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non-acylated wnts can promote signaling.wnts are a family of 19 extracellular ligands that regulate cell fate, proliferation, and migration during metazoan embryogenesis and throughout adulthood. wnts are acylated post-translationally at a conserved serine and bind the extracellular cysteine-rich domain (crd) of frizzled (fzd) seven-pass transmembrane receptors. although crystal structures suggest that acylation is essential for wnt binding to fzds, we show here that several wnts can promote signaling in xenopus laevis and danio rerio ...201930673610
effect of the flavonoid hesperidin on glucose and fructose transport, sucrase activity and glycaemic response to orange juice in a crossover trial on healthy volunteers.although polyphenols inhibit glucose absorption and transport in vitro, it is uncertain whether this activity is sufficient to attenuate glycaemic response in vivo. we examined this using orange juice, which contains high levels of hesperidin. we first used a combination of in vitro assays to evaluate the potential effect of hesperidin and other orange juice components on intestinal sugar absorption and then tested whether this translated to an effect in healthy volunteers. hesperidin attenuated ...201930670104
whole-cell photoacoustic sensor based on pigment relocalization.photoacoustic (optoacoustic) imaging can extract molecular information with deeper tissue penetration than possible by fluorescence microscopy techniques. however, there is currently still a lack of robust genetically controlled contrast agents and molecular sensors that can dynamically detect biological analytes of interest with photoacoustics. in a biomimetic approach, we took inspiration from cuttlefish who can change their color by relocalizing pigment-filled organelles in so-called chromato ...201930663315
x-linked α-thalassemia with mental retardation is downstream of protein kinase a in the meiotic cell cycle signaling cascade in xenopus oocytes and is dynamically regulated in response to dna damage†.x-linked α-thalassemia with mental retardation (atrx) is a chromatin remodeling protein that belongs to the switch/sucrose non-fermentable (swi2/snf2) family of helicase/atpases. during meiosis, atrx is necessary for heterochromatin formation and maintenance of chromosome stability in order to ensure proper assembly of the metaphase ii spindle. previously, we established atrx as a novel progesterone regulated protein during bovine meiotic maturation, in addition to being dynamically regulated in ...201930649195
the electrical block to polyspermy induced by an intracellular ca2+ increase at fertilization of the clawed frogs, xenopus laevis and xenopus tropicalis.polyspermy blocking, to ensure monospermic fertilization, is necessary for normal diploid development in most animals. we have demonstrated here that monospermy in the clawed frog, xenopus tropicalis, as well as in x. laevis, is ensured by a fast, electrical block to polyspermy on the egg plasma membrane after the entry of the first sperm, which is mediated by the positive-going fertilization potential. an intracellular ca2+ concentration ([ca2+ ]i ) at the sperm entry site was propagated as a c ...201930648313
xenopus oocytes as a heterologous expression system for analysis of tight junction proteins.claudins (cldns) represent the largest family of transmembrane tight junction (tj) proteins, determining organ-specific epithelial barrier properties. because methods for the analysis of multiple cldn interaction are limited, we have established the heterologous xenopus laevis oocyte expression system for tj protein assembly and interaction analysis. oocytes were injected with crna encoding human cldn-1, -2, or -3 or with a combination of these and were incubated in pairs for interaction analysi ...201930645152
insemination or phosphatidic acid induces an outwardly spiraling disk of elevated ca2+ to produce the ca2+ wave during xenopus laevis fertilization.during xenopus fertilization, the initial intracellular calcium ((ca2+)i) release at the sperm-egg binding site (hot spot) has not been described without the use of inhibitors, nor related to underlying er structure. without inhibitors, we now report that sperm induce an initial hot spot after sperm addition to xenopus eggs that was ~25 µm. this area is consistent with the size of er patches and clusters of ip3 receptors that have enhanced activity. furthermore, we find a new mechanism for the f ...201930641042
deuterium-free, three-plexed peptide diethylation for highly accurate quantitative proteomics.the deuterium, a frequently used stable isotope in isotopic labeling for quantitative proteomics, could deteriorate the accuracy and precision of proteome quantification owing to the retention time shift of deuterated peptides from the hydrogenated counterpart. we introduce a novel three-plexed peptide "diethylation" using only 13c isotopologues of acetaldehyde and demonstrate that the accuracy and precision of our method in proteome quantification are significantly superior to the conventional ...201930638020
purification and characterization of a urea sensitive lactate dehydrogenase from skeletal muscle of the african clawed frog, xenopus laevis.the african clawed frog, xenopus laevis endures whole body dehydration which can increase its reliance on anaerobic glycolysis for energy production. this makes the regulation of the terminal enzyme of glycolysis, lactate dehydrogenase (ldh), crucial to stress survival. we investigated the enzymatic properties and posttranslational modification state of purified ldh from the skeletal muscle of control and dehydrated (30% total body water loss) x. laevis. ldh from the muscle of dehydrated frogs s ...201930631901
rhinella marina oocytes: a suitable alternative expression system for functional characterization of aquaglyceroporins.amphibian oocytes have been extensively used for heterologous expression of membrane proteins for studying their biochemical and biophysical properties. so far, xenopus laevis is the main amphibian used as oocytes source to express aquaglyceroporins in order to assess water and solutes permeability. however, this well-established amphibian model represents a threat to the biodiversity in many countries, especially in those from tropical regions. for that reason, the import of xenopus laevis is s ...201930631140
identification of vacuolar phosphate efflux transporters in land plants.inorganic phosphate (pi) is an essential component of all life forms. land plants acquire pi from the soil through roots and associated symbioses, and it is then transported throughout the plant. when sufficient, excess pi is stored in vacuoles for remobilization following pi deficiency. although pi release from the vacuoles to the cytoplasm serves as a critical mechanism for plants to adapt to low-pi stress, the transporters responsible for vacuolar pi efflux have not been identified. here, we ...201930626920
ensa and arpp19 differentially control cell cycle progression and development.greatwall (gwl) is an essential kinase that indirectly controls pp2a-b55, the phosphatase counterbalancing cyclin b/cdk1 activity during mitosis. in xenopus laevis egg extracts, gwl-mediated phosphorylation of overexpressed arpp19 and ensa turns them into potent pp2a-b55 inhibitors. it has been shown that the gwl/ensa/pp2a-b55 axis contributes to the control of dna replication, but little is known about the role of arpp19 in cell division. by using conditional knockout mouse models, we investiga ...201930626720
