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nosip functions during vertebrate eye and cranial cartilage development.the nitric oxide synthase interacting protein (nosip) has been associated with diverse human diseases including psychological disorders. in line, early neurogenesis of mouse and xenopus is impaired upon nosip deficiency. nosip knockout mice show craniofacial defects and the down-regulation of nosip in the mouse and xenopus leads to microcephaly. until now, the exact underlying molecular mechanisms of these malformations were still unknown.201830055071
a cyclic nucleotide-gated channel, hvcngc2-3, is activated by the co-presence of na⁺ and k⁺ and permeable to na⁺ and k⁺ non-selectively.cyclic nucleotide-gated channels (cngcs) have been postulated to contribute significantly in plant development and stress resistance. however, their electrophysiological properties remain poorly understood. here, we characterized barley cngc2-3 (hvcngc2-3) by the two-electrode voltage-clamp technique in the xenopus laevis oocyte heterologous expression system. current was not observed in x. laevis oocytes injected with hvcngc2-3 complementary rna (crna) in a bathing solution containing either na ...201830049942
copper uptake mechanism of arabidopsis thaliana high-affinity copt transporters.copper (cu) is an essential plant micronutrient. under scarcity, cu2+ is reduced to cu+ and taken up through specific high-affinity transporters (copts). in arabidopsis, the copt family consists of six members, either located at the plasma membrane (copt1, copt2, and copt6) or in internal membranes (copt3 and copt5). cu uptake by copt proteins has been mainly assessed through complementation studies in corresponding yeast mutants, but the mechanism of this transport has not been elucidated. to t ...201930043153
following endocrine-disrupting effects on gene expression in xenopus laevis.endocrine-disrupting chemicals (edcs), found in all categories of chemicals, are suspected to be a cause of declining well-being and human health, both as single molecules and as mixtures. it is therefore necessary to develop high throughput methods to assess the endocrine-disrupting potential of multiple chemicals currently on the market that are as yet untested. an advantage of in vivo chemical screening is that it provides a full spectrum of physiological impacts exerted by a given chemical. ...201930042138
assessing antibody responses to pathogens or model antigens in xenopus by enzyme-linked immunosorbent assay (elisa).xenopus laevis-specific monoclonal antibodies recognize igm and igy antibodies not only from x. laevis but also x. tropicalis as well as a variety of amphibian species including ranidae, bufonidae, and even some salamanders. these reagents are very useful to assess antibody responses from the serum or other animal secretions (e.g., peritoneal fluid). we present here an enzyme-linked immunosorbent assay (elisa) optimized for amphibians that permits users to detect and titrate the presence of each ...201930042135
rare coding variants in genes encoding gabaa receptors in genetic generalised epilepsies: an exome-based case-control study.genetic generalised epilepsy is the most common type of inherited epilepsy. despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. we aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy.201830033060
des-formylflustrabromine (dfbr): a structure-activity study on its ability to potentiate the action of acetylcholine at α4β2 nicotinic acetylcholine receptors.the naturally occurring indole alkaloid des-formylflustrabromine (dfbr; 1) is one of the first agents shown to act as a selective positive allosteric modulator (pam) at α4β2 nicotinic acetylcholine receptors (nachrs). we previously deconstructed this agent to determine which of its structural features contribute to its actions and have identified an agent that might serve as the basis for a " working pharmacophore". here, we elaborate the dfbr (1; ec50 = 0.2 μm) structure to identify how various ...201830028943
transplantation of ears provides insights into inner ear afferent pathfinding properties.numerous tissue transplantations have demonstrated that otocysts can develop into normal ears in any location in all vertebrates tested thus far, though the pattern of innervation of these transplanted ears has largely been understudied. here, expanding on previous findings that transplanted ears demonstrate capability of local brainstem innervation and can also be innervated themselves by efferents, we show that inner ear afferents grow toward the spinal cord mostly along existing afferent and ...201830027559
amphibian (xenopus laevis) tadpoles and adult frogs differ in their use of expanded repertoires of type i and type iii interferon cytokines.while amphibians around the globe are facing catastrophic declines, in part because of infections with pathogens such as the frog virus 3 (fv3) ranavirus; the mechanisms governing amphibian susceptibility and resistance to such pathogens remain poorly understood. the type i and type iii interferon (ifn) cytokines represent a cornerstone of vertebrate antiviral immunity, while our recent work indicates that tadpoles and adult frogs of the amphibian xenopus laevis may differ in their ifn responses ...201830018186
the b-hlh transcription factor hes3 participates in neural plate border formation by interfering with wnt/β-catenin signaling.hes3 belongs to the hes basic helix-loop-helix family of transcriptional repressors that play central roles in maintaining progenitor cells and regulating binary cell fate decisions in the embryo. during xenopus laevis development, hes3 is expressed in the embryonic ectoderm in a horseshoe shape domain at the edge of the developing neural pate. hes3 mis-expression at early neurula stage blocks neural crest (snai2, sox8, sox9 and sox10) and cranial placode (six1 and dmrta1) gene expression, and p ...201830016640
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
plc and ip3-evoked ca2+ release initiate the fast block to polyspermy in xenopus laevis eggs.the prevention of polyspermy is essential for the successful progression of normal embryonic development in most sexually reproducing species. in external fertilizers, the process of fertilization induces a depolarization of the egg's membrane within seconds, which inhibits supernumerary sperm from entering an already-fertilized egg. this fast block requires an increase of intracellular ca2+ in the african clawed frog, xenopus laevis, which in turn activates an efflux of cl- that depolarizes the ...201830012841
comprehensive substrate characterization of 22 antituberculosis drugs for multiple solute carrier (slc) uptake transporters in vitro.the substrate potentials of antituberculosis drugs on solute carrier (slc) transporters are not well characterized to date, despite a well-established understanding of their drug dispositions and pharmacokinetics. in this study, we investigated comprehensively the substrate potentials of the 22 currently available antituberculosis drugs for slc family transporter-mediated uptake, using xenopus laevis oocytes and stably transfected hek-293 cells in vitro the result suggested that ethambutol, ison ...201830012768
