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Valerie S. Langlois - One of the best experts on this subject based on the ideXlab platform.

  • Chronic Exposure to Two Gestagens Differentially Alters Morphology and Gene Expression in Silurana tropicalis
    Archives of Environmental Contamination and Toxicology, 2021
    Co-Authors: Paisley Thomson, Viviane Yargeau, Marco Pineda, Valerie S. Langlois
    Abstract:

    Gestagens are active ingredients in human and veterinary drugs with progestogenic activity. Two gestagens—progesterone (P4), and the synthetic P4 analogue, melengestrol acetate (MGA)—are approved for use in beef cattle agriculture in North America. Both P4 and MGA have been measured in surface water receiving runoff from animal agricultural operations. This project aimed to assess the morphometric and molecular consequences of chronic exposures to P4, MGA, and their mixture during Western clawed frog metamorphosis. Chronic exposure (from embryo to metamorphosis) to MGA (1.7 µg/L) or P4 + MGA (0.22 µg/L P4 + 1.5 µg/L MGA) caused a considerable dysregulation of metamorphic timing, as evidenced by an inhibition of growth, narrower head, and lack of forelimb emergence in all animals. Molecular analysis revealed that chronic exposure to the mixture induced an additive upregulation of neurosteroid-related (GABA_A receptor subunit α6 ( gabra6 ) and steroid 5-alpha reductase 1 ( srd5α1 ) gene expression in brain tissue. Chronic P4 exposure (0.26 µg/L P4) induced a significant upregulation of the expression hypothalamic–pituitary–gonadal (HPG)-related genes ( ipgr, erα ) in the gonadal mesonephros complex (GMC). Our data suggest that exposure to P4, MGA, and their mixture induces multiple endocrine responses and adverse effects in larval Western clawed frogs. This study helps to better our understanding of the consequences of chronic gestagen exposure and suggests that the implications and risk of high gestagen use in beef cattle feeding operations may extend to the aquatic environment.

  • Lethal and sublethal effects of phthalate diesters in Silurana tropicalis larvae
    Environmental toxicology and chemistry, 2016
    Co-Authors: Justine Mathieu-denoncourt, Jennifer R. Loughery, Christopher J Martyniuk, Viviane Yargeau, Shane R. De Solla, Valerie S. Langlois
    Abstract:

    Phthalates are compounds used in polymers to increase their flexibility and are now ubiquitous in the environment as a result of widespread use. Because few studies have focused on the adverse effects of these chemicals in aquatic species, the present study aimed to determine the effects of phthalate diesters in amphibians. Western clawed frog (Silurana tropicalis) tadpoles were acutely exposed to water spiked with monomethyl phthalate (MMP; 1.3-1595.5 mg/L), dimethyl phthalate (DMP; 0.03-924.0 mg/L), or dicyclohexyl phthalate (DCHP; 0.3-99.3 mg/L). Because few studies have addressed the toxicity of these specific phthalates in most organisms, the present study used higher concentrations of these chemicals to determine their toxicity pathways in amphibians and at the same time investigate a suite of genes known to be altered by the well-studied phthalates. Both DMP and DCHP increased larval mortality (9.1-924.0 mg/L DMP and 4.1-99.3 mg/L DCHP), increased frequency of malformations in tadpoles (0.1-34.1 mg/L DMP and 4.1-19.0 mg/L DCHP), and up-regulated cellular stress-related messenger-RNA (mRNA) levels (4.1 mg/L DCHP). To characterize the molecular toxicity pathway of these phthalates in tadpoles, transcriptome analysis was conducted using a custom microarray. Parametric analysis of gene set enrichment revealed important changes in the expression of genes related to drug metabolism and transport, liver metabolism, xenobiotic clearance, and xenobiotic metabolism after DMP and DCHP treatments, although these responses were less pronounced with MMP (the metabolite of DMP). The present study is one of the few studies that demonstrated complementarity between gene expression analysis and organismal effects. Environ Toxicol Chem 2016;35:2511-2522. © 2016 SETAC.

