scholarly journals Phage gene expression and host responses lead to infection-dependent costs of CRISPR immunity

2020 ◽  
Author(s):  
Sean Meaden ◽  
Loris Capria ◽  
Ellinor Alseth ◽  
Sylvain Gandon ◽  
Ambarish Biswas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Fitness Cost ◽  
Host Responses ◽  
Phage Gene ◽  
Negative Effect ◽  
Evolution Experiment ◽  
Mechanistic Basis ◽  
Phage Receptor ◽  
The Cost

AbstractCRISPR-Cas immune systems are widespread in bacteria and archaea, but not ubiquitous. Previous work has demonstrated that CRISPR immunity is associated with an infection-induced fitness cost, which may help explain the patchy distribution observed. However, the mechanistic basis of this cost has remained unclear. Using Pseudomonas aeruginosa PA14 and its phage DMS3vir as a model, we perform a 30-day evolution experiment under phage mediated selection. We demonstrate that although CRISPR is initially selected for, bacteria carrying mutations in the phage receptor rapidly invade the population following subsequent reinfections. We then test three potential mechanisms for the observed cost of CRISPR: (1) autoimmunity from the acquisition of self-targeting spacers, (2) immunopathology or energetic costs from increased cas gene expression and (3) toxicity caused by phage gene expression prior to CRISPR-mediated cleavage. We find that phages can express genes before the immune system clears the infection and that expression of these genes can have a negative effect on host fitness. While infection does not lead to increased expression of cas genes, it does cause differential expression of multiple other host processes that may further contribute to the cost of CRISPR immunity. In contrast, we found little support for infection-induced autoimmunological and immunopathological effects. Phage gene expression prior to cleavage of the genome by the CRISPR-Cas immune system is therefore the most parsimonious explanation for the observed phage-induced fitness cost.

scholarly journals Correction: Phage gene expression and host responses lead to infection-dependent costs of CRISPR immunity

2021 ◽  
Author(s):  
Sean Meaden ◽  
Loris Capria ◽  
Ellinor Alseth ◽  
Sylvain Gandon ◽  
Ambarish Biswas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Host Responses ◽  
Phage Gene

scholarly journals Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Anna C. Aschenbrenner ◽  
◽  
Maria Mouktaroudi ◽  
Benjamin Krämer ◽  
Marie Oestreich ◽  
...  
Keyword(s):  
Immune System ◽  
Disease Severity ◽  
Whole Blood ◽  
Viral Infections ◽  
Inflammatory Diseases ◽  
Target Prediction ◽  
Data Driven ◽  
Host Responses ◽  
Drug Candidates ◽  
Drug Target Prediction

Abstract Background The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. Methods In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. Results Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. Conclusions Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.

scholarly journals Nonmonotonic Pathway Gene Expression Analysis Reveals Oncogenic Role of p27/Kip1 at Intermediate Dose

2017 ◽  
Vol 16 ◽  
pp. 117693511774013 ◽  
Author(s):  
Hien H Nguyen ◽  
Susan C Tilton ◽  
Christopher J Kemp ◽  
Mingzhou Song
Keyword(s):  
Gene Expression ◽  
Pathway Analysis ◽  
Dose Response ◽  
Response Analysis ◽  
Response Curves ◽  
Cancer Pathways ◽  
Pathway Gene ◽  
Mechanistic Basis ◽  
Functional Pathway ◽  
Squamous Cell Papilloma

The mechanistic basis by which the level of p27Kip1 expression influences tumor aggressiveness and patient mortality remains unclear. To elucidate the competing tumor-suppressing and oncogenic effects of p27Kip1 on gene expression in tumors, we analyzed the transcriptomes of squamous cell papilloma derived from Cdkn1b nullizygous, heterozygous, and wild-type mice. We developed a novel functional pathway analysis method capable of testing directional and nonmonotonic dose response. This analysis can reveal potential causal relationships that might have been missed by other nondirectional pathway analysis methods. Applying this method to capture dose-response curves in papilloma gene expression data, we show that several known cancer pathways are dominated by low-high-low gene expression responses to increasing p27 gene doses. The oncogene cyclin D1, whose expression is elevated at an intermediate p27 dose, is the most responsive gene shared by these cancer pathways. Therefore, intermediate levels of p27 may promote cellular processes favoring tumorigenesis—strikingly consistent with the dominance of heterozygous mutations in CDKN1B seen in human cancers. Our findings shed new light on regulatory mechanisms for both pro- and anti-tumorigenic roles of p27Kip1. Functional pathway dose-response analysis provides a unique opportunity to uncover nonmonotonic patterns in biological systems.

