Krueppel-like factor 15 regulates Wnt/beta-catenin transcription and controls cardiac progenitor cell fate in the postnatal heart

Wnt/beta-catenin signalling controls adult heart remodelling in part via regulation of cardiac progenitor cell (CPC) differentiation. An enhanced understanding of mechanisms controlling CPC biology might facilitate the development of new therapeutic strategies in heart failure. We identified and characterized a novel cardiac interaction between Krueppel-like factor 15 and components of the Wnt/beta-catenin pathway leading to inhibition of transcription. In vitro mutation, reporter assays and co-localization analyses revealed that KLF15 requires both the C-terminus, necessary for nuclear localization, and a minimal N-terminal regulatory region to inhibit transcription. In line with this, functional Klf15 knock-out mice exhibited cardiac beta-catenin transcriptional activation along with functional cardiac deterioration in normal homeostasis and upon hypertrophy. We further provide in vivo and in vitro evidences for preferential endothelial lineage differentiation of CPCs upon KLF15 deletion. Via inhibition of beta-catenin transcription, KLF15 controls CPC homeostasis in the adult heart similar to embryonic cardiogenesis. This knowledge may provide a tool for reactivation of this apparently dormant CPC population in the adult heart and thus be an attractive approach to enhance endogenous cardiac repair

Ozone observations and a model of marine boundary layer photochemistry during SAGA 3

A major purpose of the third joint Soviet‐American Gases and Aerosols (SAGA 3) oceanographic cruise was to examine remote tropical marine O3 and photochemical cycles in detail. On leg 1, which took place between Hilo, Hawaii, and Pago‐Pago, American Samoa, in February and March 1990, shipboard measurements were made of O3, CO, CH4, nonmethane hydrocarbons (NMHC), NO, dimethyl sulfide (DMS), H2S, H2O2, organic peroxides, and total column O3. Postcruise analysis was performed for alkyl nitrates and a second set of nonmethane hydrocarbons. A latitudinal gradient in O3 was observed on SAGA 3, with O3 north of the intertropical convergence zone (ITCZ) at 15–20 parts per billion by volume (ppbv) and less than 12 ppbv south of the ITCZ but never ≤3 ppbv as observed on some previous equatorial Pacific cruises (Piotrowicz et al., 1986; Johnson et al., 1990). Total column O3 (230–250 Dobson units (DU)) measured from the Akademik Korolev was within 8% of the corresponding total ozone mapping spectrometer (TOMS) satellite observations and confirmed the equatorial Pacific as a low O3 region. In terms of number of constituents measured, SAGA 3 may be the most photochemically complete at‐sea experiment to date. A one‐dimensional photochemical model gives a self‐consistent picture of O3‐NO‐CO‐hydrocarbon interactions taking place during SAGA 3. At typical equatorial conditions, mean O3 is 10 ppbv with a 10–15% diurnal variation and maximum near sunrise. Measurements of O3, CO, CH4, NMHC, and H2O constrain model‐calculated OH to 9 × 105 cm−3 for 10 ppbv O3 at the equator. For DMS (300–400 parts per trillion by volume (pptv)) this OH abundance requires a sea‐to‐air flux of 6–8 × 109 cm−2 s−1, which is within the uncertainty range of the flux deduced from SAGA 3 measurements of DMS in seawater (Bates et al., this issue). The concentrations of alkyl nitrates on SAGA 3 (5–15 pptv total alkyl nitrates) were up to 6 times higher than expected from currently accepted kinetics, suggesting a largely continental source for these species. However, maxima in isopropyl nitrate and bromoform near the equator (Atlas et al., this issue) as well as for nitric oxide (Torres and Thompson, this issue) may signify photochemical and biological sources of these species

A stochastic model of Escherichia coli AI-2 quorum signal circuit reveals alternative synthesis pathways

Quorum sensing (QS) is an important determinant of bacterial phenotype. Many cell functions are regulated by intricate and multimodal QS signal transduction processes. The LuxS/AI-2 QS system is highly conserved among Eubacteria and AI-2 is reported as a ‘universal' signal molecule. To understand the hierarchical organization of AI-2 circuitry, a comprehensive approach incorporating stochastic simulations was developed. We investigated the synthesis, uptake, and regulation of AI-2, developed testable hypotheses, and made several discoveries: (1) the mRNA transcript and protein levels of AI-2 synthases, Pfs and LuxS, do not contribute to the dramatically increased level of AI-2 found when cells are grown in the presence of glucose; (2) a concomitant increase in metabolic flux through this synthesis pathway in the presence of glucose only partially accounts for this difference. We predict that ‘high-flux' alternative pathways or additional biological steps are involved in AI-2 synthesis; and (3) experimental results validate this hypothesis. This work demonstrates the utility of linking cell physiology with systems-based stochastic models that can be assembled de novo with partial knowledge of biochemical pathways

