scholarly journals Molecular properties and evolutionary origins of a parvovirus-derived myosin fusion gene in guinea pigs

2019 ◽  
Author(s):  
Ignacio Valencia-Herrera ◽  
Eduardo Cena-Ahumada ◽  
Fernando Faunes ◽  
Rodrigo Ibarra-Karmy ◽  
Robert J. Gifford ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Fusion Gene ◽  
Purifying Selection ◽  
Evolutionary Origins ◽  
Evolutionarily Conserved ◽  
Mammalian Genomes ◽  
Multiple Species ◽  
The Impact

AbstractSequences derived from parvoviruses (familyParvoviridae) are relatively common in animal genomes, but the functional significance of these endogenous parvoviral element (EPV) sequences remains unclear. In this study we use a combination ofin silicoand molecular biological approaches to investigate a fusion gene encoded by guinea pigs (genusCavia) that is partially derived from an EPV. This gene, namedenRep-Myo9, encodes a predicted polypeptide gene product comprising a partialmyosin9 (Myo9)-like gene fused to a 3’ truncated, EPV- encoded replicase. We first examined the genomic and phylogenetic characteristics of the EPV locus that encodes the viral portions ofenRep-Myo9. We show that this locus, named enRep, is specific to guinea pigs and derives from an ancient representative of the parvoviral genusDependoparvovirusthat integrated into the guinea pig germline 22-35 million years ago. Despite these ancient origins, however, the regions of enRep that are incorporated into the coding sequence of theenRep-Myo9gene are conserved across multiple species in the family Caviidae (guinea pigs and cavies) consistent with purifying selection. Using molecular biological approaches, we further demonstrate that: (i)enRep-Myo9mRNA is broadly transcribed in guinea pig cells; (ii) the clonedenRep-Myo9transcript can express a protein of the expected size in guinea pig cellsin vitro, and; (iii) the expressed protein localizes to the cytosol. Our findings demonstrate that, consistent with a functional role, theenRep-Myo9fusion gene is evolutionarily conserved, broadly transcribed, and capable of expressing protein.ImportanceDNA from viruses has been ‘horizontally transferred’ to mammalian genomes during evolution, but the impact of this process on mammalian biology remains poorly understood. The findings of our study indicate that in guinea pigs a novel gene has evolved through fusion of host and virus genes.

scholarly journals Molecular Properties and Evolutionary Origins of a Parvovirus-Derived Myosin Fusion Gene in Guinea Pigs

2019 ◽  
Vol 93 (17) ◽  
Author(s):  
Ignacio Valencia-Herrera ◽  
Fernando Faunes ◽  
Eduardo Cena-Ahumada ◽  
Rodrigo Ibarra-Karmy ◽  
Robert J. Gifford ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Germ Line ◽  
Fusion Gene ◽  
Amino Acid Level ◽  
Evolutionary Origins ◽  
Mammalian Genomes ◽  
Multiple Species ◽  
The Impact

ABSTRACTSequences derived from parvoviruses (familyParvoviridae) are relatively common in animal genomes, but the functional significance of these endogenous parvoviral element (EPV) sequences remains unclear. In this study, we used a combination ofin silicoand molecular biological approaches to investigate a fusion gene carried by guinea pigs (genusCavia) that is partially derived from an EPV. This gene, namedenRep-M9l, encodes a predicted polypeptide gene product comprising a partialmyosin9-like (M9l) gene fused to a 3′ truncated, EPV-encoded replicase. We examined the genomic and phylogenetic characteristics of the EPV locus (enRep) that encodes the viral portions ofenRep-M9l, revealing that it derives from an ancient dependoparvovirus (genusDependoparvovirus) that was incorporated into the guinea pig germ line between approximately 22 and 35 million years ago (MYA). Despite these ancient origins, the regions of theenReplocus that are expressed in theenRep-M9lgene are conserved across multiple species in the family Caviidae (guinea pigs and cavies), consistent with a potential function at the amino acid level. Using molecular biological approaches, we further demonstrated that (i)enRep-M9lmRNA is broadly transcribed in guinea pig cells, (ii) the clonedenRep-M9ltranscript can express a protein of the expected size in guinea pig cellsin vitro, and (iii) the expressed protein localizes to the cytosol. Our findings demonstrate that, consistent with a functional role, theenRep-M9lfusion gene is evolutionarily conserved, broadly transcribed, and capable of expressing protein.IMPORTANCEDNA from viruses has been “horizontally transferred” to mammalian genomes during evolution, but the impact of this process on mammalian biology remains poorly understood. The findings of our study indicate that a novel gene has evolved in guinea pigs through fusion of host and virus genes.

Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

1976 ◽  
Vol 36 (02) ◽  
pp. 401-410 ◽  
Author(s):  
Buichi Fujttani ◽  
Toshimichi Tsuboi ◽  
Kazuko Takeno ◽  
Kouichi Yoshida ◽  
Masanao Shimizu
Keyword(s):  
Guinea Pig ◽  
Acetylsalicylic Acid ◽  
Guinea Pigs ◽  
Glass Bead ◽  
Animal Species ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

scholarly journals FURTHER STUDIES ON THE ROLE OF PROTEASES IN THE ALLERGIC REACTION

1961 ◽  
Vol 113 (2) ◽  
pp. 359-380 ◽  
Author(s):  
Georges Ungar ◽  
Takuso Yamura ◽  
Jacqueline B. Isola ◽  
Sidney Kobrin
Keyword(s):  
Amino Acid ◽  
Guinea Pig ◽  
Proteolytic Activity ◽  
Guinea Pigs ◽  
Protease Activity ◽  
Amino Acid Esters ◽  
Protein Substrates ◽  
Protease Activation ◽  
Acid Esters

Protease activity was measured through the hydrolysis of synthetic amino acid esters in body fluids and tissues of guinea pigs, rats, mice, and humans. Significant in vitro activation was observed in serum and lung slices of sensitized guinea pigs on addition of the specific antigen. Increased proteolytic activity was also seen in reverse anaphylaxis. More marked activation occurred when guinea pig serum was treated with peptone and guinea pig or rat serum was treated with agar. Protease activation was demonstrated in specimens of human skin under the influence of a poison ivy extract or croton oil added in vitro. Urinary protease activity of guinea pigs increased significantly during the first hours of anaphylactic shock and very markedly in peptone shock. Peptone shock, elicited in mice pretreated with H. pertussis, was accompanied by a considerable increase in protease activity in the peritoneal fluid as compared with non-pretreated mice which were insensitive to peptone. Proteolytic activity resulting from the activation procedures was due to a number of proteases. The dominant substrate affinity and inhibition patterns suggest that serum and urine proteases are similar to but not identical with plasmin. Anaphylactic activation exhibited patterns different from those resulting from the action of anaphylactoid agents. Tissue enzymes are either of cathepsin- or chymotrypsin-type or mixtures of both. Some of the activated enzymes, although remarkably effective in hydrolyzing amino acid esters, show no activity on protein substrates. This does not justify, however, their designation as "esterases." They probably belong to the class of specific proteases acting only on a single or a small number of functionally significant protein substrates. There is at present sufficient evidence to prove not only that protease activation does occur in anaphylaxis and anaphylactoid conditions but also that it is an important component of the chain of reactions leading to the allergic response.

The effects of furosemide and bumetanide on lung liquid production by in vitro lungs from fetal guinea pigs

1990 ◽  
Vol 68 (8) ◽  
pp. 1131-1135 ◽  
Author(s):  
J. Thom ◽  
A. M. Perks
Keyword(s):  
Body Weight ◽  
Guinea Pig ◽  
Guinea Pigs ◽  
Loop Diuretics ◽  
Dilution Technique ◽  
Blue Dextran ◽  
Lung Fluid ◽  
Lung Liquid ◽  
Secretion Rates

