3,514 research outputs found
Proverbi in Aristofane
No full textThe proverbs used by Aristophanes are here studied under two points of view. On the first hand, the history of the tradition of the proverb, the author studies Aristophanes' texts which transmit for the first time the proverb or reveal its original meaning, as well as cases which ought to be included in a previous tradition, eventually spread from a famous locus classicus. On the second hand, the interpretations done by Aristophanes himself, he studies the variations, in particular: inserts in specific context, re-utilisation in a paroduic key, restablishment of a realistic interpretation, additions, textual change
grp-bork/metadrugs_figures: Release of metadrugs_figure scripts and input data
No full textThis repository contains input data and notebooks to plot the figures associated with the manuscript
"Combinatorial, additive and dose-dependent drug-microbiome associations"
Authors: Sofia K. Forslund*, Rima Chakaroun*, Maria Zimmermann-Kogadeeva*, Lajos Markó*, Judith Aron-Wisnewsky*, Trine Nielsen*, The MetaCardis Consortium, Jens Nielsen, Fredrik Bäckhed, S. Dusko Ehrlich, Marc-Emmanuel Dumas, Jeroen Raes, Oluf Pedersen, Karine Clément, Michael Stumvoll, Peer Bork.
Code contributions by: Sofia K. Forslund, Lucas Moitinho-Silva, Thomas S. B. Schmidt, Till Birkner, Maria Zimmermann-Kogadeeva
grp-bork/metadrugs_figures: InitialRelease
No full textNo description provided.
This repository contains notebooks to plot the figures associated with the manuscript
"Combinatorial, additive and dose-dependent drug-microbiome associations"
Authors: Sofia K. Forslund*, Rima Chakaroun*, Maria Zimmermann-Kogadeeva*, Lajos Markó*, Judith Aron-Wisnewsky*, Trine Nielsen*, The MetaCardis Consortium, Jens Nielsen, Fredrik Bäckhed, S. Dusko Ehrlich, Marc-Emmanuel Dumas, Jeroen Raes, Oluf Pedersen, Karine Clément, Michael Stumvoll, Peer Bork.
Code contributions by: Sofia K. Forslund, Lucas Moitinho-Silva, Thomas S. B. Schmidt, Till Birkner, Maria Zimmermann-Kogadeeva
grp-bork/metadrugs_figures: Release with input data
No full textNo description provided.
This repository contains input data and notebooks to plot the figures associated with the manuscript
"Combinatorial, additive and dose-dependent drug-microbiome associations"
Authors: Sofia K. Forslund*, Rima Chakaroun*, Maria Zimmermann-Kogadeeva*, Lajos Markó*, Judith Aron-Wisnewsky*, Trine Nielsen*, The MetaCardis Consortium, Jens Nielsen, Fredrik Bäckhed, S. Dusko Ehrlich, Marc-Emmanuel Dumas, Jeroen Raes, Oluf Pedersen, Karine Clément, Michael Stumvoll, Peer Bork.
Code contributions by: Sofia K. Forslund, Lucas Moitinho-Silva, Thomas S. B. Schmidt, Till Birkner, Maria Zimmermann-Kogadeeva
On single-crystal total scattering data reduction and correction protocols for analysis in direct space. Corrigendum
No full textThe name of the third author of the article by Koch et al. [Acta Cryst. (2021).A77, 611–636] is corrected.The name of the third author in the article by Koch et al.(2021) is incorrectly given as Yiu Liu. The correct name is YuLiu, as given above.ReferencesKoch, R. J., Roth, N., Liu, Y., Ivashko, O., Dippel, A.-C., Petrovic, C.,Iversen, B. B., v. Zimmermann, M. & Bozin, E. S. (2021). Acta Cryst.A77, 611–636
Screening, identification, structure-activity, and mode of action studies with new antitrypanosomal leads of plant and fungal origin
No full textHuman African trypanosomiasis (HAT) is a neglected disease caused by the protozoan Trypanosoma brucei, which is transmitted during blood-feeding tsetse fly bites. The disease is endemic covering 36 sub-Saharan African countries and mainly impacts poor people living in remote areas, for which satisfactory treatment does not exist. As such, this protozoal disease would never be viewed as viable target market for the pharmaceutical industry. Therefore, it is referred to as a neglected disease. Chemotherapy remains the principal treatment for HAT and is based on four drugs: suramin, pentamidine, melarsoprol, eflornithine, and a recent approved eflornithine-nifurtimox combination. Reported severe side effects (e.g. melarsoprol), treatment failures of up to 25%, administration difficulties, and expensive medication urgently demand for safe, orally administered drugs, that are effective against both stages of HAT. Natural sources like plants and fungi provide a rich biological diversity with unique pharmacophores created by evolution and are therefore potential sources to discover such new drugs.
