterations of monocytes and neutrophils cannot be rejected. Although these possible changes could be associated with hypogravity, other factors such as hypergravity and acceleration or deceleration cannot be ruled out. Our findings indicate that, under this specific experimental setup, there was no significant alteration in leukocyte immunophenotyping and functional capacity when using ex vivo blood samples and short exposure to altered gravity.Peer ReviewedObjectius de Desenvolupament Sostenible::3 - Salut i BenestarPostprint (published version

First order transition and phase separation in pyrochlores with colossal-magnetoresistance

Tl$_{2}$Mn$_{2}$O$_{7}$ pyrochlores present colossal magnetoresistance (CMR) around the long range ferromagnetic ordering temperature (T$_{C}$). The character of this magnetic phase transition has been determined to be first order, by purely magnetic methods, in contrast to the second order character previously reported by Zhao et al. (Phys. Rev. Lett. 83, 219 (1999)). The highest CMR effect, as in Tl$_{1.8}$Cd$_{0.2}$Mn$_{2}$O$_{7}$, corresponds to a stronger first order character. This character implies a second type of magnetic interaction, besides the direct superexchange between the Mn$^{4+}$ ions, as well as a phase coexistence. A model is proposed, with a complete Hamiltonian (including superexchange and an indirect interaction), which reproduce the observed phenomenology.Comment: 6 pages. Figures include

Star Formation in the Starburst Cluster in NGC 3603

We have used new, deep, visible and near infrared observations of the compact starburst cluster in the giant HII region NGC 3603 and its surroundings with the WFC3 on HST and HAWK-I on the VLT to study in detail the physical properties of its intermediate mass (~ 1 - 3 M_sun) stellar population. We show that after correction for differential extinction and actively accreting stars, and the study of field star contamination, strong evidence remains for a continuous spread in the ages of pre-main sequence stars in the range ~ 2 to ~ 30 Myr within the temporal resolution available. Existing differences among presently available theoretical models account for the largest possible variation in shape of the measured age histograms within these limits. We also find that this isochronal age spread in the near infrared and visible Colour-Magnitude Diagrams cannot be reproduced by any other presently known source of astrophysical or instrumental scatter that could mimic the luminosity spread seen in our observations except, possibly, episodic accretion. The measured age spread and the stellar spatial distribution in the cluster are consistent with the hypothesis that star formation started at least 20-30 Myrs ago progressing slowly but continuously up to at least a few million years ago. All the stars in the considered mass range are distributed in a flattened oblate spheroidal pattern with the major axis oriented in an approximate South-East - North-West direction, and with the length of the equatorial axis decreasing with increasing age. This asymmetry is most likely due to the fact that star formation occurred along a filament of gas and dust in the natal molecular cloud oriented locally in this direction.Comment: 21 pages, 19 figures, accepted for publication in Astrophysics & Space Scienc

Yet Another Ranking Function for Automatic Multiword Term Extraction

International audienceTerm extraction is an essential task in domain knowledge acquisition. We propose two new measures to extract multiword terms from a domain-specific text. The first measure is both linguistic and statistical based. The second measure is graph-based, allowing assessment of the importance of a multiword term of a domain. Existing measures often solve some problems related (but not completely) to term extraction, e.g., noise, silence, low frequency, large-corpora, complexity of the multiword term extraction process. Instead, we focus on managing the entire set of problems, e.g., detecting rare terms and overcoming the low frequency issue. We show that the two proposed measures outperform precision results previously reported for automatic multiword extraction by comparing them with the state-of-the-art reference measures

Identification of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) as a possible biomarker of subclinical atherosclerosis

OBJECTIVES: Assessment of vascular risk in asymptomatic patients and the response to medical therapy is a major challenge for prevention of cardiovascular events. Our aim was to identify proteins differentially released by healthy versus atherosclerotic arterial walls, which could be found in plasma and serve as markers of atherosclerosis. METHODS AND RESULTS: We have analyzed supernatants obtained from cultured human carotid plaques and healthy arteries by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry ProteinChip System. Surface-enhanced laser-desorption/ionization analysis unveiled an 18.4-kDa peak released in lower amount by carotid plaques than normal endarteries. This protein was identified as soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK). To confirm that sTWEAK was the protein of interest, Western blot and enzyme-linked immunosorbent assay were performed. Both techniques confirmed that sTWEAK levels were decreased in carotid plaque supernatants. Subsequent measurement of sTWEAK in plasma showed a reduced concentration in subjects with carotid stenosis (N=30) compared with healthy subjects matched by sex and age (N=28) (P<0.001). Furthermore, in a test population of 106 asymptomatic subjects, we showed that sTWEAK concentrations negatively correlated with the carotid intima-media thickness (r=-0.4; P<0.001), an index of subclinical atherosclerosis. CONCLUSIONS: These results suggest that sTWEAK could be a potential biomarker of atherosclerosis