eLife, Год журнала: 2020, Номер 9
Опубликована: Дек. 2, 2020
Ciliary motility is driven by axonemal dyneins that are assembled in the cytoplasm before deployment to cilia. Motile ciliopathy can result from defects themselves or factors required for their cytoplasmic pre-assembly. Recent work demonstrates dyneins, specific assembly factors, and broadly-acting chaperones concentrated liquid-like organelles called DynAPs (Dynein Axonemal Particles). Here, we use
Язык: Английский
Frontiers in Physiology, Год журнала: 2019, Номер 10
Опубликована: Фев. 26, 2019
At a fundamental level most genes, signaling pathways, biological functions and organ systems are highly conserved between man all vertebrate species. Leveraging this conservation, researchers increasingly using the experimental advantages of amphibian Xenopus to model human disease. The online resource, Xenbase, enables disease modeling by curating literature published in PubMed integrating these data with orthologous anatomy, more recently links Online Mendelian Inheritance Man resource (OMIM) Human Disease Ontology (DO). Here we review how Xenbase supports report on meta-analysis research providing an overview different types diseases being modeled variety approaches used. Text mining over 50,000 articles imported into from identified approximately 1,000 putative disease- articles. These were manually assessed annotated ontologies, which then used classify papers based type. We found that is study diverse array three main approaches: cell-free egg extracts aspects cellular molecular biology, oocytes ion transport channel physiology embryo experiments focused congenital diseases. integrated Pages allow easy navigation information external databases. Results analysis will equip suite available or dissect pathological process. Ideally clinicians basic use foster collaborations necessary interrogate development treatment
Язык: Английский
Процитировано
76
Nucleic Acids Research, Год журнала: 2021, Номер 50(D1), С. D970 - D979
Опубликована: Окт. 13, 2021
Echinobase (www.echinobase.org) is a third generation web resource supporting genomic research on echinoderms. The new version was built by cloning the mature Xenopus model organism knowledgebase, Xenbase, refactoring data ingestion pipelines and modifying user interface to adapt multispecies echinoderm content. This approach leveraged over 15 years of previous database application development generate fully featured informatics in single year. In addition software stack, uses private cloud physical hosts that support Xenbase. currently supports six species, focused those used for genomics, developmental biology gene regulatory network analyses. Over 38 000 pages, 18 publications, improved genome assemblies, JBrowse browser BLAST + services are available supported anatomical ontology, uniformly applied formal nomenclature, consistent orthology predictions. A novel feature integrating multiple, disparate species. New genomes from diverse phylum will be added as becomes available. common code design integrated knowledgebases ensures parallel improvements each evolves. widely applicable developing resources.
Язык: Английский
Процитировано
68
Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(23), С. 12852 - 12858
Опубликована: Март 8, 2021
We report the development of in vivo subcellular high-resolution mass spectrometry (HRMS) for proteo-metabolomic molecular systems biology complex tissues. With light microscopy, we identified left-dorsal and left-ventral animal cells cleavage-stage non-sentient Xenopus laevis embryos. Using precision-translated fabricated microcapillaries, content each cell was double-probed, time swiftly (<5 s/event) aspirating <5 % volume (≈10 nL). The proteins metabolites were analyzed by home-built ultrasensitive capillary electrophoresis electrospray ionization employing orbitrap or time-of-flight HRMS. Label-free detection ≈150 (57 identified) 738 found networks with differential quantitative activities between types. spatially temporally scalable sampling, technology preserved integrity cells, neighboring embryo. 95 embryos developed into sentient tadpoles that indistinguishable from their wild-type siblings based on anatomy visual function a background color preference assay.
Язык: Английский
Процитировано
67
eLife, Год журнала: 2018, Номер 7
Опубликована: Дек. 18, 2018
Motile ciliopathies are characterized by specific defects in cilia beating that result chronic airway disease, subfertility, ectopic pregnancy, and hydrocephalus. While many patients harbor mutations the dynein motors drive beating, disease also results from so-called axonemal assembly factors (DNAAFs) act cytoplasm. The mechanisms of DNAAF action remain poorly defined. Here, we show DNAAFs concentrate together with dyneins chaperones into organelles form specifically multiciliated cells, which term DynAPs, for particles. These display hallmarks biomolecular condensates, remarkably, DynAPs enriched stress granule protein G3bp1, but not other proteins or P-body proteins. Finally, both formation liquid-like behaviors disrupted a model motile ciliopathy. findings provide unifying cell biological framework understood class human genes add ciliopathy to growing roster diseases associated phase separation.
Язык: Английский
Процитировано
63
Nucleic Acids Research, Год журнала: 2019, Номер unknown
Опубликована: Ноя. 12, 2019
Xenbase (www.xenbase.org) is a knowledge base for researchers and biomedical scientists that employ the amphibian Xenopus as model organism in research to gain deeper understanding of developmental disease processes. Through expert curation automated data provisioning from various sources strives integrate body on genomics biology together with visualization biologically significant interactions. Most current studies utilize next generation sequencing (NGS) but until now results different experiments were difficult compare not integrated other content. has developed suite tools, interfaces processing pipelines transforms NCBI Gene Expression Omnibus (GEO) NGS content into deeply gene expression chromatin data, mapping all aligned reads most recent genome builds. This can be queried visualized via multiple tools also provides basis future 'gene phenotype' regulatory network analyses.
