Arctic Ocean temperatures influence ecosystems, sea ice, species diversity, biogeochemical cycling, seafloor methane stability, deep-sea circulation, and CO
cycling. Today's Arctic Ocean and ...surrounding regions are undergoing climatic changes often attributed to "Arctic amplification" - that is, amplified warming in Arctic regions due to sea-ice loss and other processes, relative to global mean temperature. However, the long-term evolution of Arctic amplification is poorly constrained due to lack of continuous sediment proxy records of Arctic Ocean temperature, sea ice cover and circulation. Here we present reconstructions of Arctic Ocean intermediate depth water (AIW) temperatures and sea-ice cover spanning the last ~ 1.5 million years (Ma) of orbitally-paced glacial/interglacial cycles (GIC). Using Mg/Ca paleothermometry of the ostracode Krithe and sea-ice planktic and benthic indicator species, we suggest that the Mid-Brunhes Event (MBE), a major climate transition ~ 400-350 ka, involved fundamental changes in AIW temperature and sea-ice variability. Enhanced Arctic amplification at the MBE suggests a major climate threshold was reached at ~ 400 ka involving Atlantic Meridional Overturning Circulation (AMOC), inflowing warm Atlantic Layer water, ice sheet, sea-ice and ice-shelf feedbacks, and sensitivity to higher post-MBE interglacial CO
concentrations.
Research on phosphodiesterases both in academic labs and in the pharmaceutical industry has remained steady over the past 35 years. Although there have been some clinical successes, they have been ...clustered around just a couple of PDE isoforms, and disproportionate to the huge investment put forth against what seem like very druggable targets. This review attempts to uncover the reasons for the lack of productivity in PDE drug discovery, and summarizes the current hot areas of research. In addition, new insights gathered about structure–function relationships are highlighted, in particular those relating to enzyme regulation. Lastly, novel strategies for targeting the activation or inactivation of selected PDEs are proposed that may allow for a more targeted approach for PDE modulation.
The stratigraphic distributions of ostracodes and selected calcareous benthic and planktic foraminiferal species were studied in sediment cores from ~700 to 2700m water depth on the Northwind, ...Mendeleev, and Lomonosov Ridges in the western Arctic Ocean. Microfaunal records in most cores cover mid- to late Quaternary sediments deposited in the last ~600ka, with one record covering the last ~1.5Ma. Results show a progressive faunal turnover during the mid-Pleistocene transition (MPT, ~1.2 to 0.7Ma) and around the mid-Brunhes event (MBE, ~0.4Ma) reflecting major changes in Arctic Ocean temperature, circulation and sea-ice cover. The observed MPT shift is characterized by the extinction of species that today inhabit the sea-ice free subpolar North Atlantic and/or seasonally sea-ice free Nordic Seas (Echinocythereis sp., Rockallia cf. enigmatica, Krithe cf. aquilonia, Pterygocythereis vannieuwenhuisei). After a very warm interglacial during marine isotope stage (MIS) 11 dominated by the temperate planktic foraminifer Turborotalita egelida, the MBE experienced a shift to polar assemblages characteristic of predominantly perennial Arctic sea-ice cover during the interglacial and interstadial periods of the last 300ka. These include the planktic foraminifera Neogloboquadrina pachyderma, the sea-ice dwelling ostracode Acetabulastoma arcticum and associated benthic taxa Pseudocythere caudata, Pedicythere neofluitans, and Polycope spp. Several species can be used as biostratigraphic markers of specific intervals such as ostracodes Rabilimis mirabilis — MIS 5 and P. vannieuwenhuisei extinction after MIS 11, and foraminiferal abundance zones Bulimina aculeata — late MIS 5 and Bolivina arctica — MIS 5-11.
•Biostratigraphy for Quaternary marine sediments in the central Arctic Ocean.•Climate-driven paleoceanographic changes control species’ distributions.•Correlation between Arctic and extra-Arctic paleoclimate proxy records.
Microfaunal and geochemical proxies from marine sediment records from central Arctic Ocean (CAO) submarine ridges suggest a close relationship over the last 550 thousand years (kyr) between ...orbital-scale climatic oscillations, sea-ice cover, marine biological productivity and other parameters. Multiple paleoclimate proxies record glacial to interglacial cycles. To understand the climate-cryosphere-productivity relationship, we examined the cyclostratigraphy of calcareous microfossils and constructed a composite Arctic Paleoclimate Index (API) “stack” from benthic foraminiferal and ostracode density from 14 sediment cores. Following the hypothesis that API is driven mainly by changes in sea-ice related productivity, the API stack shows the Arctic experienced a series of highly productive interglacials and interstadials every ∼20 kyr. These periods signify minimal ice shelf and sea-ice cover and maximum marine productivity. Rapid transitions in productivity are seen during shifts from interglacial to glacial climate states. Discrepancies between the Arctic API curves and various global climatic, sea-level and ice-volume curves suggest abrupt growth and decay of Arctic ice shelves related to climatic and sea level oscillations.
•Analyzed cyclostratigraphy of microfossil density in central Arctic Ocean sediments.•Used microfossil density as a proxy for Arctic paleoclimate over the last 550 ka.•Microfossil density varies during interglacial and interstadial periods every ∼20 kyr.•Results suggest strong Arctic cryosphere response to orbital cycles.