xenopus slc7a5 is essential for notochord function and eye development.slc7a5 (also known as lat1), largely accepted as an amino acid transporter, has been shown to play important roles in cancer and developmental processes. because knockout mice of slc7a5 are embryonically lethal due to placental defects, it is difficult to evaluate its role in early development. in this study, expression and function of slc7a5 were evaluated in xenopus laevis embryos that develop without a placenta. expression of slc7a5 was detected in the notochord and in the eye and it was not ...201930625369
reinterpretation of the substrate specificity of the voltage-sensing phosphatase during dimerization.voltage-sensing phosphatases (vsps) cleave both 3- and 5-phosphates from inositol phospholipids in response to membrane depolarization. when low concentrations of ciona intestinalis vsp are expressed in xenopus laevis oocytes, the 5-phosphatase reaction can be observed during large membrane depolarizations. when higher concentrations are expressed, the 5-phosphatase activity is observed with smaller depolarizations, and the 3-phosphatase activity is revealed with strong depolarization. here we a ...201930622132
probing the dynamics and structural topology of the reconstituted human kcnq1 voltage sensor domain (q1-vsd) in lipid bilayers using electron paramagnetic resonance spectroscopy.kcnq1 (kv7.1 or kvlqt1) is a potassium ion channel protein found in the heart, ear, and other tissues. in complex with the kcne1 accessory protein, it plays a role during the repolarization phase of the cardiac action potential. mutations in the channel have been associated with several diseases, including congenital deafness and long qt syndrome. nuclear magnetic resonance (nmr) structural studies in detergent micelles and a cryo-electron microscopy structure of kcnq1 from xenopus laevis have s ...201930620191
immunohistochemical localization of calpains in the amphibian xenopus laevis.though histochemical techniques have been used for decades, they are still very important in basic research. they make it possible to work on fixed tissues and provide a large amount of information in a relatively short time and at a low cost. here we describe methods for indirect immunohistochemistry and immunofluorescence on sections of tadpoles and tissues of adult amphibians belonging to the species xenopus laevis. the objective is to localize calpains within tissues in order to understand t ...201930617797
a stable tetramer is not the only oligomeric state that mitochondrial single-stranded dna binding proteins can adopt.mitochondrial single-stranded dna (ssdna)-binding proteins (mtssbs) are required for mitochondrial dna replication and stability and are generally assumed to form homotetramers, and this species is proposed to be the one active for ssdna binding. however, we recently reported that the mtssb from saccharomyces cerevisiae (scrim1) forms homotetramers at high protein concentrations, whereas at low protein concentrations, it dissociates into dimers that bind ssdna with high affinity. in this work, u ...201930617184
arid3a regulates nephric tubule regeneration via evolutionarily conserved regeneration signal-response enhancers.amphibians and fish have the ability to regenerate numerous tissues, whereas mammals have a limited regenerative capacity. despite numerous developmental genes becoming reactivated during regeneration, an extensive analysis is yet to be performed on whether highly regenerative animals utilize unique cis-regulatory elements for the reactivation of genes during regeneration and how such cis-regulatory elements become activated. here, we screened regeneration signal-response enhancers at the lhx1 l ...201930616715
applications of in-cell nmr in structural biology and drug discovery.in-cell nuclear magnetic resonance (nmr) is a method to provide the structural information of a target at an atomic level under physiological conditions and a full view of the conformational changes of a protein caused by ligand binding, post-translational modifications or protein⁻protein interactions in living cells. previous in-cell nmr studies have focused on proteins that were overexpressed in bacterial cells and isotopically labeled proteins injected into oocytes of xenopus laevis or delive ...201930609728
curare alkaloids from matis dart poison: comparison with d-tubocurarine in interactions with nicotinic, 5-ht3 serotonin and gabaa receptors.several novel bisbenzylisoquinoline alkaloids (bbiqas) have recently been isolated from a matis tribe arrow poison and shown by two-electrode voltage-clamp to inhibit mouse muscle nicotinic acetylcholine receptors (nachr). here, using radioligand assay with aplysia californica achbp and radioiodinated α-bungarotoxin ([125i]-αbgt), we show that bbiqa1, bbiqa2, and d-tubocurarine (d-tc) have similar affinities to nachr orthosteric site. however, a competition with [125i]-αbgt for binding to the to ...201930608952
skin grafting in xenopus laevis: a technique for assessing development and immunological disparity.skin grafting in the amphibian xenopus laevis has been used to detect not only allogeneic antigens that differ by minor h antigens or by one mhc haplotype, but also to detect ontogeny-specific antigens (including both emerging adult- and disappearing larval-specific) during metamorphosis. to understand the mechanisms underlying allogeneic tolerance or immune responses against larval- and/or adult-specific antigens, a complete mhc homozygous, inbred strain is the most appropriate experimental mod ...201930606753
methodological improvements for fluorescence recordings in xenopus laevis oocytes.xenopus laevis oocytes are a widely used model system because of their capacity to translate exogenous mrna, but their high intrinsic background fluorescence is a disadvantage for fluorescence recordings. here, we developed two distinct methods for improving fluorescence recordings from oocytes. one was a pharmacological method in which a small-molecule salt-inducible kinase inhibitor was co-injected with the mrna of interest to stimulate melanin production. we interrogated the oocytes using cut ...201930606741
cdk phosphorylation of xenopus laevis m18bp1 promotes its metaphase centromere localization.chromosome segregation requires the centromere, the site on chromosomes where kinetochores assemble in mitosis to attach chromosomes to the mitotic spindle. centromere identity is defined epigenetically by the presence of nucleosomes containing the histone h3 variant cenp-a. new cenp-a nucleosome assembly occurs at the centromere every cell cycle during g1, but how cenp-a nucleosome assembly is spatially and temporally restricted remains poorly understood. centromere recruitment of factors requi ...201930606714
the cmg helicase bypasses dna-protein cross-links to facilitate their repair.covalent dna-protein cross-links (dpcs) impede replication fork progression and threaten genome integrity. using xenopus egg extracts, we previously showed that replication fork collision with dpcs causes their proteolysis, followed by translesion dna synthesis. we show here that when dpc proteolysis is blocked, the replicative dna helicase cmg (cdc45, mcm2-7, gins), which travels on the leading strand template, bypasses an intact leading strand dpc. single-molecule imaging reveals that gins doe ...201930595447
xenopus laevis fgf16 activates the expression of genes coding for the transcription factors sp5 and sp5l.fibroblast growth factors (fgfs) comprise a family of signalling molecules with essential roles in early embryonic development across animal species. the role of fgfs in mesoderm formation and patterning in xenopus has been particularly well studied. however, little is known about fgf16 in xenopus. using in situ hybridisation, we uncover the expression pattern of fgf16 during early xenopus laevis development, which has not been previously described. we show that the zygotic expression of fgf16 i ...201932149373
