1,037 research outputs found

    The temporal evolution of neutron-capture elements in the Galactic discs

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    Important insights into the formation and evolution of the Galactic disc(s) are contained in the chemical compositions of stars. We analysed high-resolution and high signal to noise HARPS spectra of 79 solar twin stars in order to obtain precise determinations of their atmospheric parameters, ages (σ\sigma\sim0.4 Gyr) and chemical abundances (σ\sigma<<0.01~dex) of 12 neutron-capture elements (Sr, Y, Zr, Ba, La, Ce, Pr, Nd, Sm, Eu, Gd, and Dy). This valuable dataset allows us to study the [X/Fe]-age relations over a time interval of \sim10 Gyr and among stars belonging to the thin and thick discs. These relations show that i) the ss-process has been the main channel of nucleosynthesis of nn-capture elements during the evolution of the thin disc; ii) the thick disc is rich in rr-process elements which suggests that its formation has been rapid and intensive. %; iii) a chemical continuity between the thin and thick discs is evident in the abundances of Ba. In addition, the heavy (Ba, La, Ce) and light (Sr, Y, Zr) ss-process elements revealed details on the dependence between the yields of AGB stars and the stellar mass or metallicity. Finally, we confirmed that both [Y/Mg] and [Y/Al] ratios can be employed as stellar clocks, allowing ages of solar twin stars to be estimated with an average precision of \sim0.5~Gyr

    Dispelling the myths of online education: learning via the information superhighway

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    There continues to be a perception that online education is inferior to traditional education. In the U.S. online learning is more developed than in the U.K. This paper provides insights into a U.S. provision and takes a close look at what are perceived as weaknesses of on line learning and argues that these are not necessarily inherent weaknesses of this form of educational delivery. Then, results of two major studies, undertaken in the U.S. are provided comparing the effectiveness of online education to traditional education as perceived by current MBA students and past graduates. Results of these studies suggest that students of MBA modules and MBA graduates perceive the quality and effectiveness of online education to be similar to, if not higher than, the quality and effectiveness of traditional modules and programmes

    Crystal structures of Leptospira interrogans FAD-containing ferredoxin-NADP+ reductase and its complex with NADP+

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    <p>Abstract</p> <p>Background</p> <p>Ferredoxin-NADP(H) reductases (FNRs) are flavoenzymes that catalyze the electron transfer between NADP(H) and the proteins ferredoxin or flavodoxin. A number of structural features distinguish plant and bacterial FNRs, one of which is the mode of the cofactor FAD binding. <it>Leptospira interrogans </it>is a spirochaete parasitic bacterium capable of infecting humans and mammals in general. <it>Leptospira interrogans </it>FNR (LepFNR) displays low sequence identity with plant (34% with <it>Zea mays</it>) and bacterial (31% with <it>Escherichia coli</it>) FNRs. However, LepFNR contains all consensus sequences that define the plastidic class FNRs.</p> <p>Results</p> <p>The crystal structures of the FAD-containing LepFNR and the complex of the enzyme with NADP<sup>+</sup>, were solved and compared to known FNRs. The comparison reveals significant structural similarities of the enzyme with the plastidic type FNRs and differences with the bacterial enzymes. Our small angle X-ray scattering experiments show that LepFNR is a monomeric enzyme. Moreover, our biochemical data demonstrate that the LepFNR has an enzymatic activity similar to those reported for the plastidic enzymes and that is significantly different from bacterial flavoenzymes, which display lower turnover rates.</p> <p>Conclusion</p> <p>LepFNR is the first plastidic type FNR found in bacteria and, despite of its low sequence similarity with plastidic FNRs still displays high catalytic turnover rates. The typical structural and biochemical characteristics of plant FNRs unveiled for LepFNR support a notion of a putative lateral gene transfer which presumably offers <it>Leptospira interrogans </it>evolutionary advantages. The wealth of structural information about LepFNR provides a molecular basis for advanced drugs developments against leptospirosis.</p

