The Coniacian–Santonian sedimentary record in southern Tanzania (Ruvuma Basin, East Africa): Planktonic foraminiferal evolutionary, geochemical and palaeoceanographic patterns

AbstractA 101 m thick stratigraphically complete late Coniacian–early Santonian (ca 89 to 83 Ma) sedimentary sequence drilled in Tanzania (Tanzania Drilling Project Site 39) allows, for the first time, examination of the planktonic foraminiferal biostratigraphy and evolution, the depositional history, and geochemical patterns of the subtropical–tropical Indian Ocean region. The sedimentary succession corresponds to an outer shelf to upper slope setting and is dominated by calcareous clayey siltstones and mudstones. The occurrences of Tethyan marker species enable application of the tropical biozonation including identification of the Dicarinella concavata and Dicarinella asymetrica Zones. In addition, Tanzania Drilling Project Site 39 is proposed as reference section for the Coniacian/Santonian boundary in the Indian Ocean with the boundary placed at the lowest occurrence of Globotruncana linneiana in agreement with the Global Stratotype Section and Point (Spain). The record at Tanzania Drilling Project Site 39 provides a unique opportunity to document the planktonic foraminiferal evolution in a subtropical marginal sea environment during a key period in their evolutionary history characterized by a major radiation among the deep‐dwelling taxa. Combined documentation of lithological and geochemical changes (%CaCO3, %Corg, δ13Ccarb and δ18Ocarb) reveals a setting influenced by continental‐derived nutrients in the Dicarinella concavata Zone (Lindi Formation) with a change to higher carbonate production and reduced surface water primary productivity in the overlying Dicarinella asymetrica Zone (Nangurukuru Formation). Planktonic foraminiferal assemblage changes mirror the depositional and geochemical trends and indicate a progressive shift from a more eutrophic to a more oligotrophic regime through time. At the local scale, this palaeoceanographic scenario is consistent with the deepening of coastal Tanzania in response to the Late Cretaceous marine transgression registered in south‐east Tanzania. Because the tectonic evolution and sea‐level rise along the East Africa continental margin is superimposed on the Coniacian–Campanian global long‐term sea‐level high, this study hypothesizes that the epicontinental invasion of blue waters may have favoured radiation among deep‐dwelling taxa

Late Cretaceous Paleoceanographic Evolution and the Onset of Cooling in the Santonian at Southern High Latitudes (IODP Site U1513, SE Indian Ocean)

The latest Cenomanian to Santonian sedimentary record recovered at IODP Expedition 369 Site U1513 in the Mentelle Basin (SE Indian Ocean, paleolatitude 60°S at 85 Ma) is studied to interpret the paleoceanographic evolution in the Southern Hemisphere. The planktonic foraminiferal assemblage changes, the depth ecology preferences of different species, and the surface and seafloor temperature inferred from the stable isotopic values measured on foraminiferal tests provide meaningful information to the understanding of the Late Cretaceous climate. The hothouse climate during the Turonian-Santonian, characterized by weak latitudinal temperature gradients and high atmospheric CO2 concentrations, is followed by a progressive cooling during the Campanian. At Site U1513 the beginning of this climatic transition is nicely recorded within the Santonian, as indicated by an ∼1‰ increase in δ18O values of planktonic foraminifera suggesting a decline in surface water paleotemperatures of 4°C. The onset of cooling is mirrored by changes in the planktonic foraminiferal assemblages including extinctions among surface and deep dwellers, appearances and diversification of newly evolving taxa, and changes from predominantly epifaunal oxic to infaunal dysoxic/ suboxic taxa among co-occurring benthic foraminifera. Overall, the data presented here document an interval in the Santonian during which the rate of southern high latitude cooling increased. Both surface and bottom waters were affected, although the cooling signal is more evident in the data for surface waters. This pattern of cooling ascribes the deterioration of the Late Cretaceous climate to decreased CO2 in the atmosphere and changes in the oceanic circulation correlated with enhanced meridional circulation

Testing the early Late Ordovician cool-water hypothesis with oxygen isotopes from conodont apatite

© 2017 Cambridge University Press. Latest Sandbian to early Katian sequences across Laurentia\u27s epicontinental sea exhibit a transition from lithologies characterized as \u27warm-water\u27 carbonates to those characterized as \u27cool-water\u27carbonates. This shift occurs across the regionally recognized M4/M5 sequence stratigraphic boundary and has been attributed to climatic cooling and glaciation, basin reorganization and upwelling of open ocean water, and/or increased water turbidity and terrigenous input associated with the Taconic tectophase. Documentation of oxygen isotopic trends across the M4/M5 and through bracketing strata provides a potential means of distinguishing among these alternative scenarios; however, oxygen isotopic records generated to date have failed to settle the debate. This lack of resolution is because δ18O records are open to multiple interpretations and potentially confounding factors related to local environmental conditions have not been tested by examining the critical interval in multiple areas and different depositional settings. To begin to address this shortcoming, we present new species-specific and mixed assemblage conodont δ18O values in samples spanning the M4/M5 boundary from the Upper Mississippi Valley, Alabama, and Virginia. The new results are combined with previous studies, providing a record of δ18O variability across SE Laurentia. The combined dataset allows us to test for regional trends at a resolution not previously available. Our results document a ~1.5‰ decrease in values across Laurentia instead of increasing δ18O values across the M4/M5 as predicted in various \u27cool-water\u27 scenarios. In short, these results do not support a shift to \u27cool-water\u27 conditions as an explanation for changes in early Katian carbonates across the M4/M5