ventx1.1 as a direct repressor of early neural gene zic3 in xenopus laevis.from xenopus embryo studies, the bmp4/smad1-targeted gene circuit is a key signaling pathway for specifying the cell fate between the ectoderm and neuro-ectoderm as well as the ventral and dorsal mesoderm. in this context, several bmp4/smad1 target transcriptional factors have been identified as repressors of the neuro-ectoderm. however, none of these direct target transcription factors in this pathway, including gata1b, msx1 and ventx1.1 have yet been proven as direct repressors of early neuro- ...201830590909
development of a rapid functional assay that predicts glut1 disease severity.to examine the genotype to phenotype connection in glucose transporter type 1 (glut1) deficiency and whether a simple functional assay can predict disease outcome from genetic sequence alone.201830588498
bisphenol a, bisphenol af, di-n-butyl phthalate, and 17β-estradiol have shared and unique dose-dependent effects on early embryo cleavage divisions and development in xenopus laevis.bisphenol a (bpa), bisphenol af (bpaf), and di-n-butyl phthalate (dbp) are widespread compounds used in the production of plastics. we used xenopus laevis to compare their effects on early embryo cell division and development. directly after in vitro fertilizations, embryos were exposed to bpa, bpaf, dbp, or 17β-estradiol (e2) for up to 96 h. bpa (1-50 μm) and bpaf (0.003-25 μm) caused disrupted cleavage divisions, slowed cytokinesis, and cellular dissociation within 1-6 h. flexures of the spina ...201930579998
molecular charge associated with antiarrhythmic actions in a series of amino-2-cyclohexyl ester derivatives.a series of amino-2-cyclohexyl ester derivatives were studied for their ion channel blocking and antiarrhythmic actions in the rat and a structure-activity analysis was conducted. the compounds are similar in chemical structure except for ionizable amine groups (pk values 6.1-8.9) and the positional arrangements of aromatic naphthyl moieties. ventricular arrhythmias were produced in rats by coronary-artery occlusion or electrical stimulation. the electrophysiological effects of these compounds o ...201930571955
lack of evidence for synaptic high-affinity γ-hydroxybutyric acid (ghb) transport in rat brain synaptosomes and 11 na+ -dependent slc neurotransmitter transporters.γ-hydroxybutyric acid (ghb) is an endogenous compound proposed to act as a neurotransmitter. na+ -dependent, high-affinity ghb transport has long been considered important evidence supporting this hypothesis. however, the molecular identity of such a high-affinity transporter remains unknown. in this study, we sought to identify and characterize ghb synaptic transport through a series of studies using both native and recombinant systems with the ultimate aim of providing evidence to clarify the ...201930570143
lysine demethylase 3a in craniofacial and neural development during xenopus embryogenesis.epigenetic modifier lysine demethylase 3a (kdm3a) specifically demethylates mono‑ and di‑methylated ninth lysine of histone 3 and belongs to the jumonji domain‑containing group of demethylases. kdm3a serves roles during various biological and pathophysiological processes, including spermatogenesis and metabolism, determination of sex, androgen receptor‑mediated transcription and embryonic carcinoma cell differentiation. in the present study, physiological functions of kdm3a were evaluated during ...201930569092
ospht1;3 mediates uptake, translocation, and remobilization of phosphate under extremely low phosphate regimes.plant roots rely on inorganic orthophosphate (pi) transporters to acquire soluble pi from soil solutions that exists at micromolar levels in natural ecosystems. here, we functionally characterized a rice (oryza sativa) pi transporter, os phosphate transporter-1;3 (ospht1;3), that mediates pi uptake, translocation, and remobilization. ospht1;3 was directly regulated by os phosphate starvation response-2 and, in response to pi starvation, showed enhanced expression in young leaf blades and shoot b ...201930567970
xenopus hybrids provide insight into cell and organism size control.determining how size is controlled is a fundamental question in biology that is poorly understood at the organismal, cellular, and subcellular levels. the xenopus species, x. laevis and x. tropicalis differ in size at all three of these levels. despite these differences, fertilization of x. laevis eggs with x. tropicalis sperm gives rise to viable hybrid animals that are intermediate in size. we observed that although hybrid and x. laevis embryogenesis initiates from the same sized zygote and pr ...201830564147
alteration of the retinoid acid-cbp signaling pathway in neural crest induction contributes to enteric nervous system disorder.hirschsprung disease (hscr) and/or hypoganglionosis are common pediatric disorders that arise from developmental deficiencies of enteric neural crest cells (enccs). retinoid acid (ra) signaling has been shown to affect neural crest (nc) development. however, the mechanisms underlying ra deficiency-induced hscr or hypoganglionosis are not well-defined. in this report, we found that in hscr patient bowels, the ra nuclear receptor rarα and its interacting coregulator creb-binding protein (cbp) were ...201830560112
increasing nitroxide lifetime in cells to enable in-cell protein structure and dynamics measurements by electron spin resonance spectroscopy.there is increasing evidence that the stability, structure, dynamics, and function of many proteins differ in cells versus in vitro. the determination of protein structure and dynamics within the native cellular environment may lead to better understanding of protein behavior. electron spin resonance (esr) has emerged as a technique that can report on protein structure and dynamics within cells. nitroxide based spin labels are capable of reporting on protein dynamics, structure, and backbone fle ...201930550988
dual cationic-anionic profiling of metabolites in a single identified cell in a live xenopus laevis embryo by microprobe ce-esi-ms.in situ capillary microsampling with capillary electrophoresis (ce) electrospray ionization (esi) mass spectrometry (ms) enabled the characterization of cationic metabolites in single cells in complex tissues and organisms. for deeper coverage of the metabolome and metabolic networks, analytical approaches are needed that provide complementary detection for anionic metabolites, ideally using the same instrumentation. described here is one such approach that enables sequential cationic and anioni ...201930542678
modeling underwater hearing and sound localization in the frog xenopus laevis.animals that are small compared to sound wavelengths face the challenge of localizing a sound source since the main cues to sound direction-interaural time differences (itd) and interaural level differences (ild)-both depend on size. remarkably, the majority of terrestrial vertebrates possess internally coupled ears (ice) with an air-filled cavity connecting the two eardrums and producing an inherently directional middle-ear system. underwater, longer wavelengths and faster sound-speed reduce bo ...201830522324
