Disorder within order: identification of the disordered loop of STAS domain as the inhibitory domain in SLC26A9 chloride channel.

The chloride transporter-channel SLC26A9 is mediated by a reciprocal regulatory mechanism through the interaction between its cytoplasmic STAS domain and the R domain of CFTR. In vertebrate Slc26a9s, the STAS domain structures are interrupted by a disordered loop which is conserved in mammals but is variable in non-mammals. Despite the numerous studies involving the STAS domains in SLC26 proteins, the role of the disordered loop region has not been identified.

Novel Uveal Melanoma Patient-Derived Organoid Models Recapitulate Human Disease to Support Translational Research.

Purpose: A lack of representative human disease models has limited the translation of new and more effective treatments in uveal melanoma (UM), the most common primary adult intraocular malignancy. To fill this critical need, we developed and characterized a multicenter biobank of UM patient-derived organoids (PDOs).

Methods: UM patients requiring enucleation from 2019 to 2024 donated tumor tissue for PDO generation.

Robotic Ultrasound and Novel Collagen Analyses for Polycystic Kidney Disease Research Using Mice.

Key Points: Robotic ultrasound performed favorably compared with magnetic resonance imaging for evaluating total kidney volume. Collagen evaluation by two novel methods of picrosirius red imaging were more informative than the standard method by brightfield imaging. Findings can improve research by increasing speed and access to total kidney volume determination and sensitivity of collagen assessment.

Function and regulation of the insect NaCCC2 sodium transport proteins.

NaCCC2 transport proteins, including those from Drosophila melanogaster (Ncc83) and Aedes aegypti (aeCCC2), are an insect-specific clade with sequence similarity to Na-K-2Cl cotransporters. Whereas the Na-K-2Cl cotransporters and other cation-chloride cotransporters are electroneutral, recent work indicates that Ncc83 and aeCCC2 carry charge across membranes. Here, we further characterize the regulation and transport properties of Ncc83 and aeCCC2 expressed in Xenopus oocytes.

Glycogen synthase kinase 3 activity enhances liver inflammation in MASH.

Background & Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by excessive circulating toxic lipids, hepatic steatosis, and liver inflammation. Monocyte adhesion to liver sinusoidal endothelial cells (LSECs) and transendothelial migration (TEM) are crucial in the inflammatory process. Under lipotoxic stress, LSECs develop a proinflammatory phenotype known as endotheliopathy.

Convergent gene losses and pseudogenizations in multiple lineages of stomachless fishes.

The regressive evolution of independent lineages often results in convergent phenotypes. Several teleost groups display secondary loss of the stomach, and four gastric genes, atp4a, atp4b, pgc, and pga2 have been co-deleted in agastric (stomachless) fish. Analyses of genotypic convergence among agastric fishes showed that four genes, slc26a9, kcne2, cldn18a, and vsig1, were co-deleted or pseudogenized in most agastric fishes of the four major groups.

The role of Na-coupled bicarbonate transporters (NCBT) in health and disease.

Cellular and organism survival depends upon the regulation of pH, which is regulated by highly specialized cell membrane transporters, the solute carriers (SLC) (For a comprehensive list of the solute carrier family members, see: https://www.bioparadigms.org/slc/ ).

Drosophila ClC-c Is a Homolog of Human CLC-5 and a New Model for Dent Disease Type 1.

Key Points: can be a model for Dent Disease type 1. Clc-C mutations function similar to human CLC-5 Dent 1 mutations.

Background: serve as exceptional alternative models for and research and may provide an avenue for in-depth investigation for human ClC-5 and Dent disease type 1 (DD1).

Functional Divergence in Solute Permeability between Ray-Finned Fish-Specific Paralogs of aqp10.

Aquaporin (Aqp) 10 is a member of the aquaglyceroporin subfamily of water channels, and human Aqp10 is permeable to solutes such as glycerol, urea, and boric acid. Tetrapods have a single aqp10 gene, whereas ray-finned fishes have paralogs of this gene through tandem duplication, whole-genome duplication, and subsequent deletion. A previous study on Aqps in the Japanese pufferfish Takifugu rubripes showed that one pufferfish paralog, Aqp10.

Boric acid transport activity of marine teleost aquaporins expressed in Xenopus oocytes.

Marine teleosts ingest large amounts of seawater containing various ions, including 0.4 mM boric acid, which can accumulate at toxic levels in the body. However, the molecular mechanisms by which marine teleosts absorb and excrete boric acid are not well understood.

Na/K-ATPase signaling tonically inhibits sodium reabsorption in the renal proximal tubule.

Through its classic ATP-dependent ion-pumping function, basolateral Na/K-ATPase (NKA) generates the Na gradient that drives apical Na reabsorption in the renal proximal tubule (RPT), primarily through the Na /H exchanger (NHE3). Accordingly, activation of NKA-mediated ion transport decreases natriuresis through activation of basolateral (NKA) and apical (NHE3) Na reabsorption. In contrast, activation of the more recently discovered NKA signaling function triggers cellular redistribution of RPT NKA and NHE3 and decreases Na reabsorption.

