C/EBP-induced transdifferentiation reveals granulocyte-macrophage precursor-like plasticity of B cells

The lymphoid-myeloid transdifferentiation potentials of members of the C/EBP family (C/EBP{alpha}, {beta}, {delta}, and {epsilon}) were compared in v-Abl-immortalized primary B cells. Conversion of B cells to macrophages was readily induced by the ectopic expression of any C/EBP, and enhanced by endogenous C/EBP{alpha} and {beta} activation. High transgene expression of C/EBP{beta} or C/EBP{epsilon}, but not of C/EBP{alpha} or C/EBP{delta}, also induced the formation of granulocytes. Granulocytes and macrophages emerged in a mutually exclusive manner. C/EBP{beta}-expressing B cells produced granulocyte-macrophage progenitor (GMP)-like progenitors when subjected to selective pressure to eliminate lymphoid cells. The GMP-like progenitors remained self-renewing and cytokine-independent, and continuously produced macrophages and granulocytes. In addition to their suitability to study myelomonocytic lineage bifurcation, lineage-switched GMP-like progenitors could reflect the features of the lympho-myeloid lineage switch observed in leukemic progression

Material Decomposition in Spectral CT using deep learning: A Sim2Real transfer approach

The state-of-the art for solving the nonlinear material decomposition problem in spectral computed tomography is based on variational methods, but these are computationally slow and critically depend on the particular choice of the regularization functional. Convolutional neural networks have been proposed for addressing these issues. However, learning algorithms require large amounts of experimental data sets. We propose a deep learning strategy for solving the material decomposition problem based on a U-Net architecture and a Sim2Real transfer learning approach where the knowledge that we learn from synthetic data is transferred to a real-world scenario. In order for this approach to work, synthetic data must be realistic and representative of the experimental data. For this purpose, numerical phantoms are generated from human CT volumes of the KiTS19 Challenge dataset, segmented into specific materials (soft tissue and bone). These volumes are projected into sinogram space in order to simulate photon counting data, taking into account the energy response of the scanner. We compared projection- and image-based decomposition approaches where the network is trained to decompose the materials either in the projection or in the image domain. The proposed Sim2Real transfer strategies are compared to a regularized Gauss-Newton (RGN) method on synthetic data, experimental phantom data and human thorax data

Assessment of subclinical magnesium deficiency in pregnant women

Introduction. The question of the ratio of calcium and magnesium in the body in the scientific community is not discussed as often as the role of each of these elements. Experts pay even less attention to the ratio of minerals in the body of pregnant women.Aim. To analyze the content of magnesium and calcium in the blood of pregnant women at different gestation periods and evaluate the ratio of magnesium / calcium in order to establish the calculated coefficient.Materials and methods. 272 pregnant women (age 31.85 ± 5.0 years) at different gestation periods were included in the study. The subjects did not complain, typical for the clinic of magnesium and calcium deficiency. All surveyed gave written consent to the study. A biochemical blood test (determination of the concentration of total calcium, magnesium) was carried out in the laboratory of LLC DNKOM in Moscow. Blood sampling from the cubital vein was carried out according to the standard method in the morning on an empty stomach after 10–12 hours of fasting.Results and discussion. Concentration of  total calcium in  the serum was (M  ±  SD) 2.28  ±  0.11  mmol/l, total magnesium  – 0.78 ± 0.07 mmol/l, magnesium/calcium ratio – 0.34 ± 0.03. Mean concentrations of calcium and magnesium were significantly lower in women in the II and III trimesters compared with the I trimester (p < 0.001). A decrease in magnesium concentration below the optimal for pregnant women of 0.8 mmol / l was observed in 37.5% of women in the first trimester, in 77.3% and 84.1% in the II and III trimesters, respectively. Serum magnesium concentration less than 0.7 mmol / l, reflecting a profound magnesium deficiency, was detected in the first trimester in 3.6% of women, in the second trimester – in 11.3% of women, in the third trimester – in 15.9% of pregnancies. Hypocalcemia (total calcium concentration less than 2.15 mmol/l) was recorded in 0.9%, 11.3% and 22.3% of pregnant women in the I, II and III trimesters. When calculating the magnesium/calcium ratio, subclinical magnesium deficiency was detected in 96.7% of pregnant women throughout pregnancy. Conclusion. The data obtained indicate the need for pregravid examination and early correction of metabolic disorders.>< 0.001). A decrease in magnesium concentration below the optimal for pregnant women of 0.8 mmol / l was observed in 37.5% of women in the first trimester, in 77.3% and 84.1% in the II and III trimesters, respectively. Serum magnesium concentration less than 0.7 mmol / l, reflecting a profound magnesium deficiency, was detected in the first trimester in 3.6% of women, in the second trimester – in 11.3% of women, in the third trimester – in 15.9% of pregnancies. Hypocalcemia (total calcium concentration less than 2.15 mmol/l) was recorded in 0.9%, 11.3% and 22.3% of pregnant women in the I, II and III trimesters. When calculating the magnesium/calcium ratio, subclinical magnesium deficiency was detected in 96.7% of pregnant women throughout pregnancy.Conclusion. The data obtained indicate the need for pregravid examination and early correction of metabolic disorder