silurana chromosomal evolution: a new piece to the puzzle.the african clawed frogs of the subgenus silurana comprise both diploid and tetraploid species. the root of the polyploidization event leading to the extant xenopus calcaratus, x. mellotropicalis, and x. epitropicalis is not fully understood so far. in x. mellotropicalis, we previously proposed 2 evolutionary scenarios encompassing complete (scenario a) or incomplete (scenario b) translocation of a heterochromatic block from chromosome 9 to 2 in a diploid ancestor. to resolve this puzzle, we per ...201830537723
the interplay between voluntary food intake, dietary carbohydrate-lipid ratio and nutrient metabolism in an amphibian, (xenopus laevis).digestion of food and metabolism of frogs are little studied at the moment, and such processes could be very particular in the case of amphibians, given their ectothermic and carnivorous nature which may lead them to use nutrients through specific biochemical pathways. in the present study, 24 adult xenopus laevis (six replicates with two frogs per treatment) were randomly assigned to two diets with different carbohydrate:fat ratio (4.5:1 and 2.1:1), changing the dietary glucogenic and lipogenic ...201830532132
radiobiological characteristics of descendant progeny of fish and amphibian cells that survive the initial ionizing radiation dose.to evaluate the development of delayed lethal mutations, the production of medium borne lethal bystander signals, and the acquirement of radiosensitive or radioresistant traits in distant descendant progeny of fish and amphibian cells surviving ionizing radiation materials and methods: american eel brain endothelial cells (eelb) and african clawed frog epithelial cells (a6) were initially irradiated with gamma rays at 0.5 gy or 2 gy. ionizing radiation (ir)-surviving cells were grown for 27 popu ...201930530089
a xenopus tadpole alternative model to study innate-like t cell-mediated anti-mycobacterial immunity.owing to the high incidence of multi-drug resistance and challenges posed by the complex and long duration of treatments, mycobacterium tuberculosis (mtb) infections remain a significant clinical burden, which would benefit from development of novel immuno-therapeutic-based treatment strategies. among early immune effectors, invariant or innate-like (i)t cells are attracting attention because of their potential regulatory activity, which can shape anti-mycobacterial immune responses. unlike conv ...201930521838
control of xenopus tadpole locomotion via selective expression of ih in excitatory interneurons.locomotion relies on the coordinated activity of rhythmic neurons in the hindbrain and spinal cord and depends critically on the intrinsic properties of excitatory interneurons. therefore, understanding how ion channels sculpt the properties of these interneurons, and the consequences for circuit function and behavior, is an important task. the hyperpolarization-activated cation current, ih, is known to play important roles in shaping neuronal properties and for rhythm generation in many neurona ...201830503615
genomic takeover by transposable elements in the strawberry poison frog.we sequenced the genome of the strawberry poison frog, oophaga pumilio, at a depth of 127.5× using variable insert size libraries. the total genome size is estimated to be 6.76 gb, of which 4.76 gb are from high copy number repetitive elements with low differentiation across copies. these repeats encompass dna transposons, rna transposons, and ltr retrotransposons, including at least 0.4 and 1.0 gb of mariner/tc1 and gypsy elements, respectively. expression data indicate high levels of gypsy and ...201830517748
enhanced visual experience rehabilitates the injured brain in xenopus tadpoles in an nmdar-dependent manner.traumatic brain injuries introduce functional and structural circuit deficits that must be repaired for an organism to regain function. we developed an injury model in which xenopus laevis tadpoles are given a penetrating stab wound that damages the optic tectal circuit and impairs visuomotor behavior. in tadpoles, as in other systems, injury induces neurogenesis. the newly generated neurons are thought to integrate into the existing circuit; however, whether they integrate via the same mechanis ...201930517041
effects of quinine, quinidine and chloroquine on human muscle nicotinic acetylcholine receptors.the genus cinchona is known for a range of alkaloids, such as quinine, quinidine, cinchonine, and cinchonidine. cinchona bark has been used as an antimalarial agent for more than 400 years. quinine was first isolated in 1820 and is still acknowledged in the therapy of chloroquine-resistant falciparum malaria; in lower dosage quinine has been used as treatment for leg cramps since the 1940s. here we report the effects of the quinoline derivatives quinine, quinidine, and chloroquine on human adult ...201830515099
auditory perception exhibits sexual dimorphism and left telencephalic dominance in xenopus laevis.sex differences in both vocalization and auditory processing have been commonly found in vocal animals, although the underlying neural mechanisms associated with sexual dimorphism of auditory processing are not well understood. in this study we investigated whether auditory perception exhibits sexual dimorphism in xenopus laevis to do this we measured event-related potentials (erps) evoked by white noise (wn) and conspecific calls in the telencephalon, diencephalon and mesencephalon respectively ...201830509903
sr 57227a is a partial agonist/partial antagonist of 5-ht3 receptor and inhibits subsequent 5-ht- or sr 57227a-induced 5-ht3 receptor current.the serotonin (5-hydroxytryptamine) type 3 (5-ht3) receptors are transmembrane ligand-gated ion channels. although several 5-ht3 receptor agonists have been used as preclinical tools, sr 57227a is the most commonly used 5-ht3 receptor agonist with the ability to cross the blood brain barrier. however, the precise pharmacological profile of sr 57227a remains unclear. therefore, we examined the pharmacological profile of sr 57227a at the 5-ht3a and 5-ht3ab receptors. we microinjected xenopus laevi ...201930509492
the effect of an environmentally relevant phthalate mixture on primordial germ cells of xenopus laevis embryos. 201832550375
involvement of epigenetic modifications in thyroid hormone-dependent formation of adult intestinal stem cells during amphibian metamorphosis.amphibian metamorphosis has long been used as model to study postembryonic development in vertebrates, a period around birth in mammals when many organs/tissues mature into their adult forms and is characterized by peak levels of plasma thyroid hormone (t3). of particular interest is the remodeling of the intestine during metamorphosis. in the highly-related anurans xenopus laevis and xenopus tropicalis, this remodeling process involves larval epithelial cell death and de novo formation of adult ...201930472386
solid lipid nanoparticles for the delivery of anti-microbial oligonucleotides.novel alternatives to antibiotics are urgently needed for the successful treatment of antimicrobial resistant (amr) infections. experimental antibacterial oligonucleotide therapeutics, such as transcription factor decoys (tfd), are a promising approach to circumvent amr. however, the therapeutic potential of tfd is contingent upon the development of carriers that afford efficient dna protection against nucleases and delivery of dna to the target infection site. as a carrier for tfd, here we pres ...201930468838
