Publications

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ion conduction and selectivity in acid-sensing ion channel 1.the ability of acid-sensing ion channels (asics) to discriminate among cations was assessed based on changes in conductance and reversal potential with ion substitution. human asic1a was expressed in xenopus laevis oocytes, and acid-induced currents were measured using two-electrode voltage clamp. replacement of extracellular na(+) with li(+), k(+), rb(+), or cs(+) altered inward conductance and shifted the reversal potentials consistent with a selectivity sequence of li ∼ na > k > rb > cs. perm ...201425114023
wnk-spak-ncc cascade revisited: wnk1 stimulates the activity of the na-cl cotransporter via spak, an effect antagonized by wnk4.the with-no-lysine (k) kinases, wnk1 and wnk4, are key regulators of blood pressure. their mutations lead to familial hyperkalemic hypertension (fhht), associated with an activation of the na-cl cotransporter (ncc). although it is clear that wnk4 mutants activate ncc via ste20 proline-alanine-rich kinase, the mechanisms responsible for wnk1-related fhht and alterations in ncc activity are not as clear. we tested whether wnk1 modulates ncc through wnk4, as predicted by some models, by crossing ou ...201425113964
label-free real-time imaging of myelination in the xenopus laevis tadpole by in vivo stimulated raman scattering microscopy.the myelin sheath plays an important role as the axon in the functioning of the neural system, and myelin degradation is a hallmark pathology of multiple sclerosis and spinal cord injury. electron microscopy, fluorescent microscopy, and magnetic resonance imaging are three major techniques used for myelin visualization. however, microscopic observation of myelin in living organisms remains a challenge. using a newly developed stimulated raman scattering microscopy approach, we report noninvasive ...201425104411
casein kinase 1 α phosphorylates the wnt regulator jade-1 and modulates its activity.tight regulation of wnt/β-catenin signaling is critical for vertebrate development and tissue maintenance, and deregulation can lead to a host of disease phenotypes, including developmental disorders and cancer. proteins associated with primary cilia and centrosomes have been demonstrated to negatively regulate canonical wnt signaling in interphase cells. the plant homeodomain zinc finger protein jade-1 can act as an e3 ubiquitin ligase-targeting β-catenin for proteasomal degradation and concent ...201425100726
the domain interface of the human glutamate transporter eaat1 mediates chloride permeation.the concentration of glutamate within the glutamatergic synapse is tightly regulated by the excitatory amino-acid transporters (eaats). in addition to their primary role of clearing extracellular glutamate, the eaats also possess a thermodynamically uncoupled cl(-) conductance. several crystal structures of an archaeal eaat homolog, gltph, at different stages of the transport cycle have been solved. in a recent structure, an aqueous cavity located at the interface of the transport and trimerizat ...201425099801
activation, permeability, and inhibition of astrocytic and neuronal large pore (hemi)channels.astrocytes and neurons express several large pore (hemi)channels that may open in response to various stimuli, allowing fluorescent dyes, ions, and cytoplasmic molecules such as atp and glutamate to permeate. several of these large pore (hemi)channels have similar characteristics with regard to activation, permeability, and inhibitor sensitivity. consequently, their behaviors and roles in astrocytic and neuronal (patho)physiology remain undefined. we took advantage of the xenopus laevis expressi ...201425086040
temperature-independent energy expenditure in early development of the african clawed frog xenopus laevis.the thermal dissipation of activated eggs and embryos undergoing development from cleavage to the tailbud stage of the african clawed frog xenopus laevis was measured as a function of incubation time at temperatures ranging from t = 288.2 k to 295.2 k, using a high-precision isothermal calorimeter. a23187-mediated activation of mature eggs induced stable periodic thermal oscillations lasting for 8-34 h. the frequency agreed well with the cell cycle frequency of initial cleavages at the identical ...201425078857
the molecular mechanism of intestinal levodopa absorption and its possible implications for the treatment of parkinson's disease.levodopa (l-dopa) is the naturally occurring precursor amino acid for dopamine and the main therapeutic agent for neurologic disorders due to dopamine depletion, such as parkinson's disease. l-dopa absorption in small intestine has been suggested to be mediated by the large neutral amino acids transport machinery, but the identity of the involved transporters is unknown. clinically, coadministration of l-dopa and dietary amino acids is avoided to decrease competition for transport in intestine a ...201425073474
radial intercalation is regulated by the par complex and the microtubule-stabilizing protein clamp/spef1.the directed movement of cells is critical for numerous developmental and disease processes. a developmentally reiterated form of migration is radial intercalation; the process by which cells move in a direction orthogonal to the plane of the tissue from an inner layer to an outer layer. we use the radial intercalation of cells into the skin of xenopus laevis embryos as a model to study directed cell migration within an epithelial tissue. we identify a novel function for both the microtubule-bin ...201425070955
tpx2 levels modulate meiotic spindle size and architecture in xenopus egg extracts.the spindle segregates chromosomes in dividing eukaryotic cells, and its assembly pathway and morphology vary across organisms and cell types. we investigated mechanisms underlying differences between meiotic spindles formed in egg extracts of two frog species. small xenopus tropicalis spindles resisted inhibition of two factors essential for assembly of the larger xenopus laevis spindles: rangtp, which functions in chromatin-driven spindle assembly, and the kinesin-5 motor eg5, which drives ant ...201425070954
accumulation of heme oxygenase-1 (hsp32) in xenopus laevis a6 kidney epithelial cells treated with sodium arsenite, cadmium chloride or proteasomal inhibitors.the present study examined the effect of sodium arsenite, cadmium chloride, heat shock and the proteasomal inhibitors mg132, withaferin a and celastrol on heme oxygenase-1 (ho-1; also known as hsp32) accumulation in xenopus laevis a6 kidney epithelial cells. immunoblot analysis revealed that ho-1 accumulation was not induced by heat shock but was enhanced by sodium arsenite and cadmium chloride in a dose- and time-dependent fashion. immunocytochemistry revealed that these metals induced ho-1 acc ...201425064141
global absolute quantification reveals tight regulation of protein expression in single xenopus eggs.while recent developments in genomic sequencing technology have enabled comprehensive transcriptome analyses of single cells, single cell proteomics has thus far been restricted to targeted studies. here, we perform global absolute protein quantification of fertilized xenopus laevis eggs using mass spectrometry-based proteomics, quantifying over 5800 proteins in the largest single cell proteome characterized to date. absolute protein amounts in single eggs are highly consistent, thus indicating ...201425056316
