Regulation of AQP0 water permeability is enhanced by cooperativity.

Aquaporin 0 (AQP0), essential for lens clarity, is a tetrameric protein composed of four identical monomers, each of which has its own water pore. The water permeability of AQP0 expressed in Xenopus laevis oocytes can be approximately doubled by changes in calcium concentration or pH. Although each monomer pore functions as a water channel, under certain conditions the pores act cooperatively. In other words, the tetramer is the functional unit. In this paper, we show that changes in external pH and calcium can induce an increase in water permeability that exhibits either a positive cooperativity switch-like increase in water permeability or an increase in water permeability in which each monomer acts independently and additively. Because the concentrations of calcium and hydrogen ions increase toward the center of the lens, a concentration signal could trigger a regulatory change in AQP0 water permeability. It thus seems plausible that the cooperative modes of water permeability regulation by AQP0 tetramers mediated by decreased pH and elevated calcium are the physiologically important ones in the living lens

Biotin Supplementation Ameliorates Murine Colitis by Preventing NF-κB Activation.

Background & aimsBiotin is a water-soluble vitamin that is indispensable for human health. Biotin deficiency can cause failure-to-thrive, immunodeficiency, alopecia, dermatitis, and conjunctivitis. We previously reported that biotin deficiency also can lead to severe colitis in mice, which is completely reversed with supplementation. Our aim in this study was to determine if high-dose biotin supplementation can provide a therapeutic benefit in a preclinical model for inflammatory bowel disease (IBD) and to identify the molecular mechanism by which this occurs.MethodsMice were challenged with dextran sodium sulfate to induce colitis and were treated with 1 mmol/L biotin to induce or maintain remission. Clinical response was monitored by the Disease Activity Index and fecal calprotectin levels. The colon tissue was investigated for histology, length, as well as expression of inflammatory cytokines (interleukin 6, tumor necrosis factor-α, interleukin 1β), intestinal permeability, tight junctions (zonula occludens-1 and claudin-2), and the transcription factor nuclear factor-κB (NF-κB).ResultsBiotin therapy led to delayed onset and severity of colitis as well as accelerated healing. There was improvement in the Disease Activity Index, fecal calprotectin levels, colon length, and histology. In addition, biotin-treated mice had reduced expression of inflammatory cytokines, reduced intestinal permeability, and reduced activation of NF-κB.ConclusionsOral supplementation with biotin provides benefit for maintenance and induction of remission in the dextran sodium sulfate preclinical model for IBD. Biotin does this by reducing the activation of NF-κB, which prevents the production of inflammatory cytokines and helps maintain the integrity of the intestinal barrier. Clinically, the NF-κB pathway is important in the development of IBD and this finding suggests that biotin may have therapeutic potential for patients with IBD

The effect of precipitation and application rate on dicyandiamide persistence and efficiency in two Irish grassland soils

peer-reviewedThe nitrification inhibitor dicyandiamide (DCD) has had variable success in reducing nitrate (NO3-) leaching and nitrous oxide (N2O) emissions from soils receiving nitrogen (N) fertilisers. Factors such as soil type, temperature and moisture have been linked to the variable efficacy of DCD. Since DCD is water soluble it can be leached from the rooting zone where it is intended to inhibit nitrification. Intact soil columns (15 cm diameter by 35 cm long) were taken from luvic gleysol and haplic cambisol grassland sites and placed in growth chambers. DCD was applied at 15 or 30 kg DCD ha-1, with high or low precipitation. Leaching of DCD, mineral N and the residual soil DCD concentrations were determined over eight weeks High precipitation increased DCD in leachate and decreased recovery in soil. A soil x DCD rate interaction was detected for the DCD unaccounted (proxy for degraded DCD). In the cambisol degradation of DCD was high (circa 81%) and unaffected by DCD rate. In contrast DCD degradation in the gleysol was lower and differentially affected by rate, 67 and 46% for the 15 and 30 kg ha-1 treatments, respectively. Differences DCD degradation rates between soils may be related to differences in organic matter content and associated microbiological activity. Variable degradation rates of DCD in soil, unrelated to temperature or moisture, may contribute to varying DCD efficacy. Soil properties should be considered when tailoring DCD strategies for improving nitrogen use efficiency and crop yields, through the reduction of reactive nitrogen loss.This research was financially supported under the National Development Plan, through the Research Stimulus Fund, administered by the Department of Agriculture, Food and the Marine under grants 07519 and 07545