a gene regulatory network underlying the formation of pre-placodal ectoderm in xenopus laevis.the neural plate border ectoderm gives rise to key developmental structures during embryogenesis, including the neural crest and the preplacodal ectoderm. many sensory organs and ganglia of vertebrates develop from cranial placodes, which themselves arise from preplacodal ectoderm, defined by expression of transcription factor six1 and its coactivator eya1. here we elucidate the gene regulatory network underlying the specification of the preplacodal ectoderm in xenopus, and the functional intera ...201830012125
water contaminants associated with unconventional oil and gas extraction cause immunotoxicity to amphibian tadpoles.chemicals associated with unconventional oil and gas (uog) operations have been shown to contaminate surface and ground water with a variety of endocrine disrupting compounds (edcs) inducing multiple developmental alteration in mice. however, little is known about the impacts of uog-associated contaminants on amphibian health and resistance to an emerging ranavirus infectious disease caused by viruses in the genus ranavirus, especially at the vulnerable tadpole stage. here we used tadpoles of th ...201830011011
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
thiodipeptides targeting the intestinal oligopeptide transporter as a general approach to improving oral drug delivery.the broad substrate capacity of the intestinal oligopeptide transporter, pept1, has made it a key target of research into drug delivery. whilst the substrate capacity of this transporter is broad, studies have largely been limited to small peptides and peptide-like drugs. here, we demonstrate for the first time that a diverse range of drugs can be targeted towards transport by pept1 using a hydrolysis resistant carrier. eleven prodrugs were synthesized by conjugating modified dipeptides containi ...201830006163
pharmacological and toxicological activity of rsd921, a novel sodium channel blocker.rsd921, the r,r enantiomer of the kappa (k) agonist pd117,302, lacks significant activity on opioid receptors.201829990839
fine structure of oviducal epithelium of xenopus laevis in relation to its role in secreting egg envelopes.during passage through the oviduct, the egg of xenopus laevis acquires the following substances or envelopes: electron-dense particles in the vitelline coat, the prefertilization layer in and around the vitelline coat, and four layers of jelly. both gross anatomical observation and light and scanning or transmission electron microscopic observations of various levels of oviduct revealed that the first two are produced in the pars recta 1 and 2 portions, and that jelly layers 1-4 are added in the ...198529976012
human mutations in slc2a9 (glut9) affect transport capacity for urate.slc2a9 or glut9 is a voltage sensitive urate transporter, mainly expressed in the kidneys, the liver, and the intestine. human glut9 loss-of-function mutations were identified in familial hypouricemia, and several single nucleotide polymorphisms (snps) were associated with lower serum urate, further indicating that glut9 is a major determinant of serum uric acid level. to get insights in glut9 transport characteristics, we systematically analyzed the function of known human glut9 mutants using 1 ...201829967582
the fungal alkaloid okaramine-b activates an l-glutamate-gated chloride channel from ixodes scapularis, a tick vector of lyme disease.a novel l-glutamate-gated anion channel (iscaglucl1) has been cloned from the black-legged tick, ixodes scapularis, which transmits multiple pathogens including the agents of lyme disease and human granulocytic anaplasmosis. when mrna encoding iscaglucl1 was expressed in xenopus laevis oocytes, we detected robust 50-400 na currents in response to 100 μm l-glutamate. responses to l-glutamate were concentration-dependent (pec50 3.64 ± 0.11). ibotenate was a partial agonist on iscaglucl1. we detect ...201829957333
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
multiple massive domestication and recent amplification of kolobok superfamily transposons in the clawed frog xenopus.dna transposons are generally destroyed by mutations and have short lifespans in hosts, as they are neutral or harmful to the host and therefore not conserved by natural selection. the clawed frog xenopus harbors many dna transposons and certain families, such as t2-mite, have extremely long lives. these have ancient origins, but have shown recent transposition activity. in addition, certain transposase genes may have been "domesticated" by xenopus and conserved over long time periods by natural ...201829946483
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
adamts9, a member of the adamts family, in xenopus development.extracellular matrix (ecm) remodeling by metalloproteinases is crucial during development. the adamts (a disintegrin and metalloproteinase with thrombospondin type i motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling. the human family includes 19 members. in this study we identified the 19 members of the adamts family in xenopus laevis and xenopus tropicalis. gene identificatio ...201829935379
influenza d virus m2 protein exhibits ion channel activity in xenopus laevis oocytes.a new type of influenza virus, known as type d, has recently been identified in cattle and pigs. influenza d virus infection in cattle is typically asymptomatic; however, its infection in swine can result in clinical disease. swine can also be infected with all other types of influenza viruses, namely a, b, and c. consequently, swine can serve as a "mixing vessel" for highly pathogenic influenza viruses, including those with zoonotic potential. currently, the only antiviral drug available target ...201829927982
probing proline residues in the prokaryotic ligand-gated ion channel, elic.erwinia ligand-gated ion channel (elic) is a bacterial homologue of vertebrate pentameric ligand-gated ion channels (plgics) and has proven to be a valuable model for understanding the structure and function of this important protein family. there is nevertheless still a question about whether molecular details can be accurately extrapolated from this protein to those found in eukaryotes. here we explore the role of proline residues (pros) in elic by creating mutant receptors, expressing them in ...201829927250
nuclear arp2/3 drives dna break clustering for homology-directed repair.dna double-strand breaks repaired by non-homologous end joining display limited dna end-processing and chromosomal mobility. by contrast, double-strand breaks undergoing homology-directed repair exhibit extensive processing and enhanced motion. the molecular basis of this movement is unknown. here, using xenopus laevis cell-free extracts and mammalian cells, we establish that nuclear actin, wasp, and the actin-nucleating arp2/3 complex are recruited to damaged chromatin undergoing homology-direc ...201829925947
gitelman's syndrome: characterization of a novel c.1181g>a point mutation and functional classification of the known mutations.we have investigated the mechanisms by which a novel missense point mutation (c.1181g>a) found in two sisters causes gitelman's syndrome by impairing the sodium chloride co-transporter (ncc, encoded by slc12a3 gene) function. the cdna and in vitro transcribed mrna of either wild-type or mutated slc12a3 were transfected into hek293 cells and injected into xenopus laevis oocytes, respectively. the expression, maturation, trafficking, and function of the mutated and wild-type ncc were assessed by w ...201829925901
regulation of nuclear factor of activated t cells (nfat) and downstream myogenic proteins during dehydration in the african clawed frog.xenopus laevis, otherwise known as the african clawed frog, undergoes natural dehydration of up to 30% of its total body water during the dry season in sub-saharan africa. to survive under these conditions, a variety of physiological and biochemical changes take place in x. laevis. we were interested in understanding the role that the calcineurin-nfat pathway plays during dehydration stress response in the skeletal muscles of x. laevis. immunoblotting was performed to characterize the protein le ...201829923155
semicircular canal influences on the developmental tuning of the translational vestibulo-ocular reflex.vestibulo-ocular reflexes (vors) rely on neuronal computations that transform vestibular sensory signals into spatio-temporally appropriate extraocular motor commands. the motoneuronal discharge for contractions of the superior oblique eye muscle during linear translation derives from a utricular epithelial sector that is spatially aligned with the pulling direction of this muscle. in xenopus laevis, the alignment is gradually achieved during larval development and requires motion-related semici ...201829922219
regenerative response of amputated forelimbs of xenopus laevis froglets to partial denervation.xenopus laevis froglet forelimbs normally respond to amputational injury by forming a heteromorphic cartilaginous rod-shaped outgrowth. however, partial denervation of a forelimb by ablation of the n. radialis or the n. ulnaris, followed in 2 days by amputation through the mid radius-ulna, results in a size deficiency of the regenerative outgrowth 14 and 21 days postamputation. the decreasing quantity of forelimb innervation, as a result of partial denervation by 55 or 45%, apparently has a grad ...198729921109
a wide variety of mitf transcript variants are expressed in the xenopus laevis periodic albino mutant.the periodic albino mutant of xenopus laevis has been used to study the development of pigment cells because both the retinal pigment epithelium (rpe) and melanophores are affected. in this mutant, "white pigment cells" containing both melanophore-specific and iridophore-specific pigment organelles appear. the present experiments were designed to investigate the structural organization and expression of microphthalmia-associated transcription factor (mitf) in the mutant since mitf is known to re ...201829920861
a sodium transporter hvhkt1;1 confers salt tolerance in barley via regulating tissue and cell ion homeostasis.our previous studies showed that high salt tolerance in tibetan wild barley accessions was associated with hvhkt1;1, a member of the high-affinity potassium transporter family. however, molecular mechanisms of hvhkt1;1 for salt tolerance and its roles in k+/na+ homeostasis remain to be elucidated. functional characterization of hvhkt1;1 was conducted in the present study. nacl-induced transcripts of hvhkt1;1 were significantly higher in the roots of tibetan wild barley xz16 relative to other gen ...201829917153
isolation and functional characterization of cslsi2, a cucumber silicon efflux transporter gene.silicon has been proven to exert beneficial effects on plant growth and stress tolerance, and silicon accumulation varies among different plant species. cucumber (cucumis sativus) is a widely used dicot model for silicon accumulation, but little is known about the molecular mechanism of its silicon uptake. previously, we isolated and characterized cslsi1, a silicon influx transporter gene from cucumber. in this study, we cloned a putative silicon efflux transporter gene, cslsi2, from cucumber an ...201829905780
the rna-binding complex escrt-ii in xenopus laevis eggs recognizes purine-rich sequences through its subunit, vps25.rna-binding proteins (rbp) are critical regulators of gene expression. recent studies have uncovered hundreds of mrna-binding proteins that do not contain annotated rna-binding domains and have well-established roles in other cellular processes. investigation of these nonconventional rbps is critical for revealing novel rna-binding domains and may disclose connections between rna regulation and other aspects of cell biology. the endosomal sorting complex required for transport ii (escrt-ii) is a ...201829903915
transcriptome of xenopus andrei, an octoploid frog, during embryonic development.although polyploidy occurs throughout the fish and amphibian lineages, the xenopus genus exhibits a high incidence of polyploidy, with 25 out of the 26 known species being polyploid. however, transcriptomic information is currently available for only one of these species, the tetraploid xenopus laevis. xenopus andrei, an octoploid species within the xenopus genus, offers an opportunity for assessing a novel polyploid transcriptome during vertebrate development. rna-seq data was generated at nine ...201829900348
validation and bioinformatics analysis of differentially expressed circrnas involved in developing male xenopus laevis chronically exposed to atrazine.the data presented here are related to the research article titled "identification of circular rnas and their alterations involved in developing male xenopus laevis chronically exposed to atrazine" (sai et al., 2018) [1]. circular rnas (circrnas) are implicated in multiple developmental anomalies (bachmayr-heyda et al., 2015; li et al., 2015) [2], [3]. this report describes the differentially expressed circrnas involved in developing male xenopus laevis (x. laevis) chronically exposed to atrazin ...201829900306
visualization of gene expression patterns by in situ hybridization on early stages of development of xenopus laevis.in situ hybridization performed using whole fixed embryos provides accurate and detailed visualization of gene expression patterns. these patterns are useful for investigating spatial patterns of gene expression in normally developing embryos but can also be useful in investigating the effects of genetic or environmental changes on expression of genetic markers characteristic of particular tissues, organs, or genetic pathways. our lab's protocol for whole-mount in situ hybridization is presented ...201829896701
evaluation of teratogenicity of pharmaceuticals using fetax.pharmaceuticals are chemical compounds which are used to preserve human and animal health. once administered, these compounds are metabolized or can remain unaltered until excreted. therefore, a mixture of pharmaceuticals and their metabolites enters municipal sewers and wastewater treatment plants where, depending on their polarity, water solubility, and persistence, they cannot be completely removed or transformed during the treatment process, so that unaltered pharmaceuticals and/or their met ...201829896699
