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https://www.readbyqxmd.com/read/28800244/exploiting-analysis-of-heterogeneity-to-increase-the-information-content-extracted-from-fluorescence-micrographs-of-transgenic-zebrafish-embryos
#1
Tongying Shun, Albert H Gough, Subramaniam Sanker, Neil A Hukriede, Andreas Vogt
Zebrafish embryos are a near-ideal animal model for drug discovery because of their high genetic and physiological similarity to mammals, small size, high fecundity, and optical transparency. The latter properties make zebrafish at larval stages especially suited for high-content analysis and high throughput screening (HTS). However, inherent biological complexity and the inability to screen multiple specimens in a single well present a challenge for HTS because limiting replicates and high variability often prevent assays from reaching the stringent performance criteria demanded of large-scale screening assays...
August 11, 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28791769/fluorescent-polymer-nanoparticles-for-cell-barcoding-in-vitro-and-in-vivo
#2
Bohdan Andreiuk, Andreas Reisch, Marion Lindecker, Gautier Follain, Nadine Peyriéras, Jacky G Goetz, Andrey S Klymchenko
Fluorescent polymer nanoparticles for long-term labeling and tracking of living cells with any desired color code are developed. They are built from biodegradable poly(lactic-co-glycolic acid) polymer loaded with cyanine dyes (DiO, DiI, and DiD) with the help of bulky fluorinated counterions, which minimize aggregation-caused quenching. At the single particle level, these particles are ≈20-fold brighter than quantum dots of similar color. Due to their identical 40 nm size and surface properties, these nanoparticles are endocytosed equally well by living cells...
August 9, 2017: Small
https://www.readbyqxmd.com/read/28769124/metformin-inhibits-cyst-formation-in-a-zebrafish-model-of-polycystin-2-deficiency
#3
Ming-Yang Chang, Tsu-Lin Ma, Cheng-Chieh Hung, Ya-Chung Tian, Yung-Chang Chen, Chih-Wei Yang, Yi-Chuan Cheng
Autosomal dominant polycystic kidney disease (ADPKD) is a common kidney disease caused by mutations in PKD1 or PKD2. Metformin reduces cyst growth in mouse models of PKD1. However, metformin has not been studied in animal models of PKD2, and the cellular mechanism underlying its effectiveness is not entirely clear. This study investigated the effects of metformin on cyst formation in a zebrafish model of polycystin-2 deficiency resulting from morpholino knockdown of pkd2. We added metformin (2.5 to 20 mM) to the embryo media between 4 and 48 hours post fertilisation and observed pronephric cyst formation by using the wt1b promoter-driven GFP signal in Tg(wt1b:GFP) pkd2 morphants...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28762163/polycystin-2-dependent-cardio-protective-mechanisms-revealed-by-cardiac-stress
#4
Esther Giehl, Fernanda O Lemos, Yan Huang, Frank J Giordano, Ivana Y Kuo, Barbara E Ehrlich
Although autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple kidney cysts, the most frequent cause of death in ADPKD patients is cardiovascular disease. ADPKD is linked to mutations in PKD1 or pkd2, the genes that encode for the proteins polycystin 1 and polycystin 2 (PC1 and PC2, respectively). The cardiovascular complications have been assumed to be a consequence of renal hypertension and activation of renin/angiotensin/aldosterone (RAAS) pathway. However, the expression of PC1 and PC2 in cardiac tissue suggests additional direct effects of these proteins on cardiac function...
July 31, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28753595/clinico-biological-significance-of-suppressor-of-cytokine-signaling-1-expression-in-acute-myeloid-leukemia
#5
H-A Hou, J-W Lu, T-Y Lin, C-H Tsai, W-C Chou, C-C Lin, Y-Y Kuo, C-Y Liu, M-H Tseng, Y-C Chiang, Y-L Peng, J-L Tang, Z Gong, L-I Lin, H-F Tien
Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML...
