Publications by authors named "Mathieu Gautier"

131 Publications

Phosphorus retention by granulated apatite: assessing maximum retention capacity, kinetics and retention processes.

Water Sci Technol 2021 Feb;83(4):792-802

Inrae, REVERSAAL Research Unit, 5 rue de la Doua, Villeurbanne 69100, France E-mail:

Natural apatites have previously shown a great capacity for phosphate retention from wastewater. However, its fine particle size distribution may lead to a premature clogging of the filter. Accordingly, a granulated apatite product was developed and manufactured in order to control the particle size distribution of the media. Experiments were conducted on laboratory columns to assess their phosphorus retention capacity, to identify the processes involved in phosphorus retention and to evaluate their kinetic rates. The results showed phosphorus retention capacities of 10.5 and 12.4 g PO-P·kg and kinetic rate coefficients in the range of 0.63 and 0.23 h involving lower values than those found for natural apatites in previous studies. Scanning Electron Microscopy images showed that apatite particles in the granules were embedded in the binder and were not readily accessible to act as seeds for calcium phosphate precipitation. The retention processes differ depending on the supersaturation of the solution with respect to calcium phosphate phases: at low calcium concentrations (69.8 ± 3.9 mg·L), hydroxyapatite precipitates fill up the porosity of the binder up to a depth of 100-300 μm from the granule surface; at higher calcium concentrations (112.7 ± 7.4 mg·L) precipitation occurs at the granule surface, forming successive layers of hydroxyapatite and carbonated calcium phosphates.
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http://dx.doi.org/10.2166/wst.2021.010DOI Listing
February 2021

High-dose rate brachytherapy in localized penile cancer: 5-Year clinical outcome analysis.

Clin Transl Radiat Oncol 2021 Mar 17;27:89-95. Epub 2021 Jan 17.

Department of Radiation Therapy, Antoine Lacassagne Cancer Center and University of Nice-Sophia, Nice, France.

Purpose: To analyze the oncological outcome and toxicity profile after conservative treatment based on multicatheter interstitial high-dose rate brachytherapy (MHB) for patients presenting a localized penile cancer.

Materials And Methods: Patients with histologically proven, non-metastatic (T1-T2 N0-N2 M0) localized penile cancer were treated with MHB. Needles were placed under general anesthesia into the target volume using a dedicated template. Treatment planning was performed using a post-implant CT-scan to deliver 35 Gy or 39 Gy (9f, 5d) for adjuvant or definitive treatment respectively. Five-year oncological outcome was evaluated with local relapse-free (LRFS), regional relapse-free (RRFS), and metastasis-free survival (MFS), specific (SS) and overall survival (OS). In pre-treatment and follow-up consultations, skin, urinary and sexual toxicities were investigated using CTCAEv4.0 classification, International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5-items (IIEF-5). Dosimetry data were also analyzed.

Results: From 03/2006 to 05/2020, with a median follow-up of 72.4 months [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], 29 pts, mainly T1 (75.9%) and N0 (89.7%), underwent MHB. Eleven (38%) and 18 pts (62%) received MHB as adjuvant or definitive treatment respectively. Five-year LRFS, RRFS, MFS, SS and OS were 82%, 82%, 89%, 88% and 73% respectively. Six patients (20.7%) experienced local relapse and underwent salvage penectomy leading to a penile preservation rate of 79.3%. Acute skin toxicity was reported 1 month after MHB, with 28% G1, 66% G2 and 6% G3. Late skin complications were telangiectasia for 5 pts (17%) and necrosis for 3 pts (10.3% requiring hyperbaric oxygen therapy). Comparing pre- and post-treatment status, no significant change was observed for skin appearance, IPSS and IIEF-5.

Conclusion: MHB represents an efficient first line conservative treatment option for early penile cancers. Oncological outcome and late toxicity profile appear encouraging. However, larger-scale cohorts with longer follow-up are needed to more accurately precise the features of the best candidate to MHB.
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http://dx.doi.org/10.1016/j.ctro.2020.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841215PMC
March 2021

Mg Transporters in Digestive Cancers.

Nutrients 2021 Jan 13;13(1). Epub 2021 Jan 13.

Université de Picardie Jules Verne, UFR des Sciences, UR-UPJV 4667, F-80000 Amiens, France.

Despite magnesium (Mg) representing the second most abundant cation in the cell, its role in cellular physiology and pathology is far from being elucidated. Mg homeostasis is regulated by Mg transporters including Mitochondrial RNA Splicing Protein 2 (MRS2), Transient Receptor Potential Cation Channel Subfamily M, Member 6/7 (TRPM6/7), Magnesium Transporter 1 (MAGT1), Solute Carrier Family 41 Member 1 (SCL41A1), and Cyclin and CBS Domain Divalent Metal Cation Transport Mediator (CNNM) proteins. Recent data show that Mg transporters may regulate several cancer cell hallmarks. In this review, we describe the expression of Mg transporters in digestive cancers, the most common and deadliest malignancies worldwide. Moreover, Mg transporters' expression, correlation and impact on patient overall and disease-free survival is analyzed using Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Finally, we discuss the role of these Mg transporters in the regulation of cancer cell fates and oncogenic signaling pathways.
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http://dx.doi.org/10.3390/nu13010210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828344PMC
January 2021

Temperature, rainfall and wind variables underlie environmental adaptation in natural populations of Drosophila melanogaster.

Mol Ecol 2021 02 26;30(4):938-954. Epub 2021 Jan 26.

Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra), Barcelona, Spain.

