Publications

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quercetin, morin, luteolin, and phloretin are dietary flavonoid inhibitors of monocarboxylate transporter 6.monocarboxylate transporter 6 (mct6; slc16a5) has been recognized for its role as a xenobiotic transporter, with characterized substrates probenecid, bumetanide, and nateglinide. to date, the impact of commonly ingested dietary compounds on mct6 function has not been investigated, and therefore, the objective of this study was to evaluate a variety of flavonoids for their potential mct6-specific interactions. flavonoids are a large group of polyphenolic phytochemicals found in commonly consumed ...201728513167
the nodulin 26-like intrinsic membrane protein osnip3;2 is involved in arsenite uptake by lateral roots in rice.previous studies have shown that the nodulin 26-like intrinsic membrane protein (nip) lsi1 (osnip2;1) is involved in arsenite [as(iii)] uptake in rice (oryza sativa). however, the role of other rice nips in as(iii) accumulation in planta remains unknown. in the present study, we investigated the role osnip3;2 in as(iii) uptake in rice. when expressed in xenopus laevis oocytes, osnip3;2 showed a high transport activity for as(iii). quantitative real-time rt-pcr showed that the expression of osnip ...201728505352
co-accumulation of cis-regulatory and coding mutations during the pseudogenization of the xenopus laevis homoeologs six6.l and six6.s.common models for the evolution of duplicated genes after genome duplication are subfunctionalization, neofunctionalization, and pseudogenization. although the crucial roles of cis-regulatory mutations in subfunctionalization are well-documented, their involvement in pseudogenization and/or neofunctionalization remains unclear. we addressed this issue by investigating the evolution of duplicated homeobox genes, six6.l and six6.s, in the allotetraploid frog xenopus laevis. based on a comparative ...201728501477
identification of α7 nicotinic acetylcholine receptor silent agonists based on the spirocyclic quinuclidine-δ2 -isoxazoline scaffold: synthesis and electrophysiological evaluation.compound 11 (3-(benzyloxy)-1'-methyl-1'-azonia-4h-1'-azaspiro[isoxazole-5,3'-bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic ligands as a suitable model compound for the design of new silent agonists of α7 nicotinic acetylcholine receptors (nachrs). silent agonists evoke little or no channel activation but can induce the α7 desensitized ds state, which is sensitive to a type ii positive allosteric modulator, such as pnu-120596. introduction of meta substituents into t ...201728494140
opposing effects of valproic acid treatment mediated by histone deacetylase inhibitor activity in four transgenic x. laevis models of retinitis pigmentosa.retinitis pigmentosa (rp) is an inherited retinal degeneration (rd) that leads to blindness for which no treatment is available. rp is frequently caused by mutations in rhodopsin; in some animal models, rd is exacerbated by light. valproic acid (vpa) is a proposed treatment for rp and other neurodegenerative disorders, with a phase ii trial for rp under way. however, the therapeutic mechanism is unclear, with minimal research supporting its use in rp. we investigated the effects of vpa on xenopu ...201728490005
a magnesium transporter osmgt1 plays a critical role in salt tolerance in rice.salt stress is one of the major factors limiting rice (oryza sativa) production globally. although several transporters involved in salt tolerance have been identified in rice, the mechanisms regulating their transport activity are still poorly understood. here, we show evidence that a rice mg transporter osmgt1 is required for salt tolerance probably by regulating transport activity of oshkt1;5, a key transporter for the removal of na+ from the xylem sap at the root mature zone. knockout of osm ...201728487477
hplc-based activity profiling for gabaa receptor modulators in extracts: validation of an approach utilizing a larval zebrafish locomotor assay.gamma-aminobutyric acid type a (gabaa) receptors are major inhibitory neurotransmitter receptors in the central nervous system and a target for numerous clinically important drugs used to treat anxiety, insomnia, and epilepsy. a series of allosteric gabaa receptor agonists was identified previously with the aid of hplc-based activity profiling, whereby activity was tracked with an electrophysiological assay in xenopus laevis oocytes. to accelerate the discovery process, an approach has been esta ...201728485933
the role of nitric oxide during embryonic epidermis development of xenopus laevis.nitric oxide (no) is a potent radical molecule that participates in various biological processes such as vasodilation, cell proliferation, immune response and neurotransmission. no mainly activates soluble guanylate cyclase, leading to cgmp production and activation of protein kinase g and its downstream targets. here we report the essential role of no during embryonic epidermis development. xenopus embryonic epidermis has become a useful model reflecting human epithelial tissue composition. the ...201728483981
mechanosensory stimulation evokes acute concussion-like behavior by activating girks coupled to muscarinic receptors in a simple vertebrate.most vertebrates show concussion responses when their heads are hit suddenly by heavy objects. previous studies have focused on the direct physical injuries to the neural tissue caused by the concussive blow. we study a similar behavior in a simple vertebrate, the xenopus laevis tadpole. we find that concussion-like behavior can be reliably induced by the mechanosensory stimulation of the head skin without direct physical impacts on the brain. head skin stimulation activates a cholinergic pathwa ...201728462392
functional assessment of the nmda receptor variant glun2a r586k.background: the n-methyl-d-aspartate receptor (nmdar) is an ionotropic glutamate receptor that has important roles in synaptogenesis, synaptic transmission, and synaptic plasticity. recently, a large number of rare genetic variants have been found in nmdar subunits in people with neurodevelopmental disorders, and also in healthy individuals. one such is the glun2ar586k variant, found in a person with intellectual disability. identifying the functional consequences, if any, of such variants allow ...201728459106
editorial: the xenopus laevis genome. 201728457863
role of micrornas in zygotic genome activation: modulation of mrna during embryogenesis.a fundamental process occurring during early development is the zygotic genome activation, i.e., the initiation of transcription from the embryonic genome. before that step, cellular processes in the developing embryo are dictated by transcripts produced by the maternal genome and accumulated in the egg during oogenesis. the maternal-to-zygotic transition (mzt) involves both the clearance of maternal rnas and the initiation of transcription of the embryonic genome and is a tightly regulated proc ...201728456956
analysis of active transport by fluorescence recovery after photobleaching.fluorescence recovery after photobleaching (frap) is a well-established experimental technique to study binding and diffusion of molecules in cells. although a large number of analytical and numerical models have been developed to extract binding and diffusion rates from frap recovery curves, active transport of molecules is typically not included in the existing models that are used to estimate these rates. here we present a validated numerical method for estimating diffusion, binding/unbinding ...201728445762
