Claudins in intestines

Intestines are organs that not only digest food and absorb nutrients, but also provide a defense barrier against pathogens and noxious agents ingested. Tight junctions (TJs) are the most apical component of the junctional complex, providing one form of cell-cell adhesion in enterocytes and playing a critical role in regulating paracellular barrier permeability. Alteration of TJs leads to a number of pathophysiological diseases causing malabsorption of nutrition and intestinal structure disruption, which may even contribute to systemic organ failure. Claudins are the major structural and functional components of TJs with at least 24 members in mammals. Claudins have distinct charge-selectivity, either by tightening the paracellular pathway or functioning as paracellular channels, regulating ions and small molecules passing through the paracellular pathway. In this review, we have discussed the functions of claudin family members, their distribution and localization in the intestinal tract of mammals, their alterations in intestine-related diseases and chemicals/agents that regulate the expression and localization of claudins as well as the intestinal permeability, which provide a therapeutic view for treating intestinal diseases

Recent developments of the Hierarchical Reference Theory of Fluids and its relation to the Renormalization Group

The Hierarchical Reference Theory (HRT) of fluids is a general framework for the description of phase transitions in microscopic models of classical and quantum statistical physics. The foundations of HRT are briefly reviewed in a self-consistent formulation which includes both the original sharp cut-off procedure and the smooth cut-off implementation, which has been recently investigated. The critical properties of HRT are summarized, together with the behavior of the theory at first order phase transitions. However, the emphasis of this presentation is on the close relationship between HRT and non perturbative renormalization group methods, as well as on recent generalizations of HRT to microscopic models of interest in soft matter and quantum many body physics.Comment: 17 pages, 5 figures. Review paper to appear in Molecular Physic

Correlation of microRNA levels during hypoxia with predicted target mRNAs through genome-wide microarray analysis

<p>Abstract</p> <p>Background</p> <p>Low levels of oxygen in tissues, seen in situations such as chronic lung disease, necrotic tumors, and high altitude exposures, initiate a signaling pathway that results in active transcription of genes possessing a hypoxia response element (HRE). The aim of this study was to investigate whether a change in miRNA expression following hypoxia could account for changes in the cellular transcriptome based on currently available miRNA target prediction tools.</p> <p>Methods</p> <p>To identify changes induced by hypoxia, we conducted mRNA- and miRNA-array-based experiments in HT29 cells, and performed comparative analysis of the resulting data sets based on multiple target prediction algorithms. To date, few studies have investigated an environmental perturbation for effects on genome-wide miRNA levels, or their consequent influence on mRNA output.</p> <p>Results</p> <p>Comparison of miRNAs with predicted mRNA targets indicated a lower level of concordance than expected. We did, however, find preliminary evidence of combinatorial regulation of mRNA expression by miRNA.</p> <p>Conclusion</p> <p>Target prediction programs and expression profiling techniques do not yet adequately represent the complexity of miRNA-mediated gene repression, and new methods may be required to better elucidate these pathways. Our data suggest the physiologic impact of miRNAs on cellular transcription results from a multifaceted network of miRNA and mRNA relationships, working together in an interconnected system and in context of hundreds of RNA species. The methods described here for comparative analysis of cellular miRNA and mRNA will be useful for understanding genome wide regulatory responsiveness and refining miRNA predictive algorithms.</p

Profiling Synaptic Proteins Identifies Regulators of Insulin Secretion and Lifespan

Cells are organized into distinct compartments to perform specific tasks with spatial precision. In neurons, presynaptic specializations are biochemically complex subcellular structures dedicated to neurotransmitter secretion. Activity-dependent changes in the abundance of presynaptic proteins are thought to endow synapses with different functional states; however, relatively little is known about the rules that govern changes in the composition of presynaptic terminals. We describe a genetic strategy to systematically analyze protein localization at Caenorhabditis elegans presynaptic specializations. Nine presynaptic proteins were GFP-tagged, allowing visualization of multiple presynaptic structures. Changes in the distribution and abundance of these proteins were quantified in 25 mutants that alter different aspects of neurotransmission. Global analysis of these data identified novel relationships between particular presynaptic components and provides a new method to compare gene functions by identifying shared protein localization phenotypes. Using this strategy, we identified several genes that regulate secretion of insulin-like growth factors (IGFs) and influence lifespan in a manner dependent on insulin/IGF signaling

Piscine PTHrP regulation of calcium and phosphate transport in winter flounder renal proximal tubule primary cultures

Multiple factors control calcium (Ca2 ) and inorganic phosphate (Pi) transport in the fish nephron, and the recently discovered members of the piscine parathyroid hormone-like protein family are likely participants in such regulatory mechanisms. The effects of an NH2-terminal peptide (amino acids 1–34) of Takifugu rubripes parathyroid hormone-related protein, (1–34)PTHrP, on Ca2 and Pi transport were investigated in winter flounder (Pseudopleuronectes americanus) proximal tubule cells in primary culture (fPTCs). RT-PCR performed on RNA extracted from fPTCs and from intact kidney tissue indicated that expression of PTHrP and types 1 and 3 PTH/PTHrP receptors occurred both in vivo and in vitro and that circulating levels of PTHrP measured by specific radioimmunoassay averaged 2.5 0.13 ng/ml. fPTC monolayers were mounted in Ussing chambers, and under neutral electrochemical conditions, addition of 10 nM (1–34)PTHrP to the basolateral side induced a slight increase in Ca2 transport rate from luminal to peritubular side, significantly stimulating net Ca2 reabsorption. (1–34)PTHrP also significantly increased the Pi secretory flux, and slightly reduced Pi reabsorption, evoking a significant increase in Pi net secretion. This stimulatory effect was partially inhibited by bisindolylmaleimide, an inhibitor of protein kinase C. Incubation of ex vivo flounder renal tubules with (1–34)PTHrP resulted in apparent reduction of Na -Pi cotransporter type II (NaPi-II) protein in tubule membranes. PTHrP seems therefore to participate in the modulation of Ca2 and Pi homeostasis by fish kidney