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
studies of limb regeneration in larval xenopus.a basic protocol is given for animal maintenance and surgery in studies of hindlimb regeneration in larval xenopus laevis unlike urodele limbs, those of larval frogs typically show much more variation in the extent of regeneration after amputation. such variation can be reduced by optimizing the conditions of larval maintenance to regulate the rates of growth and development, by selecting only larvae with normal rates of growth and morphological development for experimental use, and by attention ...201929895566
investigating the cellular and molecular mechanisms of wound healing in xenopus oocytes and embryos.the african clawed frog xenopus has remarkable capacities to heal wounds rapidly and to regenerate complex tissues. because of its experimental tractability, studies using xenopus oocytes, embryos, and larvae have contributed extensively to our understanding of the molecular and cellular mechanisms underpinning wound healing and tissue regeneration. in this protocol, we describe wound-healing assays following mechanical or laser injuries of oocytes and multicellular epithelia in xenopus laevis e ...201929895564
ex vivo eye tissue culture methods for xenopus.lens regeneration can be studied in whole animals following removal of the original lens (lentectomy). however, culturing a whole animal can be impractical for assays involving small molecule inhibitors or proteins. ex vivo eye tissue culture is an alternative approach for examining lens regeneration. the ex vivo culture system offers certain advantages when compared to the in vivo regeneration assay, as the percentage of cases showing lens differentiation can exceed that seen in whole animals. ...201929895561
role of thyroid hormone receptor in amphibian development.the amphibian xenopus laevis has long been used as a model for studying vertebrate cell and developmental biology largely due to the easiness to manipulate this system in vivo and in vitro. while most of the developmental studies have been on xenopus embryogenesis, considerable efforts have been made to understand its metamorphosis, a process mimicking postembryonic development in mammals when many organs mature into their adult forms in the presence of high levels of thyroid hormone (t3). amphi ...201829892830
evaluating thyroid disrupting chemicals in vivo using xenopus laevis.using in vivo animal model systems for chemical screening can permit evaluation of the signaling pathways implicated. xenopus laevis is an ideal model organism to test thyroid axis disruption as thyroid hormones are highly conserved across vertebrates. here, we describe a high-throughput assay using non-feeding embryonic stage transgenic x. laevis (th/bzip) to screen for thyroid disrupting chemicals using a 3 day exposure protocol. we further describe a protocol to detect endocrine disruption of ...201829892825
atrial fibrillation and heart failure-associated remodeling of two-pore-domain potassium (k2p) channels in murine disease models: focus on task-1.understanding molecular mechanisms involved in atrial tissue remodeling and arrhythmogenesis in atrial fibrillation (af) is essential for developing specific therapeutic approaches. two-pore-domain potassium (k2p) channels modulate cellular excitability, and task-1 (k2p3.1) currents were recently shown to alter atrial action potential duration in af and heart failure (hf). finding animal models of af that closely resemble pathophysiological alterations in human is a challenging task. this study ...201829881975
pou3f transcription factor expression during embryonic development highlights distinct pou3f3 and pou3f4 localization in the xenopus laevis kidney.the pou (pit-oct-unc) genes encode a large transcription factor family comprising 6 classes (pou1f to pou6f ) involved in many developmental processes, such as cell commitment and differentiation. the pou3f class contains four members (pou3f1, pou3f2, pou3f3, pou3f4) characterized by expression in ectodermal tissue derivatives, such as nervous system and otic vesicle, during mammalian development. in order to obtain insights into the potential conservation of this class of transcription factors ...201829877572
lrpap1 as a specific marker of proximal pronephric kidney tubuli in xenopus laevis embryos.lrpap1, also known as receptor associated protein (rap) is a small protein of 40 kda associated with six of the seven members of the evolutionary conserved family of ldl receptors. numerous studies showed that lrpap1 has a dual function, initially as a chaperone insuring proper formation of intermolecular disulfide bonds during biogenesis of low density lipoprotein (ldl) receptors and later as an escort protein during trafficking through the endoplasmic reticulum and the early golgi compartment, ...201829877571
genome-wide transcriptomics analysis of genes regulated by gata4, 5 and 6 during cardiomyogenesis in xenopus laevis.the transcription factors gata4, gata5 and gata6 play important roles in heart muscle differentiation. the data presented in this article are related to the research article entitled "genome-wide transcriptomics analysis identifies sox7 and sox18 as specifically regulated by gata4 in cardiomyogenesis" (afouda et al., 2017) [1]. the present study identifies genes regulated by these individual cardiogenic gata factors using genome-wide transcriptomics analysis. we have presented genes that are spe ...201829876429
mechanism of how augmin directly targets the γ-tubulin ring complex to microtubules.microtubules (mts) must be generated from precise locations to form the structural frameworks required for cell shape and function. mts are nucleated by the γ-tubulin ring complex (γ-turc), but it remains unclear how γ-turc gets to the right location. augmin has been suggested to be a γ-turc targeting factor and is required for mt nucleation from preexisting mts. to determine augmin's architecture and function, we purified xenopus laevis augmin from insect cells. we demonstrate that augmin is su ...201829875259
premotor neuron divergence reflects vocal evolution.to identify mechanisms of behavioral evolution, we investigated the hindbrain circuit that generates distinct vocal patterns in two closely related frog species. male xenopus laevis and xenopus petersii produce courtship calls that include a fast trill: trains of ∼60 hz sound pulses. although fast trill rates are similar, x. laevis fast trills have a longer duration and period than those of x. petersii to pinpoint the neural basis of these differences, we used whole-cell patch-clamp recordings i ...201829875228
