Pleiotropic Effect of IL-6 Produced by B-Lymphocytes During Early Phases of Adaptive Immune Responses Against TB Infection

The role of B cells migrating to the lung and forming follicles during tuberculosis (TB) inflammation is still the subject of debate. In addition to their antibody production and antigen-presenting functions, B cells secrete different cytokines and chemokines, thus participating in complex networks of innate and adaptive immunity. Importantly, lung B-cells produce high amounts of the pleiotropic gp130 cytokine IL-6. Its role during TB infection remains controversial, partly due to the fact that IL-6 is produced by different cell types. To investigate the impact of IL-6 produced by B cells on TB susceptibility and immune responses, we established a mouse strain with specific IL-6 deficiency in B cells (CD19cre-IL-6fl/fl, B-IL-6KO) on the B6 genetic background. Selective abrogation of IL-6 in B cells resulted in shortening the lifespan of TB-infected B-IL-6KO mice compare to the wild-type controls. We provide evidence that at the initial TB stages B cells serve as a critical source of IL-6. In the lung, the effect of IL-6 deficiency in B cells is associated rather with B and T cell functioning, than with macrophage polarization. TB-infected B-IL-6KO mice displayed diminished sizes of B cells themselves, CD4 + IFN-γ +, Th17 +, and CD4 + CXCR5 + follicular T cell populations. The pleiotropic effect of B-cell-derived IL-6 on T-cells demonstrated in our study bridges two major lymphocyte populations and sheds some light on B- and T-cells interactions during the stage of anti-TB response when the host switches on a plethora of acquired immune reactions

Deciphering the origin and therapeutic targets of cancer of unknown primary: a case report that illustrates the power of integrative whole-exome and transcriptome sequencing analysis

Cancer of unknown primary (CUP) represents a significant diagnostic and therapeutic challenge, being the third to fourth leading cause of cancer death, despite advances in diagnostic tools. This article presents a successful approach using a novel genomic analysis in the evaluation and treatment of a CUP patient, leveraging whole-exome sequencing (WES) and RNA sequencing (RNA-seq). The patient, with a history of multiple primary tumors including urothelial cancer, exhibited a history of rapid progression on empirical chemotherapy. The application of our approach identified a molecular target, characterized the tumor expression profile and the tumor microenvironment, and analyzed the origin of the tumor, leading to a tailored treatment. This resulted in a substantial radiological response across all metastatic sites and the predicted primary site of the tumor. We argue that a comprehensive genomic and molecular profiling approach, like the BostonGene© Tumor Portrait, can provide a more definitive, personalized treatment strategy, overcoming the limitations of current predictive assays. This approach offers a potential solution to an unmet clinical need for a standardized approach in identifying the tumor origin for the effective management of CUP

Art School of the Krasnoyarsk Region: Formation Features Analysis Through the Prism of the Fractal Concept

Статья посвящена возможностям использования фрактальной концепции для исследования региональной художественной жизни и особенностей формирования академической художественной школы. Предметом исследования является деятельность творческих лидеров на начальном этапе становления системы профессионального художественного образования в Красноярске на рубеже XIX–XX вв. Применение основных положений фрактальной концепции культуры позволило выделить базовые элементы сложения региональной художественной традиции. Исторический анализ и историографический подход к изучению становления художественного образования дает возможность определить ключевые точки происхождения региональной художественной школы, а за счет использования антропологического подхода раскрывается роль индивидов в периферийной художественной жизни. Уникальность региональной художественной культуры и особенности ее образовательной традиции на начальном этапе становления системы профессионального художественного образования определялись комплексом факторов, которые проявлялись, прежде всего, в деятельности творческих лидеров: М. А. Рученко и П. И. Иванова-Радкевича. Главные направления их работы и художественно-педагогические методы позволили выявить основные положения развития культуры региона и важные шаги на пути к исторической, географической и этнографической самоидентификации в культуре и искусстве Красноярского краяThe article is based on a study aimed to the possibility of applying the fractal concept for the region’s artistic life study and the formation of its professional art education system. There are main features of the application of the fractal concept in this study, its subject is the activity of creative leaders at the initial stage of the formation of the professional art education system in Krasnoyarsk at the turn of the XIX–XX centuries. Historical analysis and historiographic approach for studying the formation of art education makes it possible to determine the key origin points of the regional art school, and due to use of an anthropological approach the role of the individuals in the periphery artistic life reveals, as well as the launch and coordination of self-organizing processes. There were a set of factors which determined the unique appearance of the regional art culture and the features of its educational tradition at the initial stage of the professional art education system formation which were manifested primarily through the activities of creative leaders: M. A. Rutchenko and P. I. Ivanov-Radkevich, who could be called as anthropological fractals. The main directions of their work and artistic and teaching methods made it possible to determine the basic provisions for the development of the culture of the region and important steps towards the historical, geographical and ethnographic self-identification in the culture and art of Krasnoyars