  • Transcriptomic responses during early development following arsenic exposure in Western Clawed Frogs, Silurana tropicalis
    Toxicological Sciences, 2015
    Co-Authors: Jing Zhang, G. Caumette, Laura A. Gibson, Mark Button, Jennifer R. Loughery, Iris Koch, William R Cullen, Kenneth J Reimer, Christopher J Martyniuk, Valerie S. Langlois
    Abstract:

    Arsenic compounds are widespread environmental contaminants and exposure elicits serious health issues, including early developmental anomalies. Depending on the oxidation state, the intermediates of arsenic metabolism interfere with a range of subcellular events, but the fundamental molecular events that lead to speciation-dependent arsenic toxicity are not fully elucidated. This study therefore assesses the impact of arsenic exposure on early development by measuring speciation and gene expression profiles in the developing Western clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5 and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid, arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected. Microarray and pathway analyses were utilized to characterize the comprehensive transcriptomic responses to arsenic exposure. Clustering analysis of expression data showed distinct gene expression patterns in arsenate treated groups when compared with the control. Pathway enrichment revealed common biological themes enriched in both treatments, including cell signal transduction, cell survival, and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment of pathways and biological processes involved in arsenic intake or efflux, as well as histone remodeling. These compensatory responses are hypothesized to be responsible for maintaining an in-body arsenic level comparable to control animals. With no appreciable changes observed in malformation and mortality between control and exposed larvae, this is the first study to suggest that the underlying transcriptomic regulations related to signal transduction, cell survival, developmental pathways, and histone remodeling may contribute to maintaining ongoing development while coping with the potential arsenic toxicity in S. tropicalis during early development.

  • Crosstalk between the thyroid hormone and androgen axes during reproductive development in Silurana tropicalis.
    General and comparative endocrinology, 2014
    Co-Authors: Diana E.k. Flood, Valerie S. Langlois
    Abstract:

    Abstract The objectives of this study were to examine the effects of potassium perchlorate (KClO 4 ) treatment on androgen- and thyroid hormone (TH)-related transcript levels during gonadogenesis in the frog Silurana tropicalis . Androgen- and TH-related gene expression was examined in gonad–mesonephros complex (GMC) and liver tissues at stage NF 56 and stage NF 60. These stages of development coincide with the period of sexual differentiation. Real-time RT-PCR analyses revealed that androgen- and TH-related transcript levels in the GMC and liver of stage NF 56 and NF 60 frogs are responsive to KClO 4 exposure during prometamorphosis. An increase in srd5α2 mRNA levels in hepatic tissues of KClO 4 -treated NF 56 tadpoles suggests an important role for hepatic tissues in androgen metabolism. Gene transcript differences highlight possible stage- and tissue-specific sensitivities to KClO 4 . A greater number of TH- and androgen-related transcriptional changes were discerned in the hepatic tissues compared to the gonads, and overall fewer transcriptional changes were observed in stage NF 60 tadpoles compared to stage NF 56 larvae. Perchlorate suppressed somatic and hind-limb development during the 96-d exposure period. Treatment with KClO 4 had no significant effect on sex ratios, however a notable reduction in the percentage of males (33.3% M: 66.7% F) in the highest KClO 4 concentration (107 μg/L) was observed. Overall, these findings suggest that KClO 4 has secondary androgenic disrupting properties in addition to its known primary thyroid hormone-disrupting role.

  • Transcriptomic profiling in Silurana tropicalis testes exposed to finasteride.
    General and comparative endocrinology, 2014
    Co-Authors: Sonja Bissegger, Christopher J Martyniuk, Valerie S. Langlois
    Abstract:

    Investigations of endocrine disrupting chemicals found in aquatic ecosystems with estrogenic and androgenic modes of action have increased over the past two decades due to a surge of evidence of adverse effects in wildlife. Chemicals that disrupt androgen signalling and steroidogenesis can result in an imbalanced conversion of testosterone (T) into 17β-estradiol (E2) and other androgens such as 5α-dihydrotestosterone (5α-DHT). Therefore, a better understanding of how chemicals perturb these pathways is warranted. In this study, the brain, liver, and testes of Silurana tropicalis were exposed ex vivo to the human drug finasteride, a potent steroid 5α-reductase inhibitor and a model compound to study the inhibition of the conversion of T into 5α-DHT. These experiments were conducted (1) to determine organ specific changes in sex steroid production after treatment, and (2) to elucidate the transcriptomic response to finasteride in testicular tissue. Enzyme-linked immunosorbent assays were used to measure hormone levels in media following finasteride incubation for 6 h. Finasteride significantly increased T levels in the media of liver and testis tissue, but did not induce any changes in E2 and 5α-DHT production. Gene expression analysis was performed in frog testes and data revealed that finasteride treatment significantly altered 1,434 gene probes. Gene networks associated with male reproduction such as meiosis, hormone biosynthesis, sperm entry, gonadotropin releasing hormone were affected by finasteride exposure as well as other pathways such as oxysterol synthesis, apoptosis, and epigenetic regulation. For example, this study suggests that the mode of action by which finasteride induces cellular damage in testicular tissue as reported by others, is via oxidative stress in testes. This data also suggests that 5-reductase inhibition disrupts the expression of genes related to reproduction. It is proposed that androgen-disrupting chemicals may mediate their action via 5-reductases and that the effects of environmental pollutants are not limited to the androgen receptor signalling.