molecular insights into variable electron transfer in amphibian cryptochrome.cryptochrome proteins are activated by the absorption of blue light, leading to the formation of radical pairs through electron transfer in the active site. recent experimental studies have shown that once some of the amino acid residues in the active site of xenopus laevis cryptochrome dash are mutated, radical-pair formation is still observed. in this study, we computationally investigate electron-transfer pathways in the x. laevis cryptochrome dash by extensively equilibrating a previously es ...201829874607
spiral waves and vertebrate embryonic handedness.during early embryonic development, the vertebrate main body axis is segmented from head-to-tail into somites. somites emerge sequentially from the presomitic mesoderm (psm) as a consequence of oscillatory waves of genetic activity, called somitogenesis waves. here, we discuss the implications of the dynamic patterns of early x-delta-2 expression in the prospective somites (somitomeres) of xenopus laevis. we report that right somitomeres normally emerge before left to form chiral structures (i.e ...201829872025
development of the ethmoidal structures of the endocranium in the anuran pipa pipa.investigation of eight developmental stages by means of serial sections and subsequent graphic or wax model reconstructions, as well as by means of cleared-and-stained and dissected material, revealed that the ethmoidal endocranium in pipa pipa consists in early states of a single horizontal ethmoid plate lacking labial cartilages. later in the course of development, structures comparable with those in other anurans appear, though modified and of reduced size. these adult structures arise from t ...198929865644
ultrastructural changes in the connective tissue of the gastric region during the metamorphosis of xenopus laevis.development of the gastric connective tissue of xenopus laevis during metamorphosis was investigated by electron microscopy. throughout the larval period to stage 60, the layer of connective tissue underlying the gastric epithelium consists of immature fibroblasts surrounded by a sparse extracellular matrix. at the beginning of the transition from the larval to the adult epithelial form, at about stage 60, extensive changes occur in the connective tissue. the number of cells suddenly increses an ...198929865622
testicular and androgen dependence of skin gland morphology in the anurans, xenopus laevis and rana pipiens.in anuran amphibians, there is increasing evidence that exocrine glands dispersed throughout the general integument are secondary sex characters (ssc). following the recent discovery of sexually dimorphic "breeding glands" in the dorsum of male rana pipiens, we studied the effects of castration and testosterone treatment on the dorsal skin glands of male xenopus laevis and r. pipiens to determine whether the dorsal breeding glands, or any other dorsal skin glands, are androgen dependent. the dor ...199329865448
akt signaling displays multifaceted functions in neural crest development.akt signaling is an essential intracellular pathway controlling cell homeostasis, cell proliferation and survival, as well as cell migration and differentiation in adults. alterations impacting the akt pathway are involved in many pathological conditions in human disease. similarly, during development, multiple transmembrane molecules, such as fgf receptors, pdgf receptors or integrins, activate akt to control embryonic cell proliferation, migration, differentiation, and also cell fate decisions ...201829859890
comparative toxicity of ammonium and nitrate compounds to pacific treefrog and african clawed frog tadpoles.the effects of ammonium nitrate, ammonium chloride, ammonium sulfate, and sodium nitrate on survival and growth of pacific treefrog (pseudacris regilla [baird and girard]) and african clawed frog (xenopus laevis [daudin]) tadpoles were determined in static-renewal tests. the 10-d ammonium nitrate and ammonium sulfate lc50s for p. regilla were 55.2 and 89.7 mg/l nh4 -n, respectively. the 10-d lc50s for x. laevis for the three ammonium compounds ranged from 45 to 64 μg/l nh4 - n. the 10-d sodium n ...199929857645
progress toward identifying causes of maldevelopment induced in xenopus by pond water and sediment extracts from minnesota, usa.in previously conducted laboratory studies with the south african clawed frog (xenopus laevis), pond water and sediment samples collected from various sites in minnesota, usa, were demonstrated to have the potential to induce a variety of developmental abnormalities, including early embryo-larval maldevelopment, abnormal limb development, and disruption of metamorphosis. the results of exposure of x. laevis to suspect pond water and sediment samples supported the hypothesis that these samples we ...199929857636
n-terminal and central domains of apc function to regulate branch number, length and angle in developing optic axonal arbors in vivo.during formation of neuronal circuits, axons navigate long distances to reach their target locations in the brain. when axons arrive at their target tissues, in many cases, they extend collateral branches and/or terminal arbors that serve to increase the number of synaptic connections they make with target neurons. here, we investigated how adenomatous polyposis coli (apc) regulates terminal arborization of optic axons in living xenopus laevis tadpoles. the n-terminal and central domains of apc ...201829856981
in vivo mitotic spindle scaling can be modulated by changing the levels of a single protein: the microtubule polymerase xmap215.in many organisms, early embryonic development is characterized by a series of reductive cell divisions that result in rapid increases in cell number and concomitant decreases in cell size. intracellular organelles, such as the nucleus and mitotic spindle, also become progressively smaller during this developmental window, but the molecular and mechanistic underpinnings of these scaling relationships are not fully understood. for the mitotic spindle, changes in cytoplasmic volume are sufficient ...201829851557
the calcium-sensing receptor increases activity of the renal ncc through the wnk4-spak pathway.background hypercalciuria can result from activation of the basolateral calcium-sensing receptor (casr), which in the thick ascending limb of henle's loop controls ca2+ excretion and nacl reabsorption in response to extracellular ca2+ however, the function of casr in the regulation of nacl reabsorption in the distal convoluted tubule (dct) is unknown. we hypothesized that casr in this location is involved in activating the thiazide-sensitive nacl cotransporter (ncc) to prevent nacl loss.methods ...201829848507
asymmetric distribution of biomolecules of maternal origin in the xenopus laevis egg and their impact on the developmental plan.asymmetric cell division is a ubiquitous feature during the development of higher organisms. asymmetry is achieved by differential localization or activities of biological molecules such as proteins, and coding and non-coding rnas. here, we present subcellular transcriptomic and proteomic analyses along the animal-vegetal axis of xenopus laevis eggs. more than 98% of the maternal mrnas could be categorized into four localization profile groups: animal, vegetal, extremely vegetal, and a newly des ...201829844480