Язык: Английский
Процитировано
61
GigaScience, Год журнала: 2019, Номер 8(7)
Опубликована: Июль 1, 2019
Massive growth in the amount of research data and computational analysis has led to increased use pipeline managers biomedical research. However, each >100 such uses its own way describe pipelines, leading difficulty porting workflows different environments therefore poor reproducibility studies. For this reason, Common Workflow Language (CWL) was recently introduced as a specification for platform-independent workflow description, work began transition existing pipelines CWL.Herein, we present CWL-Airflow, package that adds support CWL Apache Airflow manager. CWL-Airflow version 1.0 can run on stand-alone MacOS/Linux servers, clusters, or variety cloud platforms. A sample processing chromatin immunoprecipitation sequencing is provided.CWL-Airflow will provide users with features fully fledged manager ability execute anywhere run-from laptop cluster environment. available under License, 2.0 (Apache-2.0), be downloaded from https://barski-lab.github.io/cwl-airflow, https://scicrunch.org/resolver/RRID:SCR_017196.
Язык: Английский
Процитировано
55
Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9
Опубликована: Сен. 16, 2021
The differentiation of primordial germ cells (PGCs) occurs during early embryonic development and is critical for the survival fitness sexually reproducing species. Here, we review two main mechanisms PGC specification, induction, preformation, in context four model vertebrate species: mouse, axolotl, Xenopus frogs, zebrafish. We additionally discuss some notable molecular characteristics shared across specification pathways, including expression products from three conserved germline gene families, DAZ (Deleted Azoospermia) genes, nanos-related DEAD-box RNA helicases. Then, summarize current state knowledge distribution cell determination systems kingdom Animalia, with particular attention to species, but include several categories invertebrates - ranging "proto-vertebrate" cephalochordates arthropods, cnidarians, ctenophores. also briefly highlight ongoing investigations potential lines inquiry that aim understand evolutionary relationships between these modes specification.
Язык: Английский
Процитировано
42
Nature Communications, Год журнала: 2022, Номер 13(1)
Опубликована: Май 31, 2022
Abstract Double-strand breaks (DSBs) are one of the most toxic forms DNA damage and represent a major source genomic instability. Members bromodomain extra-terminal (BET) protein family characterized as epigenetic readers that regulate gene expression. However, evidence suggests BET proteins also play more direct role in repair. Here, we establish cell-free system using Xenopus egg extracts to elucidate expression-independent functions DSB We identify BRD4 critical regulator homologous recombination describe its stimulating processing through interactions with SWI/SNF chromatin remodeling complex resection machinery. These results multifunctional binding links transcriptional activity homology-directed
Язык: Английский
Процитировано
33
The American Journal of Human Genetics, Год журнала: 2022, Номер 109(7), С. 1217 - 1241
Опубликована: Июнь 7, 2022
GRIA1 encodes the GluA1 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors, which are ligand-gated ion channels that act as excitatory receptors for neurotransmitter L-glutamate (Glu). AMPA (AMPARs) homo- or heteromeric protein complexes with four subunits, each encoded by different genes, to GRIA4. Although GluA1-containing AMPARs have a crucial role in brain function, human phenotype associated deleterious sequence variants has not been established. Subjects de novo missense and nonsense were identified through international collaboration. Detailed phenotypic genetic assessments subjects carried out pathogenicity was evaluated vitro characterize changes AMPAR function expression. In addition, two Xenopus gria1 CRISPR-Cas9 F0 models established vivo consequences. Seven unrelated individuals rare identified. One individual homozygous variant (p.Arg377Ter), six had heterozygous variations (p.Arg345Gln, p.Ala636Thr, p.Ile627Thr, p.Gly745Asp), p.Ala636Thr recurrent three individuals. The cohort revealed neurodevelopmental disorder mostly affecting cognition speech. Functional evaluation major subtypes carrying mutations showed profoundly perturb receptor function. stop-gain completely destroys expression AMPARs. show transient motor deficits, an intermittent seizure phenotype, significant impairment working memory mutants. These data support developmental caused both
Язык: Английский
Процитировано
29
Biochimie, Год журнала: 2022, Номер 207, С. 33 - 48
Опубликована: Ноя. 23, 2022
Mesenchymal stem/stromal cells (MSCs) are multipotent somatic that have been widely explored in the field of regenerative medicine. MSCs possess ability to secrete soluble factors as well lipid bound extracellular vesicles (EVs). gained increased interest and attention a result their therapeutic properties, which thought be attributed secretome. However, while use whole pose heterogeneity concerns survival issues post-transplantation, such limitations absent cell-free EV-based treatments. EVs derived from promising agents for range clinical conditions disorders owing immunomodulatory, pro-regenerative, anti-inflammatory, antifibrotic activity. Recent successes with preclinical studies using repair regeneration damaged tissues cardiac tissue, lung, liver, pancreas, bone, skin, cornea, blood diseases discussed this review. We also discuss delivery strategies biomaterials vehicles through systemic or local administration. Despite its effectiveness investigations, application MSC-EV settings will necessitate careful consideration surrounding as: i) scalability isolation, ii) biodistribution, iii) targeting specific tissues, iv) quantification characterization, v) safety efficacy dosage. The future medicine is yet still needs further investigation on enhancing efficacy, scalability, potency applications.
Язык: Английский
Процитировано
29