49 research outputs found

    Long-range regulation is a major driving force in maintaining genome integrity

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    <p>Abstract</p> <p>Background</p> <p>The availability of newly sequenced vertebrate genomes, along with more efficient and accurate alignment algorithms, have enabled the expansion of the field of comparative genomics. Large-scale genome rearrangement events modify the order of genes and non-coding conserved regions on chromosomes. While certain large genomic regions have remained intact over much of vertebrate evolution, others appear to be hotspots for genomic breakpoints. The cause of the non-uniformity of breakpoints that occurred during vertebrate evolution is poorly understood.</p> <p>Results</p> <p>We describe a machine learning method to distinguish genomic regions where breakpoints would be expected to have deleterious effects (called breakpoint-refractory regions) from those where they are expected to be neutral (called breakpoint-susceptible regions). Our predictor is trained using breakpoints that took place along the human lineage since amniote divergence. Based on our predictions, refractory and susceptible regions have very distinctive features. Refractory regions are significantly enriched for conserved non-coding elements as well as for genes involved in development, whereas susceptible regions are enriched for housekeeping genes, likely to have simpler transcriptional regulation.</p> <p>Conclusion</p> <p>We postulate that long-range transcriptional regulation strongly influences chromosome break fixation. In many regions, the fitness cost of altering the spatial association between long-range regulatory regions and their target genes may be so high that rearrangements are not allowed. Consequently, only a limited, identifiable fraction of the genome is susceptible to genome rearrangements.</p

    The effect of natural and anthropogenic nutrient and sediment loads on coral oxidative stress on runoff-exposed reefs

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    Recently, corals on the Great Barrier (GBR) have suffered mass bleaching. The link between ocean warming and coral bleaching is understood to be due to temperature-dependence of complex physiological processes in the coral host and algal symbiont. Here we use a coupled catchment-hydrodynamic-biogeochemical model, with detailed zooxanthellae photophysiology including photoadaptation, photoacclimation and reactive oxygen build-up, to investigate whether natural and anthropogenic catchment loads impact on coral bleaching on the GBR. For the wet season of 2017, simulations show the cross-shelf water quality gradient, driven by both natural and anthropogenic loads, generated a contrasting zooxanthellae physiological state on inshore versus mid-shelf reefs. The relatively small catchment flows and loads delivered during 2017, however, generated small river plumes with limited impact on water quality. Simulations show the removal of the anthropogenic fraction of the catchment loads delivered in 2017 would have had a negligible impact on bleaching rates

    Impact of catchment-derived nutrients and sediments on marine water quality on the Great Barrier Reef: an application of the eReefs marine modelling system

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    Water quality of the Great Barrier Reef (GBR) is determined by a range of natural and anthropogenic drivers that are resolved in the eReefs coupled hydrodynamic - biogeochemical marine model forced by a process-based catchment model, GBR Dynamic SedNet. Model simulations presented here quantify the impact of anthropogenic catchment loads of sediments and nutrients on a range of marine water quality variables. Simulations of 2011–2018 show that reduction of anthropogenic catchment loads results in improved water quality, especially within river plumes. Within the 16 resolved river plumes, anthropogenic loads increased chlorophyll concentration by 0.10 (0.02–0.25) mg Chl m−3. Reductions of anthropogenic loads following proposed Reef 2050 Water Quality Improvement Plan targets reduced chlorophyll concentration in the plumes by 0.04 (0.01–0.10) mg Chl m−3. Our simulations demonstrate the impact of anthropogenic loads on GBR water quality and quantify the benefits of improved catchment management

    Deprotometalation-iodolysis and computed CH acidity of 1,2,3- and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues

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    International audience1-Aryl- and 2-aryl-1,2,3-triazoles were synthesized by N-arylation of the corresponding azoles using aryl iodides. The deprotometalations of 1-phenyl-1,2,3-triazole and -1,2,4-triazole were performed using a 2,2,6,6-tetramethylpiperidino-based mixed lithium-zinc combination and occurred at the most acidic site, affording by iodolysis the 5-substituted derivatives. Dideprotonation was noted from 1-(2-thienyl)-1,2,4-triazole by increasing the amount of base. From 2-phenyl-1,2,3-triazoles, and in particular from 2-(4-trifluoromethoxy)phenyl-1,2,3-triazole, reactions at the 4 position of the triazolyl, but also ortho to the triazolyl on the phenyl group, were observed. The results were analyzed with the help of the CH acidities of the substrates, determined in THF solution using the DFT B3LYP method. 4-Iodo-2-phenyl-1,2,3-triazole and 4-iodo-2-(2-iodophenyl)-1,2,3-triazole were next involved in Suzuki coupling reactions to furnish the corresponding 4-arylated and 4,2’-diarylated derivatives. When evaluated for biological activities, the latter (which are resveratrol analogues) showed moderate antibacterial activity and promising antiproliferative effect against MDA-MB-231 cell line

