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encapsulation of xenopus egg and embryo extract spindle assembly reactions in synthetic cell-like compartments with tunable size.methods are described for preparing xenopus laevis egg and embryo cytoplasm and encapsulating extract spindle assembly reactions in cell-like compartments to investigate the effects of cell size on intracellular assembly. cytoplasm prepared from the eggs or embryos of individual frogs is screened for the ability to form interphase nuclei and metaphase spindles, and subsequently packaged, along with dna, into droplets of varying size using microfluidics. the dimensions of these cell-like droplets ...201627193845
assays to study mitotic centrosome and spindle pole assembly and regulation.faithful chromosome segregation during cell division requires proper bipolar spindle assembly and critically depends on spindle pole integrity. in most animal cells, spindle poles form as the result of the concerted action of various factors operating in two independent pathways of microtubule assembly mediated by chromatin/rangtp and by centrosomes. mutation or deregulation of a number of spindle pole-organizing proteins has been linked to human diseases, including cancer and microcephaly. our ...201627193852
identification and characterization of mitotic spindle-localized transcripts.rnas associate with the mitotic spindle in a variety of organisms, where they can spatially regulate protein production, ensure their proper segregation during cell division, or perform translation-independent roles in spindle formation. the identification of spindle-associated rnas is an important first step in understanding the biological consequences of this phenomenon. in this chapter, we describe a method to use xenopus laevis egg extracts to assemble and isolate mitotic spindles and to ide ...201627193857
novel positive allosteric modulators of gabaa receptors with anesthetic activity.gabaa receptors are the main inhibitory neurotransmitter receptors in the brain and are targets for numerous clinically important drugs such as benzodiazepines, anxiolytics and anesthetics. we previously identified novel ligands of the classical benzodiazepine binding pocket in α1β2γ2 gabaa receptors using an experiment-guided virtual screening (egvs) method. this screen also identified novel ligands for intramembrane low affinity diazepam site(s). in the current study we have further characteri ...201627198062
a single amino-acid substitution in the sodium transporter hkt1 associated with plant salt tolerance.a crucial prerequisite for plant growth and survival is the maintenance of potassium uptake, especially when high sodium surrounds the root zone. the arabidopsis high-affinity k(+) transporter1 (hkt1), and its homologs in other salt-sensitive dicots, contributes to salinity tolerance by removing na(+) from the transpiration stream. however, tshkt1;2, one of three hkt1 copies in thellungiella salsuginea, a halophytic arabidopsis relative, acts as a k(+) transporter in the presence of na(+) in yea ...201627208305
quantification of 11 thyroid hormones and associated metabolites in blood using isotope-dilution liquid chromatography tandem mass spectrometry.this paper describes a novel analytical methodology for the simultaneous determination of absolute and total concentrations of 11 native thyroid hormones and associated metabolites, viz. thyroxine (t4), 3,3', 5-triiodothyronine (t3), 3,3', 5'-triiodothyronine (rt3), 3,5-diiodothyronine (3,5-t2), 3,3'- diiodothyronine (3,3'-t2), 3-iodothyronine (t1), thyronine (t0), 3-iodothyronamine (t1am), tetraiodothyroacetic acid (tetrac), triiodothyroacetic acid (triac), and diiodothyroacetic acid (diac), in ...201627215639
the cardiac-restricted protein adp-ribosylhydrolase-like 1 is essential for heart chamber outgrowth and acts on muscle actin filament assembly.adprhl1, a member of the adp-ribosylhydrolase protein family, is expressed exclusively in the developing heart of all vertebrates. in the amphibian xenopus laevis, distribution of its mrna is biased towards actively growing chamber myocardium. morpholino oligonucleotide-mediated knockdown of all adprhl1 variants inhibits striated myofibril assembly and prevents outgrowth of the ventricle. the resulting ventricles retain normal electrical conduction and express markers of chamber muscle different ...201627217161
cadmium but not lead exposure affects xenopus laevis fertilization and embryo cleavage.among the toxicological and ecotoxicological studies, few have investigated the effects on germ cells, gametes or embryos, while an impact at these stages will result in serious damage at a population level. thus, it appeared essential to characterize consequences of environmental contaminant exposures at these stages. therefore, we proposed to assess the effects of exposure to cadmium and lead ions, alone or in a binary mixture, on early stages of xenopus laevis life cycle. fertilization and ce ...201627218424
the role of micrornas in animal cell reprogramming.our concept of cell reprogramming and cell plasticity has evolved since john gurdon transferred the nucleus of a completely differentiated cell into an enucleated xenopus laevis egg, thereby generating embryos that developed into tadpoles. more recently, induced expression of transcription factors, oct4, sox2, klf4, and c-myc has evidenced the plasticity of the genome to change the expression program and cell phenotype by driving differentiated cells to the pluripotent state. beyond these milest ...201627224014
membrane dynamics during cellular wound repair.cells rapidly reseal after damage, but how they do so is unknown. it has been hypothesized that resealing occurs due to formation of a patch derived from rapid fusion of intracellular compartments at the wound site. however, patching has never been directly visualized. here we study membrane dynamics in wounded xenopus laevis oocytes at high spatiotemporal resolution. consistent with the patch hypothesis, we find that damage triggers rampant fusion of intracellular compartments, generating a bar ...201627226483
luminal ca(2+) dynamics during ip3r mediated signals.the role of cytosolic ca(2+) on the kinetics of inositol 1,4,5-triphosphate receptors (ip3rs) and on the dynamics of ip3r-mediated ca(2+) signals has been studied at large both experimentally and by modeling. the role of luminal ca(2+) has not been investigated with that much detail although it has been found that it is relevant for signal termination in the case of ca(2+) release through ryanodine receptors. in this work we present the results of observing the dynamics of luminal and cytosolic ...201627232767
the unique myelopoiesis strategy of the amphibian xenopus laevis.myeloid progenitors reside within specific hematopoietic organs and commit to progenitor lineages bearing megakaryocyte/erythrocyte (mep) or granulocyte/macrophage potentials (gmp) within these sites. unlike other vertebrates, the amphibian xenopus laevis committed macrophage precursors are absent from the hematopoietic subcapsular liver and instead reside within their bone marrow. presently, we demonstrate that while these frogs' liver-derived cells are unresponsive to recombinant forms of prin ...201627234705
sexually dimorphic expression of dmrt1 and γh2ax in germ stem cells during gonadal development in xenopus laevis.in many animals, primordial germ cells (pgcs) migrate into developing gonads. there, they proliferate and differentiate into female and male germ stem cells (gscs), oogonia and spermatogonia, respectively. few studies have focused on the molecular mechanisms underlying the development of gsc sex determination. here, we investigated the expression of the transcription factor dmrt1 and a phosphorylated form of the histone variant h2ax (γh2ax) during gonadal development in xenopus laevis. during ea ...201627239441
