Publications

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compaction of rna duplexes in the cell.the structure and flexibility of rna depends sensitively on the microenvironment. using pulsed electron-electron double-resonance (peldor)/double electron-electron resonance (deer) spectroscopy combined with advanced labeling techniques, we show that the structure of double-stranded rna (dsrna) changes upon internalization into xenopus laevis oocytes. compared to dilute solution, the dsrna a-helix is more compact in cells. we recapitulate this compaction in a densely crowded protein solution. at ...202032804430
mucociliary epithelial organoids from xenopus embryonic cells: generation, culture and high-resolution live imaging.mucociliary epithelium provides the first line of defense by removing foreign particles through the action of mucus production and cilia-mediated clearance. many clinically relevant defects in the mucociliary epithelium are inferred as they occur deep within the body. here, we introduce a tractable 3d model for mucociliary epithelium generated from multipotent progenitors that were microsurgically isolated from xenopus laevis embryos. the mucociliary epithelial organoids are covered with newly g ...202032804169
conservation of glomerular organization in the main olfactory bulb of anuran larvae.the glomerular array in the olfactory bulb of many vertebrates is segregated into molecularly and anatomically distinct clusters linked to different olfactory functions. in anurans, glomerular clustering is so far only described in xenopus laevis. we traced olfactory projections to the bulb in tadpoles belonging to six distantly related anuran species in four families (pipidae, hylidae, bufonidae, dendrobatidae) and found that glomerular clustering is remarkably conserved. the general bauplan co ...202032792916
mutation affecting the conserved acidic wnk1 motif causes inherited hyperkalemic hyperchloremic acidosis.gain-of-function mutations in with no lysine (k) 1 (wnk1) and wnk4 genes are responsible for familial hyperkalemic hypertension (fhht), a rare, inherited disorder characterized by arterial hypertension and hyperkalemia with metabolic acidosis. more recently, fhht-causing mutations in the kelch-like 3-cullin 3 (klhl3-cul3) e3 ubiquitin ligase complex have shed light on the importance of wnk's cellular degradation on renal ion transport. using full exome sequencing for a 4-generation family and th ...202032790646
monocarboxylate transporter 12 as a guanidinoacetate efflux transporter in renal proximal tubular epithelial cells.guanidinoacetate (gaa), which is a precursor of creatine, is mainly biosynthesized in the renal proximal tubular epithelial cells (rptecs). plasma concentration of gaa has been reported to be reduced in patients with monocarboxylate transporter 12 (mct12) mutation (p.q215x). however, the mechanism underlying gaa release from the rptecs remains unclear. therefore, to elucidate the role of mct12 in renal gaa release, mct12-mediated gaa transport was evaluated using the human and rat mct12-expressi ...202032781157
heterogeneity of synonymous substitution rates in the xenopus frog genome.with the increasing availability of high quality genomic data, there is opportunity to deeply explore the genealogical relationships of different gene loci between closely related species. in this study, we utilized genomes of xenopus laevis (xla, a tetraploid species with (l) and (s) sub-genomes) and x. tropicalis (xtr, a diploid species) to investigate whether synonymous substitution rates among orthologous or homoeologous genes displayed any heterogeneity. from over 1500 orthologous/homoeolog ...202032764757
the specific molecular composition and structural arrangement of eleutherodactylus coqui gular skin tissue provide its high mechanical compliance.a male eleutherodactylus coqui (ec, a frog) expands and contracts its gular skin to a great extent during mating calls, displaying its extraordinarily compliant organ. there are striking similarities between frog gular skin and the human bladder as both organs expand and contract significantly. while the high extensibility of the urinary bladder is attributed to the unique helical ultrastructure of collagen type iii, the mechanism behind the gular skin of ec is unknown. we therefore aim to under ...202032764252
sequential purification and characterization of torpedo californica nachr-dc supplemented with chs for high-resolution crystallization studies.over the past 10 years we have been developing a multi-attribute analytical platform that allows for the preparation of milligram amounts of functional, high-pure, and stable torpedo (muscle-type) nachr detergent complexes for crystallization purpose. in the present work, we have been able to significantly improve and optimize the purity and yield of nicotinic acetylcholine receptors in detergent complexes (nachr-dc) without compromising stability and functionality. we implemented new methods in ...202032763308
comparative gene expression profiling between optic nerve and spinal cord injury in xenopus laevis reveals a core set of genes inherent in successful regeneration of vertebrate central nervous system axons.the south african claw-toed frog, xenopus laevis, is uniquely suited for studying differences between regenerative and non-regenerative responses to cns injury within the same organism, because some cns neurons (e.g., retinal ganglion cells after optic nerve crush (onc)) regenerate axons throughout life, whereas others (e.g., hindbrain neurons after spinal cord injury (sci)) lose this capacity as tadpoles metamorphose into frogs. tissues from these cns regions (frog onc eye, tadpole sci hindbrai ...202032758133
grp94 regulates the recruitment of aneural achr clusters for the assembly of postsynaptic specializations by modulating adf/cofilin activity and turnover.temperature is a physiological factor that affects neuronal growth and synaptic homeostasis at the invertebrate neuromuscular junctions (nmjs); however, whether temperature stress could also regulate the structure and function of the vertebrate nmjs remains unclear. in this study, we use xenopus laevis primary cultures as a vertebrate model system for investigating the involvement of heat shock protein 90 (hsp90) family of stress proteins in nmj development. first, cold temperature treatment or ...202032747457
exploring the relationships between amphibian (xenopus laevis) myeloid cell subsets.the differentiation of distinct leukocyte subsets is governed by lineage-specific growth factors that elicit disparate expression of transcription factors and markers by the developing cell populations. for example, macrophages (mφs) and granulocytes (grns) arise from common granulocyte-macrophage progenitors in response to distinct myeloid growth factors. in turn, myelopoiesis of the xenopus laevis anuran amphibian appears to be unique to other studied vertebrates in several respects while the ...202032745480
analysis of pallial/cortical interneurons in key vertebrate models of testudines, anurans and polypteriform fishes.the organization of the pallial derivatives across vertebrates follows a comparable elementary arrangement, although not all of them possess a layered cortical structure as sophisticated as the cerebral cortex of mammals. however, its expansion along evolution has only been possible by the development and coevolution of the cellular networks formed by excitatory neurons and inhibitory interneurons. thus, the comparative analysis of interneuron types in vertebrate models of key evolutionary signi ...202032743670
rare heterozygous gdf6 variants in patients with renal anomalies.although over 50 genes are known to cause renal malformation if mutated, the underlying genetic basis, most easily identified in syndromic cases, remains unsolved in most patients. in search of novel causative genes, whole-exome sequencing in a patient with renal, i.e., crossed fused renal ectopia, and extrarenal, i.e., skeletal, eye, and ear, malformations yielded a rare heterozygous variant in the gdf6 gene encoding growth differentiation factor 6, a member of the bmp family of ligands. previo ...202032737436
new insights in the mode of action of (+)-erythravine and (+)-11α-hydroxy-erythravine alkaloids.erythrinian alkaloids ((+)-erythravine and (+)-11-α-hydroxy-erythravine) have been pointed as the main responsible agents for the anticonvulsant and anxiolytic properties of erythrina mulungu mart ex benth. the present work provides a new set of information about the mode of action of these alkaloids by the use of a complementary approach of neurochemical and electrophysiological assays. we propose here that the antiepileptic and anxiolytic properties exhibited by both alkaloids appear not to be ...202032735983
zinc protection of fertilized eggs is an ancient feature of sexual reproduction in animals.one of the earliest and most prevalent barriers to successful reproduction is polyspermy, or fertilization of an egg by multiple sperm. to prevent these supernumerary fertilizations, eggs have evolved multiple mechanisms. it has recently been proposed that zinc released by mammalian eggs at fertilization may block additional sperm from entering. here, we demonstrate that eggs from amphibia and teleost fish also release zinc. using xenopus laevis as a model, we document that zinc reversibly block ...202032735558
