Endothelial cell-specific ETB receptor knockout: autoradiographic and histological characterisation and crucial role in the clearance of endothelin-1This article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

2010 ◽  
Vol 88 (6) ◽  
pp. 644-651 ◽  
Author(s):  
N.F. Kelland ◽  
R.E. Kuc ◽  
D.L. McLean ◽  
A. Azfer ◽  
A.J. Bagnall ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Genetic Mutation ◽  
Special Issue ◽  
Rt Pcr ◽  
Similar Extent ◽  
Relative Contribution ◽  
Liver And Kidney ◽  
Etb Receptor ◽  
Endothelin B ◽  
Selection Of

Inactivation of endothelin B receptors (ETB), either through selective pharmacological antagonism or genetic mutation, increases the circulating concentration of endothelin-1 (ET-1), suggesting ETB plays an important role in clearance of this peptide. However, the cellular site of ETB-mediated clearance has not yet been determined. We have used a novel mouse model of endothelial cell-specific knockout (KO) of ETB (EC ETB–/–) to evaluate the relative contribution of EC-ETB to the clearance of ET-1. Phenotypic evidence of EC-specific ETB KO was confirmed by immunocytochemistry and autoradiography. Binding of the radiolabelled selective ETB ligand BQ3020 was significantly and selectively decreased in EC-rich tissues of EC ETB–/– mice, including the lung, liver, and kidney. By contrast, ETA binding was unaltered. RT-PCR confirmed equal expression of ET-1 in tissue from EC ETB–/– mice and controls, despite increased concentration of plasma ET-1 in EC ETB–/–. Clearance of an intravenous bolus of [125I]ET-1 was impaired in EC ETB–/– mice. Pretreatment with the selective ETB antagonist A192621 impaired [125I]ET-1 clearance in control animals to a similar extent, but did not further impair clearance in EC ETB–/– mice. These studies suggest that EC-ETB are largely responsible for the clearance of ET-1 from the circulation.

Endothelin axis induces metalloproteinase activation and invasiveness in human lymphatic endothelial cellsThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.

2010 ◽  
Vol 88 (8) ◽  
pp. 782-787 ◽  
Author(s):  
Francesca Spinella ◽  
Valentina Caprara ◽  
Emirena Garrafa ◽  
Valeriana Di Castro ◽  
Laura Rosanò ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Molecular Mechanisms ◽  
Proteolytic Enzymes ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cells ◽  
Special Issue ◽  
Dye Transport ◽  
Specific Antagonist ◽  
Endothelin B ◽  
Selection Of

The molecular mechanisms involved in lymphangiogenesis were unknown until recently. We previously demonstrated that the endothelin-1 (ET-1) axis stimulates lymphatic endothelial cells (LEC) and lymphatic vessels to grow and invade. Here we further investigated the effect of ET-1 on lymphatic vessels and evaluated whether ET-1 actions result in the functional activation of lymphangiogenesis. Using highly purified human LEC, characterized for the expression of ET-1 axis members by quantitative real-time PCR, we found that the endothelin B receptor (ETB), upon activation by ET-1, induced matrix-metalloproteinase activation, demonstrating that ET-1 influenced the activity of the proteolytic enzymes required for LEC invasion. Functional assays performed by using intradermal lymphangiography demonstrated that ET-1 promoted the formation of lymphatic vessels and that these vessels were capable of lymphatic flow. ETB blockade with the specific antagonist BQ788 inhibited matrix-metalloproteinase activation and dye transport within the lymphatic vessels, demonstrating that ETB is involved in the regulation of the growth of and in the formation of functional vessels upon activation by ET-1. Our results suggest that ET-1 is a lymphangiogenic mediator and that targeting pharmacologically ETB may be therapeutically exploited in a variety of diseases, including cancer.

ETB receptor dependent alteration in aortic responses to ET-1 in the cardiomyopathic hamsterThis paper is one of a selection of papers published in this Special issue, entitled Second Messengers and Phosphoproteins—12th International Conference.

2006 ◽  
Vol 84 (7) ◽  
pp. 787-794 ◽  
Author(s):  
Johny Al-Khoury ◽  
Ghassan Bkaily ◽  
Mirna Chahine ◽  
Danielle Jacques ◽  
Pedro D'Orléans-Juste
Keyword(s):  
Receptor Antagonist ◽  
Second Messengers ◽  
Receptor Density ◽  
Special Issue ◽  
Cardiomyopathic Hamster ◽  
Cardiomyopathic Hamsters ◽  
Etb Receptor ◽  
Pre Treatment ◽  
Dose Dependent ◽  
Selection Of

