Polycystin-2-dependent transcriptome reveals early response of autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in polycystin genes, and , but the underlying pathogenic mechanisms are poorly understood. To identify genes and pathways that operate downstream of polycystin-2 (PC2), a comprehensive gene expression database was created, cataloging changes in the transcriptome immediately following PC2 protein depletion. To explore cyst initiation processes, an immortalized mouse inner medullary collecting duct line was developed with the ability to knock out the gene conditionally.

Genomic evidence indicates small island-resident populations and sex-biased behaviors of Hawaiian reef Manta Rays.

Background: Reef manta rays (Mobula alfredi) are globally distributed in tropical and subtropical seas. Their life history traits (slow growth, late maturity, low reproductive output) make them vulnerable to perturbations and therefore require informed management strategies. Previous studies have reported wide-spread genetic connectivity along continental shelves suggesting high gene flow along continuous habitats spanning hundreds of kilometers.

The complete mitochondrial genome of the Reef Manta Ray, , from Hawaii.

We provide the complete mitochondrial genome of the reef manta ray, , using an ezRAD approach. The total length of the mitogenome was 18,166 bp and contained 13 protein-coding genes, 22 transfer RNAs genes, two ribosomal RNA genes, and one non-coding control region. The gene organization and length are similar to other species.

Genomic assessment of larval odyssey: self-recruitment and biased settlement in the Hawaiian surgeonfish Acanthurus triostegus sandvicensis.

The gap between spawning and settlement location of marine fishes, where the larvae occupy an oceanic phase, is a great mystery in both natural history and conservation. Recent genomic approaches provide some resolution, especially in linking parent to offspring with assays of nucleotide polymorphisms. Here, the authors applied this method to the endemic Hawaiian convict tang (Acanthurus triostegus sandvicensis), a surgeonfish with a long pelagic larval stage of c.

Doxycycline Changes the Transcriptome Profile of mIMCD3 Renal Epithelial Cells.

Tetracycline-inducible gene expression systems have been used successfully to study gene function and renal epithelial models but the effects of the common inducing agent, doxycycline (DOX), on gene expression are not well appreciated. Here, we evaluated the DOX effects on the transcriptome of a widely used renal epithelial cell model, mIMCD3 cells, to establish a reference. Cells were grown on permeable filter supports in the absence and presence of DOX (3 or 6 days), and genome-wide transcriptome profiles were assessed using RNA-Seq.

Critical role of the mineralocorticoid receptor in aldosterone-dependent and aldosterone-independent regulation of ENaC in the distal nephron.

The epithelial Na channel (ENaC) constitutes the rate-limiting step for Na absorption in the aldosterone-sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), connecting tubule (CNT), and collecting duct (CD). Previously, we demonstrated that ENaC activity in the DCT2/CNT transition zone is constitutively high and independent of aldosterone, in contrast to its aldosterone dependence in the late CNT/initial cortical CD (CCD). The mineralocorticoid receptor (MR) is expressed in the entire ASDN.

Distal convoluted tubule sexual dimorphism revealed by advanced 3D imaging.

The thiazide-sensitive Na-Cl cotransporter (NCC) is more abundant in kidneys of female subjects than of male subjects. Because morphological remodeling of the distal convoluted tubule (DCT) is dependent on NCC activity, it has been generally assumed that there is a corresponding sexual dimorphism in the structure of the DCT, leading to a larger female DCT. Until now, this has never been directly examined.

Species Radiations in the Sea: What the Flock?

Species flocks are proliferations of closely-related species, usually after colonization of depauperate habitat. These radiations are abundant on oceanic islands and in ancient freshwater lakes, but rare in marine habitats. This contrast is well documented in the Hawaiian Archipelago, where terrestrial examples include the speciose silverswords (sunflower family Asteraceae), Drosophila fruit flies, and honeycreepers (passerine birds), all derived from one or a few ancestral lineages.