DYNAMICS OF COREGONUS MIGRATORIUS (COREGONIDAE) SELENGA POPULATION CONTAMINATION WITH DIPHYLLOBOTHRIUM DENDRITICUM AND DIPHYLLOBOTHRIOSIS MORBIDITY IN BURYATIA REPUBLIC

The paper is devoted to the long-term dynamics of Baikalian omul contamination with plerocercoids of Diphyllobothrium. dendriticum during the spawning migration into the Selenga River. Contamination peacks were in 2005 and 2011. Dynamic of diphyllobothriosis morbidity in Buryatia Republic in 2000-2011 have shown increasing trend of helm.inth.osis with 5-year cycle

Differential Expression of CHL1 Gene during Development of Major Human Cancers

CHL1 gene (also known as CALL) on 3p26.3 encodes a one-pass trans-membrane cell adhesion molecule (CAM). Previously CAMs of this type, including L1, were shown to be involved in cancer growth and metastasis.We used Clontech Cancer Profiling Arrays (19 different types of cancers, 395 samples) to analyze expression of the CHL1 gene. The results were further validated by RT-qPCR for breast, renal and lung cancer. Cancer Profiling Arrays revealed differential expression of the gene: down-regulation/silencing in a majority of primary tumors and up-regulation associated with invasive/metastatic growth. Frequent down-regulation (>40% of cases) was detected in 11 types of cancer (breast, kidney, rectum, colon, thyroid, stomach, skin, small intestine, bladder, vulva and pancreatic cancer) and frequent up-regulation (>40% of cases)--in 5 types (lung, ovary, uterus, liver and trachea) of cancer. Using real-time quantitative PCR (RT-qPCR) we found that CHL1 expression was decreased in 61% of breast, 60% of lung, 87% of clear cell and 89% papillary renal cancer specimens (P<0.03 for all the cases). There was a higher frequency of CHL1 mRNA decrease in lung squamous cell carcinoma compared to adenocarcinoma (81% vs. 38%, P = 0.02) without association with tumor progression.Our results suggested that CHL1 is involved in the development of different human cancers. Initially, during the primary tumor growth CHL1 could act as a putative tumor suppressor and is silenced to facilitate in situ tumor growth for 11 cancer types. We also suggested that re-expression of the gene on the edge of tumor mass might promote local invasive growth and enable further metastatic spread in ovary, colon and breast cancer. Our data also supported the role of CHL1 as a potentially novel specific biomarker in the early pathogenesis of two major histological types of renal cancer

Assessment of allergen tolerance breakdown levels in local and classical allergic rhinitis

Local allergic rhinitis, a new endotype of allergic rhinitis discerned by researchers of the Spanish Allergy School, is now in the focus of interest of international allergological community. A special feature of local allergic rhinitis, which, being similar to conventional signs of allergic rhinitis, is, however, characterized by absence of systemic atopy manifestations, e.g., an increased total serum IgE content and positive allergic skin tests. In order to assess the level of tolerance breakdown to allergens in local and classical allergic rhinitis, we have studyed concentrations of IL-4, IL-22, and IFNγ in three biological fluids, blood, nasal secretions, and skin exudate. The whole study cohort consisted of 82 patients aged 18 to 60 years with established allergic rhinitis. The diagnosis was based on counseling by allergologist/immunologist, including clinical case history and possible inheritance of atopy as well as videorhinoscopy performed by an ENT specialist. The procedure of videorhinoscopy allowed to specify allergic origin of rhinitis and exclude the patients with non-allergic forms of the disease, but it did not enable us to differentiate between the endotypes of classic and local allergic rhinitis. Subsequently, all patients have been divided into two subgroups based on the criteria of systemic atopy: (1) with a high content of serum total IgE and positive skin allergy tests (n = 41) and (2) with a significantly lower concentration of IgE and negative allergy tests (n = 41). It was concluded that the patients with classic allergic rhinitis prevailed in the 1st subgroup, whereas local rhinitis predominated in the 2nd group. The study of IL-4, IL-22 and IFNγ concentrations in the three biological fluids allowed us to presume that the 1st subgroup was characterized by increased content of IL-4 and IL-22 in blood and skin exudate in comparison with controls, and the 2nd subgroup showed a decrease in IFNγ to control values. The cytokine concentrations in nasal secretions were not representative for the subgroups studied. The result has been interpreted as the absence of tolerance breakdown to causal allergens in the patients with local allergic rhinitis at the systemic level. The obtained data could be used in development of a diagnostic biomarker system for this specific endotype of allergic rhinitis, thus avoiding potential diagnostic errors which occurred in the past, when this endotype was classified as non-allergic form of the disease, thus administering non-adequate treatment, e.g., allergen-specific immunotherapy, which could be prescribed in these cases