[xenopus laevis peroxiredoxins: gene expression during development and characterization of the enzymes].reactive oxygen species (ros) are produced via catabolic and anabolic processes during normal embryonic development, and ros content in the cell is maintained at a certain level. peroxiredoxins are a family of selenium-independent peroxidases and play a key role in maintaining redox homeostasis of the cell. in addition to regulating the ros level, peroxiredoxins are involved in intracellular and intercellular signaling, cell differentiation, and tissue development. the time course of peroxiredox ...201627239855
rattlesnake phospholipase a2 increases cftr-chloride channel current and corrects ∆f508cftr dysfunction: impact in cystic fibrosis.deletion of phe508 in the nucleotide binding domain (∆f508-nbd1) of the cystic fibrosis transmembrane regulator (cftr; a cyclic amp-regulated chloride channel) is the most frequent mutation associated with cystic fibrosis. this mutation affects the maturation and gating of cftr protein. the search for new high-affinity ligands of cftr acting as dual modulators (correctors/activators) presents a major challenge in the pharmacology of cystic fibrosis. snake venoms are a rich source of natural mult ...201627241308
development of the larval amphibian growth and development assay: effects of benzophenone-2 exposure in xenopus laevis from embryo to juvenile.the larval amphibian growth and development assay (lagda) is a globally harmonized chemical testing guideline developed by the u.s. environmental protection agency in collaboration with japan's ministry of environment to support risk assessment. the assay is employed as a higher tiered approach to evaluate effects of chronic chemical exposure throughout multiple life stages in a model amphibian species, xenopus laevis. to evaluate the utility of the initial lagda design, the assay was performed ...201627241388
impacts of climate change on the global invasion potential of the african clawed frog xenopus laevis.by altering or eliminating delicate ecological relationships, non-indigenous species are considered a major threat to biodiversity, as well as a driver of environmental change. global climate change affects ecosystems and ecological communities, leading to changes in the phenology, geographic ranges, or population abundance of several species. thus, predicting the impacts of global climate change on the current and future distribution of invasive species is an important subject in macroecologica ...201627248830
reprogramming of somatic cells and nuclei by xenopus oocyte and egg extracts.differentiated somatic cells and nuclei can be reprogrammed to a pluripotent undifferentiated state in the cytoplasm of oocytes and eggs. the ability of the gamete cells to induce reprogramming is not species-specific, so the extracts prepared from the oocytes and eggs of the african clawed frog xenopus laevis can reprogram somatic mammalian cells. thus, xenopus egg extract-mediated reprogramming may constitute an alternative or complement other experimental reprogramming approaches, such as nuc ...201627251073
regulation of human kv1.4 channel activity by the antidepressant metergoline.metergoline is an ergot-derived psychoactive drug that is a ligand for various serotonin and dopamine receptors. little is known about the effect of metergoline on different types of receptors and ion channels. potassium channels are the most diverse group of ion channels. kv1.4, a shaker family k channel alpha subunit, is one of a family of voltage gated k channels that mediates transient and rapid inactivating a-type currents and n-type inactivation. we demonstrated previously that metergoline ...201627251511
transcriptome profiles of metamorphosis in the ornamented pygmy frog microhyla fissipes clarify the functions of thyroid hormone receptors in metamorphosis.anuran metamorphosis is an excellent system in which to study postembryonic development. studies on xenopus (mesobatrachia) show that thyroid hormone receptors (trs) regulate metamorphosis in a ligand-dependent manner by coordinating the action of hundreds of genes. however, whether this mechanism is conserved among amphibians is still unknown. to understand the molecular mechanism of this universal phenomenon, we report the transcriptional profiles of the three key developmental stages in micro ...201627254593
amino acid transporter b(0)at1 (slc6a19) and ancillary protein: impact on function.amino acids play an important role in the metabolism of all organisms. their epithelial re-absorption is due to specific transport proteins, such as b(0)at1, a na(+)-coupled neutral amino acid symporter belonging to the solute carrier 6 family. here, a recently cloned fish orthologue, from the intestine of salmo salar, was electrophysiologically characterized with the two-electrode voltage clamp technique, in xenopus laevis oocytes heterologously expressing the transporter. substrate specificity ...201627255547
a tunable silk hydrogel device for studying limb regeneration in adult xenopus laevis.in certain amphibian models limb regeneration can be promoted or inhibited by the local wound bed environment. this research introduces a device that can be utilized as an experimental tool to characterize the conditions that promotes limb regeneration in the adult frog (xenopus laevis) model. in particular, this device was designed to manipulate the local wound environment via a hydrogel insert. initial characterization of the hydrogel insert revealed that this interaction had a significant inf ...201627257960
rna extraction from xenopus auditory and vestibular organs for molecular cloning and expression profiling with rna-seq and microarrays.the amphibian xenopus offers a unique model system for uncovering the genetic basis of auditory and vestibular function in an organism that is well-suited for experimental manipulation during animal development. however, many procedures for analyzing gene expression in the peripheral auditory and vestibular systems mandate the ability to isolate intact rna from inner ear tissue. methods presented here facilitate preparation of high-quality inner ear rna from larval and post-metamorphic xenopus s ...201627259922
the synthetic gestagen levonorgestrel directly affects gene expression in thyroid and pituitary glands of xenopus laevis tadpoles.the synthetic gestagen levonorgestrel (lng) was previously shown to perturb thyroid hormone-dependent metamorphosis in xenopus laevis. however, so far the mechanisms underlying the anti-metamorphic effects of lng remained unknown. therefore, a series of in vivo and ex vivo experiments was performed to identify potential target sites of lng action along the pituitary-thyroid axis of x. laevis tadpoles. prometamorphic tadpoles were treated in vivo with lng (0.01-10nm) for 72h and brain-pituitary a ...201627262936
luteinizing hormone is an effective replacement for hcg to induce ovulation in xenopus.injection of human chorionic gonadotropin (hcg) directly into the dorsal lymph sac of xenopus is a commonly used protocol for induction of ovulation, but recent shortages in the stocks of commercially available hcg as well as lack of a well tested alternative have resulted in frustrating experimental delays in laboratories that predominantly use xenopus in their research. mammalian luteinizing hormones (lh) share structural similarity, functional equivalency, and bind the same receptor as hcg; t ...201627263125
