Hydrological changes in the White Sea during the historical period inferred from analysis of dinocysts

According to available historical evidence, colonization of the White Sea region began in the 9th–8th centuries B.C. [2]. This unique region with ancient residence sites experiences progressively increasing anthropogenic load against the background of natural climatic changes. The intense economic development of the region requires complex ecological and paleogeographic studies aimed at detailed reconstruction of past sedimentation settings. The analysis of dinocysts, which makes it possible to reconstruct various parameters of water masses washing the Arctic shelf, has become a promising method in paleohydrological studies, widely used in recent years [10, 11]. Dinoflagellates, which represent one of the main phytoplankton groups in the Arctic Seas, the White Sea included, form cysts with biopolymer envelopes, which are preserved in sediments. Thus, information on glacial–hydrological conditions is recorded in marine sediments. In the White Sea, this method was first used for the study of bottom sediments only in 2003 [3, 15]. In this communication, we present the first results obtained during the thorough study of dinocysts in bottom sediment cores from the White Sea, which cover the last 250 years. The study of this microfossil group made it possible to reconstruct in detail changes in glacial–hydrological settings in the sea and reveal their relations with known climatic–hydrological events that occurred in neighboring regions during the historical period

Dinoflagellate cysts in the surface sediments of the White Sea

Dinoflagellate cysts were studied in 42 samples from the surface sediments of the White Sea. The total concentration of dinocysts varies from single cysts to 25 000 cyst/g of dry sediments, which reflects the biological productivity in the White Sea waters and the regional particular features of the sedimentation processes. The highest concentrations are observed in silts; they are related to the regions of propagation of the highly productive Barents Sea waters in the White Sea. Generally, the spatial distribution of dinocysts species in the surface sediments corresponds to the distribution of the major types of water masses in the White Sea. The cysts of the relatively warm-water species (Operculodinium centrocarpum, Spiniferites sp.) of North Atlantic origin that dominate in the sediments indicate an intensive intrusion of the Barents Sea water masses to the White Sea along with hydrological dwelling conditions in the White Sea favorable for the development of these species during their vegetation period. The cold-water dinocyst assemblage (Islandinium minutum, Polykrikos sp.) is rather strictly confined to the inner parts of shallow-water bays, firstly, those adjacent to the Onega and Severnaya Dvina river mouths

RegPredict: an integrated system for regulon inference in prokaryotes by comparative genomics approach

RegPredict web server is designed to provide comparative genomics tools for reconstruction and analysis of microbial regulons using comparative genomics approach. The server allows the user to rapidly generate reference sets of regulons and regulatory motif profiles in a group of prokaryotic genomes. The new concept of a cluster of co-regulated orthologous operons allows the user to distribute the analysis of large regulons and to perform the comparative analysis of multiple clusters independently. Two major workflows currently implemented in RegPredict are: (i) regulon reconstruction for a known regulatory motif and (ii) ab initio inference of a novel regulon using several scenarios for the generation of starting gene sets. RegPredict provides a comprehensive collection of manually curated positional weight matrices of regulatory motifs. It is based on genomic sequences, ortholog and operon predictions from the MicrobesOnline. An interactive web interface of RegPredict integrates and presents diverse genomic and functional information about the candidate regulon members from several web resources. RegPredict is freely accessible at http://regpredict.lbl.gov

Hematopoietic stem cell transplantation with alpha/beta T-lymphocyte depletion and short course of eculizumab in adolescents and young adults with paroxysmal nocturnal hemoglobinuria

The main goal is to optimize hematopoietic stem cell transplantation (HSCT) approach among adolescents and young adults with paroxysmal nocturnal hemoglobinuria (PNH) by means of Graft-versus-host disease (GVHD) and post-transplant complications risk lowering. Materials and methods. We report our experience of HSCT from HLA-matched unrelated donors using TCR alfa/beta and CD19 depletion in 5 pts (1M/4F) with PNH, developed after successful immunosuppressive therapy (IST) of acquired aplastic anemia (AA). Median age of pts at the moment of transplantation was 17,8 years (range 14,5-22,7), median interval from IST to PNH was 4 years (5mo - 6,5 y). In all patients non-severe pancytopenia was present: granulocytes 0,8х109/l (0,8-1,8 х109/l) platelets 106 х109/l (27-143 х109/l) and Hb -78 g/l, median PNH clone size in granulocytes was 94 (range 75-99)%. One pts previously developed sinus thrombosis. Conditioning consisted of thoraco-abdominal irradiation 4-6 Gy, cyclophosphamide 100 mg/kg, fludarabine 150 mg/m2 and anti-thymocyte globulin (ATG) or alemtuzumab. Eculizumab was given from day (-7) till day (+14) (every 7 days, only 4 times). GVHD prophylaxis was tacrolimus ± methotrexate. Results. Infusedgraft characteristics were: CD34+ - 8,1х106/kg, CD3TCRab·150х103/kg, CD3gd+ - 7,3х106/kg, СD19+ - 221х103/kg, NK -6,4х108/kg. Engraftment was achieved in all 5 pts with a median of 15(12-18) и 13(10-18) days for granulocytes and platelets, respectively. Skin acute GVHD grade I developed in only 1 pt, and subsided with short course of glucocorticoids. CMV reactivation occurred in 1 pt; there were no episodes of Epstein-Barr Virus (EBV) o rAdenovirus (AdV) reactivation. Full donor myeloid chimerism was established in all pts by day +30. Immune reconstitution was delayed until 6 months after transplant but no severe infections occurred. All pts are alive 1,7-5,5 years (med 4 years) after HSCT with normal hematopoiesis and immune function, full donor chimerism and no late sequelae. Conclusions. Transplantation of TCRalfa/beta and CD19 depleted hematopoietic cells from matched unrelated donor after immunoablative conditioning and supported with short course of eculizumab is perfectly safe and efficient technology leading to cure in young patients with PNH