While several studies in a diverse set of species have shed light on the genes underlying adaptation, our knowledge on the selective pressures that explain the observed patterns lags behind. Drosophila melanogaster is a valuable organism to study environmental adaptation because this species originated in Southern Africa and has recently expanded worldwide, and also because it has a functionally well-annotated genome. In this study, we aimed to decipher which environmental variables are relevant for adaptation of D. melanogaster natural populations in Europe and North America. We analysed 36 whole-genome pool-seq samples of D. melanogaster natural populations collected in 20 European and 11 North American locations. We used the BayPass software to identify single nucleotide polymorphisms (SNPs) and transposable elements (TEs) showing signature of adaptive differentiation across populations, as well as significant associations with 59 environmental variables related to temperature, rainfall, evaporation, solar radiation, wind, daylight hours, and soil type. We found that in addition to temperature and rainfall, wind related variables are also relevant for D. melanogaster environmental adaptation. Interestingly, 23%-51% of the genes that showed significant associations with environmental variables were not found overly differentiated across populations. In addition to SNPs, we also identified 10 reference transposable element insertions associated with environmental variables. Our results showed that genome-environment association analysis can identify adaptive genetic variants that are undetected by population differentiation analysis while also allowing the identification of candidate environmental drivers of adaptation.
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http://dx.doi.org/10.1111/mec.15783DOI Listing
February 2021

Unsupervised Hierarchical Clustering of Pancreatic Adenocarcinoma Dataset from TCGA Defines a Mucin Expression Profile that Impacts Overall Survival.

Cancers (Basel) 2020 11 9;12(11). Epub 2020 Nov 9.

Univ. Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, F-59000 Lille, France.

Mucins are commonly associated with pancreatic ductal adenocarcinoma (PDAC) that is a deadly disease because of the lack of early diagnosis and efficient therapies. There are 22 mucin genes encoding large -glycoproteins divided into two major subgroups: membrane-bound and secreted mucins. We investigated mucin expression and their impact on patient survival in the PDAC dataset from The Cancer Genome Atlas (PAAD-TCGA). We observed a statistically significant increased messenger RNA (mRNA) relative level of most of the membrane-bound mucins (), secreted mucins (), and atypical mucins () compared to normal pancreas. We show that mRNA levels are associated with poorer survival in the high-expression group compared to the low-expression group. Using unsupervised clustering analysis of mucin gene expression patterns, we identified two major clusters of patients. Cluster #1 harbors a higher expression of and atypical /, whereas cluster #2 is characterized by a global overexpression of membrane-bound mucins (). Cluster #2 is associated with shorter overall survival. The patient stratification appears to be independent of usual clinical features (tumor stage, differentiation grade, lymph node invasion) suggesting that the pattern of membrane-bound mucin expression could be a new prognostic marker for PDAC patients.
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http://dx.doi.org/10.3390/cancers12113309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697168PMC
November 2020

Accelerated partial breast irradiation in the elderly: 8-year oncological outcomes and prognostic factors.

Brachytherapy 2021 Jan-Feb;20(1):146-154. Epub 2020 Oct 29.

Department of Radiation Oncology, Antoine Lacassagne Cancer Center & University of Cote d'Azur, Nice, France. Electronic address:

Purpose: The purpose of the study is to evaluate long-term clinical outcomes and prognostic factors after accelerated partial breast irradiation (APBI) in the elderly using high-dose-rate interstitial multicatheter brachytherapy (HIBT).

Methods And Materials: Between 2005 and 2018, 109 patients underwent APBI using HIBT (34 Gy/10f/5d or 32 Gy/8f/4d). Based on a prospective database, outcomes were retrospectively analyzed (local relapse-free survival, metastatic-free survival, specific survival (SS), and overall survival (OS)). Prognostic factors were investigated. Late toxicity and cosmetic evaluation were reported.

Results: With a median followup of 97 months [7-159], median age was 81.7 years [58-89]. In accordance with the GEC-ESTRO APBI classification, 72.5%, 11.9%, and 15.6% were classified as low, intermediate, and high risk, respectively. The histological type was mainly invasive ductal carcinoma (87.1%). The median tumor size was 10 mm [range 1-35]. Eight-year local relapse-free survival, SS, and OS were 96.7% [95% confidence interval (CI) [0.923; 1]), 96.7% [95% CI [0.924; 1], and 72% [95% CI [0.616; 0.837], respectively. In univariate analysis, APBI classification was not considered as prognostic factor, whereas molecular classification was prognostic factor for OS (p < 0.0001), SS (p = 0.007), and metastatic-free survival (p = 0.009) but not for local recurrence (p = 0.586). No Grade ≥3 late toxicity was observed, whereas 61 patients (88.4%) and 8 patients (11.6%) presented Grade 1 and 2 toxicities, respectively. The cosmetic outcome was excellent/good for 96.4%.

Conclusions: Long-term followup confirms that HIBT is safe and effective for elderly early breast cancer. Our results suggest that selected elderly women presenting with high-risk breast cancer could be also considered for APBI.
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http://dx.doi.org/10.1016/j.brachy.2020.08.012DOI Listing
October 2020

TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration.

Front Cell Dev Biol 2020 8;8:549. Epub 2020 Jul 8.

Laboratoire de Physiologie Cellulaire et Moléculaire - UR-UPJV 4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), Amiens, France.

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a very poor prognosis due to highly metastatic profile. Cell migration is an essential step of the metastatic cascade allowing cancer cells to spread toward target tissues. Recent studies strongly suggest that bioactive elastin peptides, also named elastokines or elastin-derived peptides (EDPs), are released in the extracellular microenvironment during tumoral remodeling of the stroma. EDPs stimulate cancer cell migration by interacting with their membrane receptor, ribosomal protein SA (RPSA). Others membrane proteins like ion channels are also involved in cancer cell migration. It has been recently shown that the transient receptor potential melastatin-related 7 (TRPM7) channel regulates PDAC cell migration and invasion. The objective of this work was to study the effect of EDPs on TRPM7 channel in human pancreatic cancer cells. We showed that EDPs promote MIA PaCa-2 cell migration using Boyden chamber assay. Cells transfected with a siRNA targeting TRPM7 were not able to migrate in response to EDPs indicating that TRPM7 regulated cell migration induced by these peptides. Moreover, EDPs were able to stimulate TRPM7 currents recorded by Patch-Clamp. Finally, we showed that TRPM7 channels and RPSA receptors are colocalized at the plasma membrane of human pancreatic cancer cells. Taken together, our data suggest that TRPM7/RPSA complex regulated human pancreatic cancer cell migration. This complex may be a promising therapeutic target in PDAC.
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http://dx.doi.org/10.3389/fcell.2020.00549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360683PMC
July 2020

French vertical flow treatment wetlands in a subtropical climate: Characterization of the organic deposit layer and comparison with systems in France.