heteromeric channels with different phenotypes are generated when coexpressing two p2x2 receptor isoforms.to investigate if channels with different stoichiometry are formed from p2x2 receptor isoforms during their heterologous co-expression. the two-electrode voltage-clamp technique was used to measured atp induced currents in xenopus laevis oocytes. we used a mutant (p2x2-2bm) because its atp sensitivity is lower than p2x2-2b receptors, which highlights the differences with its splice variant p2x2-1a.currents through homomeric channels had significantly different hill coefficients. p2xr are trimeri ...201627282483
the plasticizer bisphenol a affects somatic and sexual development, but differently in pipid, hylid and bufonid anurans.due to their terrestrial habitats and aquatic reproduction, many amphibians are both very vulnerable and highly suitable bioindicators. the plasticizer bisphenol a (bpa) is one of the most produced chemical substances worldwide, and knowledge on its impacts on humans and animals is mounting. bpa is used for the industrial production of polycarbonate plastics and epoxy resins and found in a multitude of consumer products. studies on bpa have involved mammals, fish and the fully aquatic anuran mod ...201627285164
recording temperature-induced neuronal activity through monitoring calcium changes in the olfactory bulb of xenopus laevis.the olfactory system, specialized in the detection, integration and processing of chemical molecules is likely the most thoroughly studied sensory system. however, there is piling evidence that olfaction is not solely limited to chemical sensitivity, but also includes temperature sensitivity. premetamorphic xenopus laevis are translucent animals, with protruding nasal cavities deprived of the cribriform plate separating the nose and the olfactory bulb. these characteristics make them well suited ...201627286501
electrophysiological characterization of a large set of novel variants in the scn5a-gene: identification of novel lqts3 and brs mutations.scn5a encodes for the α-subunit of the cardiac voltage-gated sodium channel nav1.5. gain-of-function mutations in scn5a are related to congenital long qt syndrome (lqts3) characterized by delayed cardiac repolarization, leading to a prolonged qt interval in the ecg. loss-of-function mutations in scn5a are related to brugada syndrome (brs), characterized by an st-segment elevation in the right precordial leads (v1-v3). the aim of this study was the characterization of a large set of novel scn5a v ...201627287068
gene expression profiles in testis of developing male xenopus laevis damaged by chronic exposure of atrazine.as a widely used herbicide, atrazine (az) has been extensively studied for its adverse effects on the reproductive system, especially feminization in male animals. however, the relationship of gene expression changes and associated toxicological endpoints remains unclear. in this study, developing xenopus laevis tadpoles were exposed to concentration of az at 0.1, 1, 10 or 100 μg/l continuously. compared with froglets in the control group, there were no significant differences in body length, bo ...201627288644
cloning and functional expression of intracellular loop variants of the honey bee (apis mellifera) rdl gaba receptor.the insect gaba receptor, rdl (resistance to dieldrin), plays central roles in neuronal signalling and is the target of several classes of insecticides. to study the gaba receptor from an important pollinator species, we cloned rdl cdna from the honey bee, apis mellifera. three rdl variants were identified, arising from differential use of splice acceptor sites in the large intracellular loop between transmembrane regions 3 and 4. these variants were renamed from previously, as amel_rdlvar1, ame ...201627288983
waterborne exposure to triadimefon causes thyroid endocrine disruption and developmental delay in xenopus laevis tadpoles.triadimefon (tdf) is a triazole-derivative fungicide that is detectable in the environment and target agricultural products, prompting concern over its risk to wildlife and human health. in our study, nieuwkoop & faber stage 51 xenopus laevis tadpoles were exposed to different nominal concentrations tdf (0, 0.112, and 1.12mg/l) for 21 days while the tadpoles were undergoing pre-morphological development. developmental condition, bioaccumulation and thyroid hormone levels, and mrna expression of ...201627289584
peptidomic analysis of the extensive array of host-defense peptides in skin secretions of the dodecaploid frog xenopus ruwenzoriensis (pipidae).the uganda clawed frog xenopus ruwenzoriensis with a karyotype of 2n=108 is one of the very few vertebrates with dodecaploid status. peptidomic analysis of norepinephrine-stimulated skin secretions from this species led to the isolation and structural characterization of 23 host-defense peptides belonging to the following families: magainin (3 peptides), peptide glycine-leucine-amide (pgla; 6 peptides), xenopsin precursor fragment (xpf; 3 peptides), caerulein precursor fragment (cpf; 8 peptides) ...201627290612
sex chromosome differentiation and the w- and z-specific loci in xenopus laevis.genetic sex-determining systems in vertebrates include two basic types of heterogamety; xx (female)/xy (male) and zz (male)/zw (female) types. the african clawed frog xenopus laevis has a zz/zw-type sex-determining system. in this species, we previously identified a w-specific sex (female)-determining gene dmw, and specified w and z chromosomes, which could be morphologically indistinguishable (homomorphic). in addition to dmw, we most recently discovered two genes, named scanw and ccdc69w, and ...201727297884
conservation in the involvement of heterochronic genes and hormones during developmental transitions.developmental transitions include molting in some invertebrates and the metamorphosis of insects and amphibians. while the study of caenorhabditis elegans larval transitions was crucial to determine the genetic control of these transitions, drosophila melanogaster and xenopus laevis have been classic models to study the role of hormones in metamorphosis. here we review how heterochronic genes (lin-4, let-7, lin-28, lin-41), hormones (dafachronic acid, ecdysone, thyroid hormone) and the environme ...201627297887
in vitro models of cranial neural crest development toward toxicity tests: frog, mouse, and human.during craniofacial development, cranial neural crest (nc)-derived mesenchymal cells migrate to pharyngeal arches and contribute extensively to neurons, schwann cells, smooth muscle cells, osteoblasts, chondrocytes, and odontoblasts, forming maxillofacial structures. in vitro models using model organism cells, such as african clawed frog (xenopus laevis) and mouse (mus musculus), were developed to understand cellular and molecular mechanisms of cranial nc development. recent studies using human ...201727299949
expression pattern and pharmacological characterisation of two novel alternative splice variants of the glutamate-gated chloride channel in the small brown planthopper laodelphax striatellus.glutamate-gated chloride channels (glucl) mediate fast inhibitory neurotransmission in invertebrate nervous systems. although only one glucl gene was presented in insects, it showed diverse alternative splicing that was speculated could affect channel function and pharmacology.201727302648
