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: 5 468
Страница 176 из 547-
CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells.
BACKGROUND: CHD8 (chromodomain helicase DNA-binding protein 8), which codes for a member of the CHD family of ATP-dependent chromatin-remodeling factors, is one of the most commonly mutated genes in autism spectrum disorders (ASD) identified in exome-sequencing studies. Loss of function mutations in the gene have also been found in schizophrenia (SZ) and intellectual disabilities and influence cancer cell proliferation. We previously reported an RNA-seq analysis carried out on neural progenitor cells (NPCs) and monolayer neurons derived from induced pluripotent stem (iPS) cells that were heterozygous for CHD8 knockout (KO) alleles generated using CRISPR-Cas9 gene editing. A significant number of ASD and SZ candidate genes were among those that were differentially expressed in a comparison of heterozygous KO lines (CHD8+/-) vs isogenic controls (CHD8+/-), including the SZ and bipolar disorder (BD) candidate gene TCF4, which was markedly upregulated in CHD8+/- neuronal cells. METHODS: In the current study, RNA-seq was carried out on CHD8+/- and isogenic control (CHD8+/+) cerebral organoids, which are 3-dimensional structures derived from iPS cells that model the developing human telencephalon. RESULTS: TCF4 expression was, again, significantly upregulated. Pathway analysis carried out on differentially expressed genes (DEGs) revealed an enrichment of genes involved in neurogenesis, neuronal differentiation, forebrain development, Wnt/β-catenin signaling, and axonal guidance, similar to our previous study on NPCs and monolayer neurons. There was also significant overlap in our CHD8+/- DEGs with those found in a transcriptome analysis carried out by another group using cerebral organoids derived from a family with idiopathic ASD. Remarkably, the top DEG in our respective studies was the non-coding RNA DLX6-AS1, which was markedly upregulated in both studies; DLX6-AS1 regulates the expression of members of the DLX (distal-less homeobox) gene family. DLX1 was also upregulated in both studies. DLX genes code for transcription factors that play a key role in GABAergic interneuron differentiation. Significant overlap was also found in a transcriptome study carried out by another group using iPS cell-derived neurons from patients with BD, a condition characterized by dysregulated WNT/β-catenin signaling in a subgroup of affected individuals. CONCLUSIONS: Overall, the findings show that distinct ASD, SZ, and BD candidate genes converge on common molecular targets-an important consideration for developing novel therapeutics in genetically heterogeneous complex traits.
-
Filaments and microtubules in the gonadotrophic cell of the lizard, Anolis carolinensis.
-
The synaptic ribbons of the guinea-pig pineal gland under normal and experimental conditions.
-
Ultrastructural features of pituicytes in the neural lobe of adult rats. The peripheral processes.
-
Effects of long and short photoperiod on the ultrastructure of pinealocytes of the cotton rat (Sigmodon hispidus).
The ultrastructure of the pinealocytes of wild-captured cotton rats (Sigmodon hispidus) housed in either long or short photoperiod was examined. Quantitative comparison of selected pinealocyte organelles revealed larger relative volumes of mitochondria, granular endoplasmic reticulum and ribosomes, Golgi apparatus, and inclusion bodies, as well as a higher number of dense-core vesicles in the animals kept in short photoperiod (LD 8:16) as compared to those in animals kept in long photoperiod (LD 16:8). These observations suggest that restricting the amount of light to which animals are exposed activates pinealocytes of the cotton rat.
-
Synaptic vesicles and the nerve-muscle preparation in resinless sections.
Resinless sections have been used to study the fine structural organization of cellular organelles and fibrous components at synapses. Presynaptic elements of the neuromuscular junction, representing the P.N.S., and of cerebral cortical synapses, representing the C.N.S., are examined and compared. Typical ultrastructural features are apparent in presynaptic and postsynaptic components and in the surrounding muscle and neuronal tissue demonstrating the reliability and usefulness of the technique.
-
Ultrastructural changes of the developing blood vessels in the chick embryo adenohypophysis.
A study has been made of the ultrastructural changes undergone by the capillaries of the blood vessel network during development of the pars distalis of the adenohypophysis in the chicken embryo. The adenohypophysial sinusoids attain their full set-up during the last third of embryonic life, and the main features of the differentiation process of the capillary wall concern: (1) a progressive thinning of the endothelium commencing at the 14th i.d., accompanied by a reduction of the cytoplasmic organelles of its cells from the 16th i.d.; (2) a gradual disappearance of the largely overlapping cytoplasmic projections of adjoining endothelial cells, and a progressive increment of the pores, closed by diaphragms, in their thinnest peripheral extensions; (3) a marked narrowing, from the 14th i.d. on, of the perivascular space, which attains its definitive characteristics only at hatching, when the endothelial basement lamina forms. The significance of endothelial porous vacuoles throughout maturation of the vessel wall is discussed, and some remarks on the relationships between histogenesis and vessel development in the chicken pars distalis of the adenohypophysis are advanced.
-
Purkinje nerve cell changes caused by electric fields - ultrastructural studies on long-term effects on rabbits.
Albino rabbits exposed to E-field (50 Hz AC, 14 kV/m, undisturbed field) from foetal life period "in utero" up to 7.5 weeks postnatally gained only about half the weight of controls reared in a Faraday's cage or outside measurable E-field. The Purkinje nerve cells in the cerebellum of E-field-exposed rabbits were reduced in size and the number of Nissl's bodies was reduced, as were the profiles of endoplasmic reticulum. A new structure, not observed in the controls, appeared in large numbers, namely, lamellar bodies concomitant with loss of hypolemmal cisterns. These structures were shown to be derived from the endoplasmic reticulum. The structural changes observed are interpreted as reflecting effects of exposure to an E-field.
-
Ultrastructural localization of gonadotropin and luteinizing hormone releasing hormone in the pituitary gland of a teleost fish (the platyfish).
Immunoreactive luteinizing hormone releasing hormone (irLHRH) and immunoreactive gonadotropin (irGtH) are demonstrated in the pituitary gland of a teleost fish (Xiphophorus maculatus, the platyfish) at the ultrastructural level. Using a immunoperoxidase procedure, irGtH and irLHRH are specifically localized over the secretory granules of both gonadotropes and some cells of the pars intermedia (PI). All other pituitary cell types lack immunoreactive material. A concept of LHRH receptors on gonadotrope granules is discussed and a new function for a class of PI cells is suggested.
-
Three-dimensional aspects and synaptic relationships of a Golgi-impregnated spiny stellate cell reconstructed from serial thin sections.
A Golgi-impregnated spiny stellate cell was selected from layer IV of SmI cortex in a mouse whose ipsilateral ventrobasal complex had been lesioned. The neuron was gold-toned, thin sectioned and then reconstructed in three dimensions using wooden sheets of appropriate thickness. These procedures enabled the numbers and distribution of thalamocortical and other synapses onto the reconstructed neuron to be determined. Results show the cell body to be roughly spherical and to receive 49 symmetrical synapses and four synapses which are intermediate between the asymmetrical and symmetrical type. A single, clearly asymmetrical axosomatic synapse is made by a degenerating, thalamocortical axon terminal. Five primary dendrites and their branches were reconstructed and, interestingly, these processes are distinctly elliptical in cross-section. The reconstructed dendrites receive 68 symmetrical synapses onto their shafts and 373 synapses onto spines of which 359 are asymmetrical and 14 symmetrical. Forty-eight, or about 13%, of the asymmetrical axospinous synapses are made by degenerating, thalamocortical axon terminals. An intriguing finding is that in many regions of the dendritic tree, two or more spines involved in thalamocortical synapses are attached to the dendritic shaft at intervals of 5 +/- 0.5 micron.