CLINICAL EFFECTS OF MESENCHYMAL STROMAL CELLS IN LYMPHOMA PATIENTS WITH AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

The clinical and laboratory effects of bone-marrow derived mesenchymal stromal cells (MSC) in patients with malignant lymphomas following autologous hematopoietic stem cell transplantation (auto-HSCT) have been investigated. Co-transplantation of MSC in average dose of 0,178 106/kg was conducted in 74 patients with auto-HSCT. The control group included 83 patients eligible for standard HSCT. We revealed the decreasing of the period of neutropenia and thrombocytopenia when hematopoietic stem cells were co-transplanted with low doses ex vivo expanded autologous MSC. Patients with MSC co-transplantation were differed by more effective early lymphocyte recovery. At the same time MSC co-transplantation did not increase the incidence of infectious complications and cases of renal and. hepatic toxicity. Patients with MSC co-transplantation did not differ from opposite group by 5-year overall survival, but were characterized by significantly better progression-free survival

The Genome of the Toluene-Degrading Pseudomonas veronii Strain 1YdBTEX2 and Its Differential Gene Expression in Contaminated Sand.

The natural restoration of soils polluted by aromatic hydrocarbons such as benzene, toluene, ethylbenzene and m- and p-xylene (BTEX) may be accelerated by inoculation of specific biodegraders (bioaugmentation). Bioaugmentation mainly involves introducing bacteria that deploy their metabolic properties and adaptation potential to survive and propagate in the contaminated environment by degrading the pollutant. In order to better understand the adaptive response of cells during a transition to contaminated material, we analyzed here the genome and short-term (1 h) changes in genome-wide gene expression of the BTEX-degrading bacterium Pseudomonas veronii 1YdBTEX2 in non-sterile soil and liquid medium, both in presence or absence of toluene. We obtained a gapless genome sequence of P. veronii 1YdBTEX2 covering three individual replicons with a total size of 8 Mb, two of which are largely unrelated to current known bacterial replicons. One-hour exposure to toluene, both in soil and liquid, triggered massive transcription (up to 208-fold induction) of multiple gene clusters, such as toluene degradation pathway(s), chemotaxis and toluene efflux pumps. This clearly underlines their key role in the adaptive response to toluene. In comparison to liquid medium, cells in soil drastically changed expression of genes involved in membrane functioning (e.g., lipid composition, lipid metabolism, cell fatty acid synthesis), osmotic stress response (e.g., polyamine or trehalose synthesis, uptake of potassium) and putrescine metabolism, highlighting the immediate response mechanisms of P. veronii 1YdBTEX2 for successful establishment in polluted soil

Колебания ледников Северного и Южного ледниковых полей Патагонии по данным мониторинга с Международной космической станции

Quantitative indicators of changes in 37 glaciers of the Patagonian Northern and Southern glacial fields were determined by means of decoding and analysis of photographs obtained by astronauts from the Russian segment of the International Space Station. On the basis of this information it was concluded that in 2002–2016 the glaciers of both fields of Patagonia continued to retreat. The frontal parts of the nine glaciers retained their positions, while others reduced at an average rate of several dozen up to 430 m/year. Repeated monitoring of 16 glaciers from this selection and analysis of the data obtained in 2016–2019 confirm this conclusion. The only exception was the O’Higgins Glacier, which did not change position of its frontal part for 12 years and then retreated in 2018–2019 to 1,250 m. In some cases, a gradual decrease in area of the frontal part of the glacier was accompanied by a sharp collapse of the lower zone with the formation of extensive fields of icebergs. The dynamics of the Bruggen Glacier (Pius XI) are not typical for the region under consideration: for many years this glacier has been advancing. This development cannot be explained without detailed field investigation in the area of snow and ice accumulation of the glacier. Perhaps that was due to a snow-drift transport in an extensive area of accumulation that supported the preservation of the size of the glacier tongue, and even its advance. According to our observations, the average rate of retreat of the glaciers of the Western and Eastern slopes of the Southern Ice Field significantly decreased since 2010, i.e. their degradation slowed down. At the same time, glaciers of the Northern Ice Field continued to decrease intensively.В результате анализа фотоснимков с Международной космической станции определены изменения 37 ледников Северного и Южного ледниковых полей Патагонии. В 2002–2016 гг. ледники обоих полей продолжали отступать, но их отступание с 2010 г. замедлилось, хотя некоторые ледники Северного ледникового поля продолжают интенсивно сокращаться. Лишь ледник Брюгген (Пия XI) на Южном ледниковом поле в течение многих лет наступает