Lungs from fetal guinea pigs of 61 ± 3 days of gestation were supported in vitro for 3 h, and lung liquid secretion rates were measured by a dye dilution technique based on Blue Dextran 2000. Ten preparations that had received no treatment showed an average secretion rate of 1.12 ± 0.28 mL∙kg−1 body weight∙h−1 during the first hour, and there were no significant changes over the following 2 h. In studies of 54 fetal lungs, furosemide, bumetanide, control ethanol carrier, or saline alone were placed in the supporting medium during the middle hour of the 3-h incubations (ABA design). Furosemide at 10−3 M reduced secretion 83.4 ± 16.8%; at 10−4 and 10−5 M it produced smaller reductions. Bumetanide at 10−3 M usually produced reabsorption (129.9 ± 23.0% reduction), at 10−4 M it reduced secretion 30.9 ± 11.8%, but at 10−5 M it was ineffective. Control carrier and saline were without effect. The ability of the loop diuretics to produce reabsorption of fluid in some preparations suggests the unmasking of an active reabsorptive process. The results also suggest that lung liquid secretion in the fetal guinea pig, as in the sheep, is dependent on a Na+ and Cl− cotransport system.Key words: fetus, lung fluid, bumetanide, furosemide.

scholarly journals The potential of microdialysis to estimate rifampicin concentrations in the lung of guinea pigs

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245922
Author(s):  
Faye Lanni ◽  
Neil Burton ◽  
Debbie Harris ◽  
Susan Fotheringham ◽  
Simon Clark ◽  
...  
Keyword(s):  
Drug Development ◽  
Guinea Pigs ◽  
Sampling Technique ◽  
Tissue Fluid ◽  
Experimental Conditions ◽  
Continuous Sampling ◽  
Drug Concentrations ◽  
The Impact

Optimised pre-clinical models are required for TB drug development to better predict the pharmacokinetics of anti-tuberculosis (anti-TB) drugs to shorten the time taken for novel drugs and combinations to be approved for clinical trial. Microdialysis can be used to measure unbound drug concentrations in awake freely moving animals in order to describe the pharmacokinetics of drugs in the organs as a continuous sampling technique. The aim of this work was to develop and optimise the microdialysis methodology in guinea pigs to better understand the pharmacokinetics of rifampicin in the lung. In vitro experiments were performed before progressing into in vivo studies because the recovery (concentration of the drug in the tissue fluid related to that in the collected dialysate) of rifampicin was dependent on a variety of experimental conditions. Mass spectrometry of the dialysate was used to determine the impact of flow rate, perfusion fluid and the molecular weight cut-off and membrane length of probes on the recovery of rifampicin at physiologically relevant concentrations. Following determination of probe efficiency and identification of a correlation between rifampicin concentrations in the lung and skeletal muscle, experiments were conducted to measure rifampicin in the sacrospinalis of guinea pigs using microdialysis. Lung concentrations of rifampicin were estimated from the rifampicin concentrations measured in the sacrospinalis. These studies suggest the potential usefulness of the microdialysis methodology to determine drug concentrations of selected anti-TB drugs to support new TB drug development.

scholarly journals Use of quantitative real-time PCR for studying the dissemination of Leptospira interrogans in the guinea pig infection model of leptospirosis

2009 ◽  
Vol 58 (5) ◽  
pp. 648-655 ◽  
Author(s):  
Kristel Lourdault ◽  
Florence Aviat ◽  
Mathieu Picardeau
Keyword(s):  
Guinea Pig ◽  
Real Time ◽  
Real Time Pcr ◽  
Guinea Pigs ◽  
Infection Model ◽  
Avirulent Strain ◽  
Leptospira Interrogans ◽  
Quantitative Real Time Pcr ◽  
Guinea Pig Model

The dynamics of leptospirosis infection have been poorly studied. The purpose of this study was to determine the LD50, rate of bacterial dissemination, histopathology and antibody responses against leptospira following inoculation with the highly virulent Leptospira interrogans Fiocruz L1-130 strain in a guinea pig model of leptospirosis. Three routes of infection (intraperitoneal, conjunctival and subcutaneous inoculation) were used to establish disease in guinea pigs. The size and kinetics of leptospiral burdens in the blood and tissues of infected animals were determined over a 1 week course of infection using quantitative real-time PCR (qPCR). Bacteraemia peaked at day 5 post-infection reaching more than 5×104 leptospires ml−1. The highest spirochaetal load was found in the liver and kidneys, and was associated with alterations in organ tissues and a decline in liver and kidney functions. In contrast, lesions and bacteria were not detected in guinea pigs infected with an avirulent strain derived from a high-passage-number in vitro-passaged variant of the Fiocruz L1-130 strain. The use of qPCR supports the findings of earlier studies and provides an easy and reliable method for the quantification of L. interrogans in the tissues of infected animals. qPCR will be used in future studies to evaluate the efficacy of vaccine candidates against leptospirosis and the virulence of selected L. interrogans mutants relative to the parental strain.

