Immature hematopoietic progenitors are a constant source for renewal of hemocyte populations and the basic component of the tissue and cell repair apparatus. A unique property of these cells of ...internalizing extracellular double-stranded DNA has been previously shown. The leukostimulatory effect demonstrated in our pioneering studies was considered to be due to the feature of this cell. In the present research, we have analyzed the effects of DNA genome reconstructor preparation (DNAgr), DNAmix, and human recombinant angiogenin on both hematopoietic stem cells and multipotent progenitors. Treatment with bone marrow cells of experimental mice with these preparations stimulates colony formation by hematopoietic stem cells and proliferation of multipotent descendants. The main lineage responsible for this is the granulocyte-macrophage hematopoietic lineage. Using fluorescent microscopy as well as FACS assay, co-localization of primitive c-Kit- and Sca-1-positive progenitors and the TAMRA-labeled double-stranded DNA has been shown. Human recombinant angiogenin was used as a reference agent. Cells with specific markers were quantified in intact bone marrow and colonies grown in the presence of inducers. Quantitative analysis revealed that a total of 14,000 fragment copies of 500 bp, which is 0.2% of the haploid genome, can be delivered into early progenitors. Extracellular double-stranded DNA fragments stimulated the colony formation in early hematopoietic progenitors from the bone marrow, which assumed their effect on cells in G0. The observed number of Sca1+/c-Kit+ cells in colonies testifies to the possibility of both symmetrical and asymmetrical division of the initial hematopoietic stem cell and its progeny.
We studied suppressor potential of myeloid-derived suppressor cells (MDSC) in multiple myeloma patients, including before and after mobilization of hematopoietic stem cells (HSC), by evaluating the ...expression of arginase-1 (Arg1), indolamine-2,3-dioxygenase (IDO), and PD-L1 in MDSC subsets. The study included 20 multiple myeloma patients in remission, 5 patients with progression, as well as 10 sex-and age-matched healthy donors. The expression of Arg1, IDO, and PD-L1 in circulating granulocytic MDSC (G-MDSC, Lin
–
HLA-DR
–
CD33
+
CD66b
+
), monocytic MDSC (M-MDSC, CD14
+
HLA-DR
low/–
), and early-stage MDSC (E-MDSC, Lin
–
HLA-DR
–
CD33
+
CD66b
–
) was evaluated by flow cytometry. Multiple myeloma patients in remission were characterized by reduced expression of Arg1 in M-MDSC in comparison with donors. The expression of Arg1 in M-MDSC depended on the number of induction therapy lines performed and was significantly lower in patients who received ⩾2 lines and responded with remission. Patients with multiple myeloma progression (resistant to therapy) showed significantly increased expression of Arg1 and PD-L1 in M-MDSC, as well as increased expression of Arg1 in E-MDSC. After G-CSF-induced mobilization of HSC, the content of circulating Arg1-expressing M-MDSC increased significantly. Considering the presence of MDSC in apheresis products, MDSC suppressive activity is discussed as a factor affecting the outcomes of autologous HSC transplantation in multiple myeloma patients.
The Triple-Modular Redundancy (TMR) technique is one of the conventional approaches to provide reliable functioning of logic circuits. When using outsourcing, it is possible to inject a Trojan ...Circuit (TC) in the same line of each identical TMR module, and the TMR technique becomes vulnerable. It is necessary to withstand to vulnerability. One way of solving this problem is the application of two approximate logic circuits and one correct circuit that implements the proper functioning in the frame of the TMR technique. However, this approach, as a rule, generates an unprotected area in which a fault of one of the three circuits may be undetected. It is desirable to minimize this area. In this paper, approximate circuits are built based on deriving approximate systems of Boolean functions. These systems are then applied for an approximate circuit synthesis. The approach gives additional possibilities for cutting the unprotected area compared to the methods suggested before. Algorithms of deriving the approximate systems of the Boolean functions based on analysis of an irredundant system of sums of products (SoPs) describing the behavior of the correct circuit have been developed. The algorithm appreciating the size of the unprotected area is also given.