July 28, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28750036/generation-and-phenotypic-characterization-of-pde1a-mutant-mice
#6
Xiaofang Wang, Satsuki Yamada, Wells B LaRiviere, Hong Ye, Jason L Bakeberg, María V Irazabal, Fouad T Chebib, Jan van Deursen, Peter C Harris, Caroline R Sussman, Atta Behfar, Christopher J Ward, Vicente E Torres
It has been proposed that a reduction in intracellular calcium causes an increase in intracellular cAMP and PKA activity through stimulation of calcium inhibitable adenylyl cyclase 6 and inhibition of phosphodiesterase 1 (PDE1), the main enzymes generating and degrading cAMP in the distal nephron and collecting duct, thus contributing to the development and progression of autosomal dominant polycystic kidney disease (ADPKD). In zebrafish pde1a depletion aggravates and overexpression ameliorates the cystic phenotype...
2017: PloS One
https://www.readbyqxmd.com/read/28739882/zebrafish-b-cell-development-without-a-pre-b-cell-stage-revealed-by-cd79-fluorescence-reporter-transgenes
#7
Xingjun Liu, Yue-Sheng Li, Susan A Shinton, Jennifer Rhodes, Lingjuan Tang, Hui Feng, Cicely A Jette, A Thomas Look, Kyoko Hayakawa, Richard R Hardy
CD79a and CD79b proteins associate with Ig receptors as integral signaling components of the B cell Ag receptor complex. To study B cell development in zebrafish, we isolated orthologs of these genes and performed in situ hybridization, finding that their expression colocalized with IgH-μ in the kidney, which is the site of B cell development. CD79 transgenic lines were made by linking the promoter and upstream regulatory segments of CD79a and CD79b to enhanced GFP to identify B cells, as demonstrated by PCR analysis of IgH-μ expression in sorted cells...
July 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28739660/a-gene-implicated-in-activation-of-retinoic-acid-receptor-targets-is-a-novel-renal-agenesis-gene-in-humans
#8
Patrick D Brophy, Maria Rasmussen, Mrutyunjaya Parida, Greg Bonde, Benjamin W Darbro, Xiaojing Hong, Jason C Clarke, Kevin A Peterson, James Denegre, Michael Schneider, Caroline R Sussman, Lone Sunde, Dorte L Lildballe, Jens Michael Hertz, Robert A Cornell, Stephen A Murray, John R Manak
Renal agenesis (RA) is one of the more extreme examples of congenital anomalies of the kidney and urinary tract (CAKUT). Bilateral renal agenesis is almost invariably fatal at birth, and unilateral renal agenesis can lead to future health issues including end stage renal disease. Genetic investigations have identified several gene variants which cause RA, including EYA1, LHX1, and WT1 However, whereas compound null mutations of genes encoding α and γ retinoic acid receptors (RARs) cause RA in mice, to date there have been no reports of variants in RAR genes causing RA in humans...
July 24, 2017: Genetics
https://www.readbyqxmd.com/read/28735502/regenerative-medicine-in-kidney-disease-where-we-stand-and-where-to-go
#9
REVIEW
Fernanda T Borges, Nestor Schor
The kidney is a complex organ with more than 20 types of specialized cells that play an important role in maintaining the body's homeostasis. The epithelial tubular cell is formed during embryonic development and has little proliferative capacity under physiological conditions, but after acute injury the kidney does have regenerative capacity. However, after repetitive or severe lesions, it may undergo a maladaptation process that predisposes it to chronic kidney injury. Regenerative medicine includes various repair and regeneration techniques, and these have gained increasing attention in the scientific literature...
July 22, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28729419/the-exocyst-is-required-for-photoreceptor-ciliogenesis-and-retinal-development
#10
Glenn P Lobo, Diana Fulmer, Lilong Guo, Xiaofeng Zuo, Yujing Dang, Seok-Hyung Kim, Yanhui Su, Kola George, Elisabeth Obert, Ben Fogelgren, Deepak Nihalani, Russell A Norris, Bärbel Rohrer, Joshua H Lipschutz
We previously have shown that the highly-conserved eight-protein exocyst trafficking complex is required for ciliogenesis in kidney tubule cells. We hypothesized here that ciliogenic programs are conserved across organs and species. To determine if renal primary ciliogenic programs are conserved in the eye, and to characterize the function and mechanisms by which the exocyst regulates eye development in zebrafish, we focused on exoc5, a central component of the exocyst complex, by analyzing both exoc5 zebrafish mutants, and photoreceptor-specific Exoc5 knockout mice...
