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: 5 464
Страница 145 из 547-
CRISPRi-based radiation modifier screen identifies long non-coding RNA therapeutic targets in glioma.
BACKGROUND: Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority of lncRNAs have not been tested as potential therapeutic targets, particularly in the context of currently used cancer treatments. Malignant glioma is rapidly fatal, and ionizing radiation is part of the current standard-of-care used to slow tumor growth in both adult and pediatric patients. RESULTS: We use CRISPR interference (CRISPRi) to screen 5689 lncRNA loci in human glioblastoma (GBM) cells, identifying 467 hits that modify cell growth in the presence of clinically relevant doses of fractionated radiation. Thirty-three of these lncRNA hits sensitize cells to radiation, and based on their expression in adult and pediatric gliomas, nine of these hits are prioritized as lncRNA Glioma Radiation Sensitizers (lncGRS). Knockdown of lncGRS-1, a primate-conserved, nuclear-enriched lncRNA, inhibits the growth and proliferation of primary adult and pediatric glioma cells, but not the viability of normal brain cells. Using human brain organoids comprised of mature neural cell types as a three-dimensional tissue substrate to model the invasive growth of glioma, we find that antisense oligonucleotides targeting lncGRS-1 selectively decrease tumor growth and sensitize glioma cells to radiation therapy. CONCLUSIONS: These studies identify lncGRS-1 as a glioma-specific therapeutic target and establish a generalizable approach to rapidly identify novel therapeutic targets in the vast non-coding genome to enhance radiation therapy.
-
Morphological studies on neuroglia. II. Response of glial cells to kainic acid-induced lesions.
The cellular response of non-neuronal elements of the pyramidal cell layer of the rat hippocampus, especially the area CA3, was observed electron microscopically following destruction of this formation by means of intraventricular administration of kainic acid (KA). The neuroglial cell types responding to the KA-induced lesion included astrocytes and the "microglia-like reactive cells". In addition, numerous brain macrophages appeared in the damaged area CA3. Oligodendrocytes and pericytes revealed no morphological changes. Swollen astrocytes were seen in the KA-induced lesion during the early stage. Glial filaments gradually developed in the soma and cell processes of these cells. Brain macrophages were seen in the KA-induced lesion during the early stage; they gradually decreased in number with time. Numerous small cells displaying a dark nucleus appeared in the damaged area CA3 during the first two days after the KA-administration, and gradually increased in number. During the later stage this cell type could hardly be distinguished from the intrinsic microglial cells. It is open to discussion whether this cell type originates from the intrinsic microglial cells or from the hematogenic monocytes; therefore it is designated as "microglia-like reactive cell" in the present study.
-
An isoform of Dicer protects mammalian stem cells against multiple RNA viruses.
In mammals, early resistance to viruses relies on interferons, which protect differentiated cells but not stem cells from viral replication. Many other organisms rely instead on RNA interference (RNAi) mediated by a specialized Dicer protein that cleaves viral double-stranded RNA. Whether RNAi also contributes to mammalian antiviral immunity remains controversial. We identified an isoform of Dicer, named antiviral Dicer (aviD), that protects tissue stem cells from RNA viruses-including Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-by dicing viral double-stranded RNA to orchestrate antiviral RNAi. Our work sheds light on the molecular regulation of antiviral RNAi in mammalian innate immunity, in which different cell-intrinsic antiviral pathways can be tailored to the differentiation status of cells.
-
[Ultrastructural analysis of the phenomenon of acute neuronal swelling].
WAG rats were exposed to hyperthermia. Neurons manifested acute swelling in all portions of the brain. At the ultrastructural level these phenomena were characterized by an increase in the size of the bodies and nuclei of neurons, complete dissociation of polysomes, swelling of some cisterns of the endoplasmatic reticulum and perinuclear space, and destruction of the mitochondria of apical processes. Hyperchromic (dark) cells were found to be more resistant to acute swelling. The question is discussed whether this pathology of neural cells is reversible. The role of this pathology in the neuropathology of febrile schizophrenia is considered.
-
[Ultrastructure of the cells of surviving hippocampal slices during the incubation process].
The dynamics of ultrastructural changes in the pyramidal neurons from the CA3 area of hippocampal slices was studied. It was shown that after 5 hours' incubation changes in the reticulum, nuclear envelope and mitochondria took place. No visible changes were seen in different synapses after incubation longer than 5 hours. It might be seen that the glial cells had their structural integrity after 30 hours. The data obtained were in a good agreement with our electrophysiological observations of neurons of the same area. The present data suggests that the brain slices in vitro are convenient objects for a parallel ultrastructural and electrophysiological study of the properties of neurons within a 1-5 hours incubation.
-
Primate cell fusion disentangles gene regulatory divergence in neurodevelopment.
Among primates, humans display a unique trajectory of development that is responsible for the many traits specific to our species. However, the inaccessibility of primary human and chimpanzee tissues has limited our ability to study human evolution. Comparative in vitro approaches using primate-derived induced pluripotent stem cells have begun to reveal species differences on the cellular and molecular levels1,2. In particular, brain organoids have emerged as a promising platform to study primate neural development in vitro3-5, although cross-species comparisons of organoids are complicated by differences in developmental timing and variability of differentiation6,7. Here we develop a new platform to address these limitations by fusing human and chimpanzee induced pluripotent stem cells to generate a panel of tetraploid hybrid stem cells. We applied this approach to study species divergence in cerebral cortical development by differentiating these cells into neural organoids. We found that hybrid organoids provide a controlled system for disentangling cis- and trans-acting gene-expression divergence across cell types and developmental stages, revealing a signature of selection on astrocyte-related genes. In addition, we identified an upregulation of the human somatostatin receptor 2 gene (SSTR2), which regulates neuronal calcium signalling and is associated with neuropsychiatric disorders8,9. We reveal a human-specific response to modulation of SSTR2 function in cortical neurons, underscoring the potential of this platform for elucidating the molecular basis of human evolution.
-
Studies on the mechanism of mitosis.
-
Scanning and transmission electron microscopic study of the supraependymal macrophages in the lateral ventricles of the toad brain.
Transmission and scanning electron microscopy of the lateral ventricles of the toad brain revealed the presence of supraependymal cells that have the features of macrophages. Based solely on their surface morphology three different cell forms could be identified. The most frequently observed cells are flat and multipolar, and have a smooth or ruffled surface. The second type is spherical with a ruffled surface and occurs either singly, in which case it lacks processes, or in clusters from which processes radiate. The third type has surface blebs and numerous thin, smooth processes. However, when specimens that had been examined in the scanning electron microscope are viewed in the transmission electron microscope, all cells appear to belong to a single cell type. All cells viewed closely resemble macrophages in that they contain nuclei with clumped chromaffin, single cisternae of rough endoplasmic reticulum, numerous dense bodies, and many Golgi complexes. In addition, when horseradish peroxidase (HRP) was perfused into the ventricles, reaction product was found a short time thereafter within cytoplasmic vacuoles, and after a longer period within dense bodies. Because of their ultrastructural resemblance to macrophages and their capacity to ingest HRP, we suggest that these cells function as phagocytes and, as such, act to remove foreign materials from the cerbrospinal fluid.
-
Surface morphology of the subfornical organ in the rabbit's brain.
-
Peroxisomal abnormalities in metabolic diseases.