142 research outputs found

    Physico-chemical analysis of Albian (Lower Cretaceous) amber from San Just (Spain) : implications for palaeoenvironmental and palaeoecological studies

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    Amber from a Lower Cretaceous outcrop at San Just, located in the Eastern Iberian Peninsula (Escucha Formation, Maestrat Basin), was investigated to evaluate its physico-chemical properties. Thermogravimetric (TG) and Differential Thermogravimetric (DTG) analyses, infra-red spectroscopy, elemental and C-isotope analyses were performed. Physico-chemical differences between the internal light nuclei and the peripheral darker portions of San Just amber can be attributed to processes of diagenetic alteration that preferentially took place in the external amber border colonized by microorganisms (fungi or bacteria) when the resin was still liquid or slightly polymerized. δ13Camber values of different pieces of the same sample, from the nucleus to the external part, are remarkably homogeneous, as are δ13Camber values of the darker peripheral portions and lighter inner parts of the same samples. Hence, neither invasive microorganisms, nor diagenetic alteration changed the bulk isotopic composition of the amber. δ13C values of different amber samples range from -21.1‰ to -24‰, as expected for C3 plant-derived material. C-isotope analysis, coupled to palaeobotanical, TG and DTG data and infra-red spectra, suggests that San Just amber was exuded by only one conifer species, belonging to either the Cheirolepidiaceae or Aracauriaceae, coniferous families probably living under stable palaeoenvironmental and palaeoecological conditions

    Membrane type-1 matrix metalloproteinase activity is regulated by the endocytic collagen receptor Endo180.

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    The molecular interactions leading to organised, controlled extracellular matrix degradation are of central importance during growth, development and tissue repair, and when deregulated contribute to disease processes including cancer cell invasion. There are two major pathways for collagen degradation: one dependent on secreted and membrane-bound collagenases, the other on receptor-mediated collagen internalisation and intracellular processing. Despite the established importance of both pathways, the functional interaction between them is largely unknown. We demonstrate here, that the collagen internalisation receptor Endo180 (also known as CD280, uPARAP, MRC2) is a novel regulator of membrane-bound matrix metalloproteinase (MT1-MMP) activity, MT1-MMP-dependent MMP-2 activation and urokinase plasminogen activator (uPA) activity. We show close correlation between Endo180 expression, collagen accumulation and regulation of MT1-MMP cell-surface localisation and activity. We directly demonstrate, using collagen inhibition studies and non-collagen-binding mutants of Endo180, that the molecular mechanism underlying this regulation is the ability of Endo180 to bind and/or internalise collagens, rather than by acting as an interaction partner for pro-uPA and its receptor uPAR. These studies strongly support a functional interaction between two distinct collagen degradation pathways, define a novel mechanism regulating MT1-MMP activity and might have important implications for organised collagen clearance in the pericellular environment

    Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition

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    p300 is a transcriptional cofactor and prototype histone acetyltransferase involved in regulating multiple cellular processes. We generated p300 deficient (p300−) cells from the colon carcinoma cell line HCT116 by gene targeting. Comparison of epithelial and mesenchymal proteins in p300− with parental HCT116 cells showed that a number of genes involved in cell and extracellular matrix interactions, typical of ‘epithelial to mesenchyme transition' were differentially regulated at both the RNA and protein level. p300− cells were found to have aggressive ‘cancer' phenotypes, with loss of cell–cell adhesion, defects in cell–matrix adhesion and increased migration through collagen and matrigel. Although migration was shown to be metalloproteinase mediated, these cells actually showed a downregulation or no change in the level of key metalloproteinases, indicating that changes in cellular adhesion properties can be critical for cellular mobility

    A Method for Analyzing the Ubiquitination and Degradation of Aurora-A

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    The cell cycle machinery consists of regulatory proteins that control the progression through the cell cycle ensuring that DNA replication alternates with DNA segregation in mitosis to maintain cell integrity. Some of these key regulators have to be degraded at each cell cycle to prevent cellular dysfunction. Mitotic exit requires the inactivation of cyclin dependent kinase1 (cdk1) and it is the degradation of the cyclin subunit that inactivates the kinase. Cyclin degradation has been well characterized and it was shown that it is ubiquitin proteasome pathway that leads to the elimination of cyclins. By now, many other regulatory proteins were shown to be degraded by the same pathway, among them members of the aurora kinase family, degraded many other regulatory proteins. Aurora kinases are involved in mitotic spindle formation as well as in cytokinesis. The abundance and activity of the kinase is precisely regulated during the cell cycle. To understand how proteolysis regulates transitions through the cell cycle we describe two assays for ubiquitination and degradation of xenopus aurora kinase A using extracts from xenopus eggs or somatic cell lines

    Amber from the Triassic to Paleogene of Australia and New Zealand as exceptional preservation of poorly known terrestrial ecosystems