single cell proteomics using frog (xenopus laevis) blastomeres isolated from early stage embryos, which form a geometric progression in protein content.single cell analysis is required to understand cellular heterogeneity in biological systems. we propose that single cells (blastomeres) isolated from early stage invertebrate, amphibian, or fish embryos are ideal model systems for the development of technologies for single cell analysis. for these embryos, although cell cleavage is not exactly symmetric, the content per blastomere decreases roughly by half with each cell division, creating a geometric progression in cellular content. this progre ...201627314579
label-free quantification of proteins in single embryonic cells with neural fate in the cleavage-stage frog (xenopus laevis) embryo using capillary electrophoresis electrospray ionization high-resolution mass spectrometry (ce-esi-hrms).quantification of protein expression in single cells promises to advance a systems-level understanding of normal development. using a bottom-up proteomic workflow and multiplexing quantification by tandem mass tags, we recently demonstrated relative quantification between single embryonic cells (blastomeres) in the frog (xenopus laevis) embryo. in this study, we minimize derivatization steps to enhance analytical sensitivity and use label-free quantification (lfq) for single xenopus cells. the t ...201627317400
ddt exposure of frogs: a case study from limpopo province, south africa.amphibians are globally under pressure with environmental contaminants contributing to this. despite caution aired more than 80 years ago of threats posed to amphibians by ddt spraying for disease vector control, no data have been published on concentrations or effects of ddt contamination in frogs from areas where ddt is actively sprayed to control the insect vectors of malaria. in this study, we sampled fat bodies of xenopus laevis and xenopus muelleri naturally occurring in an area where indo ...201627317939
exploring the functions of nonclassical mhc class ib genes in xenopus laevis by the crispr/cas9 system.a large family of highly related and clustered xenopus nonclassical mhc class ib (xnc) genes influences xenopus laevis immunity and potentially other physiological functions. using rna interference (rnai) technology, we previously demonstrated that one of xnc genes, xnc10.1, is critical for the development and function of a specialized innate t (it) cell population. however, rnai limitation such as a variable and unstable degree of gene silencing in f0 and f1 generations is hampering a thorough ...201727318386
molecular mode of action of cgs 9895 at α1 β2 γ2 gabaa receptors.γ-aminobutyric type a (gabaa ) receptors are the main inhibitory neurotransmitter receptors in the brain and are targets for numerous clinically important drugs such as benzodiazepines, anxiolytics, and anesthetics. previously, pyrazoloquinoline 2-p-methoxyphenylpyrazolo [4,3-c] quinolin-3(5h)-one (cgs 9895) was described as a positive allosteric modulator acting through the α+/β- interface in the extracellular domain of gabaa receptors. the localization of the binding site was based on a steric ...201627319298
sumoylation of dna topoisomerase iiα regulates histone h3 kinase haspin and h3 phosphorylation in mitosis.dna topoisomerase ii (top2) plays a pivotal role in faithful chromosome separation through its strand-passaging activity that resolves tangled genomic dna during mitosis. additionally, top2 controls progression of mitosis by activating cell cycle checkpoints. recent work showed that the enzymatically inert c-terminal domain (ctd) of top2 and its posttranslational modification are critical to this checkpoint regulation. however, the molecular mechanism has not yet been determined. by using xenopu ...201627325792
alanine to valine substitutions in the pore helix iiip1 and linker-helix iiil45 confer cockroach sodium channel resistance to ddt and pyrethroids.pyrethroid insecticides exert toxic effects by prolonging the opening of voltage-gated sodium channels. more than 20 sodium channel mutations from arthropod pests and disease vectors have been confirmed to confer pyrethroid resistance. these mutations have been valuable in elucidating the molecular interaction between pyrethroids and sodium channels, including identification of two pyrethroid receptor sites. previously, two alanine to valine substitutions, one in the pore helix iiip1 and the oth ...201627328896
metabolic cost of osmoregulation in a hypertonic environment in the invasive african clawed frog xenopus laevis.studies of aquatic invertebrates reveal that salinity affects feeding and growth rates, reproduction, survival, and diversity. little is known, however, about how salinity impacts the energy budget of vertebrates and amphibians in particular. the few studies focused on this topic in vertebrates suggest that the ingestion of salts and the resulting osmoregulatory activity is energetically expensive. we analyzed the effect of saline acclimation on standard metabolic rates (smr) and the activities ...201627334694
wide and high resolution tension measurement using fret in embryo.during embryonic development, physical force plays an important role in morphogenesis and differentiation. stretch sensitive fluorescence resonance energy transfer (fret) has the potential to provide non-invasive tension measurements inside living tissue. in this study, we introduced a fret-based actinin tension sensor into xenopus laevis embryos and demonstrated that this sensor captures variation of tension across differentiating ectoderm. the actinin tension sensor, containing mcherry and egf ...201627335157
overexpression of leap2 impairs xenopus embryonic development and modulates fgf and activin signals.besides its widely described function in the innate immune response, no other clear physiological function has been attributed so far to the liver-expressed-antimicrobial-peptide 2 (leap2). we used the xenopus embryo model to investigate potentially new functions for this peptide. we identified the amphibian leap2 gene which is highly related to its mammalian orthologues at both structural and sequence levels. the gene is expressed in the embryo mostly in the endoderm-derived tissues. accordingl ...201627335344
slah1, a homologue of the slow type anion channel slac1, modulates shoot cl- accumulation and salt tolerance in arabidopsis thaliana.salinity tolerance is correlated with shoot chloride (cl(-)) exclusion in multiple crops, but the molecular mechanisms of long-distance cl(-) transport are poorly defined. here, we characterize the in planta role of atslah1 (a homologue of the slow type anion channel-associated 1 (slac1)). this protein, localized to the plasma membrane of root stelar cells, has its expression reduced by salt or aba, which are key predictions for a protein involved with loading cl(-) into the root xylem. artifici ...201627340232
interaction of atorvastatin with the human glial transporter slc16a1.solute carrier (slc) 16a1 is a ph-dependent carrier of 5-oxoproline, a derivative of the amino acid. slc16a1 interacts with carboxylate group-containing substrates, which are also present in atorvastatin, and might be the reason for its ability to interact with atorvastatin. does atorvastatin interact with the carrier? does it also interact with the carrier via the substrate recognition site? this study was carried out to answer these questions. polymerase chain reaction was used to determine th ...201627341998