Sci Total Environ 2020 Nov 30;742:140608. Epub 2020 Jun 30.

Department of Sanitary and Environmental Engineering, Federal University of Minas Gerais, 6627 Antônio Carlos Ave., Engineering School, Room 4622, 31270-901 Belo Horizonte, Brazil. Electronic address:

This paper presents an advanced characterization of the organic fraction of the top deposit layer collected in a French vertical flow treatment wetland (first stage) in operation in Brazil (two units with different organic deposit layer accumulation times), and compares the results with those obtained from studies in France. The organic and inorganic constituents of the samples collected were analysed by biological, chemical and thermochemical methods. The unit with the organic deposit with longer accumulation time (almost 10 years) was characterized as a mature one (organic matter - OM: 51.3 and 52.7%, thermal index - R: 0.79 and 0.85, humification index - HI: 0.61 and 1.16, respectively for the depths of 0-5 cm and 5-10 cm). The unit with the deposit organic with less than three years of accumulation also presented characteristics of a mature deposit (OM: 61.2%, R: 0.79, HI: 1.01 for the depth of 0-5 cm), indicating a rapid mineralization of the deposit under the existing subtropical environment. Despite several differences in term of conception, hydraulic and mass loading rates and accumulation rates, the characteristics of the OM of Brazilian deposits were found to be quite similar to the French ones.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140608DOI Listing
November 2020

Near-chromosome level genome assembly of the fruit pest Drosophila suzukii using long-read sequencing.

Sci Rep 2020 07 8;10(1):11227. Epub 2020 Jul 8.

Aix-Marseille Université, CNRS, IBDM, Institut de Biologie du Développement de Marseille, Marseille Cedex 9, France.

Over the past decade, the spotted wing Drosophila, Drosophila suzukii, has invaded Europe and America and has become a major agricultural pest in these areas, thereby prompting intense research activities to better understand its biology. Two draft genome assemblies already exist for this species but contain pervasive assembly errors and are highly fragmented, which limits their values. Our purpose here was to improve the assembly of the D. suzukii genome and to annotate it in a way that facilitates comparisons with D. melanogaster. For this, we generated PacBio long-read sequencing data and assembled a novel, high-quality D. suzukii genome assembly. It is one of the largest Drosophila genomes, notably because of the expansion of its repeatome. We found that despite 16 rounds of full-sib crossings the D. suzukii strain that we sequenced has maintained high levels of polymorphism in some regions of its genome. As a consequence, the quality of the assembly of these regions was reduced. We explored possible origins of this high residual diversity, including the presence of structural variants and a possible heterogeneous admixture pattern of North American and Asian ancestry. Overall, our assembly and annotation constitute a high-quality genomic resource that can be used for both high-throughput sequencing approaches, as well as manipulative genetic technologies to study D. suzukii.
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http://dx.doi.org/10.1038/s41598-020-67373-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343843PMC
July 2020

Exome-wide association study reveals largely distinct gene sets underlying specific resistance to dengue virus types 1 and 3 in Aedes aegypti.

PLoS Genet 2020 05 28;16(5):e1008794. Epub 2020 May 28.

Insect-Virus Interactions Unit, Institut Pasteur, UMR2000, CNRS, Paris, France.

Although specific interactions between host and pathogen genotypes have been well documented in invertebrates, the identification of host genes involved in discriminating pathogen genotypes remains a challenge. In the mosquito Aedes aegypti, the main dengue virus (DENV) vector worldwide, statistical associations between host genetic markers and DENV types or strains were previously detected, but the host genes underlying this genetic specificity have not been identified. In particular, it is unknown whether DENV type- or strain-specific resistance relies on allelic variants of the same genes or on distinct gene sets. Here, we investigated the genetic architecture of DENV resistance in a population of Ae. aegypti from Bakoumba, Gabon, which displays a stronger resistance phenotype to DENV type 1 (DENV-1) than to DENV type 3 (DENV-3) infection. Following experimental exposure to either DENV-1 or DENV-3, we sequenced the exomes of large phenotypic pools of mosquitoes that are either resistant or susceptible to each DENV type. Using variation in single-nucleotide polymorphism (SNP) frequencies among the pools, we computed empirical p values based on average gene scores adjusted for the differences in SNP counts, to identify genes associated with infection in a DENV type-specific manner. Among the top 5% most significant genes, 263 genes were significantly associated with resistance to both DENV-1 and DENV-3, 287 genes were only associated with DENV-1 resistance and 290 were only associated with DENV-3 resistance. The shared significant genes were enriched in genes with ATP binding activity and sulfur compound transmembrane transporter activity, whereas the genes uniquely associated with DENV-3 resistance were enriched in genes with zinc ion binding activity. Together, these results indicate that specific resistance to different DENV types relies on largely non-overlapping sets of genes in this Ae. aegypti population and pave the way for further mechanistic studies.
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http://dx.doi.org/10.1371/journal.pgen.1008794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282673PMC
May 2020

A Whole-Genome Scan for Association with Invasion Success in the Fruit Fly Drosophila suzukii Using Contrasts of Allele Frequencies Corrected for Population Structure.

Mol Biol Evol 2020 08;37(8):2369-2385

INRAE, UMR CBGP (INRAE-IRD-Cirad - Montpellier SupAgro), Montferrier-sur-Lez, France.