living xenopus oocytes, eggs, and embryos as models for cell division.xenopus laevis has long been a popular model for studies of development and, based on the use of cell-free extracts derived from its eggs, as a model for reconstitution of cell cycle regulation and other basic cellular processes. however, work over the last several years has shown that intact xenopus eggs and embryos are also powerful models for visualization and characterization of cell cycle-regulated cytoskeletal dynamics. these findings were something of a surprise, given that the relatively ...201829804672
conserved rna binding activity of a yin-yang 1 homologue in the ova of the purple sea urchin strongylocentrotus purpuratus.yin-yang 1 (yy1) is a highly conserved transcription factor possessing rna-binding activity. a putative yy1 homologue was previously identified in the developmental model organism strongylocentrotus purpuratus (the purple sea urchin) by genomic sequencing. we identified a high degree of sequence similarity with yy1 homologues of vertebrate origin which shared 100% protein sequence identity over the dna- and rna-binding zinc-finger region with high similarity in the n-terminal transcriptional act ...201829795182
a novel clcn5 pathogenic mutation supports dent disease with normal endosomal acidification.dent disease is an x-linked recessive renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure. inactivating mutations of clcn5, the gene encoding the 2cl- /h+ exchanger clc-5, have been reported in patients with dent disease 1. in vivo studies in mice harboring an artificial mutation in the "gating glutamate" of clc-5 (c.632a > c, p.glu211ala) and mathematical modeling suggest that endosomal chlori ...201829791050
rod-specific ablation using the nitroreductase/metronidazole system to investigate regeneration in xenopus.genetically controlled cell type-specific ablation provides a reproducible method to induce regeneration that can be temporally and spatially controlled. until recently, regeneration studies in xenopus have relied on surgical methods to stimulate regeneration. these methods are labor intensive and not as reproducible as a genetically controlled approach. in this protocol we describe selective ablation of rod photoreceptors in the premetamorphic xenopus laevis retina using the nitroreductase/metr ...201829789402
septin-dependent remodeling of cortical microtubule drives cell reshaping during epithelial wound healing.wounds in embryos heal rapidly through contraction of the wound edges. despite well-recognized significance of the actomyosin purse string for wound closure, roles for other cytoskeletal components are largely unknown. here, we report that the septin cytoskeleton cooperates with actomyosin and microtubules to coordinate circumferential contraction of the wound margin and concentric elongation of wound-proximal cells in xenopus laevis embryos. microtubules reoriented radially, forming bundles alo ...201829777035
dissecting and culturing animal cap explants.the animal cap explant is a simple but adaptable tool available to developmental biologists. the use of animal cap explants in demonstrating the presence of mesoderm-inducting activity in the xenopus embryo vegetal pole is one of many elegant examples of their worth. animal caps respond to a range of growth factors (e.g., wnts, fgf, tgf-β), making them especially useful for studying signal transduction pathways and gene regulatory networks. explants are also suitable for examining cell behavior ...201829769399
larval thymectomy of xenopus laevis.in jawed vertebrates from sharks to mammals, the thymus is the primary (or central) lymphoid tissue where t cells develop and mature. the particular stromal cell types, cytokine environment, and tissue organization in the thymus are essential for v(d)j recombination, positive selection for major histocompatibility complex recognition, and negative selection against self-peptide recognition of most αβ t cells. the thymectomy operation on xenopus tadpole larva described here creates a t-cell-defic ...201829769397
methods for investigating the larval period and metamorphosis in xenopus.anuran metamorphosis resembles postembryonic development in mammals, a period around birth when many organs/tissues mature into their adult form as circulating thyroid and stress hormone levels are high. unlike uterus-enclosed mammalian embryos, tadpoles develop externally and undergo the dramatic changes of hormone-dependent development totally independent of maternal influence, making them a valuable model in which to study vertebrate postembryonic organ development and maturation. various pro ...201829769395
infrared laser-mediated gene induction at the single-cell level in the regenerating tail of xenopus laevis tadpoles.we describe a precise and reproducible gene-induction method in the amphibian, xenopus laevis tetrapod amphibians are excellent models for studying the mechanisms of three-dimensional organ regeneration because they have an exceptionally high regenerative ability. however, spatial and temporal manipulation of gene expression has been difficult in amphibians, hindering studies on the molecular mechanisms of organ regeneration. recently, however, development of a xenopus transgenic system with a h ...201829769391
cell transplantation as a method to investigate spinal cord regeneration in regenerative and nonregenerative xenopus stages.mammals are not capable of regenerating their central nervous system (cns); anamniotes, however, can regenerate in response to injury. the mechanisms that explain the different regenerative capabilities include: (i) extrinsic mechanisms that consider the cellular environment and extracellular matrix composition, (ii) intrinsic factors implicating the presence or absence of genetic programs that promote axon regeneration, and (iii) the presence or absence of neural stem and progenitors cells (nsp ...201829769390
retinoic acid-induced expression of hnf1b and fzd4 is required for pancreas development in xenopus laevis.retinoic acid (ra) is required for pancreas specification in xenopus and other vertebrates. however, the gene network that is directly induced by ra signalling in this context remains to be defined. by rna sequencing of in vitro-generated pancreatic explants, we identified the genes encoding the transcription factor hnf1β and the wnt-receptor fzd4/fzd4s as direct ra target genes. functional analyses of hnf1b and fzd4/fzd4s in programmed pancreatic explants and whole embryos revealed their requir ...201829769220
coulomb and ch-π interactions in (6-4) photolyase-dna complex dominate dna binding and repair abilities.(6-4) photolyases ((6-4)pls) are flavoenzymes that repair the carcinogenic uv-induced dna damage, pyrimidine(6-4)pyrimidone photoproducts ((6-4)pps), in a light-dependent manner. although the reaction mechanism of dna photorepair by (6-4)pls has been intensively investigated, the molecular mechanism of the lesion recognition remains obscure. we show that a well-conserved arginine residue in xenopus laevis (6-4)pl (xl64) participates in dna binding, through coulomb and ch-π interactions. fragment ...201829762762