effect of triclosan on anuran development and growth in a larval amphibian growth and development assay.a larval amphibian growth and development assay was performed to evaluate the potential effects of environmentally-relevant concentrations of triclosan (tcs) on amphibian development and growth. xenopus laevis were exposed to tcs 0.0 (control), 6.3, 12.5 and 25.0 μg l-1 (estimated maximum tolerable concentration) until 10 weeks post-metamorphosis. at median metamorphosis time (nieuwkoop and faber stage 62), five larvae per replicate were collected for snout-vent length, hind limb length and body ...201728436085
daphnia magna and xenopus laevis as in vivo models to probe toxicity and uptake of quantum dots functionalized with gh625.the use of quantum dots (qds) for nanomedicine is hampered by their potential toxicologic effects and difficulties with delivery into the cell interior. we accomplished an in vivo study exploiting daphnia magna and xenopus laevis to evaluate both toxicity and uptake of qds coated with the membranotropic peptide gh625 derived from the glycoprotein h of herpes simplex virus and widely used for drug delivery studies. we evaluated and compared the effects of qds and gh625-qds on the survival, uptake ...201728435254
in situ microprobe single-cell capillary electrophoresis mass spectrometry: metabolic reorganization in single differentiating cells in the live vertebrate (xenopus laevis) embryo.knowledge of single-cell metabolism would provide a powerful look into cell activity changes as cells differentiate to all the tissues of the vertebrate embryo. however, single-cell mass spectrometry technologies have not yet been made compatible with complex three-dimensional changes and rapidly decreasing cell sizes during early development of the embryo. here, we bridge this technological gap by integrating capillary microsampling, microscale metabolite extraction, and capillary electrophores ...201728434226
endocrine disruption by environmental gestagens in amphibians - a short review supported by new in vitro data using gonads of xenopus laevis.endocrine disruption caused by various anthropogenic compounds is of persisting concern, especially for aquatic wildlife, because surface waters are the main sink of these so-called endocrine disruptors (ed). in the past, research focused on (anti)estrogenic, (anti)androgenic, and (anti)thyroidal substances, affecting primarily reproduction and development in vertebrates; however, other endocrine systems might be also targeted by ed. environmental gestagens, including natural progestogens (e.g. ...201728431277
frizzled 3 acts upstream of alcam during embryonic eye development.formation of a functional eye during vertebrate embryogenesis requires different processes such as cell differentiation, cell migration, cell-cell interactions as well as intracellular signalling processes. it was previously shown that the non-canonical wnt receptor frizzled 3 (fzd3) is required for proper eye formation, however, the underlying mechanism is poorly understood. here we demonstrate that loss of fzd3 induces severe malformations of the developing eye and that this defect is phenocop ...201728427856
xenopus egg extract: a powerful tool to study genome maintenance mechanisms.dna repair pathways are crucial to maintain the integrity of our genome and prevent genetic diseases such as cancer. there are many different types of dna damage and specific dna repair mechanisms have evolved to deal with these lesions. in addition to these repair pathways there is an extensive signaling network that regulates processes important for repair, such as cell cycle control and transcription. despite extensive research, dna damage repair and signaling are not fully understood. in vit ...201728427716
characterization of microtubule buckling in living cells.microtubules are filamentous biopolymers involved in essential biological processes. they form key structures in eukaryotic cells, and thus it is very important to determine the mechanisms involved in the formation and maintenance of the microtubule network. microtubule bucklings are transient and localized events commonly observed in living cells and characterized by a fast bending and its posterior relaxation. active forces provided by molecular motors have been indicated as responsible for mo ...201728424847
use of xenopus frogs to study renal development/repair.the xenopus genus includes several members of aquatic frogs native to africa but is perhaps best known for the species xenopus laevis and xenopus tropicalis. these species were popularized as model organisms from as early as the 1800s and have been instrumental in expanding several biological fields including cell biology, environmental toxicology, regenerative biology, and developmental biology. in fact, much of what we know about the formation and maturation of the vertebrate renal system has ...201728409343
asymmetries in cell division, cell size, and furrowing in the xenopus laevis embryo.asymmetric cell divisions produce two daughter cells with distinct fate. during embryogenesis, this mechanism is fundamental to build tissues and organs because it generates cell diversity. in adults, it remains crucial to maintain stem cells. the enthusiasm for asymmetric cell division is not only motivated by the beauty of the mechanism and the fundamental questions it raises, but has also very pragmatic reasons. indeed, misregulation of asymmetric cell divisions is believed to have dramatic c ...201728409308
asymmetric localization and distribution of factors determining cell fate during early development of xenopus laevis.asymmetric division is a property of eukaryotic cells that is fundamental to the formation of higher life forms. despite its importance, the mechanism behind it remains elusive. asymmetry in the cell is induced by polarization of cell fate determinants that become unevenly distributed among progeny cells. so far dozens of determinants have been identified. xenopus laevis is an ideal system to study asymmetric cell division during early development, because of the huge size of its oocytes and ear ...201728409307
chromosomal passenger complex hydrodynamics suggests chaperoning of the inactive state by nucleoplasmin/nucleophosmin.the chromosomal passenger complex (cpc) is a conserved, essential regulator of cell division. as such, significant anti-cancer drug development efforts have been focused on targeting it, most notably by inhibiting its aurkb kinase subunit. the cpc is activated by aurkb-catalyzed autophosphorylation on multiple subunits, but how this regulates cpc interactions with other mitotic proteins remains unclear. we investigated the hydrodynamic behavior of the cpc in xenopus laevis egg cytosol using sucr ...201728404751
masculinization-related genes and cell-mass structures during early gonadal differentiation in the african clawed frog xenopus laevis.the african clawed frog xenopus laevis has a female heterogametic zz/zw-type sex-determining system. we previously discovered a w-linked female sex-determining gene dm-w that is involved in ovary formation, probably through the up-regulation of the estrogen synthesis genes cyp19a1 and foxl2. we also reported that a unique "mass-in-line structure", which disappears from zz gonads during early testicular development, might serve as the basis for ovary differentiation in zw gonads. however, the mol ...201728397603