Vance L. Trudeau - One of the best experts on this subject based on the ideXlab platform.

  • Naphthenic Acid Mixtures and Acid-Extractable Organics from Oil Sands Process-Affected Water Impair Embryonic Development of Silurana (Xenopus) tropicalis.
    Environmental science & technology, 2019
    Co-Authors: Juan Manuel Gutierrez-villagomez, Bruce D. Pauli, Kerry M. Peru, Connor C. Edington, John V. Headley, Vance L. Trudeau
    Abstract:

    Naphthenic acids (NAs) are carboxylic acids naturally occurring in crude oils and bitumen and are suspected to be the primary toxic substances in wastewaters associated with oil refineries and mining of oil sands. Oil sands process-affected water (OSPW) generated by the extraction of bitumen from oil sands are a major source of NAs and are currently stored in tailings ponds. We report on the acute lethality and teratogenic effects of aquatic exposure of Silurana (Xenopus) tropicalis embryos to commercial NA extracts and from the acid extractable organics (AEOs) fraction of a Canadian OSPW. Using electrospray ionization-high resolution mass spectrometry, we determined that the O2 species proportion were 98.8, 98.9 and 58.6% for commercial mixtures Sigma 1 (S1M) and Sigma 2 (S2M), and AEOs, respectively. The 96h LC50 estimates were 10.4, 11.7, and 52.3 mg/L for S1M, S2M, and the AEOs, respectively. The 96h EC50 estimates based on frequencies of developmental abnormalities were 2.1, 2.6, and 14.2 mg/L for S1...

  • Early expression of aromatase and the membrane estrogen receptor GPER in neuromasts reveals a role for estrogens in the development of the frog lateral line system.
    General and comparative endocrinology, 2014
    Co-Authors: Christine K. Hamilton, Laia Navarro-martín, Miriam Neufeld, Ajoy Basak, Vance L. Trudeau
    Abstract:

    Estrogens and their receptors are present at very early stages of vertebrate embryogenesis before gonadal tissues are formed. However, the cellular source and the function of estrogens in embryogenesis remain major questions in developmental endocrinology. We demonstrate the presence of estrogen-synthesizing enzyme aromatase and G protein-coupled estrogen receptor (GPER) proteins throughout early embryogenesis in the model organism, Silurana tropicalis. We provide the first evidence of aromatase in the vertebrate lateral line. High levels of aromatase were detected in the mantle cells of neuromasts, the mechanosensory units of the lateral line, which persisted throughout the course of development (Nieuwkoop and Faber stages 34-47). We show that GPER is expressed in both the accessory and hair cells. Pharmacological activation of GPER with the agonist G-1 disrupted neuromast development and migration. Future study of this novel estrogen system in the amphibian lateral line may shed light on similar systems such as the mammalian inner ear.

  • Growth, development and incidence of deformities in amphibian larvae exposed as embryos to naphthenic acid concentrations detected in the Canadian oil sands region.
    Environmental pollution (Barking Essex : 1987), 2012
    Co-Authors: Steven D. Melvin, Vance L. Trudeau
    Abstract:

    Abstract Naphthenic acids (NA) have been identified as harmful environmental contaminants that influence survival, growth and development of wildlife. Amphibian larvae are particularly susceptible to waterborne contaminants, but little information exists regarding exposure of amphibian embryos or tadpoles to NA. Our results demonstrate that embryos of Lithobates pipiens and Silurana tropicalis exposed to 2–4 mg/l of a commercial NA blend suffer significant reductions (32% and 25%, respectively) in growth and development upon hatching. Increased incidences of deformities were observed in exposed individuals of both species, but were only significant in L. pipiens . Embryos suffered 100% mortality following exposure to 6 mg/l NAs, and narcosis at lower concentrations. LC50 estimates were 4.10 mg/l for 72-h exposure in L. pipiens and 4.13, 3.51, and 2.95 mg/l for 24-, 48-, and 72-h exposure in S. tropicalis . These data suggest that exposure to NAs at environmentally realized concentrations may negatively affect tadpole populations.