polyploidization and pseudogenization in allotetraploid frog xenopus laevis promote the evolution of aquaporin family in higher vertebrates.aquaporins (aqps), as members of the major intrinsic protein (mip) superfamily, facilitated the permeation of water and other solutes and are involved in multiple biological processes. aqp family exists in almost all living organisms and is highly diversified in vertebrates in both classification and function due to genome wide duplication. while some aqp orthologs have been lost in higher vertebrates through evolution.202032727380
postsynaptic and presynaptic nmdars have distinct roles in visual circuit development.to study contributions of n-methyl-d-aspartate receptors (nmdars) in presynaptic and postsynaptic neurons of the developing visual system, we microinject antisense morpholino oligonucleotide (mo) against glun1 into one cell of two-cell-stage xenopus laevis embryos. the resulting bilateral segregation of mo induces postsynaptic nmdar (postnmdar) knockdown in tectal neurons on one side and presynaptic nmdar (prenmdar) knockdown in ganglion cells projecting to the other side. postnmdar knockdown re ...202032726620
defective heart chamber growth and myofibrillogenesis after knockout of adprhl1 gene function by targeted disruption of the ancestral catalytic active site.adp-ribosylhydrolase-like 1 (adprhl1) is a pseudoenzyme expressed in the developing heart myocardium of all vertebrates. in the amphibian xenopus laevis, knockdown of the two cardiac adprhl1 protein species (40 and 23 kda) causes failure of chamber outgrowth but this has only been demonstrated using antisense morpholinos that interfere with rna-splicing. transgenic production of 40 kda adprhl1 provides only part rescue of these defects. crispr/cas9 technology now enables targeted mutation of the ...202032726316
gitx1(β/κ-theraphotoxin-gi1a), a novel toxin from the venom of brazilian tarantula grammostola iheringi (mygalomorphae, theraphosidae): isolation, structural assessments and activity on voltage-gated ion channels.spider venoms, despite their toxicity, represent rich sources of pharmacologically active compounds with biotechnological potential. however, in view of the large diversity of the spider species, the full potential of their venom molecules is still far from being known. in this work, we report the purification and structural and functional characterization of gitx1 (β/κ-trtx-gi1a), the first toxin purified from the venom of the brazilian tarantula spider grammostola iheringi. gitx1 was purified ...202032717411
nicotinic acetylcholine receptors: ex-vivo expression of functional, non-hybrid, heteropentameric receptors from a marine arthropod, lepeophtheirus salmonis.nicotinic acetylcholine receptors (nachrs) are ligand-gated ion channels mostly located in the post-synaptic membrane of cholinergic synapses. the natural neurotransmitter is acetylcholine, but they are also the direct targets for neonicotinoids, chemicals widely used against ectoparasites, arthropod vectors and agricultural pests. there are significant concerns regarding adverse effects of neonicotinoids on beneficial insects. in arthropods, functional nachrs made of α subunits have been expres ...202032716968
redox priming promotes aurora a activation during mitosis.cell cycle-dependent redox changes can mediate transient covalent modifications of cysteine thiols to modulate the activities of regulatory kinases and phosphatases. our previously reported finding that protein cysteine oxidation is increased during mitosis relative to other cell cycle phases suggests that redox modifications could play prominent roles in regulating mitotic processes. the aurora family of kinases and their downstream targets are key components of the cellular machinery that ensu ...202032694171
intracellular motor-driven transport of rodlike smooth organelles along microtubules.molecular motors are fascinating proteins that use the energy of atp hydrolysis to drive vesicles and organelles along cytoskeleton filaments toward their final destination within the cell. several copies of these proteins bind to the cargo and take turns transporting the cargo attaching to and detaching from the track stochastically. despite the relevance of molecular motors to cell physiology, key aspects of their collective functioning are still unknown. in this work we propose a one-dimensio ...202032688554
adverse effects of fly ashes used as immobilizing agents for highly metal-contaminated soils on xenopus laevis oocytes survival and maturation-a study performed in the north of france with field soil extracts.amphibians are now recognized as the most endangered group. one of this decline causes is the degradation of their habitat through direct contamination of water, soil leaching, or runoff from surrounding contaminated soils and environments. in the north of france, the extensive industrial activities resulted in massive soil contamination by metal compounds. mineral amendments were added to soils to decrease trace metal mobility. because of the large areas to be treated, the use of inexpensive in ...202030875069
