scholarly journals Predicting experimental designs leading to rewiring of transcription program and evolution of anticipatory regulation in E. coli

2020 ◽  
Author(s):  
Anjali Mahilkar ◽  
Akshat Mall ◽  
Supreet Saini
Keyword(s):  
Regulatory Networks ◽  
Quantitative Model ◽  
Environmental Cues ◽  
Anticipatory Response ◽  
Experimental Conditions ◽  
Bacterial Populations ◽  
E Coli ◽  
Temporal Cues ◽  
Darwinian Fitness ◽  
Pentose Sugar

AbstractEnvironmental cues in an ecological niche are temporal. In response to these temporal cues, bacteria have been known to exhibit learning or conditioning, whereby they trigger response to a yet to appear cue, anticipating its actual arrival in the near future. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature in the regulatory networks in microorganisms. However, the conditions under which an anticipatory response optimizes cellular fitness are not known. Nor has evolution of anticipatory regulation in laboratory conditions been experimentally demonstrated. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and present the key variables in cellular physiology associated with response to the cues whose modulation is likely to lead to evolution of anticipatory regulatory response. We predict experimental conditions, which are likely to lead to demonstration of rewiring of regulation, and evolution of anticipatory response in bacterial populations. Using inputs from the modeling results, we evolve E. coli in alternating environments of the pentose sugar rhamnose and paraquat, which induces oxidative stress. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation. Thus, we argue that in niches where environmental stimuli have a cyclical nature, conditioning evolves in a population as an adaptive response.

scholarly journals Experimental Evolution of Anticipatory Regulation in Escherichia coli

2022 ◽  
Vol 12 ◽  
Author(s):  
Anjali Mahilkar ◽  
Pavithra Venkataraman ◽  
Akshat Mall ◽  
Supreet Saini
Keyword(s):  
Escherichia Coli ◽  
Experimental Evolution ◽  
Adaptive Response ◽  
Regulatory Networks ◽  
Quantitative Model ◽  
Environmental Cues ◽  
Anticipatory Response ◽  
Global Regulators ◽  
Temporal Cues ◽  
Darwinian Fitness

Environmental cues in an ecological niche are often temporal in nature. For instance, in temperate climates, temperature is higher in daytime compared to during night. In response to these temporal cues, bacteria have been known to exhibit anticipatory regulation, whereby triggering response to a yet to appear cue. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature of regulatory networks in microorganisms. However, the conditions under which an anticipatory response evolves as an adaptive response are not known. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and predict variables which are likely important for evolution of anticipatory regulatory response. We follow this with experimental evolution of Escherichia coli in alternating environments of rhamnose and paraquat for ∼850 generations. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation. As a result, pre-exposure to rhamnose leads to a greater fitness in paraquat environment. Genome sequencing reveals that this anticipatory regulation is encoded via mutations in global regulators. Overall, our study contributes to understanding of how environment shapes the topology of regulatory networks in an organism.

scholarly journals Digital control of c-di-GMP in E. coli balances population-wide developmental transitions and phage sensitivity

2021 ◽  
Author(s):  
Alberto Reinders ◽  
Benjamin Sellner ◽  
Firas Fadel ◽  
Margo van Berkum ◽  
Andreas Kaczmarczyk ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Signaling Molecules ◽  
Bet Hedging ◽  
Dynamic Changes ◽  
Bacterial Populations ◽  
Developmental Transitions ◽  
E Coli ◽  
Large Numbers ◽  
Phage Sensitivity ◽  
Synthesis And Degradation

AbstractNucleotide-based signaling molecules (NSMs) are widespread in bacteria and eukaryotes, where they control important physiological and behavioral processes. In bacteria, NSM-based regulatory networks are highly complex, entailing large numbers of enzymes involved in the synthesis and degradation of active signaling molecules. How the converging input from multiple enzymes is transformed into robust and unambiguous cellular responses has remained unclear. Here we show that Escherichia coli converts dynamic changes of c-di-GMP into discrete binary signaling states, thereby generating heterogeneous populations with either high or low c-di-GMP. This is mediated by an ultrasensitive switch protein, PdeL, which senses the prevailing cellular concentration of the signaling molecule and couples this information to c-di-GMP degradation and transcription feedback boosting its own expression. We demonstrate that PdeL acts as a digital filter that facilitates precise developmental transitions, confers cellular memory, and generates functional heterogeneity in bacterial populations to evade phage predation. Based on our findings, we propose that bacteria apply ultrasensitive regulatory switches to convert dynamic changes of NSMs into binary signaling modes to allow robust decision-making and bet-hedging for improved overall population fitness.

scholarly journals MCO: towards an ontology and unified vocabulary for a framework-based annotation of microbial growth conditions

