Calcareous nannofossil assemblages across the Pliensbachian/Toarcian boundary at the Peniche section (Ponta do Trovão, Lusitanian Basin)

The Peniche section has revealed moderately-to-well preserved calcareous nannofossil assemblages across the Pliensbachian/Toarcian boundary. This good record has allowed the proposition of a refined biostratigraphic scheme. The stage boundary, as defined by ammonites, is comprised within the NJ5b C. impontus (NW Europe; BOWN & COOPER, 1998) or the NJT5b L. sigillatus (Mediterranean Tethys; MATTIOLI & ERBA, 1999) nannofossil subzones. Since in the Lusitanian Basin a mixing of N- and S-Tethyan taxa is observed, both biozonation schemes can be applied. Some nannofossil events (mainly first occurrences) are observed earlier in Portugal than in other Tethyan settings. It is still unclear if these events are real first occurrences. A diversification phase occurred across the Pliensbachian/Toarcian boundary. This phase is well recorded at Peniche, where a change is observed passing from the Pliensbachian, when assemblages are dominated by muroliths, to the Toarcian showing assemblages where placoliths are abundant. A quantification of nannofossils per gram of rock shows that absolute abundances are the highest across the Pliensbachian/Toarcian boundary. Indeed, Peniche exhibits nannofossil abundances very high with respect to correlative levels in other Tethyan settings. The pelagic carbonate fraction (produced by nannofossils) is important in the marly hemi-couplets of Peniche. In some levels, nannofossils account for more than 50% of the total carbonate fraction

Revisiting Early Jurassic Biscutaceae: Similiscutum giganteum sp. nov.

A large, broadly elliptical coccolith of the genus Similiscutum (Biscutaceae) was observed in sediments dated from the Lower Jurassic (upper Pliensbachian to Toarcian) coming from different localities of western Tethys, namely Portugal (Lusitanian Basin), France (Causses and Paris basins) and Spain (Subbetic area). This form is quite easy to find in the Toarcian GSSP (Global Stratotype Section and Point) of Peniche (Portugal), where the holotype has been described. More than 100 specimens of Similiscutum were digitally captured using a CCD camera, including this large form and two other related species, Similiscutum finchii and Similiscutum novum. The length and width of the coccoliths and the length and width of their central area were measured, and biometric analyses were performed. Results show that this large morphotype of Similiscutum is well characterized and easily differentiable by its size and morphology from the species S. finchii and S. novum, which are characterized by a similar extinction pattern in optical-microscope crossed polars . On the basis of combined differences in size and in central-area shape and structure, Similiscutum giganteum sp. nov. is introduced here. (Plant Fossil Names Registry no.: PFN003067; Act LSID: urn:lsid:plantfossilnames.org:act:3067).</p

No-nonsense:insights into the functional interplay of nonsense-mediated mRNA decay factors

Nonsense-mediated messenger RNA decay (NMD) represents one of the main surveillance pathways used by eukaryotic cells to control the quality and abundance of mRNAs and to degrade viral RNA. NMD recognises mRNAs with a premature termination codon (PTC) and targets them to decay. Markers for a mRNA with a PTC, and thus NMD, are a long a 3′-untranslated region and the presence of an exon-junction complex (EJC) downstream of the stop codon. Here, we review our structural understanding of mammalian NMD factors and their functional interplay leading to a branched network of different interconnected but specialised mRNA decay pathways. We discuss recent insights into the potential impact of EJC composition on NMD pathway choice. We highlight the coexistence and function of different isoforms of up-frameshift protein 1 (UPF1) with an emphasis of their role at the endoplasmic reticulum and during stress, and the role of the paralogs UPF3B and UPF3A, underscoring that gene regulation by mammalian NMD is tightly controlled and context-dependent being conditional on developmental stage, tissue and cell types

Phosphorylation of specific sets of tau isoforms reflects different neurofibrillary degeneration processes

AbstractTau proteins are the basic components of filaments that accumulate within neurons during neurofibrillary degeneration, a degenerating process with disease-specific phenotypes. This specificity is likely to be sustained by both phosphorylation state and isoform content of tau aggregates that form neuronal inclusions. In the present study, characterization of tau isoforms involved in neurofibrillary degeneration in Alzheimer's disease, Pick's disease, corticobasal degeneration and progressive supra-nuclear palsy was performed. Both analyses by immunoblotting using specific tau antibodies and cell transfection by tau isoform cDNAs allowed us to demonstrate the aggregation of (1) the six hyperphosphorylated tau isoforms in Alzheimer's disease, (2) tau isoforms without exon 10-encoding sequence in Pick's disease and (3) hyperphosphorylated exon 10-tau isoforms in corticobasal degeneration and progressive supranuclear palsy. Thus, neurofibrillary degeneration phenotypes are likely to be related to the phosphorylation of different combinations of tau isoforms (with and/or without exon 10-encoding sequence) in subpopulations of neurons