  • Fate and developmental effects of dietary uptake of methylmercury in Silurana tropicalis tadpoles.
    Journal of toxicology and environmental health. Part A, 2011
    Co-Authors: Melissa A. Davidson, Vance L. Trudeau, Maxine C. Croteau, Catherine S. Millar, David R. S. Lean
    Abstract:

    Adverse effects of methylmercury (MeHg) exposure during amphibian metamorphosis remain to be fully characterized. Most previous investigations determined effects of short-term exposure to elevated dose rates, without information on mercury (Hg) depuration and degradation pathways. Since metamorphosis is primarily controlled by thyroid hormones (TH), alterations in this process suggest a disruption of the TH endocrine axis. The aim of this research was to (1) characterize patterns of MeHg accumulation and depuration in tadpoles and (2) examine effects of MeHg accumulation on metamorphosis and the TH axis. Silurana tropicalis tadpoles were exposed to environmental levels of dietary MeHg until metamorphic climax. Whole-body MeHg and total Hg (THg) levels were measured, as well as the number of metamorphs, rate of metamorphosis, body size, and whole-body triiodothyronine (T3) levels at metamorphosis. Tadpoles exposed to a higher level of MeHg exhibited increased mortality and size, and reduced metamorphosis. ...

  • transcript profiles and triiodothyronine regulation of sex steroid and thyroid hormone related genes in the gonad mesonephros complex of Silurana tropicalis
    Molecular and Cellular Endocrinology, 2011
    Co-Authors: Paula Duarteguterman, Vance L. Trudeau
    Abstract:

    Abstract In amphibians, the main role of thyroid hormones (THs) is to regulate metamorphosis; however, there is evidence that THs also affect gonadal sexual differentiation. In this study, Silurana (Xenopus) tropicalis tadpoles were exposed to triiodothyronine (T3; 0, 0.5, 5 and 50 nM), the bioactive form of THs for 48 h. Real-time RT-PCR analyses in the gonad–mesonephros complex (GMC) revealed that TH- and androgen-related genes were positively regulated, while estrogen receptor β was negatively regulated by T3. Together, these results are in agreement with the masculinizing effect of THs in amphibians. Profiles of TH- and sex steroid-related genes in the GMC during metamorphosis of S. tropicalis suggest that THs are important regulators of sex steroid-related gene expression in the GMC. This study provides evidence that the GMC is a target of THs but that a complex interplay exists between THs and sex steroids during gonadal sexual development.

J. Michael Conlon - One of the best experts on this subject based on the ideXlab platform.

  • Host-Defense Peptides with Therapeutic Potential from Skin Secretions of Frogs from the Family Pipidae
    Pharmaceuticals, 2014
    Co-Authors: J. Michael Conlon, Milena Mechkarska
    Abstract:

    Skin secretions from frogs belonging to the genera Xenopus, Silurana, Hymenochirus, and Pseudhymenochirus in the family Pipidae are a rich source of host-defense peptides with varying degrees of antimicrobial activities and cytotoxicities to mammalian cells. Magainin, peptide glycine-leucine-amide (PGLa), caerulein-precursor fragment (CPF), and xenopsin-precursor fragment (XPF) peptides have been isolated from norepinephrine-stimulated skin secretions from several species of Xenopus and Silurana. Hymenochirins and pseudhymenochirins have been isolated from Hymenochirus boettgeri and Pseudhymenochirus merlini. A major obstacle to the development of these peptides as anti-infective agents is their hemolytic activities against human erythrocytes. Analogs of the magainins, CPF peptides and hymenochirin-1B with increased antimicrobial potencies and low cytotoxicities have been developed that are active (MIC < 5 μM) against multidrug-resistant clinical isolates of Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Stenotrophomonas maltophilia and Klebsiella pneumoniae. Despite this, the therapeutic potential of frog skin peptides as anti-infective agents has not been realized so that alternative clinical applications as anti-cancer, anti-viral, anti-diabetic, or immunomodulatory drugs are being explored.

  • Characterization of the host-defense peptides from skin secretions of Merlin's clawed frog Pseudhymenochirus merlini: Insights into phylogenetic relationships among the Pipidae
    Comparative Biochemistry and Physiology - Part D: Genomics and Proteomics, 2013
    Co-Authors: Manju Prajeep, Milena Mechkarska, Laurent Coquet, Hubert Vaudry, Thierry Jouenne, Jérôme Leprince, Jay King, J. Michael Conlon
    Abstract:

    The family Pipidae comprises the genera Hymenochirus, Pipa, Pseudhymenochirus, Silurana, and Xenopus but phylogenetic relationships within the family are unclear. Peptidomic analysis of norepinephrine-stimulated skin secretions from Pseudhymenochirus merlini Chabanaud, 1920, the single species within the genus Pseudhymenochirus, led to identification of 13 host-defense peptides with antimicrobial activity. Two peptides (hymenochirin-1Pa and -1Pb) show structural similarity to hymenochirin-1B from Hymenochirus boettgeri and eight peptides (hymenochirin-5Pa, -5Pb, -5Pc, -5Pd, -5Pe, -5Pf, 5Pg and -5Ph) are structurally similar to each other and to hymenochirin-5B from H. boettgeri. Two peptides differing by a single amino acid (IKIPSFFRNILKKVGKEAVSLM/I AGALKQS), termed pseudhymenochirin-1Pa and -1Pb, and pseudhymenochirin-2Pa (GIFPIFAKLLGKVIKVASSLISKGRTE) do not resemble host-defense peptides previously isolated from pipid frogs. Hymenochirin-5Pe was the most abundant peptide in the secretions and hymenochirin-1Pa the most potent against Staphylococcus aureus (MIC=2.5μM) and Escherichia coli (MIC=10μM). The data support a close phylogenetic relationship between Hymenochirus and Pseudhymenochirus that is distinct from the Xenopodinae (Xenopus+Silurana) clade with Pipa sister-group to all other extant pipids.

  • Host-defense peptides in skin secretions of the tetraploid frog Silurana epitropicalis with potent activity against methicillin-resistant Staphylococcus aureus (MRSA).
    Peptides, 2012
    Co-Authors: J. Michael Conlon, Manju Prajeep, Agnes Sonnevend, Milena Mechkarska, Laurent Coquet, Hubert Vaudry, Thierry Jouenne, Jérôme Leprince, Jay D. King
    Abstract:

    Abstract A putative genome duplication event within the Silurana lineage has given rise to the tetraploid Cameroon clawed frog Silurana epitropicalis (Fischberg, Colombelli, and Picard, 1982). Peptidomic analysis of norepinephrine-stimulated skin secretions of S. epitropicalis led to identification of 10 peptides with varying degrees of growth-inhibitory activity against Escherichia coli and Staphylococcus aureus . Structural characterization identified the peptides as belonging to the magainin family (magainin-SE1), the caerulein-precursor fragment family (CPF-SE1, -SE2 and -SE3), the xenopsin-precursor fragment family (XPF-SE1, SE-2, SE-3 and -SE4), and the peptide glycine-leucine-amide family (PGLa-SE1 and -SE2). In addition, peptide phenylalanine-glutamine-amide (FLGALLGPLMNLLQ·NH 2 ) was isolated from the secretions that lacked antimicrobial activity. Comparison of the multiplicity of orthologous peptides in S. epitropicalis and the diploid Silurana tropicalis indicates that extensive nonfunctionalization (deletion or silencing) of antimicrobial peptide genes has occurred after polyploidization in the Silurana lineage, as in the Xenopus lineage. CPF-SE2 (GFLGPLLKLGLKGAAKLLPQLLPSRQQ; MIC = 2.5 μM) and CPF-SE3 (GFLGSLLKTGLKVGSNLL·NH 2 ; MIC = 5 μM) showed potent growth-inhibitory activity against a range of clinical isolates of methicillin-resistant S. aureus (MRSA). Their utility as systemic anti-infective drugs is limited by significant hemolytic activity against human erythrocytes (LC 50  = 50 μM for CPF-SE2 and 220 μM for CPF-SE3) but the peptides may find application as topical agents in treatment of MRSA skin infections and decolonization of MRSA carriers.

  • The hymenochirins: A family of host-defense peptides from the Congo dwarf clawed frog Hymenochirus boettgeri (Pipidae)
    Peptides, 2012
    Co-Authors: Milena Mechkarska, Manju Prajeep, Laurent Coquet, Hubert Vaudry, Thierry Jouenne, Jérôme Leprince, Jay King, J. Michael Conlon
    Abstract:

    Skin secretions of frogs from the subfamily Xenopodinae (Xenopus+Silurana) within the family Pipidae are a rich source of antimicrobial peptides with therapeutic potential but species from the sister taxon Hymenochirus in the subfamily Pipinae (Hymenochirus+Pseudhymenochirus+Pipa) have not been investigated. Peptidomic analysis of norepinephrine-stimulated skin secretions from two distinct populations of the Congo dwarf clawed frog Hymenochirus boettgeri (Tornier, 1896) has led to identification of five structurally related peptides with broad-spectrum antimicrobial activity. Hymenochirin-1B (IKLSPETKDNLKKVLKGAIKGAIAVAKMV.NH(2)) is C-terminally α-amidated whereas hymenochirins-2B-5B have the general structure XKIPX(2)VKDTLKKVAKGX(2)SX(2)AGAX(3).COOH. Hymenochirin-3B (IKIPAVVKDTLKKVAKGVLSAVAGALTQ) was the most abundant peptide in the secretions. The hymenochirins show very low structural similarity with the antimicrobial peptides isolated from skin secretions of Silurana tropicalis and Xenopus laevis consistent with the proposed ancient divergence of the Pipinae and Xenopodinae. Synthetic replicates of hymenochirin-1B-4B inhibit the growth of Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus (MIC in the range 10-40 μM) and Candida albicans (MIC=80 μM). The peptides display relatively weak hemolytic activity against human erythrocytes (LC(50) in the range 160 to >300 μM).

