Interaction of Human Chorionic Gonadotropin (hCG) and Asialo-hCG with Recombinant Human Thyrotropin Receptor.

hCG is a putative thyroid stimulator. The present studies were undertaken to examine its interaction and that of its desialylated variant asialo-hCG with recombinant human TSH (hTSH) receptor (hTSHr). To this end, we transfected a human thyroid carcinoma cell line (HTC) lacking endogenous TSHr with the full-length cDNA of the hTSHr. Unlike the wild type, the transfected cells, termed HTC-TSHr cells, were able to bind bovine TSH (bTSH) with high affinity and increase cAMP production in response to bTSH stimulation. Of the hCG forms, intact hCG displayed a weak activity to inhibit [125I] bTSH binding to HTC-TSHr cells, with 100 mg/L (2.6 x 10(-6) mol/L) producing maximally a 20% inhibition, whereas asialo-hCG achieved half-maximum binding inhibition at a concentration of 8 mg/L (2.3 x 10(-7) mol/L). The inhibitory constant (Ki) of asialo-hCG for recombinant hTSHr was calculated from saturation experiments in the presence of variable doses of bTSH and a fixed concentration of asialo-hCG to be approximately 8 x 10(-8) mol/L. The interaction of asialo-hCG with TSHr was further assessed by studies of the direct binding of the radioactively labeled hormone to both HTC and HTC-TSHr cells. [125I]Asialo-hCG binding to HTC-TSHr cells was 4.7%, compared to 1.5% in the wild-type cells lacking TSHr and was displaceable by bTSH (0.1-100 IU/L), indicating specific binding of the tracer to TSHr. Functionally, hCG (up to 100 mg/L; 2.6 x 10(-6) mol/L) proved unable to evoke any significant cAMP response over basal values in HTC-TSHr cells, as did asialo-hCG. Asialo-hCG, but not hCG, inhibited bTSH-stimulated adenylate cyclase activity in the cells in a dose-dependent manner. In conclusion, the present data show that intact hCG binds only weakly to HTC-TSHr cells and produces no significant cAMP stimulation, which is at variance with data obtained in FRTL-5 and Chinese hamster ovary-TSHr cells, but in good accord with previous findings in human thyroid membranes. Asialo-hCG, on the other hand, strongly binds to recombinant TSHr and inhibits the cAMP response to bTSH in HTC-TSHr cells, indicating that the desialylated hCG variant directly interacts with the receptor and truly is an antagonist of the hTSHr

Atmospheric, climatic and environmental research

Work performed on the three tasks during the report period is summarized. The climate and atmospheric modeling studies included work on climate model development and applications, paleoclimate studies, climate change applications, and SAGE II. Climate applications of Earth and planetary observations included studies on cloud climatology and planetary studies. Studies on the chemistry of the Earth and the environment are briefly described. Publications based on the above research are listed; two of these papers are included in the appendices

Anomalous AMS radiocarbon ages for foraminifera from high-deposition-rate ocean sediments

Radiocarbon ages on handpicked foraminifera from deep-sea cores are revealing that areas of rapid sediment accumulation are in some cases subject to hiatuses, reworking and perhaps secondary calcite deposition. We present here an extreme example of the impacts of such disturbances. The message is that if precise chronologies or meaningful benthic planktic age differences are to be obtained, then it is essential to document the reliability of radiocarbon ages by making both comparisons between coexisting species of planktomc foraminifera and detailed down-core sequences of measurements

Surface water temperature, salinity, and density changes in the northeast Atlantic during the last 45,000 years: Heinrich events, deep water formation, and climatic rebounds

