Dating prograde fluid pulses during subduction by in situ U–Pb and oxygen isotope analysis

Keywords High-pressure fluids · Whiteschists · U–Pb dating · Oxygen isotopes · Ion microprobe · Metasomatism Introduction The subduction of crustal material to mantle depths and its chemical modification during burial and exhumation contribute to element recycling in the mantle and the formation of new crust through arc magmatism. Crustal rocks that Abstract The Dora-Maira whiteschists derive from metasomatically altered granites that experienced ultrahighpressure metamorphism at ~750 °C and 40 kbar during the Alpine orogeny. In order to investigate the P–T–time– fluid evolution of the whiteschists, we obtained U–Pb ages from zircon and monazite and combined those with trace element composition and oxygen isotopes of the accessory minerals and coexisting garnet. Zircon cores are the only remnants of the granitic protolith and still preserve a Permian age, magmatic trace element compositions and δ18O of ~10 ‰. Thermodynamic modelling of Si-rich and Si-poor whiteschist compositions shows that there are two main fluid pulses during prograde subduction between 20 and 40 kbar. In Si-poor samples, the breakdown of chlorite to garnet + fluid occurs at ~22 kbar. A first zircon rim directly overgrowing the cores has inclusions of prograde phlogopite and HREE-enriched patterns indicating zircon growth at the onset of garnet formation. A second main fluid pulse is documented close to peak metamorphic conditions in both Si-rich and Si-poor whiteschist when talc + kyanite react to garnet + coesite + fluid. A second metamorphic overgrowth on zircon with HREE depletion was observed in the Si-poor whiteschists, whereas a single metamorphic overgrowth capturing phengite and talc inclusions was observed in the Si-rich whiteschists. Garnet rims, zircon rims and monazite are in chemical and isotopic equilibrium for oxygen, demonstrating that they all formed at peak metamorphism at 35 Ma as constrained by the age of monazite (34.7 ± 0.4 Ma) and zircon rims (35.1 ± 0.8 Ma). The prograde zircon rim in Si-poor whiteschists has an age that is within error indistinguishable from the age of peak metamorphic conditions, consistent with a minimum rate of subduction of 2 cm/year for the Dora-Maira unit. Oxygen isotope values for zircon rims, monazite and garnet are equal within error at 6.4 ± 0.4 ‰, which is in line with closed-system equilibrium fractionation during prograde to peak temperatures. The resulting equilibrium Δ18Ozircon-monazite at 700 ± 20 °C is 0.1 ± 0.7 ‰. The in situ oxygen isotope data argue against an externally derived input of fluids into the whiteschists. Instead, fluidassisted zircon and monazite recrystallisation can be linked to internal dehydration reactions during prograde subduction. We propose that the major metasomatic event affecting the granite protolith was related to hydrothermal seafloor alteration post-dating Jurassic rifting, well before the onset of Alpine subduction.

Lethal giant discs, a novel C2 domain protein, restricts Notch activation during endocytosis

The Notch signaling pathway plays a central role in metazoan growth and patterning, and its deregulation leads to many human diseases, including cancer. It is therefore important to understand the modes of Notch signaling regulation. Recent discoveries have demonstrated that mutations in conserved endosomal pathway components such as Erupted and Vps25 can ectopically activate Notch signaling in Drosophila. Mutations in the tumor suppressor lethal giant discs (lgd) display similar but even stronger and more specific Notch activation than in the erupted and vps25 mutant animals. This Notch activation in lgd mutant tissues causes hyperplastic overgrowth of the Drosophila imaginal discs, and the eventual lethality of the animal. However, the gene that encodes Lgd, and its function in the Notch pathway have not yet been identified. ^ I have found that Lgd is a novel, conserved C2 domain protein that regulates Notch trafficking. Lgd cell-autonomously restricts Notch signaling in the Drosophila wing disc to the target cells in the D/V boundary. The function of Lgd lies at or upstream of Notch S3 activation, but Lgd doesn't affect the binding affinities between Notch and Delta. Lgd is also not required for cis-inhibition of Notch signaling by ligands. Notch accumulates on the early endosome in lgd mutant cells and signals in a ligand-independent manner, a result that has previously been seen in endosomal pathway mutants. Interestingly, Notch activation in lgd mutant cells is dependent on the endosomal protein Hrs, and Lgd activity appears to be downstream of Hrs function in endocytosis. Taken together, my data identify Lgd as a novel tumor suppressor protein that regulates Notch signaling by targeting Notch for degradation or recycling. ^