pattern of neurogenesis and identification of neuronal progenitor subtypes during pallial development in xenopus laevis.the complexity of the pallium during evolution has increased dramatically in many different respects. the highest level of complexity is found in mammals, where most of the pallium (cortex) shows a layered organization and neurons are generated during development following an inside-out order, a sequence not observed in other amniotes (birds and reptiles). species-differences may be related to major neurogenetic events, from the neural progenitors that divide and produce all pallial cells. in ma ...201728396626
the mgcracgap sxip motif tethers centralspindlin to microtubule plus ends in xenopus laevis.centralspindlin, a complex of the kinesin-6-family member mklp1 and mgcracgap (also known as kif23 and racgap1, respectively), is required for cytokinesis and cell-cell junctions. during anaphase, centralspindlin accumulates at overlapping central spindle microtubules and directs contractile ring formation by recruiting the gef ect2 to the cell equator to activate rhoa. we found that mgcracgap localized to the plus ends of equatorial astral microtubules during cytokinesis in xenopus laevis embry ...201728389580
clinical and genetic spectrum of bartter syndrome type 3.bartter syndrome type 3 is a clinically heterogeneous hereditary salt-losing tubulopathy caused by mutations of the chloride voltage-gated channel kb gene (clcnkb), which encodes the clc-kb chloride channel involved in nacl reabsorption in the renal tubule. to study phenotype/genotype correlations, we performed genetic analyses by direct sequencing and multiplex ligation-dependent probe amplification and retrospectively analyzed medical charts for 115 patients with clcnkb mutations. functional a ...201728381550
a dominant mutation in nuclear receptor interacting protein 1 causes urinary tract malformations via dysregulation of retinoic acid signaling.congenital anomalies of the kidney and urinary tract (cakut) are the most common cause of ckd in the first three decades of life. however, for most patients with cakut, the causative mutation remains unknown. we identified a kindred with an autosomal dominant form of cakut. by whole-exome sequencing, we identified a heterozygous truncating mutation (c.279delg, p.trp93fs*) of the nuclear receptor interacting protein 1 gene (nrip1) in all seven affected members. nrip1 encodes a nuclear receptor tr ...201728381549
multiple origins of embryonic and tadpole myeloid cells in xenopus laevis.rabbit anti-serum against a myeloid-cell-specific peroxidase (mpo) of xenopus laevis was generated to identify myeloid cells in adult and larval animals. smears of blood samples from adult hematopoietic organs were co-stained with mpo and with xl-2, a mouse monoclonal antibody against a leukocyte common antigen. lymphocytes found in the thymus and spleen were xl-2+mpo- and granulocytes found in peripheral blood cells and the spleen were xl-2+mpo+, indicating that double-staining with these two a ...201728374149
upregulation of matrix metalloproteinase triggers transdifferentiation of retinal pigmented epithelial cells in xenopus laevis: a link between inflammatory response and regeneration.in adult xenopus eyes, when the whole retina is removed, retinal pigmented epithelial (rpe) cells become activated to be retinal stem cells and regenerate the whole retina. in the present study, using a tissue culture model, it was examined whether upregulation of matrix metalloproteinases (mmps) triggers retinal regeneration. soon after retinal removal, xmmp9 and xmmp18 were strongly upregulated in the tissues of the rpe and the choroid. in the culture, mmp expression in the rpe cells correspon ...201728371543
population-specific resequencing associates the atp-binding cassette subfamily c member 4 gene with gout in new zealand māori and pacific men.there is no evidence for a genetic association between organic anion transporters 1-3 (slc22a6, slc22a7, and slc22a8) and multidrug resistance protein 4 (mrp4; encoded by abcc4) with the levels of serum urate or gout. the māori and pacific (polynesian) population of new zealand has the highest prevalence of gout worldwide. the aim of this study was to determine whether any polynesian population-specific genetic variants in slc22a6-8 and abcc4 are associated with gout.201728371506
interaction and developmental activation of two neuroendocrine systems that regulate light-mediated skin pigmentation.lower vertebrates use rapid light-regulated changes in skin colour for camouflage (background adaptation) or during circadian variation in irradiance levels. two neuroendocrine systems, the eye/alpha-melanocyte-stimulating hormone (α-msh) and the pineal complex/melatonin circuits, regulate the process through their respective dispersion and aggregation of pigment granules (melanosomes) in skin melanophores. during development, xenopus laevis tadpoles raised on a black background or in the dark p ...201728371026
cul-2lrr-1 and ubxn-3 drive replisome disassembly during dna replication termination and mitosis.replisome disassembly is the final step of dna replication in eukaryotes, involving the ubiquitylation and cdc48-dependent dissolution of the cmg helicase (cdc45-mcm-gins). using caenorhabditis elegans early embryos and xenopus laevis egg extracts, we show that the e3 ligase cul-2lrr-1 associates with the replisome and drives ubiquitylation and disassembly of cmg, together with the cdc-48 cofactors ufd-1 and npl-4. removal of cmg from chromatin in frog egg extracts requires cul2 neddylation, and ...201728368371
xenopus metamorphosis as a model to study thyroid hormone receptor function during vertebrate developmental transitions.a hormone-dependent developmental transition from aquatic to terrestrial existence occurs in all tetrapod vertebrates, such as birth, hatching, and metamorphosis. thyroid hormones (th) and their receptors (trs) are key players in the tissue transformations comprising vertebrate developmental transitions. the african clawed frog, xenopus, is a premier model for the role of trs in developmental transitions because of the numerous and dramatic th-dependent tissue transformations during metamorphosi ...201728363743
asymmetrically reduced expression of hand1 homeologs involving a single nucleotide substitution in a cis-regulatory element.during vertebrate evolution, whole genome duplications resulted in a number of duplicated genes, some of which eventually changed their expression patterns and/or levels via alteration of cis-regulatory sequences. however, the initial process involved in such cis-regulatory changes remains unclear. therefore, we investigated this process by analyzing the duplicated hand1 genes of xenopus laevis (hand1.l and hand1.s), which were generated by allotetraploidization 17-18 million years ago, and comp ...201728359808
the heterochronic gene lin28 regulates amphibian metamorphosis through disturbance of thyroid hormone function.metamorphosis is a classic example of developmental transition, which involves important morphological and physiological changes that prepare the organism for the adult life. it has been very well established that amphibian metamorphosis is mainly controlled by thyroid hormone (th). here, we show that the heterochronic gene lin28 is downregulated during xenopus laevis metamorphosis. lin28 overexpression before activation of th signaling delays metamorphosis and inhibits the expression of th targ ...201728359807