2017 ◽  
Author(s):  
VH Tierrafría ◽  
C Mejía-Almonte ◽  
JM Camacho-Zaragoza ◽  
H Salgado ◽  
K Alquicira ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Phenotypic Expression ◽  
Biomedical Ontology ◽  
Growth Conditions ◽  
Controlled Vocabulary ◽  
Experimental Conditions ◽  
E Coli ◽  
K 12

AbstractMotivationA major component in our understanding of the biology of an organism is the mapping of its genotypic potential into the repertoire of its phenotypic expression profiles. This genotypic to phenotypic mapping is executed by the machinery of gene regulation that turns genes on and off, which in microorganisms is essentially studied by changes in growth conditions and genetic modifications. Although many efforts have been made to systematize the annotation of experimental conditions in microbiology, the available annotation is not based on a consistent and controlled vocabulary for the unambiguous description of growth conditions, making difficult the identification of biologically meaningful comparisons of knowledge generated in different experiments or laboratories, a task urgently needed given the massive amounts of data generated by high throughput (HT) technologies.ResultsWe curated terms related to experimental conditions that affect gene expression inE. coliK-12. Since this is the best studied microorganism, the collected terms are the seed for the first version of the Microbial Conditions Ontology (MCO), a controlled and structured vocabulary that can be expanded to annotate microbial conditions in general. Moreover, we developed an annotation framework using the MCO terms to describe experimental conditions, providing the foundation to identify regulatory networks that operate under a particular condition. MCO supports comparisons of HT-derived data from different repositories. In this sense, we started to map common RegulonDB terms and Colombos bacterial expression compendia terms to MCO.Availability and ImplementationAs far as we know, MCO is the first ontology for growth conditions of any bacterial organism and it is available athttp://regulondb.ccg.unam.mx/. Furthermore, we will disseminate MCO throughout the Open Biomedical Ontology (OBO) Foundry in order to set a standard for the annotation of gene expression data derived from conventional as well as HT experiments inE. coliand other microbial organisms. This will enable the comparison of data from diverse data [email protected],[email protected]

scholarly journals Decay of Fecal Indicator Bacterial Populations and Bovine-Associated Source-Tracking Markers in Freshly Deposited Cow Pats

2013 ◽  
Vol 80 (1) ◽  
pp. 110-118 ◽  
Author(s):  
Adelumola Oladeinde ◽  
Thomas Bohrmann ◽  
Kelvin Wong ◽  
S. T. Purucker ◽  
Ken Bradshaw ◽  
...  
Keyword(s):  
Decay Rate ◽  
Fecal Indicator Bacteria ◽  
Decay Rates ◽  
Indicator Bacteria ◽  
Source Tracking ◽  
Fecal Indicator ◽  
Bacterial Populations ◽  
Content Type ◽  
E Coli ◽  
Decay Dynamic

ABSTRACTUnderstanding the survival of fecal indicator bacteria (FIB) and microbial source-tracking (MST) markers is critical to developing pathogen fate and transport models. Although pathogen survival in water microcosms and manure-amended soils is well documented, little is known about their survival in intact cow pats deposited on pastures. We conducted a study to determine decay rates of fecal indicator bacteria (Escherichia coliand enterococci) and bovine-associated MST markers (CowM3, Rum-2-bac, and GenBac) in 18 freshly deposited cattle feces from three farms in northern Georgia. Samples were randomly assigned to shaded or unshaded treatment in order to determine the effects of sunlight, moisture, and temperature on decay rates. A general linear model (GLM) framework was used to determine decay rates. Shading significantly decreased the decay rate of theE. colipopulation (P< 0.0001), with a rate of −0.176 day−1for the shaded treatment and −0.297 day−1for the unshaded treatment. Shading had no significant effect on decay rates of enterococci, CowM3, Rum-2-bac, and GenBac (P> 0.05). In addition,E. colipopulations showed a significant growth rate (0.881 day−1) in the unshaded samples during the first 5 days after deposition. UV-B was the most important parameter explaining the decay rate ofE. colipopulations. A comparison of the decay behaviors among all markers indicated that enterococcus concentrations exhibit a better correlation with the MST markers thanE. coliconcentrations. Our results indicate that bovine-associated MST markers can survive in cow pats for at least 1 month after excretion, and although their decay dynamic differs from the decay dynamic ofE. colipopulations, they seem to be reliable markers to use in combination with enterococci to monitor fecal pollution from pasture lands.