potential protective effect of l-cysteine against the toxicity of acrylamide and furan in exposed xenopus laevis embryos: an interaction study.the embryo toxicities of two food-processing-induced toxic compounds, acrylamide and furan, with and without added l-cysteine were examined individually and in mixtures using the frog embryo teratogenesis assay-xenopus (fetax). the following measures of developmental toxicity were used: (a) 96 h lc50, the median concentration causing 50% embryo lethality; (b) 96 h ec50, the median concentration causing 50% malformations of the surviving embryos; and (c) teratogenic index (96 h lc50/96 h ec50), a ...201425055136
cell-mass structures expressing the aromatase gene cyp19a1 lead to ovarian cavities in xenopus laevis.the african clawed frog, xenopus laevis, has a zz/zw-type sex-determination system. we previously reported that a w-linked gene, dm-w, can determine development as a female. however, the mechanisms of early sex differentiation remain unclear. we used microarrays to screen for genes with sexually dimorphic expression in zz and zw gonads during early sex differentiation in x laevis and found several steroidogenic genes. importantly, the steroid 17α-hydroxylase gene cyp17a1 and the aromatase gene c ...201425051437
functional evaluation of key interactions evident in the structure of the eukaryotic cys-loop receptor glucl.the publication of the first high-resolution crystal structure of a eukaryotic cys-loop receptor, gluclα, has provided valuable structural information on this important class of ligand-gated ion channels (lgic). however, limited functional data exist for the glucl receptors. before applying the structural insights from glucl to mammalian cys-loop receptors such as nicotinic acetylcholine and gaba receptors, it is important to ensure that established functional features of mammalian cys-loop rece ...201425051140
ire1α knockdown rescues tunicamycin-induced developmental defects and apoptosis in xenopus laevis.inositol requiring enzyme-1 (ire1) is highly conserved from yeasts to humans. upon endoplasmic reticulum (er) stress, ire1 activates x-box-binding protein 1 (xbp1) by unconventional splicing of xbp1 mrna, which activates unfolded protein response (upr) to restore er homeostasis. in mice, ire1α plays an essential role in extraembryonic tissues. however, its precise action during the early stage of development is unknown. in this study, the gain and loss-of-function analyses were used to investiga ...201425050111
demonstration of proteolytic activation of the epithelial sodium channel (enac) by combining current measurements with detection of cleavage fragments.the described methods can be used to investigate the effect of proteases on ion channels, receptors, and other plasma membrane proteins heterologously expressed in xenopus laevis oocytes. in combination with site-directed mutagenesis, this approach provides a powerful tool to identify functionally relevant cleavage sites. proteolytic activation is a characteristic feature of the amiloride-sensitive epithelial sodium channel (enac). the final activating step involves cleavage of the channel's γ-s ...201425045853
benzocyclobutane, benzocycloheptane and heptene derivatives as melatonin agonists and antagonists.two series of analogues were designed, synthesised and evaluated as potential human melatonin type 1 and 2 receptor (hmt1 and hmt2 ) ligands. their biological effects were assessed by a well-established, specific model of melatonin action, the pigment response of xenopus laevis melanophores. compounds containing a benzocyclobutane scaffold and a methoxy group in the "melatonin" orientation were found to be potent agonists, with one of the analogues exhibiting activity comparable to melatonin. in ...201425044938
using plustiptracker software to measure microtubule dynamics in xenopus laevis growth cones.microtubule (mt) plus-end-tracking proteins (+tips) localize to the growing plus-ends of mts and regulate mt dynamics(1,2). one of the most well-known and widely-utilized +tips for analyzing mt dynamics is the end-binding protein, eb1, which binds all growing mt plus-ends, and thus, is a marker for mt polymerization(1). many studies of eb1 behavior within growth cones have used time-consuming and biased computer-assisted, hand-tracking methods to analyze individual mts(1-3). our approach is to q ...201425225829
5-mehtyltetrahydrofolate rescues alcohol-induced neural crest cell migration abnormalities.alcohol is detrimental to early development. fetal alcohol spectrum disorders (fasd) due to maternal alcohol abuse results in a series of developmental abnormalities including cranial facial dysmorphology, ocular anomalies, congenital heart defects, microcephaly and intellectual disabilities. previous studies have been shown that ethanol exposure causes neural crest (nc) apoptosis and perturbation of neural crest migration. however, the underlying mechanism remains elusive. in this report we inv ...201425223405
the calcium-dependent ribonuclease xendou promotes er network formation through local rna degradation.how cells shape and remodel organelles in response to cellular signals is a poorly understood process. using xenopus laevis egg extract, we found that increases in cytosolic calcium lead to the activation of an endogenous ribonuclease, xendou. a fraction of xendou localizes to the endoplasmic reticulum (er) and is required for nuclear envelope assembly and er network formation in a catalysis-dependent manner. using a purified vesicle fusion assay, we show that xendou functions on the surface of ...201425287301
expression, purification, and structural insights for the human uric acid transporter, glut9, using the xenopus laevis oocytes system.the urate transporter, glut9, is responsible for the basolateral transport of urate in the proximal tubule of human kidneys and in the placenta, playing a central role in uric acid homeostasis. glut9 shares the least homology with other members of the glucose transporter family, especially with the glucose transporting members glut1-4 and is the only member of the glut family to transport urate. the recently published high-resolution structure of xyle, a bacterial d-xylose transporting homologue ...201425286413
nkx2.5 is involved in myeloid cell differentiation at anterior ventral blood islands in the xenopus embryo.we have shown previously that two populations of myeloid cells emerge in the anterior and posterior ventral blood islands (avbi and pvbi) at the different stages in xenopus laevis embryo. in order to elucidate the regulatory mechanism of myeloid cell differentiation in the avbi, we examined the role of nkx2.5, an essential transcription factor for heart differentiation, in regulation of the myeloid cell differentiation in this region. knockdown of endogenous nkx2.5 by introducing mo into the dor ...201425283688
liquid chromatography tandem mass spectrometry method using solid-phase extraction and bead-beating-assisted matrix solid-phase dispersion to quantify the fungicide tebuconazole in controlled frog exposure study: analysis of water and animal tissue.this paper presents the development, optimization, and validation of a lc-ms/ms methodology to determine the concentration of the antifungal drug and fungicide tebuconazole in a controlled exposure study of african clawed frogs (xenopus laevis). the method is validated on animal tank water and on tissue from exposed and non-exposed adult x. laevis. using solid-phase extraction (spe), the analytical method allows for quantification of tebuconazole at concentrations as low as 3.89 pg ml(-1) in 10 ...201425277103
