Squaramide-catalyzed asymmetric Mannich reaction between 1,3-dicarbonyl compounds and pyrazolinone ketimines: A pathway to enantioenriched 4-pyrazolyl- and 4-isoxazolyl-4-aminopyrazolone derivatives

Producción CientíficaA series of N-Boc ketimines derived from pyrazolin-5-ones have been used as electrophiles in enantioselective Mannich reactions with different 1,3-dicarbonyl compounds. This method provides a direct pathway to access the 4-amino-5-pyrazolone derivatives bearing a quaternary substituted stereocenter and containing two privileged structure motifs, the β-diketone and pyrazolinone substructures. The adducts were obtained in excellent yields (up to 90%) and enantioselectivities (up to 94:6 er) by employing a very low loading of 2 mol% of a quinine-derived bifunctional squaramide as an organocatalyst for a wide range of substrates. In addition, the utility of the obtained products was demonstrated through one step transformations to enantioenriched diheterocyclic systems (4-pyrazolyl-pyrazolone and 4-isoxazolyl-pyrazolone), potentially promising candidates for drug discovery

Both TLR2 and TRIF Contribute to Interferon-β Production during Listeria Infection

Synthesis of interferon-β (IFN-β) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-β synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-β production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ΔpgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-β gene, requiring TLR2 and bacterial internalization. Induction of IFN-β was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression

Spread of Avian Influenza Viruses by Common Teal (Anas crecca) in Europe

Since the recent spread of highly pathogenic (HP) H5N1 subtypes, avian influenza virus (AIV) dispersal has become an increasing focus of research. As for any other bird-borne pathogen, dispersal of these viruses is related to local and migratory movements of their hosts. In this study, we investigated potential AIV spread by Common Teal (Anas crecca) from the Camargue area, in the South of France, across Europe. Based on bird-ring recoveries, local duck population sizes and prevalence of infection with these viruses, we built an individual-based spatially explicit model describing bird movements, both locally (between wintering areas) and at the flyway scale. We investigated the effects of viral excretion duration and inactivation rate in water by simulating AIV spread with varying values for these two parameters. The results indicate that an efficient AIV dispersal in space is possible only for excretion durations longer than 7 days. Virus inactivation rate in the environment appears as a key parameter in the model because it allows local persistence of AIV over several months, the interval between two migratory periods. Virus persistence in water thus represents an important component of contamination risk as ducks migrate along their flyway. Based on the present modelling exercise, we also argue that HP H5N1 AIV is unlikely to be efficiently spread by Common Teal dispersal only

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Caractéristiques des voyageurs internationaux au centre de voyageurs à Marseille, France

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF