Marine biogeochemical responses to the North Atlantic Oscillation in a coupled climate model

In this study a coupled ocean-atmosphere model containing interactive marine biogeochemistry is used to analyze interannual, lagged, and decadal marine biogeochemical responses to the North Atlantic Oscillation (NAO), the dominant mode of North Atlantic atmospheric variability. The coupled model adequately reproduces present-day climatologies and NAO atmospheric variability. It is shown that marine biogeochemical responses to the NAO are governed by different mechanisms according to the time scale considered. On interannual time scales, local changes in vertical mixing, caused by modifications in air-sea heat, freshwater, and momentum fluxes, are most relevant in influencing phytoplankton growth through light and nutrient limitation mechanisms. At subpolar latitudes, deeper mixing occurring during positive NAO winters causes a slight decrease in late winter chlorophyll concentration due to light limitation and a 10%–20% increase in spring chlorophyll concentration due to higher nutrient availability. The lagged response of physical and biogeochemical properties to a high NAO winter shows some memory in the following 2 years. In particular, subsurface nutrient anomalies generated by local changes in mixing near the American coast are advected along the North Atlantic Current, where they are suggested to affect downstream chlorophyll concentration with 1 year lag. On decadal time scales, local and remote mechanisms act contemporaneously in shaping the decadal biogeochemical response to the NAO. The slow circulation adjustment, in response to NAO wind stress curl anomalies, causes a basin redistribution of heat, freshwater, and biogeochemical properties which, in turn, modifies the spatial structure of the subpolar chlorophyll bloom

Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues

Hormones and nutrients often induce genetic programs via signaling pathways that interface with gene-specific activators. Activation of the cAMP pathway, for example, stimulates cellular gene expression by means of the PKA-mediated phosphorylation of cAMP-response element binding protein (CREB) at Ser-133. Here, we use genome-wide approaches to characterize target genes that are regulated by CREB in different cellular contexts. CREB was found to occupy approximate to 4,000 promoter sites in vivo, depending on the presence and methylation state of consensus cAMP response elements near the promoter. The profiles for CREB occupancy were very similar in different human tissues, and exposure to a cAMP agonist stimulated CREB phosphorylation over a majority of these sites. Only a small proportion of CREB target genes was induced by cAMP in any cell type, however, due in part to the preferential recruitment of the coactivator CREB-binding protein to those promoters. These results indicate that CREB phosphorylation alone is not a reliable predictor of target gene activation and that additional CREB regulatory partners are required for recruitment of the transcriptional apparatus to the promoter

Unique reporter-based sensor platforms to monitor signalling in cells

Introduction: In recent years much progress has been made in the development of tools for systems biology to study the levels of mRNA and protein, and their interactions within cells. However, few multiplexed methodologies are available to study cell signalling directly at the transcription factor level. <p/>Methods: Here we describe a sensitive, plasmid-based RNA reporter methodology to study transcription factor activation in mammalian cells, and apply this technology to profiling 60 transcription factors in parallel. The methodology uses two robust and easily accessible detection platforms; quantitative real-time PCR for quantitative analysis and DNA microarrays for parallel, higher throughput analysis. <p/>Findings: We test the specificity of the detection platforms with ten inducers and independently validate the transcription factor activation. <p/>Conclusions: We report a methodology for the multiplexed study of transcription factor activation in mammalian cells that is direct and not theoretically limited by the number of available reporters

A novel regulatory circuit in base excision repair involving AP endonuclease 1, Creb1 and DNA polymerase β

DNA repair is required to maintain genome stability in stem cells and early embryos. At critical junctures, oxidative damage to DNA requires the base excision repair (BER) pathway. Since early zebrafish embryos lack the major polymerase in BER, DNA polymerase ß, repair proceeds via replicative polymerases, even though there is ample polb mRNA. Here, we report that Polb protein fails to appear at the appropriate time in development when AP endonuclease 1 (Apex), the upstream protein in BER, is knocked down. Because polb contains a Creb1 binding site, we examined whether knockdown of Apex affects creb1. Apex knockdown results in loss of Creb1 and Creb complex members but not Creb1 phosphorylation. This effect is independent of p53. Although both apex and creb1 mRNA rescue Creb1 and Polb after Apex knockdown, Apex is not a co-activator of creb1 transcription. This observation has broad significance, as similar results occur when Apex is inhibited in B cells from apex+/− mice. These results describe a novel regulatory circuit involving Apex, Creb1 and Polb and provide a mechanism for lethality of Apex loss in higher eukaryotes

Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: a novel mechanism for vascular protection in chronic systemic inflammation

Aims Premature cardiovascular events complicate chronic inflammatory conditions. Low-dose weekly methotrexate (MTX), the most widely used disease-modifying drug for rheumatoid arthritis (RA), reduces disease-associated cardiovascular mortality. MTX increases intracellular accumulation of adenosine monophosphate (AMP) and 5-aminoimidazole-4-carboxamide ribonucleotide which activates AMP-activated protein kinase (AMPK). We hypothesised that MTX specifically protects the vascular endothelium against inflammatory injury via induction of AMPK-regulated protective genes. Methods/results In the (NZW×BXSB)F1 murine model of inflammatory vasculopathy, MTX 1 mg/kg/week significantly reduced intramyocardial vasculopathy and attenuated end-organ damage. Studies of human umbilical vein endothelial cells (HUVEC) and arterial endothelial cells (HAEC) showed that therapeutically relevant concentrations of MTX phosphorylate AMPKαThr172, and induce cytoprotective genes including manganese superoxide dismutase (MnSOD) and haem oxygenase-1 (HO-1). These responses were preserved when HUVECs were pretreated with tumour necrosis factor-α to mimic dysfunctional endothelium. Furthermore, MTX protected against glucose deprivation-induced endothelial apoptosis. Mechanistically, MTX treatment led to cyclic AMP response element-binding protein (CREB)Ser133 phosphorylation, while AMPK depletion attenuated this response and the induction of MnSOD and HO-1. CREB siRNA inhibited upregulation of both cytoprotective genes by MTX, while chromatin immunoprecipitation demonstrated CREB binding to the MnSOD promoter in MTX-treated EC. Likewise, treatment of (NZW×BXSB)F1 mice with MTX enhanced AMPKαThr172 phosphorylation and MnSOD, and reduced aortic intercellular adhesion molecule-1 expression. Conclusions These data suggest that MTX therapeutically conditions vascular endothelium via activation of AMPK-CREB. We propose that this mechanism contributes to the protection against cardiovascular events seen in patients with RA treated with MTX

A model of the Arctic Ocean carbon cycle

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): C12020, doi:10.1029/2011JC006998.A three dimensional model of Arctic Ocean circulation and mixing, with a horizontal resolution of 18 km, is overlain by a biogeochemical model resolving the physical, chemical and biological transport and transformations of phosphorus, alkalinity, oxygen and carbon, including the air-sea exchange of dissolved gases and the riverine delivery of dissolved organic carbon. The model qualitatively captures the observed regional and seasonal trends in surface ocean PO4, dissolved inorganic carbon, total alkalinity, and pCO2. Integrated annually, over the basin, the model suggests a net annual uptake of 59 Tg C a−1, within the range of published estimates based on the extrapolation of local observations (20–199 Tg C a−1). This flux is attributable to the cooling (increasing solubility) of waters moving into the basin, mainly from the subpolar North Atlantic. The air-sea flux is regulated seasonally and regionally by sea-ice cover, which modulates both air-sea gas transfer and the photosynthetic production of organic matter, and by the delivery of riverine dissolved organic carbon (RDOC), which drive the regional contrasts in pCO2 between Eurasian and North American coastal waters. Integrated over the basin, the delivery and remineralization of RDOC reduces the net oceanic CO2 uptake by ~10%.This study has been carried out as part of ECCO2 and SASS (Synthesis of the Arctic System Science) projects funded by NASA and NSF, respectively. MM and MJF are grateful for support from the National Science Foundation (ARC-0531119 and ARC-0806229) for financial support. MM also acknowledges NASA for providing computer time, the use of the computing facilities at NAS center and also the Scripps post-doctoral program for further financial support that helped to complete the manuscript. RMK also acknowledges NOAA for support (NA08OAR4310820 and NA08OAR4320752).2012-06-1

Tracer-based assessment of the origin and biogeochemical transformation of a cyclonic eddy in the Sargasso Sea