Evidence is accumulating that evolutionary changes are not only common during biological invasions but may also contribute directly to invasion success. The genomic basis of such changes is still largely unexplored. Yet, understanding the genomic response to invasion may help to predict the conditions under which invasiveness can be enhanced or suppressed. Here, we characterized the genome response of the spotted wing drosophila Drosophila suzukii during the worldwide invasion of this pest insect species, by conducting a genome-wide association study to identify genes involved in adaptive processes during invasion. Genomic data from 22 population samples were analyzed to detect genetic variants associated with the status (invasive versus native) of the sampled populations based on a newly developed statistic, we called C2, that contrasts allele frequencies corrected for population structure. We evaluated this new statistical framework using simulated data sets and implemented it in an upgraded version of the program BayPass. We identified a relatively small set of single-nucleotide polymorphisms that show a highly significant association with the invasive status of D. suzukii populations. In particular, two genes, RhoGEF64C and cpo, contained single-nucleotide polymorphisms significantly associated with the invasive status in the two separate main invasion routes of D. suzukii. Our methodological approaches can be applied to any other invasive species, and more generally to any evolutionary model for species characterized by nonequilibrium demographic conditions for which binary covariables of interest can be defined at the population level.
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http://dx.doi.org/10.1093/molbev/msaa098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403613PMC
August 2020

Cadmium exposure enhances cell migration and invasion through modulated TRPM7 channel expression.

Arch Toxicol 2020 03 20;94(3):735-747. Epub 2020 Feb 20.

Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), 80039, Amiens, France.

Cadmium is a xenobiotic involved in neoplastic transformation. Cadmium enters the cells through divalent cation transporters including the Transient Receptor Potential Melastatin-related 7 (TRPM7) which is known to be involved in cancer cell fate. This work aimed to study the role of TRPM7 in neoplastic transformation induced by cadmium exposure in non-cancer epithelial cells. Non-cancer epithelial cells were chronically exposed to low-dose of cadmium. TRPM7 expression and function were studied by Western-Blot, Patch-Clamp and calcium and magnesium imaging. Finally, cell migration and invasion were studied by Boyden chamber assays. Chronic cadmium exposure induced TRPM7 overexpression and increased the membrane currents (P < 0.001). Cells exposed to cadmium had higher intracellular calcium and magnesium levels (P < 0.05). TRPM7 silencing restored calcium levels but strongly decreased intracellular magnesium concentration (P < 0.001). Moreover, cadmium exposure enhanced both cell migration and invasion, but TRPM7 silencing strongly decreased these features (P < 0.001). Furthermore, mammary epithelial cells exposed to cadmium became rounded and had less cell-to-cell junctions. Cadmium exposure decreased epithelial markers while the mesenchymal ones were increased. Importantly, TRPM7 silencing was able to reverse these phenotypic modifications (P < 0.05). To summarize, our data show that chronic cadmium exposure enhanced TRPM7 expression and activity in non-cancer epithelial cells. TRPM7 overexpression induced intracellular magnesium increase and stimulated cell migration and invasion. These neoplastic properties could be linked to a TRPM7-dependent epithelial-to-mesenchymal transition reprogramming in cell exposed to cadmium. These findings provide new insights into the regulation of cell fates by cadmium exposure.
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http://dx.doi.org/10.1007/s00204-020-02674-wDOI Listing
March 2020

Genomic Footprints of Recovery in the European Bison.

J Hered 2020 04;111(2):194-203

INRAE, UMR CBGP (INRAE-IRD-Cirad-Montpellier SupAgro), Montferrier-sur-Lez, France.

After extinction in the wild in the beginning of the 20th century, the European bison has been successfully recovered in 2 distinct genetic lines from only 12 and 7 captive founders. We here aimed at characterizing the levels of realized inbreeding in these 2 restored lines to provide empirical insights into the genomic footprints left by population recovery from a small number of founders. To that end, we genotyped 183 European bison born over the last 40 years with the Illumina BovineHD beadchip that contained 22 602 informative autosomal single-nucleotide polymorphisms after data filtering. We then identified homozygous-by-descent (HBD) segments and classified them into different age-related classes relying on a model-based approach. As expected, we observed that the strong and recent founder effect experienced by the 2 lines resulted in very high levels of recent inbreeding and in the presence of long HBD tracks (up to 120 Mb). These long HBD tracks were associated with ancestors living approximately from 4 to 32 generations in the past, suggesting that inbreeding accumulated over multiple generations after the bottleneck. The contribution to inbreeding of the most recent groups of ancestors was however found to be decreasing in both lines. In addition, comparison of Lowland individuals born at different time periods showed that the levels of inbreeding tended to stabilize, HBD segments being shorter in animals born more recently which indicates efficient control of inbreeding. Monitoring HBD segment lengths over generations may thus be viewed as a valuable genomic diagnostic tool for populations in conservation or recovery programs.
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http://dx.doi.org/10.1093/jhered/esaa002DOI Listing
April 2020

Five-year oncological outcome after a single fraction of accelerated partial breast irradiation in the elderly.

Radiat Oncol 2019 Dec 21;14(1):234. Epub 2019 Dec 21.

Department of Radiation Oncology, University of Côte d'Azur, Fédération Claude Lalanne, Nice, France.

Background: To update the clinical outcome of an elderly women cohort with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose-rate brachytherapy (MIB).

Material And Methods: A single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB APBI. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 5 years was reported based on local relapse free survival (LRFS), specific survival (SS) and overall survival (OS). Late toxicity was evaluated. Cosmetic results were evaluated clinically by the physician.

Results: Between January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65-92) with a median tumor size of 12 mm (range: 3-32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow-up of 64 months (range: 56-71), no local relapse occurred while 1 pt. developed an axillary relapse (2.1%). No Grade 3 or higher late toxicity was observed while 16 late toxicities occurred (G1: 14 events [87.5%) mainly G1 breast fibrosis). The rate of excellent cosmetic outcome was 76.4%.

Conclusion: We confirmed the safety of the process and remained encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a very APBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report.
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http://dx.doi.org/10.1186/s13014-019-1448-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925849PMC
December 2019

Simulation-Based Evaluation of Three Methods for Local Ancestry Deconvolution of Non-model Crop Species Genomes.

G3 (Bethesda) 2020 02 6;10(2):569-579. Epub 2020 Feb 6.