scholarly journals MULTIPLICATION IN VITRO OF PSEUDORABIES VIRUS IN THE TESTICLE TISSUE OF IMMUNIZED GUINEA PIGS

1935 ◽  
Vol 61 (6) ◽  
pp. 833-838
Author(s):  
Erich Traub
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Pseudorabies Virus ◽  
Immune Tissue

Pseudorabies virus was cultivated in vitro in washed testicle tissue from immune guinea pigs, and evidence was thus procured which indicated that the testicle cells themselves had not become immune to pseudorabies. The rate of multiplication of the virus was considerably greater in control cultures with normal guinea pig testis than in cultures with immune testis. The reason for this fact may be that even by repeated washing the immune tissue could not be completely freed from fluid antibodies, and that such antibodies somewhat inhibited the multiplication of the virus.

scholarly journals Guinea-pig liver tryptophan pyrrolase. Absence of detectable apoenzyme activity and of hormonal induction by cortisol and possible regulation by tryptophan

1974 ◽  
Vol 138 (3) ◽  
pp. 445-451 ◽  
Author(s):  
Abdulla A.-B. Badawy ◽  
Myrddin Evans
Keyword(s):  
Guinea Pig ◽  
Liver Enzyme ◽  
Guinea Pigs ◽  
Actinomycin D ◽  
The Other ◽  
Pig Liver ◽  
Latent Form ◽  
Tryptophan Pyrrolase ◽  
Guinea Pig Liver

1. When assayed in fresh homogenates, guinea-pig liver tryptophan pyrrolase exists only as holoenzyme. It does not respond to agents that activate or inhibit the rat liver enzyme in vitro. Only by aging (for 30min at 5°C) does the guinea-pig enzyme develop a requirement for ascorbate. 2. The guinea-pig liver enzyme is activated by the administration of tryptophan but not cortisol, salicylate, ethanol or 5-aminolaevulinate. 3. The tryptophan enhancement of the guinea-pig liver pyrrolase activity is prevented by 0, 34 and 86% by pretreatment with actinomycin D, cycloheximide or allopurinol respectively. 4. The guinea-pig liver tryptophan pyrrolase is more sensitive to tryptophan administration than is the rat enzyme. On the other hand, the concentrations of tryptophan in sera and livers of guinea pigs are 45–52% less than those in rats. 5. It is suggested that tryptophan may regulate the activity of guinea-pig liver tryptophan pyrrolase by mobilizing a latent form of the enzyme whose primary function is the detoxication of its substrate.

Studies on Sperm Antigenicity 6. In vivo and in Vitro Cellular Reactivity in Guinea Pigs Sensitized with Fractions of Guinea Pig Spermatozoa

1977 ◽  
Vol 6 (4) ◽  
pp. 355-371 ◽  
Author(s):  
Zvi H. Marcus ◽  
Yael Shtal ◽  
Gerald Dominique ◽  
Laslo Nebel
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs

scholarly journals Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.

1994 ◽  
Vol 179 (3) ◽  
pp. 881-887 ◽  
Author(s):  
P J Jose ◽  
D A Griffiths-Johnson ◽  
P D Collins ◽  
D T Walsh ◽  
R Moqbel ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
High Performance ◽  
Allergen Challenge ◽  
Neutrophil Accumulation ◽  
Platelet Factor ◽  
Inflammatory Reactions ◽  
Eosinophil Accumulation

Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, "eotaxin," exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1 alpha, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2 pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1 alpha, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung.

Sign in / Sign up

Export Citation Format

Share Document