Pathways of Superoxide (O2-) decay in the Eastern Tropical North Atlantic

Superoxide (O2-: IUPAC name dioxide (•1−)) is an important transient reactive oxygen species (ROS) in the ocean formed as an intermediate in the redox transformation of oxygen (O2) into hydrogen peroxide (H2O2) and vice versa. This highly reactive and very short-lived radical anion can be produced both via photochemical and biological processes in the ocean. In this paper we examine the decomposition rate of O2- throughout the water column, using new data collected in the Eastern Tropical North Atlantic (ETNA) Ocean. For this approach we applied a semi factorial experimental design, to identify and quantify the pathways of the major identified sinks in the ocean. In this work we occupied 6 stations, 2 on the West African continental shelf and 4 open ocean stations, including the CVOO time series site adjacent to Cape Verde. Our results indicate that in the surface ocean, impacted by Saharan aerosols and sediment resuspension, the main decay pathways for superoxide is via reactions with Mn(II) and organic matter

Physical mixing effects on iron biogeochemical cycling: FeCycle experiment

The effects of physical processes on the distribution, speciation, and sources/sinks for Fe in a high-nutrient low-chlorophyll (HNLC) region were assessed during FeCycle, a mesoscale SF6 tracer release during February 2003 (austral summer) to the SE of New Zealand. Physical mixing processes were prevalent during FeCycle with rapid patch growth (strain rate γ = 0.17–0.20 d−1) from a circular shape (50 km2) into a long filament of ∼400 km2 by day 10. Slippage between layers saw the patch-head overlying noninfused waters while the tail was capped by adjacent surface waters resulting in a SF6 maximum at depth. As the patch developed it entrained adjacent waters containing higher chlorophyll concentrations, but similar dissolved iron (DFe) levels, than the initial infused patch. DFe was low ∼60 pmol L−1 in surface waters during FeCycle and was dominated by organic complexation. Nighttime measurements of Fe(II) ∼20 pmol L−1 suggest the presence of Fe(II) organic complexes in the absence of an identifiable fast Fe(III) reduction process. Combining residence times and phytoplankton uptake fluxes for DFe it is cycled through the biota 140–280 times before leaving the winter mixed layer (WML). This strong Fe demand throughout the euphotic zone coupled with the low Fe:NO3 − (11.9 μmol:mol) below the ferricline suggests that vertical diffusion of Fe is insufficient to relieve chronic iron limitation, indicating the importance of atmospheric inputs of Fe to this region

Sources and cycling of dissolved and particulate organic radiocarbon in the northwest Atlantic continental margin

Continental shelves and slopes are productive and dynamic ocean margin systems that also regulate the fluxes of terrestrial, riverine, and estuarine materials between the continents and oceans. In order to evaluate the ages, potential sources, and transformations of organic matter in an ocean margin system, we measured the radiocarbon (Delta (14)C and delta (13)C distributions of total dissolved organic carbon (DOC), suspended particulate organic carbon (POC), and dissolved inorganic carbon (DIC) in waters of the Middle Atlantic Bight (MAB) continental shelf and slope in April-May 1994. The Delta (14)C of DOC was greatest (as high as -39 parts per thousand) in surface waters of the shelf, decreasing rapidly offshore and with depth, even in relatively shallow (25-50 in depth) shelf waters. The lowest Delta (14)C-DOC values were observed in deep slope waters, where they were significantly lower than values measured previously for the deep Sargasso Sea. There was a strong inverse relationship between Delta (14)C-DOC and delta (-13)C-DOC in all shelf and surface slope waters of the MAB, which is likely attributable to varying contributions of young, (14)C-enriched organic matter of terrestrial and/or riverine origin. The more highly (14)C-depleted DOC in deep : slope waters (as low as -442 parts per thousand) generally had a correspondingly lower delta (13)C (as low as -22.3 parts per thousand) component. However, this must originate from relic terrestrial material either in the MAB itself or be discharged to the MAB from rivers and estuaries. The isotopic signatures of POC were clearly differentiable from DOC and indicate that this pool also contained a broad range of both old and young material of terrestrial (delta (13)C as low as -24.9 parts per thousand) and marine (delta (13)C as high as -19.9 parts per thousand) origin throughout the MAB shelf and slope. The highest Delta (14)C-POC values (up to 78 parts per thousand) were observed in shallow shelf waters of the southern MAR Conversely, the lowest Delta (14)C-POC values (as low as -394 parts per thousand) were found in MAB deep slope waters and were also significantly more depleted in (14)C than POC from the central north Atlantic (Sargasso Sea). A multiple-source isotopic mass balance model employing both (14)C and (13)C was used to evaluate the relative contributions of both young and old terrigenous versus marine organic matter to DOC and POC in the MAR The results indicate that shelf and slope DOC is comprised of an old marine fraction (represented by offshore Sargasso Sea material) and either a young terrestrial/riverine/estuarine (TRE) component (in shelf and shallow slope waters) or a relic TRE component (in deep and some shallow slope waters). In contrast, suspended POC from the MAB appears to originate predominantly from a mixture of recent MAB primary production and an old, TRE component, similar to that observed in one of the major subestuaries of the Chesapeake Bay. These results suggest that both young and old sources of terrestrial and riverine organic matter can comprise a significant fraction of the DOC and POC in ocean margins. Preliminary calculations indicate that the export of this compositionally unique DOC and suspended POC may be significant terms in the organic carbon budgets of the MAB and other margin systems

