Combining QTL mapping and transcriptomics to decipher the genetic architecture of phenolic compounds metabolism in the conifer white spruce

Conifer forests worldwide are becoming increasingly vulnerable to the effects of climate change. Although the production of phenolic compounds (PCs) has been shown to be modulated by biotic and abiotic stresses, the genetic basis underlying the variation in their constitutive production level remains poorly documented in conifers. We used QTL mapping and RNA-Seq to explore the complex polygenic network underlying the constitutive production of PCs in a white spruce (Picea glauca) full-sib family for 2 years. QTL detection was performed for nine PCs and differentially expressed genes (DEGs) were identified between individuals with high and low PC contents for five PCs exhibiting stable QTLs across time. A total of 17 QTLs were detected for eightmetabolites, including one major QTL explaining up to 91.3% of the neolignan-2 variance. The RNA-Seq analysis highlighted 50 DEGs associated with phenylpropanoid biosynthesis, several key transcription factors, and a subset of 137 genes showing opposite expression patterns in individuals with high levels of the flavonoids gallocatechin and taxifolin glucoside. A total of 19 DEGs co-localized with QTLs. Our findings represent a significant step toward resolving the genomic architecture of PC production in spruce and facilitate the functional characterization of genes and transcriptional networks responsible for differences in constitutive production of PCs in conifers.National Sciences and Engineering Research Council of Canada, the Spruce-Up LSARP project with funding from Genome Canada and Genome Quebec and Genomics Research and Development Initiative of Canada.http://www.frontiersin.org/Plant_Scienceam2022Forestry and Agricultural Biotechnology Institute (FABI)Zoology and Entomolog

SAR Studies Leading to the Identification of a Novel Series of Metallo-β-lactamase Inhibitors for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections That Display Efficacy in an Animal Infection Model

The clinical effectiveness of carbapenem antibiotics such as meropenem is becoming increasingly compromised by the spread of both metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) enzymes on mobile genetic elements, stimulating research to find new β-lactamase inhibitors to be used in conjunction with carbapenems and other β-lactam antibiotics. Herein, we describe our initial exploration of a novel chemical series of metallo-β-lactamase inhibitors, from concept to efficacy, in a survival model using an advanced tool compound (ANT431) in conjunction with meropenem

The Pharmacology of Xenobiotics after Intracerebro Spinal Fluid Administration: Implications for the Treatment of Brain Tumors

International audienceThe incidence of brain metastasis has been increasing for 10 years, with poor prognosis, unlike the improvement in survival for extracranial tumor localizations. Since recent advances in molecular biology and the development of specific molecular targets, knowledge of the brain distribution of drugs has become a pharmaceutical challenge. Most anticancer drugs fail to cross the blood–brain barrier. In order to get around this problem and penetrate the brain parenchyma, the use of intrathecal administration has been developed, but the mechanisms governing drug distribution from the cerebrospinal fluid to the brain parenchyma are poorly understood. Thus, in this review we discuss the pharmacokinetics of drugs after intrathecal administration, their penetration of the brain parenchyma and the different systems causing their efflux from the brain to the blood

Exogenous Isoprene Confers Physiological Benefits in a Negligible Isoprene Emitter (Acer monspessulanum L.) Under Water Deficit

International audienceIsoprene, the main volatile released by plants, is known to protect the photosynthetic apparatus in isoprene emitters submitted to oxidative pressures caused by environmental constraints. Whether ambient isoprene contributes to protect negligible plant emitters under abiotic stress conditions is less clear, and no study has tested if ambient isoprene is beneficial during drought periods in plant species that naturally release negligible isoprene emissions. This study examines the effect of exogenous isoprene (20 ppbv) on net photosynthesis, stomatal conductance and production of H2O2 (a reactive oxygen species: ROS) in leaves of Acer monspessulanum (a negligible isoprene emitter) submitted to three watering treatments (optimal, moderate water stress and severe water stress). Results showed that A. monspessulanum exhibited a net photosynthesis increase (+30%) and a relative leaf H2O2 decrease when saplings were exposed to an enriched isoprene atmosphere compared to isoprene-free conditions under moderate water deficit. Such physiological improvement under isoprene exposure was not observed under optimal watering or severe water stress. These findings suggest that when negligible isoprene emitters are surrounded by a very high concentration of isoprene in the ambient air, some plant protection mechanism occurs under moderate water deficit probably related to protection against ROS damage eventually impeding photosynthesis drop

Integrated platform for home services using new products and services for senior citizens Call CNAV-CARSAT 2015.

