P53 (protein 53 kDa)

Review on P53 (protein 53 kDa), with data on DNA, on the protein encoded, and where the gene is implicated

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)

Validation of MIPAS-ENVISAT NO2 operational data

The Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) instrument was launched aboard the environmental satellite ENVISAT into its sun-synchronous orbit on 1 March 2002. The short-lived species NO₂ is one of the key target products of MIPAS that are operationally retrieved from limb emission spectra measured in the stratosphere and mesosphere. Within the MIPAS validation activities, a large number of independent observations from balloons, satellites and ground-based stations have been compared to European Space Agency (ESA) version 4.61 operational NO₂ data comprising the time period from July 2002 until March 2004 where MIPAS measured with full spectral resolution. Comparisons between MIPAS and balloon-borne observations carried out in 2002 and 2003 in the Arctic, at mid-latitudes, and in the tropics show a very good agreement below 40 km altitude with a mean deviation of roughly 3%, virtually without any significant bias. The comparison to ACE satellite observations exhibits only a small negative bias of MIPAS which appears not to be significant. The independent satellite instruments HALOE, SAGE II, and POAM III confirm in common for the spring-summer time period a negative bias of MIPAS in the Arctic and a positive bias in the Antarctic middle and upper stratosphere exceeding frequently the combined systematic error limits. In contrast to the ESA operational processor, the IMK/IAA retrieval code allows accurate inference of NO₂ volume mixing ratios under consideration of all important non-LTE processes. Large differences between both retrieval results appear especially at higher altitudes, above about 50 to 55 km. These differences might be explained at least partly by non-LTE under polar winter conditions but not at mid-latitudes. Below this altitude region mean differences between both processors remain within 5% (during night) and up to 10% (during day) under undisturbed (September 2002) conditions and up to 40% under perturbed polar night conditions (February and March 2004). The intercomparison of ground-based NDACC observations shows no significant bias between the FTIR measurements in Kiruna (68° N) and MIPAS in summer 2003 but larger deviations in autumn and winter. The mean deviation over the whole comparison period remains within 10%. A mean negative bias of 15% for MIPAS daytime and 8% for nighttime observations has been determined for UV-vis comparisons over Harestua (60° N). Results of a pole-to-pole comparison of ground-based DOAS/UV-visible sunrise and MIPAS mid-morning column data has shown that the mean agreement in 2003 falls within the accuracy limit of the comparison method. Altogether, it can be indicated that MIPAS NO₂ profiles yield valuable information on the vertical distribution of NO₂ in the lower and middle stratosphere (below about 45 km) during day and night with an overall accuracy of about 10–20% and a precision of typically 5–15% such that the data are useful for scientific studies. In cases where extremely high NO₂ occurs in the mesosphere (polar winter) retrieval results in the lower and middle stratosphere are less accurate than under undisturbed atmospheric conditions

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

ALL-1/MLL1, a homologue of Drosophila TRITHORAX, modifies chromatin and is directly involved in infant acute leukaemia

Rearrangements of the ALL-1/MLL1 gene underlie the majority of infant acute leukaemias, as well as of therapy-related leukaemias developing in cancer patients treated with inhibitors of topoisomerase II, such as VP16 and doxorubicin. The rearrangements fuse ALL-1 to any of \u3e50 partner genes or to itself. Here, we describe the unique features of ALL-1-associated leukaemias, and recent progress in understanding molecular mechanisms involved in the activity of the ALL-1 protein and of its Drosophila homologue TRITHORAX

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

Heterozygous Mutations of FREM1 Are Associated with an Increased Risk of Isolated Metopic Craniosynostosis in Humans and Mice

The premature fusion of the paired frontal bones results in metopic craniosynostosis (MC) and gives rise to the clinical phenotype of trigonocephaly. Deletions of chromosome 9p22.3 are well described as a cause of MC with variably penetrant midface hypoplasia. In order to identify the gene responsible for the trigonocephaly component of the 9p22.3 syndrome, a cohort of 109 patients were assessed by high-resolution arrays and MLPA for copy number variations (CNVs) involving 9p22. Five CNVs involving FREM1, all of which were de novo variants, were identified by array-based analyses. The remaining 104 patients with MC were then subjected to targeted FREM1 gene re-sequencing, which identified 3 further mutant alleles, one of which was de novo. Consistent with a pathogenic role, mouse Frem1 mRNA and protein expression was demonstrated in the metopic suture as well as in the pericranium and dura mater. Micro-computed tomography based analyses of the mouse posterior frontal (PF) suture, the human metopic suture equivalent, revealed advanced fusion in all mice homozygous for either of two different Frem1 mutant alleles, while heterozygotes exhibited variably penetrant PF suture anomalies. Gene dosage-related penetrance of midfacial hypoplasia was also evident in the Frem1 mutants. These data suggest that CNVs and mutations involving FREM1 can be identified in a significant percentage of people with MC with or without midface hypoplasia. Furthermore, we present Frem1 mutant mice as the first bona fide mouse model of human metopic craniosynostosis and a new model for midfacial hypoplasia