  • Host-defense peptides from skin secretions of the tetraploid frogs Xenopus petersii and Xenopus pygmaeus, and the octoploid frog Xenopus lenduensis (Pipidae)
    Peptides, 2011
    Co-Authors: Jay D. King, Milena Mechkarska, Laurent Coquet, Hubert Vaudry, Thierry Jouenne, Jérôme Leprince, Koji Takada, J. Michael Conlon
    Abstract:

    Abstract Peptidomic analysis of norepinephrine-stimulated skin secretions led to the identification of host-defense peptides belonging to the magainin, peptide glycine-leucine-amide (PGLa), and caerulein precursor fragment (CPF) families from the tetraploid frogs, Xenopus petersii (Peters’ clawed frog) and Xenopus pygmaeus (Bouchia clawed frog), and the octoploid frog Xenopus lenduensis (Lendu Plateau clawed frog). Xenopsin-precursor fragment (XPF) peptides were not detected. The primary structures of the antimicrobial peptides from X. petersii demonstrate a close, but not conspecific relationship, with Xenopus laevis whereas the X. pygmaeus peptides show appreciable variation from previously characterized orthologs from other Xenopus species. Polyploidization events within the Xenopodinae ( Silurana  +  Xenopus ) are associated with extensive gene silencing (nonfunctionization) but unexpectedly the full complement of four PGLa paralogs were isolated from X. lenduendis secretions. Consistent with previous data, the CPF peptides showed the highest growth-inhibitory activity against bacteria with CPF-PG1 (GFGSLLGKALKIGTNLL.NH 2 ) from X. pygmaeus combining high antimicrobial potency against Staphylococcus aureus (MIC = 6 μM) with relatively low hemolytic activity (LC 50  = 145 μM).

Ben J. Evans - One of the best experts on this subject based on the ideXlab platform.

  • Internal morphology of subgenera Silurana and Xenopus.
    2015
    Co-Authors: Ben J. Evans, Timothy F. Carter, Eli Greenbaum, Václav Gvoždík, Darcy B. Kelley, Patrick J. Mclaughlin, Olivier S. G. Pauwels, Daniel M. Portik, Edward L. Stanley, Richard C. Tinsley
    Abstract:

    Comparison of osteology of subgenera Xenopus (left, holotype specimen of Xenopus amieti, MHNG 2030.80 and Silurana (right, X. calcaratus, CAS 207759). Differences include (a) paired nasal bones in subgenus Silurana but not subgenus Xenopus, (b) absence of the vomer bones in the palate of subgenus Silurana but not subgenus Xenopus and (c) fusion of the first two presacral vertebrae in subgenus Silurana but not subgenus Xenopus.

  • External morphology of subgenera Silurana and Xenopus.
    2015
    Co-Authors: Ben J. Evans, Timothy F. Carter, Eli Greenbaum, Václav Gvoždík, Darcy B. Kelley, Patrick J. Mclaughlin, Olivier S. G. Pauwels, Daniel M. Portik, Edward L. Stanley, Richard C. Tinsley
    Abstract:

    Comparison of external morphology of subgenera Xenopus (right, specimen of X. victorianus CAS 250836 [DCB-202]) and Silurana (left, X. calcaratus CAS 207759) including in Silurana rougher skin, relatively smaller eyes, relatively shorter subocular tentacle (in comparison to sympatric Xenopus species), and relatively less of eye covered by lower eyelid (top), relatively shorter feet (middle), and ventrally fused cloacal lobes, claw on prehallux, and lack of skin ridge on first pedal digit from the prehallus (bottom).

  • MicroCT scans of skulls of two tetraploids in subgenus Silurana and two dodecaploid in subgenus Xenopus.
    2015
    Co-Authors: Ben J. Evans, Timothy F. Carter, Eli Greenbaum, Václav Gvoždík, Darcy B. Kelley, Patrick J. Mclaughlin, Olivier S. G. Pauwels, Daniel M. Portik, Edward L. Stanley, Richard C. Tinsley
    Abstract:

    Dorsal view is on the left and ventral view is on the right, including the lectotype specimen of Xenopus (Silurana) calcaratus (ZMB 8255A) from Cameroon and a specimen from Bioko Island (CAS 207759), holotype of X. (S.) mellotropicalis (NCSM 76797), and the holotypes of the new dodecaploid species from subgenus Xenopus: X. eysoole (MCZ A-138016) and X. kobeli (MCZ A-148037). The type specimen of X. calcaratus was preserved with its mouth ajar.