Origin of Ozone NO(x) in the Tropical Troposphere: A Photochemical Analysis of Aircraft Observations Over the South Atlantic Basin

The photochemistry of the troposphere over the South Atlantic basin is examined by modeling of aircraft observations up to 12-km altitude taken during the TRACE A expedition in September-October 1992. A close balance is found in the 0 to 12-km column between photochemical production and loss Of O3, with net production at high altitudes compensating for weak net loss at low altitudes. This balance implies that O3 concentrations in the 0-12 km column can be explained solely by in situ photochemistry; influx from the stratosphere is negligible. Simulation of H2O2, CH3OOH, and CH2O concentrations measured aboard the aircraft lends confidence in the computations of O3 production and loss rates, although there appears to be a major gap in current understanding of CH2O chemistry in the marine boundary layer. The primary sources of NO(x) over the South Atlantic Basin appear to be continental (biomass burning, lightning, soils). There is evidence that NO(x) throughout the 0 to 12-km column is recycled from its oxidation products rather than directly transported from its primary sources. There is also evidence for rapid conversion of HNO3 to NO(x) in the upper troposphere by a mechanism not included in current models. A general representation of the O3 budget in the tropical troposphere is proposed that couples the large scale Walker circulation and in situ photochemistry. Deep convection in the rising branches of the Walker circulation injects NO(x) from combustion, soils, and lightning to the upper troposphere, leading to O3 production; eventually, the air subsides and net O3 loss takes place in the lower troposphere, closing the O3 cycle. This scheme implies a great sensitivity of the oxidizing power of the atmosphere to NO(x) emissions in the tropics

Megalin/LRP2 Expression Is Induced by Peroxisome Proliferator-Activated Receptor -Alpha and -Gamma: Implications for PPARs' Roles in Renal Function

BACKGROUND: Megalin is a large endocytic receptor with relevant functions during development and adult life. It is expressed at the apical surface of several epithelial cell types, including proximal tubule cells (PTCs) in the kidney, where it internalizes apolipoproteins, vitamins and hormones with their corresponding carrier proteins and signaling molecules. Despite the important physiological roles of megalin little is known about the regulation of its expression. By analyzing the human megalin promoter, we found three response elements for the peroxisomal proliferator-activated receptor (PPAR). The objective of this study was to test whether megalin expression is regulated by the PPARs. METHODOLOGY/PRINCIPAL FINDINGS: Treatment of epithelial cell lines with PPARα or PPARγ ligands increased megalin mRNA and protein expression. The stimulation of megalin mRNA expression was blocked by the addition of specific PPARα or PPARγ antagonists. Furthermore, PPAR bound to three PPAR response elements located in the megalin promoter, as shown by EMSA, and PPARα and its agonist activated a luciferase construct containing a portion of the megalin promoter and the first response element. Accordingly, the activation of PPARα and PPARγ enhanced megalin expression in mouse kidney. As previously observed, high concentrations of bovine serum albumin (BSA) decreased megalin in PTCs in vitro; however, PTCs pretreated with PPARα and PPARγ agonists avoided this BSA-mediated reduction of megalin expression. Finally, we found that megalin expression was significantly inhibited in the PTCs of rats that were injected with BSA to induce tubulointerstitial damage and proteinuria. Treatment of these rats with PPARγ agonists counteracted the reduction in megalin expression and the proteinuria induced by BSA. CONCLUSIONS: PPARα/γ and their agonists positively control megalin expression. This regulation could have an important impact on several megalin-mediated physiological processes and on pathophysiologies such as chronic kidney disease associated with diabetes and hypertension, in which megalin expression is impaired

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science