Quotient inhibiteur de la tobramycine chez les patients de réanimation (facteurs de variation)

Objectifs: décrire chez des patients de réanimation le niveau de concentration de tobramycine après dose unique journalière, ainsi que ses facteurs de variation. Patients et méthodes: étude prospective de 2 ans sur 44 patients recevant une antibiothérapie adaptée associant tobramycine et ceftazidime. La Cmax a été dosée 30 minutes après la fin de la perfusion, la Cmin 24 heures après. Résultats : Le quotient inhibiteur QI (rapport Cmax/CMI) était 11,8 +- 8,2 et supérieur à 8 dans 72,5 % des cas. La variabilité des Cmax, composante essentielle du QI, a été évaluée par analyse Bayésienne qui montre que le volume de distribution (très augmenté) et la clairance de la tobramycine sont influencés par l'âge du patient et la clairance de la créatinine. Conclusion : le monitoring thérapeutique pharmacocinétique (QI) et bactériologique (identification du germe, antibiogramme et CMI) permet d'optimiser l'administration de tobramycine chez des patients critiques de réanimation.TOULOUSE3-BU Santé-Centrale (315552105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

PINK1-induced mitophagy promotes neuroprotection in Huntington’s disease

International audienceHuntington's disease (HD) is a fatal neurodegenerative disorder caused by aberrant expansion of CAG repeat in the huntingtin gene. Mutant Huntingtin (mHtt) alters multiple cellular processes, leading to neuronal dysfunction and death. Among those alterations, impaired mitochondrial metabolism seems to have a major role in HD pathogenesis. In this study, we used the Drosophila model system to further investigate the role of mitochondrial damages in HD. We first analyzed the impact of mHtt on mitochondrial morphology, and surprisingly, we revealed the formation of abnormal ring-shaped mitochondria in photoreceptor neurons. Because such mitochondrial spheroids were previously detected in cells where mitophagy is blocked, we analyzed the effect of PTEN-induced putative kinase 1 (PINK1), which controls Parkin-mediated mitophagy. Consistently, we found that PINK1 overexpression alleviated mitochondrial spheroid formation in HD flies. More importantly, PINK1 ameliorated ATP levels, neuronal integrity and adult fly survival, demonstrating that PINK1 counteracts the neurotoxicity of mHtt. This neuroprotection was Parkin-dependent and required mitochondrial outer membrane proteins, mitofusin and the voltage-dependent anion channel. Consistent with our observations in flies, we demonstrated that the removal of defective mitochondria was impaired in HD striatal cells derived from HdhQ111 knock-in mice, and that overexpressing PINK1 in these cells partially restored mitophagy. The presence of mHtt did not affect Parkin-mediated mitochondrial ubiquitination but decreased the targeting of mitochondria to autophagosomes. Altogether, our findings suggest that mitophagy is altered in the presence of mHtt and that increasing PINK1/Parkin mitochondrial quality control pathway may improve mitochondrial integrity and neuroprotection in HD

Overproduction and Biochemical Characterization of the Chryseobacterium meningosepticum BlaB Metallo-β-Lactamase

The BlaB metallo-β-lactamase of Chryseobacterium meningosepticum CCUG4310 was overproduced in Escherichia coli by means of a T7 promoter-based expression system. The overproducing system, scaled up in a 15-liter fermentor, yielded approximately 10 mg of BlaB protein per liter, mostly released in the culture supernatant. The enzyme was purified by two ion-exchange chromatographic steps with an overall yield of 66%. Analysis of the kinetic parameters revealed efficient activities (k(cat)/K(m) ratios of >10(6) M(−1) s(−1)) toward most penam and carbapenem compounds, with the exception of the 6-α-methoxypenam derivative temocillin and of biapenem, which were poorer substrates. Hydrolysis of cephalosporins was overall less efficient, with a remarkable variability that was largely due to variable affinities of the BlaB enzyme for different compounds. BlaB was also able to hydrolyze serine-β-lactamase inhibitors, including β-iodopenicillanate, sulbactam and, although less efficiently, tazobactam

Sustainable Palm Oil Production project synthesis: Understanding and anticipating global challenges

Several sustainability certification schemes have been developed for palm oil; however, the field impacts of these schemes remain highly uncertain. The Sustainable Palm Oil Production (SPOP) project, funded by the French National Research Agency (ANR), was aimed at consolidating and deepening the scientific basis of these schemes. - SPOP field work undertaken in Indonesia and Cameroon highlighted the large variability in practices and impacts of oil palm systems. Our main results related to the uncovering of the multiplicity of growers and their trajectories, and identifying room for improvement and the need for recommendations adapted to the various grower contexts and strategies. - The SPOP project made it explicit that visions of sustainability and global challenges vary greatly among growers and other stakeholders involved in the palm oil sector. These diverging conceptions are most likely to induce bottlenecks in the definition and implementation of good practices and should be accounted for in the refinement of sustainability criteria. - Within the SPOP project, we investigated possible futures for oil palm using participatory prospective analyses and multi-agent-based modeling work. Our research work showed that capacity development and the organizational capacity of smallholders, fair partnerships and combined forms of governance are key drivers in ensuring the uptake of good practices and sustainable development at the landscape scale