rxr ligands modulate thyroid hormone signaling competence in young xenopus laevis tadpoles.appropriate thyroid hormone (th) signaling through thyroid hormone receptors (trs) is essential for vertebrate development. amphibian metamorphosis is initiated and sustained through the action of th on trs, which are conserved across vertebrates. trs heterodimerize with retinoid x receptors (rxrs) on thyroid hormone response elements (tres) in the genome; however, in most cell line and adult animal studies, rxr ligands do not affect expression of tr target genes. we used a quantitative, precoci ...201829762675
expression variation and covariation impair analog and enable binary signaling control.due to noise in the synthesis and degradation of proteins, the concentrations of individual vertebrate signaling proteins were estimated to vary with a coefficient of variation (cv) of approximately 25% between cells. such high variation is beneficial for population-level regulation of cell functions but abolishes accurate single-cell signal transmission. here, we measure cell-to-cell variability of relative protein abundance using quantitative proteomics of individual xenopus laevis eggs and cu ...201829759982
identification of loop d domain amino acids in the human aquaporin-1 channel involved in activation of the ionic conductance and inhibition by aqb011.aquaporins are integral proteins that facilitate the transmembrane transport of water and small solutes. in addition to enabling water flux, mammalian aquaporin-1 (aqp1) channels activated by cyclic gmp can carry non-selective monovalent cation currents, selectively blocked by arylsulfonamide compounds aqb007 (ic50 170 μm) and aqb011 (ic50 14 μm). in silico models suggested that ligand docking might involve the cytoplasmic loop d (between aqp1 transmembrane domains 4 and 5), but the predicted si ...201829755973
ligand binding and activation properties of the purified bacterial cyclic nucleotide-gated channel sthk.cyclic nucleotide-modulated ion channels play several essential physiological roles. they are involved in signal transduction in photoreceptors and olfactory sensory neurons as well as pacemaking activity in the heart and brain. investigations of the molecular mechanism of their actions, including structural and electrophysiological characterization, are restricted by the availability of stable, purified protein obtained from accessible systems. here, we establish that sthk, a cyclic nucleotide- ...201829752414
retraction of rod-like mitochondria during microtubule-dependent transport.molecular motors play relevant roles on the regulation of mitochondria size and shape, essential properties for the cell homeostasis. in this work, we tracked single rod-shaped mitochondria with nanometer precision to explore the performance of microtubule motor teams during processive anterograde and retrograde transport. we analyzed simultaneously the organelle size and verified that mitochondria retracted during retrograde transport with their leading tip moving slower in comparison with the ...201829752335
determination of metals and pharmaceutical compounds released in hospital wastewater from toluca, mexico, and evaluation of their toxic impact.due to the activities inherent to medical care units, the hospital effluent released contains diverse contaminants such as tensoactives, disinfectants, metals, pharmaceutical products and chemical reagents, which are potentially toxic to the environment since they receive no treatment or are not effectively removed by such treatment before entering the drain. they are incorporated into municipal wastewater, eventually entering water bodies where they can have harmful effects on organisms and can ...201829751329
yokukansan contains compounds that antagonize the 5-ht3 receptor.we recently focused on alkaloids in uncaria hook (a constituent of the kampo medicine, yokukansan) and identified the pharmacological action of geissoschizine methyl ether on several g protein-coupled receptors. however, the functions of other identified alkaloids in uncaria hook, including hirsutine, hirsuteine, rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine, are not clear.201829747744
foxo4 activity is regulated by phosphorylation and the cellular environment during dehydration in the african clawed frog, xenopus laevis.the african clawed frog, xenopus laevis, is capable of enduring seasonal bouts of severe dehydration stress resulting from transcriptional regulation that facilitates a pro-survival response. previous studies have shown that dehydration increases antioxidant gene expression in this amphibian. as foxo4 is known to regulate several antioxidant genes, we sought to understand how differential phosphorylation and environmental factors (urea, temperature) may contribute to its transcriptional regulati ...201829746959
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
deciphering the molecular determinants of cholinergic anthelmintic sensitivity in nematodes: when novel functional validation approaches highlight major differences between the model caenorhabditis elegans and parasitic species.cholinergic agonists such as levamisole and pyrantel are widely used as anthelmintics to treat parasitic nematode infestations. these drugs elicit spastic paralysis by activating acetylcholine receptors (achrs) expressed in nematode body wall muscles. in the model nematode caenorhabditis elegans, genetic screens led to the identification of five genes encoding levamisole-sensitive-achr (l-achr) subunits: unc-38, unc-63, unc-29, lev-1 and lev-8. these subunits form a functional l-achr when hetero ...201829719008
transposable elements and polyploid evolution in animals.polyploidy in animals is much less common than in plants, where it is thought to be pervasive in all higher plant lineages. recent studies have highlighted the impact of polyploidization and the associated process of diploidy restoration on the evolution and speciation of selected taxonomic groups in the animal kingdom: from vertebrates represented by salmonid fishes and african clawed frogs to invertebrates represented by parasitic root-knot nematodes and bdelloid rotifers. in this review, we f ...201829715568
cardiac regeneration in xenopus tropicalis and xenopus laevis: discrepancies and problems.two studies have recently focused on adult heart regeneration in xenopus. while we reported on cardiac myogenic regeneration in xenopus tropicalis after injury, marshall and colleagues found no regeneration in an injured heart in xenopus laevis. here, we would like to join the discussion initiated by marshall et al. who debated the methods and species differences in both studies. we agree with their view that the species difference in cardiac regenerative capacity could lead to different results ...201829713455