This thesis describes the search of new natural products (NPs) from nature. Over the last seven years we collected 724 plants and 64 fungi. The material was subsequently extracted and tested in vitro against T. b. rhodesiense, Plasmodium falciparum (the causative agent of malaria), Leishmania donovani (leishmaniasis), and T. cruzi (Chagas disease) to find potential hits. From the total 2151 extracts, 17.9% showed activity of more than 50% at 4.81 µg/mL test concentration against at least one parasite, and 3.4% showed potency of more than 50% at 0.81 µg/mL test concentration, respectively. Overall the plant extracts had six times higher "hit-rates" (15.3%) than the fungi extracts (2.6%), both resulting in high potencies against T. b. rhodesiense and P. falciparum. Yet, with up to 5 millions fungi, which outnumber higher plants by 16:1, the kingdom remains a relatively poorly studied source.
One of the antitrypanosomal hits was a dichloromethane (DCM) extract of the cornflower Centaurea salmantica with a growth inhibition of 61% tested at 4.81 µg/mL against T. b. rhodesiense. HPLC-based activity profiling led to the identification of the sesquiterpene lactone (STL) cynaropicrin (CYN), which was the first plant NP to show in vivo efficacy in T. b. rhodesiense infected mice, treated i.p. at 10 mg/kg/b.i.d. for four consecutive days. Despite of more than 10'000 known STLs is a better understanding of the structural features, which contribute to activity, expedient. The established structure-activity relationship (SAR) study included 18 natural STLs and demonstrated that antitrypanosomal and cytotoxic effect depended on their a,ß-unsaturated enone moieties. Many bioactivities of STLs have been attributed to a nucleophilic Michael-addition of these functional motifs to biological thiols. Considering that trypanosomes depend on their unique trypanothione-based redox system to deal with oxidative stress and to maintain a reducing intracellular milieu and that CYN contains reactive exocyclic a,ß-unsaturated methylenes, we anticipated that the mechanism of action depended on a direct interference with glutathione (GSH) and trypanothione (T(SH)2) in the cells. After 5 min. of CYN's exposure to trypanosomes, the intracellular thiol pool was completely depleted and a GS-CYN-monoadduct as well as a T(S-CYN)2-bisadduct were formed. This led to apoptosis of the trypanosomes over 40 min. linked to phenotype transformations from the typical slender to a stumpy-like form. Additionally, ornithine quantification studies by tandem mass spectroscopy (MS/MS) showed that ornithine decarboxylase (ODC) is a potential secondary target for CYN.
