217 research outputs found
Recommended from our members
Spt5 Regulates Sense and Antisense Transcription Genome-Wide
No full textSpt5 is the only transcription elongation factor conserved in all three domains of life, but its molecular mechanisms are not yet thoroughly studied genomically. From an inducible depletion strain, we sequenced nascent transcripts (NET-seq), mature mRNA (RNA-seq), and RNA polymerase II-associated chromatin (ChIP-seq) to elucidate general effects of Spt5 on transcription. These show an increase in 5’ CDS antisense transcription by RNA-seq and NET-seq and a general accumulation of RNA Pol II at the 5’ ends of genes by exogenous spike-in-normalized ChIP-seq. That similar antisense transcripts appear in RNA-seq and NET-seq indicates that novel antisense transcripts are resulting from new transcription rather than aberrant decay. These results provide insight into how Spt5 functions to facilitate RNA Pol II elongation in diverse organisms.Master of Medical Sciences in Biomedical Informatic
Pulmonary embolism in COVID-19
No full textIlyina-Stohniienko V. Yu., Kharchenko Yu. P., Zaretska A. V., Savchuk A. I., Kolotvin A. I. Pulmonary embolism in COVID-19. Journal of Education, Health and Sport. 2022;12(2):285-291. eISSN 2391-8306. DOI http://dx.doi.org/10.12775/JEHS.2022.12.02.030
https://apcz.umk.pl/JEHS/article/view/JEHS.2022.12.02.030
https://zenodo.org/record/6565700
The journal has had 40 points in Ministry of Education and Science of Poland parametric evaluation. Annex to the announcement of the Minister of Education and Science of December 1, 2021. No. 32343.
Has a Journal's Unique Identifier: 201159. Scientific disciplines assigned: Physical Culture Sciences (Field of Medical sciences and health sciences); Health Sciences (Field of Medical Sciences and Health Sciences).
Punkty Ministerialne z 2019 - aktualny rok 40 punktów. Załącznik do komunikatu Ministra Edukacji i Nauki z dnia 1 grudnia 2021 r. Lp. 32343. Posiada Unikatowy Identyfikator Czasopisma: 201159.
Przypisane dyscypliny naukowe:Nauki o kulturze fizycznej (Dziedzina nauk medycznych i nauk o zdrowiu); Nauki o zdrowiu (Dziedzina nauk medycznych i nauk o zdrowiu).
© The Authors 2022;
This article is published with open access at Licensee Open Journal Systems of Nicolaus Copernicus University in Torun, Poland
Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium,
provided the original author (s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non commercial license Share alike. (http://creativecommons.org/licenses/by-nc-sa/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Received: 31.01.2022. Revised: 08.02.2022. Accepted: 28.02.2022.
PULMONARY EMBOLISM IN COVID-19
V. Yu. Ilyina-Stohniienko, Yu. P. Kharchenko, A. V. Zaretska, A. I. Savchuk,
A. I. Kolotvin
Odessa National Medical University
Abstract
COVID-19 pandemic is recognized as a present day major public health burden. Risk factors for developing a more severe course of COVID-19 include increased levels of C-reactive protein and D-dimer. Pulmonary embolism (PE) is challenging in patients with COVID-19. The purpose: to analyze clinical and paraclinical manifestations of PE in patients with COVID-19 in order to develop a system for its early diagnosis, prediction of complications, prevention and treatment. 52 patients aged 28 - 81 y.o. with a diagnosis "Acute respiratory disease COVID-19" have been examined during 2020-2021. (98.08±1.9)% of PE patients had a history of one or more comorbidities, including obesity (80.77%), coronary heart disease (96.15%), hypertension (98.08%), peripheral arteries (92.3%), type 2 diabetes mellitus (48.08%). Evaluation of laboratory parameters revealed increasing lymphocytopenia, leukocytosis, neutrophilia, thrombocytopenia (p<0.05). Biochemical parameters showed high CRP, increase in creatinine, decrease in glomerular filtration rate (p<0.05). A direct relationship was found between overweight and an increase in the content of C-RP in COVID-19 and PE patients. Conclusions: age over 65, hypertension and obesity are risk factors for severe course of COVID-19 and PE.