Abolishing the inhibitory signal of intracellular cAMP by phosphodiesterases (PDEs) is a prerequisite for effector T (Teff) cell function. While PDE4 plays a prominent role, its control of cAMP ...levels in Teff cells is not exclusive. T cell activation has been shown to induce PDE8, a PDE isoform with 40- to 100-fold greater affinity for cAMP than PDE4. Thus, we postulated that PDE8 is an important regulator of Teff cell functions.
We found that Teff cells express PDE8 in vivo. Inhibition of PDE8 by the PDE inhibitor dipyridamole (DP) activates cAMP signaling and suppresses two major integrins involved in Teff cell adhesion. Accordingly, DP as well as the novel PDE8-selective inhibitor PF-4957325-00 suppress firm attachment of Teff cells to endothelial cells. Analysis of downstream signaling shows that DP suppresses proliferation and cytokine expression of Teff cells from Crem-/- mice lacking the inducible cAMP early repressor (ICER). Importantly, endothelial cells also express PDE8. DP treatment decreases vascular adhesion molecule and chemokine expression, while upregulating the tight junction molecule claudin-5. In vivo, DP reduces CXCL12 gene expression as determined by in situ probing of the mouse microvasculature by cell-selective laser-capture microdissection.
Collectively, our data identify PDE8 as a novel target for suppression of Teff cell functions, including adhesion to endothelial cells.
An early to middle Pleistocene ostracode fauna was discovered in sediment core P1-93-AR-23 (P23, 76.95°N, 155.07°W) from 951meter water depth from the Northwind Ridge, western Arctic Ocean. Piston ...core P23 yielded more than 30,000 specimens and a total of about 30 species. Several early to mid-Pleistocene species in the genera Krithe, Echinocythereis, Pterygocythereis, and Arcacythere are now extinct in the Arctic and show taxonomic affinities to North Atlantic Ocean species. Our results suggest that there was a major ostracode faunal turnover during the global climate transitions known as the Mid-Pleistocene Transition (MPT, ~1.2 to 0.7Ma) and the Mid-Brunhes Event (MBE, ~400ka) reflecting the development of perennial sea ice during interglacial periods and large ice shelves during glacial periods over the last 400,000years.
•A new Pleistocene ostracode fauna was discovered in the western Arctic Ocean.•Early to mid-Pleistocene ostracodes exhibit affinities to North Atlantic taxa.•Several species now extinct in the Arctic Ocean were found.•Faunal turnovers occurred with the Mid-Pleistocene Transition and Mid-Brunhes Event.•Ostracodes track Pleistocene Arctic sea ice development.
The mass of the
boson, a mediator of the weak force between elementary particles, is tightly constrained by the symmetries of the standard model of particle physics. The Higgs boson was the last ...missing component of the model. After observation of the Higgs boson, a measurement of the
boson mass provides a stringent test of the model. We measure the
boson mass,
, using data corresponding to 8.8 inverse femtobarns of integrated luminosity collected in proton-antiproton collisions at a 1.96 tera-electron volt center-of-mass energy with the CDF II detector at the Fermilab Tevatron collider. A sample of approximately 4 million
boson candidates is used to obtain
, the precision of which exceeds that of all previous measurements combined (stat, statistical uncertainty; syst, systematic uncertainty; MeV, mega-electron volts;
, speed of light in a vacuum). This measurement is in significant tension with the standard model expectation.
The CDF and D0 experiments at the Fermilab Tevatron have measured the asymmetry between yields of forward- and backward-produced top and antitop quarks based on their rapidity difference and the ...asymmetry between their decay leptons. These measurements use the full data sets collected in proton-antiproton collisions at a center-of-mass energy of sqrts=1.96 TeV. We report the results of combinations of the inclusive asymmetries and their differential dependencies on relevant kinematic quantities. The combined inclusive asymmetry is A_{FB}^{ttover ¯}=0.128±0.025. The combined inclusive and differential asymmetries are consistent with recent standard model predictions.
An array of six pyridyl-substituted fused bicyclic piperidines was prepared as novel cores for medicinal chemistry. For maximum diversity, the size of the fused ring varied from three to six atoms ...and contained up to two oxygen atoms. The pyridine ring was incorporated to improve physicochemical properties and to challenge the robustness of the chemistry. The presence of the pyridine did interfere with our initial approaches to these molecules, and in several instances, a blocking strategy had to be employed. These new scaffolds possess high sp3 character and may prove useful in multiple medicinal chemistry applications.
In this article we describe the background challenges for the CUORE experiment posed by surface contamination of inert detector materials such as copper, and present three techniques explored to ...mitigate these backgrounds. Using data from a dedicated test apparatus constructed to validate and compare these techniques we demonstrate that copper surface contamination levels better than 10−7- 10−8 Bq/cm2 are achieved for 238U and 232Th. If these levels are reproduced in the final CUORE apparatus the projected 90% C.L. upper limit on the number of background counts in the region of interest is 0.02–0.03 counts/keV/kg/y depending on the adopted mitigation technique.
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