increased apoptosis and abnormal visual behavior by histone modifications with exposure to para-xylene in developing xenopus.xylene and its derivatives are raw materials widely used in industry and known to be toxic to animals. however, the mechanism underlying the neurotoxicity of para-xylene (px) to the central nervous system (cns) in vivo is less clear. here, we exposed xenopus laevis tadpoles to sub-lethal concentrations of px during the critical period of brain development to determine the effects of px on xenopus development and visual behavior. we found that the abnormality rate was significantly increased with ...201627343828
maintenance of the epithelial barrier and remodeling of cell-cell junctions during cytokinesis.epithelial integrity and barrier function must be maintained during the complex cell shape changes that occur during cytokinesis in vertebrate epithelial tissue. here, we investigate how adherens junctions and bicellular and tricellular tight junctions are maintained and remodeled during cell division in the xenopus laevis embryo. we find that epithelial barrier function is not disrupted during cytokinesis and is mediated by sustained tight junctions. using fluorescence recovery after photobleac ...201627345163
phosphocholine - an agonist of metabotropic but not of ionotropic functions of α9-containing nicotinic acetylcholine receptors.we demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit atp-dependent release of interleukin-1β from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nachr). interleukin-1β is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. control of interleukin-1β release is vital as excessively high systemic levels cause life threatening inflammatory diseases. in spite of ...201627349288
expression and localization of the xenopus laevis small heat shock protein, hspb6 (hsp20), in a6 kidney epithelial cells.small heat shock proteins (shsps) are molecular chaperones that bind to unfolded protein, inhibit the formation of toxic aggregates and facilitate their refolding and/or degradation. previously, the only shsps that have been studied in detail in the model frog system, xenopus laevis, were members of the hsp30 family and hspb1 (hsp27). we now report the analysis of x. laevis hspb6, an ortholog of mammalian hspb6. x. laevis hspb6 cdna encodes a 168 aa protein that contains an α-crystallin domain, ...201627354198
evolution of innate-like t cells and their selection by mhc class i-like molecules.until recently, major histocompatibility complex (mhc) class i-like-restricted innate-like αβt (it) cells expressing an invariant or semi-invariant t cell receptor (tcr) repertoire were thought to be a recent evolutionary acquisition restricted to mammals. however, molecular and functional studies in xenopus laevis have demonstrated that it cells, defined as mhc class i-like-restricted innate-like αβt cells with a semi-invariant tcr, are evolutionarily conserved and prominent from early developm ...201627368412
the enigma of the dichotomic pressure response of glun1-4a/b splice variants of nmda receptor: experimental and statistical analyses.professional deep-water divers, exposed to hyperbaric pressure (hp) above 1.1 mpa, develop high pressure neurological syndrome (hpns), which is associated with central nervous system (cns) hyperexcitability. it was previously reported that hp augments n-methyl-d-aspartate receptor (nmdar) synaptic response, increases neuronal excitability and potentially causes irreversible neuronal damage. our laboratory has reported differential current responses under hp conditions in nmdar subtypes that cont ...201627375428
loss of function of napiiia causes nephrocalcinosis and possibly kidney insufficiency.inherited metabolic disorders associated with nephrocalcinosis are rare conditions. the aim of this study was to identify the genetic cause of an israeli-arab boy from a consanguineous family with severe nephrocalcinosis and kidney insufficiency.201627378183
inter- and intra-subunit butanol/isoflurane sites of action in the human glycine receptor.glycine receptors (glyrs) mediate inhibitory neurotransmission and are targets for alcohols and anesthetics in brain. glyr transmembrane (tm) domains contain critical residues for alcohol/anesthetic action: amino acid a288 in tm3 forms crosslinks with tm1 (i229) in the adjacent subunit as well as tm2 (s267) and tm4 (y406, w407, i409, y410) in the same subunit. we hypothesized that these residues may participate in intra-subunit and inter-subunit sites of alcohol/anesthetic action. the following ...201627378846
in-cell protein structures from 2d nmr experiments.in-cell nmr spectroscopy provides atomic resolution insights into the structural properties of proteins in cells, but it is rarely used to solve entire protein structures de novo. here, we introduce a paramagnetic lanthanide-tag to simultaneously measure protein pseudocontact shifts (pcss) and residual dipolar couplings (rdcs) to be used as input for structure calculation routines within the rosetta program. we employ this approach to determine the structure of the protein g b1 domain (gb1) in i ...201627379949
analysis of cell size in the gastrula of ten frog species reveals a correlation of egg with cell sizes, and a conserved pattern of small cells in the marginal zone.we investigated the relationship between egg and cell sizes in the early gastrula of ten species of frogs with eggs of 1,100-3,500 μm diameters. we asked whether differences in cell size of the vegetal region, blastocoel roof, and marginal zone of the early gastrula were associated with egg size. alternatively, we proposed that cell size differences may associate with gastrulation characteristics. the analyzed species were as follows: xenopus laevis, engystomops randi, engystomops coloradorum, e ...201727381278
comparative expression study of sipa family members during early xenopus laevis development.the signal-induced proliferation-associated (sipa) protein family belongs to the rapgap protein superfamily. previous studies mainly focused on the expression and function of sipa genes in vertebrate neuronal tissue. only limited data about the embryonic expression pattern of the genes are currently available. our study provides the first expression analysis of sipa1, sipa1l1, sipa1l2, and sipa1l3 during early development of the vertebrate organism xenopus laevis. in silico, analysis revealed th ...201627384056
noggin 1 overexpression in retinal progenitors affects bipolar cell generation.waves of bone morphogenetic proteins (bmps) and their antagonists are present during initial eye development, but their possible roles in retinogenesis are still unknown. we have recently shown that noggin 1, a bmp antagonist, renders pluripotent cells able to differentiate into retinal precursors, and might be involved in the maintenance of retinal structures in the adult vertebrate eye. here, we report that noggin 1, differently from noggin 2 and noggin 4, is expressed during all phases of xen ...201627389985
platelet derived growth factor b gene expression in the xenopus laevis developing central nervous system.platelet-derived growth factor b (pdgf-b) belongs to the mitogen and growth factor family and like the other members it has many roles in cell differentiation, proliferation and migration during development, adult life and in pathological conditions. among them it has been observed that aberrant pdgf signalling is frequently linked to glioma development and progression, and pdgf-b over-expression in mouse neural progenitors leads to the formation of gliomas. despite this evidence, the mechanisms ...201627389987