Pathophysiological Changes in the Enteric Nervous System of Rotenone-Exposed Mice as Early Radiological Markers for Parkinson's Disease

Parkinson's disease (PD) is known to involve the peripheral nervous system (PNS) and the enteric nervous system (ENS). Functional changes in PNS and ENS appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients like constipation, that can precede the appearance of motor symptoms by years. Here we analyzed the effect of the pesticide rotenone, a mitochondrial Complex I inhibitor, on the function and neuronal composition of the ENS by measuring intestinal contractility in a tissue bath and by analyzing related protein expression. Our results show that rotenone changes the normal physiological response of the intestine to carbachol, dopamine and electric field stimulation (EFS). Changes in the reaction to EFS seem to be related to the reduction in the cholinergic input but also related to the noradrenergic input, as suggested by the non-adrenergic non-cholinergic (NANC) reaction to the EFS in rotenone-exposed mice. The magnitude and direction of these alterations varies between intestinal regions and exposure times and is associated with an early up-regulation of dopaminergic, cholinergic and adrenergic receptors and an irregular reduction in the amount of enteric neurons in rotenone-exposed mice. The early appearance of these alterations, that start occurring before the substantia nigra is affected in this mouse model, suggests that these alterations could be also observed in patients before the onset of motor symptoms and makes them ideal potential candidates to be used as radiological markers for the detection of Parkinson's disease in its early stages

Base of the Toarcian Stage of the Lower Jurassic defined by the Global Boundary Stratotype Section and Point (GSSP) at the Peniche section (Portugal)

This is the final version of the article. Available from the publisher via the DOI in this record.The Global Stratotype Section and Point (GSSP) for the base of Toarcian Stage, Lower Jurassic, is placed at the base of micritic limestone bed 15e at Ponta do Trovão (Peniche, Lusitanian Basin, Portugal; coordinates: 39°22'15''N, 9°23'07''W), 80km north of Lisbon, and coincides with the mass occurrence of the ammonite Dactylioceras (Eodactylites). The Pliensbachian/ Toarcian boundary (PLB/TOA) is contained in a continuous section forming over 450m of carbonate-rich sediments. Tectonics, syn-sedimentary disturbance, metamorphism or significant diagenesis do not significantly affect this area. At the PLB/TOA, no vertical facies changes, stratigraphical gaps or hiatuses have been recorded. The base of the Toarcian Stage is marked in the bed 15e by the first occurrence of D. (E.) simplex, co-occurring with D. (E.) pseudocommune and D. (E.) polymorphum. The ammonite association of D. (Eodactylites) ssp. and other species e.g. Protogrammoceras (Paltarpites) cf. paltum, Lioceratoides aff. ballinense and Tiltoniceras aff. capillatum is particularly significant for the boundary definition and correlation with sections in different basins. Ammonites of the PLB/ TOA are taxa characteristic of both the Mediterranean and Northwest European provinces that allow reliable, global correlations. The PLB/TOA is also characterized by other biostratigraphical markers (brachiopods, calcareous nannofossils, ostracods and benthic foraminifers) and by high-resolution stable carbon and oxygen isotopes, and 87Sr/86Sr ratios that show distinctive changes just above the PLB/TOA, thus providing additional, powerful tools for global correlations. The PBL-TOA lies at the end of a second (and third) order cycle of sea-level change, and the top of bed 15e is interpreted as a sequence boundary. Cyclostratigraphy analysis is available for the Lower Toarcian of Ponta do Trovão. Detailed correlations with the Almonacid de la Cuba section (Iberian Range, Spain) provide complementary data of the ammonite succession in the Northwest European Hawskerense and Paltum Subzones, and magnetostratigraphical data that allow supraregional correlations. The proposal was voted on by the Toarcian Working Group in June, 2012, and by the International Subcommission on Jurassic Stratigraphy in September, 2012, approved by the ICS in November, 2014, and ratified by the IUGS in December, 2014. With this Toarcian GSSP, all international stages of the Lower Jurassic have been officially defined.Several scientists have been members of the Toarcian Working Group. We would like to acknowledge all of them. We are also grateful to the ISJS and ICS members who have made valuable comments on a previous version of this manuscript. We warmly thank Marc Philippe for his help with the literature on Pliensbachian/Toarcian continental successions. We warmly thank Christian Meister and Jim Ogg for their helpful review. Constructive remarks by Jim Ogg on an early version of the paper were greatly appreciated. We also acknowledge the precious help of David Besson for providing the ammonite specimens from the Mouterde collection (Musée des Confluences, Lyon). Ammonite photographs were taken by Emmanuel Robert (Collections de Géologie de Lyon). This paper is dedicated to the memory of Abbé René Mouterde and Serge Elmi, who died in 2007 after having been for years the main supporters of the Peniche section as GSSP of Toarcian Stage. Calcareous nannofossil slides are curated at the Collections de Géologie de Lyon (No. FSL 766535-766617). This work has been supported by the BIOSCALES Project (POCTI/ 36438/PAL/2000), coordinated by the Universidade NOVA de Lisboa; R. B. Rocha thanks the support of A. F. Soares, J. C. Kullberg, P. S. Caetano and P. H. Verdial. Financial support was provided to L. V. Duarte, S. Pinto and M. C. Cabral by Projects PDCTE/CTA/44907/2002 and PTDC/CTE-GIX/098968/2008

