Vitamins are more Funky than Casimir thought

We celebrate; 2012, as the centenary of the discovery of the 'Vitamine'. Dr Casimir Funk first conceived the concept of ";;vital amines";;; essential nutrients with a specific action, requiring only minute quantities to cure a specific disease. Thus he is the godfather of the vitamin industry. His legacy is the heuristic that all vitamins are simple amines with one mode of action and thus effective in a single disease.  Whilst this may be true for thiamine, it is not for other vitamins that have many modes of action and are implicated in many diseases.  The limitations do not detract from the genius of his theory, its influence on medical thinking, and the founding the vitamin industry. However it is time to progress to a 21st Century understanding of vitamins.  

Origin and significance of 'dispersed facies' basal ice: Svínafellsjökull, Iceland

Dispersed facies basal ice - massive (i.e. structureless) ice with dispersed debris aggregates - is present at the margins of many glaciers and, as a product of internal glacial processes, has the potential to provide important information about the mechanisms of glacier flow and the nature of the subglacial environment. The origin of dispersed facies is poorly understood, with several hypotheses having been advanced for its formation, and there is disagreement as to whether it is largely a sedimentary or a tectonic feature. We test these established hypotheses at the temperate glacier Svfnafellsjokull, Iceland, and find that none fully account for dispersed facies characteristics at this location. Instead, dispersed facies physical, sedimentological and stable-isotope (5180, 8D) characteristics favour a predominantly tectonic origin that we suggest comprises the regelation and straininduced metamorphism of debris-rich basal ice that has been entrained into an englacial position by tectonic processes operating at the base of an icefall. Further thickening of the resultant dispersed facies may also occur tectonically as a result of ice flow against the reverse bed slope of a terminal overdeepening. Lack of efficient subglacial drainage in the region of the overdeepening may limit basal melting and thus favour basal ice preservation, including the preservation of dispersed facies. Despite the relatively low sediment content of dispersed facies (~1.6% by volume), its thickness (up to 25 m) and ubiquity at Svfnafellsjokull results in a significant contribution to annual sediment discharge (1635-3270 m3 a"1) that is ~6.5 times that contributed by debris-rich stratified facies basal ice

A rational roadmap for SARS-CoV-2/COVID-19 pharmacotherapeutic research and development: IUPHAR Review 29.

In this review, we identify opportunities for drug discovery in the treatment of COVID-19 and, in so doing, provide a rational roadmap whereby pharmacology and pharmacologists can mitigate against the global pandemic. We assess the scope for targeting key host and viral targets in the mid-term, by first screening these targets against drugs already licensed, an agenda for drug repurposing, which should allow rapid translation to clinical trials. A simultaneous, multi-pronged approach using conventional drug discovery methods aimed at discovering novel chemical and biological means of targeting a short list of host and viral entities which should extend the arsenal of anti-SARS-CoV-2 agents. This longer term strategy would provide a deeper pool of drug choices for future-proofing against acquired drug resistance. Second, there will be further viral threats, which will inevitably evade existing vaccines. This will require a coherent therapeutic strategy which pharmacology and pharmacologists are best placed to provide. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.Welcome Trust 107715/Z/15/

Eliza Haywoods geschichte des fräuleins Elisabeth Thoughtless (1756): frühe selbsterkenntnis und ehekritik in der englischen ubersetzungsliteratur

Die Tradition, Frauenerleben aus weiblicher Perspektive zum Mittelpunkt eines Romans zu machen, beginnt in Deutschland nicht mit Sophie La Roches Geschichte des Fräuleins von Sternheim (1771), sondern mit den Werken englischer Schriftstellerinnen, die bereits bedeutend früher in deutschen Übersetzungen erschienen und bisher von der Germanistik nicht beachtet worden sind. An Eliza Haywoods Geschichte des Fräuleins Elisabeth Thoughtless (1756) soll hier exemplarisch gezeigt werden, wie in Deutschland Mitte des 18. Jahrhunderts bereits eine Form der Literatur von Frauen erscheint, die die Entwicklung eines weiblichen Charakters zum Mittelpunkt hat. Obwohl der Übersetzer die in diesem Roman enthaltene Kritik an der patriarchalisch geführten Ehe und der Idealisierung der Frau durch eine bewusst gewählte Übersetzungsstrategie abschwächt, um der Leserschaft den für deutsche Verhältnisse zu radikalen Text angenehmer zu machen, ist dieser, von Lessing als das Werk eines Genies bewertete Roman ein Meilenstein in der Literatur von Frauen

The IUPHAR/BPS Guide to PHARMACOLOGY in 2024

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb; https://www.guidetopharmacology.org) is an open-access, expert-curated, online database that provides succinct overviews and key references for pharmacological targets and their recommended experimental ligands. It includes over 3039 protein targets and 12 163 ligand molecules, including approved drugs, small molecules, peptides and antibodies. Here, we report recent developments to the resource and describe expansion in content over the six database releases made during the last two years. The database update section of this paper focuses on two areas relating to important global health challenges. The first, SARS-CoV-2 COVID-19, remains a major concern and we describe our efforts to expand the database to include a new family of coronavirus proteins. The second area is antimicrobial resistance, for which we have extended our coverage of antibacterials in partnership with AntibioticDB, a collaboration that has continued through support from GARDP. We discuss other areas of curation and also focus on our external links to resources such as PubChem that bring important synergies to the resources. [Abstract copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.

The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY.

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb, www.guidetopharmacology.org) and its precursor IUPHAR-DB, have captured expert-curated interactions between targets and ligands from selected papers in pharmacology and drug discovery since 2003. This resource continues to be developed in conjunction with the International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society (BPS). As previously described, our unique model of content selection and quality control is based on 96 target-class subcommittees comprising 512 scientists collaborating with in-house curators. This update describes content expansion, new features and interoperability improvements introduced in the 10 releases since August 2015. Our relationship matrix now describes ∼9000 ligands, ∼15 000 binding constants, ∼6000 papers and ∼1700 human proteins. As an important addition, we also introduce our newly funded project for the Guide to IMMUNOPHARMACOLOGY (GtoImmuPdb, www.guidetoimmunopharmacology.org). This has been 'forked' from the well-established GtoPdb data model and expanded into new types of data related to the immune system and inflammatory processes. This includes new ligands, targets, pathways, cell types and diseases for which we are recruiting new IUPHAR expert committees. Designed as an immunopharmacological gateway, it also has an emphasis on potential therapeutic interventions

The Concise Guide to PHARMACOLOGY 2023/24:Introduction and Other Protein Targets

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.</p

THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Introduction and Other Protein Targets.

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14747. In addition to this overview, in which are identified Other protein targets which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Advances in Malaria Pharmacology and the online Guide to MALARIA PHARMACOLOGY: IUPHAR Review X

Antimalarial drug discovery has until recently been driven by high-throughput phenotypic cellular screening, allowing millions of compounds to be assayed and delivering clinical drug candidates. In this review, we will focus on target-based approaches, describing recent advances in our understanding of druggable targets in the malaria parasite. Targeting multiple stages of the Plasmodium lifecycle, rather than just the clinically symptomatic asexual blood stage, has become a requirement for new antimalarial medicines, and we link pharmacological data clearly to the parasite stages to which it applies. Finally, we highlight the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY, a web resource developed for the malaria research community that provides open and optimized access to published data on malaria pharmacology