Key words: COVID-19; PE; D-dimer; coagulopath
Recommended from our members
Somatic genome evolution in cancer and aging through the lens of transcription
No full textDNA mutations accumulate in somatic cells throughout our lifetime, making the tissues in our body patchwork of mutant clones that evolve over time. This phenomenon, referred to as “somatic evolution”, underlies the initiation and progression of cancer as well as other age-related diseases.
Limitations in existing analytical tools have largely constrained our understanding of somatic genome evolution in cancer and normal tissues. Although recent advances in single-cell DNA sequencing have enabled the characterization of genomic variations at the level of individual cells, they do not produce phenotypic measurements needed for assessing variant impact. Detecting genetic aberrations from single-cell RNA sequencing (scRNA-seq) data has the potential to overcome this limitation by coupling genetic and transcriptomic measurements within the same cell. In the first part of this dissertation, I describe a novel computational method, Numbat, that utilizes population-based haplotype phasing to achieve reliable detection of chromosomal alterations and clonal phylogeny from scRNA-seq data. Analysis of tumor samples from a wide range of cancer types shows that Numbat can accurately reconstruct the tumor copy number profile, precisely identify malignant cells in the tumor microenvironment, and resolve genetic subpopulations with transcriptional signatures relevant to tumor progression and therapy resistance.
Although aneuploidy is a defining feature of cancer cells, its extent and consequences in normal tissues remain largely unknown. In the second part of this dissertation, I describe an analysis of 16,672 RNA-seq samples from 948 healthy individuals in the GTEx project using an extension of the Numbat algorithm, representing the first large-scale pan-tissue survey of mosaic chromosomal alterations (mCAs) in the human body. We found that approximately a quarter of healthy individuals carry a clonally-expanded mCA in at least one tissue, with incidence strongly correlated with age. The prevalence and genome-wide patterns of mCAs vary considerably across tissue types, suggesting tissue-specific mutagenic exposure and selection pressures. The mCA landscapes in normal adrenal and pituitary glands resemble those in tumors arising from these tissues, whereas the same is not true for the esophagus and skin. Finally, scRNA-seq analysis of a normal adult adrenal gland harboring mCAs revealed gene expression changes related to cellular proliferation and hormone secretion. Together, these findings show a widespread age-dependent emergence of mCAs across normal human tissues with intricate connections to tumorigenesis.Medical SciencesMedical Science
Особливості соціального інтелекту курсантів, які навчаються в закладах вищої освіти зі специфічними умовами навчання
No full textIt has been noted that the data on the development of the abilities of students’ social intelligence during their studies in higher education institutions, which are presented in the literature, are ambiguous and need to be clarified.
The author of the article has analyzed the peculiarities of the abilities of social intelligence of cadets of institutions of higher education with specific learning conditions in different years (time interval between studies – 15 years) and at different courses. The research was conducted at Kharkiv National University of Internal Affairs in 2002 and 2017 by using J. J. Guilford’s Social Intelligence Methodology. 4 groups of cadets participated in the study. They were future psychologists who studied at 1, 3 (2 groups) and 5 courses.
According to the results of the study, cadets are most often diagnosed with the average and lower than the average levels of social intelligence (high level of social intelligence among the surveyed cadets in 2017 was not diagnosed), the most advanced ability of social intelligence was the ability to predict the effects of behavior. The smallest changes over time were established regarding the cadets’ abilities to logical generalization, the allocation of common essential features in various nonverbal responses of a person. In general, there was a certain decrease in the level of the development of cadets’ abilities of social intelligence, especially the ability to understand the internal motives of people’s behavior; the author of the study suggests that this may be due to the negative influence of a number of factors in the social environment, where the abilities of social intelligence are formed.