EGFR and Notch signaling pathways are regulated by distinct isoforms of Drosophila cbl

Activation of cell surface receptors transduces extracellular signals into cellular responses such as proliferation, differentiation and survival. However, the appropriate spatial and temporal down-regulation of signaling receptors is essential for normal development and homeostasis. The Cbl family of E3-ubiquitin ligases plays a major role for the ligand-dependent inactivation of growth factor receptors through ubiquitin-mediated endocytosis and lysosomal degradation. Here, we report the D-cbl mutant phenotypes in the Drosophila eye. D-cbl mutants display overgrowth, inhibition of apoptosis, differentiation defects and increased ommatidial spacing. Many of these phenotypes are caused by lack of down-regulation of the Drosophila EGFR signaling. However, not all D-cbl phenotypes can be explained by inappropriate EGFR activity. We found that D-Cbl also negatively regulates Notch activity during eye and wing development. D-cbl produces two isoforms by alternative splicing. Strikingly, the long isoform, D-CblL, preferentially regulates the EGFR, whereas the short isoform, D-CblS, preferentially regulates Notch. Taken together, these data suggest that D-Cbl controls at least two signaling pathways, EGFR and Notch, through production of two alternatively spliced isoforms during development in Drosophila.^

Analysis of the E1-ubiquitin activating enzyme, Uba1, in cell death and tissue growth in Drosophila

Ubiquitination is an essential process involved in basic biological processes such as the cell cycle and cell death. Ubiquitination is initiated by ubiquitin-activating enzymes (E1), which activate and transfer ubiquitin to ubiquitin-conjugating enzymes (E2). Subsequently, ubiquitin is transferred to target proteins via ubiquitin ligases (E3). Defects in ubiquitin conjugation have been implicated in several forms of malignancy, the pathogenesis of several genetic diseases, immune surveillance/viral pathogenesis, and the pathology of muscle wasting. However, the consequences of partial or complete loss of ubiquitin conjugation in multi-cellular organisms are not well understood. Here, we report the characterization of nba1, the sole E1 in Drosophila. We have determined that weak and strong nba1 alleluias behave genetically different and sometimes in opposing phenotypes. For example, weak uba1 alleluias protect cells from cell death whereas cells containing strong loss-of-function alleluias are highly apoptotic. These opposing phenotypes are due to differing sensitivities of cell death pathway components to ubiquitination level alterations. In addition, strong uba1 alleluias induce cell cycle arrest due to defects in the protein degradation of Cyclins. Surprisingly, clones of strong uba1 mutant alleluias stimulate neighboring wild-type tissue to undergo cell division in a non-autonomous manner resulting in severe overgrowth phenotypes in the mosaic fly. I have determined that the observed overgrowth phenotypes were due to a failure to downregulate the Notch signaling pathway in nba1 mutant cells. Aberrant Notch signaling results in the secretion of a local cytokine and activation of JAK/STAT pathway in neighboring cells. In addition, we elucidated a model describing the regulation of the caspase Dronc in surviving cells. Binding of Dronc by its inhibitor Diap1 is necessary but not sufficient to inhibit Dronc function. Ubiquitin conjugation and Uba1 function is necessary for the negative regulation of Dronc. ^

Demographic and social factors which influence periodontal disease using the National Health and Nutritional Examination Survey (NHANES)

Periodontal diseases include the various forms of gingivitis and periodontitis. Scientific literature submits 80% of the population suffers from some form of periodontal disease. The comparison of studies measuring periodontal disease is difficult because researchers use various parameters and indexes to define disease severity. The purposes of this paper were to examine the associations of gingival bleeding and 3 or more millimeters periodontal attachment loss, and age, sex, income, race/ethnicity, current tobacco use, dental visits, health insurance, stroke, heart attack, and diabetes using the periodontal examination population from the National Health and Nutritional Examination Survey (NHANES) 1999-2004. ^ When all risk factors were analyzed in the model as a whole sex, race/ethnicity, poverty, and education were statistically significant for bleeding on probing. When all risk factors were analyzed in the model as a whole sex, age, and education were statistically significant for loss of attachment. ^