Biotic and Paleoceanographic Changes Across the Late Cretaceous Oceanic Anoxic Event 2 in the Southern High Latitudes (IODP Sites U1513 and U1516, SE Indian Ocean)

Oceanic Anoxic Event 2, spanning the Cenomanian/Turonian boundary (93.9 Ma), was an episode of major perturbations in the global carbon cycle. To investigate the response of biota and the paleoceanographic conditions across this event, we present data from International Ocean Discovery Program sites U1513 and U1516 in the Mentelle Basin (offshore SW Australia; paleolatitude 59°–60°S in the mid-Cretaceous) that register the first complete records of OAE 2 at southern high latitudes. Calcareous nannofossils provide a reliable bio-chronostratigraphic framework. The distribution and abundance patterns of planktonic and benthic foraminifera, radiolaria, and calcispheres permit interpretation of the dynamics of the water mass stratification and provide support for the paleobathymetric reconstruction of the two sites, with Site U1513 located northwest of the Mentelle Basin depocenter and at a deeper depth than Site U1516. The lower OAE 2 interval is characterized by reduced water mass stratification with alternating episodes of enhanced surface water productivity and variations of the thickness of the mixed layer as indicated by the fluctuations in abundance of the intermediate dwelling planktonic foraminifera. The middle OAE 2 interval contains lithologies composed almost entirely of radiolaria reflecting extremely high marine productivity; the low CaCO3 content is consistent with marked shoaling of the Carbonate Compensation Depth and ocean acidification because of CaCO3 undersaturation. Conditions moderated after deposition of the silica-rich, CaCO3-poor rocks as reflected by the microfossil changes indicating a relatively stable water column although episodes of enhanced eutrophy did continue into the lower Turonian at Site U1516

Pathway profiling of a novel SRC inhibitor, AZD0424, in combination with MEK inhibitors

A more comprehensive understanding of how cells respond to drug intervention, the likely immediate signalling responses and how resistance may develop within different microenvironments will help inform treatment regimes. The nonreceptor tyrosine kinase SRC regulates many cellular signalling processes, and pharmacological inhibition has long been a target of cancer drug discovery projects. Here, we describe the in vitro and in vivo characterisation of the small‐molecule SRC inhibitor AZD0424. We show that AZD0424 potently inhibits the phosphorylation of tyrosine‐419 of SRC (IC50 ~ 100 nm) in many cancer cell lines; however, inhibition of cell viability, via a G1 cell cycle arrest, was observed only in a subset of cancer cell lines in the low (on target) micromolar range. We profiled the changes in intracellular pathway signalling in cancer cells following exposure to AZD0424 and other targeted therapies using reverse‐phase protein array (RPPA) analysis. We demonstrate that SRC is activated in response to treatment of KRAS‐mutant colorectal cell lines with MEK inhibitors (trametinib or AZD6244) and that AZD0424 abrogates this. Cell lines treated with trametinib or AZD6244 in combination with AZD0424 had reduced EGFR, FAK and SRC compensatory activation, and cell viability was synergistically inhibited. In vivo, trametinib treatment of mice‐bearing HCT116 tumours increased phosphorylation of SRC on Tyr419, and, when combined with AZD0424, inhibition of tumour growth was greater than with trametinib alone. We also demonstrate that drug‐induced resistance to trametinib is not re‐sensitised by AZD0424 treatment in vitro, likely as a result of multiple compensatory signalling mechanisms; however, inhibition of SRC remains an effective way to block invasion of trametinib‐resistant tumour cells. These data imply that SRC inhibition may offer a useful addition to MEK inhibitor combination strategies

NODAL/TGFβ signalling mediates the self-sustained stemness induced by PIK3CAH1047R homozygosity in pluripotent stem cells

Activating PIK3CA mutations are known “drivers” of human cancer and developmental overgrowth syndromes. We recently demonstrated that the "hotspot" PIK3CAH1047R variant exerts unexpected allele dose-dependent effects on stemness in human pluripotent stem cells (hPSCs). In the present study, we combine high-depth transcriptomics, total proteomics and reverse-phase protein arrays to reveal potentially disease-related alterations in heterozygous cells, and to assess the contribution of activated TGFβ signalling to the stemness phenotype of homozygous PIK3CAH1047R cells. We demonstrate signalling rewiring as a function of oncogenic PI3K signalling strength, and provide experimental evidence that self-sustained stemness is causally related to enhanced autocrine NODAL/TGFβ signalling. A significant transcriptomic signature of TGFβ pathway activation in heterozygous PIK3CAH1047R was observed but was modest and was not associated with the stemness phenotype seen in homozygous mutants. Notably, the stemness gene expression in homozygous PIK3CAH1047R iPSCs was reversed by pharmacological inhibition of NODAL/TGFβ signalling, but not by pharmacological PI3Kα pathway inhibition. Altogether, this provides the first in-depth analysis of PI3K signalling in human pluripotent stem cells and directly links strong PI3K activation to developmental NODAL/TGFβ signalling. This work illustrates the importance of allele dosage and expression when artificial systems are used to model human genetic disease caused by activating PIK3CA mutations

ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling

ISG15 is an ubiquitin-like modifier that is associated with reduced survival rates in breast cancer patients. The mechanism by which ISG15 achieves this however remains elusive. We demonstrate that modification of Rab GDP-Dissociation Inhibitor Beta (GDI2) by ISG15 (ISGylation) alters endocytic recycling of the EGF receptor (EGFR) in non-interferon stimulated cells using CRISPR-knock out models for ISGylation. By regulating EGFR trafficking, ISGylation enhances EGFR recycling and sustains Akt-signalling. We further show that Akt signalling positively correlates with levels of ISG15 and its E2-ligase in basal breast cancer cohorts, confirming the link between ISGylation and Akt signalling in human tumours. Persistent and enhanced Akt activation explains the more aggressive tumour behaviour observed in human breast cancers. We show that ISGylation can act as a driver of tumour progression rather than merely being a bystander.</p

The Time-Domain Spectroscopic Survey: Understanding the Optically Variable Sky with SEQUELS in SDSS-III

The Time-Domain Spectroscopic Survey (TDSS) is an SDSS-IV eBOSS subproject primarily aimed at obtaining identification spectra of ~220,000 optically-variable objects systematically selected from SDSS/Pan-STARRS1 multi-epoch imaging. We present a preview of the science enabled by TDSS, based on TDSS spectra taken over ~320 deg^2 of sky as part of the SEQUELS survey in SDSS-III, which is in part a pilot survey for eBOSS in SDSS-IV. Using the 15,746 TDSS-selected single-epoch spectra of photometrically variable objects in SEQUELS, we determine the demographics of our variability-selected sample, and investigate the unique spectral characteristics inherent in samples selected by variability. We show that variability-based selection of quasars complements color-based selection by selecting additional redder quasars, and mitigates redshift biases to produce a smooth quasar redshift distribution over a wide range of redshifts. The resulting quasar sample contains systematically higher fractions of blazars and broad absorption line quasars than from color-selected samples. Similarly, we show that M-dwarfs in the TDSS-selected stellar sample have systematically higher chromospheric active fractions than the underlying M-dwarf population, based on their H-alpha emission. TDSS also contains a large number of RR Lyrae and eclipsing binary stars with main-sequence colors, including a few composite-spectrum binaries. Finally, our visual inspection of TDSS spectra uncovers a significant number of peculiar spectra, and we highlight a few cases of these interesting objects. With a factor of ~15 more spectra, the main TDSS survey in SDSS-IV will leverage the lessons learned from these early results for a variety of time-domain science applications.Comment: 17 pages, 14 figures, submitted to Ap

A lower to middle Eocene astrochronology for the Mentelle Basin (Australia) and its implications for the geologic time scale

The geologic time scale for the Cenozoic Era has been notably improved over the last decades by virtue of integrated stratigraphy, combining high-resolution astrochronologies, biostratigraphy and magnetostratigraphy with high-precision radioisotopic dates. However, the middle Eocene remains a weak link. The so-called “Eocene time scale gap” reflects the scarcity of suitable study sections with clear astronomically-forced variations in carbonate content, primarily because large parts of the oceans were starved of carbonate during the Eocene greenhouse. International Ocean Discovery Program (IODP) Expedition 369 cored a carbonate-rich sedimentary sequence of Eocene age in the Mentelle Basin (Site U1514, offshore southwest Australia). The sequence consists of nannofossil chalk and exhibits rhythmic clay content variability. Here, we show that IODP Site U1514 allows for the extraction of an astronomical signal and the construction of an Eocene astrochronology, using 3-cm resolution X-Ray fluorescence (XRF) core scans. The XRF-derived ratio between calcium and iron content (Ca/Fe) tracks the lithologic variability and serves as the basis for our U1514 astrochronology. We present a 16 million-year-long (40-56 Ma) nearly continuous history of Eocene sedimentation with variations paced by eccentricity and obliquity. We supplement the high-resolution XRF data with low-resolution bulk carbon and oxygen isotopes, recording the long-term cooling trend from the Paleocene-Eocene Thermal Maximum (PETM – ca. 56 Ma) into the middle Eocene (ca. 40 Ma). Our early Eocene astrochronology corroborates existing chronologies based on deep-sea sites and Italian land sections. For the middle Eocene, the sedimentological record at U1514 provides a single-site geochemical backbone and thus offers a further step towards a fully integrated Cenozoic geologic time scale at orbital resolution