is adult cardiac regeneration absent in xenopus laevis yet present in xenopus tropicalis?we recently used an endoscopy-based resection method to explore the consequences of cardiac injury in adult xenopus laevis, obtaining the result that the adult xenopus heart is unable to regenerate. at 11 months post-amputation, cellular and biological marks of scarring persisted. we thus concluded that, contrary to urodeles and teleosts, adult anurans share a cardiac injury outcome similar to adult mammals. however, in their work published in this journal on the 13 december 2017, liao et al. sh ...201829713454
nmda receptor signaling is important for neural tube formation and for preventing antiepileptic drug-induced neural tube defects.failure of neural tube closure leads to neural tube defects (ntds), which can have serious neurological consequences or be lethal. use of antiepileptic drugs (aeds) during pregnancy increases the incidence of ntds in offspring by unknown mechanisms. here we show that during xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. we demonstrate that nmda receptors are important for the formation of the neura ...201829712790
xenopus laevis oocyte as a model for the study of the cytoskeleton.at the beginning of diplotene, the oocyte of xenopus laevis is a cell of about 10-20 microns destined to increase 10,000-fold its size when the oocyte becomes filled with yolk platelets and has accumulated a great number of pigment granules in a half of its periphery. its internal architecture is gradually accomplished during growth because of several factors, especially because of cytoskeletal changes. in the fully-grown oocyte, the cytoskeleton appears to sustain the eccentrically located germ ...201829705198
roles of xenopus chemokine ligand cxclh (xcxclh) in early embryogenesis.several chemokine molecules control cell movements during early morphogenesis. however, it is unclear whether chemokine molecules affect cell fate. here, we identified and characterized the cxc-type chemokine ligand in xenopus laevis, xenopus cxclh (xcxclh), during early embryogenesis. xcxclh is expressed in the dorsal vegetal region at the gastrula stage. both overexpression and knockdown of xcxclh in the dorsal region inhibited gastrulation. xcxclh contributed to the attraction of mesendoderma ...201829700804
effect of hemin, baicalein and heme oxygenase-1 (ho-1) enzyme activity inhibitors on cd-induced accumulation of ho-1, hsps and aggresome-like structures in xenopus kidney epithelial cells.cadmium is a highly toxic environmental pollutant that can cause many adverse effects including cancer, neurological disease and kidney damage. aquatic amphibians are particularly susceptible to this toxicant as it was shown to cause developmental abnormalities and genotoxic effects. in mammalian cells, the accumulation of heme oxygenase-1 (ho-1), which catalyzes the breakdown of heme into co, free iron and biliverdin, was reported to protect cells against potentially lethal concentrations of cd ...201829698685
microvascular anatomy of the brain of the adult pipid frog, xenopus laevis (daudin): a scanning electron microscopic study of vascular corrosion casts.to demonstrate the 3d microvascular anatomy of the brain of the model organism xenopus laevis daudin scanning electron microscopy of vascular corrosion casts was correlated with light microscopy of stained 7 µm thick serial tissues sections. results showed that supplying arteries descended from the leptomeningeal surface without remarkable branchings straight to the subventricular zone where they branched and capillarized. capillaries showed few h- and/or y-shaped anastomoses during their centri ...201829693258
developmental toxicity of dibutyl phthalate and citrate ester plasticizers in xenopus laevis embryos.citrate esters have been considered as alternatives to phthalate plasticizers. being considered to have low toxicity in mammals, their toxicological information for aquatic animals remains poorly understood. we examined the developmental toxicity of citrate esters including tributyl o-acetylcitrate (atbc), triethyl 2-acetylcitrate (atec), and trihexyl o-acetylcitrate (athc) together with dibutyl phthalate (dbp) based on the frog embryo teratogenesis assay-xenopus (fetax). atbc has the lowest 96  ...201829684872
new apetx-like peptides from sea anemone heteractis crispa modulate asic1a channels.sea anemones are an abundant source of various biologically active peptides. the hydrophobic 20% ethanol fraction of tropical sea anemone heteractis crispa was shown to contain at least 159 peptide compounds including neurotoxins, proteinase and α-amylase inhibitors, as well as modulators of acid-sensing ion channels (asics). the three new peptides, π-anmtx hcr 1b-2, -3, and -4 (41 aa) (short names hcr 1b-2, -3, -4), identified by a combination of reversed-phase liquid chromatography and mass sp ...201829684594
comparison of oocyte mrna localization patterns in sterlet acipenser ruthenus and african clawed frog xenopus laevis.in oocytes, rna localization has critical implications, as assembly of proteins in particular subcellular domains is crucial to embryo development. the distribution of mrna molecules can identify and characterize localized transcripts. the goal of this study was to clarify the origin of primordial germ cells in the oocyte body plan and to reveal the generation of cell lineages by localized rnas. the distribution of 12 selected mrnas in sterlet acipenser ruthenus oocytes was investigated by qpcr ...201829682883
effects of multiple life stage exposure to the fungicide prochloraz in xenopus laevis: manifestations of antiandrogenic and other modes of toxicity.the larval amphibian growth and development assay (lagda) is an internationally harmonized testing guideline for evaluating effects of chronic chemical exposure in amphibians. in order to evaluate the effects of chronic exposure to an antiandrogenic chemical in an amphibian model, prochloraz was tested using a variation of the lagda design. exposure was initiated with <1d post-fertilization embryos at nominal concentrations of 0, 6.7, 20, 60 and 180 μg/l (0, 18, 53, 159, 478 nm) and continued in ...201829674245
fluorescent anesthetics.methods for using exogenous fluorophore and general anesthetic 1-aminoanthracene (1-ama) and its photoactive derivative 1-azidoanthracene (1-aza) are provided. 1-ama potentiates gabaa chloride currents and immobilizes xenopus laevis tadpoles. cellular and tissue anesthetic distribution can be imaged for quantifying "on-pathway" and "off-pathway" targets. 1-aza shares targets with 1-ama and offers further optoanesthetic spatial and temporal control upon near-uv laser irradiation. furthermore, 1-a ...201829673536
galantamine is not a positive allosteric modulator of human α4β2 or α7 nicotinic acetylcholine receptors.the alkaloid galantamine was originally isolated from the green snowdrop galanthus woronowii and is currently marketed as a drug for treatment of mild to moderate dementia in patients with alzheimer's disease. in addition to a well-documented proficiency to inhibit acetylcholinesterase, galantamine has been reported to increase neuronal nicotinic ach (nach) receptor function by acting as a positive allosteric modulator. yet there remains controversy regarding these findings in the literature. to ...201829669164
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