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

Two-Dimensional Electrophoresis of Tau Mutants Reveals Specific Phosphorylation Pattern Likely Linked to Early Tau Conformational Changes

The role of Tau phosphorylation in neurofibrillary degeneration linked to Alzheimer's disease remains to be established. While transgenic mice based on FTDP-17 Tau mutations recapitulate hallmarks of neurofibrillary degeneration, cell models could be helpful for exploratory studies on molecular mechanisms underlying Tau pathology. Here, “human neuronal cell lines” overexpressing Wild Type or mutated Tau were established. Two-dimensional electrophoresis highlights that mutated Tau displayed a specific phosphorylation pattern, which occurs in parallel to the formation of Tau clusters as visualized by electron microscopy. In fact, this pattern is also displayed before Tau pathology onset in a well established mouse model relevant to Tau aggregation in Alzheimer's disease. This study suggests first that pathological Tau mutations may change the distribution of phosphate groups. Secondly, it is possible that this molecular event could be one of the first Tau modifications in the neurofibrillary degenerative process, as this phenomenon appears prior to Tau pathology in an in vivo model and is linked to early steps of Tau nucleation in Tau mutants cell lines. Such cell lines consist in suitable and evolving models to investigate additional factors involved in molecular pathways leading to whole Tau aggregation

On the structure and function of the phytoene desaturase CRTI from Pantoea ananatis, a membrane-peripheral and FAD-dependent oxidase/isomerase

CRTI-type phytoene desaturases prevailing in bacteria and fungi can form lycopene directly from phytoene while plants employ two distinct desaturases and two cis-tans isomerases for the same purpose. This property renders CRTI a valuable gene to engineer provitamin A-formation to help combat vitamin A malnutrition, such as with Golden Rice. To understand the biochemical processes involved, recombinant CRTI was produced and obtained in homogeneous form that shows high enzymatic activity with the lipophilic substrate phytoene contained in phosphatidyl-choline (PC) liposome membranes. The first crystal structure of apo-CRTI reveals that CRTI belongs to the flavoprotein superfamily comprising protoporphyrinogen IX oxidoreductase and monoamine oxidase. CRTI is a membrane-peripheral oxidoreductase which utilizes FAD as the sole redox-active cofactor. Oxygen, replaceable by quinones in its absence, is needed as the terminal electron acceptor. FAD, besides its catalytic role also displays a structural function by enabling the formation of enzymatically active CRTI membrane associates. Under anaerobic conditions the enzyme can act as a carotene cis-trans isomerase. In silico-docking experiments yielded information on substrate binding sites, potential catalytic residues and is in favor of single half-site recognition of the symmetrical C(40) hydrocarbon substrate

Propofol Directly Increases Tau Phosphorylation

In Alzheimer's disease (AD) and other tauopathies, the microtubule-associated protein tau can undergo aberrant hyperphosphorylation potentially leading to the development of neurofibrillary pathology. Anesthetics have been previously shown to induce tau hyperphosphorylation through a mechanism involving hypothermia-induced inhibition of protein phosphatase 2A (PP2A) activity. However, the effects of propofol, a common clinically used intravenous anesthetic, on tau phosphorylation under normothermic conditions are unknown. We investigated the effects of a general anesthetic dose of propofol on levels of phosphorylated tau in the mouse hippocampus and cortex under normothermic conditions. Thirty min following the administration of propofol 250 mg/kg i.p., significant increases in tau phosphorylation were observed at the AT8, CP13, and PHF-1 phosphoepitopes in the hippocampus, as well as at AT8, PHF-1, MC6, pS262, and pS422 epitopes in the cortex. However, we did not detect somatodendritic relocalization of tau. In both brain regions, tau hyperphosphorylation persisted at the AT8 epitope 2 h following propofol, although the sedative effects of the drug were no longer evident at this time point. By 6 h following propofol, levels of phosphorylated tau at AT8 returned to control levels. An initial decrease in the activity and expression of PP2A were observed, suggesting that PP2A inhibition is at least partly responsible for the hyperphosphorylation of tau at multiple sites following 30 min of propofol exposure. We also examined tau phosphorylation in SH-SY5Y cells transfected to overexpress human tau. A 1 h exposure to a clinically relevant concentration of propofol in vitro was also associated with tau hyperphosphorylation. These findings suggest that propofol increases tau phosphorylation both in vivo and in vitro under normothermic conditions, and further studies are warranted to determine the impact of this anesthetic on the acceleration of neurofibrillary pathology