atomic force microscopy on plasma membranes from xenopus laevis oocytes containing human aquaporin 4.atomic force microscopy (afm) is a unique tool for imaging membrane proteins in near-native environment (embedded in a membrane and in buffer solution) at ~1 nm spatial resolution. it has been most successful on membrane proteins reconstituted in 2d crystals and on some specialized and densely packed native membranes. here, we report on afm imaging of purified plasma membranes from xenopus laevis oocytes, a commonly used system for the heterologous expression of membrane proteins. isoform m23 of ...201425277091
photoactivation-induced instability of rhodopsin mutants t4k and t17m in rod outer segments underlies retinal degeneration in x. laevis transgenic models of retinitis pigmentosa.retinitis pigmentosa (rp) is an inherited neurodegenerative disease involving progressive vision loss, and is often linked to mutations in the rhodopsin gene. mutations that abolish n-terminal glycosylation of rhodopsin (t4k and t17m) cause sector rp in which the inferior retina preferentially degenerates, possibly due to greater light exposure of this region. transgenic animal models expressing rhodopsin glycosylation mutants also exhibit light exacerbated retinal degeneration (rd). in this stu ...201425274813
getting to know your neighbor: cell polarization in early embryos.polarization of early embryos along cell contact patterns--referred to in this paper as radial polarization--provides a foundation for the initial cell fate decisions and morphogenetic movements of embryogenesis. although polarity can be established through distinct upstream mechanisms in caenorhabditis elegans, xenopus laevis, and mouse embryos, in each species, it results in the restriction of par polarity proteins to contact-free surfaces of blastomeres. in turn, par proteins influence cell f ...201425267293
cdc6 controls dynamics of the first embryonic m-phase entry and progression via cdk1 inhibition.cdc6 is essential for s-phase to initiate dna replication. it also regulates m-phase exit by inhibiting the activity of the major m-phase protein kinase cdk1. here we show that addition of recombinant cdc6 to xenopus embryo cycling extract delays the m-phase entry and inhibits cdk1 during the whole m-phase. down regulation of endogenous cdc6 accelerates the m-phase entry, abolishes the initial slow and progressive phase of histone h1 kinase activation and increases the level of cdk1 activity dur ...201425264619
upregulation of eif5b controls cell-cycle arrest and specific developmental stages.proliferation arrest and distinct developmental stages alter and decrease general translation yet maintain ongoing translation. the factors that support translation in these conditions remain to be characterized. we investigated an altered translation factor in three cell states considered to have reduced general translation: immature xenopus laevis oocytes, mouse es cells, and the transition state of proliferating mammalian cells to quiescence (g0) upon growth-factor deprivation. our data revea ...201425261552
cathepsin b contributes to na+ hyperabsorption in cystic fibrosis airway epithelial cultures.in cystic fibrosis (cf) lung disease, the absence of functional cf transmembrane conductance regulator results in cl(-)/hco3 (-) hyposecretion and triggers na(+) hyperabsorption through the epithelial na(+) channel (enac), which contribute to reduced airway surface liquid (asl) ph and volume. prostasin, a membrane-anchored serine protease with trypsin-like substrate specificity has previously been shown to activate enac in cf airways. however, prostasin is typically inactive below ph 7.0, sugges ...201425260629
sperm and spermatids contain different proteins and bind distinct egg factors.spermatozoa are more efficient at supporting normal embryonic development than spermatids, their immature, immediate precursors. this suggests that the sperm acquires the ability to support embryonic development during spermiogenesis (spermatid to sperm maturation). here, using xenopus laevis as a model organism, we performed 2-d fluorescence difference gel electrophoresis (2d-dige) and mass spectrometry analysis of differentially expressed proteins between sperm and spermatids in order to ident ...201425244019
circadian genes, xbmal1 and xnocturnin, modulate the timing and differentiation of somites in xenopus laevis.we have been investigating whether xbmal1 and xnocturnin play a role in somitogenesis, a cyclic developmental process with an ultradian period. previous work from our lab shows that circadian genes (xperiod1, xperiod2, xbmal1, and xnocturnin) are expressed in developing somites. somites eventually form the vertebrae, muscles of the back, and dermis. in xenopus, a pair of somites is formed about every 50 minutes from anterior to posterior. we were intrigued by the co-localization of circadian gen ...201425238599
extracellular gentamicin reduces the activity of connexin hemichannels and interferes with purinergic ca(2+) signaling in hela cells.gap junction channels (gjcs) and hemichannels (hcs) are composed of protein subunits termed connexins (cxs) and are permeable to ions and small molecules. in most organs, gjcs communicate the cytoplasm of adjacent cells, while hcs communicate the intra and extracellular compartments. in this way, both channel types coordinate physiological responses of cell communities. cx mutations explain several genetic diseases, including about 50% of autosomal recessive non-syndromic hearing loss. however, ...201425237294
aqp4 plasma membrane trafficking or channel gating is not significantly modulated by phosphorylation at cooh-terminal serine residues.aquaporin 4 (aqp4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain-blood interface. aqp4 serves as a water entry site during brain edema formation, and regulation of aqp4 may therefore be of therapeutic interest. phosphorylation of aquaporins can regulate plasma membrane localization and, possibly, the unit water permeability via gating of the aqp channel itself. in vivo phosphorylation of six serine residues in the c ...201425231107
the need of mmp-2 on the sperm surface for xenopus fertilization: its role in a fast electrical block to polyspermy.monospermic fertilization in the frog, xenopus laevis, is ensured by a fast-rising, positive fertilization potential to prevent polyspermy on the fertilized egg, followed by a slow block with the formation of a fertilization envelope over the egg surface. in this paper, we found that not only the enzymatic activity of sperm matrix metalloproteinase-2 (mmp-2) was necessary for a sperm to bind and/or pass through the extracellular coat of vitelline envelope, but also the hemopexin (hpx) domain of ...201425296387
correlative light and electron microscopy for a free-floating spindle in xenopus laevis egg extracts.cryoimmobilization is an optimal method of preserving sample ultrastructure in electron microscopy studies. however, cryoimmobilization is limited to thin samples and this limitation may necessitate the isolation of the structure of interest. for cellular structures that are found in low number, or only during certain phases of the cell cycle, an added benefit of isolation is the possibility to concentrate the structures. we developed a method to perform correlative light and electron microscopy ...201425287839
twin xenopus laevis embryos appearing from flattened eggs.remarkable progress has recently been made in molecular biology of double axis formation in xenopus laevis. leaving aside, for the time being, the problem of the gene expressions regulating xenopus laevis development, here i show that pulse treatment could induce formation of a secondary axis in a fertilized xenopus laevis egg. at 3 min after insemination, metal oxides were added to xenopus fertilized eggs, and then twin embryos appeared. zirconium oxide (zro2) was the most effective metal oxide ...201425311141
