scholarly journals The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR

Biology Open ◽  
2015 ◽  
Vol 4 (11) ◽  
pp. 1356-1366 ◽  
Author(s):  
M. Roxo-Rosa ◽  
R. Jacinto ◽  
P. Sampaio ◽  
S. S. Lopes
Keyword(s):  
Molecular Mechanisms ◽  
Model System ◽  
Kupffer’S Vesicle ◽  
Kupffer's Vesicle ◽  
Stimulation Of

Cellular and molecular basis of increased ammoniagenesis in potassium deprivation

2011 ◽  
Vol 301 (5) ◽  
pp. F969-F978 ◽  
Author(s):  
Shaikh Abu Hossain ◽  
Farrukh A. Chaudhry ◽  
Kamyar Zahedi ◽  
Faraaz Siddiqui ◽  
Hassane Amlal
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Molecular Mechanisms ◽  
Intracellular Acidosis ◽  
Deficient Diet ◽  
Proximal Tubule Cells ◽  
Glutamine Transporter ◽  
Additive Increase ◽  
Acid Base Status ◽  
Low K ◽  
Stimulation Of

Hypokalemia is associated with increased ammoniagenesis and stimulation of net acid excretion by the kidney in both humans and experimental animals. The molecular mechanisms underlying these effects remain unknown. Toward this end, rats were placed in metabolic cages and fed a control or K+-deficient diet (KD) for up to 6 days. Rats subjected to KD showed normal acid-base status and serum electrolytes composition. Interestingly, urinary NH4+ excretion increased significantly and correlated with a parallel decrease in urine K+ excretion in KD vs. control animals. Molecular studies showed a specific upregulation of the glutamine transporter SN1, which correlated with the upregulation of glutaminase (GA), glutamate dehydrogenase (GDH), and phosphoenolpyruvate carboxykinase. These effects occurred as early as day 2 of KD. Rats subjected to a combined KD and 280 mM NH4Cl loading (to induce metabolic acidosis) for 2 days showed an additive increase in NH4+ excretion along with an additive increment in the expression levels of ammoniagenic enzymes GA and GDH compared with KD or NH4Cl loading alone. The incubation of cultured proximal tubule cells NRK 52E or LLC-PK1 in low-K+ medium did not affect NH4+ production and did not alter the expression of SN1, GA, or GDH in NRK cells. These results demonstrate that K+ deprivation stimulates ammoniagenesis through a coordinated upregulation of glutamine transporter SN1 and ammoniagenesis enzymes. This effect is developed before the onset of hypokalemia. The signaling pathway mediating these events is likely independent of KD-induced intracellular acidosis. Finally, the correlation between increased NH4+ production and decreased K+ excretion indicate that NH4+ synthesis and transport likely play an important role in renal K+ conservation during hypokalemia.

scholarly journals Bardet–Biedl syndrome genes are important in retrograde intracellular trafficking and Kupffer's vesicle cilia function

2006 ◽  
Vol 15 (5) ◽  
pp. 667-677 ◽  
Author(s):  
Hsan-Jan Yen ◽  
Marwan K. Tayeh ◽  
Robert F. Mullins ◽  
Edwin M. Stone ◽  
Val C. Sheffield ◽  
...  
Keyword(s):  
Intracellular Trafficking ◽  
Bardet Biedl Syndrome ◽  
Kupffer’S Vesicle ◽  
Kupffer's Vesicle

scholarly journals Rare variants in axonogenesis genes connect three families with sound–color synesthesia

2018 ◽  
Vol 115 (12) ◽  
pp. 3168-3173 ◽  
Author(s):  
Amanda K. Tilot ◽  
Katerina S. Kucera ◽  
Arianna Vino ◽  
Julian E. Asher ◽  
Simon Baron-Cohen ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rare Variants ◽  
Autism Spectrum ◽  
Sensory Experiences ◽  
Limited Success ◽  
Whole Exome ◽  
Rare Genetic Variants ◽  
Sound Color ◽  
Stimulation Of

Synesthesia is a rare nonpathological phenomenon where stimulation of one sense automatically provokes a secondary perception in another. Hypothesized to result from differences in cortical wiring during development, synesthetes show atypical structural and functional neural connectivity, but the underlying molecular mechanisms are unknown. The trait also appears to be more common among people with autism spectrum disorder and savant abilities. Previous linkage studies searching for shared loci of large effect size across multiple families have had limited success. To address the critical lack of candidate genes, we applied whole-exome sequencing to three families with sound–color (auditory–visual) synesthesia affecting multiple relatives across three or more generations. We identified rare genetic variants that fully cosegregate with synesthesia in each family, uncovering 37 genes of interest. Consistent with reports indicating genetic heterogeneity, no variants were shared across families. Gene ontology analyses highlighted six genes—COL4A1, ITGA2, MYO10, ROBO3, SLC9A6, and SLIT2—associated with axonogenesis and expressed during early childhood when synesthetic associations are formed. These results are consistent with neuroimaging-based hypotheses about the role of hyperconnectivity in the etiology of synesthesia and offer a potential entry point into the neurobiology that organizes our sensory experiences.

scholarly journals DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in the coral modelAiptasia

2017 ◽  
Author(s):  
Yong Li ◽  
Yi Jin Liew ◽  
Guoxin Cui ◽  
Maha J Cziesielski ◽  
Noura Zahran ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Model System ◽  
Epigenetic Mechanism ◽  
Symbiotic Relationship ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
Spurious Transcription ◽  
Coral Reef Ecosystems