The effect of cattle slurry in combination with nitrate and the nitrification inhibitor dicyandiamide on in situ nitrous oxide and dinitrogen emissions

peer-reviewedA field study was conducted to determine the effect of the nitrification inhibitor dicyandiamide (DCD) on N2O and N2 emissions after cattle slurry (CS) application in the presence of nitrate (NO3) fertiliser on seven different occasions (between March 2009 and March 2011). N2O emissions from CS in the presence of NO3 fertiliser were very high (0.4–8.7% of applied N) over a 20-day period, under mild moist conditions. Emissions were significantly larger from the CS treatment compared to an NH4+-N source, supplying the same rate of N as in the slurry. This study supports the view that organic fertilisers should not be applied at the same time as nitrate-based fertilisers, as significant increases in N2O emissions occur. The average N2O mole fraction (N2O/(N2O + N2)) over all seven application dates was 0.34 for CSNO3 compared to 0.24 for the NH4ClNO3 treatment, indicating the dominance of N2 emissions. The rate of nitrification in CSNO3 was slower than in NH4ClNO3, and DCD was found to be an effective nitrification inhibitor in both treatments. However, as N2O emissions were found to be predominantly associated with the NO3 pool, the effect of DCD in lowering N2O emissions is limited in the presence of a NO3 fertiliser. To obtain the maximum cost-benefit of DCD in lowering N2O emissions, under mild moist conditions, it should not be applied to a nitrate containing fertiliser (e.g. ammonium nitrate or calcium ammonium nitrate), and therefore the application of DCD should be restricted to ammonium-based organic or synthetic fertilisers.This research was funded by the Irish National Development Plan, through the Research Stimulus Fund (RSF 07 519), administered by the Irish Department of Agriculture, Food and the Marine

Statistical Derivation of the Evolution Equation of Liquid Water Path Fluctuations in Clouds

How to distinguish and quantify deterministic and random influences on the statistics of turbulence data in meteorology cases is discussed from first principles. Liquid water path (LWP) changes in clouds, as retrieved from radio signals, upon different delay times, can be regarded as a stochastic Markov process. A detrended fluctuation analysis method indicates the existence of long range time correlations. The Fokker-Planck equation which models very precisely the LWP $fluctuation$ empirical probability distributions, in particular, their non-Gaussian heavy tails is explicitly derived and written in terms of a drift and a diffusion coefficient. Furthermore, Kramers-Moyal coefficients, as estimated from the empirical data, are found to be in good agreement with their first principle derivation. Finally, the equivalent Langevin equation is written for the LWP increments themselves. Thus rather than the existence of hierarchical structures, like an energy cascade process, {\it strong correlations} on different $time$ $scales$, from small to large ones, are considered to be proven as intrinsic ingredients of such cloud evolutions.Comment: 17 pages, 6 figures; to be published in Journal of Geophysical Research - Atmosphere