We developed a new method to calculate sea surface salinities (SSS) and densities (SSD) from planktonic foraminiferal delta(18)O and sea surface temperatures (SST) as determined from planktonic foraminiferal species abundances. SST, SSS, and SSD records were calculated for the last 45,000 years for Biogeochemical Oceanic Flux Study (BOFS) cores 5K and 8K recovered from the northeast Atlantic. The strongest feature is the dramatic drop in all three parameters during the Heinrich ''ice-rafting'' events. We modelled the possibility of deepwater formation in the northeast Atlantic from the SSD records, by assuming that the surface waters at our sites cooled as they flowed further north. Comparison with modelled North Atlantic deepwater densities indicates that there could have been periods of deepwater formation between 45,000 and 30,000 C-14 years B.P. (interrupted by iceberg meltwater input of Heinrich event 3 and 4, at 27,000 and 38,000 C-14 years B.P.) and during the Holocene. No amount of cooling in the northeast Atlantic between 30,000 and 13,000 years could cause deep water to form, because of the low salinities resulting from the high meltwater inputs from icebergs. Our records indicate that after each Heinrich event there were periods of climatic rebound, with milder conditions persisting for up to 2000 years, as indicated by the presence of warmer and more saline water masses. After these warm periods conditions returned to average glacial levels. These short term cold and warm episodes in the northeast Atlantic ate superimposed on the general trend towards colder conditions of the Last Glacial Maximum (LGM). Heinrich event 1 appears to be unique as it occurs as insolation rose and was coeval with the initial melting of the Fennoscandian ice sheet. We propose that meltwater input of Heinrich event 1 significantly reduced North Atlantic Deep Water formation reducing the heat exchange between the low and high latitudes, thus delaying deglaciation by about 1500 radiocarbon years (2000 calendar years)

A Human Development Framework for CO2 Reductions

Although developing countries are called to participate in CO2 emission reduction efforts to avoid dangerous climate change, the implications of proposed reduction schemes in human development standards of developing countries remain a matter of debate. We show the existence of a positive and time-dependent correlation between the Human Development Index (HDI) and per capita CO2 emissions from fossil fuel combustion. Employing this empirical relation, extrapolating the HDI, and using three population scenarios, the cumulative CO2 emissions necessary for developing countries to achieve particular HDI thresholds are assessed following a Development As Usual approach (DAU). If current demographic and development trends are maintained, we estimate that by 2050 around 85% of the world's population will live in countries with high HDI (above 0.8). In particular, 300Gt of cumulative CO2 emissions between 2000 and 2050 are estimated to be necessary for the development of 104 developing countries in the year 2000. This value represents between 20% to 30% of previously calculated CO2 budgets limiting global warming to 2{\deg}C. These constraints and results are incorporated into a CO2 reduction framework involving four domains of climate action for individual countries. The framework reserves a fair emission path for developing countries to proceed with their development by indexing country-dependent reduction rates proportional to the HDI in order to preserve the 2{\deg}C target after a particular development threshold is reached. Under this approach, global cumulative emissions by 2050 are estimated to range from 850 up to 1100Gt of CO2. These values are within the uncertainty range of emissions to limit global temperatures to 2{\deg}C.Comment: 14 pages, 7 figures, 1 tabl

Destabilization of the thermohaline circulation by transient perturbations to the hydrological cycle

We reconsider the problem of the stability of the thermohaline circulation as described by a two-dimensional Boussinesq model with mixed boundary conditions. We determine how the stability properties of the system depend on the intensity of the hydrological cycle. We define a two-dimensional parameters' space descriptive of the hydrology of the system and determine, by considering suitable quasi-static perturbations, a bounded region where multiple equilibria of the system are realized. We then focus on how the response of the system to finite-amplitude surface freshwater forcings depends on their rate of increase. We show that it is possible to define a robust separation between slow and fast regimes of forcing. Such separation is obtained by singling out an estimate of the critical growth rate for the anomalous forcing, which can be related to the characteristic advective time scale of the system.Comment: 37 pages, 8 figures, submitted to Clim. Dy

Examining reliability of seasonal to decadal sea surface temperature forecasts: the role of ensemble dispersion

Useful probabilistic climate forecasts on decadal timescales should be reliable (i.e. forecast probabilities match the observed relative frequencies) but this is seldom examined. This paper assesses a necessary condition for reliability, that the ratio of ensemble spread to forecast error being close to one, for seasonal to decadal sea surface temperature retrospective forecasts from the Met Office Decadal Prediction System (DePreSys). Factors which may affect reliability are diagnosed by comparing this spread-error ratio for an initial condition ensemble and two perturbed physics ensembles for initialized and uninitialized predictions. At lead times less than 2 years, the initialized ensembles tend to be under-dispersed, and hence produce overconfident and hence unreliable forecasts. For longer lead times, all three ensembles are predominantly over-dispersed. Such over-dispersion is primarily related to excessive inter-annual variability in the climate model. These findings highlight the need to carefully evaluate simulated variability in seasonal and decadal prediction systems.Useful probabilistic climate forecasts on decadal timescales should be reliable (i.e. forecast probabilities match the observed relative frequencies) but this is seldom examined. This paper assesses a necessary condition for reliability, that the ratio of ensemble spread to forecast error being close to one, for seasonal to decadal sea surface temperature retrospective forecasts from the Met Office Decadal Prediction System (DePreSys). Factors which may affect reliability are diagnosed by comparing this spread-error ratio for an initial condition ensemble and two perturbed physics ensembles for initialized and uninitialized predictions. At lead times less than 2 years, the initialized ensembles tend to be under-dispersed, and hence produce overconfident and hence unreliable forecasts. For longer lead times, all three ensembles are predominantly over-dispersed. Such over-dispersion is primarily related to excessive inter-annual variability in the climate model. These findings highlight the need to carefully evaluate simulated variability in seasonal and decadal prediction systems