Premiere etude sur les performances d'un systeme de connexion par goujons visses pour des constructions mixtes acier-beton

CNRS AR 12849 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Identification of microRNAs in <i>Macaca fascicularis</i> (Cynomolgus Monkey) by Homology Search and Experimental Validation by Small RNA-Seq and RT-qPCR Using Kidney Cortex Tissues

<div><p>MicroRNAs (miRNAs) present in tissues and biofluids are emerging as sensitive and specific safety biomarkers. MiRNAs have not been thoroughly described in <i>M</i>. <i>fascicularis</i>, an animal model used in pharmaceutical industry especially in drug safety evaluation. Here we investigated the miRNAs in <i>M</i>. <i>fascicularis</i>. For <i>Macaca mulatta</i>, a closely related species of <i>M</i>. <i>fascicularis</i>, 619 stem-loop precursor miRNAs (pre-miRNAs) and 914 mature miRNAs are available in miRBase version 21. Using <i>M</i>. <i>mulatta</i> miRNAs as a reference list and homology search tools, we identified 604 pre-miRNAs and 913 mature miRNAs in the genome of <i>M</i>. <i>fascicularis</i>. In order to validate the miRNAs identified by homology search we attempted to sequence miRNAs expressed in kidney cortex from <i>M</i>. <i>fascicularis</i>. MiRNAs expressed in kidney cortex may indeed be released in urine upon kidney cortex damage and be potentially used to monitor drug induced kidney injury. Hence small RNA sequencing libraries were prepared using kidney cortex tissues obtained from three naive <i>M</i>. <i>fascicularis</i> and sequenced. Analysis of sequencing data indicated that 432 out of 913 mature miRNAs were expressed in kidney cortex tissues. Assigning these 432 miRNAs to pre-miRNAs revealed that 273 were expressed from both the -5p and -3p arms of 150 pre-miRNAs and 159 miRNAs expressed from either the -5p or -3p arm of 176 pre-miRNAs. Mapping sequencing reads to pre-miRNAs also facilitated the detection of twenty-two new miRNAs. To substantiate miRNAs identified by small RNA sequencing, 313 miRNAs were examined by RT-qPCR. Expression of 262 miRNAs in kidney cortex tissues ware confirmed by TaqMan microRNA RT-qPCR assays. Analysis of kidney cortex miRNA targeted genes suggested that they play important role in kidney development and function. Data presented in this study may serve as a valuable resource to assess the renal safety biomarker potential of miRNAs in Cynomolgus monkeys.</p></div

Premiere etude sur les performances d'un systeme de connexion par goujons visses pour des constructions mixtes acier-beton

CNRS AR 12849 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

Twelve new patients with 13q deletion syndrome: Genotype-phenotype analyses in progress.

International audience13q deletion is characterized by a wide phenotypic spectrum resulting from a partial deletion of the long arm of chromosome 13. The main clinical features are mental retardation, growth retardation, craniofacial dysmorphy and various congenital defects. Only one recent Italian study was aimed at determining genotype-phenotype correlations among 13q deletions from a group of mainly live born children, using array-CGH and FISH. In order to improve the molecular characterization of 13q monosomy, 12 new patients (9 foetuses and 3 children) were collected based on a cohort of holoprosencephaly (HPE) linked to ZIC2 gene deletion and/or patients with 13q deletion diagnosed by standard karyotype. First, quantitative gene screening using MLPA (Multiplex Ligation dependent Probe Amplification) was performed to look for ZIC2 gene deletion and then, CGH array analysis was carried out using the Agilent Human Genome CGH microarray 4x44K (Agilent Technologies, Santa Clara, USA). All the foetuses had severe cerebral midline malformations associated with a deletion including the ZIC2 gene. We report one patient with Steinfeld phenotype linked to this chromosomal anomaly, and suggest that some of the associations between cerebral midline malformation and limb defects might be related to 13q deletion. Further candidate genes are suspected to explain the malformations associated with cerebral anomalies in the hypothesis of a contiguous gene syndrome: SPRY2 in 13q31.1 is implicated in lens cell proliferation and differentiation for congenital cataract; GPC5 in 13q32 is mainly expressed in the mesenchyme of the developing limb bud for upper limb anomalies