59 research outputs found

    Laudato si\u27 and the call to ecological conversion: implications for Christian spirituality in a technocratic age

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    This paper examines Laudato si’ and a few of its key themes as they pertain to Christian spirituality and self-awareness. In particular, it focuses on the notion of “ecological conversion,” by which, Pope Francis writes, the person’s encounter with Jesus Christ become evident in her relationship with the world. It is, as already mentioned, an extension of the Catholic moral principle of solidarity to include not just other human beings, but also all of God’s creatures, who belong to one ontological family. But more than just a new development in the Church’s body of social teaching, ecological conversion has profound implications for Christian spirituality because it proposes a re-fashioning of the person’s most deeply held convictions about God, creation, and herself. Its particular relevance is the present “technocratic paradigm,” which Pope Francis names as one of the root causes of the ecological crisis. Ecological conversion is, for men and women who have been instructed by technocracy, a path of conversion and deep interior renewal

    Antimalarial drug discovery - the path towards eradication

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    Malaria is a disease that still affects a significant proportion of the global human population. Whilst advances have been made in lowering the numbers of cases and deaths, it is clear that a strategy based solely on disease control year on year, without reducing transmission and ultimately eradicating the parasite, is unsustainable. This article highlights the current mainstay treatments alongside a selection of emerging new clinical molecules from the portfolio of Medicines for Malaria Venture (MMV) and our partners. In each case, the key highlights from each research phase are described to demonstrate how these new potential medicines were discovered. Given the increased focus of the community on eradicating the disease, the strategy for next generation combination medicines that will provide such potential is explaine

    Properties of Linear Contrails Detected in 2012 Northern Hemisphere MODIS Imagery

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    Observation of linear contrail cirrus coverage and retrieval of their optical properties are valuable data for validating atmospheric climate models that represent contrail formation explicitly. These data can reduce our uncertainty of the regional effects of contrail-generated cirrus on global radiative forcing, and thus improve our estimation of the impact of commercial aviation on climate change. We use an automated contrail detection algorithm (CDA) to determine the coverage of linear persistent contrails over the Northern Hemisphere during 2012. The contrail detection algorithm is a modified form of the Mannstein et al. (1999) method, and uses several channels from thermal infrared MODIS data to reduce the occurrence of false positive detections. A set of contrail masks of varying sensitivity is produced to define the potential range of uncertainty in contrail coverage estimated by the CDA. Global aircraft emissions waypoint data provided by FAA allow comparison of detected contrails with commercial aircraft flight tracks. A pixel-level product based on the advected flight tracks defined by the waypoint data and U-V wind component profiles from the NASA GMAO GEOS-4 reanalysis has been developed to assign a confidence of contrail detection for the contrail mask. To account for possible contrail cirrus missed by the CDA, a post-processing method based on the assumption that pixels adjacent to detected linear contrails will have radiative signatures similar to those of the detected contrails is applied to the Northern Hemisphere data. Results from several months of MODIS observations during 2012 will be presented, representing a near-global climatology of contrail coverage. Linear contrail coverage will be compared with coverage estimates determined previously from 2006 MODIS data

    Volume 02

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    Introduction from Dean Dr. Charles Ross Mike\u27s Nite: New Jazz for an Old Instrument by Joseph A. Mann Investigation of the use of Cucumis Sativus for Remediation Of Chromium from Contaminated Environmental Matrices: An Interdisciplinary Instrumental Analysis Project by Kathryn J. Greenly, Scott E. Jenkins, and Andrew E. Puckette Development of GC-MS and Chemometric Methods for the Analysis of Accelerants in Arson Cases by Scott Jenkins Building and Measuring Scalable Computing Systems by Daniel M. Honey and Jeffery P. Ravenhorst Nomini Hall: A Case Study in the Use of Archival Resources as Guides for Excavation at An Archaeological Site by Jamie Elizabeth Mesrobian Two Stories: In Ohio and How to Stay Out of the Brazilian Army by Thomas Scott Forgerson des Hommes/Stealing the Steel in Zola\u27s Men by Jay Crowell Paul Gauguin\u27s Escape into Primitivism by Sarah Spangenberg Lee Krasner, Abstract Expressionist by Amy S. Eason Artist Book “Paris” by Kenny Wolfe Artist Book “Sequence of Every Day” by Liz Hale Artist Book “Apple Tree” by Rachel Bouchard Artist Book “Not so Pretty in Pink” by Will Semonco Artist Book “Look into the Moon” by Carley York Artist Books “Extra” and “Green” by Ryan Higgenbothom Artist Book “Re-growing Appalachia” by Adrienne Heinbaugh Artist Books “Cheeziest”, “Uh-oh” and “The Girl with the Glasses” by Melissa Dorton “Self-Reflection” by Madeline Hunter Artist Book “The Princess and the Frog” by June Ashmore “Hunter’s Niche” and “The Wild” by Clark Barkley “To Thine Own Self be True” by Jay Haley “Not Funny” Ten-Minute Play Festiva

    Photodegradation of the Mycobacterium ulcerans Toxin, Mycolactones: Considerations for Handling and Storage

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    Background: Mycolactones are toxins secreted by M. ulcerans, the etiological agent of Buruli ulcer. These toxins, which are the main virulence factors of the bacilli, are responsible for skin lesions. Considering their specificity for M. ulcerans and their presence in skin lesions even at early stages, mycolactones are promising candidates for the development of a diagnostic tool for M. ulcerans infection. Stability of purified mycolactones towards light and heat has not yet been investigated, despite the importance of such parameters in the selection of strategies for a diagnosis tool development. In this context, the effects of UV, light and temperature on mycolactone stability and biological activity were studied. Methodology/Principal Findings: To investigate the effect of these physical parameters, mycolactones were exposed to different wavelengths in several solvents and temperatures. Structural changes and biological activity were monitored. Whilst high temperature had no effect on mycolactones, UV irradiation (UV-A, UV-B and UV-C) and sunlight exposure caused a considerable degradation, as revealed by LC-MS and NMR analysis, correlated with a loss of biological activity. Moreover, effect of UVs on mycolactone caused a photodegradation rather than a phototransformation due to the identification of degradation product. Conclusion/Significance: This study demonstrates the high sensitivity of mycolactones to UVs as such it defines instruction

    Mycolactone subverts immunity by selectively blocking the Sec61 translocon

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    Mycolactone, an immunosuppressive macrolide released by the human pathogen Mycobacterium ulcerans, was previously shown to impair Sec61-dependent protein translocation, but the underlying molecular mechanism was not identified. In this study, we show that mycolactone directly targets the alpha subunit of the Sec61 translocon to block the production of secreted and integral membrane proteins with high potency. We identify a single-amino acid mutation conferring resistance to mycolactone, which localizes its interaction site near the lumenal plug of Sec61 alpha. Quantitative proteomics reveals that during T cell activation, mycolactone-mediated Sec61 blockade affects a selective subset of secretory proteins including key signal-transmitting receptors and adhesion molecules. Expression of mutant Sec61 alpha in mycolactone-treated T cells rescued their homing potential and effector functions. Furthermore, when expressed in macrophages, the mycolactone-resistant mutant restored IFN-gamma receptor-mediated antimicrobial responses. Thus, our data provide definitive genetic evidence that Sec61 is the host receptor mediating the diverse immunomodulatory effects of mycolactone and identify Sec61 as a novel regulator of immune cell functions.Peer reviewe

    The International Virus Bioinformatics Meeting 2023

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    The 2023 International Virus Bioinformatics Meeting was held in Valencia, Spain, from 24–26 May 2023, attracting approximately 180 participants worldwide. The primary objective of the conference was to establish a dynamic scientific environment conducive to discussion, collaboration, and the generation of novel research ideas. As the first in-person event following the SARS-CoV-2 pandemic, the meeting facilitated highly interactive exchanges among attendees. It served as a pivotal gathering for gaining insights into the current status of virus bioinformatics research and engaging with leading researchers and emerging scientists. The event comprised eight invited talks, 19 contributed talks, and 74 poster presentations across eleven sessions spanning three days. Topics covered included machine learning, bacteriophages, virus discovery, virus classification, virus visualization, viral infection, viromics, molecular epidemiology, phylodynamic analysis, RNA viruses, viral sequence analysis, viral surveillance, and metagenomics. This report provides rewritten abstracts of the presentations, a summary of the key research findings, and highlights shared during the meeting

    Setting our sights on infectious diseases

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    In May 2019, the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee, UK, held an international conference with the aim of discussing some key questions around discovering new medicines for infectious diseases and a particular focus on diseases affecting Low and Middle Income Countries. There is an urgent need for new drugs to treat most infectious diseases. We were keen to see if there were lessons that we could learn across different disease areas and between the preclinical and clinical phases with the aim of exploring how we can improve and speed up the drug discovery, translational, and clinical development processes. We started with an introductory session on the current situation and then worked backward from clinical development to combination therapy, pharmacokinetic/pharmacodynamic (PK/PD) studies, drug discovery pathways, and new starting points and targets. This Viewpoint aims to capture some of the learnings

    Tracking Virus-Specific CD4+ T Cells during and after Acute Hepatitis C Virus Infection

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    CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays. Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C. During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists

    Bioinformatics in translational drug discovery

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    Bioinformatics approaches are becoming ever more essential in translational drug discovery both in academia and within the pharmaceutical industry. Computational exploitation of the increasing volumes of data generated during all phases of drug discovery is enabling key challenges of the process to be addressed. Here, we highlight some of the areas in which bioinformatics resources and methods are being developed to support the drug discovery pipeline. These include the creation of large data warehouses, bioinformatics algorithms to analyse ‘big data’ that identify novel drug targets and/or biomarkers, programs to assess the tractability of targets, and prediction of repositioning opportunities that use licensed drugs to treat additional indications
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