Возможная роль трансформирующего фактора роста β как маркерного цитокина Т-хелперов типа 3 в патогенезе атопического дерматита

The role of transforming growth factor β (TGF-β) in atopic dermatitis pathogenesis is discussed basing on the analysis of existing data of cellular and molecular mechanisms of allergic inflammation. Up-to date data of the main T-helper (T-h) lymphocyte subpopulations including Tx1, Tx2, Tx3 has been presented. Functions of regulatory T-cell populations and produced cytokines have been described. The main attention has been accented on the TGF-β structure and biological activity as a main Tx3 cytokine. The current information of TGF-β influence on different cell populations and its biological activity realization mechanism is thoroughly discussed. Information relating to the mechanism of cytokine regulation during atopic dermatitis has been summarized. A deep analysis of possible participation of TGF-β in disbalance formation on Tx1 and Tx2 levels, in disturbances of histological derma structure and allergic inflammation timing has been made.На основании анализа существующих сведений о клеточных и молекулярных механизмах аллергического воспаления рассматривается роль трансформирующего фактора роста β (ТФР-β) в патогенезе атопического дерматита. Представлены современные данные об основных субпопуляциях Т-хелперных (Тх) лимфоцитов, включая Тх1, Тх2, Тх3. Охарактеризованы функции регуляторных субпопуляций Т-клеток и продуцируемых ими цитокинов. Основное внимание акцентируется на структуре и биологической активности ТФР-β как главного цитокина Тх3. Всесторонне обсуждаются имеющиеся в настоящее время сведения о влиянии ТФР-β на различные клеточные популяции и механизмы реализации его биологической активности. Обобщена информация, касающаяся механизмов цитокиновой регуляции при атопическом дерматите. Проведен глубокий анализ возможного участия ТФР-β в формировании дисбаланса на уровне Тх1 и Тх2, в нарушениях гистологической структуры дермы и хронизации аллергического воспаления

Т-лимфоциты - ключевые иммунорегуляторные клетки

Phenotypical and functional heterogeneity of immune regulating subpopulations of T-lymphocytes having suppressor activity is discussed in the article. Natural regulators and inducible regulating cells are characterized in more details.Обсуждается фенотипическая и функциональная гетерогенность иммунорегуляторных субпопуляций Т-лимфоцитов с супрессорной активностью. Наиболее подробно охарактеризованы натуральные регуляторные и индуцибельные регуляторные клетки

Tumor suppressor function of the SEMA3B gene in human lung and renal cancers

The SEMA3B gene is located in the 3p21.3 LUCA region, which is frequently affected in different types of cancer. The objective of our study was to expand our knowledge of the SEMA3B gene as a tumor suppressor and the mechanisms of its inactivation. In this study, several experimental approaches were used: tumor growth analyses and apoptosis assays in vitro and in SCID mice, expression and methylation assays and other. With the use of the small cell lung cancer cell line U2020 we confirmed the function of SEMA3B as a tumor suppressor, and showed that the suppression can be realized through the induction of apoptosis and, possibly, associated with the inhibition of angiogenesis. In addition, for the first time, high methylation frequencies have been observed in both intronic (32-39%) and promoter (44-52%) CpG-islands in 38 non-small cell lung carcinomas, including 16 squamous cell carcinomas (SCC) and 22 adenocarcinomas (ADC), and in 83 clear cell renal cell carcinomas (ccRCC). Correlations between the methylation frequencies of the promoter and the intronic CpG-islands of SEMA3B with tumor stage and grade have been revealed for SCC, ADC and ccRCC. The association between the decrease of the SEMA3B mRNA level and hypermethylation of the promoter and the intronic CpG-islands has been estimated in renal primary tumors (P < 0.01). Using qPCR, we observed on the average 10- and 14-fold decrease of the SEMA3B mRNA level in SCC and ADC, respectively, and a 4-fold decrease in ccRCC. The frequency of this effect was high in both lung (92-95%) and renal (84%) tumor samples. Moreover, we showed a clear difference (P < 0.05) of the SEMA3B relative mRNA levels in ADC with and without lymph node metastases. We conclude that aberrant expression and methylation of SEMA3B could be suggested as markers of lung and renal cancer progression