  • Summary phylogeny.
    2015
    Co-Authors: Ben J. Evans, Timothy F. Carter, Eli Greenbaum, Václav Gvoždík, Darcy B. Kelley, Patrick J. Mclaughlin, Olivier S. G. Pauwels, Daniel M. Portik, Edward L. Stanley, Richard C. Tinsley
    Abstract:

    A summary phylogeny inferred by comparing the mitochondrial and autosomal gene trees depicted in Figs 1 and 2. New and resurrected species described here are in red. S, A, L, and M refer to subgenus Silurana, and the amieti, laevis, and muelleri species groups within subgenus Xenopus respectively. Dotted lines indicate paternal ancestral lineages. Circles over internal nodes indicate allopolyploidization events; shapes on branch tips indicate ploidy of extant species; colored next to these shapes circles indicate call type inferred from this study and Tobias et al. [42]. Letters over red dots refer to ancestors whose homeologous lineages are labled in Fig 2. Daggers indicate lost ancestors, including up to three diploid species (assuming allotetraploidization in subgenus Xenopus) and at least three tetraploid ancestors (A, B, and C).

  • Genomic Dynamics of Transposable Elements in the Western Clawed Frog (Silurana tropicalis)
    Genome biology and evolution, 2013
    Co-Authors: Jiangshan Jane Shen, Frédéric J J Chain, Adam J Bewick, Jonathan Dushoff, Ben J. Evans
    Abstract:

    Transposable elements (TEs) are repetitive DNA sequences that can make new copies of themselves that are inserted elsewhere in a host genome. The abundance and distributions of TEs vary considerably among phylogenetically diverse hosts. With the aim of exploring the basis of this variation, we evaluated correlations between several genomic variables and the presence of TEs and non-TE repeats in the complete genome sequence of the Western clawed frog (Silurana tropicalis). This analysis reveals patterns of TE insertion consistent with gene disruption but not with the insertional preference model. Analysis of non-TE repeats recovered unique features of their genome-wide distribution when compared with TE repeats, including no strong correlation with exons and a particularly strong negative correlation with GC content. We also collected polymorphism data from 25 TE insertion sites in 19 wild-caught S. tropicalis individuals. DNA transposon insertions were fixed at eight of nine sites and at a high frequency at one of nine, whereas insertions of long terminal repeat (LTR) and non-LTR retrotransposons were fixed at only 4 of 16 sites and at low frequency at 12 of 16. A maximum likelihood model failed to attribute these differences in insertion frequencies to variation in selection pressure on different classes of TE, opening the possibility that other phenomena such as variation in rates of replication or duration of residence in the genome could play a role. Taken together, these results identify factors that sculpt heterogeneity in TE distribution in S. tropicalis and illustrate that genomic dynamics differ markedly among TE classes and between TE and non-TE repeats.

Jay D. King - One of the best experts on this subject based on the ideXlab platform.

  • Host-defense peptides in skin secretions of the tetraploid frog Silurana epitropicalis with potent activity against methicillin-resistant Staphylococcus aureus (MRSA).
    Peptides, 2012
    Co-Authors: J. Michael Conlon, Manju Prajeep, Agnes Sonnevend, Milena Mechkarska, Laurent Coquet, Hubert Vaudry, Thierry Jouenne, Jérôme Leprince, Jay D. King
    Abstract:

    Abstract A putative genome duplication event within the Silurana lineage has given rise to the tetraploid Cameroon clawed frog Silurana epitropicalis (Fischberg, Colombelli, and Picard, 1982). Peptidomic analysis of norepinephrine-stimulated skin secretions of S. epitropicalis led to identification of 10 peptides with varying degrees of growth-inhibitory activity against Escherichia coli and Staphylococcus aureus . Structural characterization identified the peptides as belonging to the magainin family (magainin-SE1), the caerulein-precursor fragment family (CPF-SE1, -SE2 and -SE3), the xenopsin-precursor fragment family (XPF-SE1, SE-2, SE-3 and -SE4), and the peptide glycine-leucine-amide family (PGLa-SE1 and -SE2). In addition, peptide phenylalanine-glutamine-amide (FLGALLGPLMNLLQ·NH 2 ) was isolated from the secretions that lacked antimicrobial activity. Comparison of the multiplicity of orthologous peptides in S. epitropicalis and the diploid Silurana tropicalis indicates that extensive nonfunctionalization (deletion or silencing) of antimicrobial peptide genes has occurred after polyploidization in the Silurana lineage, as in the Xenopus lineage. CPF-SE2 (GFLGPLLKLGLKGAAKLLPQLLPSRQQ; MIC = 2.5 μM) and CPF-SE3 (GFLGSLLKTGLKVGSNLL·NH 2 ; MIC = 5 μM) showed potent growth-inhibitory activity against a range of clinical isolates of methicillin-resistant S. aureus (MRSA). Their utility as systemic anti-infective drugs is limited by significant hemolytic activity against human erythrocytes (LC 50  = 50 μM for CPF-SE2 and 220 μM for CPF-SE3) but the peptides may find application as topical agents in treatment of MRSA skin infections and decolonization of MRSA carriers.

  • Host-defense peptides from skin secretions of the tetraploid frogs Xenopus petersii and Xenopus pygmaeus, and the octoploid frog Xenopus lenduensis (Pipidae)
    Peptides, 2011
    Co-Authors: Jay D. King, Milena Mechkarska, Laurent Coquet, Hubert Vaudry, Thierry Jouenne, Jérôme Leprince, Koji Takada, J. Michael Conlon
    Abstract:

    Abstract Peptidomic analysis of norepinephrine-stimulated skin secretions led to the identification of host-defense peptides belonging to the magainin, peptide glycine-leucine-amide (PGLa), and caerulein precursor fragment (CPF) families from the tetraploid frogs, Xenopus petersii (Peters’ clawed frog) and Xenopus pygmaeus (Bouchia clawed frog), and the octoploid frog Xenopus lenduensis (Lendu Plateau clawed frog). Xenopsin-precursor fragment (XPF) peptides were not detected. The primary structures of the antimicrobial peptides from X. petersii demonstrate a close, but not conspecific relationship, with Xenopus laevis whereas the X. pygmaeus peptides show appreciable variation from previously characterized orthologs from other Xenopus species. Polyploidization events within the Xenopodinae ( Silurana  +  Xenopus ) are associated with extensive gene silencing (nonfunctionization) but unexpectedly the full complement of four PGLa paralogs were isolated from X. lenduendis secretions. Consistent with previous data, the CPF peptides showed the highest growth-inhibitory activity against bacteria with CPF-PG1 (GFGSLLGKALKIGTNLL.NH 2 ) from X. pygmaeus combining high antimicrobial potency against Staphylococcus aureus (MIC = 6 μM) with relatively low hemolytic activity (LC 50  = 145 μM).

  • Host-defense peptides in skin secretions of African clawed frogs (Xenopodinae, Pipidae).
    General and Comparative Endocrinology, 2011
    Co-Authors: J. Michael Conlon, Milena Mechkarska, Jay D. King
    Abstract:

    Abstract African clawed frogs of the Xenopodinae ( Xenopus  +  Silurana ) constitute a well-defined system in which to study the evolutionary trajectory of duplicated genes and are a source of antimicrobial peptides with therapeutic potential. Allopolyploidization events within the Xenopodinae have given rise to tetraploid, octoploid, and dodecaploid species. The primary structures and distributions of host-defense peptides from the tetraploid frogs Xenopus borealis , Xenopus clivii , Xenopus laevis , Xenopus muelleri , “X. muelleri West”, and Xenopus petersii may be compared with those from the octoploid frogs Xenopus amieti and X . andrei . Similarly, components in skin secretions from the diploid frog Silurana tropicalis may be compared with those from the tetraploid frog Silurana paratropicalis . All Xenopus antimicrobial peptides may be classified in the magainin, peptide glycine-leucine-amide (PGLa), caerulein-precursor fragment (CPF), and xenopsin-precursor fragment (XPF) families. However, the numbers of paralogs from the octoploid frogs were not significantly greater than the corresponding numbers from the tetraploid frogs. Magainins were not identified in skin secretions of Silurana frogs and the multiplicity of the PGLa, CPF, and XPF peptides from S . paratropicalis was not greater than that of S . tropicalis . The data indicate, therefore, that nonfunctionalization (gene silencing) has been the most common fate of antimicrobial peptide genes following polyploidization. While some duplicated gene products retain high antimicrobial potency (subfunctionalization), the very low activity of others suggests that they may be evolving towards a new biological role (neofunctionalization). CPF-AM1 and PGLa-AM1 from X . amieti show potential for development into anti-infective agents for use against antibiotic-resistant Gram-negative bacteria.