INRAE, UMR CBGP, F-34988 Montferrier-sur-Lez Cedex, France

Hybridizations between species and subspecies represented major steps in the history of many crop species. Such events generally lead to genomes with mosaic patterns of chromosomal segments of various origins that may be assessed by local ancestry inference methods. However, these methods have mainly been developed in the context of human population genetics with implicit assumptions that may not always fit plant models. The purpose of this study was to evaluate the suitability of three state-of-the-art inference methods (SABER, ELAI and WINPOP) for local ancestry inference under scenarios that can be encountered in plant species. For this, we developed an R package to simulate genotyping data under such scenarios. The tested inference methods performed similarly well as far as representatives of source populations were available. As expected, the higher the level of differentiation between ancestral source populations and the lower the number of generations since admixture, the more accurate were the results. Interestingly, the accuracy of the methods was only marginally affected by i) the number of ancestries (up to six tested); ii) the sample design (, unbalanced representation of source populations); and iii) the reproduction mode (, selfing, vegetative propagation). If a source population was not represented in the data set, no bias was observed in inference accuracy for regions originating from represented sources and regions from the missing source were assigned differently depending on the methods. Overall, the selected ancestry inference methods may be used for crop plant analysis if all ancestral sources are known.
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http://dx.doi.org/10.1534/g3.119.400873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003078PMC
February 2020

Accelerated partial breast irradiation in the elderly: 5-Year results of the single fraction elderly breast irradiation (SiFEBI) phase I/II trial.

Brachytherapy 2020 Jan - Feb;19(1):90-96. Epub 2019 Nov 23.

Department of Radiation Oncology, Antoine Lacassagne Cancer Center, University of Cote d'Azur, Nice, France.

Purpose: To evaluate the clinical outcomes of a very-accelerated partial breast irradiation (vAPBI) in the elderly based on a single fraction of multicatheter interstitial high-dose rate brachytherapy (MIB). Mature results with a median follow-up of 5 years.

Methods And Materials: From November 2012 to September 2014, 26 patients (pts) (≥70) with early breast cancer were enrolled in a prospective phase II trial (NCT01727011). After lumpectomy, intraoperative catheter implant was performed for postoperative APBI (single fraction 16 Gy). Surveillance was performed twice a year after APBI. Oncologic outcome (local [LRFS], metastasis-free survival, cancer-specific survival, and overall survival [OS]) as well as late toxicity and cosmetic outcome were investigated.

Results: Median age was 77 years [69-89]. After a median follow-up of 63 months [60-68], 5-year LRFS, metastasis-free survival, cancer-specific survival, and overall survival rates were 100%, 95.5%, 100%, and 88.5%, respectively. Late toxicity was observed in 5 pts (19.2%) with a total of five events: 3 pts G1 (60%); and 2 pts G2 (40%). The observed late side effects were breast pain in 1 pt (G2 cytosteatonecrosis with occasional acetaminophen consumption), hypopigmentation (puncture site) in 2 pts (G1) and breast fibrosis in 2 pts (G1: 1 pt; G2: 1 pt). Cosmetic evaluation was excellent for 21 pts (81%) and good for 2 pts (19%).

Conclusion: For elderly with early breast cancer, a vAPBI using a single fraction of postoperative MIB (16 Gy) provides excellent oncologic results, mainly in terms of local control and cancer death. Late toxicity and cosmetic profile are acceptable.
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http://dx.doi.org/10.1016/j.brachy.2019.10.007DOI Listing
September 2020

Coronary angiography in the setting of acute infective endocarditis requiring surgical treatment.

Arch Cardiovasc Dis 2020 Jan 13;113(1):50-58. Epub 2019 Nov 13.

Department of Cardiology, Rangueil University Hospital, 31059 Toulouse, France. Electronic address:

Background: International guidelines recommend that preoperative coronary angiography is performed on patients at risk of coronary disease who have infective endocarditis requiring surgical treatment. However, the risks of contrast-induced nephropathy or vegetation embolization in case of aortic endocarditis should be considered.

Aims: To assess the safety, therapeutic implications and prognostic impact of coronary angiography in patients requiring surgical treatment for active infective endocarditis.

Methods: This retrospective monocentric study was conducted in patients referred to a tertiary care centre for active endocarditis management with a theoretical indication for surgery between January 2013 and February 2017.

Results: One hundred and ninety-three patients were included; 73.1% were men, the mean age was 61.9±16.3 years and the median EuroSCORE II was 5.8%. One hundred and nineteen patients (61.7%) had aortic endocarditis, which was associated with aortic vegetation in 74 cases (38.3%). Invasive coronary angiography was performed in 142 patients (73.6%) - 130 (91.6%) by radial approach - and 14 patients were evaluated by coronary multislice computed tomography (one patient had exploration with both techniques). Acute renal failure after coronary angiography was observed in 15 patients (10.6%), two patients (1.4%) presented a stroke within 24h after coronary angiography, but none had aortic endocarditis. Among the 178 patients (92.2%) who underwent surgery, 35 (19.7%) had significant coronary lesion(s) and 25 (14.0%) underwent an associated coronary artery bypass graft.

Conclusions: Preoperative coronary angiography in patients affected by infective endocarditis provides relevant information in a significant proportion of patients and can be performed safely.
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http://dx.doi.org/10.1016/j.acvd.2019.09.007DOI Listing
January 2020

Ca channels in cancer.

Cell Calcium 2019 Dec 26;84:102083. Epub 2019 Sep 26.

Laboratoire de Physiologie Cellulaire et Moléculaire - EA4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), F-80039, Amiens, France.

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http://dx.doi.org/10.1016/j.ceca.2019.102083DOI Listing
December 2019

Ca homeostasis and cancer.

Cell Calcium 2019 Dec 26;84:102084. Epub 2019 Sep 26.

Laboratoire de Physiologie Cellulaire et Moléculaire - EA4667, UFR Sciences, Université de Picardie Jules Verne (UPJV), F-80039, Amiens, France.

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http://dx.doi.org/10.1016/j.ceca.2019.102084DOI Listing
December 2019

[Legal issues surrounding data protection].

