Mitochondrial Roles and Cytoprotection in Chronic Liver Injury

The liver is one of the richest organs in terms of number and density of mitochondria. Most chronic liver diseases are associated with the accumulation of damaged mitochondria. Hepatic mitochondria have unique features compared to other organs' mitochondria, since they are the hub that integrates hepatic metabolism of carbohydrates, lipids and proteins. Mitochondria are also essential in hepatocyte survival as mediator of apoptosis and necrosis. Hepatocytes have developed different mechanisms to keep mitochondrial integrity or to prevent the effects of mitochondrial lesions, in particular regulating organelle biogenesis and degradation. In this paper, we will focus on the role of mitochondria in liver physiology, such as hepatic metabolism, reactive oxygen species homeostasis and cell survival. We will also focus on chronic liver pathologies, especially those linked to alcohol, virus, drugs or metabolic syndrome and we will discuss how mitochondria could provide a promising therapeutic target in these contexts

Hypoxia response in Arabidopsis roots infected by Plasmodiophora brassicae supports the development of clubroot

BackgroundThe induction of alcohol fermentation in roots is a plant adaptive response to flooding stress and oxygen deprivation. Available transcriptomic data suggest that fermentation-related genes are also frequently induced in roots infected with gall forming pathogens, but the biological significance of this induction is unclear. In this study, we addressed the role of hypoxia responses in Arabidopsis roots during infection by the clubroot agent Plasmodiophora brassicae.ResultsThe hypoxia-related gene markers PYRUVATE DECARBOXYLASE 1 (PDC1), PYRUVATE DECARBOXYLASE 2 (PDC2) and ALCOHOL DEHYDROGENASE 1 (ADH1) were induced during secondary infection by two isolates of P. brassicae, eH and e2. PDC2 was highly induced as soon as 7 days post inoculation (dpi), i.e., before the development of gall symptoms, and GUS staining revealed that ADH1 induction was localised in infected cortical cells of root galls at 21 dpi. Clubroot symptoms were significantly milder in the pdc1 and pdc2 mutants compared with Col-0, but a null T-DNA insertional mutation of ADH1 did not affect clubroot susceptibility. The Arg/N-end rule pathway of ubiquitin-mediated proteolysis controls oxygen sensing in plants. Mutants of components of this pathway, ate1 ate2 and prt6, that both exhibit constitutive hypoxia responses, showed enhanced clubroot symptoms. In contrast, gall development was reduced in quintuple and sextuple mutants where the activity of all oxygen-sensing Group VII Ethylene Response Factor transcription factors (ERFVIIs) is absent (erfVII and prt6 erfVII).ConclusionsOur data demonstrate that the induction of PDC1 and PDC2 during the secondary infection of roots by P. brassicae contributes positively to clubroot development, and that this is controlled by oxygen-sensing through ERFVIIs. The absence of any major role of ADH1 in symptom development may also suggest that PDC activity could contribute to the formation of galls through the activation of a PDH bypass

Pilot study: The Acceptability of a Program for the Daily Delivery and Supervision of Psychotropic Medication for High-risk Patients with Severe and Persistent Mental Illness

Objective: Forensic outpatients with a history of repeated hospitalization and violence have demonstrated a willingness to voluntarily accept the services of a new, innovative, and recovery-oriented program called Daily Dispensing, which offers daily medication dispensing and supervision. While it appears that patients are amenable to the program, there has been no formal investigation of its acceptability. The purpose of the pilot study was to investigate the acceptability of this intervention to forensic patients and program stakeholders. Methods: We administered to patients and stakeholders surveys about satisfaction, coercion, and/or healthcare and legal outcomes. A crossover design that compares patients’ healthcare services utilization and criminal justice outcomes before and after program enrollment was employed to corroborate the outcomes reported by study participants. Results: Stakeholders’ and patients’ feedback expressed satisfaction with the program and patients generally did not perceive the program as coercive. Stakeholders thought that the program increased medication adherence and decreased the likelihood that patients would end up in hospital or get in trouble with the law. Conclusion: The stakeholders’ and patients’ survey responses supported the acceptability of the program. A formal evaluation of the program’s effects on patients’ crisis service utilization and contact with the criminal justice system is recommended