ADHERENS JUNCTIONS AND THE ACTOMYOSIN NETWORK REGULATE ORGAN GROWTH BY MODULATING HIPPO PATHWAY ACTIVITY IN DROSOPHILA

Adherens junctions (AJs) and basolateral modules are important for the establishment and maintenance of apico-basal polarity. Loss of AJs and basolateral module members lead to tumor formation, as well as poor prognosis for metastasis. Recently, in mammalian studies it has been shown that loss of either AJ or basolateral module members deregulate Yorkie activity, the downstream transcriptional effector of the Hippo pathway. Importantly, it is unclear if AJ and basolateral components act through the same or parallel mechanisms to regulate Yorkie activity. Here, we dissect how loss of AJ and basolateral components affects Hippo signaling in Drosophila. Surprisingly, while scrib knock-down tissue displays increased reporter activity autonomously, α-cat knock-down tissue shows a cell autonomous decrease and a cell non-autonomous increase of Hippo reporter activity. We provided several lines of evidence to show the differential regulation in polarity protein localizations and oncogenic cooperative overgrowth by AJs and basolateral complexes. Finally, we show that Hippo pathway activity is induced in α-cat and scrib double knocked-down tissue. Taken together, our results provide evidence to show that basolateral modules and AJs act in parallel to modulate Hippo pathway activity. Non-muscle myosin II is an actomyosin component that interacts with the actin. Non-muscle myosin II also interacts with lgl, though the function of this interaction is not clear. Our lab demonstrated that modulating F-actin regulates Hippo pathway activity, and lgl also has been described as a Hippo pathway regulator. Therefore we suspect that myosin II is also involved in Hippo pathway regulation. We first characterized non-muscle Myosin II as a novel tumor suppressor gene by affecting Hippo pathway activity. Upstream regulators of Myosin II, members in the Rho signaling pathway, also displayed similar phenotypes as the Myosin II knock-down tissues. Apoptosis is also induced in myosin II knock-down tissues, however, blocking cell death does not affect myosin II knock-down induced Hippo activation. Our data suggested hyperactivating myosin II induced F-actin accumulation so therefore induces Hippo target activation. Unexpectedly, we also observed that reducing F-actin activity induced Hippo target activation in vivo. These controversial data indicated that actomyosin may regulate the Hippo pathway through multiple mechanisms.

Rifaximin-mediated changes to the epithelial cell proteome: 2-D gel analysis

Diarrhea remains a significant cause of worldwide morbidity and mortality. Over 4 million children die of diarrhea annually. Although antibiotics can be used as prophylaxis or for treatment of diarrhea, concern remains over antibiotic resistance. Rifaximin is a semi-synthetic rifamycin derivative that can be used to treat symptoms of infectious diarrhea, inflammatory bowel syndrome, bacterial overgrowth of the small bowel, pouchitis, and fulminant ulcerative colitis. Rifaximin is of particular interest because it is poorly adsorbed in the intestines, shows no indication of inducing bacterial resistance, and has minimal effect on intestinal flora. In order to better understand how rifaximin functions, we sought to compare the protein expression profile of cells pretreated with rifaximin, as compared to cells treated with acetone, rifamycin (control antibiotic), or media (untreated). 2-D gel electrophoresis identified 38 protein spots that were up- or down-regulated by over 2-fold in rifaximin treated cells compared to controls. 16 of these spots were down-regulated, including keratin, annexin A5, intestinal-type alkaline phosphatase, histone h4, and histone-binding protein RbbP4. 22 spots were up-regulated, including heat shock protein HSP 90 alpha, alkaline phosphatase, and fascin. Many of the identified proteins are associated with cell structure and cytoskeleton, transcription and translation, and cellular metabolism. A better understanding of the functionality of rifaximin will identify additional potential uses for rifaximin and determine for whom the drug is best suited. ^

