As particulate organic carbon rains down from the surface ocean it is respired back to carbon dioxide and released into the ocean's interior. The depth at which this sinking carbon is converted back to carbon dioxide-known as the remineralization depth-depends on the balance between particle sinking speeds and their rate of decay. A host of climate-sensitive factors can affect this balance, including temperature 1 , oxygen concentration 2 , stratification, community composition 3,4 and the mineral content of the sinking particles 5 . Here we use a three-dimensional global ocean biogeochemistry model to show that a modest change in remineralization depth can have a substantial impact on atmospheric carbon dioxide concentrations. For example, when the depth at which 63% of sinking carbon is respired increases by 24 m globally, atmospheric carbon dioxide concentrations fall by 10-27 ppm. This reduction in atmospheric carbon dioxide concentration results from the redistribution of remineralized carbon from intermediate waters to bottom waters. As a consequence of the reduced concentration of respired carbon in upper ocean waters, atmospheric carbon dioxide is preferentially stored in newly formed North Atlantic Deep Water. We suggest that atmospheric carbon dioxide concentrations are highly sensitive to the potential changes in remineralization depth that may be caused by climate change.The downward flux of particulate organic carbon, F , at a depth z below the base of the euphotic zone z c is often represented by the power law function F (z) = F (z c ) × (z/z c ) −b (ref. 6) where the exponent b controls the efficiency of transfer of particulate organic carbon to depth. The global mean value of the exponent b estimated using ocean biogeochemical tracer data is 0.9-1.0 (refs 7-9). Sediment trap observations indicate that the downward transfer efficiency may vary regionally and temporally 10 with the exponent b ranging from 0.5 to 2.0 (refs 4, 11-14). Previous studies using three-dimensional global ocean biogeochemistry models showed that the remineralization depth has an important role in controlling the global distributions of nutrients and carbon 7,8 . In ref. 7, a large change in atmospheric pCO 2 (partial pressure of carbon dioxide) of ∼100 ppm was obtained when the exponent b was changed from 0.9 to 2.0. We show here that even a small change in remineralization depth results in a substantial change in atmospheric pCO 2 and we explore the underlying mechanisms of this large sensitivity.We performed a systematic sensitivity analysis of the distributions of nutrients and carbon to changes in remineralization depth using a 3D global ocean biogeochemistry model 8 (see the Methods section) coupled with a one-box model of the atmosphere. Because the response of the new production of organic matter to nutrient supply is uncertain, we bracketed the ocean's response to changes in the remineralization profile by considering two extreme cases: a

The E2F1 transcription factor can promote proliferation or apoptosis when activated, and is a key downstream target of the retinoblastoma tumor suppressor protein (pRB). Here we show that E2F1 is a potent and specific inhibitor of β-catenin/T-cell factor (TCF)-dependent transcription, and that this function contributes to E2F1-induced apoptosis. E2F1 deregulation suppresses β- catenin activity in an adenomatous polyposis coli (APC)/glycogen synthase kinase-3 (GSK3)-independent manner, reducing the expression of key β-catenin targets including c-MYC. This interaction explains why colorectal tumors, which depend on β-catenin transcription for their abnormal proliferation, keep RB1 intact. Remarkably, E2F1 activity is also repressed by cyclin-dependent kinase-8 (CDK8), a colorectal oncoprotein1. Elevated levels of CDK8 protect β-catenin/TCF-dependent transcription from inhibition by E2F1. Thus, by retaining RB1 and amplifying CDK8, colorectal tumor cells select conditions that collectively suppress E2F1 and enhance the activity of β-catenin.

Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucineenkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide-and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases.

Along the continental margins, rivers and submarine groundwater supply nutrients, trace elements, and radionuclides to the coastal ocean, supporting coastal ecosystems and, increasingly, causing harmful algal blooms and eutrophication. While the global magnitude of gauged riverine water discharge is well known, the magnitude of submarine groundwater discharge (SGD) is poorly constrained. Using an inverse model combined with a global compilation of 228 Ra observations, we show that the SGD integrated over the Atlantic and Indo-Pacific Oceans between 60°S and 70°N is (12 ± 3) × 10 13 m 3 yr À1, which is 3 to 4 times greater than the freshwater fluxes into the oceans by rivers. Unlike the rivers, where more than half of the total flux is discharged into the Atlantic, about 70% of SGD flows into the Indo-Pacific Oceans. We suggest that SGD is the dominant pathway for dissolved terrestrial materials to the global ocean, and this necessitates revisions for the budgets of chemical elements including carbon.

