scholarly journals Clinical and Molecular Insights in Erythropoiesis Regulation of Signal Transduction Pathways in Myelodysplastic Syndromes and β-Thalassemia

2021 ◽  
Vol 22 (2) ◽  
pp. 827
Author(s):  
Sarah Parisi ◽  
Carlo Finelli ◽  
Antonietta Fazio ◽  
Alessia De Stefano ◽  
Sara Mongiorgi ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Transforming Growth Factor ◽  
Early Stage ◽  
Hypoxia Inducible Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
And Function ◽  
Preclinical And Clinical Studies ◽  
Role And Function

Erythropoiesis regulation is essential in normal physiology and pathology, particularly in myelodysplastic syndromes (MDS) and β-thalassemia. Several signaling transduction processes, including those regulated by inositides, are implicated in erythropoiesis, and the latest MDS or β-thalassemia preclinical and clinical studies are now based on their regulation. Among others, the main pathways involved are those regulated by transforming growth factor (TGF)-β, which negatively regulates erythrocyte differentiation and maturation, and erythropoietin (EPO), which acts on the early-stage erythropoiesis. Also small mother against decapentaplegic (SMAD) signaling molecules play a role in pathology, and activin receptor ligand traps are being investigated for future clinical applications. Even inositide-dependent signaling, which is important in the regulation of cell proliferation and differentiation, is specifically associated with erythropoiesis, with phospholipase C (PLC) and phosphatidylinositol 3-kinase (PI3K) as key players that are becoming increasingly important as new promising therapeutic targets. Additionally, Roxadustat, a new erythropoiesis stimulating agent targeting hypoxia inducible factor (HIF), is under clinical development. Here, we review the role and function of the above-mentioned signaling pathways, and we describe the state of the art and new perspectives of erythropoiesis regulation in MDS and β-thalassemia.

scholarly journals MicroRNAs in brain development and cerebrovascular pathophysiology

2019 ◽  
Vol 317 (1) ◽  
pp. C3-C19 ◽  
Author(s):  
Qingyi Ma ◽  
Lubo Zhang ◽  
William J. Pearce
Keyword(s):  
Brain Development ◽  
Synapse Formation ◽  
Current Knowledge ◽  
Great Promise ◽  
Ischemic Brain ◽  
Neural Lineage ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
And Function

MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs with 21–25 nucleotides in length and play an important role in regulating gene expression at the posttranscriptional level via base-paring with complementary sequences of the 3′-untranslated region of the target gene mRNA, leading to either transcript degradation or translation inhibition. Brain-enriched miRNAs act as versatile regulators of brain development and function, including neural lineage and subtype determination, neurogenesis, synapse formation and plasticity, neural stem cell proliferation and differentiation, and responses to insults. Herein, we summarize the current knowledge regarding the role of miRNAs in brain development and cerebrovascular pathophysiology. We review recent progress of the miRNA-based mechanisms in neuronal and cerebrovascular development as well as their role in hypoxic-ischemic brain injury. These findings hold great promise, not just for deeper understanding of basic brain biology but also for building new therapeutic strategies for prevention and treatment of pathologies such as cerebral ischemia.

scholarly journals Timing as a mechanism of development and evolution in the cerebral cortex

2021 ◽  
Author(s):  
Laura R. Fenlon
Keyword(s):  
Phenotypic Variation ◽  
Cognitive Abilities ◽  
Individual Variability ◽  
Cell Proliferation And Differentiation ◽  
Single Organism ◽  
Proliferation And Differentiation ◽  
And Function ◽  
Axonal Targeting ◽  
The Brain ◽  
Development And Evolution

One of the biggest mysteries in neurobiology concerns the mechanisms responsible for the diversification of the brain over different time scales i.e. during development and evolution. Subtle differences in the timing of biological processes during development, e.g. onset, offset, duration, speed and sequence, can trigger large changes in phenotypic outcomes. At the level of a single organism, altered timing of developmental events can lead to individual variability, as well as malformation and disease. At the level of phylogeny, there are known interspecies differences in the timing of developmental events, and this is thought to be an important factor that drives phenotypic variation across evolution, known as heterochrony. A particularly striking example of phenotypic variation is the evolution of human cognitive abilities, which has largely been attributed to the development of the mammalian-specific neocortex and its subsequent expansion in higher primates. Here, I review how the timing of different aspects of cortical development specifies developmental outcomes within species, including processes of cell proliferation and differentiation, neuronal migration and lamination, and axonal targeting and circuit maturation. Some examples of the ways that different processes might “keep time” in the cortex are explored, reviewing potential cell-intrinsic and -extrinsic mechanisms. Further, by combining this knowledge with known differences in timing across species, timing changes that may have occurred during evolution are identified, which perhaps drove the phylogenetic diversification of neocortical structure and function.

scholarly journals TABOO AND TABULAR VOCABULARY IN THE KAZAKH LANGUAGE

2020 ◽  
pp. 164-170
Author(s):  
A. Onalbayeva ◽  
◽  
G. Orynkhanova ◽  
G. Askarova ◽  
◽  
...  
Keyword(s):  
Language Development ◽  
Religious Beliefs ◽  
Early Stage ◽  
Moral Norms ◽  
Social Basis ◽  
The People ◽  
And Function ◽  
Role And Function

This article examines the linguistic and ethnographic nature of taboos and euphemisms as one of the topical issues of lexicology and stylistics of the Kazakh language. The question of the origin and spread of taboos has been studied in detail. The classification of taboos and euphemisms of the Kazakh language is given. Taboos and euphemisms that arose at an early stage of language development due to religious beliefs, as well as customs that once existed among the people, are studied. Forbidden words and euphemisms that arose on a different social basis, which includes etiquette, established moral norms, etc., are classified, techniques and language means of euphemization are identified. The role and function of taboos and euphemisms in changing the meaning of words and enriching the vocabulary and developing the culture of speech are defined.

Changes of alkaline phosphatase activity in response to different stressors in planarian Dugesia japonica

Biologia ◽  
2013 ◽  
Vol 68 (2) ◽  
Author(s):  
Guang-Wen Chen ◽  
Ke-Xue Ma ◽  
De-Zeng Liu
Keyword(s):  
Alkaline Phosphatase ◽  
Heat Shock ◽  
Early Stage ◽  
High Concentration ◽  
Experimental Conditions ◽  
Alp Activity ◽  
Planarian Regeneration ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Dugesia Japonica

AbstractThe aims of this work are to provide some properties of alkaline phosphatase (ALP) in the planarian Dugesia japonica and detect its activity in response to different stressors, as well as to introduce renatured SDS-PAGE to study enzyme activity in planarians. Our results indicate that ALPs in planarians are mainly membrane-bound form, identified as three mainly enzyme-bands (approximately MW 260 kD, 180 kD, 160 kD, respectively). Under our experimental conditions, ALPs activity had no apparent changes in response to low concentration of Hg2+ (25 μg L−1) and Pb2+ (125 μg L−1, 250 μg L−1) exposure, but were severely inhibited in response to high concentration of Hg2+ (50 μg L−1, 150 μg L−1, 300 μg L−1) and Pb2+ (500 μg L−1, 1000 μg L−1) exposure. Mild heat shock (25°C for 2 days) elevated ALP activity, but severely heat shock (25°C for 2 days, followed by 30°C for 2 days and 32°C for 2 days) inactivated ALP activity. Interestingly, ALP and other cytosolic phosphatases (MW from ∼45 kD to ∼60 kD) activity increased noticeably during the early stage of planarians regeneration, which may be involved in cell proliferation and differentiation. Contrary to regeneration, prolonged starvation suppressed ALP activity. The above findings provide valuable information about the role of ALP in planarian regeneration and for its use as an indicator in ecotoxicology.

scholarly journals Clonal analysis of sucrase-isomaltase expression in the human colon adenocarcinoma Caco-2 cells

1991 ◽  
Vol 280 (3) ◽  
pp. 599-608 ◽  
Author(s):  
J F Beaulieu ◽  
A Quaroni
Keyword(s):  
Growth Factor ◽  
Culture Medium ◽  
Transforming Growth Factor ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Human Colon Carcinoma Cell ◽  
Cell Proliferation And Differentiation ◽  
Cell Clones ◽  
Proliferation And Differentiation ◽  
Clonal Cell Lines

To investigate the biosynthetic basis for the mosaic expression of brush border enzymes in confluent Caco-2 cells, a human colon carcinoma cell line exhibiting characteristics of adult small intestinal enterocytes, we have obtained a series of clones differing markedly in their growth rates, amounts of transforming growth factor-alpha/epidermal growth factor-like activity released into the culture medium, and sucrase-isomaltase (SI) activity. Other intestinal markers (aminopeptidase N, dipeptidylpeptidase IV, lactase, alkaline phosphatase and ‘crypt cell antigen’) displayed a much more limited variability in expression, suggesting that the Caco-2 cell clones we have obtained did not differ in their overall ability to differentiate. Immunofluorescence staining, metabolic labelling with radioactive methionine and hybridization analysis of SI mRNA abundance were used to investigate SI synthesis and its regulation in clones endowed with low, intermediate or high sucrase activity. The results obtained have demonstrated heterogeneous SI expression, even in clonal cell lines, and a negative correlation between SI expression and growth factor concentrations in the culture medium, suggesting an autocrine regulation of cell proliferation and differentiation in confluent Caco-2 cells. Pulse-chase experiments using the two clones endowed with the lowest and highest levels of SI activity, followed by immunoprecipitation of labelled SI with epitope-specific antibodies and SDS/PAGE analysis, suggested that both transcriptional and post-translational mechanisms play a role in the regulation of SI expression in intestinal cells.

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