    Use of remote-sensing reflectance to constrain a data assimilating marine biogeochemical model of the Great Barrier Reef

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    Skillful marine biogeochemical (BGC) models are required to understand a range of coastal and global phenomena such as changes in nitrogen and carbon cycles. The refinement of BGC models through the assimilation of variables calculated from observed in-water inherent optical properties (IOPs), such as phytoplankton absorption, is problematic. Empirically derived relationships between IOPs and variables such as chlorophyll-a concentration (Chl a), total suspended solids (TSS) and coloured dissolved organic matter (CDOM) have been shown to have errors that can exceed 100% of the observed quantity. These errors are greatest in shallow coastal regions, such as the Great Barrier Reef (GBR), due to the additional signal from bottom reflectance. Rather than assimilate quantities calculated using IOP algorithms, this study demonstrates the advantages of assimilating quantities calculated directly from the less error-prone satellite remote-sensing reflectance (RSR). To assimilate the observed RSR, we use an in-water optical model to produce an equivalent simulated RSR and calculate the mismatch between the observed and simulated quantities to constrain the BGC model with a deterministic ensemble Kalman filter (DEnKF). The traditional assumption that simulated surface Chl a is equivalent to the remotely sensed OC3M estimate of Chl a resulted in a forecast error of approximately 75 %. We show this error can be halved by instead using simulated RSR to constrain the model via the assimilation system. When the analysis and forecast fields from the RSR-based assimilation system are compared with the non-assimilating model, a comparison against independent in situ observations of Chl a, TSS and dissolved inorganic nutrients (NO3, NH4 and DIP) showed that errors are reduced by up to 90 %. In all cases, the assimilation system improves the simulation compared to the non-assimilating model. Our approach allows for the incorporation of vast quantities of remote-sensing observations that have in the past been discarded due to shallow water and/or artefacts introduced by terrestrially derived TSS and CDOM or the lack of a calibrated regional IOP algorithm

    The exposure of the Great Barrier Reef to ocean acidification

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    The Great Barrier Reef (GBR) is founded on reef-building corals. Corals build their exoskeleton with aragonite, but ocean acidification is lowering the aragonite saturation state of seawater (Omega(a)). The downscaling of ocean acidification projections from global to GBR scales requires the set of regional drivers controlling Omega(a) to be resolved. Here we use a regional coupled circulation-biogeochemical model and observations to estimate the Omega(a) experienced by the 3,581 reefs of the GBR, and to apportion the contributions of the hydrological cycle, regional hydrodynamics and metabolism on Omega(a) variability. We find more detail, and a greater range (1.43), than previously compiled coarse maps of Omega(a) of the region (0.4), or in observations (1.0). Most of the variability in Omega(a) is due to processes upstream of the reef in question. As a result, future decline in Omega(a) is likely to be steeper on the GBR than currently projected by the IPCC assessment report

    Combining Computational Prediction of Cis-Regulatory Elements with a New Enhancer Assay to Efficiently Label Neuronal Structures in the Medaka Fish

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    The developing vertebrate nervous system contains a remarkable array of neural cells organized into complex, evolutionarily conserved structures. The labeling of living cells in these structures is key for the understanding of brain development and function, yet the generation of stable lines expressing reporter genes in specific spatio-temporal patterns remains a limiting step. In this study we present a fast and reliable pipeline to efficiently generate a set of stable lines expressing a reporter gene in multiple neuronal structures in the developing nervous system in medaka. The pipeline combines both the accurate computational genome-wide prediction of neuronal specific cis-regulatory modules (CRMs) and a newly developed experimental setup to rapidly obtain transgenic lines in a cost-effective and highly reproducible manner. 95% of the CRMs tested in our experimental setup show enhancer activity in various and numerous neuronal structures belonging to all major brain subdivisions. This pipeline represents a significant step towards the dissection of embryonic neuronal development in vertebrates

