Браузер не даёт сохранять данные (например, приватный режим): закладки пропадут после закрытия вкладки.
Поиск статей PubMed
Ключевые слова, автор, журнал, годы — результаты из PubMed, аннотации с переводом на русский, закладки в браузере.
Найдено: 5 456
Страница 112 из 546-
Preparation of membrane-depleted polygonal coat structures from isolated coated vesicles.
When coated vesicles isolated from porcine brain are treated with buffers containing 2 M urea and subjected to ultracentrifugation, pellets are obtained which consist of largely smooth-surfaced, i.e. coat-free, vesicles. On dialysis of the urea from the supernatant solution spheroidal particles can be pelleted which are of similar size to the coated vesicles and show the typical polygonal lattice arrays but do not reveal any vesicle membrane profiles. Gel electrophoresis of these membrane-depleted polygonal arrangements demonstrates the predominance, if not exclusive occurrence, of the polypeptide band component with an apparent molecular weight of about 180,000. This suggests that the polygonal coat structure contains only clathrin.
-
Changes in acetylcholine content of rat brain by toxic doses of di-isopropyl phosphofluoridate.
-
Choroid plexus defects in Down syndrome brain organoids enhance neurotropism of SARS-CoV-2.
Why individuals with Down syndrome (DS) are more susceptible to SARS-CoV-2-induced neuropathology remains elusive. Choroid plexus (ChP) plays critical roles in barrier function and immune response modulation and expresses the ACE2 receptor and the chromosome 21-encoded TMPRSS2 protease, suggesting its substantial role in establishing SARS-CoV-2 infection in the brain. To explore this, we established brain organoids from DS and isogenic euploid iPSC that consist of a core of functional cortical neurons surrounded by a functional ChP-like epithelium (ChPCOs). DS-ChPCOs recapitulated abnormal DS cortical development and revealed defects in ciliogenesis and epithelial cell polarity in ChP-like epithelium. We then demonstrated that the ChP-like epithelium facilitates infection and replication of SARS-CoV-2 in cortical neurons and that this is increased in DS. Inhibiting TMPRSS2 and furin activity reduced viral replication in DS-ChPCOs to euploid levels. This model enables dissection of the role of ChP in neurotropic virus infection and euploid forebrain development and permits screening of therapeutics for SARS-CoV-2-induced neuropathogenesis.
-
Realizing the potential of organoids-an interview with Hans Clevers.
-
Disaggregation of brain polysomes induced by electroconvulsive treatment.
-
THE MORPHOLOGY AND ACETYLCHOLINE CONTENT OF ISOLATED CEREBRAL CORTICAL SYNAPTIC VESICLES.
-
Unlocking Neural Function with 3D In Vitro Models: A Technical Review of Self-Assembled, Guided, and Bioprinted Brain Organoids and Their Applications in the Study of Neurodevelopmental and Neurodegenerative Disorders.
Understanding the complexities of the human brain and its associated disorders poses a significant challenge in neuroscience. Traditional research methods have limitations in replicating its intricacies, necessitating the development of in vitro models that can simulate its structure and function. Three-dimensional in vitro models, including organoids, cerebral organoids, bioprinted brain models, and functionalized brain organoids, offer promising platforms for studying human brain development, physiology, and disease. These models accurately replicate key aspects of human brain anatomy, gene expression, and cellular behavior, enabling drug discovery and toxicology studies while providing insights into human-specific phenomena not easily studied in animal models. The use of human-induced pluripotent stem cells has revolutionized the generation of 3D brain structures, with various techniques developed to generate specific brain regions. These advancements facilitate the study of brain structure development and function, overcoming previous limitations due to the scarcity of human brain samples. This technical review provides an overview of current 3D in vitro models of the human cortex, their development, characterization, and limitations, and explores the state of the art and future directions in the field, with a specific focus on their applications in studying neurodevelopmental and neurodegenerative disorders.
-
Study on the spatiotemporal regulation of interferon-stimulated genes during Zika virus infection.
BACKGROUND: Zika virus (ZIKV) can cause severe neurological disorders such as congenital microcephaly, and there are currently no approved prevention or treatment measures. Elucidating the antiviral mechanism of the host interferon-stimulated genes (ISGs) is crucial for the development of therapeutic strategies. METHODS: This study integrated multisystem transcriptomic data [human brain organoids, monocyte-derived dendritic cells (moDCs), and peripheral blood mononuclear cells (PBMCs) from infected patients], combined with cellular experiments and bioinformatics analysis, to systematically investigate the spatiotemporal regulation characteristics and functions of ISGs during ZIKV infection. RESULTS: The results showed that treatment with interferon beta (IFN-β) significantly activated the ISGs (e.g., IRF7 and IFITM3) in the ZIKV-infected brain organoids, which were enriched in virus defense-related pathways. Single-cell transcriptomics revealed cellular heterogeneity in the IFN-β-driven ISG responses in moDCs. Transcriptomic analysis of the PBMCs identified 210 differentially expressed genes between the acute and convalescent phases. Core ISGs (e.g., RSAD2 and OAS3) were transiently upregulated in the acute phase. Through cross-analysis, 22 cross-system shared ISGs were screened out. Least absolute shrinkage and selection operator (LASSO) regression identified 11 potential diagnostic biomarkers for ZIKV infection. Small interfering RNA (siRNA) knockdown experiments confirmed that IFI35, IFI44, and OAS3 exerted antiviral effects by inhibiting ZIKV replication. CONCLUSION: This study reveals the functional plasticity of ISGs and provides key targets and theoretical support for the prevention and treatment of ZIKV.
-
The promise of organoids for unraveling the proteomic landscape of the developing human brain.
Cerebral organoids offer an opportunity to bioengineer experimental avatars of the developing human brain and have already begun garnering relevant insights into complex neurobiological processes and disease. Thus far, investigations into their heterogeneous cellular composition and developmental trajectories have been largely limited to transcriptional readouts. Recent advances in global proteomic technologies have enabled a new range of techniques to explore dynamic and non-overlapping spatiotemporal protein-level programs operational in these humanoid neural structures. Here we discuss these early protein-based studies and their potentially essential role for unraveling critical secreted paracrine signals, processes with poor proteogenomic correlations, or neurodevelopmental proteins requiring post-translational modification for biological activity. Integrating emerging proteomic tools with these faithful human-derived neurodevelopmental models could transform our understanding of complex neural cell phenotypes and neurobiological processes, not exclusively driven by transcriptional regulation. These insights, less accessible by exclusive RNA-based approaches, could reveal new knowledge into human brain development and guide improvements in neural regenerative medicine efforts.
-
Secretory phenomena at the ependyma of the IIIrd ventricle of the embryonic rat.
On the basis of previous observations of the third ventricle, the brains of rat embryos in the 17 to 21 gestation days were examined by light- and electron microscope as well as histochemically. Following results were obtained: 1. Between the 18th and 20th gestation days supraependymal secretion spherules and intraventricular secretion masses were observed in the rostral part of the third ventricular lumen. The intraventricular structures are not demonstrable with neurosecretory stains; they are PAS-negative and do not stain with periodic-acid-bisulfite-aldehydethionine. All histochemical reactions performed were negative. 2. The morphological finding in the same frontal plane is not uniform. Dorso-ventral difference exist between one ependymal region which lies caudal to the subfornical organ and an area in the same plane which is situated further ventrally near the entrance to the foramina Monroi (Fig. 1 a). In the superior portion, the supraependymal structures are spherical or bottle-shaped formations and are easily definable. In the lower ventricular portion densely situated ependymal protrusions are seen which become sperical only in the ventricular lumen. 3. In both instances (the spherical and flask-shaped protrusions of the superior portion and the strongly shaped protrusions of the lower portion of the third ventricle) cytoplasmic protuberances containing more or less dense, fine-grain ground plasma and a differentiated number of polyribosomes can be seen. Using the Richardson stain, chromophobe protrusions are seen to possess a diffuse ground plasma and only a few ribosomes, while chromophile protrusions have a dense ground plasma and numerous polyribosomes rosettes. Only rarely are single vesicles observed in the protrusions. 4. The ependyma cells contain densely packed, rough-walled endoplasmic reticulum whose cisterns are irregularly dilated and filled with electron-dense material; they also contain many ribosomes and dictyosomes. The organelles are accumulated mainly in the apical cell portions. A terminal web spans the cell surface and attaches to the zonulae adhaerentes, preventing the flow of cell organelles into the organelle-free secretory protrusions. 5. The functional implication of the ependymal secretion, which appears in the third ventricle for a few days only, during embryonic development, is still unknown and is the goal of subsequent examinations.