paxillin and embryonic polyadenylation binding protein (epabp) engage to regulate androgen-dependent xenopus laevis oocyte maturation - a model of kinase-dependent regulation of protein expression.steroid-triggered xenopus laevis oocyte maturation is an elegant physiologic model of nongenomic steroid signaling, as it proceeds completely independent of transcription. we previously demonstrated that androgens are the main physiologic stimulator of oocyte maturation in xenopus oocytes, and that the adaptor protein paxillin plays a crucial role in mediating this process through a positive feedback loop in which paxillin first enhances mos protein translation, ensued by erk2 activation and erk ...201728359799
pkc-mediated phosphorylation of nuclear lamins at a single serine residue regulates interphase nuclear size in xenopus and mammalian cells.how nuclear size is regulated is a fundamental cell-biological question with relevance to cancers, which often exhibit enlarged nuclei. we previously reported that conventional protein kinase c (cpkc) contributes to nuclear size reductions that occur during early xenopus development. here we report that pkc-mediated phosphorylation of lamin b3 (lb3) contributes to this mechanism of nuclear size regulation. by mapping pkc phosphorylation sites on lb3 and testing the effects of phosphomutants in x ...201728356420
spemann organizer transcriptome induction by early beta-catenin, wnt, nodal, and siamois signals in xenopus laevis.the earliest event in xenopus development is the dorsal accumulation of nuclear β-catenin under the influence of cytoplasmic determinants displaced by fertilization. in this study, a genome-wide approach was used to examine transcription of the 43,673 genes annotated in the xenopus laevis genome under a variety of conditions that inhibit or promote formation of the spemann organizer signaling center. loss of function of β-catenin with antisense morpholinos reproducibly reduced the expression of ...201728348214
osptr7 (osnpf8.1), a putative peptide transporter in rice, is involved in dimethylarsenate accumulation in rice grain.rice (oryza sativa) is a major dietary source of arsenic (as) for the population consuming rice as their staple food. rice grain contains both inorganic as and methylated as species, especially dimethyarsinate (dma). dma is highly mobile in long-distance translocation in plants, but the underlying mechanism remains unknown. in the present study, we showed that osptr7 (osnpf8.1), a putative peptide transporter in rice, was permeable to dma in xenopus laevis oocytes. transient expression of the os ...201728340032
glycans in the intestinal peptide transporter pept1 contribute to function and protect from proteolysis.despite the fact that many membrane proteins carry extracellular glycans, little is known about whether the glycan chains also affect protein function. we recently demonstrated that the proton-coupled oligopeptide transporter 1 (pept1) in the intestine is glycosylated at six asparagine residues (n50, n406, n439, n510, n515, and n532). mutagenesis-induced disruption of the individual n-glycosylation site n50, which is highly conserved among mammals, was detected to significantly enhance the pept1 ...201728336547
the modulation of two motor behaviors by persistent sodium currents in xenopus laevis tadpoles.persistent sodium currents (inap) are common in neuronal circuitries and have been implicated in several diseases, such as amyotrophic lateral sclerosis (als) and epilepsy. however, the role of inap in the regulation of specific behaviors is still poorly understood. in this study we have characterized inap and investigated its role in the swimming and struggling behavior of xenopus tadpoles. inap was identified in three groups of neurons, namely, sensory rohon-beard neurons (rb neurons), descend ...201728331009
actomyosin-generated tension on cadherin is similar between dividing and non-dividing epithelial cells in early xenopus laevis embryos.epithelia represent a unique situation where polarized cells must maintain sufficiently strong cell-cell contacts to guarantee the epithelial integrity indispensable for barrier functions. nevertheless, epithelia must also keep sufficient plasticity which is crucial during development and morphogenesis. adherens junctions and mechanical forces produced by the actomyosin cytoskeleton are major players for epithelial integrity maintenance and plasticity regulations. to understand how the epitheliu ...201728327558
direct regulation of histidine ammonia-lyase 2 gene by thyroid hormone in the developing adult intestinal stem cells.most vertebrate organs use adult stem cells to maintain homeostasis and ensure proper repair when damaged. how such organ-specific stem cells are formed during vertebrate development is largely unexplored. we have been using the thyroid hormone (t3)-dependent amphibian metamorphosis to address this issue. early studies in xenopus laevis have shown that intestinal remodeling involves complete degeneration of the larval epithelium and de novo formation of adult stem cells through dedifferentiation ...201728323994
sall1 and sall4 repress pou5f3 family expression to allow neural patterning, differentiation, and morphogenesis in xenopus laevis.the embryonic precursor of the vertebrate central nervous system, the neural plate, is patterned along the anterior-posterior axis and shaped by morphogenetic movements early in development. we previously identified the genes sall1 and sall4, known regulators of pluripotency in other contexts, as transcriptional targets of developmental signaling pathways that regulate neural development. here, we demonstrate that these two genes are required for induction of posterior neural fates, the cell sha ...201728322736
teratogenic hazard of bpei-coated silver nanoparticles to xenopus laevis.silver nanoparticles (agnps) are among the most exploited antimicrobial agents and are used in many consumer products. size and surface reactivity are critical physico-chemical properties responsible for nps toxicity, and surface coatings, often used to functionalize or stabilize agnps, can influence their toxic profile and biocompatibility. in the current study the developmental toxicity of (1) negatively charged citrate-coated agnps (cit-agnps), (2) positively charged branched polyethylenimine ...201728318347
jak-stat pathway activation in response to spinal cord injury in regenerative and non-regenerative stages of xenopus laevis.xenopus laevis tadpoles can regenerate the spinal cord after injury but this capability is lost during metamorphosis. comparative studies between pre-metamorphic and metamorphic xenopus stages can aid towards understanding the molecular mechanisms of spinal cord regeneration. analysis of a previous transcriptome-wide study suggests that, in response to injury, the jak-stat pathway is differentially activated in regenerative and non-regenerative stages. we characterized the activation of the jak- ...201728316792
a cellular mechanism for inverse effectiveness in multisensory integration.to build a coherent view of the external world, an organism needs to integrate multiple types of sensory information from different sources, a process known as multisensory integration (msi). previously, we showed that the temporal dependence of msi in the optic tectum of xenopus laevis tadpoles is mediated by the network dynamics of the recruitment of local inhibition by sensory input (felch et al., 2016). this was one of the first cellular-level mechanisms described for msi. here, we expand th ...201728315524