xenopus laevis nkx5.3 and sensory organ homeobox (soho) are expressed in developing sensory organs and ganglia of the head and anterior trunk.nkx5 family members are homeobox transcription factors important for sensory organ development. several members of the nkx5 family are expressed in the eye, brain, developing ear, and lateral line. members of this family have been previously identified in medaka, chick, and mouse. here, we characterize two members of the nkx5 family, nkx5.3 and soho, in xenopus laevis. we verify the identity of x. laevis nkx5.3 and soho by phylogenetic comparison to chicken, medaka, and zebrafish orthologs. both ...201627392729
three-step test system for the identification of novel gabaa receptor modulating food plants.potentiation of γ-amino butyric acid (gaba)-induced gabaa receptor (gabaar) activation is a common pathway to achieve sedative, sleep-enhancing, anxiolytic, and antidepressant effects. presently, a three-component test system was established for the identification of novel gabaar modulating food plants. in the first step, potentiation of gaba-induced response of the gabaar was analysed by two-electrode voltage clamp (tevc) for activity on human α1β2-gabaar expressed in xenopus laevis oocytes. po ...201627392961
genes coding for cyclin-dependent kinase inhibitors are fragile in xenopus.cell proliferation is strictly regulated by the dosage balance among cell-cycle regulators such as cdk/cyclin complexes and cdk-inhibitors. even in the allotetraploid genome of xenopus laevis, the dosage balance must be maintained for animals to stay alive, and the duplicated homeologous genes seem to have gradually changed, through evolution, resulting in the best genes for them to thrive. in the xenopus laevis genome, while homeologous gene pairs of cdks are fundamentally maintained and a few ...201727393661
effects of elevated in ovo selenium exposure on late stage development of xenopus laevis tadpoles.the effects of elevated in ovo selenium (se) exposure on late stage larval xenopus laevis development were investigated. adult females were fed diets augmented with selenomethionine for 68 days and bred with untreated males to obtain embryos with measured concentrations of 1.6 (control), 10.8, 28.1 and 81.7 μg se/g dry mass. embryos were reared under uncontaminated conditions until 50 % of individuals within an aquarium had completed metamorphosis. the highest in ovo se exposure group exhibited ...201627412338
teratogenic effects of five anticancer drugs on xenopus laevis embryos.in recent years, the environmental presence of pharmaceuticals - including anticancer drugs - is an emerging issue. because of the lack of appropriate critical studies about anticancer drug effects in frogs, the aim of the present study was to investigate lethal and teratogenic effects of five anticancer drugs widely used in large quantities, i.e. 5-flourouracil, capecitabine, cisplatin, etoposide, and imatinib, in the embryos of the south african clawed frog, xenopus laevis, using fetax - frog ...201627423131
impaired gonadal and somatic development corroborate vulnerability differences to the synthetic estrogen ethinylestradiol among deeply diverged anuran lineages.amphibians are undergoing a global decline. one poorly investigated reason could be the pollution of aquatic habitats by endocrine disrupting compounds (edcs). we tested the susceptibility to the synthetically stabilized estrogen 17α-ethinylestradiol (ee2) in three deeply diverged anuran species, differing in sex determination systems, types of gonadogenesis and larval ecologies. to understand whether data from the amphibian model xenopus laevis (pipidae) are analogous and applicable to only dis ...201627434076
carbon monoxide modulates connexin function through a lipid peroxidation-dependent process: a hypothesis.hemichannels are ion channels composed of six connexins (cxs), and they have the peculiarity to be permeable not only to ions, but also to molecules such as atp and glutamate. under physiological conditions they present a low open probability, which is sufficient to enable them to participate in several physiological functions. however, massive and/or prolonged hemichannel opening induces or accelerates cell death. therefore, the study of the molecular mechanisms that control hemichannel activit ...201627445849
infrared spectroscopy detects changes in an amphibian cell line induced by fungicides: comparison of single and mixture effects.amphibians are regarded as sensitive sentinels of environmental pollution due to their permeable skin and complex life cycle, which usually involves reproduction and development in the aquatic environment. fungicides are widely applied agrochemicals and have been associated with developmental defects in amphibians; thus, it is important to determine chronic effects of environmentally-relevant concentrations of such contaminants in target cells. infrared (ir) spectroscopy has been employed to sig ...201627450236
a functional comparison of cardiac troponin c from representatives of three vertebrate taxa: linking phylogeny and protein function.the ca2+ affinity of cardiac troponin c (ctnc) from rainbow trout is significantly greater than that of ctnc from mammalian species. this high affinity is thought to enable cardiac function in trout at low physiological temperatures and is due to residues asn2, ile28, gln29, and asp30 (gillis et al., 2005, physiol genomics, 22, 1-7). interestingly, the ctnc of the african clawed frog xenopus laevis (frog ctnc) contains gln29 and asp30 but the residues at positions 2 and 28 are those found in all ...201627453566
boric acid is reproductively toxic to adult xenopus laevis, but not endocrine active.the potential reproductive and endocrine toxicity of boric acid (ba) in the african clawed frog, xenopus laevis, was evaluated using a 30-day exposure of adult frogs. adult female and male frogs established as breeders were exposed to a culture water control and 4 target (nominal) test concentrations [5.0, 7.5, 10.0, and 15 mg boron (b)/l, equivalent to 28.5, 42.8, 57.0, and 85.5 mg ba/l] using flow-through diluter exposure system. the primary endpoints measured were adult survival, growth (weig ...201627466210
translational profiling of retinal ganglion cell optic nerve regeneration in xenopus laevis.unlike adult mammals, adult frogs regrow their optic nerve following a crush injury, making xenopus laevis a compelling model for studying the molecular mechanisms that underlie neuronal regeneration. using translational ribosome affinity purification (trap), a method to isolate ribosome-associated mrnas from a target cell population, we have generated a transcriptional profile by rna-seq for retinal ganglion cells (rgc) during the period of recovery following an optic nerve injury. based on bio ...201727471010
functional expression and characterization of plant abc transporters in xenopus laevis oocytes for transport engineering purposes.transport engineering in bioengineering is aimed at efficient export of the final product to reduce toxicity and feedback inhibition and to increase yield. the atp-binding cassette (abc) transporters with their highly diverse substrate specificity and role in cellular efflux are potentially suitable in transport engineering approaches, although their size and high number of introns make them notoriously difficult to clone. here, we report a novel in planta "exon engineering" strategy for cloning ...201627480688
extensions to in silico bioactivity predictions using pathway annotations and differential pharmacology analysis: application to xenopus laevis phenotypic readouts.the simultaneous increase of computational power and the availability of chemical and biological data have contributed to the recent popularity of in silico bioactivity prediction algorithms. such methods are commonly used to infer the 'mechanism of action' of small molecules and they can also be employed in cases where full bioactivity profiles have not been established experimentally. however, protein target predictions by themselves do not necessarily capture information about the effect of a ...201327481146