The aim of this study was to verify whether an alteration in the aortic endothelin-1 (ET-1) response takes place in UM-X7.1 cardiomyopathic hamsters. Our results showed that ET-1 (10−12 – 10−5 mol/L) induces dose-dependent sustained increases in tension in the intact and endothelium denuded aortas from both normal and cardiomyopathic hamsters. The EC50 values of ET-1 of both intact and endothelium denuded aortas of normal hamsters were similar (2.2 × 10−9 mol/L and 1.8 × 10−9 mol/L, respectively). However, in cardiomyopathic hamsters, the EC50 of ET-1 in intact aortas was higher (1.5 × 10−8 mol/L) than that of the endothelium denuded preparations (2.7 × 10−9 mol/L). The EC50 of ET-1 in normal and cardiomyopathic hamster denuded aortas were similar. However, the EC50 of ET-1 in intact aortas of cardiomyopathic hamster was higher (1.5 × 10−8 mol/L) than that of normal hamsters (2.2 × 10−9 mol/L). Pre-treatment with the ETA receptor antagonist ABT-627 (10−5 mol/L) of intact and endothelium denuded aortas from both normal and cardiomyopathic hamsters significantly prevented ET-1 (10−7 mol/L) from inducing an increase in tension. Pre-treatment with the ETB receptor antagonist A-192621 (10−5 mol/L) had no effect on the ET-1-induced increase in tension in endothelium denuded aortas of both normal and cardiomyopathic hamsters, as well as in intact preparations of normal animals. However, blockade of the ETB receptors in intact aortas of cardiomyopathic hamsters significantly (p < 0.001) potentiated the ET-1-induced increase in tension. In summary, an attenuation of the contraction response to ET-1 was found in UM-X7.1 cardiomyopathic hamsters when compared with normal age-matched hamsters. This alteration of the ET-1 effect in the aortas of cardiomyopathic hamsters seems to be dependent on the presence of the endothelium and could be due, in part, to an increase in the contribution of endothelial ETB receptors to relaxation, which in turn acts as a physiological depressor of ET-1 vasoconstriction. Our results suggest that an increase in the endothelium ETB receptor density may play a role in the development of hypotension in UM-X7.1 cardiomyopathic hamsters.

Introduction: Affixes and bases

2011 ◽  
Vol 4 (2) ◽  
pp. 161-168
Author(s):  
Stela Manova
Keyword(s):  
Special Issue ◽  
Affix Order ◽  
Selection Of ◽  
Affix Ordering

This special issue includes a selection of papers presented at the 2nd Vienna Workshop on Affix Order held in Vienna, Austria on June 4–5, 2009. The workshop was in honor of Wolfgang U. Dressler on the occasion of his 70th birthday. However, this special issue differs from the classical Festschrift dedicated to a renowned scholar and is ‘more special’ in two respects at least: 1) not all authors are Dressler's friends and colleagues, some of them are only indirectly related to him, through his students; and 2) since the papers were presented at a topic-oriented workshop, they are thematically uniform. In other words, this special issue is a kind of scientific genealogy in terms of affix ordering. Thus, the title Affixes and bases should be understood in two ways: literally – affixes and bases as linguistic notions, and metaphorically – affixes and bases as linguists related directly and indirectly to a prominent base: Wolfgang U. Dressler.

tti2002: Introduction and Conference Overview

2003 ◽  
Vol 17 (1) ◽  
pp. 9-14 ◽  
Author(s):  
E. H. Robson
Keyword(s):  
Higher Education ◽  
Technology Transfer ◽  
Special Issue ◽  
International Convention ◽  
International Conference ◽  
Introductory Paper ◽  
Personal Reflections ◽  
Selection Of

This special issue of Industry and Higher Education is devoted to a selection of papers and reports from tti2002, an international conference on technology transfer and innovation held at the International Convention Centre, Birmingham, UK in July 2002. In this introductory paper, the author provides the context of the conference, summarizes the presentations given by invited speakers and offers personal reflections on the event.

scholarly journals Recent Advances in Kinase Drug Discovery Part I: The Editors’ Take

2021 ◽  
Vol 22 (14) ◽  
pp. 7560
Author(s):  
Julie A. Tucker ◽  
Mathew P. Martin
Keyword(s):  
Drug Discovery ◽  
Research Articles ◽  
Special Issue ◽  
Recent Advances ◽  
Enzyme Family ◽  
Selection Of

This special issue on Advances in Kinase Drug Discovery provides a selection of research articles and topical reviews covering all aspects of drug discovery targeting the phosphotransferase enzyme family [...]

scholarly journals Exposure and Health Impacts Related to Outdoor and Indoor Air Pollutants

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 105
Author(s):  
Haider A. Khwaja
Keyword(s):  
Indoor Air ◽  
Air Pollutants ◽  
Health Impacts ◽  
Special Issue ◽  
Indoor Air Pollutants ◽  
Selection Of

The five papers included in this Special Issue represent a diverse selection of contributions [...]

