Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Intraspecific venom variation of Mexican West Coast Rattlesnakes (Crotalus basiliscus) and its implications for antivenom production

14 páginas, 9 figuras, 3 tablasIntraspecific variation in snake venoms has been widely documented worldwide. However, there are few studies on this subject in Mexico. Venom characterization studies provide important data used to predict clinical syndromes, to evaluate the efficacy of antivenoms and, in some cases, to improve immunogenic mixtures in the production of antivenoms. In the present work, we evaluated the intraspecific venom variation of Crotalus basiliscus, a rattlesnake of medical importance and whose venom is used in the immunization of horses to produce one of the Mexican antivenoms. Our results demonstrate that there is variation in biological and biochemical activities among adult venoms and that there is an ontogenetic change from juvenile to adult venoms. Juvenile venoms were more lethal and had higher percentages of crotamine and crotoxin, while adult venoms had higher percentages of snake venom metalloproteases (SVMPs). Additionally, we documented crotoxin-like PLA2 variation in which specimens from Zacatecas, Sinaloa and Michoacán (except 1) lacked the neurotoxin, while the rest of the venoms had it. Finally, we evaluated the efficacy of three lots of Birmex antivenom and all three were able to neutralize the lethality of four representative venoms but were not able to neutralize crotamine. We also observed significant differences in the LD50 values neutralized per vial among the different lots. Based on these results, we recommend including venoms containing crotamine in the production of antivenom for a better immunogenic mixture and to improve the homogeneity of lots.This study was financially supported by DGAPA-PAPIIT (project IN211621), CONACYT (project264255); FORDECYT PRONACE (project 1715618/2020), FORDECYT (project 303045), Clemson University and the National Science Foundation (DEB 1822417) to CLP.Peer reviewe

Copper(II) coordination chain complex with the 2,5-bis(2-pyridyl)-1,3,4-thiadiazole ligand and an asymmetric μ₂-1,1-azido double-bridged: Synthesis, crystal structure and magnetic properties

A new asymmetric μ2-1,1-azido double bridged cooper (II), with 2,5-bis(2-pyridyl)-1,3,4-thiadiazole (L), has been synthesized and characterized using single crystal X-ray diffraction, FT-IR, UV-Visible spectroscopic and magnetic measurements. The asymmetric unit of the title compound contains half molecule of formula, C12H8CuN10S, which crystallizes in the triclinic system, space group P1¯, with a = 6.5916 (4)Å, b = 10.6905 (7) Å, c = 11.5037 (7) Å, α = 106.508 (3)°, β = 105.538 (3)°, γ = 90.233 (4)°, V = 745.99 (8) Å3 and Z = 2. The structure consists of two [CuN5] prismatic polyhedra linked together by edge-sharing to build up a [Cu2N8] dimer arranged in chain. The connectivity along the chain is performed by [Formula presented] edge sharing between dimers. In the crystal, the molecules are linked together by [Formula presented] hydrogen bonds and by π—π interactions between parallel pyridyl rings of neighboring molecules. The interpretation of FT-IR and UV-Vis spectra is consistent with the crystal structure determined by X-ray diffraction. The magnetic properties of the complex confirm the picture of an alternated … Cu-J1-Cu ….J2 … Cu-J1-Cu … magnetic chains. We found in the dimers weak antiferromagnetic exchange interactions JJ1/k = −5.9 (1) k and between them JJ2/k = −2.3 k

As-doping effect on magnetic, optical and transport properties of Zn 0.9Co0.1O diluted magnetic semiconductor

We report on the structural, magnetic, optical and transport properties of As-doped Zn0.9Co0.1O thin films. X-ray diffraction indicates highly (0 0 0 1) textured samples free of secondary phases. Transmission UV-Vis spectroscopy shows that Co is in the +2 oxidation state and substitute for the Zn2+ ions of the ZnO matrix. ZnCoO was doped with 0.5% As which lead to n-type doping. Before and after As-implantation, the films remain ferromagnetic up to 350 K and the magnetization is unchanged. Surprisingly, there is no real influence of the doping process on the exchange interaction mediated by itinerant carriers between magnetic ions. © 2006 Elsevier B.V. All rights reserved

Macroporosity Enhancement of Scaffold Oxide Layers Using Self‐Assembled Polymer Beads for Photovoltaic Applications

Molding of a dense film of spherical poly(acrylate/methyl methacrylate) (PAA‐PMMA) beads is used as unique templating agent to obtain TiO2 scaffold layers with controlled porosity. The porosity obtained is of hundreds of nanometers, much larger than the one typically reported for the porous layers of Grätzel‐ or perovskite‐ type cells. It is shown that the film thickness and roughness, and the pore size are strongly dependent on the roughness of the substrate for identical deposition conditions. In order enhance the conductivity of the TiO2 scaffold layer, a sol‐gel mixture of titanium and tin is also successfully tested. Such films are potentially interesting as electron transport layer in perovskite solar cells since they allow an enhanced specific surface and a better control of the interface with the infiltrated photoactive material which are essential for an efficient charge collection

Optical and structural properties of Nd doped SnO2 powder fabricated by the sol-gel method

Équipe 104 : NanomatériauxInternational audienceWe report on the structural and optical properties of undoped and neodymium doped SnO2 powders (0, 1, 3, and 5 at% of Nd) synthesized by the sol-gel method. SEM and TEM microscopy techniques reveal a nanometric scale of the powders. We show that the tetragonal rutile phase is achieved after annealing at 700 degrees C. The crystallite size of the doped SnO2 is found to decrease gradually with the increase of Nd content without changing the SnO2 structure. A strong decrease in the intensity of the Raman peaks is noted for doped powders, which can be attributed to the location of Nd3+ ions at the Sn sites indicating Nd incorporation into the host matrix. For the first time the optical properties were studied by UV-VisNIR spectroscopy and revealed Nd related absorption bands in the SnO2 matrix. The investigation of the photoluminescence properties shows broad emission centred around 550-650 nm originating from defects present in the SnO2 host matrix. Under 325 nm laser excitation, a strong photoluminescence of trivalent Nd is observed in the infrared region and shows Nd related emission peaks at 885, 1065, and 1336 nm. Such a strong PL signal under laser excitation indicates that Nd3+ is optically active. The excitation dependent PL (PLE) recorded in the 450-700 nm range confirms the presence of active Nd3+ successfully inserted into the SnO2 host matrix

Investigation of LaVO3 based compounds as a photovoltaic absorber

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