Climatic and palaeoceanographic changes during the Pliensbachian (Early Jurassic) 2 inferred from clay mineralogy and stable isotope (C-O) geochemistry (NW Europe)

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Available online 17 January 2017The Early Jurassic was broadly a greenhouse climate period that was punctuated by short warm and cold climatic events, positive and negative excursions of carbon isotopes, and episodes of enhanced organic matter burial. Clay minerals from Pliensbachian sediments recovered from two boreholes in the Paris Basin, are used here as proxies of detrital supplies, runoff conditions, and palaeoceanographic changes. The combined use of these minerals with ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT stable isotope data (C-O) from bulk carbonates and organic matter allows palaeoclimatic reconstructions to be refined for the Pliensbachian. Kaolinite/illite ratio is discussed as a reliable proxy of the hydrological cycle and runoff from landmasses. Three periods of enhanced runoff are recognised within the Pliensbachian. The first one at the SinemurianPliensbachian transition shows a significant increase of kaolinite concomitant with the negative carbon isotope excursion at the so-called Sinemurian Pliensbachian Boundary Event (SPBE). The Early/Late Pliensbachian transition was also characterised by more humid conditions. This warm interval is associated with a major change in oceanic circulation during the Davoei Zone, likely triggered by sea-level rise; the newly created palaeogeography, notably the flooding of the London-Brabant Massif, allowed boreal detrital supplies, including kaolinite and chlorite, to be exported to the Paris Basin. The last event of enhanced runoff occurred during the late Pliensbachian (Subdonosus Subzone of the Margaritatus Zone), which occurred also during a warm period, favouring organic matter production and preservation. Our study highlights the major role of the London Brabant Massif in influencing oceanic circulation of the NW European area, as a topographic barrier (emerged lands) during periods of lowstand sea-level and its flooding during period of high sea-level. This massif was the unique source of smectite in the Paris Basin. Two episodes of smectite-rich sedimentation (‘smectite events’), coincide with regressive intervals, indicating emersion of the London Brabant Massif and thus suggesting that an amplitude of sea-level change high enough to be linked to glacio-eustasy. This mechanism is consistent with sedimentological and geochemical evidences of continental ice growth notably during the Latest Pliensbachian (Spinatum Zone), and possibly during the Early Pliensbachian (late Jamesoni/early Ibex Zones).The study was supported by the “Agence Nationale pour la Gestion des Déchets Radioactifs” (Andra––French National Radioactive Waste Management Agency)

Predicting selective drug targets in cancer through metabolic networks

The authors develop a genome-scale model of cancer metabolism and use it to predict genes that are essential for cancer cell growth. An array of target combinations are then identified that could potentially provide novel selective treatments for specific cancers

dbCRID: a database of chromosomal rearrangements in human diseases

Chromosomal rearrangement (CR) events result from abnormal breaking and rejoining of the DNA molecules, or from crossing-over between repetitive DNA sequences, and they are involved in many tumor and non-tumor diseases. Investigations of disease-associated CR events can not only lead to important discoveries about DNA breakage and repair mechanisms, but also offer important clues about the pathologic causes and the diagnostic/therapeutic targets of these diseases. We have developed a database of Chromosomal Rearrangements In Diseases (dbCRID, http://dbCRID.biolead.org), a comprehensive database of human CR events and their associated diseases. For each reported CR event, dbCRID documents the type of the event, the disease or symptoms associated, and—when possible—detailed information about the CR event including precise breakpoint positions, junction sequences, genes and gene regions disrupted and experimental techniques applied to discover/analyze the CR event. With 2643 records of disease-associated CR events curated from 1172 original studies, dbCRID is a comprehensive and dynamic resource useful for studying DNA breakage and repair mechanisms, and for analyzing the genetic basis of human tumor and non-tumor diseases

MethyCancer: the database of human DNA methylation and cancer

Cancer is ranked as one of the top killers in all human diseases and continues to have a devastating effect on the population around the globe. Current research efforts are aiming to accelerate our understanding of the molecular basis of cancer and develop effective means for cancer diagnostics, treatment and prognosis. An altered pattern of epigenetic modifications, most importantly DNA methylation events, plays a critical role in tumorigenesis through regulating oncogene activation, tumor suppressor gene silencing and chromosomal instability. To study interplay of DNA methylation, gene expression and cancer, we developed a publicly accessible database for human DNA Methylation and Cancer (MethyCancer, http://methycancer.genomics.org.cn). MethyCancer hosts both highly integrated data of DNA methylation, cancer-related gene, mutation and cancer information from public resources, and the CpG Island (CGI) clones derived from our large-scale sequencing. Interconnections between different data types were analyzed and presented. Furthermore, a powerful search tool is developed to provide user-friendly access to all the data and data connections. A graphical MethyView shows DNA methylation in context of genomics and genetics data facilitating the research in cancer to understand genetic and epigenetic mechanisms that make dramatic changes in gene expression of tumor cells