Soins 2019 Sep;64(838):36-39

Cabinet Vatier, 41, avenue de Friedland, 75008 Paris, France. Electronic address:

Protecting personal information provided by a patient must now be automatic for all health professionals, whether they work in a health or medical-social facility or in private practice, alone or alongside other professionals. While their level of responsibility may vary depending on the chosen method of practice, the health professional is an essential link in the chain with regard to data security as well as patients' rights. Understanding what constitutes personal information or sensitive information and the different obligations resulting from its processing is essential in order to be able to comply with data security and protection regulations imposed by French and European law.
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http://dx.doi.org/10.1016/j.soin.2019.06.007DOI Listing
September 2019

Combination of Lagrangian Discrete Phase Model and sediment physico-chemical characteristics for the prediction of the distribution of trace metal contamination in a stormwater detention basin.

Sci Total Environ 2020 Jan 3;698:134263. Epub 2019 Sep 3.

Univ Lyon, INSA Lyon, DEEP, F-69621 Villeurbanne Cedex, France.

Elevated trace metal concentrations in sediments pose a major problem for the management of stormwater detention basins. These basins provide a nature-based solution to remove particulate pollutants through settling, but the resuspension of these contaminated deposits may impact the quality of both surface and groundwater. A better understanding of trace metal distribution will help to improve basin design and sediment management. This study aims to predict the distribution of trace metal contamination in a stormwater detention basin through (i) investigation of the correlation between metal content in sediments and their settling velocity, and (ii) the coupling of such correlation with a Lagrangian Discrete Phase Model (LDPM). The correlation between Fe, Cr, Cu, Ni, Pb contents and the settling velocity is firstly investigated, based on the sediments collected from 6 sites (inlet and 5 traps at the bottom of a detention basin situated in Chassieu, France) during 5 campaigns in 2017. Results show that Fe is strongly correlated to settling velocity and can be considered as a good indicator of trace metal contents. The derived correlation is then combined with a LDPM for the prediction of trace metal distribution, producing results consistent with in situ measurements. The proposed methodology can be applied for other stormwater basins (dry or wet). As described in this article, the interactions between hydrodynamics and sediment physico-chemical characteristics is crucial for the design and management of stormwater detention basins, allowing managers to target the highest contaminated sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2019.134263DOI Listing
January 2020

Oviposition Preference and Larval Performance of Drosophila suzukii (Diptera: Drosophilidae), Spotted-Wing Drosophila: Effects of Fruit Identity and Composition.

Environ Entomol 2019 08;48(4):867-881

CBGP, INRA, CIRAD, IRD, Montpellier SupAgro, Univ Montpellier, Montpellier, France.

A better understanding of the factors affecting host plant use by spotted-wing drosophila (Drosophila suzukii) could aid in the development of efficient management tools and practices to control this pest. Here, proxies of both preference (maternal oviposition behavior) and performance (adult emergence) were evaluated for 12 different fruits in the form of purees. The effect of the chemical composition of the fruits on preference and performance traits was then estimated. We synthesized the literature to interpret our findings in the light of previous studies that measured oviposition preference and larval performance of D. suzukii. We show that fruit identity influences different parts of the life cycle, including oviposition preference under both choice and no-choice conditions, emergence rate, development time, and number of emerging adults. Blackcurrant was always among the most preferred fruit we used, while grape and tomato were the least preferred fruits. Larvae performed better in cranberry, raspberry, strawberry, and cherry than in the other fruits tested. We found that fruit chemical compounds can explain part of the effect of fruit on D. suzukii traits. In particular, oviposition preference under choice conditions was strongly influenced by fruit phosphorus content. In general, the consensus across studies is that raspberry, blackberry, and strawberry are among the best hosts while blackcurrant, grape and rose hips are poor hosts. Our results generally confirm this view but also suggest that oviposition preferences do not necessarily match larval performances. We discuss opportunities to use our results to develop new approaches for pest management.
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http://dx.doi.org/10.1093/ee/nvz062DOI Listing
August 2019

Ion Channels: New Actors Playing in Chemotherapeutic Resistance.

Cancers (Basel) 2019 Mar 16;11(3). Epub 2019 Mar 16.

Laboratoire de Physiologie Cellulaire et Moléculaire (EA 4667), Université de Picardie Jules Verne, UFR des Sciences, 33 Rue St Leu, 80039 Amiens, France.

In the battle against cancer cells, therapeutic modalities are drastically limited by intrinsic or acquired drug resistance. Resistance to therapy is not only common, but expected: if systemic agents used for cancer treatment are usually active at the beginning of therapy (i.e., 90% of primary breast cancers and 50% of metastases), about 30% of patients with early-stage breast cancer will have recurrent disease. Altered expression of ion channels is now considered as one of the hallmarks of cancer, and several ion channels have been linked to cancer cell resistance. While ion channels have been associated with cell death, apoptosis and even chemoresistance since the late 80s, the molecular mechanisms linking ion channel expression and/or function with chemotherapy have mostly emerged in the last ten years. In this review, we will highlight the relationships between ion channels and resistance to chemotherapy, with a special emphasis on the underlying molecular mechanisms.
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http://dx.doi.org/10.3390/cancers11030376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468599PMC
March 2019

Efficacy and tolerance of high-dose-rate brachytherapy boost after external radiotherapy in the treatment of squamous cell carcinoma of the anal canal.

J Contemp Brachytherapy 2018 Dec 28;10(6):522-531. Epub 2018 Dec 28.

Department of Radiation Oncology, Centre Antoine Lacassagne.

Purpose: The aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachytherapy (HDR-BT) boost in anal squamous cell carcinoma (ASCC).

Material And Methods: This was a monocentric retrospective study involving patients treated by external irradiation (± chemotherapy), with HDR-BT boost, for a localized ASCC. Clinical evaluation was performed every six months. Oncological results were analyzed with: local relapse-free survival (LRFS), colostomy-free survival (CFS), metastatic-free survival (MFS), disease-free survival (DFS), and overall survival (OS). Acute and late toxicities were collected (CTCV4.0) and LENT/SOMA score was performed.