    Lipid nanocarriers for hyperproliferative skin diseases

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    Hyperproliferative skin diseases (HSD) are a group of diseases that include cancers, pre-cancerous lesions and diseases of unknown etiology that present different skin manifestations in terms of the degree and distribution of the injuries. Anti-proliferative agents used to treat these diseases are so diverse, including 5-aminolevulinic acid, 5-fluorouracil, imiquimod, methotrexate, paclitaxel, podophyllotoxin, realgar, and corticosteroids in general. These drugs usually have low aqueous solubility, which consequently decreases skin permeation. Thus, their incorporation in lipid nanocarriers has been proposed with the main objective to increase the effectiveness of topical treatment and reduce side effects. This manuscript aims to describe the advantages of using lipid nanoparticles and liposomes that can be used to load diversity of chemically different drugs for the treatment of HSD.This research was funded by the Portuguese Science and Technology Foundation (FCT/MCT), European Funds (PRODER/COMPETE)—project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020. The work is also supported by the National Science Centre within the MINIATURA 4 for a single research activity (grant no: 2020/04/X/ST5/00789) and by the START 2021 Program of the Foundation for Polish Science (FNP) granted to Aleksandra Zielínskainfo:eu-repo/semantics/publishedVersio

    Antioxidant and Antinociceptive Effects of Citrus limon Essential Oil in Mice

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    The antioxidant and antinociceptive activities of Citrus limon essential oil (EO) were assessed in mice or in vitro tests. EO possesses a strong antioxidant potential according to the scavenging assays. Moreover, it presented scavenger activity against all in vitro tests. Orally, EO (50, 100, and 150 mg/kg) significantly reduced the number of writhes, and, at highest doses, it reduced the number of paw licks. Whereas naloxone antagonized the antinociceptive action of EO (highest doses), this suggested, at least, the participation of the opioid system. Further studies currently in progress will enable us to understand the action mechanisms of EO

    Prognostic implications of the ID1 expression in acute myeloid leukemia patients treated in a resource-constrained setting

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    Introduction: The aberrant expression of the inhibitor of DNA binding (ID1) gene has been frequently associated with the leukemogenesis and prognostication acute myeloid leukemia (AML), although its clinical importance has never been investigated in patients treated outside well-controlled clinical trials. Methods: Using quantitative real-time polymerase chain reaction, we investigated the role of the ID1 expression in the clinical outcomes of non-selected patients with acute myeloid leukemia treated in a real-life setting. Results: Overall, 128 patients were enrolled. Patients with high ID1 expression had a lower 3-year overall survival (OS) rate of 9%, with the 95% confidence interval (95%CI) at 3 to 20%, compared to patients with a low ID1 expression (22%, 95%CI: 11 - 34%) (p = 0.037), although these findings did not retain significance after adjustment (hazard ratio (HR): 1.5, 95%CI: 0.98 - 2.28; p = 0.057). The ID1 expression had no impact on post-induction outcomes (disease-free survival, p = 0.648; cumulative incidence of relapse, p = 0.584). Conclusions: Although we are aware thar our data are confronted with many variables that cannot be fully controlled, including drug unavailability, risk-adapted treatment, comorbidities and the time from diagnosis to treatment initiation, we are firm believers that such an initiative can provide more realistic data on understudied populations, in particular those from low- and middle-income countries.</p

    MeerKLASS: MeerKAT Large Area Synoptic Survey

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    We discuss the ground-breaking science that will be possible with a wide area survey, using the MeerKAT telescope, known as MeerKLASS (MeerKAT Large Area Synoptic Survey). The current specifications of MeerKAT make it a great fit for science applications that require large survey speeds but not necessarily high angular resolutions. In particular, for cosmology, a large survey over 4,000deg2\sim 4,000 \, {\rm deg}^2 for 4,000\sim 4,000 hours will potentially provide the first ever measurements of the baryon acoustic oscillations using the 21cm intensity mapping technique, with enough accuracy to impose constraints on the nature of dark energy. The combination with multi-wavelength data will give unique additional information, such as exquisite constraints on primordial non-Gaussianity using the multi-tracer technique, as well as a better handle on foregrounds and systematics. Such a wide survey with MeerKAT is also a great match for HI galaxy studies, providing unrivalled statistics in the pre-SKA era for galaxies resolved in the HI emission line beyond local structures at z > 0.01. It will also produce a large continuum galaxy sample down to a depth of about 5\,μ\muJy in L-band, which is quite unique over such large areas and will allow studies of the large-scale structure of the Universe out to high redshifts, complementing the galaxy HI survey to form a transformational multi-wavelength approach to study galaxy dynamics and evolution. Finally, the same survey will supply unique information for a range of other science applications, including a large statistical investigation of galaxy clusters as well as produce a rotation measure map across a huge swathe of the sky. The MeerKLASS survey will be a crucial step on the road to using SKA1-MID for cosmological applications and other commensal surveys, as described in the top priority SKA key science projects (abridged).Comment: Larger version of the paper submitted to the Proceedings of Science, "MeerKAT Science: On the Pathway to the SKA", Stellenbosch, 25-27 May 201

    From cheek swabs to consensus sequences : an A to Z protocol for high-throughput DNA sequencing of complete human mitochondrial genomes

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    Background: Next-generation DNA sequencing (NGS) technologies have made huge impacts in many fields of biological research, but especially in evolutionary biology. One area where NGS has shown potential is for high-throughput sequencing of complete mtDNA genomes (of humans and other animals). Despite the increasing use of NGS technologies and a better appreciation of their importance in answering biological questions, there remain significant obstacles to the successful implementation of NGS-based projects, especially for new users. Results: Here we present an ‘A to Z’ protocol for obtaining complete human mitochondrial (mtDNA) genomes – from DNA extraction to consensus sequence. Although designed for use on humans, this protocol could also be used to sequence small, organellar genomes from other species, and also nuclear loci. This protocol includes DNA extraction, PCR amplification, fragmentation of PCR products, barcoding of fragments, sequencing using the 454 GS FLX platform, and a complete bioinformatics pipeline (primer removal, reference-based mapping, output of coverage plots and SNP calling). Conclusions: All steps in this protocol are designed to be straightforward to implement, especially for researchers who are undertaking next-generation sequencing for the first time. The molecular steps are scalable to large numbers (hundreds) of individuals and all steps post-DNA extraction can be carried out in 96-well plate format. Also, the protocol has been assembled so that individual ‘modules’ can be swapped out to suit available resources

    Genome-wide multi-trait analysis of irritable bowel syndrome and related mental conditions identifies 38 new independent variants

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    Irritable bowel syndrome (IBS) is a chronic disorder of gut-brain interaction frequently accompanied by mental conditions, including depression and anxiety. Despite showing substantial heritability and being partly determined by a genetic component, the genetic underpinnings explaining the high rates of comorbidity remain largely unclear and there are no conclusive data on the temporal relationship between them. Exploring the overlapping genetic architecture between IBS and mental conditions may help to identify novel genetic loci and biological mechanisms underlying IBS and causal relationships between them. We quantified the genetic overlap between IBS, neuroticism, depression and anxiety, conducted a multi-trait genome-wide association study (GWAS) considering these traits and investigated causal relationships between them by using the largest GWAS to date. IBS showed to be a highly polygenic disorder with extensive genetic sharing with mental conditions. Multi-trait analysis of IBS and neuroticism, depression and anxiety identified 42 genome-wide significant variants for IBS, of which 38 are novel. Fine-mapping risk loci highlighted 289 genes enriched in genes upregulated during early embryonic brain development and gene-sets related with psychiatric, digestive and autoimmune disorders. IBS-associated genes were enriched for target genes of anti-inflammatory and antirheumatic drugs, anesthetics and opioid dependence pharmacological treatment. Mendelian-randomization analysis accounting for correlated pleiotropy identified bidirectional causal effects between IBS and neuroticism and depression and causal effects of the genetic liability of IBS on anxiety. These findings provide evidence of the polygenic architecture of IBS, identify novel genome-wide significant variants for IBS and extend previous knowledge on the genetic overlap and relationship between gastrointestinal and mental disorders. The online version contains supplementary material available at 10.1186/s12967-023-04107-5
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