July 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28719799/mesencephalic-astrocyte-derived-neurotrophic-factor-manf-a-new-player-in-endoplasmic-reticulum-diseases-structure-biology-and-therapeutic-roles
#11
Yeawon Kim, Sun-Ji Park, Ying Maggie Chen
Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified 18-kDa soluble protein, localizes to the luminal endoplasmic reticulum (ER), whose stress can stimulate MANF expression and secretion. In Drosophila and zebrafish, MANF regulates dopaminergic neuron development. In contrast, in mice, MANF deficiency leads to diabetes and activation of the unfolded protein response. Recent studies in rodent models have demonstrated that MANF mitigates diabetes, exerts neurotrophic function in neurodegenerative disease, protects cardiomyocytes and neurons in myocardial infarction and cerebral ischemia, respectively, and promotes immune cell phenotype switch from proinflammatory macrophages to prorepair anti-inflammatory macrophages...
June 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28698677/precise-spatio-temporal-control-of-rapid-optogenetic-cell-ablation-with-mem-killerred-in-zebrafish
#12
C Buckley, M T Carvalho, L K Young, S A Rider, C McFadden, C Berlage, R F Verdon, J M Taylor, J M Girkin, J J Mullins
The ability to kill individual or groups of cells in vivo is important for studying cellular processes and their physiological function. Cell-specific genetically encoded photosensitizing proteins, such as KillerRed, permit spatiotemporal optogenetic ablation with low-power laser light. We report dramatically improved resolution and speed of cell targeting in the zebrafish kidney through the use of a selective plane illumination microscope (SPIM). Furthermore, through the novel incorporation of a Bessel beam into the SPIM imaging arm, we were able to improve on targeting speed and precision...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28695384/carbonic-anhydrase-inhibitors-induce-developmental-toxicity-during-zebrafish-embryogenesis-especially-in-the-inner-ear
#13
Hiroko Matsumoto, Shoko Fujiwara, Hisako Miyagi, Nobuhiro Nakamura, Yasuhiro Shiga, Toshihiro Ohta, Mikio Tsuzuki
In vertebrates, carbonic anhydrases (CAs) play important roles in ion transport and pH regulation in many organs, including the eyes, kidneys, central nervous system, and inner ear. In aquatic organisms, the enzyme is inhibited by various chemicals present in the environment, such as heavy metals, pesticides, and pharmaceuticals. In this study, the effects of CA inhibitors, i.e., sulfonamides [ethoxyzolamide (EZA), acetazolamide (AZA), and dorzolamide (DZA)], on zebrafish embryogenesis were investigated. In embryos treated with the sulfonamides, abnormal development, such as smaller otoliths, an enlarged heart, an irregular pectoral fin, and aberrant swimming behavior, was observed...
July 10, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28673044/ctenopharyngodon-idella-ikk%C3%AE-interacts-with-pkr-and-i%C3%AE%C2%BAb%C3%AE
#14
Haizhou Wang, Qun Xu, Xiaowen Xu, Yousheng Hu, Qunhao Hou, Youlin Zhu, Chengyu Hu
Inhibitor of nuclear factor kappa-B kinase β (IKKβ) is a subunit of the IKK complex. It can activate the NF-κB pathway through phosphorylating IκB in response to a wide range of stimuli. In the present study, an IKKβ gene from grass carp (Ctenopharyngodon idella; KT282114) was cloned and identified by homologous cloning and rapid-amplification of cDNA ends (RACE) technique. The complete CiIKKβ cDNA is 3428 bp in length, with the longest open reading frame (ORF) of 2337 bp encoding a polypeptide of 778 amino acids...
August 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28656378/comparative-transcriptomic-analysis-identifies-evolutionarily-conserved-gene-products-in-the-vertebrate-renal-distal-convoluted-tubule
#15
REVIEW
Yuya Sugano, Chiara Cianciolo Cosentino, Dominique Loffing-Cueni, Stephan C F Neuhauss, Johannes Loffing
Understanding the molecular basis of the complex regulatory networks controlling renal ion transports is of major physiological and clinical importance. In this study, we aimed to identify evolutionarily conserved critical players in the function of the renal distal convoluted tubule (DCT) by a comparative transcriptomic approach. We generated a transgenic zebrafish line with expression of the red fluorescent mCherry protein under the control of the zebrafish DCT-specific promoter of the thiazide-sensitive NaCl cotransporter (NCC)...
