Human intestinal anion exchanger isoforms: expression, distribution, and membrane localization

AbstractA family of anion exchangers (AEs) including AE1, AE2 and AE3 has been described. AE3 gene has been shown to encode two alternatively spliced isoforms termed as bAE3 (brain subtype) and cAE3 (cardiac subtype). The identity of the AE(s) involved in the human intestinal NaCl absorption is not fully understood. Current studies were undertaken to identify the AE isoforms expressed in the human intestine, to define their regional and vertical axis (crypt vs. surface cells) distribution, and to elucidate their membrane localization in the epithelial cells along the entire length of the human intestine. Our studies utilizing reverse transcription (RT)-PCR with total RNA extracted from pinch biopsies from various regions of the human intestine demonstrate that AE2 and bAE3 but not AE1 or cAE3 were expressed in all the regions of the human intestine. Utilizing in situ RT-PCR, we demonstrated that the message of AE2 was expressed throughout the vertical surface–crypt axis of the colon. Our Western blotting studies demonstrated that AE2 and bAE3 are localized to the basolateral but not the apical membranes of the intestinal epithelial cells from the human ileum and colon. In conclusion, our results demonstrated that in the human intestine, AE2 and bAE3, but not AE1 or cAE3, are expressed throughout the tract with the highest expression in the colon compared to the ileum and jejunum. Both the isoforms were found to be localized to the basolateral but not the apical membranes of the epithelial cells. We speculate that, in the human intestine, AE2 and bAE3 may be the ‘housekeeping’ isoforms, and the apical AE, the potential candidate for chloride absorption, remains to be identified

Quenched bond randomness in marginal and non-marginal Ising spin models in 2D

We investigate and contrast, via entropic sampling based on the Wang-Landau algorithm, the effects of quenched bond randomness on the critical behavior of two Ising spin models in 2D. The random bond version of the superantiferromagnetic (SAF) square model with nearest- and next-nearest-neighbor competing interactions and the corresponding version of the simple Ising model are studied and their general universality aspects are inspected by a detailed finite-size scaling (FSS) analysis. We find that, the random bond SAF model obeys weak universality, hyperscaling, and exhibits a strong saturating behavior of the specific heat due to the competing nature of interactions. On the other hand, for the random Ising model we encounter some difficulties for a definite discrimination between the two well-known scenarios of the logarithmic corrections versus the weak universality. Yet, a careful FSS analysis of our data favors the field-theoretically predicted logarithmic corrections.Comment: 19 pages, 5 figures, final versio

Wetting of a symmetrical binary fluid mixture on a wall

We study the wetting behaviour of a symmetrical binary fluid below the demixing temperature at a non-selective attractive wall. Although it demixes in the bulk, a sufficiently thin liquid film remains mixed. On approaching liquid/vapour coexistence, however, the thickness of the liquid film increases and it may demix and then wet the substrate. We show that the wetting properties are determined by an interplay of the two length scales related to the density and the composition fluctuations. The problem is analysed within the framework of a generic two component Ginzburg-Landau functional (appropriate for systems with short-ranged interactions). This functional is minimized both numerically and analytically within a piecewise parabolic potential approximation. A number of novel surface transitions are found, including first order demixing and prewetting, continuous demixing, a tricritical point connecting the two regimes, or a critical end point beyond which the prewetting line separates a strongly and a weakly demixed film. Our results are supported by detailed Monte Carlo simulations of a symmetrical binary Lennard-Jones fluid at an attractive wall.Comment: submitted to Phys. Rev.

Critical aspects of the random-field Ising model

We investigate the critical behavior of the three-dimensional random-field Ising model (RFIM) with a Gaussian field distribution at zero temperature. By implementing a computational approach that maps the ground-state of the RFIM to the maximum-flow optimization problem of a network, we simulate large ensembles of disorder realizations of the model for a broad range of values of the disorder strength h and system sizes  = L3, with L ≤ 156. Our averaging procedure outcomes previous studies of the model, increasing the sampling of ground states by a factor of 103. Using well-established finite-size scaling schemes, the fourth-order’s Binder cumulant, and the sample-to-sample fluctuations of various thermodynamic quantities, we provide high-accuracy estimates for the critical field hc, as well as the critical exponents ν, β/ν, and γ̅/ν of the correlation length, order parameter, and disconnected susceptibility, respectively. Moreover, using properly defined noise to signal ratios, we depict the variation of the self-averaging property of the model, by crossing the phase boundary into the ordered phase. Finally, we discuss the controversial issue of the specific heat based on a scaling analysis of the bond energy, providing evidence that its critical exponent α ≈ 0−

Molecular cloning of a human small intestinal apolipoprotein B mRNA editing protein.

Mammalian small intestinal apolipoprotein B (apo B) mRNA undergoes posttranscriptional cytidine deamination with the production of an in frame stop codon and the translation of apo B48. We have isolated a cDNA from human jejunum which mediates in vitro editing of a synthetic apo B RNA template upon complementation with chicken intestinal S100 extracts. The cDNA specifies a 236 residue protein which is 69% identical to the apo B mRNA editing protein (REPR) cloned from rat small intestine [Teng, B., Burant, C. F. and Davidson, N. O. (1993) Science 260, 1816-1819] and which, by analogy, is referred to as HEPR. HEPR does not contain the carboxyl-terminus leucine zipper motif identified in REPR but contains consensus phosphorylation sites as well as the conserved histidine and both cysteine residues identified as a Zn2+ binding motif in other cytidine deaminases. The distribution of HEPR mRNA was predominantly confined to the adult small intestine with lower levels detectable by reverse-transcription polymerase chain reaction amplification in the stomach, colon and testis. These differences in the structure and distribution of the human as compared to the rat apo B mRNA editing protein suggest an important evolutionary adaptation in the mechanisms restricting apo B48 production to the small intestine

Entropic sampling via Wang-Landau random walks in dominant energy subspaces

Dominant energy subspaces of statistical systems are defined with the help of restrictive conditions on various characteristics of the energy distribution, such as the probability density and the forth order Binder's cumulant. Our analysis generalizes the ideas of the critical minimum energy-subspace (CrMES) technique \cite{malakis04}, applied previously to study the specific heat's finite-size scaling. Here, we illustrate alternatives that are useful for the analysis of further finite-size anomalies and the behavior of the corresponding dominant subspaces is presented for the 2D Baxter-Wu, the 2D and 3D Ising models. In order to show that a CrMES technique is adequate for the study of magnetic anomalies, we study and test simple methods which provide the means for an accurate determination of the energy - order-parameter ($E-M$) histograms via Wang-Landau random walks. The 2D Ising model is used as a test case and it is shown that high-level Wang-Landau sampling schemes yield excellent estimates for all magnetic properties. Our estimates compare very well with those of the traditional Metropolis method. The relevant dominant energy subspaces and dominant magnetization subspaces scale as expected with exponents $\alpha/\nu$ and $\gamma/\nu$ respectively. Using the Metropolis method we examine the time evolution of the corresponding dominant magnetization subspaces and we uncover the reasons behind the inadequacy of the Metropolis method to produce a reliable estimation scheme for the tail-regime of the order parameter distribution.Comment: 32 pages, 12 figures, version as accepted for publication to Phys. Rev.