novel short antimicrobial peptide isolated from xenopus laevis skin.a rich source of bioactive peptides, including a large number of antimicrobial peptides, has been found in amphibian skin. in this study, a novel short antimicrobial peptide was purified from xenopus laevis skin and characterised through reversed-phase high-performance liquid chromatography, edman degradation and matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. the peptide was composed of six amino acids with a sequence of dedlde and thus named x. laevis antibacteria ...201728299865
when size matters: transient receptor potential vanilloid 4 channel as a volume-sensor rather than an osmo-sensor.mammalian cells are frequently exposed to stressors causing volume changes. the transient receptor potential vanilloid 4 (trpv4) channel translates osmotic stress into ion flux. the molecular mechanism coupling osmolarity to trpv4 activation remains elusive. trpv4 responds to isosmolar cell swelling and osmolarity translated via different aquaporins. trpv4 functions as a volume-sensing ion channel irrespective of the origin of the cell swelling.201728295351
functional organization of vestibulo-ocular responses in abducens motoneurons.vestibulo-ocular reflexes (vors) are the dominating contributors to gaze stabilization in all vertebrates. during horizontal head movements, abducens motoneurons form the final element of the reflex arc that integrates visuovestibular inputs into temporally precise motor commands for the lateral rectus eye muscle. here, we studied a possible differentiation of abducens motoneurons into subtypes by evaluating their morphology, discharge properties, and synaptic pharmacology in semi-intact in vitr ...201728292832
transcriptomic insights into genetic diversity of protein-coding genes in x. laevis.we characterize the genetic diversity of xenopus laevis strains using rna-seq data and allele-specific analysis. this data provides a catalogue of coding variation, which can be used for improving the genomic sequence, as well as for better sequence alignment, probe design, and proteomic analysis. in addition, we paint a broad picture of the genetic landscape of the species by functionally annotating different classes of mutations with a well-established prediction tool (polyphen-2). further, we ...201728283406
persistent fibrosis, hypertrophy and sarcomere disorganisation after endoscopy-guided heart resection in adult xenopus.models of cardiac repair are needed to understand mechanisms underlying failure to regenerate in human cardiac tissue. such studies are currently dominated by the use of zebrafish and mice. remarkably, it is between these two evolutionary separated species that the adult cardiac regenerative capacity is thought to be lost, but causes of this difference remain largely unknown. amphibians, evolutionary positioned between these two models, are of particular interest to help fill this lack of knowle ...201728278282
xenmine: a genomic interaction tool for the xenopus community.the xenopus community has embraced recent advances in sequencing technology, resulting in the accumulation of numerous rna-seq and chip-seq datasets. however, easily accessing and comparing datasets generated by multiple laboratories is challenging. thus, we have created a central space to view, search and analyze data, providing essential information on gene expression changes and regulatory elements present in the genome. xenmine (www.xenmine.org) is a user-friendly website containing publishe ...201727157655
evaluating the teratogenicity of the selective ß3-adrenoceptor agonist, cl 316.243 hydrate by employing fetax (frog embryo teratogenesis assay).in this study, the frog embryo teratogenesis assay (fetax - xenopus) technique was employed to evaluate the potential teratogenicity of the selective ß-adrenoceptor (ar) agonist, cl 316.243. in this context, cl 316.243 was applied to the south african clawed frog (xenopus laevis) embryos. the media containing the cl 316.24-exposed embryos were monitored and changed/replaced once every 24 hours. using fetax, we determined the minimum concentrations to inhibit growth (mcig) for cl 316.243. the 96- ...201727063898
evaluation of microtransplantation of rat brain neurolemma into xenopus laevis oocytes as a technique to study the effect of neurotoxicants on endogenous voltage-sensitive ion channels.microtransplantation of mammalian brain neurolemma into the plasma membrane of xenopus oocytes is used to study ion channels in their native form as they appear in the central nervous system. use of microtransplanted neurolemma is advantageous for various reasons: tissue can be obtained from various sources and at different developmental stages; ion channels and receptors are present in their native configuration in their proper lipid environment along with appropriate auxiliary subunits; allowi ...201727063102
pharmacological characterization of histamine-gated chloride channels from the housefly musca domestica.the biogenic amine histamine (ha) is not only the neurotransmitter of photoreceptors but also has important roles in mechanosensory reception, temperature preference, sleep and olfactory processing in insects. two cdnas (mdhcla and mdhclb) that encode ha-gated chloride channel subunits (mdhcla and mdhclb) were cloned from the housefly musca domestica. the crnas were injected into xenopus laevis oocytes to examine the functions and pharmacological characteristics of mdhcla and mdhclb channels usi ...201727139242
expanding the genetic toolkit in xenopus: approaches and opportunities for human disease modeling.the amphibian model xenopus, has been used extensively over the past century to study multiple aspects of cell and developmental biology. xenopus offers advantages of a non-mammalian system, including high fecundity, external development, and simple housing requirements, with additional advantages of large embryos, highly conserved developmental processes, and close evolutionary relationship to higher vertebrates. there are two main species of xenopus used in biomedical research, xenopus laevis ...201727109192
genome-wide analysis of dorsal and ventral transcriptomes of the xenopus laevis gastrula.rna sequencing has allowed high-throughput screening of differential gene expression in many tissues and organisms. xenopus laevis is a classical embryological and cell-free extract model system, but its genomic sequence had been lacking due to difficulties arising from allotetraploidy. there is currently much excitement surrounding the release of the completed x. laevis genome (version 9.1) by the joint genome institute (jgi), which provides a platform for genome-wide studies. here we present a ...201727016259
xenopus genomic data and browser resources.the two species of xenopus most commonly used in biomedical research are the diploid xenopus (silurana) tropicalis and the tetraploid xenopus laevis. the x. tropicalis genome sequence has been available since 2010 and this year the x. laevis, genome from two distinct genetic backgrounds has been published. multiple genome assemblies available for both species and transcriptomic and epigenetic data sets are growing rapidly, all of which are available from a variety of web resources. this review d ...201727039265