Seawater fish use an electrogenic boric acid transporter, Slc4a11A, for boric acid excretion by the kidney.

Boric acid is a vital micronutrient in animals; however, excess amounts are toxic to them. Little is known about whole-body boric acid homeostasis in animals. Seawater (SW) contains 0.

Membrane Transport Proteins Expressed in the Renal Tubular Epithelial Cells of Seawater and Freshwater Teleost Fishes.

The kidney is an important organ that maintains body fluid homeostasis in seawater and freshwater teleost fishes. Seawater teleosts excrete sulfate and magnesium in small amounts of isotonic urine, and freshwater teleosts excrete water in large amounts of hypo-osmotic urine. The volume, osmolality, and ionic compositions of the urine are regulated mainly by membrane transport proteins expressed in the renal tubular epithelial cells.

Drosophila melanogaster: a simple genetic model of kidney structure, function and disease.

Although the genetic basis of many kidney diseases is being rapidly elucidated, their experimental study remains problematic owing to the lack of suitable models. The fruitfly Drosophila melanogaster provides a rapid, ethical and cost-effective model system of the kidney. The unique advantages of D.

Sequence analysis and function of mosquito aeCCC2 and Drosophila Ncc83 orthologs.

Dipteran insects have genes that code for two different Na-dependent cation-chloride cotransporter (CCC) paralogs. Aedes aegypti aeNKCC1 is an ortholog of Drosophila melanogaster Ncc69, a bumetanide-sensitive Na-K-2Cl cotransporter (NKCC). Aedes aegypti aeCCC2 and aeCCC3 are orthologs of Drosophila Ncc83.

Electrogenic sodium bicarbonate cotransporter NBCe1 regulates pancreatic β cell function in type 2 diabetes.

Pancreatic β cell failure in type 2 diabetes mellitus (T2DM) is attributed to perturbations of the β cell's transcriptional landscape resulting in impaired glucose-stimulated insulin secretion. Recent studies identified SLC4A4 (a gene encoding an electrogenic Na+-coupled HCO3- cotransporter and intracellular pH regulator, NBCe1) as one of the misexpressed genes in β cells of patients with T2DM. Thus, in the current study, we set out to test the hypothesis that misexpression of SLC4A4/NBCe1 in T2DM β cells contributes to β cell dysfunction and impaired glucose homeostasis.

Use of 3D Robotic Ultrasound for In Vivo Analysis of Mouse Kidneys.

Common modalities for in vivo imaging of rodents include positron emission tomography (PET), computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound (US). Each method has limitations and advantages, including availability, ease of use, cost, size, and the use of ionizing radiation or magnetic fields. This protocol describes the use of 3D robotic US for in vivo imaging of rodent kidneys and heart, subsequent data analysis, and possible research applications.

Transporters and tubule crystals in the insect Malpighian tubule.

The insect renal (Malpighian) tubules are functionally homologous to the mammalian kidney. Accumulating evidence indicates that renal tubule crystals form in a manner similar to mammalian kidney stones. In Drosophila melanogaster, crystals can be induced by diet, toxic substances, or genetic mutations that reflect circumstances influencing or eliciting kidney stones in mammals.

Human kidney stones: a natural record of universal biomineralization.

GeoBioMed - a new transdisciplinary approach that integrates the fields of geology, biology and medicine - reveals that kidney stones composed of calcium-rich minerals precipitate from a continuum of repeated events of crystallization, dissolution and recrystallization that result from the same fundamental natural processes that have governed billions of years of biomineralization on Earth. This contextual change in our understanding of renal stone formation opens fundamentally new avenues of human kidney stone investigation that include analyses of crystalline structure and stratigraphy, diagenetic phase transitions, and paragenetic sequences across broad length scales from hundreds of nanometres to centimetres (five Powers of 10). This paradigm shift has also enabled the development of a new kidney stone classification scheme according to thermodynamic energetics and crystalline architecture.

Bicarbonate ion transport by the electrogenic Na /HCO cotransporter, NBCe1, is required for normal electrical slow-wave activity in mouse small intestine.

Background: Normal gastrointestinal motility depends on electrical slow-wave activity generated by interstitial cells of Cajal (ICC) in the tunica muscularis of the gastrointestinal tract. A requirement for HCO in extracellular solutions used to record slow waves indicates a role for HCO transport in ICC pacemaking. The Slc4a4 gene transcript encoding the electrogenic Na /HCO cotransporter, NBCe1, is enriched in mouse small intestinal myenteric region ICC (ICC-MY) that generate slow waves.

Assessing Polycystic Kidney Disease in Rodents: Comparison of Robotic 3D Ultrasound and Magnetic Resonance Imaging.

Polycystic kidney disease (PKD) is an inherited disorder characterized by renal cyst formation and enlargement of the kidney. PKD severity can be staged noninvasively by measuring total kidney volume (TKV), a promising biomarker that has recently received regulatory qualification. In preclinical mouse models, where the disease is studied and potential therapeutics are evaluated, the most popular noninvasive method of measuring TKV is magnetic resonance imaging (MRI).