thyroid hormone levels and temperature during development alter thermal tolerance and energetics of xenopus laevis larvae.environmental variation induced by natural and anthropogenic processes including climate change may threaten species by causing environmental stress. anuran larvae experiencing environmental stress may display altered thyroid hormone (th) status with potential implications for physiological traits. therefore, any capacity to adapt to environmental changes through plastic responses provides a key to determining species vulnerability to environmental variation. we investigated whether developmenta ...201830464840
expression pattern and histone acetylation of energy metabolic genes in xenopus laevis liver in response to diet statuses.amphibians can survive without food for relatively longer periods by reducing the locomotor activity and metabolic rate and can recover quickly with refeeding from a dormant state. to clarify the molecular mechanism underlying this survival strategy, we investigated serum biochemical parameters, the transcript levels of energy metabolic genes, and global and gene-specific histone modifications in the liver of adult male xenopus laevis, which were fed, fasted, or refed after fasting. glucose, tri ...201930460762
how thyroid hormones and their inhibitors affect cartilage growth and shape in the frog xenopus laevis.understanding how skeleton changes shape in ontogeny is fundamental to understanding how its shape diversifies in phylogeny. amphibians pose a special case because their jaw and throat skeleton consists of cartilages that are dramatically reshaped midway through life to support new feeding and breathing styles. although amphibian metamorphosis is commonly studied by immersing larvae in thyroid hormones (th), how individual cartilages respond to th is poorly understood. this study documents the e ...201930456781
class a scavenger receptors mediate extracellular dsrna sensing, leading to downstream antiviral gene expression in a novel american toad cell line, bufotad.viral double-stranded (ds)rna is a potent pathogen-associated molecular pattern (pamp), capable of inducing a strong antiviral state within the cell, protecting the cell from virus infection. in mammals and fish, sensing extracellular dsrna is mediated by cell-surface class a scavenger receptors (sr-as). currently, very little is known about sr-as in amphibians, including: sequence, expression patterns and function. to this end, sr-a expression and function was studied in a novel american toad ( ...201930452932
cellspecks: a software for automated detection and analysis of calcium channels in live cells.to couple the fidelity of patch-clamp recording with a more high-throughput screening capability, we pioneered a, to our knowledge, novel approach to single-channel recording that we named "optical patch clamp." by using highly sensitive fluorescent ca2+ indicator dyes in conjunction with total internal fluorescence microscopy techniques, we monitor ca2+ flux through individual ca2+-permeable channels. this approach provides information about channel gating analogous to patch-clamp recording at ...201830447989
automating event-detection of brain neuron synaptic activity and action potential firing in vivo using a random-access multiphoton laser scanning microscope for real-time analysis.determining how a neuron computes requires an understanding of the complex spatiotemporal relationship between its input (e.g. synaptic input as a result of external stimuli) and action potential output. recent advances in in vivo, laser-scanning multiphoton technology, known as random-access microscopy (ram), can capture this relationship by imaging fluorescent light, emitted from calcium-sensitive biosensors responding to synaptic and action potential firing in a neuron's full dendritic arbor ...201830440280
expression of hyaluronan synthases upregulated by thyroid hormone is involved in intestinal stem cell development during xenopus laevis metamorphosis.during amphibian intestinal remodeling, thyroid hormone (th) induces adult stem cells, which newly generate the absorptive epithelium analogous to the mammalian one. we have previously shown that hyaluronan (ha) is newly synthesized and plays an essential role in the development of the stem cells via its major receptor cd44 in the xenopus laevis intestine. we here focused on ha synthase (has) and examined how the expression of has family genes is regulated during natural and th-induced metamorph ...201830430240
novel findings on the impact of chytridiomycosis on the cardiac function of anurans: sensitive vs. tolerant species.understanding of the physiological effects of chytridiomycosis is crucial to worldwide amphibian conservation. therefore, we analyzed the cardiac function of two anuran species (xenopus laevis and physalaemus albonotatus) with different susceptibilities to infection by the causative agent of chytridiomycosis, batrachochytrium dendrobatidis (hereafter bd).201830425891
a taxonomically and geographically constrained information base limits non-native reptile and amphibian risk assessment: a systematic review.for many taxa, new records of non-native introductions globally occur at a near exponential rate. we undertook a systematic review of peer-reviewed publications on non-native herpetofauna, to assess the information base available for assessing risks of future invasions, resulting in 836 relevant papers. the taxonomic and geographic scope of the literature was also compared to a published database of all known invasions globally. we found 1,116 species of herpetofauna, 95% of which were present i ...201830425887
development of an acute method to deliver transgenes into the brains of adult xenopus laevis.the central vocal pathway of the african clawed frog, xenopus laevis, is a powerful vertebrate model to understand mechanisms underlying central pattern generation. however, fast and efficient methods of introducing exogenous genes into the neurons of adult x. laevis are currently not available. here, we systematically tested methods of transgene delivery into adult x. laevis neurons. although successfully used for tadpole neurons for over a decade, electroporation was not efficient in transfect ...201830416430
proteolytic activation of bmps: analysis of cleavage in xenopus oocytes and embryos.bone morphogenetic proteins (bmps) are synthesized as inactive precursors that are cleaved to generate active ligands, along with prodomain fragments that can modulate growth factor activity. here we provide three protocols that can be used to examine the process of proteolytic activation of bmps. the first protocol describes how to generate radiolabeled bmp precursor proteins in xenopus oocytes and then analyze the time course of precursor cleavage by recombinant enzymes in vitro. the second pr ...201930414129
trypanosoma brucei aquaglyceroporins mediate the transport of metabolic end-products: methylglyoxal, d-lactate, l-lactate and acetate.bloodstream forms of trypanosoma (t.) brucei, the causative agent of african sleeping sickness, possess a highly active glycolysis, which generates as main end-products: pyruvate under aerobic conditions, and pyruvate and glycerol under anaerobic conditions. to secrete them into the extracellular milieu, the parasites have at least two main specific membrane proteins, the pyruvate transporter and the aquaglyceroporins however, there are several other minor products from the glycolysis that must ...201830409521
brief local application of progesterone via a wearable bioreactor induces long-term regenerative response in adult xenopus hindlimb.the induction of limb repair in adult vertebrates is a pressing, unsolved problem. here, we characterize the effects of an integrated device that delivers drugs to severed hindlimbs of adult xenopus laevis, which normally regenerate cartilaginous spikes after amputation. a wearable bioreactor containing a silk protein-based hydrogel that delivered progesterone to the wound site immediately after hindlimb amputation for only 24 hr induced the regeneration of paddle-like structures in adult frogs. ...201830404012
