Thyroid Hormone in the Pathogenesis of Congenital Intestinal Dysganglionosis

2020 ◽  
Vol 23 (4) ◽  
pp. 285-295
Author(s):  
Fang Wang ◽  
Ping Jing ◽  
Peiyan Zhan ◽  
Hongyi Zhang
Keyword(s):  
Thyroid Hormone ◽  
Intestinal Motility ◽  
The Body ◽  
Enteric Neurons ◽  
Fluorescent Tracers ◽  
Zebrafish Model ◽  
Larval Zebrafish ◽  
Intestinal Length ◽  
Intestinal Dysganglionosis

Introduction The objective of this study is to investigate the role of thyroid hormone (TH) in the pathogenesis of intestinal dysganglionosis (ID). Methods A zebrafish model of congenital hypothyroidism (CH) was created by exposing the larvae to the 6-propyl-2-thiouracil (PTU). The enteric neurons were labeled with anti-HuC/D antibodies. The number of enteric neurons was counted. The larval intestine was dissociated and stained with anti-p75 and anti-α4 integrin antibodies. Mitosis and apoptosis of the p75+ α4 integrin+ enteric neural crest cells (ENCCs) were studied using flow cytometry. Intestinal motility was studied by analyzing the transit of fluorescent tracers. Results PTU (25 mg/L) significantly reduced TH production at 6- and 9-days post fertilization without changing the body length, body weight, and intestinal length of the larvae. Furthermore, PTU inhibited mitosis of ENCCs and reduced the number of enteric neurons throughout the larval zebrafish intestine. Importantly, PTU inhibited intestinal transit of fluorescent tracers. Finally, thyroxine supplementation restored ENCC mitosis, increased the number of enteric neurons, and recovered intestinal motility in the PTU-treated larvae. Conclusions PTU inhibited TH production, reduced the number of enteric neurons, impaired intestinal motility, and impeded ENCC mitosis in zebrafish, suggesting a possible role of CH in the pathogenesis of ID.

scholarly journals Swimming Hydrodynamics and Maneuverability in C-Start of Zebrafish Larvae: An Integrated Computational Study

2011 ◽  
Author(s):  
Gen Li ◽  
Hao Liu ◽  
Ulrike K. Mu¨ller ◽  
Johan L. van Leeuwen
Keyword(s):  
Vortex Ring ◽  
Degrees Of Freedom ◽  
Computational Study ◽  
Equations Of Motion ◽  
The Body ◽  
Free Swimming ◽  
Double Row ◽  
Zebrafish Model ◽  
Larval Zebrafish ◽  
Ring Structures

Fishes often exhibit stable body undulating in body and caudal fin (BCF) mode during cyclic swimming, but can perform remarkable maneuverability with significantly different swimming modes in case of C-start. Aiming at unveiling the mechanisms of swimming hydrodynamics and maneuverability of C-start, we have developed an integrated computational framework to model a free-swimming larval zebrafish (Danio rerio) by coupling the equations of 3DoF (Degrees of Freedom) motion and Navier-Stokes (NS) equations. Unsteady hydrodynamics is resolved by integrating models of realistic fin-body morphology and body-undulatory kinematics with an in-house NS solver. The instantaneous forces and moments on the body provided by the NS-solutions serve as input for 3DoF equations of motion. In this study, with a specific focus on a C- start as well as a subsequent transient phase till the cyclic swimming phase, we construct a larval zebrafish model, which can mimics realistic body motions and deformations based on measurements. Validation of the simulation is discussed by comparing model predictions with experimental measurements, which indicates that the present integrated model is capable to accurately predict free-swimming dynamics and hydrodynamics. The model successfully simulated a swimming bout of C-start and cyclic swimming: a wake topology of double row vortex ring structures is observed behind the fish; and a strong jet is visible at the center of the vortex ring, pushing water backward as the fish accelerates.

scholarly journals An Acromegaly Disease Zebrafish Model Reveals Decline in Body Stem Cell Number along with Signs of Premature Aging

Biology ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 120
Author(s):  
Abdalla Elbialy ◽  
Yoji Igarashi ◽  
Shuichi Asakawa ◽  
Shugo Watabe ◽  
Shigeharu Kinoshita
Keyword(s):  
Stem Cells ◽  
Growth Hormone ◽  
Pathological Condition ◽  
Cell Number ◽  
Cellular Level ◽  
The Body ◽  
Premature Aging ◽  
Cell Integrity ◽  
Zebrafish Model

In our previous publication, it was shown that growth hormone (GH) excess in acromegaly affects the cell integrity of somatic cells through increased DNA damage throughout the body and impaired DNA repair pathways. Acromegaly is a hormone disorder pathological condition that develops as a result of growth hormone over-secretion from the pituitary gland. We produced a zebrafish acromegaly model to gain a better understanding of the excess GH effects at the cellular level. Here we show that the acromegaly zebrafish model progressively reduced the number of stem cells in different organs and increased oxidative stress in stem cells. Importantly, the decline in the stem cells was even more apparent than in aged fish. The controversy and debate over the use of GH as an anti-aging therapy have been going on for several years. In this study, excess GH induced aging signs such as increased senescence-associated (SA)-β-galactosidase staining of abdominal skin and similarity of the pattern of gene expression between aged and acromegaly zebrafish. Thus, this study highlights the role of excess GH in acromegaly stem cells.