УГНЕТЕНИЕ ПРОТИВООПУХОЛЕВОЙ ЦИТОТОКСИЧЕСКОЙ АКТИВНОСТИ ДЕНДРИТНЫХ КЛЕТОК У БОЛЬНЫХ ЗЛОКАЧЕСТВЕННЫМИ ЛИМФОМАМИ, ОБУСЛОВЛЕННОЕ ИЗМЕНЕННОЙ ЭКСПРЕССИЕЙ ФАКТОРА НЕКРОЗА ОПУХОЛИ АЛЬФА

Recent research revealed dendritic cells (DCs) to have direct antitumor cytotoxic activity and to inhibit the growth and proliferation of tumor cells in vitro. The aim of the present study was to investigate the association between the cytotoxic activity of dendritic cells generated in the presence of interferon alpha (IFN-DCs) and TNFα expression by IFN-DCs in patients with malignant lymphomas. It was shown that IFN-DCs of malignant lymphoma patients possessed low cytotoxic activity against tumor cell line HEp-2 associated with low expression of transmembrane TNFα (tmTNFα) and high level of soluble TNFα (sTNFα) secretion. Reduced DC cytotoxic activity and low tmTNFα expression on DC surface were observed mainly in Hodgkin’s lymphoma patients. In contrast, IFN-DCs of patients with non-Hodgkin lymphoma were endowed with the ability to lysis of HEp-2 cells and tmTNFα molecule expression was similar to that in IFN-DCs from healthy donors. It was determined that the increase of expression of tmTNFα molecule on lymphoma patient IFN-DCs induced by the addition of TNFα-converting enzyme inhibitor into IFN-DC cultures was associated with the enhancement of IFN-DC cytotoxic activity against HEp-2 cells. Исследования последних лет демонстрируют, что дендритные клетки (ДК) обладают прямой противоопухолевой цитотоксической активностью и способны подавлять рост и пролиферацию опухолевых клеток. Целью настоящей работы явилось исследование взаимосвязи между цитотоксической активностью генерируемых в присутствии IFNα дендритных клеток (ИФН-ДК) и экспрессией дендритными клетками TNFα у больных злокачественными лимфомами. Показано, что ИФН-ДК больных злокачественными лимфомами обладают слабой цитотоксической активностью против опухолевых клеток НЕр-2, что ассоциируется с низкой экспрессией траснмембранной формы tmTNFα (tmTNFα) и высоким уровнем продукции растворимой формы TNFα (sTNFα). Установлено, что угнетение цитотоксической активности ДК и низкая экспрессия tmTNFα в культурах ИФН-ДК характерны в большей степени для лимфом Ходжкина. При этом ИФН-ДК больных неходжкинскими лимофомами обладают сохранной цитотоксичностью против клеток НЕр-2, а экспрессия tmTNFα на ДК сопоставима с аналогичным показателем в культурах ИФН-ДК здоровых доноров. Установлено, что увеличение экспрессии tmTNFα в культурах IFN-ДК исследуемых больных, индуцированное добавлением на этапе конечного созревания ДК ингибитора TNFα-конвертирующего фермента, ассоциируется с усилением цитотоксической активности ИФН-ДК против клеток НЕр-2

Biological function in the twilight zone of sequence conservation

Abstract Strong DNA conservation among divergent species is an indicator of enduring functionality. With weaker sequence conservation we enter a vast ‘twilight zone’ in which sequence subject to transient or lower constraint cannot be distinguished easily from neutrally evolving, non-functional sequence. Twilight zone functional sequence is illuminated instead by principles of selective constraint and positive selection using genomic data acquired from within a species’ population. Application of these principles reveals that despite being biochemically active, most twilight zone sequence is not functional

Pharmaceuticals removal by adsorption with montmorillonite nanoclay

The problem of purifying domestic and hospital wastewater from pharmaceutical compounds is becoming more and more urgent every year, because of the continuous accumulation of chemical pollutants in the environment and the limited availability of freshwater resources. Clay adsorbents have been repeatedly proposed as adsorbents for treatment purposes, but natural clays are hydrophilic and can be inefficient for catching hydrophobic pharmaceuticals. In this paper, a comparison of adsorption properties of pristine montmorillonite (MMT) and montmorillonite modified with stearyl trimethyl ammonium (hydrophobic MMT-STA) towards carbamazepine, ibuprofen, and paracetamol pharmaceuticals was performed. The efficiency of adsorption was investigated under varying solution pH, temperature, contact time, initial concentration of pharmaceuticals, and adsorbate/adsorbent mass ratio. MMT-STA was better than pristine MMT at removing all the pharmaceuticals studied. The adsorption capacity of hydrophobic montmorillonite to pharmaceuticals decreased in the following order: carbamazepine (97%) >ibuprofen (95%) > paracetamol (63–67%). Adsorption isotherms were best described by Freundlich model. Within the pharmaceutical concentration range of 10–50 µg/mL, the most optimal mass ratio of adsorbates to adsorbents was 1:300, pH 6, and a temperature of 25◦ C. Thus, MMT-STA could be used as an efficient adsorbent for deconta×ating water of carbamazepine, ibuprofen, and paracetamol