A functional analysis of ACP-20, an adult-specific cuticular protein gene from the beetle Tenebrio: role of an intronic sequence in transcriptional activation during the late metamorphic period

0962-1075 (Print) Comparative Study Journal Article Research Support, Non-U.S. Gov'tInternational audienceA gene encoding the adult cuticular protein ACP-20 was isolated in Tenebrio. It consists of three exons interspersed by two introns, intron 1 interrupting the signal peptide. To understand the regulatory mechanisms of ACP-20 expression, ACP-20 promoter-luciferase reporter gene constructs were transfected into cultured pharate adult wing epidermis. Transfection assays needed the presence of 20-hydroxyecdysone, confirming that ACP-20 is up-regulated by ecdysteroids. Analysis of 5' deletion constructs revealed that three regions are necessary for high levels of transcription. Interaction experiments between intronic fragments and epidermal nuclear proteins confirmed the importance of intron 1 in ACP-20 transcriptional control, which results from the combined activity of regulatory cis-acting elements of the promoter and those of intron 1

Marker-assisted pyramiding of two cereal cyst nematode resistance genes from Aegilops variabilis in wheat

International audienceThe cereal cyst nematode (CCN) Heterodera avenae, is a significant pathogen of wheat. The wild grass Aegilops variabilis Accession No.1 has been found to be resistant to pathotypes of CCN; at least two genes transferred to wheat, designated as CreX and CreY, are involved in the resistance response. The CreY gene may be the same as Rkn-mn1, which confers resistance to root knot nematode (RKN) Meloidogyne naasi. The objective of this work was to pyramid the two CCN resistance genes in a wheat background through marker-assisted selection. As a first step, molecular markers flanking CreX were identified. The completely linked RAPD marker of Rkn-mn1 (CreY), OpY16-(1065,) previously obtained, was converted into a SCAR. All these dominant markers were used to incorporate in the same genotype the two Ae. variabilis chromosome segments carrying the two genes for resistance. CCN bioassays with the Ha12 pathotype showed that the level of resistance of the pyramided line was significantly higher than that of CreX and CreY single introgression lines, but lower than that of Ae. variabilis. This study thus illustrates the utilization of molecular markers in breeding for host resistanc

Differential growth of Leptosphaeria maculans in the stem of susceptible and partially resistant oilseed rape (Brassica napus L.) genotypes

International audienceQuantitative resistance (QR) to Leptosphaeria maculans in Brassica napus has proven to be very useful for breeding resistant varieties with increased potential for durability. To date, however, QR has been assessed primarily in the field after a long plant developmental cycle and its expression is influenced by environmental conditions. An evaluation method in controlled conditions would offer the possibility to evaluate the level of QR in a shorter time and to study the kinetics of fungal growth in the stem in relation to susceptibility/resistance levels conferred by quantitative trait loci (QTL). We used a cut-petiole inoculation method coupled with both visual and PCR-based phenotyping at different time-points after inoculation, which revealed different kinetics of symptom development and pathogen growth among varieties. The results obtained with this method were partly consistent with field resistance phenotyping data, and allowed detection of the effect of at least two resistance QTL alleles introduced in near-isogenic lines. This method would be useful to compare a wider range of host varieties, to study the spectrum effect of resistance QTL or to decipher the mechanisms underlying this quantitative resistance

Development of 1AS.1AL-1DL durum wheat chromosome carrying Glu-D1a locus encoding high molecular weight glutenin subunits 2 + 12