Among the factors that negatively affected the level of development of the abilities of social intelligence of the study participants, the author has distinguished the following: changes in child-parent communication; change in the content of education and attitudes towards children in secondary schools; reduction of the intensity of direct friendship communication and increase of the importance of communication in social networks. The author has proved the necessity to improve the educational and pedagogical conditions aimed at developing the abilities of social intelligence of modern professionals in the law enforcement sphere.Представлены результаты изучения способностей социального интеллекта курсантов учреждения высшего образования со специфическими условиями обучения в разные годы (интервал между исследованиями – 15 лет) и на разных курсах обучения. У курсантов чаще всего диагностировался средний уровень социального интеллекта, а наиболее развитой способностью была способность предвидеть последствия поведения. Со временем у них произошло некоторое снижение уровня способностей социального интеллекта, наименьшие изменения произошли в уровне способности к логическому обобщению и выделению общих существенных признаков в разных невербальных реакциях человека.Презентовано результати вивчення здібностей соціального інтелекту курсантів закладів вищої освіти зі специфічними умовами навчання в різні роки (інтервал між дослідженнями – 15 років) і різних курсів навчання. У них найчастіше діагностувався середній рівень соціального інтелекту, а найбільш розвинутою здібністю була здібність передбачати наслідки поведінки. Із часом у них відбулося певне зниження рівня здібностей соціального інтелекту, найменші зміни сталися із здібністю до логічного узагальнення й виділення загальних істотних ознак у різних невербальних реакціях людини
Publisher Correction: The triumphs and limitations of computational methods for scRNA-seq
No full textRecommended from our members
Multiplexed Methods and Applications of Single Cell Genome and Transcriptome Sequencing
No full textBiological tissues are a complex mixture of specialized cell types which display heterogeneity at the level of gene expression and in some cases at the level of the genome. Single cell studies thus have the potential to reveal important biological insights that are hidden in bulk measurements. However, realizing this potential requires overcoming technical challenges unique to single cell measurements. Single cell sequencing requires amplification, which introduces errors that must be minimized. Moreover, dissecting a heterogeneous system requires methods capable of examining large numbers of cells in a timely and cost-effective manner. We present a set of methods for single cell whole genome and transcriptome amplification that provide high accuracy and sensitivity and readily scale to allow analysis of thousands of cells. Using these methods, we present applications to cancer and developmental biology and demonstrate that biological insights can be revealed by measuring noise within a homogenous population.Biophysic
Recommended from our members
Deconstructing Cell Intrinsic Immunity and Host-Pathogen Interactions Using Single-Cell Genomics
No full textThe outcome of infection by a virus or microorganism is determined by a complex set of interactions between host tissues and the virulence mechanisms of the invading agent. Among directly infected and bystander cells, the concerted efforts of immune and stromal cellular communities can neutralize and clear the pathogen with minimal inflammatory damage, or can be circumvented by the pathogen, leading to excessive immunopathology without effective neutralization. At barrier tissues and within their draining lymphoid organs, diverse cell types, microenvironments, commensal organisms, and pathogens create an immensely complicated network of intracellular and intercellular interactions. To understand the basic biology of infectious diseases and to design effective therapeutics, we must chart the critical “nodes” within these host-pathogen networks that lead to emergent properties and outcomes. Methods in single-cell genomics have transformed our ability to comprehensively map host cell types and their behavior during health and disease. Emerging technical and computational approaches expand our toolbox from solely mapping host transcription to the inclusion of data on gene regulatory elements, genomic material from co-resident microbes, cell and tissue developmental dynamics, and the complex cellular communities underlying tissue structure. In the work presented here, we develop and apply new approaches in single-cell genomics to offer deeper understanding into fundamental organismal biology and immunology. First, we detail our work to understand how seemingly disparate organ systems – the sensory arm of the peripheral nervous system and the immune system within lymphoid tissues – together orchestrate the host response to barrier tissue injury. Here, we describe a previously-unappreciated neuro-immune circuit which can respond to pathogenic insult and be manipulated by neuro-tropic viruses (Chapter 2). Next, we map the putative cellular tropism of SARS-CoV-2, the virus that causes COVID-19, and discover mechanisms of viral exploitation and evasion of conserved host defenses (Chapters 3-4). Further, we develop molecular and computational techniques to directly tie intracellular pathogen life cycles across diverse viruses and microbes to host cell biology on an individual cell level (Chapter 4). Finally, using engineered fluorescent small molecules, we advance our capacity to specifically tag and manipulate cells within 2D and 3D systems by their morphology, molecular phenotype, and microenvironment (Chapter 5). Collectively, this work advances the molecular and computational approaches for interrogating host-pathogen interactions underlying major human infectious diseases, with a focus on enabling a deep understanding of pathogen biology, the scope and variance in human disease pathophysiology, and the complex dynamics of host mucosal and systemic immunity. We propose that systems for rapid and comprehensive characterization of emerging infectious agents are critical tools in the efforts to curb current disease outbreaks, and will likely prove instrumental in addressing future pandemic diseases
Recommended from our members
Spatial and temporal dynamics of immune cell interactions
No full textIn this thesis, I explore spatial and temporal methods for studying immune cell interactions.