P81

Numerous studies have shown that high-dose chemotherapy and autologous hematopoietic stem cell transplantation (AHSCT) led to a profound and long-lasting state of immunodeficiency characterized by persisting low levels of T cells in hemoblastosis patients. Well-timed T-cell reconstitution is crucial for early restoration of anti-infectious and anti- tumor immune response. Lymphocyte recovery is mediated through the two main mechanisms – a homeostatic proliferation of T cells and generation of new naive T cells via thymopoiesis. It is known, that homeostatic proliferation is important for the restoration of T cell count in immune competent host during the 1st year following AHSCT. Thymus begins to fill up T cell repertoire approximately from the 6th month following AHSCT. We have investigated dynamics of CD4+FOXP3+ Treg recovery following AHSCT and possible relationship between Tregs and clinical outcomes since the suppressive activity of Tregs under lymphopenic conditions may influence on peripheral expansion of T cells. Thymic activity following AHSCT has been evaluated by measuring amounts of CD4+ CD45RA+CD31+ naïve T cells, i.e. “recent thymic emigrants” (RTEs).109 patients with non-Hodgkin’s lymphomas, Hodgkin’s lymphoma and multiple myeloma underwent AHSCT in 2009–2014. The content of circulating CD4+FOXP3+ Tregs and CD4+CD45RA+CD31+ T cells was evaluated using flow cytometry before AHSCT, at the day of engraftment, and following 6 and 12 months. Pre-transplant count of CD4+FOXP3+ Tregs was significantly higher compared to healthy controls (5.4 ± 2.9 vs 3.8 ± 1.9%; pU = 0.011; here and below data presented as Mean ± SD). Percentage of Tregs restored rapidly and reached initially high level at the time of engraftment, and then subsequently decreased within a year until it lowered to healthy donors‘ values. CD4+FOXP3+ Tregs at the time of engraftment were increased in patients with relapse or progression of disease within 6 and 12 months following AHSCT compared to non-relapsed patients (11.0 ± 6.1 vs 6.2 ± 3.0%; pU = 0.016, and 10.1 ± 5.2 vs 6.1 ± 3.8%; pU = 0.008). Pre-transplant count of CD4+CD45RA+CD31+ T cells was significantly lower compared to healthy controls (17.1 ± 11.4 vs 30.3 ± 11.2%, pU = 0.0005) and did not reach donors‘ values following 12 month (23.1 ± 13.5%, pU = 0.032). Relapsed patients had the same quantity of RTEs as the patients with remission within the 1st year following AHSCT. There was no any significant association between RTEs and Tregs counts. Surprisingly, we have found high levels of circulating CD4+CD45RA- T cells co-expressing CD31 molecule in patients before AHSCT, since this molecule is infrequent on memory subsets in healthy controls (20.7 ± 12.0 vs 8.2 ± 2.1%,pU < 0.00001). Relative amount of CD4+CD45RA-CD31+ T cells highly correlated with CD4+CD45RO+CD31+ population (rS=0.72; p < 0.00001). The count of CD4+CD45RA-CD31+ T cells recovered intensively and reached the pre-transplant level within the 1st month following AHSCT, and remained at the same level throughout the follow-up. There were no any differences in relative count of CD4+CD45RA-CD31+ T cells between patients with early relapse and remission during the 1st post-transplant year. Our data of Tregs reconstitution may confirm the earlier assumption that the presence of Tregs during the period of immune recovery preserves optimal T cell receptors diversity. However, the excess of these cells leads to the inhibition of proliferative activity and immune response and is associated with early relapse. Conversely, relatively slow recovery of RTEs determines theirlack of influence on survival within the 1st post-transplant year. The biological role and the way of appearance of CD31 molecule on T cell memory subset (CD4+CD45RA- and/or CD4+CD45RO+) still remain unclear. Further studies are required to enlighten the role of CD31+ memory T cells on lymphoproliferative disorders pathogenesis