Life-history characteristics of an exploited bonefish Albula glossodonta population in a remote South Pacific atoll.

Bonefishes Albula spp. are important components of subsistence fisheries and lucrative sport fishing industries throughout their circumtropical distribution. In Oceania, however, Albula spp.

Shifting reef fish assemblages along a depth gradient in Pohnpei, Micronesia.

Mesophotic coral ecosystems (MCEs) continue to be understudied, especially in island locations spread across the Indo-Pacific Ocean. Pohnpei is the largest island in the Federated States of Micronesia, with a well-developed barrier reef, and steep slopes that descend to more than 1,000 m. Here we conducted visual surveys along a depth gradient of 0 to 60 m in addition to video surveys that extend to 130 m, with 72 belt transects and 12 roving surveys using closed-circuit rebreathers, to test for changes in reef fish composition from shallow to mesophotic depths.

The little shrimp that could: phylogeography of the circumtropical (Crustacea: Decapoda), reveals divergent Atlantic and Pacific lineages.

The banded coral shrimp, (Crustacea: Decapoda: Stenopodidea) is a popular marine ornamental species with a circumtropical distribution. The planktonic larval stage lasts ∼120-253 days, indicating considerable dispersal potential, but few studies have investigated genetic connectivity on a global scale in marine invertebrates. To resolve patterns of divergence and phylogeography of , we surveyed 525 bp of mitochondrial cytochrome oxidase subunit I (COI) from 198 individuals sampled at 10 locations across ∼27,000 km of the species range.

Renal and colonic potassium transporters in the pregnant rat.

Gestational potassium retention, most of which occurs during late pregnancy, is essential for fetal development. The purpose of this study was to examine mechanisms underlying changes in potassium handling by the kidney and colon in pregnancy. We found that potassium intake and renal excretion increased in late pregnancy while fecal potassium excretion remained unchanged and that pregnant rats exhibited net potassium retention.

The sport participation legacy of major events in the UK.

This paper examines the extent to which attending major sporting events leads to subsequent changes in the sport participation behaviour of spectators. The research covered seven single-sport events of World or European level held in the UK in 2014 and was concerned with spectators (aged 16 and over) who attended one of these events. Baseline data was gathered from a sample of spectators at each event using a face-to-face survey.

Constitutively Active SPAK Causes Hyperkalemia by Activating NCC and Remodeling Distal Tubules.

Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering the view that hyperactivation of the thiazide-sensitive sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling in the aldosterone-sensitive distal nephron (ASDN) and inhibition of the potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated.

Regal phylogeography: Range-wide survey of the marine angelfish Pygoplites diacanthus reveals evolutionary partitions between the Red Sea, Indian Ocean, and Pacific Ocean.

The regal angelfish (Pygoplites diacanthus; family Pomacanthidae) occurs on reefs from the Red Sea to the central Pacific, with an Indian Ocean/Rea Sea color morph distinct from a Pacific Ocean morph. To assess population differentiation and evaluate the possibility of cryptic evolutionary partitions in this monotypic genus, we surveyed mtDNA cytochrome b and two nuclear introns (S7 and RAG2) in 547 individuals from 15 locations. Phylogeographic analyses revealed four mtDNA lineages (d=0.

Ecological and morphological traits predict depth-generalist fishes on coral reefs.

Ecological communities that occupy similar habitats may exhibit functional convergence despite significant geographical distances and taxonomic dissimilarity. On coral reefs, steep gradients in key environmental variables (e.g.

The urothelium of a hibernator: the American black bear.

The American black bear undergoes a 3-5 month winter hibernation during which time bears do not eat, drink, defecate, or urinate. During hibernation renal function (GFR) is 16-50% of normal but urine is reabsorbed across the urinary bladder (UB) urothelium thus enabling metabolic recycling of all urinary constituents. To elucidate the mechanism(s) whereby urine is reabsorbed, we examined the UBs of five nonhibernating wild bears using light, electron (EM), and confocal immunofluorescent (IF) microscopy-concentrating on two components of the urothelial permeability barrier - the umbrella cell apical membranes and tight junctions (TJ).