The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research is focusing on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, which have been implicated in transcriptional regulation and acclimation to environmental change, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model systemAiptasia. We find methylated genes are marked by histone H3K36me3 and show significant reduction of spurious transcription and transcriptional noise, revealing a role of DNA methylation in the maintenance of transcriptional homeostasis. Changes in DNA methylation and expression show enrichment for symbiosis-related processes such as immunity, apoptosis, phagocytosis recognition and phagosome formation, and unveil intricate interactions between the underlying pathways. Our results demonstrate that DNA methylation provides an epigenetic mechanism of transcriptional homeostasis during symbiosis.

scholarly journals Quantification of Iron Release from Native Ferritin and Magnetoferritin Induced by Vitamins B2 and C

2020 ◽  
Vol 21 (17) ◽  
pp. 6332
Author(s):  
Oliver Strbak ◽  
Lucia Balejcikova ◽  
Martina Kmetova ◽  
Jan Gombos ◽  
Alzbeta Trancikova ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Alternative Hypothesis ◽  
Model System ◽  
Oxide Nanoparticles ◽  
Iron Release ◽  
Ferrous Ions ◽  
Significant Difference ◽  
Mineral Core ◽  
Biogenic Iron ◽  
Over Time

Various pathological processes in humans are associated with biogenic iron accumulation and the mineralization of iron oxide nanoparticles, especially magnetite. Ferritin has been proposed as a precursor to pathological magnetite mineralization. This study quantifies spectroscopically the release of ferrous ions from native ferritin and magnetoferritin as a model system for pathological ferritin in the presence of potent natural reducing agents (vitamins C and B2) over time. Ferrous cations are required for the transformation of ferrihydrite (physiological) into a magnetite (pathological) mineral core and are considered toxic at elevated levels. The study shows a significant difference in the reduction and iron release from native ferritin compared to magnetoferritin for both vitamins. The amount of reduced iron formed from a magnetoferritin mineral core is two to five times higher than from native ferritin. Surprisingly, increasing the concentration of the reducing agent affects only iron release from native ferritin. Magnetoferritin cores with different loading factors seem to be insensitive to different concentrations of vitamins. An alternative hypothesis of human tissue magnetite mineralization and the process of iron-induced pathology is proposed. The results could contribute to evidence of the molecular mechanisms of various iron-related pathologies, including neurodegeneration.

scholarly journals A Yeast-Based Model for Hereditary Motor and Sensory Neuropathies: A Simple System for Complex, Heterogeneous Diseases

2020 ◽  
Vol 21 (12) ◽  
pp. 4277 ◽  
Author(s):  
Weronika Rzepnikowska ◽  
Joanna Kaminska ◽  
Dagmara Kabzińska ◽  
Katarzyna Binięda ◽  
Andrzej Kochański
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Model System ◽  
Research Field ◽  
Therapeutic Approaches ◽  
Rare Disorders ◽  
Advantages And Disadvantages ◽  
Pathogenic Variants ◽  
Disease Subtypes

Charcot–Marie–Tooth (CMT) disease encompasses a group of rare disorders that are characterized by similar clinical manifestations and a high genetic heterogeneity. Such excessive diversity presents many problems. Firstly, it makes a proper genetic diagnosis much more difficult and, even when using the most advanced tools, does not guarantee that the cause of the disease will be revealed. Secondly, the molecular mechanisms underlying the observed symptoms are extremely diverse and are probably different for most of the disease subtypes. Finally, there is no possibility of finding one efficient cure for all, or even the majority of CMT diseases. Every subtype of CMT needs an individual approach backed up by its own research field. Thus, it is little surprise that our knowledge of CMT disease as a whole is selective and therapeutic approaches are limited. There is an urgent need to develop new CMT models to fill the gaps. In this review, we discuss the advantages and disadvantages of yeast as a model system in which to study CMT diseases. We show how this single-cell organism may be used to discriminate between pathogenic variants, to uncover the mechanism of pathogenesis, and to discover new therapies for CMT disease.

Trans-stimulation of 13NH4+ efflux provides evidence for the cytosolic origin of tracer in the compartmental analysis of barley roots

2003 ◽  
Vol 30 (12) ◽  
pp. 1233 ◽  
Author(s):  
Dev T. Britto ◽  
Herbert J. Kronzucker
Keyword(s):  
Compartmental Analysis ◽  
Fold Increase ◽  
Model System ◽  
Hordeum Vulgare L ◽  
Root Cells ◽  
Transport Studies ◽  
Efflux Kinetics ◽  
Insight Into ◽  
Pool Sizes ◽  
Stimulation Of

The analysis of tracer efflux kinetics is fundamental to membrane transport studies, but requires the rigorous identification of subcellular tracer sources. We present a solution to this problem through the analysis of sharp increases in 13NH4+ efflux from roots of radiolabelled barley (Hordeum vulgare L.) seedlings, in response to a 100-fold increase in external [NH4+]. By comparing these trans-stimulation data with a mathematical model incorporating changes in subcellular NH4+ fluxes and pool sizes, we show that the cytosol of root cells is the origin of the tracer efflux. Our analysis provides new insight into the rapidly occurring events underlying compensatory flux regulation during transitions from one nutritional steady state to another, and confirms the validity of compartmental analysis by tracer efflux (CATE) in this important model system.

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