Scientific substantiation and development of innovative processes for the extraction of zirconium and rare earth elements in the deep and comprehensive treatment of eudialyte concentrate

Based on a package of modern analysis methods, the influence of various acids and energy effects on the morphology, elemental composition, structural and chemical transformations of the mineral surface, and the efficiency of eudialyte concentrate leaching was studied. The mechanism and the optimal conditions and specific features of the destruction of eudialyte and rock minerals and the extraction of zirconium and REE under the influence of various acids, powerful nanosecond pulses, dielectric barrier discharge, electrochemical processing, mechanochemical activation and ultrasound were revealed. The mechanism of formation and the optimal conditions for the dispersion of silica gel, depending on the methods and parameters of energy effects, was theoretically and experimentally substantiated. A combined three-stage circuit of nitric acid leaching of eudialyte concentrate with ultrasonic treatment of the suspension, providing 97.1 % extraction of zirconium and 94.5 % REE, were scientifically substantiated and tested. The conditions for the selective deposition of zirconium and REE were theoretically and experimentally substantiated

The contribution of PA-X to the virulence of pandemic 2009 H1N1 and highly pathogenic H5N1 avian influenza viruses

PA-X is a novel protein encoded by PA mRNA and is found to decrease the pathogenicity of pandemic 1918 H1N1 virus in mice. However, the importance of PA-X proteins in current epidemiologically important influenza A virus strains is not known. In this study, we report on the pathogenicity and pathological effects of PA-X deficient 2009 pandemic H1N1 (pH1N1) and highly pathogenic avian influenza H5N1 viruses. We found that loss of PA-X expression in pH1N1 and H5N1 viruses increased viral replication and apoptosis in A549 cells and increased virulence and host inflammatory response in mice. In addition, PA-X deficient pH1N1 and H5N1 viruses up-regulated PA mRNA and protein synthesis and increased viral polymerase activity. Loss of PA-X was also accompanied by accelerated nuclear accumulation of PA protein and reduced suppression of PA on non-viral protein expression. Our study highlights the effects of PA-X on the moderation of viral pathogenesis and pathogenicity

Субпопуляции интратуморальных эффекторных клеток при раке молочной железы (обзор литературы и представление собственных данных)