Integrated compensatory network is activated in the absence of NCC phosphorylation.

Thiazide diuretics are used to treat hypertension; however, compensatory processes in the kidney can limit antihypertensive responses to this class of drugs. Here, we evaluated compensatory pathways in SPAK kinase-deficient mice, which are unable to activate the thiazide-sensitive sodium chloride cotransporter NCC (encoded by Slc12a3). Global transcriptional profiling, combined with biochemical, cell biological, and physiological phenotyping, identified the gene expression signature of the response and revealed how it establishes an adaptive physiology.

Genomic signatures of geographic isolation and natural selection in coral reef fishes.

The drivers of speciation remain among the most controversial topics in evolutionary biology. Initially, Darwin emphasized natural selection as a primary mechanism of speciation, but the architects of the modern synthesis largely abandoned that view in favour of divergence by geographic isolation. The balance between selection and isolation is still at the forefront of the evolutionary debate, especially for the world's tropical oceans where biodiversity is high, but isolating barriers are few.

SPAK-mediated NCC regulation in response to low-K+ diet.

The NaCl cotransporter (NCC) of the renal distal convoluted tubule is stimulated by low-K(+) diet by an unknown mechanism. Since recent work has shown that the STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) can function to stimulate NCC by phosphorylation of specific N-terminal sites, we investigated whether the NCC response to low-K(+) diet is mediated by SPAK. Using phospho-specific antibodies in Western blot and immunolocalization studies of wild-type and SPAK knockout (SPAK(-/-)) mice fed a low-K(+) or control diet for 4 days, we found that low-K(+) diet strongly increased total NCC expression and phosphorylation of NCC.

Large-scale introduction of the Indo-Pacific damselfish Abudefduf vaigiensis into Hawai'i promotes genetic swamping of the endemic congener A. abdominalis.

Hybridization in the ocean was once considered rare, a process prohibited by the rapid evolution of intrinsic reproductive barriers in a high-dispersal medium. However, recent genetic surveys have prompted a reappraisal of marine hybridization as an important demographic and evolutionary process. The Hawaiian Archipelago offers an unusual case history in this arena, due to the recent arrival of the widely distributed Indo-Pacific sergeant (Abudefduf vaigiensis), which is hybridizing with the endemic congener, A.

SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron-specific manner.

STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) and oxidative stress-related kinase (OSR1) activate the potassium-dependent sodium-chloride co-transporter, NKCC2, and thiazide-sensitive sodium-chloride cotransporter, NCC, in vitro, and both co-localize with a kinase regulatory molecule, Cab39/MO25α, at the apical membrane of the thick ascending limb (TAL) and distal convoluted tubule (DCT). Yet genetic ablation of SPAK in mice causes a selective loss of NCC function, whereas NKCC2 becomes hyperphosphorylated. Here, we explore the underlying mechanisms in wild-type and SPAK-null mice.

Colonic injury from temporary epicardial pacing wires.

A 72-year-old man who had undergone a three-vessel coronary artery bypass grafting, aortic valve replacement, and tricuspid valve repair became comatose 1 week after the procedure. Signs of intraabdominal sepsis developed 6 days later, leading to laparotomy on his 12th postoperative day. The Intraoperative finding was a perforating injury to the transverse colon caused by the ventricular temporary pacing wires.

Role of NKCC in BK channel-mediated net K⁺ secretion in the CCD.

Apical SK/ROMK and BK channels mediate baseline and flow-induced K secretion (FIKS), respectively, in the cortical collecting duct (CCD). BK channels are detected in acid-base transporting intercalated (IC) and Na-absorbing principal (PC) cells. Although the density of BK channels is greater in IC than PC, Na-K-ATPase activity in IC is considered inadequate to sustain high rates of urinary K secretion.