phosphorylation and arginine methylation mark histone h2a prior to deposition during xenopus laevis development.stored, soluble histones in eggs are essential for early development, in particular during the maternally controlled early cell cycles in the absence of transcription. histone post-translational modifications (ptms) direct and regulate chromatin-templated transactions, so understanding the nature and function of pre-deposition maternal histones is essential to deciphering mechanisms of regulation of development, chromatin assembly, and transcription. little is known about histone h2a pre-deposit ...201425302076
vitamin supplementation by gut symbionts ensures metabolic homeostasis in an insect host.despite the demonstrated functional importance of gut microbes, our understanding of how animals regulate their metabolism in response to nutritionally beneficial symbionts remains limited. here, we elucidate the functional importance of the african cotton stainer's (dysdercus fasciatus) association with two actinobacterial gut symbionts and subsequently examine the insect's transcriptional response following symbiont elimination. in line with bioassays demonstrating the symbionts' contribution ...201425339726
gd(iii)-pymta label is suitable for in-cell epr.distance measurement in the nanometer range by electron paramagnetic resonance spectroscopy (epr) in combination with site-directed spin labeling is a very powerful tool to monitor the structure and dynamics of biomacromolecules in their natural environment. however, in-cell application is hampered by the short lifetime of the commonly used nitroxide spin labels in the reducing milieu inside a cell. here, we demonstrate that the gd(iii) based spin label gd-pymta is suitable for in-cell epr. gd-p ...201425325832
regulation of clc-2 activity by spak and osr1.spak (sps1-related proline/alanine-rich kinase) and osr1 (oxidative stress-responsive kinase 1) are powerful regulators of diverse transport processes. both kinases are activated by cell shrinkage and participate in stimulation of regulatory cell volume increase (rvi). execution of rvi involves inhibition of cl- channels. the present study explored whether spak and/or osr1 regulate the activity of the cl- channel clc-2.201425323061
calcium signaling and meiotic exit at fertilization in xenopus egg.calcium is a universal messenger that mediates egg activation at fertilization in all sexually reproducing species studied. however, signaling pathways leading to calcium generation and the mechanisms of calcium-induced exit from meiotic arrest vary substantially among species. here, we review the pathways of calcium signaling and the mechanisms of meiotic exit at fertilization in the eggs of the established developmental model, african clawed frog, xenopus laevis. we also discuss calcium involv ...201425322156
nucleotide bound to rab11a controls localization in rod cells but not interaction with rhodopsin.precise vectorial transport of rhodopsin is essential for rod photoreceptor health and function. mutations that truncate or extend the c terminus of rhodopsin disrupt this transport, and lead to retinal degeneration and blindness in human patients and in mouse models. here we show that such mutations disrupt the binding of rhodopsin to the small gtpase rab11a. the rhodopsin-rab11a interaction is a direct binding interaction that does not depend on the nucleotide binding state of rab11a. expressi ...201425378153
spak dependent regulation of peptide transporters pept1 and pept2.spak (ste20-related proline/alanine-rich kinase) is a powerful regulator of renal tubular ion transport and blood pressure. moreover, spak contributes to the regulation of cell volume. little is known, however, about a role of spak in the regulation or organic solutes. the present study thus addressed the influence of spak on the peptide transporters pept1 and pept2.201425376088
optogenetic control of apoptosis in targeted tissues of xenopus laevis embryos.killerred (kr) is a recently discovered fluorescent protein that, when activated with green light, releases reactive oxygen species (ros) into the cytoplasm, triggering apoptosis in a kr-expressing cell. this property allows for the use of kr as a means of killing cells in an organism with great temporal and spatial specificity, while minimizing the nonspecific effects that can result from mechanical or chemical exposure damage techniques. such optogenetic control of cell death, and the resultin ...201425374461
an adhesome comprising laminin, dystroglycan and myosin iia is required during notochord development in xenopus laevis.dystroglycan (dg) is a transmembrane receptor for laminin that must be expressed at the right time and place in order to be involved in notochord morphogenesis. the function of dg was examined in xenopus laevis embryos by knockdown of dg and overexpression and replacement of the endogenous dg with a mutated form of the protein. this analysis revealed that dg is required for correct laminin assembly, for cell polarization during mediolateral intercalation and for proper differentiation of vacuole ...201425359726
transporters involved in renal excretion of n-carbamoylglutamate, an orphan drug to treat inborn n-acetylglutamate synthase deficiency.inborn defects in n-acetylglutamate (nag) synthase (nags) cause a reduction of nag, an essential cofactor for the initiation of the urea cycle. as a consequence, blood ammonium concentrations are elevated, leading to severe neurological disorders. the orphan drug n-carbamoylglutamate (ncg; carbaglu), efficiently overcomes nags deficiency. however, not much is known about the transporters involved in the uptake, distribution, and elimination of the divalent organic anion ncg. organic anion-transp ...201425354943
two different vestigial like 4 genes are differentially expressed during xenopus laevis development.the vestigial gene (vg) was first characterized in drosophila and several homologues were identified in vertebrates and called vestigial like 1-4 (vgll1-4). vgll proteins interact with the transcription factors tef-1 and mef-2 through a conserved region called tondu (tdu). vgll4s are characterized by two tandem tdu domains which differentiate them from other members of the vestigial family. in xenopus two genes were identified as vgll4. our bioinformatic analysis demonstrated that these two gene ...201425354458
differential expression of arid5b isoforms in xenopus laevis pronephros.arid5b belongs to the arid family of transcription factors characterised by a helix-turn-helix motif- based dna-binding domain called arid (a-t rich interaction domain). in human, alternative splicing leads to long and short isoforms (isoform1 and 2, respectively) which differ in their n-terminal part. in this study, we report the cloning and expression pattern of xenopus laevis arid5b. we have isolated a full length cdna that shows homology with the human arid5b isoform1. furthermore, 5'race ex ...201425354457
lack of negatively charged residues at the external mouth of kir2.2 channels enable the voltage-dependent block by external mg2+.kir channels display voltage-dependent block by cytosolic cations such as mg2+ and polyamines that causes inward rectification. in fact, cations can regulate k channel activity from both the extracellular and intracellular sides. previous studies have provided insight into the up-regulation of kir channel activity by extracellular k+ concentration. in contrast, extracellular mg2+ has been found to reduce the amplitude of the single-channel current at milimolar concentrations. however, little is ...201425350118