Results: From May 2005 to January 2018, 46 patients (pts) were analyzed. The median follow-up was 61 months (10-145 months), the median age was 65 years (34-84 years), with a sex ratio M/F = 0.24. The TNM classification was as follows: T1 - 13 pts (21.7%), T2 - 34 pts (73.9%), T3 - 2 pts (4.3%), N+ - 6 pts (13.1%). External beam radiotherapy (EBRT) delivered a median dose of 45 Gy (36-50.4 Gy) in 25 fractions, and HDR-BT 12 Gy (10-18 Gy) in 3 fractions. The median overall treatment time (OTT) was 58 days (41-101 days), with a median EBRT/brachytherapy interval of 17 days (4-60 days). Oncological findings showed 5-year rates of LRFS 81.2%, MFS 88.7%, DFS 70%, and OS 90%. All abdominoperineal amputations were performed in case of local relapse (4 pts, 8.7%), leading to a 5-year CFS of 79.5%. Acute urinary toxicities were frequent (G1 41.3%, G2 4.3%). The acute digestive toxicities were: G1 71.7%, G2 6.5%, and G3 2.2%. The late urinary toxicities were: G1 4.3%, G2 2.2%, and G3 2.2%. Late digestive toxicities were: G1 56.5%, G2 8.7%, G3 2.2%, and G4 2.2%.

Conclusions: In ASCC management, HDR-BT boost appears to be a treatment with a long-term acceptable toxicity profile, shorter than EBRT boost, with a reduction of side effects.
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http://dx.doi.org/10.5114/jcb.2018.81025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6335558PMC
December 2018

A genomic map of climate adaptation in Mediterranean cattle breeds.

Mol Ecol 2019 03;28(5):1009-1029

CBGP, INRA, CIRAD, IRD, University of Montpellier, Montferrier-sur-Lez, France.

Domestic species such as cattle (Bos taurus taurus and B. t. indicus) represent attractive biological models to characterize the genetic basis of short-term evolutionary response to climate pressure induced by their post-domestication history. Here, using newly generated dense SNP genotyping data, we assessed the structuring of genetic diversity of 21 autochtonous cattle breeds from the whole Mediterranean basin and performed genome-wide association analyses with covariables discriminating the different Mediterranean climate subtypes. This provided insights into both the demographic and adaptive histories of Mediterranean cattle. In particular, a detailed functional annotation of genes surrounding variants associated with climate variations highlighted several biological functions involved in Mediterranean climate adaptation such as thermotolerance, UV protection, pathogen resistance or metabolism with strong candidate genes identified (e.g., NDUFB3, FBN1, METTL3, LEF1, ANTXR2 and TCF7). Accordingly, our results suggest that main selective pressures affecting cattle in Mediterranean area may have been related to variation in heat and UV exposure, in food resources availability and in exposure to pathogens, such as anthrax bacteria (Bacillus anthracis). Furthermore, the observed contribution of the three main bovine ancestries (indicine, European and African taurine) in these different populations suggested that adaptation to local climate conditions may have either relied on standing genomic variation of taurine origin, or adaptive introgression from indicine origin, depending on the local breed origins. Taken together, our results highlight the genetic uniqueness of local Mediterranean cattle breeds and strongly support conservation of these populations.
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http://dx.doi.org/10.1111/mec.15004DOI Listing
March 2019

Preliminary insights into the genetics of bank vole tolerance to Puumala hantavirus in Sweden.

Ecol Evol 2018 Nov 26;8(22):11273-11292. Epub 2018 Oct 26.

CBGP, INRA, CIRAD, IRD, Montpellier SupAgro Univ. Montpellier Montpellier France.

Natural reservoirs of zoonotic pathogens generally seem to be capable of tolerating infections. Tolerance and its underlying mechanisms remain difficult to assess using experiments or wildlife surveys. High-throughput sequencing technologies give the opportunity to investigate the genetic bases of tolerance, and the variability of its mechanisms in natural populations. In particular, population genomics may provide preliminary insights into the genes shaping tolerance and potentially influencing epidemiological dynamics. Here, we addressed these questions in the bank vole , the specific asymptomatic reservoir host of Puumala hantavirus (PUUV), which causes nephropathia epidemica (NE) in humans. Despite the continuous spatial distribution of in Sweden, NE is endemic to the northern part of the country. Northern bank vole populations in Sweden might exhibit tolerance strategies as a result of coadaptation with PUUV. This may favor the circulation and maintenance of PUUV and lead to high spatial risk of NE in northern Sweden. We performed a genome-scan study to detect signatures of selection potentially correlated with spatial variations in tolerance to PUUV. We analyzed six bank vole populations from Sweden, sampled from northern NE-endemic to southern NE-free areas. We combined candidate gene analyses (, , and genes) and high-throughput sequencing of restriction site-associated DNA (RAD) markers. Outlier loci showed high levels of genetic differentiation and significant associations with environmental data including variations in the regional number of NE human cases. Among the 108 outliers that matched to mouse protein-coding genes, 14 corresponded to immune-related genes. The main biological pathways found to be significantly enriched corresponded to immune processes and responses to hantavirus, including the regulation of cytokine productions, TLR cascades, and IL-7, VEGF, and JAK-STAT signaling. In the future, genome-scan replicates and functional experimentations should enable to assess the role of these biological pathways in tolerance to PUUV.
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http://dx.doi.org/10.1002/ece3.4603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6262921PMC
November 2018

Brachytherapy versus external beam radiotherapy boost for prostate cancer: Systematic review with meta-analysis of randomized trials.

Cancer Treat Rev 2018 Nov 11;70:265-271. Epub 2018 Oct 11.

Department of Radiotherapy, Centre Antoine Lacassagne, University of Cote d'Azur, Nice, France. Electronic address:

Background: Brachytherapy boost after external beam radiotherapy for intermediate and high-risk prostate cancer is presented as an attractive technique in numerous retrospective and prospective studies. Currently, three randomized controlled trials comparing brachytherapy versus external beam radiotherapy boost used non-homogenous irradiation features. Therefore, we analyzed the oncological outcomes by a systematic review with meta-analysis of the randomized controlled trials.

Methods: We performed a systematic literature review of MEDLINE and COCHRANE databases up to 30/04/10 and we considered all published randomized controlled trials comparing brachytherapy versus external beam radiotherapy boost for intermediate and high-risk prostate cancer according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The review was assessed using Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool and the identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT). Eight publications from 3 RCTs were selected.