atlht1 transporter can facilitate the uptake and translocation of a glycinergic-chlorantraniliprole conjugate in arabidopsis thaliana.understanding of the transporters involved in the uptake and translocation of agrochemicals in plants could provide an opportunity to guide pesticide to the site of insect feeding. the product of arabidopsis thaliana gene atlht1 makes a major contribution to the uptake into the roots of free amino acids and some of their derivatives. here, a chlorantraniliprole-glycine conjugate (cap-gly-1) was tested for its affinity to atlht1 both in planta and in vitro. seedlings deficient in atlht1 exhibited ...201830403859
microtransplantation of human brain receptors into oocytes to tackle key questions in drug discovery.it is important in drug discovery to demonstrate that activity of novel drugs found by screening on recombinant receptors translates to activity on native human receptors in brain areas affected by disease. in this review, we summarise the development and use of the microtransplantation technique. native receptors are reconstituted from human brain tissues into oocytes from the frog xenopus laevis where they can be functionally assessed. oocytes microtransplanted with hippocampal tissue from an ...201930395928
transcriptome analysis of xenopus orofacial tissues deficient in retinoic acid receptor function.development of the face and mouth is orchestrated by a large number of transcription factors, signaling pathways and epigenetic regulators. while we know many of these regulators, our understanding of how they interact with each other and implement changes in gene expression during orofacial development is still in its infancy. therefore, this study focuses on uncovering potential cooperation between transcriptional regulators and one important signaling pathway, retinoic acid, during developmen ...201830390632
flow cytometric analysis of xenopus laevis and x. tropicalis blood cells using acridine orange.automated blood cell counters can distinguish cells based on their size and the presence or absence of a nucleus. however, most vertebrates have nucleated blood cells that cannot be counted automatically. we established an alternative automatic method for counting peripheral blood cells by staining cells with the fluorescent dye acridine orange (ao) and analysing cell populations using flow cytometry (fcm). as promising new animal models, we chose xenopus laevis and three inbred strains of x. tr ...201830390005
size-dependent functional response of xenopus laevis feeding on mosquito larvae.predators can play an important role in regulating prey abundance and diversity, determining food web structure and function, and contributing to important ecosystem services, including the regulation of agricultural pests and disease vectors. thus, the ability to predict predator impact on prey is an important goal in ecology. often, predators of the same species are assumed to be functionally equivalent, despite considerable individual variation in predator traits known to be important for sha ...201830386704
comprehensive analysis of formin localization in xenopus epithelial cells.reorganization of the actin cytoskeleton is crucial for cellular processes, including cytokinesis and cell-cell junction remodeling. formins are conserved processive actin-polymerizing machines that regulate actin dynamics by nucleating, elongating, and bundling linear actin filaments. because the formin family is large, with at least 15 members in vertebrates, there have not been any comprehensive studies examining formin localization and function within a common cell type. here, we characteriz ...201930379611
anticipation of food intake induces phosphorylation switch to regulate basolateral amino acid transporter lat4 (slc43a2) function.amino acid absorption requires luminal uptake into and subsequent basolateral efflux out of epithelial cells, with the latter step being critical to regulate the intracellular concentration of the amino acids. the basolateral essential neutral amino acid uniporter lat4 (slc43a2) has been suggested to drive the net efflux of non-essential and cationic amino acids via parallel amino acid antiporters by recycling some of their substrates; its deletion has been shown to cause defective postnatal gro ...201930379325
calcineurin promotes apc/c activation at meiotic exit by acting on both xerp1 and cdc20.vertebrate oocytes await fertilization arrested at metaphase of the second meiotic division. fertilization triggers a transient calcium wave, which induces the activation of the anaphase-promoting complex/cyclosome (apc/c) and its co-activator cdc20 resulting in the destruction of cyclin b and hence meiotic exit. two calcium-dependent enzymes are implicated in fertilization-induced apc/ccdc20 activation: calcium-/calmodulin-dependent kinase type ii (camkii) and calcineurin (can). while the role ...201830373936
assessment of the complex refractive indices of xenopus laevis sciatic nerve for the optimization of optical (nir) neurostimulation.despite an increasing interest in the use of light for neural stimulation, there is little information on how it interacts with neural tissue. the choice of wavelength in most of the optical stimulation literature is based on already available light sources designed for other applications. this paper is the first one to report the complex refractive index of the sciatic nerve of xenopus laevis, which is a crucial parameter for identifying the optimal wavelength of optical stimuli. the xenopus la ...201830371379
the receptor-like pseudokinase ghr1 is required for stomatal closure.guard cells control the aperture of stomatal pores to balance photosynthetic carbon dioxide uptake with evaporative water loss. stomatal closure is triggered by several stimuli that initiate complex signaling networks to govern the activity of ion channels. activation of slow anion channel1 (slac1) is central to the process of stomatal closure and requires the leucine-rich repeat receptor-like kinase (lrr-rlk) guard cell hydrogen peroxide-resistant1 (ghr1), among other signaling components. here ...201830361234
a modified tripeptide motif of rs1 (rsc1a1) down-regulates exocytotic pathways of human na+-d-glucose cotransporters sglt1, sglt2, and glucose sensor sglt3 in the presence of glucose.a domain of protein rs1 (rsc1a1) called rs1-reg down-regulates the plasma membrane abundance of na+-d-glucose cotransporter sglt1 by blocking the exocytotic pathway at the trans-golgi. this effect is blunted by intracellular glucose but prevails when serine in a qsp (gln-ser-pro) motif is replaced by glutamate [rs1-reg(s20e)]. rs1-reg binds to ornithine decarboxylase (odc) and inhibits odc in a glucose-dependent manner. because the odc inhibitor difluoromethylornithine (dfmo) acts like rs1-reg(s ...201930355744
functional studies of transcriptional cofactors via microinjection-mediated gene editing in xenopus.the anuran xenopus laevis has been studied for decades as a model for vertebrate cell and developmental biology. more recently, the highly related species xenopus tropicalis has offered the opportunity to carry out genetic studies due to its diploid genome as compared to the pseudo-tetraploid xenopus laevis. amphibians undergo a biphasic development: embryogenesis to produce a free-living tadpoles and subsequent metamorphosis to transform the tadpole to a frog. this second phase mimics the so-ca ...201930353533
