scholarly journals MOLECULAR-GENETIC MECHANISMS OF PLASMODIUM FALCIPARUM VIRULENCE AND TROPICAL MALARIA PATHOGENESIS

2018 ◽  
Vol 10 (3) ◽  
pp. 23-29
Author(s):  
A. N. Uskov ◽  
A. I. Soloviev ◽  
V. Yu. Kravtsov ◽  
R. V. Gudkov ◽  
E. V. Kolomoets ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Membrane Surface ◽  
Complex Structure ◽  
Molecular Genetic ◽  
Regulation Of Gene Expression ◽  
Clinical Malaria ◽  
Tissue Level ◽  
Cellular Level ◽  
Genetic Mechanisms ◽  
Main Factor

There is introduced the analysis of molecular-genetic mechanisms of tropical malaria pathogenesis and P. falciparum virulence. It is shown, that pathogenesis of tropical malaria is associated with the properties of red blood cells membrane surface (RBCs or erythrocytes) that are infected by P. falciparum. There are «knobs structures» on membrane surface infected RBCs. Knobs structures contains a complex of P. falciparum proteins – PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1). PfEMP1 is associated with virulence of P. falciparum. Complex PfEMP1 has difficult polymorphous structure. Domains of PfEMP1 are able to associate with different cell receptors. Virulence`s individual components of the main factor are selectively sensitive to different tissues and organs. The severity of the clinical malaria infection course depends on the complex structure PfEMP1 of malaria parasites. Composition of polypeptide PfEMP1 is determined by var-complex. Nowadays there are 60 variants of var-complex. Regulation of gene expression, forming part of the var-complex, is carried out on a molecular-genetic level, cellular level, tissue level. Modern research in this area are aimed to explore genes polymorphism of the virulence`s main factor, to identify mechanism of its differential expression. Search of molecular – genetic markers is relevant to develop methods of gene diagnostic and malaria vaccine.

Molecular genetic mechanisms of drug resistance in Plasmodium falciparum

2020 ◽  
Vol 4_2020 ◽  
pp. 80-87
Author(s):  
Solovyev A.I. Solovyev ◽  
Uskov A.N. Uskov ◽  
Kovalenko A.N. Kovalenko ◽  
Kapatsyna V.A. Kapatsyna ◽  
Rakin A.I. Rakin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Genetic ◽  
Genetic Mechanisms

Molecular genetic mechanisms of drug resistance in Plasmodium falciparum

2020 ◽  
Vol 4_2020 ◽  
pp. 80-87
Author(s):  
Solovyev A.I. Solovyev ◽  
Uskov A.N. Uskov ◽  
Kovalenko A.N. Kovalenko ◽  
Kapatsyna V.A. Kapatsyna ◽  
Rakin A.I. Rakin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Genetic ◽  
Genetic Mechanisms

Molecular genetic mechanisms of drug resistance in Plasmodium falciparum

2020 ◽  
Vol 4_2020 ◽  
pp. 80-87
Author(s):  
Solovyev A.I. Solovyev ◽  
Uskov A.N. Uskov ◽  
Kovalenko A.N. Kovalenko ◽  
Kapatsyna V.A. Kapatsyna ◽  
Rakin A.I. Rakin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Molecular Genetic ◽  
Genetic Mechanisms

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals Hierarchical modeling of mechano-chemical dynamics of epithelial sheets across cells and tissue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoshifumi Asakura ◽  
Yohei Kondo ◽  
Kazuhiro Aoki ◽  
Honda Naoki
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Continuum Model ◽  
Tissue Level ◽  
Chemical Signals ◽  
Cellular Level ◽  
Mathematical Framework ◽  
Collective Cell Migration ◽  
The Continuum ◽  
Cell Cell

AbstractCollective cell migration is a fundamental process in embryonic development and tissue homeostasis. This is a macroscopic population-level phenomenon that emerges across hierarchy from microscopic cell-cell interactions; however, the underlying mechanism remains unclear. Here, we addressed this issue by focusing on epithelial collective cell migration, driven by the mechanical force regulated by chemical signals of traveling ERK activation waves, observed in wound healing. We propose a hierarchical mathematical framework for understanding how cells are orchestrated through mechanochemical cell-cell interaction. In this framework, we mathematically transformed a particle-based model at the cellular level into a continuum model at the tissue level. The continuum model described relationships between cell migration and mechanochemical variables, namely, ERK activity gradients, cell density, and velocity field, which could be compared with live-cell imaging data. Through numerical simulations, the continuum model recapitulated the ERK wave-induced collective cell migration in wound healing. We also numerically confirmed a consistency between these two models. Thus, our hierarchical approach offers a new theoretical platform to reveal a causality between macroscopic tissue-level and microscopic cellular-level phenomena. Furthermore, our model is also capable of deriving a theoretical insight on both of mechanical and chemical signals, in the causality of tissue and cellular dynamics.

Co-ordinate regulation of genes involved in storage lipid mobilization in Arabidopsis thaliana

2001 ◽  
Vol 29 (2) ◽  
pp. 283-286 ◽  
Author(s):  
E. L. Rylott ◽  
M. A. Hooks ◽  
I. A. Graham
Keyword(s):  
Arabidopsis Thaliana ◽  
Enzyme Activities ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Isocitrate Lyase ◽  
Glyoxylate Cycle ◽  
Molecular Genetic ◽  
Regulation Of Gene Expression ◽  
Growth Period ◽  
Malate Synthase ◽  
The Glyoxylate Cycle

Molecular genetic approaches in the model plant Arabidopsis thaliana (ColO) are shedding new light on the role and control of the pathways associated with the mobilization of lipid reserves during oilseed germination and post-germinative growth. Numerous independent studies have reported on the expression of individual genes encoding enzymes from the three major pathways: β-oxidation, the glyoxylate cycle and gluconeogenesis. However, a single comprehensive study of representative genes and enzymes from the different pathways in a single plant species has not been done. Here we present results from Arabidopsis that demonstrate the co-ordinate regulation of gene expression and enzyme activities for the acyl-CoA oxidase- and 3-ketoacyl-CoA thiolasemediated steps of β-oxidation, the isocitrate lyase and malate synthase steps of the glyoxylate cycle and the phosphoenolpyruvate carboxykinase step of gluconeogenesis. The mRNA abundance and enzyme activities increase to a peak at stage 2, 48 h after the onset of seed germination, and decline thereafter either to undetectable levels (for malate synthase and isocitrate lyase) or low basal levels (for the genes of β-oxidation and gluconeogenesis). The co-ordinate induction of all these genes at the onset of germination raises the possibility that a global regulatory mechanism operates to induce the expression of genes associated with the mobilization of storage reserves during the heterotrophic growth period.

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