Pathogenesis of antibiotic-associated diarrhea (AAD)---a systematic review

A common complication of antibiotic use is the development of diarrheal illness. The pathogenesis of antibiotic associated diarrhea (AAD) may be mediated through alteration of intestinal microbiota, overgrowth of opportunistic pathogens, and direct drug toxicity on the gut. Alterations in the intestinal microbiota result in metabolic imbalances, loss of colonization resistance and in turn allow proliferation of opportunistic pathogens. Currently less than 33% of AAD cases can be attributable to Clostridium difficile leaving a large number of cases undiagnosed and poorly treated. Although the pathogenesis of Clostridium difficile infection (CDI) has been well documented, the role of other putative microbial etiologies (Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida species) and their pathogenic mechanisms in AAD has been unclear. This review provides a comprehensive and systematic approach to the existing data on AAD and includes concise descriptions of the pathogenesis of CDI and non-CDI AAD in the form of figures.^

Distribution of abundance of planktic foraminifera and calcareous nannofossils at DSDP Sites 17-167 and 62-463

New paleomagnetic and paleontologic data from Pacific DSDP Sites 463 and 167 define the magnetic reversals that predate the Cretaceous Normal Polarity Superchron (K-N). Data from Mid-Pacific Mountain Site 463 provide the first definition of polarity chron M0 in the Pacific deep-sea sedimentary record. Foraminiferal biostratigraphy suggests that polarity chron M0 is contained entirely within the lower Aptian Hedbergella similis Zone, in agreement with foraminiferal data from the Italian Southern Alps and Atlantic Ocean. Nannofossil assemblages also suggest an early Aptian age for polarity chron M0, contrary to results from the Italian Umbrian Apennines and Southern Alps, which place polarity chron M0 on the Barremian-Aptian boundary. Biostratigraphic dating discrepancies caused by the time-transgressive, preservational, or provincial nature of paleontological species might be reconciled by the use of magnetostratigraphy, specifically polarity chron M0 which lies close to the Barremian-Aptian boundary. At Magellan Rise Site 167, five reversed polarity zones are recorded in Hauterivian to Aptian sediments. Correlation with M-anomalies is complicated by synsedimentary and postsedimentary sliding about 25 m.y. after basement formation, producing gaps in, and duplications of, the stratigraphic sequence. The magnitude and timing of such sliding must be addressed when evaluating the stratigraphy of these oceanic-rise environments.

Seaweed - epiphyte - mesograzer communities were tested for their responses to elevated seawater temperature and [CO2] in benthic mesocosms experiments across four consecutive seasons of one year in Kiel, Germany

Rising seawater temperature and CO2 concentrations (ocean acidification) represent two of the most influential factors impacting marine ecosystems in the face of global climate change. In ecological climate change research full-factorial experiments across seasons in multi-species, cross-trophic level set-ups are essential as they allow making realistic estimations about direct and indirect effects and the relative importance of both major environmental stressors on ecosystems. In benthic mesocosm experiments we tested the responses of coastal Baltic Sea Fucus vesiculosus communities to elevated seawater temperature and CO2 concentrations across four seasons of one year. While increasing [CO2] levels only had minor effects, warming had strong and persistent effects on grazers which affected the Fucus community differently depending on season. In late summer a temperature-driven collapse of grazers caused a cascading effect from the consumers to the foundation species resulting in overgrowth of Fucus thalli by epiphytes. In fall/ winter, outside the growing season of epiphytes, intensified grazing under warming resulted in a significant reduction of Fucus biomass. Thus, we confirm the prediction that future increasing water temperatures influence marine food-web processes by altering top-down control, but we also show that specific consequences for food-web structure depend on season. Since Fucus vesiculosus is the dominant habitat-forming brown algal system in the Baltic Sea, its potential decline under global warming implicates the loss of key functions and services such as provision of nutrient storage, substrate, food, shelter and nursery grounds for a diverse community of marine invertebrates and fish in Baltic Sea coastal waters.