The functional phenotype of macrophages (Mφ) is determined by both differentiation factors and polarization stimuli. In mouse Mφ could be easily divided into the distinct Mφ subtypes. However, the ...identification of human M1 and M2 cells is much more difficult due to the lack of M1- or M2-specific markers. We assumed that the Mφ capacity to induce T cell proliferation in mixed leukocyte culture, or allostimulatory activity, may be a marker of Mφ functional phenotype. We compared the allostimulatory activity of Mφ differentiated with GM-CSF or M-CSF and polarized into M1, M2a, M2c subtypes using appropriate stimuli. GM-CSF-differentiated M1 Mφ showed pronounced allostimulatory activity whereas the polarization into M2a and M2c of GM-CSF-differentiated Mφ was associated with decreased allostimulatory activity. M-CSF-differentiated M1 Mφ demonstrated the moderate increasing of allostimulatory activity but its level has never reached that of GM-CSF-activated M1. The level of allostimulatory activity of M2a and M2c M-CSF-induced Mφ was comparable to that of GM-CSF-induced M2a and M2c Mφ. Thus, low allostimulatory activity is a common property of human M2a and M2c macrophages regardless of the differentiating factor and a polarizing stimulus and can be used to distinguish between M1 and M2 phenotypes.
The purpose of this study was to assess the capability of recombinant angiogenin isolated from
yeasts to stimulate regenerative processes in the dermis of experimental animals.
Wistar rats were ...administered with recombinant angiogenin intracutaneously. Morphological examination of the skin and the assessment of the proliferative activity of the epidermal cells were carried out. Additionally, cytokine production by human whole blood cells exposed to angiogenin was analyzed ex vivo.
Administration of angiogenin stimulates collagen fiber formation and angiogenesis. This stimulation is tightly associated with an increase in the number of fibroblasts, an increased numerical density of dermal blood vessels and an increased density of collagen fibers; also, it activates the proliferation of basal cells. Angiogenin induces the production of MCP, IL-8, IL-6, IL-1β, TNF-α, IL-10, TGF-β, and VEGF by blood cells.
The results obtained indicate a broad spectrum of actions of recombinant angiogenin during regenerative processes in the basal layer of the dermis.
Abstract
The paper focuses on the possibilities of using the technology of geographic information systems (GIS-technologies) and data on the Earth remote sensing to determine the morphometric ...parameters of the river basin on the example of the upper part of the Charysh River (Russia). The authors conclude that a river basin is a holistic natural complex in which all physical parameters are interdependent and have specific features for each basin. Geographic information methods are used to study hydrological objects and in the modeling of drainage basins as natural compound complexes. In combination with GIS technologies, remote sensing methods are convenient for deciphering and assessing the hydrological situation of territories. For the upper part of the Charysh River basin, a complex of morphometric calculations was performed. Based on DEM and satellite images, thematic layers for GIS were built, and the thematic layers were designed as maps.
A device for noninvasive measurement of the repetition frequency of single-motor-unit action potential is described. The device was built using virtual instruments in LabVIEW software. The ...mathematical foundations of the measurement method and results are presented.
Myeloid dendritic cells (DCs) play an important role in the immune response; therefore, the search for compounds that can effectively activate DCs is a needful goal. This study was aimed to ...investigate the effect of synthetic CpG oligodeoxynucleotides (CpG-ODN) on the maturation and allostimulatory activity of myeloid DCs in comparison with other PAMP and DAMP molecules. For the research, we synthesized known CpG-ODN class C (SD-101 and D-SL03) containing thiophosphate internucleotide groups, and their original phosphate-modified analogues (SD-101M and D- SL03M) with mesylphosphoramide internucleotide groups (M = μ-modification). The effects of CpG-ODN and other activators were evaluated on DCs generated from blood monocytes in the presence of GM-CSF and IFN-α (IFN-DC) or IL-4 (IL4-DC). Evaluation of the intracellular TLR-9 expression showed that both types of DCs (IFN-DC and IL4-DC) contained on average 52 and 80 % of TLR-9-positive cells, respectively. The CpG-ODNs studied enhanced the allostimulatory activity of IFN-DCs, and the effect of μ-modified CpG-ODNs was higher than that of CpG-ODNs with thiophosphate groups. The stimulating effect of CpG-ODN at a dose of 1.0 μg/ml was comparable (for D-SL03, D-SL03M, SD-101) with or exceeded (for SD-101M) the effect of LPS at a dose of 10 μg/ml. At the same time, IFN-DCs were characterized by greater sensitivity to the action of CpG-ODNs than IL4-DCs. The enhancement of DC allostimulatory activity in the presence of CpG-ODNs was associated with the induction of final DC maturation, which was confirmed by a significant decrease in the number of CD14+DC, an increase in mature CD83+DC and a trend towards an increase in CD86+DC. Interestingly, the characteristic ability of LPS to enhance the expression of the co-stimulatory molecule OX40L on DCs was revealed only for the μ-analogue SD-101M. In addition, CpG-ODNs (SD-101 and SD-101M) had a stimulatory effect on IFN-γ production comparable to the action of LPS. The data obtained indicate a stimulating effect of CpG-ODN on the maturation and allostimulatory activity of human myeloid DCs, which is more pronounced for μ-modified analogs.
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