divergent subgenome evolution after allopolyploidization in african clawed frogs (xenopus).whole genome duplication (wgd), the doubling of the nuclear dna of a species, contributes to biological innovation by creating genetic redundancy. one mode of wgd is allopolyploidization, wherein each genome from two ancestral species becomes a 'subgenome' of a polyploid descendant species. the evolutionary trajectory of a duplicated gene that arises from wgd is influenced both by natural selection that may favour redundant, new or partitioned functions, and by gene silencing (pseudogenization). ...201830341989
synthetic light-activated ion channels for optogenetic activation and inhibition.optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (chr2). chr2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. however, its calcium (ca2+) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular ca2+ might be desirable. moreover, there is need for an efficient lig ...201830333716
multiple combinations of rdl subunits diversify the repertoire of gaba receptors in the honey bee parasite varroa destructor.in insects, γ-aminobutyric acid (gaba) is the major inhibitory neurotransmitter, and gaba-gated ion channels are the target of different classes of insecticides, including fipronil. we report here the cloning of six subunits (four rdl, one lcch3, and one grd) that constitute the repertoire of the gaba-gated ion channel family of the varroa mite (varroa destructor), a honey bee ectoparasite. we also isolated a truncated grd subunit with a premature stop codon. we found that when expressed in xeno ...201830333227
emerin induces nuclear breakage in xenopus extract and early embryos.emerin is an inner nuclear membrane protein often mutated in emery-dreifuss muscular dystrophy. because emerin has diverse roles in nuclear mechanics, cytoskeletal organization, and gene expression, it has been difficult to elucidate its contribution to nuclear structure and disease pathology. in this study, we investigated emerin's impact on nuclei assembled in xenopus laevis egg extract, a simplified biochemical system that lacks potentially confounding cellular factors and activities. notably ...201830332321
early redox activities modulate xenopus tail regeneration.redox state sustained by reactive oxygen species (ros) is crucial for regeneration; however, the interplay between oxygen (o2), ros and hypoxia-inducible factors (hif) remains elusive. here we observe, using an optic-based probe (optrode), an elevated and steady o2 influx immediately upon amputation. the spatiotemporal o2 influx profile correlates with the regeneration of xenopus laevis tadpole tails. inhibition of ros production but not ros scavenging decreases o2 influx. inhibition of hif-1α i ...201830327466
expression of trpv channels during xenopus laevis embryogenesis.transient receptor potential (trp) cation channel genes code for an extensive family of conserved proteins responsible for a variety of physiological processes, including sensory perception, ion homeostasis, and chemical signal transduction. the trp superfamily consists of seven subgroups, one of which is the transient receptor potential vanilloid (trpv) channel family. while trpv channels are relatively well studied in adult vertebrate organisms given their role in functions such as nociception ...201830326274
high-affinity k+ transporters from a halophyte, sporobolus virginicus, mediate both k+ and na+ transport in transgenic arabidopsis, x. laevis oocytes and yeast.class ii high-affinity potassium transporters (hkts) have been proposed to mediate na+-k+ co-transport in plants, as well as na+ and k+ homeostasis under k+-starved and saline environments. we identified class ii hkts, namely svhkt2;1 and svhkt2;2 (svhkts), from the halophytic turf grass, sporobolus virginicus. svhkt2;2 expression in s. virginicus was up-regulated by nacl treatment, while svhkt2;1 expression was assumed to be up-regulated by k+ starvation and down-regulated by nacl treatment. lo ...201930325438
generation and analysis of xenopus laevis models of retinal degeneration using crispr/cas9.xenopus laevis have proven to be a useful system for rapid generation and analysis of transgenic models of human retinal disease. however, experimental approaches in this system were limited by lack of a robust knockdown or knockout technology. here we describe a protocol for generation of cas9-edited x. laevis embryos. the technique introduces point mutations into the genome of x. laevis resulting in in-frame and out-of-frame insertions and deletions that allow modeling of both dominant and rec ...201930324446
morphomechanical reactions and mechanically stressed structures in amphibian embryos, as related to gastrulation and axial organs formation.reactions of embryonic tissues to a distributed and concentrated stretching are described and compared with the mechanics of the normal gastrulation movements. a role of mechanically stressed dynamic cell structures in the gastrulation, demarcation of notochord borders and in providing proportionality of the axial rudiments is demonstrated. a morphomechanical scheme of amphibian gastrulation is presented.201830321583
reconstitution of cell-cycle oscillations in microemulsions of cell-free xenopus egg extracts.real-time measurement of oscillations at the single-cell level is important to uncover the mechanisms of biological clocks. although bulk extracts prepared from xenopus laevis eggs have been powerful in dissecting biochemical networks underlying the cell-cycle progression, their ensemble average measurement typically leads to a damped oscillation, despite each individual oscillator being sustained. this is due to the difficulty of perfect synchronization among individual oscillators in noisy bio ...201830320763
assembly of protein complexes restricts diffusion of wnt3a proteins.members of the wnt protein family play roles in many aspects of embryogenesis and homeostasis. despite their biological significance, characteristics of wnt proteins still remain unclear, mainly due to their insolubility after the removal of serum. here we examine wnt proteins in serum-containing media by using analytical ultracentrifugation with a fluorescence detection system. this analysis reveals that wnt3a assembles into high-molecular-weight complexes that become dissociable by interaction ...201830320232
polystyrene microplastics did not affect body growth and swimming activity in xenopus laevis tadpoles.a growing number of studies have highlighted the contamination and the effects towards organisms of diverse microplastics (μps) in the marine environment. surprisingly, although the main sources of μps for marine environments are inland surface waters, the information on the occurrence and the effects of μps in freshwater ecosystems is still scant. thus, the aim of the present work is to investigate the ingestion and possible adverse effects due to the exposure to polystyrene μps (psμps; ø = 3 μ ...201830317408
comparisons of socs mrna and protein levels in xenopus provide insights into optic nerve regenerative success.in vertebrates from fishes to mammals, optic nerve injury induces increased expression ofsuppressor of cytokine signaling 3(socs3) mrna, a modulator of cytokine signaling that is known to inhibit cns axon regeneration. unlike amniotes, however, anamniotes successfully regenerate optic axons, despite this increase. to address this seeming paradox, we examined the socs3 response to optic nerve injury in the frog,xenopus laevis, at both the mrna and protein levels. far from being only transiently i ...201930315759
