Mechanisms and Regulation of Intestinal Phosphate Absorption.

States of hypo- and hyperphosphatemia have deleterious consequences including rickets/osteomalacia and renal/cardiovascular disease, respectively. Therefore, the maintenance of appropriate plasma levels of phosphate is an essential requirement for health. This control is executed by the collaborative action of intestine and kidney whose capacities to (re)absorb phosphate are regulated by a number of hormonal and metabolic factors, among them parathyroid hormone, fibroblast growth factor 23, 1,25(OH) vitamin D , and dietary phosphate.

Regulation of vitamin D metabolizing enzymes in murine renal and extrarenal tissues by dietary phosphate, FGF23, and 1,25(OH)2D3.

Background: The 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) together with parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) regulates calcium (Ca2+) and phosphate (Pi) homeostasis, 1,25(OH)2D3 synthesis is mediated by hydroxylases of the cytochrome P450 (Cyp) family. Vitamin D is first modified in the liver by the 25-hydroxylases CYP2R1 and CYP27A1 and further activated in the kidney by the 1α-hydroxylase CYP27B1, while the renal 24-hydroxylase CYP24A1 catalyzes the first step of its inactivation. While the kidney is the main organ responsible for circulating levels of active 1,25(OH)2D3, other organs also express some of these enzymes.

The elevation of circulating fibroblast growth factor 23 without kidney disease does not increase cardiovascular disease risk.

High circulating fibroblast growth factor 23 (FGF23) levels are probably a major risk factor for cardiovascular disease in chronic kidney disease. FGF23 interacts with the receptor FGFR4 in cardiomyocytes inducing left ventricular hypertrophy. Moreover, in the liver FGF23 via FGFR4 increases the risk of inflammation which is also found in chronic kidney disease.

Renal phosphate handling and inherited disorders of phosphate reabsorption: an update.

Renal phosphate handling critically determines plasma phosphate and whole body phosphate levels. Filtered phosphate is mostly reabsorbed by Na-dependent phosphate transporters located in the brush border membrane of the proximal tubule: NaPi-IIa (SLC34A1), NaPi-IIc (SLC34A3), and Pit-2 (SLC20A2). Here we review new evidence for the role and relevance of these transporters in inherited disorders of renal phosphate handling.

SmilesDrawer: Parsing and Drawing SMILES-Encoded Molecular Structures Using Client-Side JavaScript.

Here we present SmilesDrawer, a dependency-free JavaScript component capable of both parsing and drawing SMILES-encoded molecular structures client-side, developed to be easily integrated into web projects and to display organic molecules in large numbers and fast succession. SmilesDrawer can draw structurally and stereochemically complex structures such as maitotoxin and C without using templates, yet has an exceptionally small computational footprint and low memory usage without the requirement for loading images or any other form of client-server communication, making it easy to integrate even in secure (intranet, firewalled) or offline applications. These features allow the rendering of thousands of molecular structure drawings on a single web page within seconds on a wide range of hardware supporting modern browsers.

Changes in urinary risk profile after short-term low sodium and low calcium diet in recurrent Swiss kidney stone formers.

Background: Kidney stone disease is common in industrialized countries. Recently, it has attracted growing attention, because of its significant association with adverse renal outcomes, including end stage renal disease. Calcium-containing kidney stones are frequent with high recurrence rates.

FUn: a framework for interactive visualizations of large, high-dimensional datasets on the web.

Motivation: During the past decade, big data have become a major tool in scientific endeavors. Although statistical methods and algorithms are well-suited for analyzing and summarizing enormous amounts of data, the results do not allow for a visual inspection of the entire data. Current scientific software, including R packages and Python libraries such as ggplot2, matplotlib and plot.

Pathophysiology, diagnosis and treatment of inherited distal renal tubular acidosis.

