The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized primarily at the apical or luminal surfaces of epithelial cells that line the airway, gut, and exocrine glands; it is well established that CFTR plays a pivotal role in cholera toxin (CTX)-induced secretory diarrhea. Lysophosphatidic acid (LPA), a naturally occurring phospholipid present in blood and foods, has been reported to play a vital role in a variety of conditions involving gastrointestinal wound repair, apoptosis, inflammatory bowel disease, and diarrhea. Here we show, for the first time, that type 2 LPA receptors (LPA2) are expressed at the apical surface of intestinal epithelial cells, where they form a macromolecular complex with Na+/H+ exchanger regulatory factor–2 and CFTR through a PSD95/Dlg/ZO-1–based interaction. LPA inhibited CFTR-dependent iodide efflux through LPA2-mediated Gi pathway, and LPA inhibited CFTR-mediated short-circuit currents in a compartmentalized fashion. CFTR-dependent intestinal fluid secretion induced by CTX in mice was reduced substantially by LPA administration; disruption of this complex using a cell-permeant LPA2-specific peptide reversed LPA2-mediated inhibition. Thus, LPA-rich foods may represent an alternative method of treating certain forms of diarrhea.
Shelf sediments underlying temperate and oxic waters of the Celtic Sea (NW European Shelf) were found to have shallow oxygen penetrations depths from late spring to late summer (2.2-5.8 mm below seafloor) with the shallowest during/after the spring-bloom (mid-April to mid-May) when the organic carbon content was highest. Sediment porewater dissolved iron (dFe,\0.15 lm) mainly ([85%) consisted of Fe(II) and gradually increased from 0.4 to 15 lM at the sediment surface to *100-170 lM at about 6 cm depth. During the late spring this Fe(II) was found to be mainly present as soluble Fe(II) ([85% sFe, \0.02 lm). Sub-surface dFe(II) maxima were enriched in light isotopes (d 56 Fe -2.0 to -1.5%), which is attributed to dissimilatory iron reduction (DIR) during the bacterial decomposition of organic matter. As porewater Fe(II) was oxidised to insoluble Fe(III) in the surface sediment layer, residual Fe(II) was further enriched in light isotopes (down to -3.0%). Ferrozine-reactive Fe(II) was found in surface porewaters and in overlying core top waters, and was highest in the late spring period. Shipboard experiments showed that depletion of bottom water Responsible Editor: Martin Solan.Electronic supplementary material The online version of this article (doi:10.1007/s10533-017-0309-x) contains supplementary material, which is available to authorized users. 49-67 DOI 10.1007/s10533-017-0309-x oxygen in late spring can lead to a substantial release of Fe(II). Reoxygenation of bottom water caused this Fe(II) to be rapidly lost from solution, but residual dFe(II) and dFe(III) remained (12 and 33 nM) after [7 h. Iron(II) oxidation experiments in core top and bottom waters also showed removal from solution but at rates up to 5-times slower than predicted from theoretical reaction kinetics. These data imply the presence of ligands capable of complexing Fe(II) and supressing oxidation. The lower oxidation rate allows more time for the diffusion of Fe(II) from the sediments into the overlying water column. Modelling indicates significant diffusive fluxes of Fe(II) (on the order of 23-31 lmol m -2 day -1 ) are possible during late spring when oxygen penetration depths are shallow, and pore water Fe(II) concentrations are highest. In the water column this stabilised Fe(II) will gradually be oxidised and become part of the dFe(III) pool. Thus oxic continental shelves can supply dFe to the water column, which is enhanced during a small period of the year after phytoplankton bloom events when organic matter is transferred to the seafloor. This input is based on conservative assumptions for solute exchange (diffusion-reaction), whereas (bio)physical advection and resuspension events are likely to accelerate these solute exchanges in shelf-seas.
Pearson now uses a technology‐based testing platform, Q‐Interactive, to administer tests previously available in paper versions. The same norms are used for both versions; Pearson's in‐house equivalency studies indicated that both versions are equated. The goal of the current study is to independently evaluate equivalency findings. For the current study, equivalency was measured using the three‐part test set forth by American Psychological Association in 1986. First, the researchers examined rank order similarity; then, they examined mean score similarity; and finally, they examined score‐distribution similarity. One of these equivalency standards (rank order similarity) was not met, and one other standard is debatable (mean score similarity); therefore, the authors noted concerns about the use of Peabody Picture Vocabulary Test, Fourth Edition Q‐Interactive for preschoolers. New normative data should be collected.
Documented and forecasted trends in rising sea levels and changes in storminess patterns have the potential to increase the frequency, magnitude, and spatial extent of coastal change hazards. To develop realistic adaptation strategies, coastal planners need information about coastal change hazards that recognizes the dynamic temporal and spatial scales of beach morphology, the climate controls on coastal change hazards, and the uncertainties surrounding the drivers and impacts of climate change. We present a probabilistic approach for quantifying and mapping coastal change hazards that incorporates the uncertainty associated with both climate change and morphological variability. To demonstrate the approach, coastal change hazard zones of arbitrary confidence levels are developed for the Tillamook County (State of Oregon, USA) coastline using a suite of simple models and a range of possible climate futures related to wave climate, sea-level rise projections, and the frequency of major El Niño events. Extreme total water levels are 123Nat Hazards (2015) 75:2081-2102 DOI 10.1007/s11069-014-1417 more influenced by wave height variability, whereas the magnitude of erosion is more influenced by sea-level rise scenarios. Morphological variability has a stronger influence on the width of coastal hazard zones than the uncertainty associated with the range of climate change scenarios.
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