continued studies on the effects of simazine on the liver histological structure and metamorphosis in the developing xenopus laevis.this study continued our previous work (sai et al. in bull environ contam toxicol 95:157-163, 2015a) by analysing the effects of simazine on the liver histological structure and metamorphosis in the developing xenopus laevis. tadpoles (nieuwkoop-faber stage 46) were exposed to simazine at 0.1, 1.2, 11.0 and 100.9 μg/l for 100 days. when tadpoles were exposed to simazine at 11.0 and 100.9 µg/l, an increased mortality and damaged liver tissues were observed together with significant inhibition of ...201627485009
purification of human and mammalian membrane proteins expressed in xenopus laevis frog oocytes for structural studies.this protocol describes the isolation of recombinant human and mammalian membrane proteins expressed in xenopus laevis frog oocytes for structural studies. the cdna-derived crna of the desired genes is injected into several hundreds of oocytes, which are incubated for several days to allow protein expression. recombinant proteins are then purified via affinity chromatography. the novelty of this method comes from the design of a plasmid that produces multi-tagged proteins and, most importantly, ...201627485339
development of a new decision tree to rapidly screen chemical estrogenic activities of xenopus laevis.during the last past decades, there is an increasing number of studies about estrogenic activities of the environmental pollutants on amphibians and many determination methods have been proposed. however, these determination methods are time-consuming and expensive, and a rapid and simple method to screen and test the chemicals for estrogenic activities to amphibians is therefore imperative. herein is proposed a new decision tree formulated not only with physicochemical parameters but also a bio ...201427485568
nodal signalling in xenopus: the role of xnr5 in left/right asymmetry and heart development.nodal class tgf-β signalling molecules play essential roles in establishing the vertebrate body plan. in all vertebrates, nodal family members have specific waves of expression required for tissue specification and axis formation. in xenopus laevis, six nodal genes are expressed before gastrulation, raising the question of whether they have specific roles or act redundantly with each other. here, we examine the role of xnr5. we find it acts at the late blastula stage as a mesoderm inducer and re ...201627488374
the sequential activation of the mitotic microtubule assembly pathways favors bipolar spindle formation.centrosome maturation is the process by which the duplicated centrosomes recruit pericentriolar components and increase their microtubule nucleation activity before mitosis. the role of this process in cells entering mitosis has been mostly related to the separation of the duplicated centrosomes and thereby to the assembly of a bipolar spindle. however, spindles can form without centrosomes. in fact, all cells, whether they have centrosomes or not, rely on chromatin-driven microtubule assembly t ...201627489339
mechanism of antineoplastic activity of lonidamine.lonidamine (lnd) was initially introduced as an antispermatogenic agent. it was later found to have anticancer activity sensitizing tumors to chemo-, radio-, and photodynamic-therapy and hyperthermia. although the mechanism of action remained unclear, lnd treatment has been known to target metabolic pathways in cancer cells. it has been reported to alter the bioenergetics of tumor cells by inhibiting glycolysis and mitochondrial respiration, while indirect evidence suggested that it also inhibit ...201627497601
ectopic blastema induction by nerve deviation and skin wounding: a new regeneration model in xenopus laevis.recently, the accessory limb model (alm) has become an alternative study system for limb regeneration studies in axolotls instead of using an amputated limb. alm progresses limb regeneration study in axolotls because of its advantages. to apply and/or to compare knowledge in axolotl alm studies to other vertebrates is a conceivable next step. first, xenopus laevis, an anuran amphibian, was investigated. a xenopus frog has hypomorphic regeneration ability. its regeneration ability has been consid ...201427499859
distinct patterns of endosulfatase gene expression during xenopus laevis limb development and regeneration.the heparan sulfate 6-o-endosulfatases sulf1 and sulf2 regulate multiple cellular processes and organ development. sulfs modulate a range of heparan-sulfate-dependent extracellular pathways, including the fibroblast growth factor, bone morphogenetic protein, and wingless/wnt signaling pathways. known patterns of sulf transcript expression together with functional experiments have implicated the sulfs in chondrogenesis and muscle regeneration in mammals. here, we describe the expression patterns ...201527499864
functional joint regeneration is achieved using reintegration mechanism in xenopus laevis.a functional joint requires integration of multiple tissues: the apposing skeletal elements should form an interlocking structure, and muscles should insert into skeletal tissues via tendons across the joint. whereas newts can regenerate functional joints after amputation, xenopus laevis regenerates a cartilaginous rod without joints, a "spike." previously we reported that the reintegration mechanism between the remaining and regenerated tissues has a significant effect on regenerating joint mor ...201627499877
ginsenoside rg3, a gating modifier of eag family k+ channels.ginsenoside 20(s)-rg3 (rg3) is a steroid glycoside that induces human ether-à-go-go-related gene type 1 (herg1, kv11.1) channels to activate at more negative potentials and to deactivate more slowly than normal. however, it is unknown whether this action is unique to herg1 channels. here we compare and contrast the mechanisms of actions of rg3 on herg1 with three other members of the ether-à-go-go (eag) k(+) channel gene family, including eag1 (kv10.1), erg3 (kv11.3), and elk1 (kv12.1). all four ...201627502018
fragile x mental retardation protein knockdown in the developing xenopus tadpole optic tectum results in enhanced feedforward inhibition and behavioral deficits.fragile x syndrome is the leading monogenetic cause of autism and most common form of intellectual disability. previous studies have implicated changes in dendritic spine architecture as the primary result of loss of fragile x mental retardation protein (fmrp), but recent work has shown that neural proliferation is decreased and cell death is increased with either loss of fmrp or overexpression of fmrp. the purpose of this study was to investigate the effects of loss of fmrp on behavior and cell ...201627503008
involvement of protein acyltransferase zdhhc3 in maintaining oocyte meiotic arrest in xenopus laevis.fully grown oocytes of most vertebrates are arrested at prophase i of meiosis (g2 arrest). upon exposure to steroid hormones, oocytes resume meiotic process, also called g2/m transition. the g protein-signaling pathway has been shown to play essential roles in the meiotic arrest at g2 phase. previously, we showed that long chain fatty acyl-coenzyme a synthetase acsl1b was required for maintaining the meiotic arrest in xenopus acsl1b presumably synthesizes palmitoyl-coenzyme a that can be utilize ...201627512151