Windowed and Wavelet Analysis of Marine Stratocumulus Cloud Inhomogeneity

To improve radiative transfer calculations for inhomogeneous clouds, a consistent means of modeling inhomogeneity is needed. One current method of modeling cloud inhomogeneity is through the use of fractal parameters. This method is based on the supposition that cloud inhomogeneity over a large range of scales is related. An analysis technique named wavelet analysis provides a means of studying the multiscale nature of cloud inhomogeneity. In this paper, the authors discuss the analysis and modeling of cloud inhomogeneity through the use of wavelet analysis. Wavelet analysis as well as other windowed analysis techniques are used to study liquid water path (LWP) measurements obtained during the marine stratocumulus phase of the First ISCCP (International Satellite Cloud Climatology Project) Regional Experiment. Statistics obtained using analysis windows, which are translated to span the LWP dataset, are used to study the local (small scale) properties of the cloud field as well as their time dependence. The LWP data are transformed onto an orthogonal wavelet basis that represents the data as a number of times series. Each of these time series lies within a frequency band and has a mean frequency that is half the frequency of the previous band. Wavelet analysis combined with translated analysis windows reveals that the local standard deviation of each frequency band is correlated with the local standard deviation of the other frequency bands. The ratio between the standard deviation of adjacent frequency bands is 0.9 and remains constant with respect to time. This ratio defined as the variance coupling parameter is applicable to all of the frequency bands studied and appears to be related to the slope of the data's power spectrum. Similar analyses are performed on two cloud inhomogeneity models, which use fractal-based concepts to introduce inhomogeneity into a uniform cloud field. The bounded cascade model does this by iteratively redistributing LWP at each scale using the value of the local mean. This model is reformulated into a wavelet multiresolution framework, thereby presenting a number of variants of the bounded cascade model. One variant introduced in this paper is the 'variance coupled model,' which redistributes LWP using the local standard deviation and the variance coupling parameter. While the bounded cascade model provides an elegant two- parameter model for generating cloud inhomogeneity, the multiresolution framework provides more flexibility at the expense of model complexity. Comparisons are made with the results from the LWP data analysis to demonstrate both the strengths and weaknesses of these models

Hard scattering and jets--from p-p collisions in the 1970's to Au+Au collisions at RHIC

Hard scattering in p-p collisions, discovered at the CERN ISR in 1972 by the method of leading particles, proved that the partons of Deeply Inelastic Scattering strongly interacted with each other. Further ISR measurements utilizing inclusive single or pairs of hadrons established that high pT particles are produced from states with two roughly back-to-back jets which are the result of scattering of constituents of the nucleons as described by Quantum Chromodynamics (QCD), which was developed during the course of these measurements. These techniques, which are the only practical method to study hard-scattering and jet phenomena in Au+Au central collisions, are reviewed, with application to measurements at RHIC.Comment: 4 pages, 5 figures, Proceedings of Hard Probes 2004, International Conference on Hard and Electromagnetic Probes of High Energy Nuclear Collisions, Nov 4-10, 2004, to appear in EPJ

Nanoscale patterning of STIM1 and Orai1 during store-operated Ca2+ entry

Stromal interacting molecule (STIM) and Orai proteins constitute the core machinery of store-operated calcium entry. We used transmission and freeze-fracture electron microscopy to visualize STIM1 and Orai1 at endoplasmic reticulum (ER)-plasma membrane (PM) junctions in HEK 293 cells. Compared with control cells, thin sections of STIM1-transfected cells possessed far more ER elements, which took the form of complex stackable cisternae and labyrinthine structures adjoining the PM at junctional couplings (JCs). JC formation required STIM1 expression but not store depletion, induced here by thapsigargin (TG). Extended molecules, indicative of STIM1, decorated the cytoplasmic surface of ER, bridged a 12-nm ER-PM gap, and showed clear rearrangement into small clusters following TG treatment. Freeze-fracture replicas of the PM of Orai1-transfected cells showed extensive domains packed with characteristic "particles"; TG treatment led to aggregation of these particles into sharply delimited "puncta" positioned upon raised membrane subdomains. The size and spacing of Orai1 channels were consistent with the Orai crystal structure, and stoichiometry was unchanged by store depletion, coexpression with STIM1, or an Orai1 mutation (L273D) affecting STIM1 association. Although the arrangement of Orai1 channels in puncta was substantially unstructured, a portion of channels were spaced at ?15 nm. Monte Carlo analysis supported a nonrandom distribution for a portion of channels spaced at ∼15 nm. These images offer dramatic, direct views of STIM1 aggregation and Orai1 clustering in store-depleted cells and provide evidence for the interaction of a single Orai1 channel with small clusters of STIM1 molecules