BTK, NuTM2A, and PRPF19 are Novel KMT2A Partner Genes in Childhood Acute Leukemia

Chromosomal rearrangements of the human KMT2A/MLL gene are associated with acute leukemias, especially in infants. KMT2A is rearranged with a big variety of partner genes and in multiple breakpoint locations. Detection of all types of KMT2A rearrangements is an essential part of acute leukemia initial diagnostics and follow-up, as it has a strong impact on the patients’ outcome. Due to their high heterogeneity, KMT2A rearrangements are most effectively uncovered by next-generation sequencing (NGS), which, however, requires a thorough prescreening by cytogenetics. Here, we aimed to characterize uncommon KMT2A rearrangements in childhood acute leukemia by conventional karyotyping, FISH, and targeted NGS on both DNA and RNA level with subse-quent validation. As a result of this comprehensive approach, three novel KMT2A rearrangements were discovered: ins(X;11)(q26;q13q25)/KMT2A-BTK, t(10;11)(q22;q23.3)/KMT2A-NUTM2A, and inv(11)(q12.2q23.3)/KMT2A-PRPF19. These novel KMT2A-chimeric genes expand our knowledge of the mechanisms of KMT2A-associated leukemogenesis and allow tracing the dynamics of minimal residual disease in the given patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: KMT2A rearrangement assessment was supported by the Russian Science Foundation (grant no. 19-75-10056). Quantitative RT-PCR for MRD monitoring was supported by Russian Presidential (grant no. MK-1645.2020.7)

Exploratory Study of the Long-Term Persistence of <i>Yersinia pestis</i> in the Cells of Soil-Inhabiting Ameba - <i>Acanthamoeba Sp.</i>

Objective of the study is to explore the feasibility of the long-term persistence of Yersinia pestis strains in association with ameba - Acanthamoeba sp. Materials and methods. Investigated has been interaction of ameba - Acanthamoeba sp., isolated from rodent burrows in the Pre-Caspian sandy, Volga-Ural steppe, and Pre-Caspian North-Western steppe natural foci, with 4 strains of Y. pestis of the main subspecies, 1 strain of caucasica and 1 strain of altai subspecies. Results and discussion. It is established that the strains of the main subspecies survive in the cells of ameba at 26 °C and 20 % humidity (modeling of the drought conditions in the natural plague foci) within 2-4 months of experiment, and 10-20 times longer that in pure culture. Two strains of the non-main ssp. have not demonstrated an increase in persistency in association with Acanthamoeba sp., which may occur due to degraded resistance to phagocytosis in the ameba of this specie. Using fluorescent and transmission electronic microscopy, it is determined that the cells of plague agent persist in ameba cells in individual vacuoles, enclosed in endoplasmic reticulum. The data obtained may testify to the possible involvement of ameba Acanthamoeba sp. . into sustainment of Y. pestis in soil biocoenoses of natural plague foci

Studies of Biofilm Formation in Non-Pigmented and Plasmid-Deprived Mutants of <I>Yersinia pestis</I> on Biotic Surfaces, <I>in vivo</I> and <I>in vitro</I> Conditions

In non-pigmented and plasmid-deprived mutants – isogenic variants of highly virulent Yersinia pestis 231 strain – studied is the mechanism of biofilm formation on biotic surfaces, both in vitro (on the laboratory model of nematode Caenorhabdiitis elegans) and in vivo (inside the alimentary tract of Nosopsyllus laeviceps flea). It is determined that spontaneous loss of ability to form biofilms and generate pigmented colonies in the mutants is probably caused not only by the deletion of the whole chromosome pigmentation fragment, but also by a point(single base) mutation in structural hms operon. It is demonstrated that the absence of pCad, pFra or pPst plasmids does not have an impact on the ability of plasmid-deprived mutants to form biofilm on the cuticle of nematode C. elegans