Million-year-scale alternation of warm–humid and semi-arid periods as a mid-latitude climate mode in the Early Jurassic (late Sinemurian, Laurasian Seaway)

Clay mineral and stable isotope (C, O) data are reported from the upper Sinemurian (Lower Jurassic) of the Cardigan Bay Basin (Llanbedr–Mochras Farm borehole, northwestern Wales) and the Paris Basin (Montcornet borehole, northern France) to highlight the prevailing environmental and climatic conditions. In both basins, located at similar palaeolatitudes of 30–35∘ N, the clay mineral assemblages comprise chlorite, illite, illite–smectite mixed layers (R1 I-S), smectite, and kaolinite in various proportions. Because the influence of burial diagenesis and authigenesis is negligible in both boreholes, the clay minerals are interpreted to be derived from the erosion of the Caledonian and Variscan massifs, including their basement and pedogenic cover. In the Cardigan Bay Basin, the variations in the proportions of smectite and kaolinite are inversely related to each other through the entire upper Sinemurian. As in the succeeding Pliensbachian, the upper Sinemurian stratigraphic distribution reveals an alternation of kaolinite-rich intervals reflecting strong hydrolysing conditions and smectite-rich intervals indicating a semi-arid climate. Kaolinite is particularly abundant in the upper part of the obtusum zone and in the oxynotum zone, suggesting more intense hydrolysing conditions likely coeval with warm conditions responsible for an acceleration of the hydrological cycle. In the north of the Paris Basin, the succession is less continuous compared to the Cardigan Bay Basin site, as the oxynotum zone and the upper raricostatum zone are either absent or highly condensed. The clay assemblages are dominantly composed of illite and kaolinite without significant stratigraphic trends, but a smectite-rich interval identified in the obtusum zone is interpreted as a consequence of the emersion of the London–Brabant Massif following a lowering of sea level. Following a slight negative carbon isotope excursion at the obtusum–oxynotum zone transition, a long-term decrease in δ13Corg from the late oxynotum–early raricostatum zones is recorded in the two sites and may precede or partly include the negative carbon isotope excursion of the Sinemurian–Pliensbachian Boundary Event, which is recognised in most basins worldwide and interpreted to signify a late pulse of the Central Atlantic Magmatic Province volcanism

Preliminary results from the ECOCADIZ 2020-07 Spanish acoustic survey (01 – 14 August 2020)

The present working document summarises a part of the main results obtained from the Spanish (pelagic ecosystem-) acoustic survey conducted by IEO between 01st and 14th August 2020 in the Portuguese and Spanish shelf waters (20-200 m isobaths) off the Gulf of Cadiz (GoC) onboard the R/V Miguel Oliver. The 21 foreseen acoustic transects were sampled. A total of 26 valid fishing hauls were carried out for echo-trace ground-truthing purposes. Four additional night trawls were conducted to collect anchovy hydrated females (DEPM). This working document only provides abundance and biomass estimates for anchovy, sardine and chub mackerel, which are presented without age structure. The distribution of all the mid-sized and small pelagic fish species susceptible of being acoustically assessed is also shown from the mapping of their back-scattering energies. GoC anchovy acoustic estimates in summer 2020 were of 5153 million fish and 44 877 tones, with the bulk of the population occurring in the Spanish waters. The current biomass estimate becomes in the second historical maximum within the time-series. The estimates of sardine abundance and biomass in summer 2020 were 1923 million fish and 50 721 t, estimates close to the historical average, but lower than the values estimated last year and the most recent maxima reached in 2018. A total of 32 854 t and 448 million fish were estimated for Chub mackerel, estimates similar to the most recent ones and very close to the time-series average

Core module biomarker identification with network exploration for breast cancer metastasis

<p>Abstract</p> <p>Background</p> <p>In a complex disease, the expression of many genes can be significantly altered, leading to the appearance of a differentially expressed "disease module". Some of these genes directly correspond to the disease phenotype, (i.e. "driver" genes), while others represent closely-related first-degree neighbours in gene interaction space. The remaining genes consist of further removed "passenger" genes, which are often not directly related to the original cause of the disease. For prognostic and diagnostic purposes, it is crucial to be able to separate the group of "driver" genes and their first-degree neighbours, (i.e. "core module") from the general "disease module".</p> <p>Results</p> <p>We have developed COMBINER: COre Module Biomarker Identification with Network ExploRation. COMBINER is a novel pathway-based approach for selecting highly reproducible discriminative biomarkers. We applied COMBINER to three benchmark breast cancer datasets for identifying prognostic biomarkers. COMBINER-derived biomarkers exhibited 10-fold higher reproducibility than other methods, with up to 30-fold greater enrichment for known cancer-related genes, and 4-fold enrichment for known breast cancer susceptible genes. More than 50% and 40% of the resulting biomarkers were cancer and breast cancer specific, respectively. The identified modules were overlaid onto a map of intracellular pathways that comprehensively highlighted the hallmarks of cancer. Furthermore, we constructed a global regulatory network intertwining several functional clusters and uncovered 13 confident "driver" genes of breast cancer metastasis.</p> <p>Conclusions</p> <p>COMBINER can efficiently and robustly identify disease core module genes and construct their associated regulatory network. In the same way, it is potentially applicable in the characterization of any disease that can be probed with microarrays.</p

Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2-mutated breast cancers

Background: Genomic gains and losses are a result of genomic instability in many types of cancers. BRCA1- and BRCA2-mutated breast cancers are associated with increased amounts of chromosomal aberrations, presumably due their functions in genome repair. Some of these genomic aberrations may harbor genes whose absence or overexpression may give rise to cellular growth advantage. So far, it has not been easy to identify the driver genes underlying gains and losses. A powerful approach to identify these driver genes could be a cross-species comparison of array comparative genomic hybridization (aCGH) data from cognate mouse and human tumors. Orthologous regions of mouse and human tumors that are commonly gained or lost might represent essential genomic regions selected for gain or loss during tumor development. Methods: To identify genomic regions that are associated with BRCA1- and BRCA2-mutated breast cancers we compared aCGH data from 130 mouse Brca1?/?;p53?/?, Brca2?/?;p53?/? and p53?/? mammary tumor groups with 103 human BRCA1-mutated, BRCA2-mutated and non-hereditary breast cancers. Results: Our genome-wide cross-species analysis yielded a complete collection of loci and genes that are commonly gained or lost in mouse and human breast cancer. Principal common CNAs were the well known MYCassociated gain and RB1/INTS6-associated loss that occurred in all mouse and human tumor groups, and the AURKA-associated gain occurred in BRCA2-related tumors from both species. However, there were also important differences between tumor profiles of both species, such as the prominent gain on chromosome 10 in mouse Brca2?/?;p53?/? tumors and the PIK3CA associated 3q gain in human BRCA1-mutated tumors, which occurred in tumors from one species but not in tumors from the other species. This disparity in recurrent aberrations in mouse and human tumors might be due to differences in tumor cell type or genomic organization between both species. Conclusions: The selection of the oncogenome during mouse and human breast tumor development is markedly different, apart from the MYC gain and RB1-associated loss. These differences should be kept in mind when using mouse models for preclinical studies.MediamaticsElectrical Engineering, Mathematics and Computer Scienc

BRCA1-mutated and basal-like breast cancers have similar aCGH profiles and a high incidence of protein truncating TP53 mutations

<p>Abstract</p> <p>Background</p> <p>Basal-like breast cancers (BLBC) are aggressive breast cancers for which, so far, no targeted therapy is available because they typically lack expression of hormone receptors and HER2. Phenotypic features of BLBCs, such as clinical presentation and early age of onset, resemble those of breast tumors from <it>BRCA1</it>-mutation carriers. The genomic instability of <it>BRCA1</it>-mutated tumors can be effectively targeted with DNA-damaging agents and poly-(ADP-ribose) polymerase 1 (PARP1) inhibitors. Molecular similarities between BLBCs and <it>BRCA1</it>-mutated tumors may therefore provide predictive markers for therapeutic response of BLBCs.</p> <p>Methods</p> <p>There are several known molecular features characteristic for <it>BRCA1</it>-mutated breast tumors: 1) increased numbers of genomic aberrations, 2) a distinct pattern of genomic aberrations, 3) a high frequency of <it>TP53 </it>mutations and 4) a high incidence of complex, protein-truncating <it>TP53 </it>mutations. We compared the frequency of <it>TP53 </it>mutations and the pattern and amount of genomic aberrations between <it>BRCA1</it>-mutated breast tumors, BLBCs and luminal breast tumors by <it>TP53 </it>gene sequencing and array-based comparative genomics hybridization (aCGH) analysis.</p> <p>Results</p> <p>We found that the high incidence of protein truncating <it>TP53 </it>mutations and the pattern and amount of genomic aberrations specific for BRCA1-mutated breast tumors are also characteristic for BLBCs and different from luminal breast tumors.</p> <p>Conclusions</p> <p>Complex, protein truncating TP53 mutations in BRCA1-mutated tumors may be a direct consequence of genomic instability caused by BRCA1 loss, therefore, the presence of these types of TP53 mutations in sporadic BLBCs might be a hallmark of BRCAness and a potential biomarker for sensitivity to PARP inhibition. Also, our data suggest that a small subset of genomic regions may be used to identify BRCA1-like BLBCs. BLBCs share molecular features that were previously found to be specific for BRCA1-mutated breast tumors. These features might be useful for the identification of tumors with increased sensitivity to (high-dose or dose-dense) alkylating agents and PARP inhibitors.</p