Effect of UVB irradiation on the immune system and gene expression of the skin

2008 ◽  
Vol 180 ◽  
pp. S214
Author(s):  
Jeong Pyo Lee ◽  
Jung Hun Ju ◽  
Jong Kwon Lee ◽  
Kyung Hee Sohn ◽  
Chae Hyung Lim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Uvb Irradiation

Polyamine supplementation in infant formula: Influence on lymphocyte populations and immune system-related gene expression in a Balb/cOlaHsd mouse model

2014 ◽  
Vol 59 ◽  
pp. 8-15 ◽  
Author(s):  
Carlos Gómez-Gallego ◽  
Rafael Frias ◽  
Gaspar Pérez-Martínez ◽  
María José Bernal ◽  
María Jesús Periago ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Mouse Model ◽  
Infant Formula ◽  
Related Gene ◽  
Lymphocyte Populations

scholarly journals Stochastic Kinetic Analysis of Developmental Pathway Bifurcation in Phage λ-Infected Escherichia coli Cells

Genetics ◽  
1998 ◽  
Vol 149 (4) ◽  
pp. 1633-1648 ◽  
Author(s):  
Adam Arkin ◽  
John Ross ◽  
Harley H McAdams
Keyword(s):  
Gene Expression ◽  
Kinetic Model ◽  
Kinetic Analysis ◽  
Molecular Level ◽  
Host Responses ◽  
Statistical Thermodynamic ◽  
Regulatory Systems ◽  
Regulatory Circuit ◽  
Phenotype Selection ◽  
Decision Circuit

Abstract Fluctuations in rates of gene expression can produce highly erratic time patterns of protein production in individual cells and wide diversity in instantaneous protein concentrations across cell populations. When two independently produced regulatory proteins acting at low cellular concentrations competitively control a switch point in a pathway, stochastic variations in their concentrations can produce probabilistic pathway selection, so that an initially homogeneous cell population partitions into distinct phenotypic subpopulations. Many pathogenic organisms, for example, use this mechanism to randomly switch surface features to evade host responses. This coupling between molecular-level fluctuations and macroscopic phenotype selection is analyzed using the phage λ lysis-lysogeny decision circuit as a model system. The fraction of infected cells selecting the lysogenic pathway at different phage:cell ratios, predicted using a molecular-level stochastic kinetic model of the genetic regulatory circuit, is consistent with experimental observations. The kinetic model of the decision circuit uses the stochastic formulation of chemical kinetics, stochastic mechanisms of gene expression, and a statistical-thermodynamic model of promoter regulation. Conventional deterministic kinetics cannot be used to predict statistics of regulatory systems that produce probabilistic outcomes. Rather, a stochastic kinetic analysis must be used to predict statistics of regulatory outcomes for such stochastically regulated systems.

Use of immunocorrectors in patients with chronic lymph leukemia

1986 ◽  
Vol 67 (2) ◽  
pp. 99-101
Author(s):  
V. Ya. Shustov ◽  
N. A. Afanasyeva ◽  
P. P. Kuznetsov ◽  
A. K. Myshkina
Keyword(s):  
Immune System ◽  
Outpatient Treatment ◽  
Infectious Complications ◽  
Chronic Lymphatic Leukemia ◽  
Cytostatic Drugs ◽  
Ability To Work ◽  
Lymphatic Leukemia ◽  
Long Time ◽  
Negative Effect

Chronic lymphatic leukemia is second only to acute leukemia in the frequency of infectious complications. In most cases, severe infectious complications are the cause of death in these patients. Modern chemotherapy makes it possible to preserve the ability to work and the life expectancy of patients for a long time. However, the negative effect of cytostatic drugs on the already altered immune system leads to an even greater suppression of immunity and an increase in the number of infectious complications. The search for new ways to combat infections has shown the advisability of long-term outpatient treatment with antibacterial drugs.

Opioid Receptor Gene Expression in the Porcine Immune System

1998 ◽  
pp. 59-65 ◽  
Author(s):  
Mary S. Pampusch ◽  
Mark A. Osinski ◽  
Janet R. Serie ◽  
Michael P. Murtaugh ◽  
David R. Brown
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Opioid Receptor ◽  
Receptor Gene ◽  
Receptor Gene Expression

scholarly journals Rethinking rehabilitation of salt-affected land: new perspectives from Australian experience

2021 ◽  
Author(s):  
John Leake ◽  
Victor Squires ◽  
S Shabala
Keyword(s):  
Ecosystem Services ◽  
Agricultural Production ◽  
Production Systems ◽  
Concerted Effort ◽  
Plant Soil ◽  
Mechanistic Basis ◽  
Australian Experience ◽  
Evolution Of Ideas ◽  
The Cost ◽  
Agricultural Production Systems

Soil salinity is emerging as a major threat to the sustainability of modern agricultural production systems and, historically, land and water degradation due to salinity has defeated civilisations whenever the cost of remediation exceeded the benefits. This work discusses the complexity inherent in working with salinity, and the opportunities where salt damaged land and water is viewed as a resource. It takes a wider look at land and waterscapes, seeing them as systems that link damage and repair across time and space to bridge the divide between the main beneficiaries of ecosystem services and the main actors, farmers, and land managers. We first discuss the mechanistic basis of crop reduction by salinity and evolution of ideas about how to shape the plant-soil-water nexus. We then discuss the needs of farmers and other land users required for adequate planning and land management within the constraints of existing policy. Lastly, an approach that provides a new technical and economic tool for the remediation of land in several land use categories is presented. We conclude that a more concerted effort is required to turn payments for ecosystem services into a true market, accepted as such by the land managers, whose agency is essential so the ‘knowledge of what can be done can be transformed into benefits’. Achieving this will require a transformation in the paradigm of how natural resources are managed.

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