    Le concept de Redfield en océanographie (révision de son utilisation à l'aide de l'outil modélisation)

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    Les programmes océanographiques à différentes échelles réalisées depuis deux décennies ont mis en évidence la variabilité de la composition de la matière organique ainsi que les rapports entre éléments biogènes qui s'écartent parfois de ceux déterminés par Redfield (1934, 1958). Cette thèse propose de revisiter les travaux de Redfield et de ces successeurs à l'aide de l'outil modélisation, à travers deux questions principales : (1) les rapports de Redfield sont-ils variables et à quelles échelles ? (2) en tenant compte de la variabilité de ces rapports faut-il remettre en question notre vision du fonctionnement de l'écosystème marin ? Après une introduction sur les progrès de la biogéochimie marine, pour répondre à ces 3 questions, un modèle biogéochimique simple dans lequel la composition élémentaire de la matière organique est variable est présenté. Prenant comme point de départ le modèle de croissance phytoplanctonique de Droop (1974) , l'outil est appliqué aux stations permanentes : Bermuda Atlantic Times series (BATS) dans la mer des Bermudes (Atlantique), KERFIX dans le secteur indien de l'océan austral, et Hawaii Ocean Time Series (HOT) dans le Pacifique sub-tropical nord. La première application au système oligotrophe de BATS permet la mise en place du modèle : à l'échelle annuelle, les sorties du modèle reproduisent les profils de POC/PON observés, les écarts entre les résultats du modèle et les estimations de la production exportée à partir des pièges à particules et les méthodes chimiques sont expliqués, au niveau du cycle du silicium, la faible productivité des diatomées dans ce type de système est interprétée. Les systèmes oligotrophes de type BATS peuvent présenter une forte variabilité dans la composition de la matière organique, tant temporellement que verticalement. Dans le cas de KERFIX, le modèle biogéochimique, en tenant compte de la limitation de croissance cellulaire et permet d'identifier la combinaison de facteurs typiques du caractère High Nutrient Low Chorophyll (HNLC) de l'écosystème antarctique; les rapports élémentaires de la composition de la matière organique y sont relativement constants. La troisième application à HOT (Pacifique) permet d'expliquer la faible variabilité à l'échelle annuelle et la forte variabilité verticale de la composition de la matière organique observée dans ce type de système hyper-oligothrophe. Dans une partie synthétique, les avantages des modèles biogéochimiques à composition flexible sont présentés et discutés avant de donner réponse aux 3 questions scientifiques posées.Oceanographic programs held over the past twenty years put forward the evidence that the elemental composition of the organic matter in the ocean is much more variable than previously thought. Strong deviation from the Redfiels's proportion is to be found in the ocean. After revisiting Redfield and his successors efforts in describing the ratios of elements in the ocean using modeling tools, implication for the biogeochemical cycle are discussed. This work addresses two core questions : (1) are the ratios of elements in the ocean variable, on which scales ? (2) Knowing those variations, should we reassess our vision of the ecosystem functioning ?After a general introduction about the recent progress in biogeochemistry, a flexible composition model of the upper ocean is presented to answer those questions. Starting with the Droop (1974) cell quota production model, our tool is applied to the Bermuda Atlantic Times Series (BATS) in the Sargasso sea (Atlantic), to the KERFIX station in the indian sector of the Southern Ocean and to the Hawaii Time Series (HOT) in the subtropical Pacific. The first application in the oligotrophic system BATS is used as a model validation study. On the annual scale, model outputs simulate the observed POC/PON profiles, and the difference between model fluxes and export fluxes from sediment traps and chemical methods is explained. In this typical oligotrophe region, elemental composition of the organic matter is highly variable spatially and temporally. The second application at the KERFIX station, simulating low iron concentration, light limitation and grazing pressure effect on primary production, leads to the typical HNLC system of the southern ocean in a more realistic way. The elemental ratio in these conditions only shows a small variability. The third application for the HOT system (pacific ocean) only shows vertical variations of the organic matter elemental ratios with no seasonal variability. The last part of the manuscrit goes back on the advantage of the flexible composition biogeochemical model and expose the result and variability of the elemental in order to answer the questions raised during this work.BREST-BU Droit-Sciences-Sports (290192103) / SudocPLOUZANE-Bibl.La Pérouse (290195209) / SudocSudocFranceF
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