Transcriptome dynamics of a broad host-range cyanophage and its hosts

Cyanobacteria are highly abundant in the oceans and are constantly exposed to lytic viruses. The T4-like cyanomyoviruses are abundant in the marine environment and have broad host-ranges relative to other cyanophages. It is currently unknown whether broad host-range phages specifically tailor their infection program for each host, or employ the same program irrespective of the host infected. Also unknown is how different hosts respond to infection by the same phage. Here we used microarray and RNA-seq analyses to investigate the interaction between the Syn9 T4-like cyanophage and three phylogenetically, ecologically and genomically distinct marine Synechococcus strains: WH7803, WH8102 and WH8109. Strikingly, Syn9 led a nearly identical infection and transcriptional program in all three hosts. Different to previous assumptions for T4-like cyanophages, three temporally regulated gene expression classes were observed. Furthermore, a novel regulatory element controlled early-gene transcription, and host-like promoters drove middle gene transcription, different to the regulatory paradigm for T4. Similar results were found for the P-TIM40 phage during infection of Prochlorococcus NATL2A. Moreover, genomic and metagenomic analyses indicate that these regulatory elements are abundant and conserved among T4-like cyanophages. In contrast to the near-identical transcriptional program employed by Syn9, host responses to infection involved host-specific genes primarily located in hypervariable genomic islands, substantiating islands as a major axis of phage-cyanobacteria interactions. Our findings suggest that the ability of broad host-range phages to infect multiple hosts is more likely dependent on the effectiveness of host defense strategies than on differential tailoring of the infection process by the phage

Creative destruction in science

Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents\u2019 reasoning about day care options, and gender discrimination in hiring decisions. Significance statement It is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void\u2014 reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building. Scientific transparency statement The materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article

Development and Validation of a Symptom-Based Activity Index for Adults With Eosinophilic Esophagitis

Standardized instruments are needed to assess the activity of eosinophilic esophagitis (EoE), to provide endpoints for clinical trials and observational studies. We aimed to develop and validate a patient-reported outcome (PRO) instrument and score, based on items that could account for variations in patients’ assessments of disease severity. We also evaluated relationships between patients’ assessment of disease severity and EoE-associated endoscopic, histologic, and laboratory findings

SynTracker: a synteny based tool for tracking microbial strains

In the human gut microbiome, specific strains emerge due to within-host evolution and can occasionally be transferred to or from other hosts. Phenotypic variance among such strains can have implications for strain transmission and interaction with the host. Surveilling strains of the same species, within and between individuals, can further our knowledge about the way in which microbial diversity is generated and maintained in host populations. Existing methods to estimate the biological relatedness of similar strains usually rely on either detection of single nucleotide polymorphisms (SNP), which may include sequencing errors, or on the analysis of pangenomes, which can be limited by the requirement for extensive gene databases. To complement existing methods, we developed SynTracker. This strain-comparison tool is based on synteny comparisons between strains, or the comparison of the arrangement of sequence blocks in two homologous genomic regions in pairs of metagenomic assemblies or genomes. Our method is executed in a species-specific manner, has a low sensitivity to SNPs, does not require a pre-existing database, and can correctly resolve strains using complete or draft genomes and metagenomic samples using <5% of the genome length. When applied to metagenomic datasets, we detected person-specific strains with an average sensitivity of 97% and specificity of 99%, and strain-sharing events in mother-infant pairs. SynTracker can be used to study the population structure of specific microbial species between and within environments, to identify evolutionary trajectories in longitudinal datasets, and to further understanding of strain sharing networks

The developing infant gut microbiome: A strain-level view

At birth, neonates provide a vast habitat awaiting microbial colonization. Microbiome assembly is a complex process involving microbial seeding and succession driven by ecological forces and subject to environmental conditions. These successional events not only significantly affect the ecology and function of the microbiome, but also impact host health. While the establishment of the infant microbiome has been a point of interest for decades, an integrated view focusing on strain level colonization has been lacking until recently. Technological and computational advancements enabling strain-level analyses of the infant microbiome have demonstrated the immense complexity of this system and allowed for an improved understanding of how strains of the same species spread, colonize, evolve, and affect the host. Here, we review the current knowledge of the establishment and maturation of the infant gut microbiome with particular emphasis on newer discoveries achieved through strain-centric analyses

Isolation and characterization of a novel Lambda-like phage infecting the bloom-forming cyanobacteria Cylindrospermopsis raciborskii

Cylindrospermopsis raciborskii is a central bloom-forming cyanobacteria. However, despite its ecological significance, little is known of its interactions with the phages that infect it. Currently, only a single sequenced genome of a Cylindrospermopsis-infecting phage is publicly available. Here we describe the isolation and characterization of Cr-LKS3, a second phage infecting Cylindrospermopsis. Cr-LKS3 is a siphovirus with a higher genome similarity to prophages within heterotrophic bacteria genomes than to any other cyanophage/cyano-prophage, suggesting that it represents a novel cyanophage group. The function, order and orientation of the 72 genes in the Cr-LKS3 genome are highly similar to those of Escherichia virus Lambda (hereafter Lambda), despite the very low sequence similarity between these phages, showing high evolutionary convergence despite the substantial difference in host characteristics. Similarly to Lambda, the genome of Cr-LKS3 contains various genes that are known to be central to lysogeny, suggesting it can enter a lysogenic cycle. Cr-LKS3 has a unique ability to infect a host with a dramatically different GC content, without carrying any tRNA genes to compensate for this difference. This ability, together with its potential lysogenic lifestyle shed light on the complex interactions between C. raciborskii and its phages

Global ATM security Management - D5.1 Validation Exercise Plan

This document (Validation Exercise Plan), as output of Task 5.1, points out the GAMMA validation objectives (Chapter 3) and strategy (Chapter 4). Then, the validation scenarios are identified (Chapter 5) and the exercise plans are defined (Chapter 6). Thereby, the GAMMA validation activities will mainly follow the procedure advocated in the European standard E-OCVM. However, the procedure will be slightly adapted in order to consider the experiences made by the partners in other projects. The GAMMA validation strategy is, thus, a combination of a well-accepted European standard and best practice. The Validation Exercise Plan is a document containing all relevant planning information to be considered in the execution of the validation exercises (WP9), including the Validation Scenarios Definition and Description

Global ATM security Management - D5.2 Validation Platform System Requirements Document

Based on the ATM security requirements (T4.1), ATM security architecture (T4.2) and Scenarios, methods and means for validation exercises (T5.1), the high level system requirements for the validation environment, for the prototypes and for the validation platform subsets (wherever used in SMP stand alone, partial or full validation exercises) have to be fulfilled. In particular the system requirements for each single validation platform subset will address input / output protocols and interfaces towards any other possible prototype and/or validation platform subset interconnected. The definition of these requirements is done in Task 5.2 and documented in this report