Extensive dissolution of live pteropods in the Southern Ocean

The carbonate chemistry of the surface ocean is rapidly changing with ocean acidification, a result of human activities. In the upper layers of the Southern Ocean, aragonite—a metastable form of calcium carbonate with rapid dissolution kinetics—may become undersaturated by 2050 (ref. 2). Aragonite undersaturation is likely to affect aragonite-shelled organisms, which can dominate surface water communities in polar regions. Here we present analyses of specimens of the pteropod Limacina helicina antarctica that were extracted live from the Southern Ocean early in 2008. We sampled from the top 200m of the water column, where aragonite saturation levels were around 1, as upwelled deep water is mixed with surface water containing anthropogenic CO2. Comparing the shell structure with samples from aragonite-supersaturated regions elsewhere under a scanning electron microscope, we found severe levels of shell dissolution in the undersaturated region alone. According to laboratory incubations of intact samples with a range of aragonite saturation levels, eight days of incubation in aragonite saturation levels of 0.94– 1.12 produces equivalent levels of dissolution. As deep-water upwelling and CO2 absorption by surface waters is likely to increase as a result of human activities2,4, we conclude that upper ocean regions where aragonite-shelled organisms are affected by dissolution are likely to expand

Derivation of Del180 from sediment core log data\u27 Implications for millennial-scale climate change in the Labrador Sea

Sediment core logs from six sediment cores in the Labrador Sea show millennial-scale climate variability during the last glacial by recording all Heinrich events and several major Dansgaard-Oeschger cycles. The same millennial-scale climate change is documented for surface water δ18O records of Neogloboquadrina pachyderma (left coiled); hence the surface water δ18O record can be derived from sediment core logging by means of multiple linear regression, providing a paleoclimate proxy record at very high temporal resolution (70 years). For the Labrador Sea, sediment core logs contain important information about deepwater current velocities and also reflect the variable input of ice-rafted debris from different sources as inferred from grain-size analysis, the relation of density and P wave velocity, and magnetic susceptibility. For the last glacial, faster deepwater currents, which correspond to highs in sediment physical properties, occurred during iceberg discharge and lasted from several centuries to a few millennia. Those enhanced currents might have contributed to increased production of intermediate waters during times of reduced production of North Atlantic Deep Water. Hudson Strait might have acted as a major supplier of detrital carbonate only during lowered sea level (greater ice extent). During coldest atmospheric temperatures over Greenland, deepwater currents increased during iceberg discharge in the Labrador Sea, then surface water freshened shortly thereafter, while the abrupt atmospheric temperature rise happened after a larger time lag of ≥ 1 kyr. The correlation implies a strong link and common forcing for atmosphere, sea surface, and deep water during the last glacial at millennial timescales but decoupling at orbital timescales

Tracing Noble Gas Radionuclides in the Environment

Trace analysis of radionuclides is an essential and versatile tool in modern science and technology. Due to their ideal geophysical and geochemical properties, long-lived noble gas radionuclides, in particular, 39Ar (t1/2 = 269 yr), 81Kr (t1/2 = 2.3x10^5 yr) and 85Kr (t1/2 = 10.8 yr), have long been recognized to have a wide range of important applications in Earth sciences. In recent years, significant progress has been made in the development of practical analytical methods, and has led to applications of these isotopes in the hydrosphere (tracing the flow of groundwater and ocean water). In this article, we introduce the applications of these isotopes and review three leading analytical methods: Low-Level Counting (LLC), Accelerator Mass Spectrometry (AMS) and Atom Trap Trace Analysis (ATTA)