unusual light-reflecting pigment cells appear in the xenopus neural tube culture system in the presence of guanosine.isolation and culture of xenopus laevis neural tubes resulted in differentiation of melanophores and iridophores from neural crest cells; the differentiated melanophores and iridophores were then maintained in culture for more than 6 months. guanosine has been reported to promote reflecting platelet formation in melanin-producing pigment cells; however, the process of pigment organellogenesis is still unclear. in the present study, unusual light-reflecting pigment cells were observed upon additi ...201830309510
uroplakins play conserved roles in egg fertilization and acquired additional urothelial functions during mammalian divergence.uroplakin (up) tetraspanins and their associated proteins are major mammalian urothelial differentiation products that form unique two-dimensional crystals of 16-nm particles ("urothelial plaques") covering the apical urothelial surface. although uroplakins are highly expressed only in mammalian urothelium and are often referred to as being urothelium specific, they are also expressed in several mouse nonurothelial cell types in stomach, kidney, prostate, epididymis, testis/sperms, and ovary/ooc ...201830303751
retinal tissue preparation for high-resolution live imaging of photoreceptors expressing multiple transgenes.live imaging has become the favorite method in recent years to study the protein transport, localization and dynamics in live cells. protein transport is extremely essential for proper function of photoreceptors. aberration in the proper transport of proteins gives rise to the loss of photoreceptor and blindness. on the other hand, the ease of generation of transgenic xenopus laevis tadpoles and the advantage of high resolution live confocal imaging provide new insight into understanding protein ...201830302320
antibacterial and antibiofilm activity and mode of action of magainin 2 against drug-resistant acinetobacter baumannii.antimicrobial peptides (amps) are promising therapeutic agents for treating antibiotic-resistant bacterial infections. previous studies showed that magainin 2 (isolated from african clawed fogs xenopus laevis) has antimicrobial activity against gram-positive and gram-negative bacteria. the present study was conducted to investigate the antibacterial activity of magainin 2 against acinetobacter baumannii. magainin 2 showed excellent antibacterial activity against a. baumannii strains and high sta ...201830301180
design, synthesis, and pharmacological evaluation of novel β2/3 subunit-selective γ-aminobutyric acid type a (gabaa) receptor modulators.subunit-selective modulation of γ-aminobutyric acid type a receptors (gabaar) is considered to exert fewer side effects compared to unselective clinically used drugs. here, the β2/3 subunit-selective gabaar modulators valerenic acid (va) and loreclezole (lor) guided the synthesis of novel subunit-selective ligands with simplified structures. we studied their effects on gabaars expressed in xenopus laevis oocytes using two-microelectrode voltage clamp technique. five compounds showed significantl ...201930289721
functional analysis of a triplet deletion in the gene encoding the sodium glucose transporter 3, a potential risk factor for adhd.sodium-glucose transporters (sglt) belong to the solute carrier 5 family, which is characterized by sodium dependent transport of sugars and other solutes. in contrast, the human sglt3 (hsglt3) isoform, encoded by slc5a4, acts as a glucose sensor that does not transport sugar but induces membrane depolarization by na+ currents upon ligand binding. whole-exome sequencing (wes) of several extended pedigrees with high density of attention-deficit/hyperactivity disorder (adhd) identified a triplet a ...201830286162
nucleosomes and the three glycosylases: high, medium, and low levels of excision by the uracil dna glycosylase superfamily.human cells express the udg superfamily of glycosylases, which excise uracil (u) from the genome. the three members of this structural superfamily are uracil dna glycosylase (ung/udg), single-strand selective monofunctional uracil dna glycosylase (smug1), and thymine dna glycosylase (tdg). we previously reported that udg is efficient at removing u from dna packaged into nucleosome core particles (ncp) and is minimally affected by the histone proteins when acting on an outward-facing u in the dya ...201830268365
a xenopus oocyte model system to study action potentials.action potentials (aps) are the functional units of fast electrical signaling in excitable cells. the upstroke and downstroke of an ap is generated by the competing and asynchronous action of na+- and k+-selective voltage-gated conductances. although a mixture of voltage-gated channels has been long recognized to contribute to the generation and temporal characteristics of the ap, understanding how each of these proteins function and are regulated during electrical signaling remains the subject ...201830266757
expression of the hormonal fgf co-receptor klotho beta in the xenopus laevis model.klotho beta (klb), a single-pass transmembrane protein, has been described as a co-receptor for endocrine fgfs, such as fgf15/19 and fgf21, to regulate critical metabolic processes in multiple organs and tissues in adult mice. however, its function during early embryonic development remains largely unknown. in this paper, we evaluated for the first time the expression of klb mrna during early development of xenopus laevis by rt-pcr and whole mount in situ hybridization. rt-pcr experiments showed ...201930259590
amphibian (xenopus laevis) interleukin-8 (cxcl8): a perspective on the evolutionary divergence of granulocyte chemotaxis.the glutamic acid-leucine-arginine (elr) motif is a hallmark feature shared by mammalian inflammatory cxc chemokines such the granulocyte chemo-attractant cxcl8 (interleukin-8, il-8). by contrast, most teleost fish inflammatory chemokines lack this motif. interestingly, the amphibian xenopus laevis encodes multiple isoforms of cxcl8, one of which (cxcl8a) possesses an elr motif, while another (cxcl8b) does not. these cxcl8 isoforms exhibit distinct expression patterns during frog development and ...201830258441
molecular determinants of α-conotoxin potency for inhibition of human and rat α6β4 nicotinic acetylcholine receptors.nicotinic acetylcholine receptors (nachrs) containing α6 and β4 subunits are expressed by dorsal root ganglion neurons and have been implicated in neuropathic pain. rodent models are often used to evaluate the efficacy of analgesic compounds, but species differences may affect the activity of some nachr ligands. a previous candidate α-conotoxin-based therapeutic yielded promising results in rodent models, but failed in human clinical trials, emphasizing the importance of understanding species di ...201830249616
the balance of two opposing factors mad and myc regulates cell fate during tissue remodeling.cell proliferation and differentiation are two distinct yet coupled processes in development in diverse organisms. understanding the molecular mechanisms that regulate this process is a central theme in developmental biology. the intestinal epithelium is a highly complex tissue that relies on the coordination of cell proliferation within the crypts and apoptosis mainly at the tip of the villi, preservation of epithelial function through differentiation, and homeostatic cell migration along the c ...201830237868
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