scholarly journals Role of enteric neurons and smooth muscle in development of zebrafish intestinal motility

2011 ◽  
Vol 356 (1) ◽  
pp. 162
Author(s):  
Kenneth Wallace ◽  
Gillian Roach ◽  
Amy Cameron
Keyword(s):  
Smooth Muscle ◽  
Intestinal Motility ◽  
Enteric Neurons

scholarly journals A role for sodium-chloride cotransporters in the rapid regulation of ion uptake following acute environmental acidosis: new insights from the zebrafish model

2016 ◽  
Vol 311 (6) ◽  
pp. C931-C941 ◽  
Author(s):  
Raymond W. M. Kwong ◽  
Steve F. Perry
Keyword(s):  
Acid Exposure ◽  
Whole Body ◽  
Cell Type ◽  
Acidic Water ◽  
Zebrafish Model ◽  
Larval Zebrafish ◽  
Water Ph ◽  
Control Water ◽  
Compensatory Regulation

The effects of acute exposure to acidic water on Na+ and Cl− homeostasis, and the mechanisms underlying their compensatory regulation, were investigated in the larval zebrafish Danio rerio. Exposure to acidic water (pH 4.0; control pH 7.6) for 2 h significantly reduced Na+ uptake and whole body Na+ content. Nevertheless, the capacity for Na+ uptake was substantially increased in fish preexposed to acidic water but measured in control water. Based on the accumulation of the Na+-selective dye, Sodium Green, two ionocyte subtypes exhibited intracellular Na+ enrichment after preexposure to acidic water: H+-ATPase rich (HR) cells, which coexpress the Na+/H+ exchanger isoform 3b (NHE3b), and a non-HR cell population. In fish experiencing Na+-Cl− cotransporter (NCC) knockdown, we observed no Sodium Green accumulation in the latter cell type, suggesting the non-HR cells were NCC cells. Elimination of NHE3b-expressing HR cells did not prevent the increased Na+ uptake following acid exposure. On the other hand, the increased Na+ uptake was abolished when the acidic water was enriched with Na+ and Cl−, but not with Na+ only, indicating that the elevated Na+ uptake after acid exposure was associated with the compensatory regulation of Cl−. Further examinations demonstrated that acute acid exposure also reduced whole body Cl− levels and increased the capacity for Cl− uptake. Moreover, knockdown of NCC prevented the increased uptake of both Na+ and Cl− after exposure to acidic water. Together, the results of the present study revealed a novel role of NCC in the compensatory regulation of Na+ and Cl− uptake following acute acidosis.

ADAMTS13-/-zebrafish Model Created By Crispr/Cas Reveals a Novel Role of ADAMTS13 in Vascular Development and Prothrombotic Phenotype

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1446-1446
Author(s):  
Liang Zheng ◽  
X. Long Zheng
Keyword(s):  
Vascular Development ◽  
Fluorescent Microscopy ◽  
Premature Stop Codon ◽  
The Body ◽  
Fluorescence Signal ◽  
Wild Type ◽  
Zebrafish Model ◽  
Growth Environment ◽  
Caudal Vein

Abstract Background: Deficiency of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), a von Willebrand factor (VWF)-cleaving enzyme, in humans results in thrombotic thrombocytopenic purpura (TTP), a potentially fatal syndrome. Previous studies have demonstrated that ADAMTS13, particularly the C-terminal domains of ADAMTS13 may stimulate or inhibit angiogenesis, depending on the growth environment. However, the role of ADAMTS13 in vascular development in vivo is not known. Objective: To identify the novel function of ADAMTS13 beyond the proteolysis of VWF, we generated ADAMTS13 knockdown and knockout zebrafish to determine the vascular development and propensity for development of thrombosis. Methods: Morpholino anti-sense RNA was microinjected to the embryos of a double transgenic Tg (gata1:dsRed; fli1:eGFP)zebrafish to transiently block ADAMTS13 translation. Also, CRSIPR/Cas9 system was employed to generate ADAMTS13 knockout zebrafish. The vascular development and thrombus formation were determined by fluorescent microscopy. Results: Approximately 30% of ADAMTS13 knockdown zebrafish exhibited vascular abnormalities in the dwarf intersegmental vessels and narrow caudal vein plexus (Fig. 1A and B). To confirm the phenotype, ADAMTS13 knockout using CRSIPR/Cas system was performed. Approximately 85% of the F0 fish carried insertion or deletion mutations in the targeted region. The founder fish were outcrossed to wild type fish to generate heterozygous F1 fish. Fourteen different mutation sequences with germ line transmission were identified in 33 F1 mutants. The siblings carrying an 8-bp deletion mutation, which created a premature stop codon in the signal peptide region of ADAMTS13, were then crossed to produce F2 progeny. The genotypes and protein expression were further confirmed by sequencing and by Western blot, respectively. As shown, a significant higher rate of vascular development defects, particularly in intersegmental vessels and caudal vein, was observed in homozygous ADAMTS13 knockout fish compared to the heterozygous and wild type fish (Fig. 1C). Thrombosis was triggered by incubation of larvae with various low concentrations (0.06%-0.25%) of FeCl3 and determined by the real-time change of fluorescence intensity within 10 min in the head region of larvae under a fluorescent microscope. When compared with wild type fish, ADAMTS13-/- fish demonstrated dramatically decreased fluorescence signal (Fig.1D), indicative of the cessation of blood flow elsewhere in the body after FeCl3injury. Conclusion: Our results demonstrate that severe deficiency of ADAMTS13 in zebrafish results in abnormalities of vascular development and increases the propensity of thrombosis after oxidative injury in fish larvae. These results suggest that ADAMTS13 may have other substrates than VWF. The zebrafish model may turn out to be a powerful tool for identifying a novel pro-angiogenic or anti-thrombotic agent. Disclosures Zheng: Alexion: Research Funding; Ablynx: Consultancy.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