International audienceHigh molecular weight glutenin subunits (HMW-GS) are well-known to directly influence the bread wheat quality. In a previous paper, our group reported the replacement of the locus Glu-A1 by the locus Glu-D1allele Glu-D1a encoding the HMW-GS (2-12)in a partial isohomoeoallelic lines of the French bread wheat variety cv. Courtot. We plan to exploit the novel translocated 1AS.1AL-1DL chromosome in durum wheat in order to develop durum lines presenting novel properties. The translocated chromosome was first introduced into durum wheat. However, as the distal translocated 1DL segment represents 25% (i.e., 84Mb) of the recombinant 1AL length, it appeared worthwhile to shorten it through homoeologous recombination induced by the ph1c mutation. Two rounds of recombination were made. The shortest interstitial 1DL segment detected through SNP genotyping measured 9.19Mb and could not be visualized by genomic in situ hybridization. Such reduced transfer not previously achieved hitherto provides regularity of the meiotic pairing and will allow the use of those subunits absent in durum wheat species for direct exploitability in breedin

Etude des nourriceries de la Baie de Seine orientale et de l'estuaire de la Seine

This study, carried out from 1995 to 1997, within the framework of "Le Havre" harbour extension project, concerned halieutic populations and the characterization of a coastal nursery in the oriental part of the Seine bay and the Seine estuary . The main objective was to describe the specific and demographic composition of marine populations and their spatio-temporal distribution, and so assess the biological and halieutic role of this area. This study also included a research about the dietary needs of fish juveniles living in the estuary. Autumn and winter surveys results show that the estuary and area under direct influence are the richest from a biological and halieutic point of view. The mouth estuary isthe richest area in terms of diversity of species and marine animals abundance. The Northern area of the estuary ("Fosse Nord") is characterized by a biologic specificity and seems to be important, especially for bass, herring, sole, flounder juveniles and shrimps, which are numerically dominant in this area. We might consider that, regarding the entire zone subject to the survey, which extends up to 20 meters depth in average, the area under 10 m depths is the most favourable for fish juveniles. The proportion of under 2 years old juveniles is high in this area and often reaches more than 90%. The intertidal zone is quite different from the subtidal zone. In the intertidal area we captured only less than 1 year old fishes. They are shorter than the fishesof the same age which are captured in the subtidal area. The results of the surveys show a high interannual abundance variability for most of the species, like bass or soles juveniles. The same observation has been made in other zones like the Somme bay (Eastern Channel). It might be considered as a particular feature of nurseries. In spite of this variability, the characterization of the Seine nursery is based on the observation of the capacity of this zone to receive a large range of fish juveniles. All the species will not be regularly present on the nursery or identically distributed each year. The dietary needs of fish juveniles of 6 species captured in the Seine estuary were studied. The preys which have been identified from stomach contents belongto three major types of environment: mud intertidal benthic, muddy fine sand subtidal benthic of downstream estuary, suprabenthic of estuary and chenal of Seine. Each environment is used by the various predators according to their biological stages. Each length group of fishes has a particular typology of preys. Thus bass, sole, flounder, plaice, pout, and whiting nurseries depend on these three complementary environments which are essential for total dietary availability. This report includes a four page English summary which presents the main results of this study.L'étude, menée de 1995 à 1997 dans le cadre du projet d'extension du Port Autonome du Havre, a porté sur la description des peuplements halieutiques et la caractérisation d'une nourricerie côtière dans l'estuaire et la baie de Seine orientale. Elle a eu pour objectif principal de décrire la composition spécifique et démographique des peuplements marins ainsi que leur distribution spatio-temporelle, et d'évaluer ainsi la fonctionnalité biologique et halieutique de ce site. Cette étude comportait aussi une recherche sur les exigences alimentaires locales des juvéniles de poissons séjournant dans l'estuaire. Les résultats des prospections automnales et hivernales montrent que l'ensemble formé par l'estuaire et sa zone d'influence directe est le plus riche des points de vue biologique et halieutique, les fonds situés juste à la sortie de l'estuaire étant les plus riches en diversité et en abondance. Le secteur estuarien de la Fosse Nord se caractérise par une certaine spécificité biologique et semble jouer un rôle particulièrement important pour les juvéniles de Dicentrarchus labrax, Clupea harengus, Solea solea, Platichthys flesus et pour la crevette grise Crangon crangon, espèces dominantes dans ce secteur. On peut considérer que, par rapport à la totalité du site étudié (jusqu'aux fonds supérieurs à 20 mètres), les fonds de moins de 10 mètres apparaissent comme les plus riches en juvéniles de poissons. La proportion d'individus de moins de 2 ans dans les captures y est élevée et souvent supérieure à 90 %. La zone intertidale, pour sa part, se distingue par la présence exclusive d'individus de moins d'un an dont la taille est inférieure à celle des poissons de même âge pêchés plus au large. Au cours des différentes campagnes est apparue une forte variabilité interannuelle d'abondance de la plupart des espèces, y compris les formes juvéniles de nombreux poissons tels le D. labrax ou S. solea. Cette observation a été faite sur d'autres sites, en particulier la baie de Somme, et doit être considérée comme une caractéristique des nourriceries. Malgré cette variabilité, la caractérisation, désormais sans ambiguïté, d'une nourricerie de Seine s'appuie sur le constat des potentialités du site à abriter une large gamme de juvéniles d'espèces dont toutes ne seront pas régulièrement présentes, ou par exemple distribuées à l'identique, chaque année. L'étude des exigences alimentaires des juvéniles de six espèces de poissons pêchées dans l'estuaire et son embouchure fait apparaître des proies différentes appartenant à trois grands types de milieux : le domaine benthique intertidal vaseux, le domaine benthique subtidal des sables fins envasés de la partie aval de l'estuaire, le domaine suprabenthique plutôt cantonné aux fosses et aux chenaux. Chacun de ces milieux est utilisé par les différents prédateurs à des stades successifs de leur cycle biologique, chaque groupe de taille ayant une typologie particulière de proies. Les nourriceries de bar, de sole, de flet, de plie, de tacaud et de merlan sont ainsi tributaires de ces trois milieux complémentaires qui leur sont indispensables en termes de disponibilité alimentaire globale. * Le présent rapport comporte un résumé de quatre pages, en anglais, présentant les principaux résultats acquis au cours de cette étude

Impact of country of birth on genetic testing of metastatic lung adenocarcinomas in France : African women exhibit a mutational spectrum more similar to Asians than to Caucasians

Background: Limited data are available on the prevalence of oncogenic driver mutations in Caucasian populations, and especially in Europeans. Aim: To evaluate the targetable mutational spectra in unselected patients with lung adenocarcinoma in routine clinical practice from several French hospitals, using the same molecular platform. Patients and Methods: Samples from 2,219 consecutive patients with histologically-proven advanced lung adenocarcinoma were centrally analysed at a referenced and certified diagnostic platform in order to test for activating and resistance mutations in EGFR, KRAS, BRAF, ERBB2 and PI3KCA. Demographic and clinical features were retrieved from the medical charts. Multivariate binary logistic regression was used to determine the independent predictive factors for the occurrence of specific mutations, in the whole study population or in selected subgroups. Findings: The overall respective incidence of EGFR, KRAS, BRAF, ERBB2 and PI3KCA mutations was 10.5%, 0.9%, 25%, 1.5%, 2.1% and 1.4%, in our study sample including 87.4% white Caucasians, 10.8% Africans and 1.8% Asians; 60.6% men, 30.7% never smoker (median age: 68.3 years). Ethnicity was an independent predictor for EGFR, KRAS and ERBB2 gene abnormalities. In all cases, a significantly higher prevalence of targetable EGFR and ERBB2, and a lower prevalence of resistance KRAS mutations were observed in African women as compared to African men or Caucasians. Conclusions: In real life conditions of routine genetic testing, we have identified subsets of patients with specific targetable activating somatic mutations according to ethnicity, who could preferentially benefit from anti-EGFR and anti-ERBB2 targeted therapies