scholarly journals The Boron & De Weer Model of Intracellular pH Regulation

2020 ◽  
Author(s):  
Rossana Occhipinti ◽  
Soroush Safaei ◽  
Peter J. Hunter ◽  
Walter F. Boron
Keyword(s):  
Cell Membrane ◽  
Intracellular Ph ◽  
Ph Regulation ◽  
Quantitative Model ◽  
Historical Background ◽  
Acid Base ◽  
Experimental Conditions ◽  
Subsequent Work ◽  
Energy Dependent ◽  
Parameter Values

The classic Boron & De Weer (1976) paper provided the first evidence of active regulation of pH} in cells by an energy-dependent acid-base transporter. These authors also developed a quantitative model --- comprising passive fluxes of acid-base equivalents across the cell membrane, intracellular reactions, and an active transport mechanism in the cell membrane (modelled as a proton pump) --- to help interpret their measurements of intracellular pH under perturbations of both extracellular CO2/HCO3- and extracellular NH3/NH4+. This Physiome paper seeks to make that model, and the experimental conditions under which it was developed, available in a reproducible and well-documented form, along with a software implementation that makes the model easy to use and understand. We have also taken the opportunity to update some of the units used in the original paper, and to provide a few parameter values that were missing in the original paper. Finally, we provide an historical background to the Boron & De Weer (1976) proposal for active pH regulation and a commentary on subsequent work that has enriched our understanding of this most basic aspect of cellular physiology.

scholarly journals Normalisr: normalization and association testing for single-cell CRISPR screen and co-expression

2021 ◽  
Author(s):  
Lingfei Wang
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Large Scale ◽  
High Sensitivity ◽  
Statistical Hypothesis ◽  
P Value ◽  
Statistical Hypothesis Testing ◽  
Experimental Conditions ◽  
Library Size ◽  
Association Testing

AbstractSingle-cell RNA sequencing (scRNA-seq) provides unprecedented technical and statistical potential to study gene regulation but is subject to technical variations and sparsity. Here we present Normalisr, a linear-model-based normalization and statistical hypothesis testing framework that unifies single-cell differential expression, co-expression, and CRISPR scRNA-seq screen analyses. By systematically detecting and removing nonlinear confounding from library size, Normalisr achieves high sensitivity, specificity, speed, and generalizability across multiple scRNA-seq protocols and experimental conditions with unbiased P-value estimation. We use Normalisr to reconstruct robust gene regulatory networks from trans-effects of gRNAs in large-scale CRISPRi scRNA-seq screens and gene-level co-expression networks from conventional scRNA-seq.

scholarly journals Viral fitness predicts the magnitude and direction of perturbations in the infected host transcriptome

2017 ◽  
Author(s):  
Héctor Cervera ◽  
Silvia Ambrós ◽  
Guillermo P. Bernet ◽  
Guillermo Rodrigo ◽  
Santiago F. Elena
Keyword(s):  
Rna Silencing ◽  
Regulatory Networks ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Viral Fitness ◽  
Evolutionary Potential ◽  
Expression Of Genes ◽  
Darwinian Fitness ◽  
Functional Classes ◽  
Host Genes

Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a mesoscopic property that captures into a single figure differences in performance at every stage of viral infection. But to which extent viral fitness results from particular molecular interactions with host factors and regulatory networks during infection? Can we identify host genes, and then functional classes, whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus (TEV) that differ in fitness. We found that the larger the fitness differences among genotypes, the more dissimilar the transcriptomic profiles are. Consistently, two different mutations, one in the viral RNA polymerase and another in the viral suppressor of RNA silencing, that led to close fitness values, also resulted in significantly similar gene expression profiles. Moreover, we identified host genes whose expression showed a significant correlation, positive or negative, with TEV fitness. Over-expression of genes with positive correlation activates hormone-and RNA silencing-mediated pathways of plant defense. By contrast, under-expression of genes negatively correlated reduces metabolism, growth, and development. Overall, these results reveal the high information content of viral fitness, and suggest its potential use to predict differences in genomic profiles of infected hosts.

scholarly journals Universal attenuators and their interactions with feedback loops in gene regulatory networks

2016 ◽  
Author(s):  
Dianbo Liu ◽  
Luca Albergante ◽  
Timothy J Newman
Keyword(s):  
Gene Expression ◽  
Gene Regulatory Networks ◽  
Gene Networks ◽  
Regulatory Networks ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Feedback Loops ◽  
Human Cancer Cell ◽  
E Coli ◽  
Gene Regulatory

