Когнітивні структури репрезентації хрематонімійних знань

В запропонованій статті розглядаються основні структури репрезентації хрематонімів в ментальному лексиконі індивіда. Питання побудови моделей та схем організації ментального лексикону привертає велику увагу лінгвістів сьогодні.В предложенной статье рассматриваются основные структуры репрезентации хрематонимов в ментальном лексиконе индивида. Вопрос построения моделей и схем организации ментального лексикона привлекает огромное внимание лингвистов.The article deals with the main representation structures of chrematonyms in the mental lexicon of an individual. The task of model construction and scheme organization of mental lexicon attracts much attention of linguists today

Wnt3a protein reduces growth factor-driven expansion of human hematopoietic stem and progenitor cells in serum-free cultures

Abstract Ex vivo expansion of hematopoietic stem and progenitor cells (HSPC) is a promising approach to improve insufficient engraftment after umbilical cord blood stem cell transplantation (UCB-SCT). Although culturing HSPC with hematopoietic cytokines results in robust proliferation, it is accompanied with extensive differentiation and loss of self-renewal capacity. Wnt signaling has been implicated in regulating HSPC fate decisions in vivo and in promoting HSPC self-renewal by inhibition of differentiation, but the effects of Wnt on the ex vivo expansion of HSPC are controversial. Here, we demonstrate that exogenous Wnt3a protein suppresses rather than promotes the expansion of UCB-derived CD34+ cells in serum free expansion cultures. The reduced expansion was also observed in cultures initiated with LinCD34+ CD38lowCD45RACD90+ cells which are highly enriched in HSC and was also observed in response to activation of beta-catenin signaling by GSK3 inhibition. The presence of Wnt3a protein during the culture reduced the frequency of multilineage CFU-GEMM and the long-term repopulation ability of the expanded HSPC. These data suggest that Wnt signaling reduces expansion of human HSPC in growth factor-driven expansion cultures by promoting differentiation of HSPC

Osteoblasts secrete miRNA-containing extracellular vesicles that enhance expansion of human umbilical cord blood cells

Osteolineage cells represent one of the critical bone marrow niche components that support maintenance of hematopoietic stem and progenitor cells (HSPCs). Recent studies demonstrate that extracellular vesicles (EVs) regulate stem cell development via horizontal transfer of bioactive cargo, including microRNAs (miRNAs). Using next-generation sequencing we show that human osteoblast-derived EVs contain highly abundant miRNAs specifically enriched in EVs, including critical regulators of hematopoietic proliferation (e.g., miR-29a). EV treatment of human umbilical cord blood-derived CD34 + HSPCs alters the expression of candidate miRNA targets, such as HBP1, BCL2 and PTEN. Furthermore, EVs enhance proliferation of CD34 + cells and their immature subsets in growth factor-driven ex vivo expansion cultures. Importantly, EV-expanded cells retain their differentiation capacity in vitro and successfully engraft in vivo. These discoveries reveal a novel osteoblast-derived EV-mediated mechanism for regulation of HSPC proliferation and warrant consideration of EV-miRNAs for the development of expansion strategies to treat hematological disorders

Identification of osteolineage cell-derived extracellular vesicle cargo implicated in hematopoietic support

Osteolineage cell-derived extracellular vesicles (EVs) play a regulatory role in hematopoiesis and have been shown to promote the ex vivo expansion of human hematopoietic stem and progenitor cells (HSPCs). Here, we demonstrate that EVs from different human osteolineage sources do not have the same HSPC expansion promoting potential. Comparison of stimulatory and non-stimulatory osteolineage EVs by next-generation sequencing and mass spectrometry analyses revealed distinct microRNA and protein signatures identifying EV-derived candidate regulators of ex vivo HSPC expansion. Accordingly, the treatment of umbilical cord blood-derived CD34+ HSPCs with stimulatory EVs-altered HSPC transcriptome, including genes with known roles in cell proliferation. An integrative bioinformatics approach, which connects the HSPC gene expression data with the candidate cargo in stimulatory EVs, delineated the potentially targeted biological functions and pathways during hematopoietic cell expansion and development. In conclusion, our study giv

Magnetic Resonance Detection of CD34+ Cells from Umbilical Cord Blood Using a 19F Label.

Impaired homing and delayed recovery upon hematopoietic stem cell transplantation (HSCT) with hematopoietic stem cells (HSC) derived from umbilical cord blood (UCB) is a major problem. Tracking transplanted cells in vivo will be helpful to detect impaired homing at an early stage and allows early interventions to improve engraftment and outcome after transplantation. In this study, we show sufficient intracellular labeling of UCB-derived CD34+ cells, with 19F-containing PLGA nanoparticles which were detectable with both flow cytometry and magnetic resonance spectroscopy (MRS). In addition, labeled CD34+ cells maintain their capacity to proliferate and differentiate, which is pivotal for successful engraftment after transplantation in vivo. These results set the stage for in vivo tracking experiments, through which the homing efficiency of transplanted cells can be studied

Uptake of the label is an active process and results in intracellular accumulation of the label.

<p>(A) Fluorescence histogram for mock-labeled control cells (red) and cells labeled 20 hours at 37°C (turquoise) or 4°C (orange). Horizontal axes show the intensity of the FITC signal, representing the ¹⁹F -PLGA nanoparticles. (B) Differential Interference Contrast image (left) and fluorescent image (right) of CD34⁺ cells labeled with ¹⁹F -PLGA nanoparticles, showing the blue DAPI-signal (nucleus of the cell) and the green FITC-signal (¹⁹F -PLGA nanoparticles).</p

Labeling with ¹⁹F-PLGA does not affect the relative proportion of committed hematopoietic progenitors and cell viability.

<p><b>(A)</b> Total number of colonies per 500 CD34⁺ cells for BFU-E (red), CFU-GM (white) and CFU-GEMM (gray). (B) Percentage of life cells at input (white), and after 4 (green) and 20 (black) hours of labeling with 20 μl/ml ¹⁹F-PLGA (n = 5).</p

CD34⁺ cells can be labeled efficiently with ¹⁹F -PLGA nanoparticles with the intensity increasing with longer incubation time and higher labeling concentration.

<p>(A) Fluorescence histograms of cells labeled with 0 (red), 5 (turquoise), 10 (orange), 20 (green) and 40 (blue) μl/ml nanoparticles at incubation times of 4 (left panel) or 20 (right panel) hours. Horizontal axes show the intensity of the FITC signal, representing the ¹⁹F -PLGA nanoparticles. (B) Median fluorescence intensity per labeling concentration after 4 (circle) and 20 (square) hours of labeling. Figs 1A and 1B show a representative experiment out of 2 experiments. (C) Median fluorescence intensity of cells labeled with 20 μl/ml ¹⁹F -PLGA nanoparticles for 4 and 20 hours (n = 5). * = p<0.05.</p

Detection of labeled CD34⁺ cells by magnetic resonance spectroscopy and imaging.

<p>Left and right panel show the ¹⁹F MRS spectrum of 2 agar gel phantoms containing 10⁵ and 10⁴ labeled CD34⁺ cells in 150 μl respectively. Shown is the ¹⁹F resonance line, the horizontal axes shows the frequency offset from the transmitter. Here the transmitter frequency has been set to the resonance frequency of the ¹⁹F in PFCE. Labeled cells were labeled with 20 μl/ml ¹⁹F -PLGA nanoparticles with an incubation time of 20 hours.</p