First, I review Slide-TCR-seq, a method we developed for measuring T cell receptor (TCR) sequences in the tissue context. T cells mediate antigen-specific immune responses to disease through the specificity and diversity of their clonotypic TCRs. We confirmed the ability of Slide-TCR-seq to map the characteristic locations of T cells and their receptors in mouse spleen. In human lymphoid germinal centers, we identified spatially distinct TCR repertoires. Profiling T cells in renal cell carcinoma and melanoma specimens revealed heterogeneous immune responses: T cell states and infiltration differed intra- and inter-clonally, and adjacent tumor and immune cells exhibited distinct gene expression. Our method yields insights into the spatial relationships between clonality, neighboring cell types, and gene expression that drive T cell responses.
Second, I will discuss an application of Slide-TCR-seq to study immunological aging in the thymus in human and mouse contexts, as well as strategies for regeneration. Humans have elaborate immune defenses to protect against infectious agents and the damage they cause. The thymus is a key part of the immune system, providing a unique environment for developing T cells, and contributing to the recognition and destruction of intracellular pathogens. During development, precursors of T cells migrate from the bone marrow to the thymus, where they undergo maturation and selection, leading to a vast repertoire poised to recognize and clear foreign pathogens. In mammals, this process of T cell maturation occurs early in development, and as the animals age, the thymus gradually decreases in size, nearly disappearing altogether, a process called involution. Here we show that thymic involution is a highly orchestrated process, coupling degradation of organ architecture to loss of function, and eventually, the decline of peripheral T cell diversity. We established a spatial and single-cell reference of thymus stromal cells, thymocytes and peripheral T cells that integrates organ systems and time.
Last, I will discuss various projects I've worked on and thought about exploring recording cell interactions and time in cells, ranging from direct cell modifications to secreted protein tags
Recommended from our members
Towards a Systematic Approach for Characterizing Regulatory Variation
No full textA growing body of evidence suggests that genetic variants that alter gene expression are responsible for many phenotypic differences across individuals, particularly for the risk of developing common diseases. However, the molecular mechanisms that underlie the vast majority of associations between genetic variants and their phenotypes remain unknown. An important limiting factor is that genetic variants remain difficult to interpret, particularly in noncoding sequences. Developing truly systematic approaches for characterizing regulatory variants will require: (a) improved annotations for the genomic sequences that control gene expression, (b) a more complete understanding of the molecular mechanisms through which genetic variants, both coding and noncoding, can affect gene expression, and (c) better experimental tools for testing hypotheses about regulatory variants.
In this dissertation, I present conceptual and methodological advances that directly contribute to each of these goals. A recurring theme in all of these developments is the statistical modeling of protein-DNA interactions and its integration with other data types. First, I describe enhancer-FACS-Seq, a high-throughput experimental approach for screening candidate enhancer sequences to test for in vivo, tissue-specific activity. Second, I present an integrative computational analysis of the in vivo binding of NF-kappaB, a key regulator of the immune system, yielding new insights into how genetic variants can affect NF-kappaB binding. Next, I describe the first comprehensive survey of coding variation in human transcription factors and what it reveals about additional sources of genetic variation that can affect gene expression. Finally, I present SIFTED, a statistical framework and web tool for the optimal design of TAL effectors, which have been used successfully in genome editing and can thus be used to test hypotheses about regulatory variants. Together, these developments help fulfill key needs in the quest to understand the molecular basis of human phenotypic variation.BiophysicsRegulatory genomics; gene regulatio
- …