International audienceThis project is part of: i) the risks of ageing prevention policy of the French retirement and occupational health insurance agency of Languedoc Roussillon (Carsat-LR) and ii) the European innovation partnership on active and healthy ageing (EIP on AHA). It aims to support senior citizens who live independently and have been identified at risk of frailty on a social or health level. The purpose is to increase legibility as well as technical and financial access to innovations for vulnerable seniors who are remote from the digital era, through a multiservice user-friendly platform. Launched at the end of 2015, the project rallies over 10 actors of the silver economy currently developing personalised ICT tools to improve the safety and comfort of seniors and the coordination between health and social care. The objective is threefold: i) developing new adapted technologies, ii) having them evaluated by retirees and professionals and iii) making them accessible to the ICT web platform which will provide tutorials and prices and collect opinions from users and professionals. 500 retirees selected by CARSAT-LR will be testing these new devices and solutions which will be provided without charge. The following will be evaluated: i) feedback from users; ii) benefits gained through accessing comprehensive and appropriate information; iii) coordination of caregivers and professionals; iv) enjoyment from using the products (access to games, social links, customer confidence, sense of safety). This is a unique opportunity to mobilise solutions in a structured manner, bringing together competing businesses under a consortium agreement. Advantages for these businesses include acceleration of development and availability of their adapted solutions as well as the possibility to test their products on a significant panel of people. Professional caregiver's data follow-up will identify seniors at risk of frailty, proposing preventive actions and local services tailored to their needs

Higher levels of Pseudomonas aeruginosa LasB elastase expression are associated with early-stage infection in cystic fibrosis patients

Abstract Pseudomonas aeruginosa is a common pathogen in cystic fibrosis (CF) patients and a major contributor to progressive lung damage. P. aeruginosa elastase (LasB), a key virulence factor, has been identified as a potential target for anti-virulence therapy. Here, we sought to differentiate the P. aeruginosa isolates from early versus established stages of infection in CF patients and to determine if LasB was associated with either stage. The lasB gene was amplified from 255 P. aeruginosa clinical isolates from 70 CF patients from the Toulouse region (France). Nine LasB variants were identified and 69% of the isolates produced detectable levels of LasB activity. Hierarchical clustering using experimental and clinical data distinguished two classes of isolates, designated as ‘Early’ and ‘Established’ infection. Multivariate analysis revealed that the isolates from the Early infection class show higher LasB activity, fast growth, tobramycin susceptibility, non-mucoid, pigmented colonies and wild-type lasR genotype. These traits were associated with younger patients with polymicrobial infections and high pFEV1. Our findings show a correlation between elevated LasB activity in P. aeruginosa isolates and early-stage infection in CF patients. Hence, it is this patient group, prior to the onset of chronic disease, that may benefit most from novel therapies targeting LasB

The germline genetics of mild-to-moderate penetrance: An intriguing role of PRAME in multiple carcinogenesis

International audienc

The evolution of resistance and tolerance as cancer defences

International audienceAlthough there is a plethora of cancer associated-factors that can ultimately culminate in death (cachexia, organ impairment, metastases, opportunistic infections, etc.), the focal element of every terminal malignancy is the failure of our natural defences to control unlimited cell proliferation. The reasons why our defences apparently lack efficiency is a complex question, potentially indicating that, under Darwinian terms, solutions other than preventing cancer progression are also important contributors. In analogy with host-parasite systems, we propose to call this latter option ‘tolerance’ to cancer. Here, we argue that the ubiquity of oncogenic processes among metazoans is at least partially attributable to both the limitations of resistance mechanisms and to the evolution of tolerance to cancer. Deciphering the ecological contexts of alternative responses to the cancer burden is not a semantic question, but rather a focal point in understanding the evolutionary ecology of host-tumour relationships, the evolution of our defences, as well as why and when certain cancers are likely to be detrimental for survival

Increased risk of brain metastases among patients with melanoma and PROM2 expression in metastatic lymph nodes

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