sulfonylureas suppress the stimulatory action of mg-nucleotides on kir6.2/sur1 but not kir6.2/sur2a katp channels: a mechanistic study.sulfonylureas, which stimulate insulin secretion from pancreatic β-cells, are widely used to treat both type 2 diabetes and neonatal diabetes. these drugs mediate their effects by binding to the sulfonylurea receptor subunit (sur) of the atp-sensitive k(+) (katp) channel and inducing channel closure. the mechanism of channel inhibition is unusually complex. first, sulfonylureas act as partial antagonists of channel activity, and second, their effect is modulated by mgadp. we analyzed the molecul ...201425348414
cell volume changes regulate slick (slo2.1), but not slack (slo2.2) k+ channels.slick (slo2.1) and slack (slo2.2) channels belong to the family of high-conductance k+ channels and have been found widely distributed in the cns. both channels are activated by na+ and cl- and, in addition, slick channels are regulated by atp. therefore, the roles of these channels in regulation of cell excitability as well as ion transport processes, like regulation of cell volume, have been hypothesized. it is the aim of this work to evaluate the sensitivity of slick and slack channels to sma ...201425347289
polyubiquitylation drives replisome disassembly at the termination of dna replication.resolution of replication forks during termination of dna replication is essential for accurate duplication of eukaryotic genomes. here we present evidence consistent with the idea that polyubiquitylation of a replisome component (mcm7) leads to its disassembly at the converging terminating forks because of the action of the p97/vcp/cdc48 protein remodeler. using xenopus laevis egg extract, we have shown that blocking polyubiquitylation results in the prolonged association of the active helicase ...201425342805
carbon monoxide (co) is a novel inhibitor of connexin hemichannels.hemichannels (hcs) are hexamers of connexins that can form gap-junction channels at points of cell contacts or "free hcs" at non-contacting regions. hcs are involved in paracrine and autocrine cell signaling, and under pathological conditions may induce and/or accelerate cell death. therefore, studies of hc regulation are of great significance. nitric oxide affects the activity of cx43 and cx46 hcs, whereas carbon monoxide (co), another gaseous transmitter, modulates the activity of several ion ...201425384983
recruitment of gβγ controls the basal activity of g-protein coupled inwardly rectifying potassium (girk) channels: crucial role of distal c terminus of girk1.the g-protein coupled inwardly rectifying potassium (girk, or kir3) channels are important mediators of inhibitory neurotransmission via activation of g-protein coupled receptors (gpcrs). girk channels are tetramers comprising combinations of subunits (girk1-4), activated by direct binding of the gβγ subunit of gi/o proteins. heterologously expressed girk1/2 exhibit high, gβγ-dependent basal currents (ibasal) and a modest activation by gpcr or coexpressed gβγ. inversely, the girk2 homotetramers ...201425384780
the virtual xenbase: transitioning an online bioinformatics resource to a private cloud.as a model organism database, xenbase has been providing informatics and genomic data on xenopus (silurana) tropicalis and xenopus laevis frogs for more than a decade. the xenbase database contains curated, as well as community-contributed and automatically harvested literature, gene and genomic data. a gbrowse genome browser, a blast+ server and stock center support are available on the site. when this resource was first built, all software services and components in xenbase ran on a single phy ...201425380782
diurnal variation of tight junction integrity associates inversely with matrix metalloproteinase expression in xenopus laevis corneal epithelium: implications for circadian regulation of homeostatic surface cell desquamation.the corneal epithelium provides a protective barrier against pathogen entrance and abrasive forces, largely due to the intercellular junctional complexes between neighboring cells. after a prescribed duration at the corneal surface, tight junctions between squamous surface cells must be disrupted to enable them to desquamate as a component of the tissue homeostatic renewal. we hypothesize that matrix metalloproteinase (mmps) are secreted by corneal epithelial cells and cleave intercellular junct ...201425412440
assessment of natural variation in the first pore domain of the tomato hkt1;2 transporter and characterization of mutated versions of slhkt1;2 expressed in xenopus laevis oocytes and via complementation of the salt sensitive athkt1;1 mutant.single nucleotide polymorphisms (snps) within the coding sequence of hkt transporters are important for the functioning of these transporters in several plant species. to unravel the functioning of hkt transporters analysis of natural variation and multiple site-directed mutations studies are crucial. also the in vivo functioning of hkt proteins, via complementation studies performed with athkt1;1 plants, could provide essential information about these transporters. in this work, we analyzed the ...201425408697
the olfactory system as a model to study axonal growth patterns and morphology in vivo.the olfactory system has the unusual capacity to generate new neurons throughout the lifetime of an organism. olfactory stem cells in the basal portion of the olfactory epithelium continuously give rise to new sensory neurons that extend their axons into the olfactory bulb, where they face the challenge to integrate into existing circuitry. because of this particular feature, the olfactory system represents a unique opportunity to monitor axonal wiring and guidance, and to investigate synapse fo ...201425406975
dynein light intermediate chains maintain spindle bipolarity by functioning in centriole cohesion.cytoplasmic dynein 1 (dynein) is a minus end-directed microtubule motor protein with many cellular functions, including during cell division. the role of the light intermediate chains (lics; dync1li1 and 2) within the complex is poorly understood. in this paper, we have used small interfering rnas or morpholino oligonucleotides to deplete the lics in human cell lines and xenopus laevis early embryos to dissect the lics' role in cell division. we show that although dynein lacking lics drives micr ...201425422374
identifying direct targets of transcription factor rfx2 that coordinate ciliogenesis and cell movement.recently, using the frog xenopus laevis as a model system, we showed that transcription factor rfx2 coordinates many genes involved in ciliogenesis and cell movement in multiciliated cells (chung et al., 2014). to our knowledge, it was the first paper to utilize the genomic resources, including genome sequences and interim gene annotations, from the ongoing xenopus laevis genome project. for researchers who are interested in the application of genomics and systems biology approaches in xenopus s ...201425419512
differential regulation of the glutamate transporters glt-1 and glast by gsk3β.the glutamate transporters glast and glt-1 are mainly expressed in glial cells and regulate glutamate levels in the synapses. glast and glt-1 are the targets of several signaling pathways. in this study we explore the possible functional interaction between these transporters and gsk3β. this kinase is involved in multiple cellular processes including neuronal development and synaptic plasticity. to evaluate whether glt-1 and glast were regulated by gsk3β, we coexpressed these proteins in heterol ...201425454285
