Analogues 4-désoxy-galactosylcéramides à activité immunorégulatrice (synthèse et évaluation biologique in vitro et in vivo)

NANTES-BU Sciences (441092104) / SudocSudocFranceF

Oxidation as an early stage in the multistep thermal decomposition of uranium(IV) oxalate into U3O8

International audienceThe thermal decomposition of actinides oxalates greatly depends on the oxidation state of the cation, the gas involved and the physical characteristics of the precursor. In the actinides series, uranium(IV) oxalate U(C 2 O 4) 2 .6H 2 O can be viewed as a peculiar case, as its sensibility towards oxidation leads to a specific series of reactions when heating under oxygen atmosphere. In order to clarify the disagreements existing in the literature, particularly concerning potential carbonate intermediates and the possible transitory existence of UO 3 , we show here an extended characterization of the different intermediates through a combination of X-Ray diffraction, vibrational spectroscopies and X-Ray absorption near edge spectroscopy. In this frame, uranium oxidation was found to occur at low temperature (200°C) concomitantly to the onset of oxalate groups decomposition, leading to an amorphous oxo-oxalato compound. Pursuing the thermal conversion up to 350°C led to complete oxidation of U(IV) into U(VI), then to the formation of amorphous UO 3 still bearing adsorbed carbonates. The first pure oxide formed during the thermal conversion was further identified to sub-stoichiometric UO 3- after heating at 550°C. Finally, U 3 O 8 was obtained as the final stable phase after heating above 660°C. The mechanism of thermal conversion of uranium(IV) oxalate into oxide under oxygen is then driven by a complex interplay between redox reactions and decomposition of the organic fractions. Such chemical reactions were also found to significantly modify the morphology of the powder through HT-ESEM observations : decomposition led the size of the aggregates to reduce by 20% while uranium oxidation clearly promoted growth within the agglomerates.

Outcome of long gap esophageal atresia at 6 years: A prospective case control cohort study

International audienceBackground data: EA is the most frequent congenital esophageal malformation. Long gap EA remains a therapeutic challenge for pediatric surgeons. A case case-control prospective study from a multi-institutional national French data base was performed to assess the outcome, at age of 1 and 6 years, of long gap esophageal atresia (EA) compared with non-long gap EA/tracheo-esophageal fistula (TEF). The secondary aim was to assess whether initial treatment (delayed primary anastomosis of native esophagus vs. esophageal replacement) influenced mortality and morbidity at ages 1 and 6 years.Methods: A multicentric population-based prospective study was performed and included all patients who underwent EA surgery in France from January 1, 2008 to December 31, 2010. A comparative study was performed with non-long gap EA/TEF patients. Morbidity at birth, 1 year, and 6 years was assessed.Results: Thirty-one patients with long gap EA were compared with 62 non-long gap EA/TEF patients. At age 1 year, the long gap EA group had longer parenteral nutrition support and longer hospital stay and were significantly more likely to have complications both early post-operatively and before age 1 year compared with the non-long gap EA/TEF group. At 6 years, digestive complications were more frequent in long gap compared to non-long gap EA/TEF patients. Tracheomalacia was the only respiratory complication that differed between the groups. Spine deformation was less frequent in the long gap group. There were no differences between conservative and replacement groups at ages 1 and 6 years except feeding difficulties that were more common in the native esophagus group.Conclusions: Long gap strongly influenced digestive morbidity at age 6 years.Keywords: Complications; Dysphagia; Esophageal atresia; Esophageal replacement; Gastro-esophageal reflux disease; Long gap esophageal atresia; Midterm outcomes

3-Fluoro- and 3,3-Difluoro-3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice

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Synthesis and Biological Evaluation of 4′-C,3′-O-Propylene-Linked Bicyclic Nucleosides

International audienceA set of pyrimidine nucleosides fused with a 4'-C,3'-O-propylene bridge was successfully synthesised in 12 steps from 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose, an inexpensive starting material, based on a ring-closing metathesis (RCM) reaction followed by Vorbruggen-type nucleobase coupling. Antiviral and cytotoxicity activities of the targeted modified nucleosides, as well as their phosphoramidate prodrugs, are described

Molecular Structure - Optical Property Relationships for a Series of Non-Centrosymmetric Two-photon Absorbing Push-Pull Triarylamine Molecules

This article reports on a comprehensive study of the two-photon absorption (2PA) properties of six novel push-pull octupolar triarylamine compounds as a function of the nature of the electron-withdrawing groups. These compounds present an octupolar structure consisting of a triarylamine core bearing two 3,39-bis(trifluoromethyl) phenyl arms and a third group with varying electron-withdrawing strength (H < CN < CHO < NO2 < Cyet < Vin). The 2PA cross-sections, measured by using the femtosecond open-aperture Z-scan technique, showed significant enhancement from 45 up to 125 GM for the lowest energy band and from 95 up to 270 GMfor the highest energy band. The results were elucidated based on the large changes in the transition and permanent dipole moments and in terms of (i) EWGstrength, (ii) degree of donor-acceptor charge transfer and (iii) electronic coupling between the arms. The 2PA results were eventually supported and confronted with theoretical DFT calculations of the two-photon transition oscillator strengths

Concurrent CDX2 cis -deregulation and UBTF::ATXN7L3 fusion define a novel high-risk subtype of B-cell ALL

Oncogenic alterations underlying B-cell acute lymphoblastic leukemia (B-ALL) in adults remain incompletely elucidated. To uncover novel oncogenic drivers, we performed RNA sequencing and whole-genome analyses in a large cohort of unresolved B-ALL. We identified a novel subtype characterized by a distinct gene expression signature and the unique association of 2 genomic microdeletions. The 17q21.31 microdeletion resulted in a UBTF::ATXN7L3 fusion transcript encoding a chimeric protein. The 13q12.2 deletion resulted in monoallelic ectopic expression of the homeobox transcription factor CDX2, located 138 kb in cis from the deletion. Using 4C-sequencing and CRISPR interference experiments, we elucidated the mechanism of CDX2 cis-deregulation, involving PAN3 enhancer hijacking. CDX2/UBTF ALL (n = 26) harbored a distinct pattern of additional alterations including 1q gain and CXCR4 activating mutations. Within adult patients with Ph- B-ALL enrolled in GRAALL trials, patients with CDX2/UBTF ALL (n = 17/723, 2.4%) were young (median age, 31 years) and dramatically enriched in females (male/female ratio, 0.2, P = .002). They commonly presented with a pro-B phenotype ALL and moderate blast cell infiltration. They had poor response to treatment including a higher risk of failure to first induction course (19% vs 3%, P = .017) and higher post-induction minimal residual disease (MRD) levels (MRD ≥ 10-4, 93% vs 46%, P < .001). This early resistance to treatment translated into a significantly higher cumulative incidence of relapse (75.0% vs 32.4%, P = .004) in univariate and multivariate analyses. In conclusion, we discovered a novel B-ALL entity defined by the unique combination of CDX2 cis-deregulation and UBTF::ATXN7L3 fusion, representing a high-risk disease in young adults

3-Fluoro- and 3,3-Difluoro-3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice

We propose here the synthesis and biological evaluation of 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues <b>8</b> and <b>9</b>, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T_H1 or T_H2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation