Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
ISSN: 0018-067X

hal-01084548
https://hal-agroparistech.archives-ouvertes.fr/hal-01084548
DOI : 10.1038/hdy.2009.134

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: Homologous recombination is the key process that generates genetic diversity and drives evolution. SPO11 protein triggers recombination by introducing DNA double stranded breaks at discreet areas of the genome called recombination hotspots. The hotspot locations are largely determined by the DNA binding specificity of the PRDM9 protein in human, mice and most other mammals. In budding yeast Saccharomyces cerevisae, which lacks a Prdm9 gene, meiotic breaks are formed opportunistically in the regions of accessible chromatin, primarily at gene promoters. The genome-wide distribution of hotspots in this organism can be altered by tethering Spo11 protein to Gal4 recognition sequences in the strain expressing Spo11 attached to the DNA binding domain of the Gal4 transcription factor. To establish whether similar re-targeting of meiotic breaks can be achieved in PRDM9-containing organisms we have generated a Gal4BD-Spo11 mouse that expresses SPO11 protein joined to the DNA binding domain of yeast Gal4. RESULTS: We have mapped the genome-wide distribution of the recombination initiation sites in the Gal4BD-Spo11 mice. More than two hundred of the hotspots in these mice were novel and were likely defined by Gal4BD, as the Gal4 consensus motif was clustered around the centers in these hotspots. Surprisingly, meiotic DNA breaks in the Gal4BD-Spo11 mice were significantly depleted near the ends of chromosomes. The effect is particularly striking at the pseudoautosomal region of the X and Y chromosomes -- normally the hottest region in the genome. CONCLUSIONS: Our data suggest that specific, yet-unidentified factors influence the initiation of meiotic recombination at subtelomeric chromosomal regions.
ISSN: 1471-2164

inserm-00849779
http://www.hal.inserm.fr/inserm-00849779
http://www.hal.inserm.fr/inserm-00849779/document
http://www.hal.inserm.fr/inserm-00849779/file/1471-2164-14-493.pdf
DOI : 10.1186/1471-2164-14-493

Éditeur(s) : HAL CCSD
Résumé : International audience
In French Guiana, located on the northeastern coast of South America, bats of different species are very numerous. The infection of bats and their ticks with zoonotic bacteria, especially Rickettsia species, is so far unknown. In order to improve knowledge of these zoonotic pathogens in this French overseas department, the presence and diversity of tick-borne bacteria was investigated with molecular tools in bat ticks. In the beginning of 2013, 32 bats were caught in Saint-Jean-du-Maroni, an area close to the coast of French Guiana, and the ticks of these animals were collected. A total of 354 larvae of Argasidae soft ticks (Ornithodoros hasei) from 12 bats (Noctilio albiventris) were collected and 107 of them were analysed. DNA was extracted from the samples and quantitative real-time PCR was carried out to detect Rickettsia spp., Bartonella spp., Borrelia spp. and Coxiella burnetii. All tested samples were negative for Bartonella spp., Borrelia spp. and Coxiella burnetii. Rickettsia DNA was detected in 31 (28.9%) ticks. An almost entire (1118 base pairs long) sequence of the gltA gene was obtained after the amplification of some positive samples on conventional PCR and sequencing. A Bayesian tree was constructed using concatenated rrs, gltA, ompA, ompB, and gene D sequences. The study of characteristic sequences shows that this Rickettsia species is very close (98.3-99.8%) genetically to R. peacockii. Nevertheless, the comparative analysis of sequences obtained from gltA, ompA, ompB, rrs and gene D fragments demonstrated that this Rickettsia is different from the other members of the spotted fever group. The sequences of this new species were deposited in GenBank as Candidatus Rickettsia wissemanii. This is the first report showing the presence of nucleic acid of Rickettsia in Ornithodoros hasei ticks from South American bats. (C) 2016 Elsevier GmbH. All rights reserved.
TICKS AND TICK-BORNE DISEASES

hal-01459758
https://hal.archives-ouvertes.fr/hal-01459758
DOI : 10.1016/j.ttbdis.2016.09.004

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The tree model and tree-based methods have played a major, fruitful role in evolutionary studies. However, with the increasing realization of the quantitative and qualitative importance of reticulate evolutionary processes, affecting all levels of biological organization, complementary network-based models and methods are now flourishing, inviting evolutionary biology to experience a network-thinking era. We show how relatively recent comers in this field of study, that is, sequence-similarity networks, genome networks, and gene families–genomes bipartite graphs, already allow for a significantly enhanced usage of molecular datasets in comparative studies. Analyses of these networks provide tools for tackling a multitude of complex phenomena, including the evolution of gene transfer, composite genes and genomes, evolutionary transitions, and holobionts.
ISSN: 0966-842X

Droits : http://creativecommons.org/licenses/by-nc-nd/
hal-01300043
http://hal.upmc.fr/hal-01300043
http://hal.upmc.fr/hal-01300043/document
http://hal.upmc.fr/hal-01300043/file/Network-Thinking.pdf
DOI : 10.1016/j.tim.2015.12.003

Éditeur(s) : HAL CCSD BioScientifica
Résumé : International audience
Spermatogenesis is a complex and tightly regulated process leading to the continuous production of male gametes, the spermatozoa. This developmental process requires the sequential and coordinated expression of thousands of genes, including many that are testis-specific. The molecular networks underlying normal and pathological spermatogenesis have been widely investigated in recent decades, and many high-throughput expression studies have studied genes and proteins involved in male fertility. In this review, we focus on studies that have attempted to correlate transcription and translation during spermatogenesis by comparing the testicular transcriptome and proteome. We also discuss the recent development and use of new transcriptomic approaches that provide a better proxy for the proteome, from both qualitative and quantitative perspectives. Finally, we provide illustrations of how testis-derived transcriptomic and proteomic data can be integrated to address new questions and how the 'proteomics informed by transcriptomics' technique, by combining RNA-seq and MS-based proteomics, can contribute significantly to the discovery of new protein-coding genes or new protein isoforms expressed during spermatogenesis.
ISSN: 1470-1626

hal-01214005
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01214005
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01214005/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01214005/file/Linking%20transcriptomics%20and%20proteomics%20in%20spermatogenesis.pdf
DOI : 10.1530/REP-15-0073

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Lung cancer is a serious public health problem. Although there has been significant progress in chemotherapy, non-small cell lung cancer is still resistant to current treatments, primarily because of the slow rate of cell development. It is thus important to find new molecules directed against targets other than proliferation agents. Considering the high proportion of mutant proteins in tumor cells, and the high rate of mutation of the TP53 gene in all cancers, and in NSCLC in particular, this gene is a perfect target. Certain new molecules have been shown to restore the activity of mutated p53 protein, for example PRIMA-1, which reactivates the His273 mutant p53. In a previous study, we presented triazine A190, a molecule with a cytostatic activity that blocks cells in the G1 phase and induces apoptosis. Here, we show that A190 not only restores mutant p53 activity, but also induces an overexpression of the NEDD9 gene, leading to apoptotic death. These findings might offer hope for the development of new targeted therapies, specific to tumor cells, which spare healthy cells
ISSN: 2045-2322

hal-01165439
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01165439
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01165439/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01165439/file/TP53%20transcription%20factor.pdf
DOI : 10.1038/srep10356

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The TGF-β transforming growth factor is the most pleiotropic cytokine controlling a broad range of cellular responses that include proliferation, differentiation and apoptosis. The context-dependent multifunctional nature of TGF-β is associated with complex signaling pathways. Differential models describe the dynamics of the TGF-β canonical pathway, but modeling the non-canonical networks constitutes a major challenge. Here, we propose a qualitative approach to explore all TGF-β-dependent signaling pathways. RESULTS: Using a new formalism, CADBIOM, which is based on guarded transitions and includes temporal parameters, we have built the first discrete model of TGF-β signaling networks by automatically integrating the 137 human signaling maps from the Pathway Interaction Database into a single unified dynamic model. Temporal property-checking analyses of 15934 trajectories that regulate 145 TGF-β target genes reveal the association of specific pathways with distinct biological processes. We identify 31 different combinations of TGF-β with other extracellular stimuli involved in non-canonical TGF-β pathways that regulate specific gene networks. Extensive analysis of gene expression data further demonstrates that genes sharing CADBIOM trajectories tend to be co-regulated. CONCLUSIONS: As applied here to TGF-β signaling, CADBIOM allows, for the first time, a full integration of highly complex signaling pathways into dynamic models that permit to explore cell responses to complex microenvironment stimuli.
ISSN: 1752-0509

inserm-00978313
http://www.hal.inserm.fr/inserm-00978313
http://www.hal.inserm.fr/inserm-00978313/document
http://www.hal.inserm.fr/inserm-00978313/file/1752-0509-8-30.pdf
DOI : 10.1186/1752-0509-8-30

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
The retroviral genome consists of an intron-containing transcript that has essential cytoplasmic functions in the infected cell. This viral transcript can escape splicing, circumvent the nuclear checkpoint mechanisms and be transported to the cytoplasm by hijacking the host machinery. Once in the cytoplasm, viral unspliced RNA acts as mRNA to be translated and as genomic RNA to be packaged into nascent viruses. The murine leukemia virus (MLV) is among the first retroviruses discovered and is classified as simple Retroviridae due to its minimal encoding capacity. The oncogenic and transduction abilities of MLV are extensively studied, whereas surprisingly the crucial step of its nuclear export has remained unsolved until 2014. Recent work has revealed the recruitment by MLV of the cellular NXF1/Tap-dependent pathway for export. Unconventionally, MLV uses of Tap to export both spliced and unspliced viral RNAs. Unlike other retroviruses, MLV does not harbor a unique RNA signal for export. Indeed, multiple sequences throughout the MLV genome appear to promote export of the unspliced MLV RNA. We review here the current understanding of the export mechanism and highlight the determinants that influence MLV export. As the molecular mechanism of MLV export is elucidated, we will gain insight into the contribution of the export pathway to the cytoplasmic fate of the viral RNA
ISSN: 1547-6286

hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01217990/file/Insights%20into%20the%20nuclear%20export%20of%20murine%20leukemia%20virus%20intron-containing%20RNA.pdf
DOI : 10.1080/15476286.2015.1065375

Éditeur(s) : HAL CCSD
Résumé : International audience
Smoking is well-known to impair pharmacokinetics, through inducing expression of drug metabolizing enzymes. In the present study, we demonstrated that cigarette smoke condensate (CSC) also alters activity and expression of hepatic drug transporters, which are now recognized as major actors of hepatobiliary elimination of drugs. CSC thus directly inhibited activities of sinusoidal transporters such as OATP1B1, OATP1B3, OCT1 and NTCP as well as those of canalicular transporters like P-glycoprotein, MRP2, BCRP and MATE1, in hepatic transporters-overexpressing cells. CSC similarly counteracted constitutive OATP, NTCP and OCT1 activities in human highly-differentiated hepatic HepaRG cells. In parallel, CSC induced expression of BCRP at both mRNA and protein level in HepaRG cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B1, OATP2B1, OAT2, NTCP, OCT1 and BSEP, and enhanced that of MRP4. Such changes in transporter gene expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin, a reference activator of the aryl hydrocarbon receptor (AhR) pathway, and were counteracted, for some of them, by siRNA-mediated AhR silencing. This suggests that CSC alters hepatic drug transporter levels via activation of the AhR cascade. Importantly, drug transporter expression regulations as well as some transporter activity inhibitions occurred for a range of CSC concentrations similar to those required for inducing drug metabolizing enzymes and may therefore be hypothesized to be relevant for smokers. Taken together, these data established human hepatic transporters as targets of cigarette smoke, which could contribute to known alteration of pharmacokinetics and some liver adverse effects caused by smoking. © 2016 Elsevier Ireland Ltd
Toxicology

hal-01367143
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01367143
DOI : 10.1016/j.tox.2016.07.011
PUBMED : 27450509

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Subcutaneous fat tissues from an indigenous fat-type breed and an intensively-lean selected breed were studied in juvenile pigs. Combining DIGE with bioinformatics and target analyses of key genes, enzymes or terminal routes, this study identifies metabolic and homeostatic processes, response to organic substances, and acute-phase responses as the main pathways whose proteins were regulated in association with adiposity. Breed-related differences in abundance and activities of malic enzyme and glucose-6-phosphate dehydrogenase NADPH-supplying enzymes suggested up-regulation of the lipogenic pathway to dispose for a greater adiposity. Over-abundance in the lipolytic protein carboxylesterase-1 was revealed in fat-type piglets. A panel of pro- and anti-inflammatory proteins such as serpins, had an altered abundance in the fat-type piglets, suggesting adverse consequences of fat accumulation even in early post-weaning stages. Propensity to low-grade inflammation in fat pigs was reinforced by the up-regulation of genes encoding pro-inflammatory cytokines IL6 and TNF-α in these piglets. Differential abundance in annexin-A5 and pericentrin suggested a positive regulation of cell apoptosis in lean piglets. Our results are relevant in the context of data linking the accretion of body lipids to the physiology and pathology of adipose tissue in models other than rodents for a better control of human health and nutrition.
ISSN: 1874-3919

hal-01122161
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122161
PUBMED : 22061664
DOI : 10.1016/j.jprot.2011.10.012

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Analysis of microbial biodiversity is hampered by a lack of reference genomes from most bacteria, viruses, and algae. This necessitates either the cultivation of a restricted number of species for standard sequencing projects or the analysis of highly complex environmental DNA metagenome data. Single-cell genomics (SCG) offers a solution to this problem by constraining the studied DNA sample to an individual cell and its associated symbionts, prey, and pathogens. We used SCG to study marine heterotrophic amoebae related to Paulinella ovalis (A. Wulff) P.W. Johnson, P.E. Hargraves & J.M. Sieburth (Rhizaria). The genus Paulinella is best known for its photosynthetic members such as P.chromatophora Lauterborn that is the only case of plastid primary endosymbiosis known outside of algae and plants. Here, we studied the phagotrophic sister taxa of P.chromatophora that are related to P.ovalis and found one SCG assembly to contain -cyanobacterial DNA. These cyanobacterial contigs are presumably derived from prey. We also uncovered an associated cyanophage lineage (provisionally named phage PoL_MC2). Phylogenomic analysis of the fragmented genome assembly suggested a minimum genome size of 200Kbp for phage PoL_MC2 that encodes 179 proteins and is most closely related to Synechococcus phage S-SM2. For this phage, gene network analysis demonstrates a highly modular genome structure typical of other cyanophages. Our work demonstrates that SCG is a powerful approach for discovering algal and protist biodiversity and for elucidating biotic interactions in natural samples.
ISSN: 0022-3646

hal-01544797
https://hal.archives-ouvertes.fr/hal-01544797
DOI : 10.1111/jpy.12028

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : We aimed to enhance understanding of the molecular diversity of arbuscular mycorrhizal fungi (AMF) by building a new global dataset targeting previously unstudied geographical areas. In total, we sampled 96 plant species from 25 sites that encompassed all continents except Antarctica. AMF in plant roots were detected by sequencing the nuclear SSU rRNA gene fragment using either cloning followed by Sanger sequencing or 454-sequencing. A total of 204 AMF phylogroups (virtual taxa, VT) were recorded, increasing the described number of Glomeromycota VT from 308 to 341 globally. Novel VT were detected from 21 sites; three novel but nevertheless widespread VT (Glomus spp. MO-G52, MO-G53, MO-G57) were recorded from six continents. The largest increases in regional VT number were recorded in previously little-studied Oceania and in the boreal and polar climatic zones - this study providing the first molecular data from the latter. Ordination revealed differences in AM fungal communities between different continents and climatic zones, suggesting that both biogeographic history and environmental conditions underlie the global variation of those communities. Our results show that a considerable proportion of Glomeromycota diversity has been recorded in many regions, though further large increases in richness can be expected in remaining unstudied areas.
ISSN: 0940-6360

hal-01190520
https://hal.archives-ouvertes.fr/hal-01190520
DOI : 10.1007/s00572-013-0482-2
PRODINRA : 206968

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Whilst it used to affect mostly intravenous drug users and patients who underwent valvular surgery with suboptimal infection control procedures, fungal endocarditis is now mostly observed in patients with severe immunodeficiency (onco-haematology), in association with chronic central venous access and broad-spectrum antibiotic use. The incidence of fungal endocarditis has probably decreased in most developed countries with access to harm-reduction policies (i.e. needle exchange programmes) and with improved infection control procedures during cardiac surgery. Use of specific blood culture bottles for diagnosis of fungal endocarditis has decreased due to optimisation of media and automated culture systems. Meanwhile, the advent of rapid techniques, including fungal antigen detection (galactomannan, mannan/anti-mannan antibodies and β-1,3-d-glucans) and PCR (e.g. universal fungal PCR targeting 18S rRNA genes), shall improve sensitivity and reduce diagnostics delays, although limited data are available on their use for the diagnosis of fungal endocarditis. New antifungal agents available since the early 2000s may represent dramatic improvement for fungal endocarditis: (i) a new class, the echinocandins, has the potential to improve the management of Candida endocarditis owing to its fungicidal effect on yeasts as well as tolerability of increased dosages; and (ii) improved survival in patients with invasive aspergillosis with voriconazole compared with amphotericin B, and this may apply to Aspergillus sp. endocarditis as well, although its prognosis remains dismal. These achievements may allow selected patients to be cured with prolonged medical treatment alone when surgery is considered too risky.
ISSN: 0924-8579

hal-01118441
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118441
DOI : 10.1016/j.ijantimicag.2014.07.003
PUBMED : 25178919

Résumé : Le maintien de ressources génétiques suffisamment larges est nécessaire pour assurer la viabilité et le potentiel évolutif des populations naturelles. Cette thèse a le principal objectif de caractériser la diversité et la variabilité génétique chez le genre Virola (Myristicaceae) pour décrire les processus évolutifs qui en sont à l'origine. Premièrement,une étude de la régénération d'un échantillonnage exhaustif de V. michelii a été menée dans une parcelle du dispositif expérimental de Paracou ayant subi une exploitation forestière de faible intensité et comparée à une parcelle témoin. La diversité génétique mesurée à partir de marqueurs AFLP (Amplified Fragment-Length Polymorphism, N=229) en zones perturbées s'est révélée être plis grande qu'en zone non-perturbées. Puis, l'adaptation locale a été étudiée à travers ces mêmes individus et certains loci (AFLP) montrent une sélection divergente pour des environnements contrastés, indiquant un signe d'adaptation. Enfin, l'étude des niveaux de divergence génétique chez trois espèces de Virola du bouclier guyanais (V. michelii, V. surinamensis et V. kwatae) montrent que deux d'entre elles (V. surinamensis et V. kwatae) montrent de fortes similarités génétiques malgré leur distribution sur des environnements contrastés. des Flux de gènes intersécifiques ont été mis en évidence chez ces deux espèces-soeurs et l'hypothèse d'une spéciation écologique est avancée. Ce travail a permis d'aborder différents processus évolutifs à l'origine de la diversité génétique actuelle chez ces espèces forestières tropicales et peut fournir une contribution pour appréhender le devenir des populations.
Genetic diversity is an essential component of biodiversity. The maintenance of sufficient genetic resources is needed to ensure the adaptive potential and the viability of natural populations. In the current context of global changes, the study of adaptation in living organisms is a key task, particularly for tropical forest trees that are dominant components (in terms of biomass and as ecological drivers) of some of the most diverse ecosystems on Earth. The main objective of this thesis is to characterize genetic diversity and genetic variability to understand the evolutionary processes that act on them. This ecological-genetic study was carried out at the interspecific and intraspecific level in the Virola genus.If overall high levels of genetic diversity are a guarantee of prosperity for the future of the species, it seems essential to perform studies on the impact of environmental disturbance on genetic diversity. In the first section, the genetic consequences of regeneration dynamics were studied in an exhaustive sample of V. michelii in a low-intensity logging plot and in a control plot at the Paracou experimental site. A greater genetic diversity, measured from AFLP markers (Amplified Fragment Length Polymorphism, N = 229), was found in perturbed areas. Because studying genetic diversity within species may be useful for understanding species adaptation to environmental changes, in the second section. I studied local adaptation in a population of V. michelii on the Paracou experimental site. A genome scan approach with AFLPs (N = 229) was conducted on 77 adult individuals and 401 juveniles to identify genetic differences between populations associated to contrasting conditions for an array of environmental variables. Some loci (N = 2) were found to be subject to divergent selection, indicating adaptation to contrasting habitats.In the third section, the study of levels of genetic divergence in three Virola species of the Guiana Shield (V. michelii, V. surinamensis and V. kwatae) was investigated for nuclear and chloroplast molecular markers. V. surinamensis and V. kwatae showed strong genetic similarities despite their contrasting habitats preferences. Coalescent analyses have revealed, on one hand, a recent divergence between these two species suggesting an ecological speciation, and one the other hand that interspecific gene flow occurs between these sister-species.This work focuses on understanding evolutionary processes shaping genetic diversity and provides a useful contribution for biodiversity conservation programs.

http://www.theses.fr/2011AGUY0480/document

Éditeur(s) : HAL CCSD Oxford University Press
Résumé : International audience
We present gene prioritization system (GPSy), a cross-species gene prioritization system that facilitates the arduous but critical task of prioritizing genes for follow-up functional analyses. GPSy's modular design with regard to species, data sets and scoring strategies enables users to formulate queries in a highly flexible manner. Currently, the system encompasses 20 topics related to conserved biological processes including male gamete development discussed in this article. The web server-based tool is freely available at http://gpsy.genouest.org.
ISSN: 0305-1048

inserm-00696905
http://www.hal.inserm.fr/inserm-00696905
http://www.hal.inserm.fr/inserm-00696905/document
http://www.hal.inserm.fr/inserm-00696905/file/nar.gks380.full.pdf
DOI : 10.1093/nar/gks380

Éditeur(s) : HAL CCSD Impact journals
Résumé : International audience
Targeted therapies have substantially changed the management of non-small cell lung cancer (NSCLC) patients with driver oncogenes. Given the high frequency, EGFR and ALK aberrations were the first to be detected and paved the way for tyrosine kinase inhibitor (TKI) treatments. Other kinases such as ROS1 and more recently RET have emerged as promising targets, and ROS1 and RET TKIs are already available for precision medicine. We screened a large cohort of 713 Caucasian non-squamous NSCLC patients lacking EGFR/KRAS/BRAF/HER2/PI3KCA/ALK aberrations for ROS1 and RET rearrangements using fluorescence in situ hybridization to determine the frequency and clinicopathological characteristics of ROS1- and RET-positive patients. Frequencies of ROS1 and RET rearrangements were 2.1% and 2.52%, respectively. Contrary to common belief, both ROS1 and RET rearrangements were detected in patients with a history of smoking, and the RET-positive patients were not younger than the negative patients. Moreover, RET but not ROS1 rearrangement was associated with the female gender. Nearly half of the ROS1-rearranged patients were successfully treated with ROS1 TKIs. In contrast, only 5/18 RET-positive patients received off-label RET TKIs. Two patients had stable disease, and three experienced disease progression. In addition to the 18 RET-positive cases, 10 showed isolated 5' signals. The clinical relevance is unknown but if the frequency is confirmed by other groups, the question whether these patients are eligible to TKIs will arise. More potent RET TKIs are under development and may improve the response rate in RET-positive patients. Therefore, we recommend the routine implementation of RET testing in non-squamous NSCLC patients, including those with a history of smoking.
ISSN: 1949-2553

hal-01578586
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01578586
DOI : 10.18632/oncotarget.18408
PUBMED : 28881815

Éditeur(s) : HAL CCSD MDPI AG, Basel, Switzerland
Résumé : International audience
Abstract View references (46)This work shows the preparation of silica membranes by a two-step sol-gel method using tetraethyl orthosilicate in ethanolic solution by employing nitric acid and ammonia as co-catalysts. The sols prepared in pH 6 resulted in the lowest concentration of silanol (Si-OH) species to improve hydrostability and the optimized conditions for film coating. The membrane was tested to desalinate 0.3-15 wt % synthetic sodium chloride (NaCl) solutions at a feed temperature of 22 °C followed by long term membrane performance of up to 250 h in 3.5 wt % NaCl solution. Results show that the water flux (and salt rejection) decrease with increasing salt concentration delivering an average value of 9.5 kg m-2 h-1 (99.6%) and 1.55 kg m-2 h-1 (89.2%) from the 0.3 and 15 wt % saline feed solutions, respectively. Furthermore, the permeate salt concentration was measured to be less than 600 ppm for testing conditions up to 5 wt % saline feed solutions, achieving below the recommended standard for potable water. Long term stability shows that the membrane performance in water flux was stable for up to 150 h, and slightly reduced from thereon, possibly due to the blockage of large hydrated ions in the micropore constrictions of the silica matrix. However, the integrity of the silica matrix was not affected by the long term testing as excellent salt rejection of >99% was maintained for over 250 h. © 2013 by the authors; licensee MDPI, Basel, Switzerland.
ISSN: 2077-0375

hal-01683203
https://hal.univ-antilles.fr/hal-01683203
DOI : 10.3390/membranes3030136

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
This work relates to the characterisation of the predominant gill protein of the white clam, Codakia orbicularis (Linné, 1758), which harbours endosymbiotic sulphur-oxidising chemoautotrophic bacteria. Total RNA was extracted from the clam to perform 3'rapid amplification of cDNA ends (3'RACE) using degenerate oligonucleotides prepared from a partial sequence of a predominant protein of about 14kDa, termed codakine. The partial peptide sequence was obtained by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and Edman degradation. Clones isolated from the cDNA library and containing the gene of interest were used in polymerase chain reaction (PCR). The PCR and RACE-PCR products were sequenced to determine the entire coding DNA sequence of codakine. BLAST analysis revealed about 23% to 29% sequence identity between codakine and various animal C-type lectins that are often involved in symbiosis and immune defences. Codakine also contains the motifs and domains of Ca(2+)-dependent C-type lectins, and in particular the tripeptide EPN motif frequently found in mannose-binding lectins (MBLs). Analysis of the protein by affinity chromatography on a mannose-agarose column is consistent with the findings that codakine is a dimeric Ca(2+)-dependent MBL of about 29kDa. Based on the present results, it is hypothesised that this novel C. orbicularis gill protein is involved in the recognition of symbiotic and pathogenic bacteria.
ISSN: 1050-4648

hal-00746015
https://hal.univ-antilles.fr/hal-00746015
DOI : 10.1016/j.fsi.2006.06.013
PUBMED : 17169576

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.
ISSN: 1098-3600

hal-01134364
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01134364
DOI : 10.1038/gim.2015.29
PUBMED : 25790162

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Despite the unique nature of endemic species, their origin and population history remain poorly studied. We investigated the population history of 28 coral reef fish species, close related, from the Gambier and Marquesas Islands, from five families, with range size varying from widespread to small-range endemic. We analyzed both mitochondrial and nuclear sequence data using neutrality test and Bayesian analysis (EBSP and ABC). We found evidence for demographic expansions for most species (24 of 28), irrespective of range size, reproduction strategy or archipelago. The timing of the expansions varied greatly among species, from 8,000 to 2,000,000 years ago. The typical hypothesis for reef fish that links population expansions to the Last Glacial Maximum fit for 14 of the 24 demographic expansions. We propose two evolutionary processes that could lead to expansions older than the LGM: (a) we are retrieving the signature of an old colonization process for widespread, large-range endemic and paleoendemic species or (b) speciation; the expansion reflects the birth of the species for neoendemic species. We show for the first time that the demographic histories of endemic and widespread reef fish are not distinctly different and suggest that a number of processes drive endemism.
ISSN: 2045-2322

hal-01469339
https://hal-univ-perp.archives-ouvertes.fr/hal-01469339
https://hal-univ-perp.archives-ouvertes.fr/hal-01469339/document
https://hal-univ-perp.archives-ouvertes.fr/hal-01469339/file/population%20expansions.pdf
DOI : 10.1038/srep40519