AbstractUsing a combination of mathematical modelling, statistical simulation and large-scale data analysis we study the properties of linear regulatory chains (LRCs) within gene regulatory networks (GRNs). Our modelling indicates that downstream genes embedded within LRCs are highly insulated from the variation in expression of upstream genes, and thus LRCs act as attenuators. This observation implies a progressively weaker functionality of LRCs as their length increases. When analysing the preponderance of LRCs in the GRNs of E. coli K12 and several other organisms, we find that very long LRCs are essentially absent. In both E. coli and M. tuberculosis we find that four-gene LRCs are intimately linked to identical feedback loops that are involved in potentially chaotic stress response, indicating that the dynamics of these potentially destabilising motifs are strongly restrained under homeostatic conditions. The same relationship is observed in a human cancer cell line (K562), and we postulate that four-gene LRCs act as “universal attenuators”. These findings suggest a role for long LRCs in dampening variation in gene expression, thereby protecting cell identity, and in controlling dramatic shifts in cell-wide gene expression through inhibiting chaos-generating motifs.In briefWe present a general principle that linear regulatory chains exponentially attenuate the range of expression in gene regulatory networks. The discovery of a universal interplay between linear regulatory chains and genetic feedback loops in microorganisms and a human cancer cell line is analysed and discussed.HighlightsWithin gene networks, linear regulatory chains act as exponentially strong attenuators of upstream variationBecause of their exponential behaviour, linear regulatory chains beyond a few genes provide no additional functionality and are rarely observed in gene networks across a range of different organismsNovel interactions between four-gene linear regulatory chains and feedback loops were discovered in E. coli, M. tuberculosis and human cancer cells, suggesting a universal mechanism of control.

The electro-deposition of silver on stationary and rotating glassy carbon discs

1977 ◽  
Vol 55 (23) ◽  
pp. 4037-4044 ◽  
Author(s):  
Remigio Germano Barradas ◽  
Stephen Fletcher ◽  
Sandor Szabo
Keyword(s):  
Experimental Data ◽  
Mass Transport ◽  
Glassy Carbon ◽  
Quantitative Model ◽  
Nucleation And Growth ◽  
Experimental Conditions ◽  
Electro Deposition ◽  
Transport Effects ◽  
Mass Transport Effects

The deposition of silver onto glassy carbon is described. The solution consisted of 10−2 M AgClO4 in 1.0 M HClO4. Experiments reveal the difficulties in trying to separate nucleation and growth phenomena from mass transport effects. A simple semi-quantitative model is proposed to explain the experimental data. It is also shown that the deposition reaction is not completely reversible under certain experimental conditions.

Microbiological Status of Fresh Beef Cuts

2006 ◽  
Vol 69 (6) ◽  
pp. 1456-1459 ◽  
Author(s):  
J. D. STOPFORTH ◽  
M. LOPES ◽  
J. E. SHULTZ ◽  
R. R. MIKSCH ◽  
M. SAMADPOUR
Keyword(s):  
Total Coliform ◽  
Incidence Rates ◽  
Microbial Populations ◽  
Plate Count ◽  
Bacterial Populations ◽  
E Coli ◽  
Coliform Count ◽  
Processing Plants ◽  
Aerobic Plate Count ◽  
Whole Muscle

Fresh beef samples (n = 1,022) obtained from two processing plants in the Midwest (July to December 2003) were analyzed for levels of microbial populations (total aerobic plate count, total coliform count, and Escherichia coli count) and for the presence or absence of E. coli O157:H7 and Salmonella. A fresh beef cut sample was a 360-g composite of 6-g portions excised from the surface of 60 individual representative cuts in a production lot. Samples of fresh beef cuts yielded levels of 4.0 to 6.2, 1.1 to 1.8, and 0.8 to 1.0 log CFU/g for total aerobic plate count, total coliform count, and E. coli count, respectively. There did not appear to be substantial differences or obvious trends in bacterial populations on different cuts. These data may be useful in establishing a baseline or a benchmark of microbiological levels of contamination of beef cuts. Mean incidence rates of E. coli O157:H7 and Salmonella on raw beef cuts were 0.3 and 2.2%, respectively. Of the 1,022 samples analyzed, cuts testing positive for E. coli O157:H7 included top sirloin butt (0.9%) and butt, ball tip (2.1%) and for Salmonella included short loins (3.4%), strip loins (9.6%), rib eye roll (0.8%), shoulder clod (3.4%), and clod, top blade (1.8%). These data provide evidence of noticeable incidence of pathogens on whole muscle beef and raise the importance of such contamination on product that may be mechanically tenderized. Levels of total aerobic plate count, total coliform count, and E. coli count did not (P ≥ 0.05) appear to be associated with the presence of E. coli O157:H7 and Salmonella on fresh beef cuts. E. O157:H7 was exclusively isolated from cuts derived from the sirloin area of the carcass. Salmonella was exclusively isolated from cuts derived from the chuck, rib, and loin areas of the carcass. Results of this study suggest that contamination of beef cuts may be influenced by the region of the carcass from which they are derived.

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