Breast cancer (BC) is most prevalent female malignancy worldwide. Despite advances in BC diagnosis and progress in drug therapy, a series of challenges associated with emergent tumour resistance causing the disease escalation still remain. Immune evasion is among the driving forces of tumour resistance against modern treatments, which promotes world-active research into the mechanisms of tumour—immune interaction.Tumour microenvironment is known to contribute greatly to the nature of this interaction. Immune cells are constitutive of tumour microenvironment as tumour-associated macrophages, myeloid-derived suppressor cells and tumour-infi ltrating lymphocytes. Tumour-infi ltrating lymphocytes are represented by B-, T- and NK-cells, which localisation and subpopulation structure in tumour may possess a prognostic and clinical significance. Th e infi ltration density by certain effector cell types prior to chemotherapy is an important predictor of patient survival. Putting otherwise, the presence of effector lymphocyte subpopulations in tumour defi nes the strength of antitumour immunity and may establish the success of drug treatment.This study analysed the infiltration levels of CD3, CD4, CD20 and CD38 lymphocytes in several molecular BC subtypes. Tumour immunophenotyping was performed in cryosectioning and immunofl uorescence assays with a ZEISS AXIOSKOP microscope, Germany. We analysed 96 luminal BC (37 subtype A (38.5 %), 52 B-Her2-negative subtype (54.2 %), 7 B-Her2-positive subtype (7.3 %)) and non-luminal BC samples (3 HER2+ subtype (14.3 %), 18 triple-negative subtype (85.7 %)). The infiltration and antigen expression patterns have been assessed. Analyses of tumour-infi ltrating subpopulations revealed lower infiltration in luminal BC vs. other subtypes, albeit at no significance.Рак молочной железы (РМЖ) является самым распространенным злокачественным новообразованием у женщин в мире. Несмотря на достигнутые успехи в диагностике РМЖ и новейшие лекарственные режимы лечения, остается еще целый ряд нерешенных задач, связанных с  развитием опухолевой резистентности и, как следствие, прогрессированием заболевания. Одним из факторов, определяющих устойчивость опухоли к современным методам лечения, является ее способность уклоняться от иммунного ответа. Поэтому на сегодняшний день учеными всего мира достаточно много внимания уделяется изучению механизмов взаимодействия опухоли с иммунной системой организма.Известно, что микроокружение опухоли вносит значительный вклад в формирование характера данного взаимодействия. Частью микроокружения опухоли являются иммунные клетки, которые могут быть опухольассоциированными макрофагами, супрессорными клетками миелоидного происхождения, опухоль-инфильтрирующими лимфоцитами. Лимфоциты, инфильтрирующие опухоль, представлены В-, Т-, NK-клетками, локализация которых и их субпопуляционный состав в опухоли могут иметь разное прогностическое и клиническое значение. Плотность инфильтрации отдельными видами эффекторных клеток до химиотерапии служит важным предиктором выживаемости больных. Иными словами, присутствие субпопуляций эффекторных лимфоцитов в опухоли характеризует степень напряженности противоопухолевого иммунного ответа и может определять успешность лекарственного лечения.В данном исследовании проанализированы уровни инфильтрации CD3, CD4, CD20, СD38  лимфоцитами при нескольких молекулярных подтипах РМЖ. Иммунофенотипирование опухоли проведено на криостатных срезах методом иммунофлуоресценции (микроскоп Zeiss (Axioskop, Германия)). Проанализированы 96  образцов люминального РМЖ (37 (38,5  %)  — подтип А; 52 (54,2  %)  — В-Her2-негативный подтип; 7 (7,3  %)  — В-Her2-позитивный подтип) и нелюминального РМЖ (3 (14,3 %) — HER2+ подтип; 18 (85,7 %) — трижды негативный подтип). Оценивались характер инфильтрации и выраженность экспрессии антигенов. Анализ уровня инфильтрации субпопуляциями лимфоцитов установил, что при люминальном РМЖ выраженность инфильтрации меньше, чем при других подтипах, однако достоверной связи не обнаружено

PB1-F2 Proteins from H5N1 and 20th Century Pandemic Influenza Viruses Cause Immunopathology

With the recent emergence of a novel pandemic strain, there is presently intense interest in understanding the molecular signatures of virulence of influenza viruses. PB1-F2 proteins from epidemiologically important influenza A virus strains were studied to determine their function and contribution to virulence. Using 27-mer peptides derived from the C-terminal sequence of PB1-F2 and chimeric viruses engineered on a common background, we demonstrated that induction of cell death through PB1-F2 is dependent upon BAK/BAX mediated cytochrome c release from mitochondria. This function was specific for the PB1-F2 protein of A/Puerto Rico/8/34 and was not seen using PB1-F2 peptides derived from past pandemic strains. However, PB1-F2 proteins from the three pandemic strains of the 20th century and a highly pathogenic strain of the H5N1 subtype were shown to enhance the lung inflammatory response resulting in increased pathology. Recently circulating seasonal influenza A strains were not capable of this pro-inflammatory function, having lost the PB1-F2 protein's immunostimulatory activity through truncation or mutation during adaptation in humans. These data suggest that the PB1-F2 protein contributes to the virulence of pandemic strains when the PB1 gene segment is recently derived from the avian reservoir

Myostatin Inhibition in Muscle, but Not Adipose Tissue, Decreases Fat Mass and Improves Insulin Sensitivity

Myostatin (Mstn) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn−/− mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn−/− mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn−/− mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn−/− mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn−/− mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn−/− mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes

Transcriptomic Analysis of Host Immune and Cell Death Responses Associated with the Influenza A Virus PB1-F2 Protein

