Author as a corporal subject of a. Huxley’s works

The relevance of the problem studied in the article is conditioned by the fact that A. Huxley’s works are regarded in the context of the modern theory of mimesis for the first time. The aim of the article is to analyze the author’s problem as a corporal subject of Huxley’s works in the context of the modern theory of mimesis. The leading method for studying this problem is the analytical anthropology of literature which allows describing mimetic features and the author’s image as a corporal subject of Huxley’s works. The main attention in the article is paid to the artistically embodied forms of the author’s corporality. The article may be useful for philologists, philosophers, for developing courses and seminars on the history of the English literature, and also within courses on the anthropology of literature. © 2016 Falaleeva et al

Transcription of the Streptococcus Pyogenes Hyaluronic Acid Capsule Biosynthesis Operon is Regulated by Previously Unknown Upstream Elements

The important human pathogen Streptococcus pyogenes (group A Streptococcus [GAS]) produces a hyaluronic acid (HA) capsule that plays critical roles in immune evasion. Previous studies showed that the hasABC operon encoding the capsule biosynthesis enzymes is under the control of a single promoter, P1, which is negatively regulated by the two-component regulatory system CovR/S. In this work, we characterize the sequence upstream of P1 and identify a novel regulatory region controlling transcription of the capsule biosynthesis operon in the M1 serotype strain MGAS2221. This region consists of a promoter, P2, which initiates transcription of a novel small RNA, HasS, an intrinsic transcriptional terminator that inefficiently terminates HasS, permitting read-through transcription of hasABC, and a putative promoter which lies upstream of P2. Electrophoretic mobility shift assays, quantitative reverse transcription-PCR, and transcriptional reporter data identified CovR as a negative regulator of P2. We found that the P1 and P2 promoters are completely repressed by CovR, and capsule expression is regulated by the putative promoter upstream of P2. Deletion of hasS or of the terminator eliminates CovR-binding sequences, relieving repression and increasing read-through, hasA transcription, and capsule production. Sequence analysis of 44 GAS genomes revealed a high level of polymorphism in the HasS sequence region. Most of the HasS variations were located in the terminator sequences, suggesting that this region is under strong selective pressure. We discovered that the terminator deletion mutant is highly resistant to neutrophil-mediated killing and is significantly more virulent in a mouse model of GAS invasive disease than the wild-type strain. Together, these results are consistent with the naturally occurring mutations in this region modulating GAS virulence

Molecular Characterization of a Patient Presumed to Have Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is caused by the loss of RNA expression from an imprinted region on chromosome 15 that includes SNRPN, SNORD115, and SNORD116. Currently, there are no mouse models that faithfully reflect the human phenotype and investigations rely on human post-mortem material. During molecular characterization of tissue deposited in a public brain bank from a patient diagnosed with Prader-Willi syndrome, we found RNA expression from SNRPN, SNORD115, and SNORD116 which does not support a genetic diagnosis of Prader-Willi syndrome. The patient was a female, Caucasian nursing home resident with history of morbid obesity (BMI 56.3) and mental retardation. She died at age of 56 from pulmonary embolism. SNORD115 and SNORD116 are unexpectedly stable in post mortem tissue and can be used for post-mortem diagnosis. Molecular characterization of PWS tissue donors can confirm the diagnosis and identify those patients that have been misdiagnosed

Противоопухолевый эффект рекомбинантного интерферона гамма в экспериментальной модели билатеральной солидной карциномы Эрлиха

Introduction. Immunotherapy, which is part of the complex and combined cancer therapy, is one of the priority areas in the treatment of cancer patients. However, the effectiveness of the use of immunotherapeutic drugs of the latest generation is not so high, and in some patients the effect of therapy was short-lived. Factors that prevent the full realization of the antitumor effect of cytostatics and immunopreparations may be the features of the antigenic composition of the tumor, as well as its cellular and stromal microenvironment. These facts contributed to the development of a new strategy, designated as immunoredaction of cancer by exposure to various biologically active agents that can change the body – tumor ratio in favor of the patient and make the tumor available for the implementation of antitumor effects of the host immune system.The study objective – experimental substantiation of the development of new immunotherapeutic approaches in the treatment of aggressive forms of cancer.Materials and methods. An experimental study of the effect of human recombinant interferon-gamma (IFNγ) on the growth of Ehrlich’s carcinoma during subcutaneous bilateral transplantation of tumor cells to animals was carried out. Transplantation of Ehrlich’s carcinoma to male F1 hybrids (SWAhC57Bl6) was performed by subcutaneous injection of 2.0 × 106 tumor cells (7‑day culture) in 0.1 ml of suspension into the lateral surface of the right and left femur with imitation of multicentric growth.Results. A day after the course of drug administration (day 6 of tumor node growth), the effect of suppressing tumor growth in relation to growth in the control group was noted. The maximum inhibition effect of 19.8 % (p <0.05) of tumor growth was obtained 5 days after the course of the drug (10 days of tumor growth, right node) and 18.5 % (p <0.001) 9 days after administration (14 days of tumor growth, left node).Conclusion. Thus, a distinct, statistically significant antitumor effect of IFNγ was established in relation to a tumor with a multicentric growth pattern.Введение. Иммунотерапия, входящая в состав комплексной и комбинированной терапии рака, является одним из приоритетных направлений в лечении онкологических больных. Однако эффективность применения иммунотерапевтических препаратов последнего поколения не так высока, а у некоторых больных эффект терапии оказался кратковременным. Факторами, препятствующими полноценной реализации противоопухолевого эффекта цитостатиков и иммунопрепаратов, возможно, являются особенности антигенного состава опухоли, а также ее клеточного и стромального микроокружения. Данные факты способствовали развитию новой стратегии, обозначенной как иммуноредактирование рака посредством воздействия различных биологически активных агентов, способных изменить соотношение организм – опухоль в пользу больного и сделать опухоль доступной для реализации противоопухолевого воздействия иммунной системы хозяина.Цель исследования – экспериментальное обоснование разработки новых иммунотерапевтических подходов в лечении агрессивных форм рака.Материалы и методы. Проведено экспериментальное изучение влияния человеческого рекомбинантного интерферона гамма (IFNγ) на рост карциномы Эрлиха при подкожной билатеральной трансплантации клеток опухоли животным. Трансплантацию карциномы Эрлиха мышам-самцам гибридам F1 (СВАхС57Вl6) проводили подкожным  введением 2,0 × 106 опухолевых клеток (7‑дневная культура) в 0,1 мл суспензии в область латеральной поверхности правого и левого бедер с имитацией мультицентричного роста.Результаты. Через сутки после курса введения препарата (6‑е сутки роста опухолевых узлов) отмечен эффект подавления роста опухоли по отношению к росту в контрольной группе. Максимальный эффект торможения, составляющий 19,8 % (р <0,05) роста опухоли, получен через 5 сут после курса препарата (10‑е сутки опухолевого роста, правый узел) и 18,5 % (р <0,001) через 9 суток после введения (14‑е сутки опухолевого роста, левый узел).Заключение. Таким образом, установлен отчетливый, статистически значимый противоопухолевый эффект IFNγ в отношении опухоли с мультицентричным характером роста

Specialized box C/D snoRNPs act as antisense guides to target RNA base acetylation

Box C/D snoRNAs are known to guide site-specific ribose methylation of ribosomal RNA. Here, we demonstrate a novel and unexpected role for box C/D snoRNAs in guiding 18S rRNA acetylation in yeast. Our results demonstrate, for the first time, that the acetylation of two cytosine residues in 18S rRNA catalyzed by Kre33 is guided by two orphan box C/D snoRNAs–snR4 and snR45 –not known to be involved in methylation in yeast. We identified Kre33 binding sites on these snoRNAs as well as on the 18S rRNA, and demonstrate that both snR4 and snR45 establish extended bipartite complementarity around the cytosines targeted for acetylation, similar to pseudouridylation pocket formation by the H/ACA snoRNPs. We show that base pairing between these snoRNAs and 18S rRNA requires the putative helicase activity of Kre33, which is also needed to aid early pre-rRNA processing. Compared to yeast, the number of orphan box C/D snoRNAs in higher eukaryotes is much larger and we hypothesize that several of these may be involved in base-modifications