generation of a xenopus laevis f1 albino j strain by genome editing and oocyte host-transfer.completion of the xenopus laevis genome sequence from inbred j strain animals has facilitated the generation of germline mutant x. laevis using targeted genome editing. in the last few years, numerous reports have demonstrated that talens are able to induce mutations in f0 xenopus embryos, but none has demonstrated germline transmission of such mutations in x. laevis. in this report we used the oocyte host-transfer method to generate mutations in both tyrosinase homeologs and found highly-penetr ...201726993591
xenopus: leaping forward in kidney organogenesis.while kidney donations stagnate, the number of people in need of kidney transplants continues to grow. although transplanting culture-grown organs is years away, pursuing the engineering of the kidney de novo is a valid means of closing the gap between the supply and demand of kidneys for transplantation. the structural organization of a mouse kidney is similar to that of humans. therefore, mice have traditionally served as the primary model system for the study of kidney development. the mouse ...201727099217
extinction of an introduced warm-climate alien species, xenopus laevis, by extreme weather events.invasive, non-native species represent a major threat to biodiversity worldwide. the african amphibian xenopus laevis is widely regarded as an invasive species and a threat to local faunas. populations originating at the western cape, south africa, have been introduced on four continents, mostly in areas with a similar mediterranean climate. some introduced populations are also established in cooler environments where persistence for many decades suggests a capacity for long-term adaptation. in ...201726430383
trrap is a central regulator of human multiciliated cell formation.the multiciliated cell (mcc) is an evolutionarily conserved cell type, which in vertebrates functions to promote directional fluid flow across epithelial tissues. in the conducting airway, mccs are generated by basal stem/progenitor cells and act in concert with secretory cells to perform mucociliary clearance to expel pathogens from the lung. studies in multiple systems, includingxenopus laevisepidermis, murine trachea, and zebrafish kidney, have uncovered a transcriptional network that regulat ...201829588376
embryonic lethality is not sufficient to explain hourglass-like conservation of vertebrate embryos.understanding the general trends in developmental changes during animal evolution, which are often associated with morphological diversification, has long been a central issue in evolutionary developmental biology. recent comparative transcriptomic studies revealed that gene expression profiles of mid-embryonic period tend to be more evolutionarily conserved than those in earlier or later periods. while the hourglass-like divergence of developmental processes has been demonstrated in a variety o ...201829568479
characterization of pax3 and sox10 transgenic xenopus laevis embryos as tools to study neural crest development.the neural crest is a multipotent population of cells that originates a variety of cell types. many animal models are used to study neural crest induction, migration and differentiation, with amphibians and birds being the most widely used systems. a major technological advance to study neural crest development in mouse, chick and zebrafish has been the generation of transgenic animals in which neural crest specific enhancers/promoters drive the expression of either fluorescent proteins for use ...201829522707
molecular and functional characterization of the gulf toadfish serotonin transporter (sert; slc6a4).the serotonin transporter (sert) functions in the uptake of the neurotransmitter serotonin (5-ht) from the extracellular milieu and is the molecular target of the selective serotonin reuptake inhibitors (ssris), a common group of antidepressants. the current study comprehensively assesses the sequence, tissue distribution, transport kinetics, and physiological function of a teleost sert. the 2,022-bp toadfish sert sequence encodes a protein of 673 amino acids, which shows 83% similarity to zebra ...201829487159
fam60al as a novel factor involved in reprogramming of somatic cell nuclear transfer in zebrafish (danio rerio).the main reason for abnormal development of cloned animals or embryos, and inefficient animal cloning, is a poor understanding of the reprogramming mechanism. to better comprehend reprogramming and subsequent generation of pluripotent stem cells, we must investigate factors related to reprogramming of somatic cells as nuclear donors. as we know,fam60al(family with sequence similarity 60, member a, like) is a coding gene only found in zebrafish and frog (xenopus laevis) among vertebrates. however ...201829483827
chemical screening using cell-freexenopusegg extract.most drug screening methods use purified proteins, cultured cells, and/or small model organisms such asxenopus, zebrafish, flies, or nematodes. these systems have proven successes in drug discovery, but they also have weaknesses. although purified cellular components allow for identification of compounds with activity against specific targets, such systems lack the complex biological interactions present in cellular and organismal screens. in vivo systems overcome these weaknesses, but the lack ...201829475996
expression of the adhesion g protein-coupled receptor a2 (adgra2) during xenopus laevis development.the adhesion g protein-coupled receptor a2 (adgra2) is a seven transmembrane receptor that has been described to be a regulator for angiogenesis in mice. furthermore, the zebrafish ouchless mutant is unable to develop dorsal root ganglia through a disrupted trafficking of adgra2. besides rna sequencing data, nothing is reported about adgra2 in the south african crawled frog xenopus laevis. in this study, we investigated for the first time the spatio-temporal expression of adgra2 during early xen ...201829462671
physiological effects of kdm5c on neural crest migration and eye formation during vertebrate development.lysine-specific histone demethylase 5c (kdm5c) belongs to the jumonji family of demethylases and is specific for the di- and tri-demethylation of lysine 4 residues on histone 3 (h3k4 me2/3). kdm5c is expressed in the brain and skeletal muscles of humans and is associated with various biologically significant processes. kdm5c is known to be associated with x-linked mental retardation and is also involved in the development of cancer. however, the developmental significance of kdm5c has not been e ...201830522514
ivermectin promotes peripheral nerve regeneration during wound healing.peripheral nerves have the capacity to regenerate due to the presence of neuroprotective glia of the peripheral nervous system, schwann cells. upon peripheral nerve injury, schwann cells create a permissive microenvironment for neuronal regrowth by taking up cytotoxic glutamate and secreting neurotrophic signaling molecules. impaired peripheral nerve repair is often caused by a defective schwann cell response after injury, and there is a critical need to develop new strategies to enhance nerve r ...201830411007
i spy with my little eye: a simple behavioral assay to test color sensitivity on digital displays.passive and interactive virtual reality (vr) environments are becoming increasingly popular in the field of behavioral neuroscience. while the technique was originally developed for human observers, corresponding applications have been adopted for the research of visual-driven behavior and neural circuits in animals. rgb color reproduction using red, green and blue primary color pixels is generally calibrated for humans, questioning if the distinct parameters are also readily transferable to oth ...201830127095