leishmania heme uptake involves lmflvcrb, a novel porphyrin transporter essential for the parasite.leishmaniasis comprises a group of neglected diseases caused by the protozoan parasite leishmania spp. as is the case for other trypanosomatid parasites, leishmania is auxotrophic for heme and must scavenge this essential compound from its human host. in mammals, the slc transporter flvcr2 mediates heme import across the plasma membrane. herein we identify and characterize leishmania major flvcrb (lmflvcrb), the first member of the flvcr family studied in a non-metazoan organism. this protein lo ...202031372684
coexposure to environmental concentrations of cis-bifenthrin and graphene oxide: adverse effects on the nervous system during metamorphic development of xenopus laevis.despite the great concerns associated with the combined biological effects of nanoparticles and insecticides, the current understanding of the corresponding ecological risks remains limited. xenopus laevis (x. laevis) tadpoles were exposed to various concentrations of typical pyrethroid (cis-bifenthrin; cis-bf), either alone or in combination with graphene oxide (go), for 21 days. the presence of go resulted in increased bioconcentration of cis-bf and a higher 1s-enantiomer fraction. exposure to ...202031425913
smooth muscle in cardiac chambers is common in turtles and extensive in the emydid turtle, trachemys scripta.a prominent layer of smooth muscle lining the luminal side of the atria of freshwater turtles (emydidae) was described more than a century ago. we recently demonstrated that this smooth muscle provides a previously unrecognized mechanism to change cardiac output in the emydid red-eared slider (trachemys scripta) that possibly contributes to their tremendous diving capacity. the purpose of the present immunohistochemical study was firstly to screen major groups of vertebrates for the presence of ...202031509333
morpholino studies in xenopus brain development.antisense morpholino oligonucleotides (mos) have become a valuable method to knockdown protein levels, to block with mrna splicing and to interfere with mirna function. mos are widely used to alter gene expression in development of xenopus and zebrafish, where they are typically injected into the fertilized egg or blastomeres. here we present methods to use electroporation to target delivery of mos to the central nervous system of xenopus laevis or xenopus tropicalis tadpoles. briefly, mo electr ...202031552666
odontomas in frogs.odontomas are variably differentiated, hamartoma-like proliferations of odontogenic epithelium, pulp ectomesenchyme (odontoblasts), and dental matrix. frogs are polyphyodont and homodont. their teeth also differ from mammals in that they are restricted to the upper jaw in adults and lack a periodontal ligament and cementum, attaching directly to the underlying bone. odontomas were identified in an african clawed frog (xenopus laevis), a false tomato frog (dyscophus guineti), and a tomato frog of ...202031551010
the expression of key guidance genes at a forebrain axon turning point is maintained by distinct fgfr isoforms but a common downstream signal transduction mechanism.during development the axons of neurons grow toward and locate their synaptic partners to form functional neural circuits. axons do so by reading a map of guidance cues expressed by surrounding tissues. guidance cues are expressed at a precise space and time, but how guidance cue expression is regulated, and in a coordinated manner, is poorly understood. semaphorins (semas) and slits are families of molecular ligands that guide axons. we showed previously that fibroblast growth factor (fgf) sign ...202030993182
sorafenib activity and disposition in liver cancer does not depend on organic cation transporter 1.systemic therapy of advanced hepatocellular carcinoma (hcc) with the small-molecule multikinase inhibitor sorafenib is associated with large interindividual pharmacokinetic variability and unpredictable side effects potentially requiring dose reduction or treatment termination. organic cation transporter (oct1; gene slc22a1) has been proposed as a clinical biomarker of hcc response. because proof is lacking that oct1 transports sorafenib, we used a combinatorial approach to define how oct1 contr ...202031350763