The Role of Computer Modeling in Electrocardiography

1990 ◽  
Vol 29 (04) ◽  
pp. 282-288 ◽  
Author(s):  
A. van Oosterom
Keyword(s):  
Electrical Activity ◽  
Computer Modeling ◽  
Body Surface ◽  
Electrical Current ◽  
The Body ◽  
Volume Conductor ◽  
Current Generator ◽  
Cardiac Electrical Activity ◽  
Source Models

AbstractThis paper introduces some levels at which the computer has been incorporated in the research into the basis of electrocardiography. The emphasis lies on the modeling of the heart as an electrical current generator and of the properties of the body as a volume conductor, both playing a major role in the shaping of the electrocardiographic waveforms recorded at the body surface. It is claimed that the Forward-Problem of electrocardiography is no longer a problem. Several source models of cardiac electrical activity are considered, one of which can be directly interpreted in terms of the underlying electrophysiology (the depolarization sequence of the ventricles). The importance of using tailored rather than textbook geometry in inverse procedures is stressed.

Questions on the role of biofilms for the adaptation of microorganisms to unfavorable environmental factors by the example of P. aeruginosa

2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Environmental Factors ◽  
Barrier Function ◽  
Infectious Agent ◽  
Antagonistic Activity ◽  
The Body ◽  
Main Function ◽  
Pathogenic Potential ◽  
The Face

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.

Receptions of the Past: Commemoration, Racism, Desire

Somatechnics ◽  
2017 ◽  
Vol 7 (2) ◽  
pp. 288-303
Author(s):  
Michael Connors Jackman
Keyword(s):  
Critical Point ◽  
Social Relations ◽  
White Privilege ◽  
Body Politic ◽  
The Body ◽  
Race And Racism ◽  
Lesbian And Gay ◽  
The Past ◽  
History Of

This article investigates the ways in which the work of The Body Politic (TBP), the first major lesbian and gay newspaper in Canada, comes to be commemorated in queer publics and how it figures in the memories of those who were involved in producing the paper. In revisiting a critical point in the history of TBP from 1985 when controversy erupted over race and racism within the editorial collective, this discussion considers the role of memory in the reproduction of whiteness and in the rupture of standard narratives about the past. As the controversy continues to haunt contemporary queer activism in Canada, the productive work of memory must be considered an essential aspect of how, when and for what reasons the work of TBP comes to be commemorated. By revisiting the events of 1985 and by sifting through interviews with individuals who contributed to the work of TBP, this article complicates the narrative of TBP as a bluntly racist endeavour whilst questioning the white privilege and racially-charged demands that undergird its commemoration. The work of producing and preserving queer history is a vital means of challenging the intentional and strategic erasure of queer existence, but those who engage in such efforts must remain attentive to the unequal terrain of social relations within which remembering forms its objects.

A Good Sentencing Precedent is Hard to Find

2020 ◽  
Vol 32 (3) ◽  
pp. 138-144
Author(s):  
Brian A. Jacobs
Keyword(s):  
United States ◽  
Significant Role ◽  
College Admissions ◽  
The Body ◽  
Federal Law ◽  
Criminal Cases ◽  
Federal Sentencing

In federal criminal cases, federal law requires that judges consider the sentences other courts have imposed in factually similar matters. Courts and parties, however, face significant challenges in finding applicable sentencing precedents because judges do not typically issue written sentencing opinions, and transcripts of sentencings are not readily available in advanced searchable databases. At the same time, particularly since the Supreme Court’s 2005 decision in United States v. Booker, sentencing precedent has come to play a significant role in federal sentencing proceedings. By way of example, this article discusses recent cases involving defendants with gambling addictions, and recent cases involving college admissions or testing fraud. The article explores the ways the parties in those cases have used sentencing precedent in their advocacy, as well as the ways the courts involved have used sentencing precedent to justify their decisions. Given the important role of sentencing precedent in federal criminal cases, the article finally looks at ways in which the body of sentencing law could be made more readily available to parties and courts alike.

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