Airway inflammation plays a major role in the pathogenesis of influenza viruses and can lead to a fatal outcome. One of the challenging objectives in the field of influenza research is the identification of the molecular bases associated to the immunopathological disorders developed during infection. While its precise function in the virus cycle is still unclear, the viral protein PB1-F2 is proposed to exert a deleterious activity within the infected host. Using an engineered recombinant virus unable to express PB1-F2 and its wild-type homolog, we analyzed and compared the pathogenicity and host response developed by the two viruses in a mouse model. We confirmed that the deletion of PB1-F2 renders the virus less virulent. The global transcriptomic analyses of the infected lungs revealed a potent impact of PB1-F2 on the response developed by the host. Thus, after two days post-infection, PB1-F2 invalidation severely decreased the number of genes activated by the host. PB1-F2 expression induced an increase in the number and level of expression of activated genes linked to cell death, inflammatory response and neutrophil chemotaxis. When generating interactive gene networks specific to PB1-F2, we identified IFN-γ as a central regulator of PB1-F2-regulated genes. The enhanced cell death of airway-recruited leukocytes was evidenced using an apoptosis assay, confirming the pro-apoptotic properties of PB1-F2. Using a NF-kB luciferase adenoviral vector, we were able to quantify in vivo the implication of NF-kB in the inflammation mediated by the influenza virus infection; we found that PB1-F2 expression intensifies the NF-kB activity. Finally, we quantified the neutrophil recruitment within the airways, and showed that this type of leukocyte is more abundant during the infection of the wild-type virus. Collectively, these data demonstrate that PB1-F2 strongly influences the early host response during IAV infection and provides new insights into the mechanisms by which PB1-F2 mediates virulence

A Case of Medullary Carcinoma of the Jejunum Combined with the Intestinal Lymphangiectasia Accompanied by the Malabsorption Syndrome

Aim: to present a clinical and morphological observation of an extremely rare combination of medullary carcinoma of the jejunum and intestinal lymphangiectasia in a 33-year-old patient with clinical features of malabsorption syndrome over the 10 years.Key points. An autopsy revealed a tumor formation spreading from the wall of the jejunum to the mesentery, with metastases to the mesenteric lymph nodes. The medullary carcinoma with positive expression of СD117, DOG1, EMA, PanCK, PDL-1, vimentin, mosaic non-intense expression of CA19-9, calretinin, CD10, CDX2, CEA, MUC-5AC, SATB2, and negative reaction to ALK, CD3, CD8, CD20, CD30, CD31, CD34, CD45, CD56, chromogranin, CK7, CK20, desmin. The proliferative index was high: Ki-67 > 80 %. Moreover, during the histological examination of the intestinal wall, intestinal lymphangiectasia complicated by the malabsorption syndrome was revealed.Conclusion. The uniqueness of this clinical and morphological case is in the combination of medullary carcinoma of the jejunum metastasized to the mesenteric lymph nodes with the underlying intestinal lymphangiectasia accompanied by the development of malabsorption syndrome

The WEBT BL Lacertae Campaign 2001 and its extension : Optical light curves and colour analysis 1994–2002

BL Lacertae has been the target of four observing campaigns by the Whole Earth Blazar Telescope (WEBT) collaboration. In this paper we present UBVRI light curves obtained by theWEBT from 1994 to 2002, including the last, extended BL Lac 2001 campaign. A total of about 7500 optical observations performed by 31 telescopes from Japan to Mexico have been collected, to be added to the ∼15 600 observations of the BL Lac Campaign 2000. All these data allow one to follow the source optical emission behaviour with unprecedented detail. The analysis of the colour indices reveals that the flux variability can be interpreted in terms of two components: longer-term variations occurring on a fewday time scale appear as mildly-chromatic events, while a strong bluer-when-brighter chromatism characterizes very fast (intraday) flares. By decoupling the two components, we quantify the degree of chromatism inferring that longer-term flux changes imply moving along a ∼0.1 bluerwhen- brighter slope in the B − R versus R plane; a steeper slope of ∼0.4 would distinguish the shorter-term variations. This means that, when considering the long-term trend, the B-band flux level is related to the R-band one according to a power law of index ∼1.1. Doppler factor variations on a “convex” spectrum could be the mechanism accounting for both the long-term variations and their slight chromatism.Reig Torres, Pablo, [email protected]