apkc phosphorylates p27xic1, providing a mechanistic link between apicobasal polarity and cell-cycle control.during the development of the nervous system, apicobasally polarized stem cells are characterized by a shorter cell cycle than nonpolar progenitors, leading to a lower differentiation potential of these cells. however, how polarization might be directly linked to the kinetics of the cell cycle is not understood. here, we report that apicobasally polarized neuroepithelial cells in xenopus laevis have a shorter cell cycle than nonpolar progenitors, consistent with mammalian systems. we show that t ...201425490266
transmembrane signal transduction in oocyte maturation and fertilization: focusing on xenopus laevis as a model animal.fertilization is a cell biological phenomenon of crucial importance for the birth of new life in a variety of multicellular and sexual reproduction species such as algae, animal and plants. fertilization involves a sequence of events, in which the female gamete "egg" and the male gamete "spermatozoon (sperm)" develop, acquire their functions, meet and fuse with each other, to initiate embryonic and zygotic development. here, it will be briefly reviewed how oocyte cytoplasmic components are orche ...201425546390
microtubule nucleation remote from centrosomes may explain how asters span large cells.a major challenge in cell biology is to understand how nanometer-sized molecules can organize micrometer-sized cells in space and time. one solution in many animal cells is a radial array of microtubules called an aster, which is nucleated by a central organizing center and spans the entire cytoplasm. frog (here xenopus laevis) embryos are more than 1 mm in diameter and divide with a defined geometry every 30 min. like smaller cells, they are organized by asters, which grow, interact, and move t ...201425468969
calcium-dependent neuroepithelial contractions expel damaged cells from the developing brain.both developing and adult organisms need efficient strategies for wound repair. in adult mammals, wounding triggers an inflammatory response that can exacerbate tissue injury and lead to scarring. in contrast, embryonic wounds heal quickly and with minimal inflammation, but how this is achieved remains incompletely understood. using in vivo imaging in the developing brain of xenopus laevis, we show that atp release from damaged cells and subsequent activation of purinergic receptors induce long- ...201425468753
negative regulation of the creatine transporter slc6a8 by spak and osr1.transport regulation involves several kinases including spak (sps1-related proline/alanine-rich kinase) and osr1 (oxidative stress-responsive kinase 1), which are under control of wnk (with-no-k[lys]) kinases. the present study explored whether spak and/or osr1 participate in the regulation of the creatine transporter creat (slc6a8), which accomplishes na+ coupled cellular uptake of creatine in several tissues including kidney, intestine, heart, skeletal muscle and brain.201425531585
pancreatic carcinoma in an african clawed frog (xenopus laevis).this report describes the histologic features of a pancreatic carcinoma in an adult female african clawed frog (xenopus laevis). the animal was found to be in poor body condition and subsequently euthanized for a complete necropsy. histologically, the pancreas was effaced by packets of polyhedral cells consistent with a pancreatic islet cell carcinoma. metastatic disease was not identified. pancreatic tumors are uncommon in amphibians, and this report is the first to describe a pancreatic carcin ...201425527022
vertical signalling involves transmission of hox information from gastrula mesoderm to neurectoderm.development and patterning of neural tissue in the vertebrate embryo involves a set of molecules and processes whose relationships are not fully understood. classical embryology revealed a remarkable phenomenon known as vertical signalling, a gastrulation stage mechanism that copies anterior-posterior positional information from mesoderm to prospective neural tissue. vertical signalling mediates unambiguous copying of complex information from one tissue layer to another. in this study, we report ...201425514127
subcellular metabolite and lipid analysis of xenopus laevis eggs by laesi mass spectrometry.xenopus laevis eggs are used as a biological model system for studying fertilization and early embryonic development in vertebrates. most methods used for their molecular analysis require elaborate sample preparation including separate protocols for the water soluble and lipid components. in this study, laser ablation electrospray ionization (laesi), an ambient ionization technique, was used for direct mass spectrometric analysis of x. laevis eggs and early stage embryos up to five cleavage cycl ...201425506922
long-range gap junctional signaling controls oncogene-mediated tumorigenesis in xenopus laevis embryos.in addition to the immediate microenvironment, long-range signaling may be an important component of cancer. molecular-genetic analyses have implicated gap junctions-key mediators of cell-cell communication-in carcinogenesis. we recently showed that the resting voltage potential of distant cell groups is a key determinant of metastatic transformation and tumor induction. here, we show in the xenopus laevis model that gap junctional communication (gjc) is a modulator of the long-range bioelectric ...201425646081
left-right patterning in xenopus conjoined twin embryos requires serotonin signaling and gap junctions.a number of processes operating during the first cell cleavages enable the left-right (lr) axis to be consistently oriented during xenopus laevis development. prior work showed that secondary organizers induced in frog embryos after cleavage stages (i.e. conjoined twins arising from ectopic induced primary axes) correctly pattern their own lr axis only when a primary (early) organizer is also present. this instructive effect confirms the unique lr patterning functions that occur during early emb ...201425896280
optogenetics in developmental biology: using light to control ion flux-dependent signals in xenopus embryos.developmental bioelectricity, electrical signaling among non-excitable cells, is now known to regulate proliferation, apoptosis, gene expression, and patterning during development. the extraordinary temporal and spatial resolution offered by optogenetics could revolutionize the study of bioelectricity the same way it has revolutionized neuroscience. there is, however, no guide to adapting optogenetics to patterning systems. to fill this gap, we used optogenetic reagents, both proteins and photoc ...201425896279
involvement of histidine residue his382 in ph regulation of mct4 activity.monocarboxylate transporter 4 (mct4) is a ph-dependent bi-directional lactate transporter. transport of lactate via mct4 is increased by extracellular acidification. we investigated the critical histidine residue involved in ph regulation of mct4 function. transport of lactate via mct4 was measured by using a xenopus laevis oocyte expression system. mct4-mediated lactate transport was inhibited by zn2+ in a ph physiological condition but not in an acidic condition. the histidine modifier depc (d ...201425919709