Distal renal tubular acidosis (dRTA) is a tubular disorder with a primary defect of urinary acidification and acid excretion in the collecting duct system. Consequently, patients develop hyperchloremic metabolic acidosis with an inappropriately alkaline urine. Inherited forms of dRTA are due to mutations in at least three distinct genes: SLC4A1, ATP6V1B1, ATP6V0A4.

The intestinal phosphate transporter NaPi-IIb (Slc34a2) is required to protect bone during dietary phosphate restriction.

NaPi-IIb/Slc34a2 is a Na-dependent phosphate transporter that accounts for the majority of active phosphate transport into intestinal epithelial cells. Its abundance is regulated by dietary phosphate, being high during dietary phosphate restriction. Intestinal ablation of NaPi-IIb in mice leads to increased fecal excretion of phosphate, which is compensated by enhanced renal reabsorption.

Acute regulated expression of pendrin in human urinary exosomes.

It is well known that pendrin, an apical Cl/HCOexchanger in type B intercalated cells, is modulated by chronic acid-base disturbances and electrolyte intake. To study this adaptation further at the acute level, we analyzed urinary exosomes from individuals subjected to oral acute acid, alkali, and NaCl loading. Acute oral NHCl loading (n = 8) elicited systemic acidemia with a drop in urinary pH and an increase in urinary NH excretion.

The matricellular protein CYR61 promotes breast cancer lung metastasis by facilitating tumor cell extravasation and suppressing anoikis.

Matricellular proteins play multiple roles in primary tumor growth, local invasion and tumor angiogenesis. However, their contribution to metastasis and the putative mechanisms involved are less well characterized. In ER-negative human breast cancer, elevated expression levels of the matricellular protein Cysteine-rich angiogenic inducer 61 (CYR61) are associated with more aggressive progression.

The matricellular protein CYR61 interferes with normal pancreatic islets architecture and promotes pancreatic neuroendocrine tumor progression.

The significance of matricellular proteins during development and cancer progression is widely recognized. However, how these proteins actively contribute to physiological development and pathological cancer progression is only partially elucidated. In this study, we investigated the role of the matricellular protein Cysteine-rich 61 (CYR61) in pancreatic islet development and carcinogenesis.

Discovery of a 29-gene panel in peripheral blood mononuclear cells for the detection of colorectal cancer and adenomas using high throughput real-time PCR.

Colorectal cancer (CRC) is the second leading cause of cancer-related death in developed countries. Early detection of CRC leads to decreased CRC mortality. A blood-based CRC screening test is highly desirable due to limited invasiveness and high acceptance rate among patients compared to currently used fecal occult blood testing and colonoscopy.

Regulation of telomere addition at DNA double-strand breaks.

Telomeres constitute the ends of linear eukaryotic chromosomes. Due to the conventional mode of DNA replication, telomeric DNA erodes at each cell division. To counteract this, a specialized reverse transcriptase, telomerase, can elongate chromosome ends to maintain them at a constant average length.

Keeping mRNPs in check during assembly and nuclear export.

The cell nucleus is an intricate organelle that coordinates multiple activities that are associated with DNA replication and gene expression. In all eukaryotes, it stores the genetic information and the machineries that control the production of mature and export-competent messenger ribonucleoproteins (mRNPs), a multistep process that is regulated in a spatial and temporal manner. Recent studies suggest that post-translational modifications play a part in coordinating the co-transcriptional assembly, remodelling and export of mRNP complexes through nuclear pores, adding a new level of regulation to the process of gene expression.

DNA breaks are masked by multiple Rap1 binding in yeast: implications for telomere capping and telomerase regulation.

Eukaryotic cells distinguish their chromosome ends from accidental DNA double-strand breaks by packaging them in a protective structure referred to as the telomere "cap." Here we investigate the nature of the telomere cap by examining events at DNA breaks generated adjacent to either natural telomeric sequences (TG repeats) or arrays of Rap1-binding sites that vary in length. Although DNA breaks adjacent to either short or long telomeric sequences are efficiently converted into stable telomeres, they elicit very different initial responses.