synthesis of deuterium labeled cholesterol and steroids and their use for metabolic studies.a simple method is described for the preparation of [6,7,7(-2)h3] sterols and steroids. the synthesis starts with a δ(5)-sterol or steroid and involves preparation of the 6-oxo-3α,5α-cyclosteroid, base exchange in the presence of deuterium oxide to introduce two deuteriums at the c-7 position and sodium borodeuteride reduction of the 6-oxo group to introduce the third deuterium atom at c-6. rearrangement of the [6,7,7(-2)h3]6α-hydroxy-3α,5α-cyclosteroid then gives the desired [6,7,7(-2)h3]-δ(5) ...198227519440
phenotypic spectrum of gabra1: from generalized epilepsies to severe epileptic encephalopathies.to delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with gabra1 gene mutations.201627521439
identification and comparative analyses of siamois cluster genes in xenopus laevis and tropicalis.two siamois-related homeobox genes siamois (sia1) and twin (sia2), have been reported in xenopus laevis. these genes are expressed in the blastula chordin- and noggin-expressing (bcne) center and the nieuwkoop center, and have complete secondary axis-inducing activity when over-expressed on the ventral side of the embryo. using whole genome sequences of x. tropicalis and x. laevis, we identified two additional siamois-related genes, which are tandemly duplicated near sia1 and sia2 to form the si ...201727522305
ubiquitin-mediated proteolysis in xenopus extract.the small protein modifier, ubiquitin, can be covalently attached to proteins in the process of ubiquitylation, resulting in a variety of functional outcomes. in particular, the most commonly-associated and well-studied fate for proteins modified with ubiquitin is their ultimate destruction: degradation by the 26s proteasome via the ubiquitin-proteasome system, or digestion in lysosomes by proteolytic enzymes. from the earliest days of ubiquitylation research, a reliable and versatile "cell-in-a ...201627528041
small gtpases rab8a and rab11a are dispensable for rhodopsin transport in mouse photoreceptors.rab11a and rab8a are ubiquitous small gtpases shown as required for rhodopsin transport in xenopus laevis and zebrafish photoreceptors by dominant negative (dn) disruption of function. here, we generated retina-specific rab11a (retrab11a) and rab8a (retrab8a) single and double knockout mice to explore the consequences in mouse photoreceptors. rhodopsin and other outer segment (os) membrane proteins targeted correctly to os and electroretinogram (erg) responses in all three mutant mouse lines wer ...201627529348
up-regulation of the large-conductance ca2+-activated k+ channel by glycogen synthase kinase gsk3β.the pleotropic functions of the large conductance ca2+-activated k+ channels (maxi k+ channel or bk channels) include regulation of neuronal excitation and cell volume. kinases participating in those functions include the glycogen synthase kinase gsk3 ß which is under negative control of protein kinase b (pkb/akt). gsk3ß is inhibited by the antidepressant lithium. the present study thus explored whether gsk3ß modifies the activity of bk channels.201627537208
gene expression analysis of developing cell groups in the pretectal region of xenopus laevis.our previous analysis of progenitor domains in the pretectum of xenopus revealed three molecularly distinct anteroposterior subdivisions, identified as precommissural (pcp), juxtacommissural (jcp), and commissural (cop) histogenetic domains (morona et al. [2011] j comp neurol 519:1024-1050). here we analyzed at later developmental stages the nuclei derived from these areas, attending to their gene expression patterns and histogenesis. transcription-factor gene markers were used to selectively ma ...201727539385
characterisation and vascular expression of nitric oxide synthase 3 in amphibians.in mammals, nitric oxide (no) produced by nitric oxide synthase 3 (nos3) localised in vascular endothelial cells is an important vasodilator but the presence of nos3 in the endothelium of amphibians has been concluded to be absent, based on physiological studies. in this study, a nos3 cdna was sequenced from the toad, rhinella marina. the open reading frame of r. marina nos3 encoded an 1170 amino acid protein that showed 81 % sequence identity to the recently cloned xenopus tropicalis nos3. rhin ...201627543051
a recurrent mutation in kcna2 as a novel cause of hereditary spastic paraplegia and ataxia.the hereditary spastic paraplegias (hsps) are heterogeneous neurodegenerative disorders with over 50 known causative genes. we identified a recurrent mutation in kcna2 (c.881g>a, p.r294h), encoding the voltage-gated k(+) -channel, kv 1.2, in two unrelated families with hsp, intellectual disability (id), and ataxia. follow-up analysis of > 2,000 patients with various neurological phenotypes identified a de novo p.r294h mutation in a proband with ataxia and id. two-electrode voltage-clamp recordin ...201627543892
robust identification of ptbp1-dependent splicing events by a junction-centric approach in xenopus laevis.regulation of alternative splicing is an important process for cell differentiation and development. down-regulation of ptbp1, a regulatory rna-binding protein, leads to developmental skin defects in xenopus laevis. to identify ptbp1-dependent splicing events potentially related to the phenotype, we conducted rnaseq experiments following ptbp1 depletion. we systematically compared exon-centric and junction-centric approaches to detect differential splicing events. we showed that the junction-cen ...201727546377
de novo and inherited mutations in the x-linked gene clcn4 are associated with syndromic intellectual disability and behavior and seizure disorders in males and females.variants in clcn4, which encodes the chloride/hydrogen ion exchanger cic-4 prominently expressed in brain, were recently described to cause x-linked intellectual disability and epilepsy. we present detailed phenotypic information on 52 individuals from 16 families with clcn4-related disorder: 5 affected females and 2 affected males with a de novo variant in clcn4 (6 individuals previously unreported) and 27 affected males, 3 affected females and 15 asymptomatic female carriers from 9 families wi ...201627550844
thyroid hormone regulation of adult intestinal stem cells: implications on intestinal development and homeostasis.organ-specific adult stem cells are essential for organ homeostasis, tissue repair and regeneration. the formation of such stem cells often takes place during postembryonic development, a period around birth in mammals when plasma thyroid hormone concentration is high. the life-long self-renewal of the intestinal epithelium has made mammalian intestine a valuable model to study the function and regulation and adult stem cells. on the other hand, much less is known about how the adult intestinal ...201627554108
the aryl hydrocarbon receptor controls cyclin o to promote epithelial multiciliogenesis.epithelia function as barriers against environmental insults and express the transcription factor aryl hydrocarbon receptor (ahr). however, ahr function in these tissues is unknown. here we show that ahr regulates multiciliogenesis in both murine airway epithelia and in xenopus laevis epidermis. in air-exposed airway epithelia, induction of factors required for multiciliogenesis, including cyclin o (ccno) and multicilin (mcidas), is ahr dependent, and air exposure induces ahr binding to the ccno ...201627554288
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