biological concerns on the selection of animal models for teratogenic testing.during pregnancy fetus can be exposed to a variety of chemicals which may induce abortion and malformations. due to the amounts of new substances coming into the market every year, a high demand for a rapid, reliable, and cost-effective method to detect potential toxicity is necessary. different species have been used as animal models for teratogen screening, most of them sharing similar development processes with humans. however, the application of embryology knowledge to teratology is hampered ...201829896687
transgenic xenopus laevis line for in vivo labeling of nephrons within the kidney.xenopus laevis embryos are an established model for studying kidney development. the nephron structure and genetic pathways that regulate nephrogenesis are conserved between xenopus and humans, allowing for the study of human disease-causing genes. xenopus embryos are also amenable to large-scale screening, but studies of kidney disease-related genes have been impeded because assessment of kidney development has largely been limited to examining fixed embryos. to overcome this problem, we have g ...201829642376
pharmacological profile of vestibular inhibitory inputs to superior oblique motoneurons.vestibulo-ocular reflexes (vor) are mediated by three-neuronal brainstem pathways that transform semicircular canal and otolith sensory signals into motor commands for the contraction of spatially specific sets of eye muscles. the vestibular excitation and inhibition of extraocular motoneurons underlying this reflex is reciprocally organized and allows coordinated activation of particular eye muscles and concurrent relaxation of their antagonistic counterparts. here, we demonstrate in isolated p ...201829556714
divergent axial morphogenesis and earlyshhexpression in vertebrate prospective floor plate.the notochord has organizer properties and is required for floor plate induction and dorsoventral patterning of the neural tube. this activity has been attributed to sonic hedgehog (shh) signaling, which originates in the notochord, forms a gradient, and autoinducesshhexpression in the floor plate. however, reported data are inconsistent and the spatiotemporal development of the relevantshhexpression domains has not been studied in detail. we therefore studied the expression dynamics ofshhin rab ...201829423139
cloning and spatiotemporal expression of xenopus laevis apolipoprotein ci.apolipoprotein ci (apoci) belongs to the apolipoprotein superfamily, members of which are involved in lipid transport, uptake and homeostasis. excessive apoci has been implicated in atherosclerosis and alzheimer's disease in humans. in this study we report the isolation of xenopus laevis apoci and describe the expression pattern of this gene during early development, using reverse transcription polymerase chain reaction and whole mount in situ hybridization. xenopus apoci is enriched in the dors ...201829346450
investigation of non-cb1, non-cb2 win55212-2-sensitive g-protein-coupled receptors in the brains of mammals, birds, and amphibians.previous studies have found non-cb1 non-cb2 g-protein-coupled receptors in rodents that are activated by the aminoalkylindole cannabinoid agonist win55212-2. this work obtained evidence for the presence or absence of similar receptors in the brains of other mammals, birds and amphibians.201830376752
cardiovascular pharmacology of k2p17.1 (task-4, talk-2) two-pore-domain k+ channels.k2p17.1 (task-4, talk-2) potassium channels are expressed in the heart and represent potential targets for pharmacological management of atrial and ventricular arrhythmias. reduced k2p17.1 expression was found in atria and ventricles of heart failure (hf) patients. modulation of k2p17.1 currents by antiarrhythmic compounds has not been comprehensively studied to date. the objective of this study was to investigate acute effects of clinically relevant antiarrhythmic drugs on human k2p17.1 channel ...201830008082
combined effects of mutations in loop c and the loop d-e-g triangle on neonicotinoid interactions with drosophila dα1/chicken β2 hybrid nachrs.neonicotinoid insecticides interact with the orthosteric sites of nicotinic acetylcholine receptors (nachrs) formed at the interfaces of (a) two adjacent α subunits and (b) α and non-α subunits. however, little is known of the detailed contributions of these two orthosteric sites to neonicotinoid actions. we therefore applied voltage-clamp electrophysiology to the dα1/chicken β2 hybrid nachr expressed in xenopus laevis oocytes to explore the agonist actions of imidacloprid and thiacloprid on wil ...201830704712
the publications of embryologist lev v. beloussov.a list of papers and books of the late lev v. beloussov was compiled and is available in word and endnote supplements. the breadth of his work is briefly described.201830321582
bapx1 is required for jaw joint development in amphibians.the acquisition of a movable jaw and a jaw joint are key events in gnathostome evolution. jaws are derived from the neural crest derived pharyngeal skeleton and the transition from jawless to jawed vertebrates consists of major morphological changes, which must have a genetic foundation. recent studies on the effects of bapx1 knockdown in fish and chicken indicate that bapx1 has acquired such a role in primary jaw joint development during vertebrate evolution, but evidence from amphibians is mis ...201830168254
spindle assembly in egg extracts of the marsabit clawed frog, xenopus borealis.egg extracts of the african clawed frog xenopus laevis have provided a cell-free system instrumental in elucidating events of the cell cycle, including mechanisms of spindle assembly. comparison with extracts from the diploid western clawed frog, xenopus tropicalis, which is smaller at the organism, cellular and subcellular levels, has enabled the identification of spindle size scaling factors. we set out to characterize the marsabit clawed frog, xenopus borealis, which is intermediate in size b ...201829573195
cell cycles during early steps of amphibian embryogenesis: a review.the published data on cell cycles during the initial (pregastrular) period of embryonic development in representatives of the class amphibia have been critically discussed. we have also used the literature data on ontogenetic diversity of these animals. the relatively small eggs of two principal model species for amphibian embryology, the mexican axolotl and the african clawed frog, undergo the extensive series of rapid synchronous cleavage divisions, after which the midblastula transition (mbt) ...201830240720
the tmem16a channel mediates the fast polyspermy block in xenopus laevis.in externally fertilizing animals, such as sea urchins and frogs, prolonged depolarization of the egg immediately after fertilization inhibits the entry of additional sperm-a phenomenon known as the fast block to polyspermy. in the african clawed frog xenopus laevis, this depolarization is driven by ca2+-activated cl- efflux. although the prominent ca2+-activated cl- currents generated in immature x. laevis oocytes are mediated by x. laevis transmembrane protein 16a (xtmem16a) channels, little i ...201830012842
skin regeneration of amphibians: a novel model for skin regeneration as adults.adult mammals do not regenerate the dermis of the skin but form a scar after a deep skin injury. since a scar causes serious medical problems, skin regeneration, instead of formation of a scar, has been strongly desired from a clinical point of view. recent studies have suggested multiple origins of myofibroblasts, which are scar-forming cells in skin wound healing of mammals. while amphibians have skin structures that are basically common to mammals as tetrapods, both urodele and anuran amphibi ...201829947057