extracellular lysine 38 plays a crucial role in ph-dependent transport via human monocarboxylate transporter 1.human monocarboxylate transporters (hmcts) are expressed in many tissues and mediate the transport of various substrates across the plasma membrane. among hmcts, hmct1-4 cotransport h+ with monocarboxylates such as pyruvate and l-lactate, implying that these proteins recognize both substrate and h+. however, the mechanism of translocation, and particularly that of hmct1 ph-dependent transport, remains largely unknown. this study aimed at identifying residues involved in the ph dependence of hmct ...202031593685
cytosolic gaba inhibits anion transport by wheat almt1.anion transport by aluminium-activated malate transporter (almt) proteins is negatively regulated by gamma-aminobutyric acid (gaba), which increases in concentration during stress. here, the interaction between gaba and wheat (triticum aestivum, ta) taalmt1 heterologously-expressed in xenopus laevis oocytes was investigated. gaba inhibited anion transport by taalmt1 in membrane patches from the cytosolic, not extracellular membrane face, via a reduction in open probability (npopen ), not an inhi ...202031591723
lin28b increases neural crest cell migration and leads to transformation of trunk sympathoadrenal precursors.the rna-binding protein lin28b regulates developmental timing and determines stem cell identity by suppressing the let-7 family of micrornas. postembryonic reactivation of lin28b impairs cell commitment to differentiation, prompting their transformation. in this study, we assessed the extent to which ectopic lin28b expression modulates the physiological behavior of neural crest cells (ncc) and governs their transformation in the trunk region of developing embryos. we provide evidence that the ov ...202031601998
effects of glyphosate and a commercial formulation roundup® exposures on maturation of xenopus laevis oocytes.pesticides are often found at high concentrations in small ponds near agricultural field where amphibians are used to live and reproduce. even if there are many studies on the impacts of phytopharmaceutical active ingredients in amphibian toxicology, only a few are interested in the earlier steps of their life cycle. while their populations are highly threatened with extinction. the aim of this work is to characterize the effects of glyphosate and its commercial formulation roundup® gt max on th ...202030835066
clearance of activity-evoked k+ transients and associated glia cell swelling occur independently of aqp4: a study with an isoform-selective aqp4 inhibitor.the mammalian brain consists of 80% water, which is continuously shifted between different compartments and cellular structures by mechanisms that are, to a large extent, unresolved. aquaporin 4 (aqp4) is abundantly expressed in glia and ependymal cells of the mammalian brain and has been proposed to act as a gatekeeper for brain water dynamics, predominantly based on studies utilizing aqp4-deficient mice. however, these mice have a range of secondary effects due to the gene deletion. an efficie ...202132506554
xenopus deep cell aggregates: a 3d tissue model for mesenchymal-to-epithelial transition.mesenchymal-to-epithelial transition (met) describes the ability of loosely associated migratory cells to form a more adherent sheet-like assembly of cells. met is a conserved motif occurring throughout organogenesis and plays a key role in regeneration and cancer metastasis, and is the first step in producing induced pluripotent stem cells (ipscs). to resolve fundamental biological questions about met, its relation to epithelial-to-mesenchymal transition, and to explore met's role in tissue ass ...202132939727
characterizing channelrhodopsin channel properties via two-electrode voltage clamp and kinetic modeling.two-electrode voltage clamp (tevc) is a preferred electrophysiological technique used to study gating kinetics and ion selectivity of light-activated channelrhodopsins (chrs). the method uses two intracellular microelectrodes to hold, or clamp, the membrane potential at a specific value and measure the flow of ions across the plasma membrane. here, we describe the use of tevc and a simple solution exchange protocol to measure cation selectivity and analyze gating kinetics of the c1c2 chimera exp ...202132865738
epigenetic control of myeloid cells behavior by histone deacetylase activity (hdac) during tissue and organ regeneration in xenopus laevis.in the present work we have focused on the histone deacetylase (hdac) control of myeloid cells behavior during xenopus tail regeneration. here we show that myeloid differentiation is crucial to modulate the regenerative ability of xenopus tadpoles in a hdac activity-dependent fashion. hdac activity inhibition during the first wave of myeloid differentiation disrupted myeloid cells dynamics in the regenerative bud as well the mrna expression pattern of myeloid markers, such as lurp, mpox, spib an ...202132858087
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