Romance and Latin approaches to word structure features

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elisabeth Gibert-Sotelo ◽  
Isabel Pujol Payet
Keyword(s):  
The Other ◽  
Special Issue ◽  
Valuable Contribution ◽  
Field Of Study ◽  
Word Structure ◽  
New Approaches ◽  
Theoretical Approaches ◽  
Special Collection ◽  
Introductory Paper ◽  
Selection Of

Abstract The interest in morphology and its interaction with the other grammatical components has increased in the last twenty years, with new approaches coming into stage so as to get more accurate analyses of the processes involved in morphological construal. This special issue is a valuable contribution to this field of study. It gathers a selection of five papers from the Morphology and Syntax workshop (University of Girona, July 2017) which, on the basis of Romance and Latin phenomena, discuss word structure and its decomposition into hierarchies of features. Even though the papers share a compositional view of lexical items, they adopt different formal theoretical approaches to the lexicon-syntax interface, thus showing the benefit of bearing in mind the possibilities that each framework provides. This introductory paper serves as a guide for the readers of this special collection and offers an overview of the topics dealt in each contribution.

scholarly journals Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders

2021 ◽  
Vol 22 (9) ◽  
pp. 4333
Author(s):  
Yutaka Koyama
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurotrophic Factors ◽  
Drug Target ◽  
Therapeutic Strategy ◽  
Reactive Astrocytes ◽  
Brain Disorders ◽  
Etb Receptor ◽  
Target Molecules ◽  
Endothelin B

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ETB) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ETB receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ETB receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ETB-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ETB receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ETB receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.

Antimicrobial resistance in zoonotic bacteria: lessons learned from host-specific pathogens

2008 ◽  
Vol 9 (2) ◽  
pp. 177-186 ◽  
Author(s):  
Trudy M. Wassenaar ◽  
Peter Silley
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Species ◽  
Lessons Learned ◽  
Animal Host ◽  
Relative Contribution ◽  
Single Animal ◽  
Resistance Patterns ◽  
Animal Hosts ◽  
Zoonotic Bacteria ◽  
Selection Of

AbstractThe relative contribution of veterinary and human clinical treatments to the selection of antimicrobial resistance in zoonotic pathogens remains controversial. In this review, we consider bacterial pathogens that differ in host specificity and address their resistance profiles: pathogens that only occur in the human host, pathogens that are specific to particular food-producing animals and pathogens that occur in both host types. Compared with those pathogens restricted to a single animal host, pathogens found in both human and animal hosts appear to have higher incidences of resistance. However, the most urgent and severe resistance problems occur with pathogens exclusively infecting humans. Differences exist in the available genetic repertoire of a bacterial species and these are reflected in the observed resistance patterns; it is important to note that different bacterial species do not automatically result in similarly resistant populations when they undergo comparable selection in different host species. Thus, within a bacterial species, prevalence of resistance can differ between populations isolated from different hosts. For some species, fluctuations in dominant subpopulations, for instance particular serotypes, can be the most important factor determining resistance. The frequently expressed opinion that veterinary use of antimicrobials is at the heart of many resistance problems may be an oversimplification of the complex forces at play.

scholarly journals Involvement of RpoN in Regulating Bacterial Arsenite Oxidation

2012 ◽  
Vol 78 (16) ◽  
pp. 5638-5645 ◽  
Author(s):  
Yoon-Suk Kang ◽  
Brian Bothner ◽  
Christopher Rensing ◽  
Timothy R. McDermott
Keyword(s):  
Binding Site ◽  
Sigma Factor ◽  
Model Organism ◽  
Coding Region ◽  
Rt Pcr ◽  
Obvious Effect ◽  
Content Type ◽  
Definitive Evidence ◽  
Relative Contribution ◽  
Insertional Inactivation

ABSTRACTIn this study with the model organismAgrobacterium tumefaciens, we used a combination oflacZgene fusions, reverse transcriptase PCR (RT-PCR), and deletion and insertional inactivation mutations to show unambiguously that the alternative sigma factor RpoN participates in the regulation of AsIIIoxidation. A deletion mutation that removed the RpoN binding site from theaioBApromoter and anaacC3(gentamicin resistance) cassette insertional inactivation of therpoNcoding region eliminatedaioBAexpression and AsIIIoxidation, althoughrpoNexpression was not related to cell exposure to AsIII. Putative RpoN binding sites were identified throughout the genome and, as examples, included promoters foraioB,phoB1,pstS1,dctA,glnA,glnB, andflgBthat were examined by using qualitative RT-PCR andlacZreporter fusions to assess the relative contribution of RpoN to their transcription. The expressions ofaioBanddctAin the wild-type strain were considerably enhanced in cells exposed to AsIII, and both genes were silent in therpoN::aacC3mutant regardless of AsIII. The expression level ofglnAwas not influenced by AsIIIbut was reduced (but not silent) in therpoN::aacC3mutant and further reduced in the mutant under N starvation conditions. TherpoN::aacC3mutation had no obvious effect on the expression ofglnB,pstS1,phoB1, orflgB. These experiments provide definitive evidence to document the requirement of RpoN for AsIIIoxidation but also illustrate that the presence of a consensus RpoN binding site does not necessarily link the associated gene with regulation by AsIIIor by this sigma factor.

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