Quaternary and Paleogene calcareous nannofossils of ODP Leg 115

The occurrences of ten datum events for the Quaternary and top Pliocene nannofossils are identified at nine Leg 115 sites. A quantitative investigation of Paleogene nannofossils in 470 samples selected from 11 holes at 9 sites yielded 197 taxa, including one new species and 10 unidentified taxa that are likely to be new species. Regional differences in the timing of some biostratigraphically important events are recognized, and a set of datum events useful for biostratigra- phy in the tropical Indian Ocean is presented. Biogeographical differences are minor for Paleogene cores from the tropical sites (Sites 707-716); however, the Quaternary and late early Oligocene floras observed at the two subtropical sites (Sites 705 and 706) differ significantly from the corresponding floras of the tropical sites. Bathymetrically controlled dissolution is recognized by the reduction of species diversity in the Paleogene flora. Selective dissolution of nannofossils is also evidenced by the percentage reduction of three holococcolith taxa, Lanternithus minutus, Zygrhablithus bijugatus, and Holococcolith type A as well as by the increase of Coccolithus pelagicusand Cribrocentrum reticulatumin the deeper sites.

Upper Triassic nannofossils from Wombat Plateau, Northwest Australia

A taxonomic and biostratigraphic investigation has been carried out on Upper Triassic (Carnian-Rhaetian) nannofossils from Sites 759, 760, 761 and 764 drilled on the Wombat Plateau during ODP Leg 122. The recovery of continuous sequences containing well preserved nannofossils has enabled us to refine the previous taxonomy and biostratigraphy of this interval. Fossil assemblages are of two major types: (1) previously described calcareous taxa were recovered at Sites 761 and 764; and (2) sideritic forms, which may represent diagenetic replacement of calcareous nannofossils, were observed in material from Sites 759 and 760. The sideritic forms proved difficult to study taxonomically due to inadequate optical properties. Calcareous nannofossil assemblages in the Upper Triassic are dominated by Prinsiosphaera triassica. We show that the multitude of identities of this species in the light microscope are the result of selective etching on a layered structure. We propose an evolutionary lineage for the earliest known coccoliths, with Crucirhabdus primulus as the ancestor. This species gave rise to C. minutus and Archaeozygodiscus koessenensis. The Upper Triassic can be subdivided based on the sequential first occurrences of C. primulus and Eoconusphaera zlambachensis in the upper Norian. The late Norian and Rhaetian were times of slow evolution of calcareous nannofossils. However, we noted three morphometric changes in this time-interval which possess biostratigraphic utility: (1) P. triassica increases in diameter from an average of 6 µm to over 9 µm; (2) E. zlambachensis evolves from a stubby to an elongated shape; and (3) C. primulus increases in size. Upper Triassic assemblages from the Wombat Plateau are similar in composition and diversity to those which have been described in detail from the Alps. In both areas, nannofossiliferous sediments interfinger with massive limestones deposited in reef and peri-platform environments. Stable isotopic analyses of Wombat Plateau nannofossil assemblages indicate that they thrived in open ocean conditions. Biostratigraphy allows sequence chronostratigraphic interpretation of ODP Site 761 and supports the chronostratigraphic cycle charts of Haq et al. (1987).

A Middle Pleistocene nannofossil record of sediment core MD03-2699

Changes in paleoclimate and paleoproductivity patterns have been identified by analysing, in conjunction with other available proxy data, the coccolithophore assemblages from core MD03-2699, located in the Portuguese margin in the time interval from the Marine Isotope Stage (MIS) 13/14 boundary to MIS 9 (535 to 300 ka). During the Mid-Brunhes event, the assemblages associated with the eccentricity minima are characterised by higher nannoplankton accumulation rate (NAR) values and by the blooming of the opportunistic genus Gephyrocapsa. Changes in coccolithophore abundance are also related to glacial-interglacial cycles. Higher NAR and numbers of coccoliths/g mainly occurred during the interglacial periods, while these values decreased during the glacial periods. Superimposed on the glacial/interglacial cycles, climatic and paleoceanographic variability has been observed on precessional timescales. The structure of the assemblages highlights the prevailing long-term influence of the Portugal (PC) and Iberian Poleward (IPC) Currents, following half and full precession harmonics, related to the migration of the Azores High (AH) Pressure System. Small Gephyrocapsa and Coccolithus pelagicus braarudii are regarded as good indicators for periods of prevailing PC influence. Gephyrocapsa caribbeanica, Syracosphaera spp., Rhabdosphaera spp. and Umbilicosphaera sibogae denote periods of IPC influence. Our data also highlights the increased percentages of Coccolithus pelagicus pelagicus during the occurrence of episodes of very cold and low salinity surface water, probably related to abrupt climatic events and millennial-scale oscillations of the AH/Icelandic Low (IL) System.