To improve CYN's pharmacokinetic (PK) profile the a,ß-unsaturated exocyclic double bond at the lactone was masked to create an amine prodrug with increased aqueous solubility and reduced unspecific binding to biological thiols. Through subsequent bioactivation the prodrug would be converted back to CYN and it would display a higher concentration on the target side. The lead optimization did not reward any better antitrypanosomal in vivo efficacy after oral application, but the prodrug had an improved in vivo cytotoxic profile. Further PK studies with other orally applied STL amino derivatives are needed to demonstrate if the use of amino STLs as prodrugs is a reasonable approach to improve STLs suitability as antitrypanosomal drug
Methods to assess iron and iodine status
No full textFour methods are recommended for assessment of iodine nutrition: urinary iodine concentration, the goitre rate, and blood concentrations of thyroid stimulating hormone and thyroglobulin. These indicators are complementary, in that urinary iodine is a sensitive indicator of recent iodine intake (days) and thyroglobulin shows an intermediate response (weeks to months), whereas changes in the goitre rate reflect long-term iodine nutrition (months to years). Spot urinary iodine concentrations are highly variable from day-to-day and should not be used to classify iodine status of individuals. International reference criteria for thyroid volume in children have recently been published and can be used for identifying even small goitres using thyroid ultrasound. Recent development of a dried blood spot thyroglobulin assay makes sample collection practical even in remote areas. Thyroid stimulating hormone is a useful indicator of iodine nutrition in the newborn, but not in other age groups. For assessing iron status, haemoglobin measurement alone has low specificity and sensitivity. Serum ferritin remains the best indicator of iron stores in the absence of inflammation. Measures of iron-deficient erythropoiesis include transferrin iron saturation and erythrocyte zinc protoporphyrin, but these often do not distinguish anaemia due to iron deficiency from the anaemia of chronic disease. The serum transferrin receptor is useful in this setting, but the assay requires standardization. In the absence of inflammation, a sensitive method to assess iron status is to combine the use of serum ferritin as a measure of iron stores and the serum transferrin receptor as a measure of tissue iron deficiency
Heterocyclic amine directed synthesis of metal(II)-oxalates: investigating the magnetic properties of two complete series of chains with S = 5/2 to S = 1/2
No full textWe report here two series of coordination polymer chains: the first being [M(II)(ox)(bnz)2]n (M = Mn 1, Fe 2, Co 3, Ni 4, Cu 5 and Zn 6; ox = oxalate C2O42-; bnz = benzimidazole) and the second [M(II)(ox)(btz)2]n (M = Mn 7, Fe 8, Co 9, Ni 10, Cu 11 and Zn 12; btz = benzotriazole). The first series displays an unusual homometallic [–Mi–Mii–Mii–]n chain topology and the second series is isostructural to [Fe(II)(ox)(btz)2]n, originally reported by Jia et al. (Collect. Czech. Chem. Commun., 2002, 67, 1609–1615). These two series allow us to make comparisons between the spin state of each metal and the magnetic coupling interaction within an isostructural series spanning the full range of spin states available in 3d metals and to investigate which models are the best to use in each case. Compound 8 is a single-chain magnet, the behaviour through spin-canting arising from a Dzyaloshinskii-Moriya interaction. Additionally, we have synthesised a two-dimensional coordination polymer {[Zn(II)(bnz)4][Zn(II)2(ox)3]}n ( 13), in which distorted hexagonal [Zn(II)2(ox)3]n2n- layers are hydrogen bonded by [Zn(II)(bnz)4]2+ cations to give an interlayer separation of 12.001(2) Å
Il mimo popolare come 'letteratura sommersa': il caso della Moicheutria
No full textP.Oxy. III 413 preserves two texts, respectively known as Charition and Moicheu- tria, which represent without doubt the most important surviving testimonies for the so called ‘popular’ mime: these two texts appear to have been originally conceived for perfor- mance, and are of exceptional importance to the study of the history of the genre during the Roman Empire. It has been demonstrated that literary and popular mimes should not be viewed as separate spheres but as interdependent and engaged in an intense and dy- namic exchange: an example of which is provided by the structural and narrative analogies between Charition and Euripides’ Iphigenia in Tauris, Helen, Cyclops (inspired by the Od- yssey, Book 9), and by similarities between Herondas’ fifth Mimiamb and the Moicheutria. This paper aims to demonstrate that Moicheutria has another literary model: the intrigue, based on a mors ficta, is at the base of the plot of Menander’s Aspis. The narrative and dramaturgical affinities between the two texts suggest the hypothesis that the anonymous author of the Moicheutria could have been inspired by Menandrian Comedy
Sensitive phases in the development of rodent social behavior
No full textSachser N, Zimmermann TD, Hennessy MB, Kaiser S. Sensitive phases in the development of rodent social behavior. Current Opinion in Behavioral Sciences. 2020;36:63-70
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