bapx1 upregulation is associated with ectopic mandibular cartilage development in amphibians.the emergence of novel structures during evolution is crucial for creating variation among organisms, but the underlying processes which lead to the emergence of evolutionary novelties are poorly understood. the gnathostome jaw joint is such a novelty, and the incorporation of bapx1 expression into the intermediate first pharyngeal arch may have played a major role in the evolution of this joint. knockdown experiments revealed that loss of bapx1 function leads to the loss of the jaw joint, becau ...201829942645
musashi and plasticity of xenopus and axolotl spinal cord ependymal cells.the differentiated state of spinal cord ependymal cells in regeneration-competent amphibians varies between a constitutively active state in what is essentially a developing organism, the tadpole of the frog xenopus laevis, and a quiescent, activatable state in a slowly growing adult salamander ambystoma mexicanum, the axolotl. ependymal cells are epithelial in intact spinal cord of all vertebrates. after transection, body region ependymal epithelium in both xenopus and the axolotl disorganizes ...201829535610
morphological and transcriptomic analyses reveal three discrete primary stages of postembryonic development in the common fire salamander, salamandra salamandra.the postembryonic development of amphibians has been characterized as divided into three predominant periods, hereafter named primary developmental stages: premetamorphosis (prem), prometamorphosis (prom), metamorphic climax (meta), and completion of metamorphosis (postm), largely based on examination of anuran development. here, we categorized the postembryonic development of larvae of a poisonous fire salamander (salamandra salamandra) by integrating morphology and gene expression (transcripto ...201829504232
a role for sox9 in post-transcriptional processes: insights from the amphibian oocyte.sox9 is a member of the gene family of sox transcription factors, which is highly conserved among vertebrates. it is involved in different developmental processes including gonadogenesis. in all amniote species examined thus far, sox9 is expressed in the sertoli cells of the male gonad, suggesting an evolutionarily conserved role in testis development. however, in the anamniotes, fishes and amphibians, it is also expressed in the oocyte but the significance of such an expression remains to be el ...201829740094
high-throughput screening to identify anesthetic ligands using xenopus laevis tadpoles.general anesthetics are considered among the most significant advances in modern medicine; however, they are also some of the most dangerous commonly administered drugs. despite this, the discovery of novel anesthetics has been slow, with few clinically used agents regardless of their nearly 200-year history. xenopus laevis frogs have a long history as a model organism and provide a vital bridge between in vitro and preclinical mammalian assays. the provided protocols are efficient and cost-effe ...201829588028
mitochondrial ros cause motor deficits induced by synaptic inactivity: implications for synapse pruning.developmental synapse pruning refines burgeoning connectomes. the basic mechanisms of mitochondrial reactive oxygen species (ros) production suggest they select inactive synapses for pruning: whether they do so is unknown. to begin to unravel whether mitochondrial ros regulate pruning, we made the local consequences of neuromuscular junction (nmj) pruning detectable as motor deficits by using disparate exogenous and endogenous models to induce synaptic inactivity en masse in developing xenopus l ...201829587245
unexplained cardiac arrest: a tale of conflicting interpretations of kcnq1 genetic test results.unexplained cardiac arrest (uca) is often the first manifestation of an inherited arrhythmogenic disease. genetic testing in uca is challenging due to the complexities of variant interpretation in the absence of supporting cardiac phenotype. we aimed to investigate if a kcnq1 variant [p.(pro64_pro70del)], previously reported as pathogenic, contributes to the long-qt syndrome phenotype, co-segregates with disease or affects kcnq1 function in vitro.201829582136
orthogonality of pyrrolysine trna in the xenopus oocyte.chemical aminoacylation of orthogonal trna allows for the genetic encoding of a wide range of synthetic amino acids without the need to evolve specific aminoacyl-trna synthetases. this method, when paired with protein expression in the xenopus laevis oocyte expression system, can extract atomic scale functional data from a protein structure to advance the study of membrane proteins. the utility of the method depends on the orthogonality of the trna species used to deliver the amino acid. here, w ...201829581437
delay models for the early embryonic cell cycle oscillator.time delays are known to play a crucial role in generating biological oscillations. the early embryonic cell cycle in the frog xenopus laevis is one such example. although various mathematical models of this oscillating system exist, it is not clear how to best model the required time delay. here, we study a simple cell cycle model that produces oscillations due to the presence of an ultrasensitive, time-delayed negative feedback loop. we implement the time delay in three qualitatively different ...201829579091
proteomic characterization of the neural ectoderm fated cell clones in the xenopus laevis embryo by high-resolution mass spectrometry.the molecular program by which embryonic ectoderm is induced to form neural tissue is essential to understanding normal and impaired development of the central nervous system. xenopus has been a powerful vertebrate model in which to elucidate this process. however, abundant vitellogenin (yolk) proteins in cells of the early xenopus embryo interfere with protein detection by high-resolution mass spectrometry (hrms), the technology of choice for identifying these gene products. here, we systematic ...201829578674
the right thalamus may play an important role in anesthesia-awakening regulation in frogs.previous studies have shown that the mammalian thalamus is a key structure for anesthesia-induced unconsciousness and anesthesia-awakening regulation. however, both the dynamic characteristics and probable lateralization of thalamic functioning during anesthesia-awakening regulation are not fully understood, and little is known of the evolutionary basis of the role of the thalamus in anesthesia-awakening regulation.201829576980
incorporation of the δ-subunit into the epithelial sodium channel (enac) generates protease-resistant enacs in xenopus laevis.the epithelial sodium channel (enac) is a critical regulator of vertebrate electrolyte homeostasis. enac is the only constitutively open ion channel in the degenerin/enac protein family, and its expression, membrane abundance, and open probability therefore are tightly controlled. the canonical enac is composed of three subunits (α, β, and γ), but a fourth δ-subunit may replace α and form atypical δβγ-enacs. using xenopus laevis as a model, here we found that mrnas of the α- and δ-subunits are d ...201829576549
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