endothelin modulates the circadian expression of non-visual opsins.the non-visual opsin, melanopsin, expressed in the mammalian retina, is considered a circadian photopigment because it is responsible to entrain the endogenous biological clock. this photopigment is also present in the melanophores of xenopus laevis, where it was first described, but its role in these cells is not fully understood. x. laevis melanophores respond to light with melanin granule dispersion, the maximal response being achieved at the wavelength of melanopsin maximal excitation. pigme ...201424816266
single cell wound generates electric current circuit and cell membrane potential variations that requires calcium influx.breaching of the cell membrane is one of the earliest and most common causes of cell injury, tissue damage, and disease. if the compromise in cell membrane is not repaired quickly, irreversible cell damage, cell death and defective organ functions will result. it is therefore fundamentally important to efficiently repair damage to the cell membrane. while the molecular aspects of single cell wound healing are starting to be deciphered, its bio-physical counterpart has been poorly investigated. u ...201424801267
caging, but not air deprivation, slows tadpole growth and development in the amphibian xenopus laevis.xenopus laevis tadpoles raised in submerged cages in normoxic water develop more slowly than tadpoles raised with access to air. this study distinguishes between the effects of being caged and being deprived access to air on development and growth. tadpoles were raised in high and low density control tanks and in cages in the same tank that were either completely submerged or with the top exposed to air. experiments were repeated with the cages in different positions relative to the air stones a ...201424799365
maternal syntabulin is required for dorsal axis formation and is a germ plasm component in xenopus.in amphibians and teleosts, early embryonic axial development is driven by maternally deposited mrnas and proteins, called dorsal determinants, which migrate to the presumptive dorsal side of the embryo in a microtubule-dependent manner after fertilization. syntabulin is an adapter protein that binds to kinesin kif5b and to the transmembrane protein syntaxin1. in zebrafish, a mutation in syntabulin causes complete embryo ventralization. it is unknown whether syntabulin plays an analogous role du ...201424798204
structural and functional similarity of amphibian constitutive androstane receptor with mammalian pregnane x receptor.the nuclear receptors and xenosensors constitutive androstane receptor (car, nr1i3) and pregnane x receptor (pxr, nr1i2) induce the expression of xenobiotic metabolizing enzymes and transporters, which also affects various endobiotics. while human and mouse car feature a high basal activity and low induction upon ligand exposure, we recently identified two constitutive androstane receptors in xenopus laevis (xlcará and â) that possess pxr-like characteristics such as low basal activity and activ ...201424797902
thyroid hormones in the skeletogenesis and accessory sources of endogenous hormones in xenopus laevis (amphibia; anura) ontogeny: experimental evidence.skeletal development was studied in normal and goitrogen-treated xenopus laevis tadpoles reared under thyroid hormone (th) deficiency. early stages of skeletal development proceed similarly in both groups. later stages are retarded or completely arrested in goitrogen-treated tadpoles. after goitrogen-treated tadpoles were transferred into pure water or into a medium containing both goitrogen and exogenous th, tadpoles resumed development. consequently, late stages of skeletogenesis are th-depend ...201424795191
investigating physical chromatin associations across the xenopus genome by chromatin immunoprecipitation.chromatin immunoprecipitation (chip) combined with genomic analysis techniques provide a global snapshot of protein-dna interactions in the context of chromatin, yielding insights into which genomic loci might be regulated by the dna-associated protein under investigation. this protocol describes how to perform chip on intact or dissected xenopus embryos. the chip-isolated dna fragments are suitable for high-throughput sequencing (chip-seq) or for quantitative pcr (chip-qpcr). in this protocol, ...201424786504
african clawed toads (xenopus laevis) sense the distance of lateral line stimuli.sighted african clawed toads use their lateral lines to detect stimulus distance, although accuracy and precision are poorer than for stimulus direction. single surface wave trains elicited discrete turns and/or swims towards the wave origin. most responses were brief, ending with the toad stationary (70% overall; 54-86% individual toads) or pausing before turning away (11%; 1-24%). lunges or capturing movements with the arms (13%; 10-22%) also indicated where toads expected to find prey. overal ...201424781249
nucleoside transporters and human organic cation transporter 1 determine the cellular handling of dna-methyltransferase inhibitors.inhibitors of dna methyltransferases (dnmts), such as azacytidine, decitabine and zebularine, are used for the epigenetic treatment of cancer. their action may depend upon their translocation across the plasma membrane. the aim of this study was to identify transporter proteins contributing to dnmt inhibitor action.201424780098
biomechanics and the thermotolerance of development.successful completion of development requires coordination of patterning events with morphogenetic movements. environmental variability challenges this coordination. for example, developing organisms encounter varying environmental temperatures that can strongly influence developmental rates. we hypothesized that the mechanics of morphogenesis would have to be finely adjusted to allow for normal morphogenesis across a wide range of developmental rates. we formulated our hypothesis as a simple mo ...201424776615
unusual evolutionary conservation and further species-specific adaptations of a large family of nonclassical mhc class ib genes across different degrees of genome ploidy in the amphibian subfamily xenopodinae.nonclassical mhc class ib (class ib) genes are a family of highly diverse and rapidly evolving genes wherein gene numbers, organization, and expression markedly differ even among closely related species rendering class ib phylogeny difficult to establish. whereas among mammals there are few unambiguous class ib gene orthologs, different amphibian species belonging to the anuran subfamily xenopodinae exhibit an unusually high degree of conservation among multiple class ib gene lineages. comparati ...201424771209
the wnt/jnk signaling target gene alcam is required for embryonic kidney development.proper development of nephrons is essential for kidney function. β-catenin-independent wnt signaling through fzd8, inversin, daam1, rhoa and myosin is required for nephric tubule morphogenesis. here, we provide a novel mechanism through which non-canonical wnt signaling contributes to tubular development. using xenopus laevis as a model system, we found that the cell-adhesion molecule alcam is required for proper nephrogenesis and functions downstream of fzd3 during embryonic kidney development. ...201424764076
monoterpene glycoside esk246 from pittosporum targets lat3 amino acid transport and prostate cancer cell growth.the l-type amino acid transporter (lat) family consists of four members (lat1-4) that mediate uptake of neutral amino acids including leucine. leucine is not only important as a building block for proteins, but plays a critical role in mtorc1 signaling leading to protein translation. as such, lat family members are commonly upregulated in cancer in order to fuel increased protein translation and cell growth. to identify potential lat-specific inhibitors, we established a function-based high-thro ...201424762008