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 113 (2008): C10006, doi:10.1029/2008JC004840.Mechanisms of nutrient supply in oligotrophic ocean systems remain inadequately understood and quantified. In the North Atlantic Subtropical Gyre, for example, the observed rates of new production are apparently not balanced by nutrient supply via vertical mixing. Mesoscale eddies have been hypothesized as a mechanism for vertical nutrient pumping into the euphotic zone, but the full range and magnitude of biogeochemical impacts by eddies remain uncertain. We evaluated a cyclonic eddy located near Bermuda for its effect on water column biogeochemistry. In the density range σ θ 26.1 to 26.7, an eddy core with anomalous salinity, temperature, and biogeochemical properties was observed, suggesting that the eddy was not formed with local water (i.e., not formed of the waters surrounding the eddy at the time of observations), hence complicating efforts to quantify biogeochemical processes in the eddy. We combined conservative hydrographic tracers (density versus potential temperature and salinity) and quasi-conservative biogeochemical tracers (density versus NO, PO, and total organic carbon) to propose the origin of the eddy core water to have been several hundred kilometers to the southeast of the eddy location at sampling. By comparing the observed eddy core's biogeochemical properties with those near the proposed origin, we estimate the net changes in biogeochemical properties that occurred. A conservative estimate of export was 0.5 ± 0.34 mol N m−2 via sinking particles, with export occurring prior to our period of direct observation. Our results suggest that biogeochemical signals induced by mesoscale eddies could survive to be transported over long distances, thus providing a mechanism for lateral fluxes of nutrients and AOU (apparent oxygen utilization). Given that the proposed source area of this eddy is relatively broad, and the eddy-mixing history before our sampling is unknown, uncertainty remains in our assessment of the true biogeochemical impact of mesoscale eddies in the gyre.Support for the EDDIES project came from the U.S. National Science Foundation. D.J.M. was also partially supported by NASA

Modeling the impact of Trichodesmium and nitrogen fixation in the Atlantic Ocean

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95044/1/jgrc9275.pd

Direct targets of Klf5 transcription factor contribute to the maintenance of mouse embryonic stem cell undifferentiated state

<p>Abstract</p> <p>Background</p> <p>A growing body of evidence has shown that Krüppel-like transcription factors play a crucial role in maintaining embryonic stem cell (ESC) pluripotency and in governing ESC fate decisions. Krüppel-like factor 5 (Klf5) appears to play a critical role in these processes, but detailed knowledge of the molecular mechanisms of this function is still not completely addressed.</p> <p>Results</p> <p>By combining genome-wide chromatin immunoprecipitation and microarray analysis, we have identified 161 putative primary targets of Klf5 in ESCs. We address three main points: (1) the relevance of the pathways governed by Klf5, demonstrating that suppression or constitutive expression of single Klf5 targets robustly affect the ESC undifferentiated phenotype; (2) the specificity of Klf5 compared to factors belonging to the same family, demonstrating that many Klf5 targets are not regulated by Klf2 and Klf4; and (3) the specificity of Klf5 function in ESCs, demonstrated by the significant differences between Klf5 targets in ESCs compared to adult cells, such as keratinocytes.</p> <p>Conclusions</p> <p>Taken together, these results, through the definition of a detailed list of Klf5 transcriptional targets in mouse ESCs, support the important and specific functional role of Klf5 in the maintenance of the undifferentiated ESC phenotype.</p> <p>See: <url>http://www.biomedcental.com/1741-7007/8/125</url></p

Patterns of Pacific decadal variability recorded by Indian Ocean corals

We investigate Pacific Decadal Oscillation (PDO) signals recorded by two bimonthly resolved coral δ18O series from La Réunion and Ifaty (West Madagascar), Indian Ocean from 1882 to 1993. To isolate the main PDO frequencies, we apply a band pass filter to the time series passing only periodicities from 16 to 28 years. We investigate the covariance patterns of the coral time series with sea surface temperature (SST) and sea level pressure (SLP) of the Indian and Pacific Oceans. In addition, the empirical orthogonal functions of the filtered SST and SLP fields (single and coupled) are related to the filtered coral times series. The covariance maps show the typical PDO pattern for SST and SLP, confirming the coupling between the Indian and Pacific Oceans. Both corals show the strongest signal in boreal summer. The La Réunion (Ifaty) coral better records SST (SLP) than SLP (SST) pattern variability. We suggest that the filtered La Réunion coral δ18O represents δ18O of seawater that varies with the South Equatorial Current, which, in turn, is linked with the SST PDO. The filtered Ifaty coral δ18O represents SST and is remotely linked with the SLP PDO variability. A combined coral record of the Ifaty and La Réunion boreal summer δ18O series explains about 64% of the variance of the coupled SST/SLP PDO time series