Results: There was a significant benefit in 5-year biochemical-progression-free survival in favor of BT versus EBRT boost (HR: 0.49 [95% CI, 0.37-0.66], p < 0.01). There was no difference at 5 years in overall survival (HR: 0.92 [95% CI, 0.64-1.33], p = 0.65), ≥ grade 3 late genito-urinary (RR: 2.19 [95%CI, 0.76-6.30], p = 0.15) and late gastro-intestinal toxicities (RR: 1.85 [95%CI, 1.00-3.41] p = 0.05).

Conclusion: This meta-analysis provides further evidence in favor of BT boost for intermediate and high-risk prostate cancer in terms of b-PFS improvement, leading to suggest BT boost as level I and grade A recommendation. However, the risk of grade ≥ 3 late toxicity must be carefully investigated.
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http://dx.doi.org/10.1016/j.ctrv.2018.10.004DOI Listing
November 2018

Single fraction of accelerated partial breast irradiation in the elderly: early clinical outcome.

Radiat Oncol 2018 Sep 12;13(1):174. Epub 2018 Sep 12.

Department of Radiation Oncology, Centre Antoine Lacassagne - University of Cote d'Azur, 33 avenue de Valombrose, 06000, Nice, France.

Background: To analyze the clinical outcome of elderly women with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose-rate brachytherapy (MIB).

Methods: A single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 3 years was reported based on local relapse free survival (3-y LRFS), specific survival (SS) and overall survival (OS). Acute (< 180 days after APBI) and late toxicity were evaluated. Cosmetic results were clinically evaluated by the physician.

Results: Between January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65-92) with a median tumor size of 12 mm (range: 3-32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow-up of 40 months (range: 36-42), no local relapse occurred while 1 pt. developed axillary relapse (2.1%). The 3-y LRFS, SS and OS rates were 100%, 100% and 93.1% respectively. Forty-five acute events were remained. The most frequent acute toxicity was grade (G) 1 hyperpigmentation (26.7%), 3 pts. (6.3%) presented G3 acute toxicity (2 breast hematomas, 1 breast abscess). No ≥ G3 late toxicity was observed while 15 late toxicities occurred (G1: 13 events - 86.7%) mainly breast fibrosis). The rate of excellent cosmetic outcome was 76.4%.

Conclusion: We reported promising and encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a sfAPBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report. More mature results (number of patients and follow-up) are needed.
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http://dx.doi.org/10.1186/s13014-018-1119-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136182PMC
September 2018

Leaching behavior of major and trace elements from sludge deposits of a French vertical flow constructed wetland.

Sci Total Environ 2019 Feb 27;649:544-553. Epub 2018 Aug 27.

Univ Lyon, INSA Lyon, DEEP (Déchets Eaux Environnement Pollutions), EA 7429, 69621 Villeurbanne Cedex, France.

Surface sludge deposits were collected from a French Vertical Flow Constructed Wetland (French VFCW) sewage treatment plant. The objectives were to characterize the retention of major elements and trace metals within the sludge deposits particles under regular operating conditions, and the influence of extreme pH conditions on their potential release which may occur in situations when the plant malfunctions or after land application of the dredged sludge. A sequential extraction protocol was first used to assess the distribution of the elements within the sludge deposits. Results showed that most of Cu and Pb were associated to organic matter within the oxidizable fraction. Zn, Ni and Cd were distributed in several fractions, notably bound to Fe-Mn oxides and associated to organic matter. Cr was analyzed mostly in the residual fraction. Aliquot fractions of sludge deposits were also submitted to Acid and Base Neutralization Capacity tests (ANC-BNC) where the samples were suspended into acidic or alkaline aqueous solutions, and the solutions analyzed after 48 h contact time. Results showed a pH-dependent leaching profile for all monitored elements. The role of organic matter was observed for almost all metals. It was particularly dominant for Cu which was leached more extensively under alkaline than acidic conditions. Since Cu is not an amphoteric element, this leaching pattern was attributed to the leaching of organic matter which followed a similar pH-dependent profile than Cu. Spectrometric indices were used to characterize soluble organic compounds. Results showed that complex and humified dissolved organic compounds were mostly released under alkaline conditions.
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http://dx.doi.org/10.1016/j.scitotenv.2018.08.364DOI Listing
February 2019

The Genomic Basis of Color Pattern Polymorphism in the Harlequin Ladybird.

Curr Biol 2018 10 23;28(20):3296-3302.e7. Epub 2018 Aug 23.

Aix Marseille Université, CNRS, IBDM, Marseille, France. Electronic address:

Many animal species comprise discrete phenotypic forms. A common example in natural populations of insects is the occurrence of different color patterns, which has motivated a rich body of ecological and genetic research [1-6]. The occurrence of dark, i.e., melanic, forms displaying discrete color patterns is found across multiple taxa, but the underlying genomic basis remains poorly characterized. In numerous ladybird species (Coccinellidae), the spatial arrangement of black and red patches on adult elytra varies wildly within species, forming strikingly different complex color patterns [7, 8]. In the harlequin ladybird, Harmonia axyridis, more than 200 distinct color forms have been described, which classic genetic studies suggest result from allelic variation at a single, unknown, locus [9, 10]. Here, we combined whole-genome sequencing, population-based genome-wide association studies, gene expression, and functional analyses to establish that the transcription factor Pannier controls melanic pattern polymorphism in H. axyridis. We show that pannier is necessary for the formation of melanic elements on the elytra. Allelic variation in pannier leads to protein expression in distinct domains on the elytra and thus determines the distinct color patterns in H. axyridis. Recombination between pannier alleles may be reduced by a highly divergent sequence of ∼170 kb in the cis-regulatory regions of pannier, with a 50 kb inversion between color forms. This most likely helps maintain the distinct alleles found in natural populations. Thus, we propose that highly variable discrete color forms can arise in natural populations through cis-regulatory allelic variation of a single gene.
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http://dx.doi.org/10.1016/j.cub.2018.08.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203698PMC
October 2018