[1] A new implicit method for obtaining equilibrium solutions and their sensitivity to changes in parameters is described and applied to an OCMIP-2 type oceanbiogeochemistry model. The method is used to optimize model parameters by minimizing the difference between the observed and simulated PO 4 distribution. The optimized parameters include (1) the exponent a in the power law vertical profile for particulate organic matter (POM) fluxes, (2) the fraction s of biological production allocated to dissolved organic matter (DOM) and (3) the rate constant k for the remineralization of DOM. Global PO 4 observations constrain s and k but not independently because their sensitivity patterns are highly correlated. In contrast, the sensitivity pattern for a is uncorrelated to those of the other parameters, allowing it to be independently constrained. We show that export production from POC is well constrained by the distribution of PO 4 in an OCMIP-2 type model, but that new production and export production from DOC are not well constrained. With the optimal parameter set (a = À1.0, s = 0.74, and k = 1.0 yrs À1 ) the fraction of the spatial PO 4 variance captured by our model increases from 60% with the reference OCMIP-2 parameters to 70%. Combined changes in s and k account for most of the improvements by reducing but not completely eliminating the nutrient trapping effect in the Eastern Equatorial Pacific and northern Indian Ocean that causes the model to overpredict PO 4 concentrations. Important remaining model-data misfits in the deep North Atlantic where PO 4 is over predicted and in the North Pacific where the model does not produce the observed sharp nutricline are likely attributable to deficiencies in ocean transport. The fact that the fraction of unexplained variance is large at the optimal parameter values highlights the importance of properly simulating physical transport for ocean biogeochemical modeling.Citation: Kwon, E. Y., and F. Primeau (2006), Optimization and sensitivity study of a biogeochemistry ocean model using an implicit solver and in situ phosphate data, Global Biogeochem. Cycles, 20, GB4009,

The distribution of radiocarbon (14C) in the ocean and atmosphere has fluctuated on time scales ranging from seasons to millennia. It is thought that these fluctuations partly reflect variability in the climate system, offering a rich potential source of information to help understand mechanisms of past climate change. Here, a long simulation with a new, coupled model is used to explore the mechanisms that redistribute 14C within the earth system on interannual to centennial time scales. The model, the Geophysical Fluid Dynamics Laboratory Climate Model version 2 (GFDL CM2) with Modular Ocean Model version 4p1(MOM4p1) at coarse-resolution (CM2Mc), is a lower-resolution version of the Geophysical Fluid Dynamics Laboratory’s CM2M model, uses no flux adjustments, and is run here with a simple prognostic ocean biogeochemistry model including 14C. The atmospheric 14C and radiative boundary conditions are held constant so that the oceanic distribution of 14C is only a function of internal climate variability. The simulation displays previously described relationships between tropical sea surface 14C and the model equivalents of the El Niño–Southern Oscillation and Indonesian Throughflow. Sea surface 14C variability also arises from fluctuations in the circulations of the subarctic Pacific and Southern Ocean, including North Pacific decadal variability and episodic ventilation events in the Weddell Sea that are reminiscent of the Weddell Polynya of 1974–76. Interannual variability in the air–sea balance of 14C is dominated by exchange within the belt of intense “Southern Westerly” winds, rather than at the convective locations where the surface 14C is most variable. Despite significant interannual variability, the simulated impact on air–sea exchange is an order of magnitude smaller than the recorded atmospheric 14C variability of the past millennium. This result partly reflects the importance of variability in the production rate of 14C in determining atmospheric 14C but may also reflect an underestimate of natural climate variability, particularly in the Southern Westerly winds.

E2F transcription factors are generally believed to be positive regulators of apoptosis. In this study, we show that dE2F1 and dDP are important for the normal pattern of DNA damage-induced apoptosis in Drosophila wing discs. Unexpectedly, the role that E2F plays varies depending on the position of the cells within the disc. In irradiated wild-type discs, intervein cells show a high level of DNA damage-induced apoptosis, while cells within the D/V boundary are protected. In irradiated discs lacking E2F regulation, intervein cells are largely protected, but apoptotic cells are found at the D/V boundary. The protective effect of E2F at the D/V boundary is due to a spatially restricted role in the repression of hid. These loss-of-function experiments demonstrate that E2F cannot be classified simply as a pro- or antiapoptotic factor. Instead, the overall role of E2F in the damage response varies greatly and depends on the cellular context.

[1] Time-series analysis of Earth's major dust source regions reveals common traits in responses of wind erosion to climate anomalies. Lag cross-correlations of monthly mean aerosol optical depth, precipitation, vegetation, and wind speed are examined from 1979-1993. The response to monthly climate anomalies can differ greatly from the response to seasonal mean climate. The signs, magnitudes, and lags of highly significant ( p < 0.01) correlations show that 14 important mineral dust source areas characterized by Prospero et al. (2002) fall into four response categories. Each category represents distinct mechanisms by which climate anomalies influence subsequent atmospheric dust loading on seasonal to interannual timescales. In most regions, precipitation and vegetation together strongly constrain dust anomalies on multiple timescales. In these regions, dry anomalies increase, and wet anomalies reduce, dust emission. Interestingly, in many other regions the contrary is true: Dust and precipitation anomalies correlate positively, consistent with sediment-supply factors. The response timescales are consistent with loss of surface crusts (less than 1 month) and with alluvial transport and dessication (interannual lags). Supply-limited dust emission appears more prevalent than previously thought and is not accounted for in models. Reproducing these wind erodibility responses in models may help remediate underprediction of observed seasonal to interannual dust variability.