August 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28647853/are-podocytes-motile
#16
REVIEW
Nicole Endlich, Florian Siegerist, Karlhans Endlich
Podocytes, the postmitotic and highly branched epithelial cells of the glomerulus, play a pivotal role for the function of the glomerular filtration barrier and the development of chronic kidney disease. It has long been discussed whether podocytes in vivo are motile and can laterally migrate in a coordinated way along the capillaries until they reach the position of naked glomerular basement membrane often found in podocytopathies. Such motility would also be the prerequisite for the replacement of lost podocytes by progenitor cells...
August 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28630014/impact-of-molecular-hydrogen-treatments-on-the-innate-immune-activity-and-survival-of-zebrafish-danio-rerio-challenged-with-aeromonas-hydrophila
#17
Zhenyu Hu, Bingqian Wu, Fanhong Meng, Zejian Zhou, Hui Lu, Heng Zhao
Recently, molecular hydrogen has been reported to have a suppressive effect on inflammation in human and rodent models. The aim of this study was to evaluate the preventive effects of hydrogen-rich water (HRW) on zebrafish challenged by A. hydrophila. We have found an increased survival rate of bacteria-challenged zebrafish subjected to the HRW immersion treatment. Furthermore, we have revealed that HRW was able to block multiplication of A. hydrophila in zebrafish. In addition, treatment of zebrafish infected by A...
August 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28629823/characterization-and-biological-function-analysis-of-the-trim47-gene-from-common-carp-cyprinus-carpio
#18
Yeda Wang, Ming Kuang, Yuanan Lu, Li Lin, Xueqin Liu
The TRIM family protein was known to play an important role in many cellular processes, including potential antiviral activity, which has attracted lots of attention. In this study, a TRIM47 homolog from common carp (Cyprinus carpio) was cloned and the full length coding DNA sequence (CDS) of this gene was analyzed, results showed that there was a 97% similarity between common carp and zebrafish (Danio rerio), but only 18% similarity with that of human (Homo sapiens) and mouse (Mus musculus). The tissue distribution analysis showed TRIM47 had the highest mRNA level in the brain, a few immune related organs such as liver and kidney also had a relatively high level of TRIM47 expression...
June 16, 2017: Gene
https://www.readbyqxmd.com/read/28627438/genome-wide-identification-phylogeny-and-expression-of-bone-morphogenetic-protein-genes-in-tetraploidized-common-carp-cyprinus-carpio
#19
Lin Chen, Chuanju Dong, Shengnan Kong, Jiangfan Zhang, Xuejun Li, Peng Xu
Bone morphogenetic proteins (Bmps) are a group of signaling molecules known to play important roles during formation and maintenance of various organs, not only bone, but also muscle, blood and so on. Common carp (Cyprinus carpio) is one of the most intensively studied fish due to its economic and environmental importance. Besides, common carp has encountered an additional round of whole genome duplication (WGD) compared with many closely related diploid teleost, which make it one of the most important models for genome evolutionary studies in teleost...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28625504/mutations-in-armc9-which-encodes-a-basal-body-protein-cause-joubert-syndrome-in-humans-and-ciliopathy-phenotypes-in-zebrafish
#20
Julie C Van De Weghe, Tamara D S Rusterholz, Brooke Latour, Megan E Grout, Kimberly A Aldinger, Ranad Shaheen, Jennifer C Dempsey, Sateesh Maddirevula, Yong-Han H Cheng, Ian G Phelps, Matthias Gesemann, Himanshu Goel, Ohad S Birk, Talal Alanzi, Rifaat Rawashdeh, Arif O Khan, Michael J Bamshad, Deborah A Nickerson, Stephan C F Neuhauss, William B Dobyns, Fowzan S Alkuraya, Ronald Roepman, Ruxandra Bachmann-Gagescu, Dan Doherty
Joubert syndrome (JS) is a recessive neurodevelopmental disorder characterized by hypotonia, ataxia, abnormal eye movements, and variable cognitive impairment. It is defined by a distinctive brain malformation known as the "molar tooth sign" on axial MRI. Subsets of affected individuals have malformations such as coloboma, polydactyly, and encephalocele, as well as progressive retinal dystrophy, fibrocystic kidney disease, and liver fibrosis. More than 35 genes have been associated with JS, but in a subset of families the genetic cause remains unknown...
July 6, 2017: American Journal of Human Genetics
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