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    The Northern Hemisphere dominates our knowledge of Mesozoic and Cenozoic fossilized tree resin (amber) with few fndings from the high southern paleolatitudes of Southern Pangea and Southern Gondwana. Here we report new Pangean and Gondwana amber occurrences dating from ~230 to 40 Ma from Australia (Late Triassic and Paleogene of Tasmania; Late Cretaceous Gippsland Basin in Victoria; Paleocene and late middle Eocene of Victoria) and New Zealand (Late Cretaceous Chatham Islands). The Paleogene, richly fossiliferous deposits contain signifcant and diverse inclusions of arthropods, plants and fungi. These austral discoveries open six new windows to diferent but crucial intervals of the Mesozoic and early Cenozoic, providing the earliest occurrence(s) of some taxa in the modern fauna and flora giving new insights into the ecology and evolution of polar and subpolar terrestrial ecosystems.Tis publication represents aresearch output from Australian Research Council Discovery Grant ARC-DP140102515 (2014–2017) to J.S., D.B.and D.C., a Robert Blackwood Seed grant to J.S., and from Spanish AEI/FEDER, UE Grant CGL2017–84419 (theCRE project) to A.A. and E.P. Additional funds provided to C.M. for feldwork and preparation by the NationalGeographic Society (Grant 9761–15) and the Paleontological Society</p

    Follow-up of atheroma burden with sequential whole body contrast enhanced MR angiography:a feasibility study

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    Assess the feasibility of whole body magnetic resonance angiography (WB-MRA) for monitoring global atheroma burden in a population with peripheral arterial disease (PAD). 50 consecutive patients with symptomatic PAD referred for clinically indicated MRA were recruited. Whole body MRA (WB-MRA) was performed at baseline, 6 months and 3 years. The vasculature was split into 31 anatomical arterial segments. Each segment was scored according to degree of luminal narrowing: 0 = normal, 1 = <50 %, 2 = 50–70 %, 3 = 71–99 %, 4 = vessel occlusion. The score from all assessable segments was summed, and then normalised to the number of assessable vessels. This normalised score was divided by four (the maximum vessel score) and multiplied by 100 to give a final standardised atheroma score (SAS) with a score of 0–100. Progression was assessed with repeat measure ANOVA. 36 patients were scanned at 0 and 6 months, with 26 patients scanned at the 3 years follow up. Only those who completed all three visits were included in the final analysis. Baseline atherosclerotic burden was high with a mean SAS of 15.7 ± 10.3. No significant progression was present at 6 months (mean SAS 16.4 ± 10.5, p = 0.67), however there was significant disease progression at 3 years (mean SAS 17.7 ± 11.5, p = 0.01). Those with atheroma progression at follow-up were less likely to be on statin therapy (79 vs 100 %, p = 0.04), and had significantly higher baseline SAS (17.6 ± 11.2 vs 10.7 ± 5.1, p = 0.043). Follow up of atheroma burden is possible with WB-MRA, which can successfully quantify and monitor atherosclerosis progression at 3 years follow-up

    Разработка и исследование конструкции привода управляемого задерживающего устройства шароструйно-эжекторного бурового снаряда

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    В работе рассмотрены принципы шароструйного бурения, а так же устройство шаростуйно-эжекторного снаряда. Предложены варианты модернизации данного снаряда.In this paper, the principles of pellet impact drilling, as well as the construction of a pellet-ejector projectile, are considered. Variants of modernization of this projectile are offered

    Expression of Constitutively Active CDK1 Stabilizes APC-Cdh1 Substrates and Potentiates Premature Spindle Assembly and Checkpoint Function in G1 Cells

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    Mitotic progression in eukaryotic cells depends upon the activation of cyclin-dependent kinase 1 (CDK1), followed by its inactivation through the anaphase-promoting complex (APC)/cyclosome-mediated degradation of M-phase cyclins. Previous work revealed that expression of a constitutively active CDK1 (CDK1AF) in HeLa cells permitted their division, but yielded G1 daughter cells that underwent premature S-phase and early mitotic events. While CDK1AF was found to impede the sustained activity of APC-Cdh1, it was unknown if this defect improperly stabilized mitotic substrates and contributed to the occurrence of these premature M phases. Here, we show that CDK1AF expression in HeLa cells improperly stabilized APC-Cdh1 substrates in G1-phase daughter cells, including mitotic kinases and the APC adaptor, Cdc20. Division of CDK1AF-expressing cells produced G1 daughters with an accelerated S-phase onset, interrupted by the formation of premature bipolar spindles capable of spindle assembly checkpoint function. Further characterization of these phenotypes induced by CDK1AF expression revealed that this early spindle formation depended upon premature CDK1 and Aurora B activities, and their inhibition induced rapid spindle disassembly. Following its normal M-phase degradation, we found that the absence of Wee1 in these prematurely cycling daughter cells permitted the endogenous CDK1 to contribute to these premature mitotic events, since expression of a non-degradable Wee1 reduced the number of cells that exhibited premature cyclin B1oscillations. Lastly, we discovered that Cdh1-ablated cells could not be forced into a premature M phase, despite cyclin B1 overexpression and proteasome inhibition. Together, these results demonstrate that expression of constitutively active CDK1AF hampers the destruction of critical APC-Cdh1 targets, and that this type of condition could prevent newly divided cells from properly maintaining a prolonged interphase state. We propose that this more subtle type of defect in activity of the APC-driven negative-feedback loop may have implications for triggering genome instability and tumorigenesis

    The cellular geography of Aurora kinases

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    Aurora is the name given to a family of highly conserved protein kinases with essential roles in many aspects of cell division. Yeasts have a single Aurora kinase, whereas mammals have three: Aurora A, B and C. During mitosis, Aurora kinases regulate the structure and function of the cytoskeleton and chromosomes and the interactions between these two at the kinetochore. They also regulate signalling by the spindle-assembly checkpoint pathway and cytokinesis. Perturbation of Aurora kinase expression or function might lead to cancer
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