a device for emulating cuff recordings of action potentials propagating along peripheral nerves.this paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. the system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential ...201424760928
11-trifluoromethyl-phenyldiazirinyl neurosteroid analogues: potent general anesthetics and photolabeling reagents for gabaa receptors.while neurosteroids are well-described positive allosteric modulators of gamma-aminobutyric acid type a (gabaa) receptors, the binding sites that mediate these actions have not been definitively identified.201424756762
facial transplants in xenopus laevis embryos.craniofacial birth defects occur in 1 out of every 700 live births, but etiology is rarely known due to limited understanding of craniofacial development. to identify where signaling pathways and tissues act during patterning of the developing face, a 'face transplant' technique has been developed in embryos of the frog xenopus laevis. a region of presumptive facial tissue (the "extreme anterior domain" (ead)) is removed from a donor embryo at tailbud stage, and transplanted to a host embryo of ...201424748020
trpc2 is expressed in two olfactory subsystems, the main and the vomeronasal system of larval xenopus laevis.complete segregation of the main olfactory epithelium (moe) and the vomeronasal epithelium is first observed in amphibians. in contrast, teleost fishes possess a single olfactory surface, in which genetic components of the main and vomeronasal olfactory systems are intermingled. the transient receptor potential channel trpc2, a marker of vomeronasal neurons, is present in the single fish sensory surface, but is already restricted to the vomeronasal epithelium in a terrestrial amphibian, the red- ...201424737764
chd7, the gene mutated in charge syndrome, regulates genes involved in neural crest cell guidance.heterozygous loss of function mutations in chd7 (chromodomain helicase dna-binding protein 7) lead to charge syndrome, a complex developmental disorder affecting craniofacial structures, cranial nerves and several organ systems. recently, it was demonstrated that chd7 is essential for the formation of multipotent migratory neural crest cells, which migrate from the neural tube to many regions of the embryo, where they differentiate into various tissues including craniofacial and heart structures ...201424728844
prolonged in vivo imaging of xenopus laevis.while live imaging of embryonic development over long periods of time is a well established method for embryos of the frog xenopus laevis, once development has progressed to the swimming stages, continuous live imaging becomes more challenging because the tadpoles must be immobilized. current imaging techniques for these advanced stages generally require bringing the tadpoles in and out of anesthesia for short imaging sessions at selected time points, severely limiting the resolution of the data ...201424723337
functional analysis of a missense mutation in the serine protease inhibitor spint2 associated with congenital sodium diarrhea.membrane-bound serine proteases play important roles in different biological processes. their regulation by endogenous inhibitors is poorly understood. a y163c mutation in the spint2 gene encoding the serine protease inhibitor hepatocyte growth factor inhibitor hai-2 is associated with a congenital sodium diarrhea. the functional consequences of this mutation on hai-2 activity and its physiological targets are unknown. we established a cellular assay in xenopus laevis oocytes to study functional ...201424722141
immunohistochemical analysis of pax6 and pax7 expression in the cns of adult xenopus laevis.pax6 and pax7 are transcription factors essential for the development of the cns. in addition, increasing data, mainly obtained in amniotes, support that they are expressed in subsets of neurons in the adult, likely playing a role in maintaining neuron type identity. in the present study we analyzed the detailed distribution of pax6 and pax7 cells in the adult cns of xenopus laevis. immunohistochemistry with antibodies that are required for high-resolution analysis of pax-expressing cells was co ...201424717807
the egg membrane microdomain-associated uroplakin iii-src system becomes functional during oocyte maturation and is required for bidirectional gamete signaling at fertilization in xenopus laevis.in xenopus laevis, sperm-egg interaction promotes partial proteolysis and/or tyrosine phosphorylation of uroplakin iii (upiii) and the tyrosine kinase src, which both localize to the cholesterol-enriched egg membrane microdomains (mds). here we show that sperm promote proteolysis and/or tyrosine phosphorylation of upiii and src in mds isolated from ovulated and unfertilized eggs (uf-mds). an antibody against the extracellular domain of upiii interferes with these events. inhibition of fertilizat ...201424715460
differential modulation of gaba(a) receptor function by aryl pyrazoles.several aryl pyrazoles characterized by a different molecular structure (flexible vs constrained), but chemically related to rimonabant and am251, were tested for their ability to modulate the function of recombinant α1β2γ2l gabaa receptors expressed in xenopus laevis oocytes. the effects of 6bio-r, 14bio-r, ness 0327, gp1a and gp2a (0.3-30 μm) were evaluated using a two-electrode voltage-clamp technique. 6bio-r and 14bio-r potentiated gaba-evoked cl(-) currents. ness 0327, gp1a and gp2a did not ...201424704372
behavioral observation of xenopus tadpole swimming for neuroscience labs.neuroscience labs benefit from reliable, easily-monitored neural responses mediated by well-studied neural pathways. xenopus laevis tadpoles have been used as a simple vertebrate model preparation in motor control studies. most of the neuronal pathways underlying different aspects of tadpole swimming behavior have been revealed. these include the skin mechanosensory touch and pineal eye light-sensing pathways whose activation can initiate swimming, and the cement gland pressure-sensing pathway r ...201424693257
marine natural products acting on the acetylcholine-binding protein and nicotinic receptors: from computer modeling to binding studies and electrophysiology.for a small library of natural products from marine sponges and ascidians, in silico docking to the lymnaea stagnalis acetylcholine-binding protein (achbp), a model for the ligand-binding domains of nicotinic acetylcholine receptors (nachrs), was carried out and the possibility of complex formation was revealed. it was further experimentally confirmed via competition with radioiodinated α-bungarotoxin ([¹²⁵i]-αbgt) for binding to achbp of the majority of analyzed compounds. alkaloids pibocin, va ...201424686559
ire1α is essential for xenopus pancreas development.inositol requiring enzyme-1 (ire1) is highly conserved from yeasts to humans. upon the endoplasmic reticulum (er) stress, ire1 activates x-box-binding protein 1 (xbp1) by unconventionally splicing xbp1 mrna, which activates the unfolded protein response (upr) to restore er homeostasis. in mice, ire1α inactivity leads to embryonic death and ire1α plays an essential role in extraembryonic tissues and the placenta. however, its precise action in the embryo proper is still unknown. in this study, th ...201424683410
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