scholarly journals Prophages in Lactobacillus reuteri Are Associated with Fitness Trade-Offs but Can Increase Competitiveness in the Gut Ecosystem

2019 ◽  
Vol 86 (1) ◽  
Author(s):  
Jee-Hwan Oh ◽  
Xiaoxi B. Lin ◽  
Shenwei Zhang ◽  
Stephanie L. Tollenaar ◽  
Mustafa Özçam ◽  
...  
Keyword(s):  
Competitive Advantage ◽  
Intestinal Tract ◽  
Lactobacillus Reuteri ◽  
Distal Colon ◽  
Biologically Active ◽  
Trade Off ◽  
Content Type ◽  
Trade Offs ◽  
Phage Production

ABSTRACT The gut microbiota harbors a diverse phage population that is largely derived from lysogens, which are bacteria that contain dormant phages in their genome. While the diversity of phages in gut ecosystems is getting increasingly well characterized, knowledge is limited on how phages contribute to the evolution and ecology of their host bacteria. Here, we show that biologically active prophages are widely distributed in phylogenetically diverse strains of the gut symbiont Lactobacillus reuteri. Nearly all human- and rodent-derived strains, but less than half of the tested strains of porcine origin, contain active prophages, suggesting different roles of phages in the evolution of host-specific lineages. To gain insight into the ecological role of L. reuteri phages, we developed L. reuteri strain 6475 as a model to study its phages. After administration to mice, L. reuteri 6475 produces active phages throughout the intestinal tract, with the highest number detected in the distal colon. Inactivation of recA abolished in vivo phage production, which suggests that activation of the SOS response drives phage production in the gut. In conventional mice, phage production reduces bacterial fitness as fewer wild-type bacteria survive gut transit compared to the mutant lacking prophages. However, in gnotobiotic mice, phage production provides L. reuteri with a competitive advantage over a sensitive host. Collectively, we uncovered that the presence of prophages, although associated with a fitness trade-off, can be advantageous for a gut symbiont by killing a competitor strain in its intestinal niche. IMPORTANCE Bacteriophages derived from lysogens are abundant in gut microbiomes. Currently, mechanistic knowledge is lacking on the ecological ramifications of prophage carriage yet is essential to explain the abundance of lysogens in the gut. An extensive screen of the bacterial gut symbiont Lactobacillus reuteri revealed that biologically active prophages are widely distributed in this species. L. reuteri 6475 produces phages throughout the mouse intestinal tract, but phage production is associated with reduced fitness of the lysogen. However, phage production provides a competitive advantage in direct competition with a nonlysogenic strain of L. reuteri that is sensitive to these phages. This combination of increased competition with a fitness trade-off provides a potential explanation for the domination of lysogens in gut ecosystem and how lysogens can coexist with sensitive hosts.

scholarly journals Exploiting Prophage-Mediated Lysis for Biotherapeutic Release byLactobacillus reuteri

2019 ◽  
Vol 85 (10) ◽  
Author(s):  
Laura M. Alexander ◽  
Jee-Hwan Oh ◽  
Donald S. Stapleton ◽  
Kathryn L. Schueler ◽  
Mark P. Keller ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Secretory Pathway ◽  
Lactobacillus Reuteri ◽  
Gastrointestinal Transit ◽  
Biologically Active ◽  
Content Type ◽  
Extracellular Milieu ◽  
Therapeutic Molecules

ABSTRACTLactobacillus reuterihas the potential to be developed as a microbial therapeutic delivery platform because of an established safety profile, health-promoting properties, and available genome editing tools. Here, we show thatL. reuteriVPL1014 exhibits a low mutation rate compared to other Gram-positive bacteria, which we expect will contribute to the stability of genetically modified strains. VPL1014 encodes two biologically active prophages, which are induced during gastrointestinal transit. We hypothesized that intracellularly accumulated recombinant protein can be released following bacteriophage-mediated lysis. To test this, we engineered VPL1014 to accumulate leptin, our model protein, inside the cell.In vitroprophage induction of recombinant VPL1014 released leptin into the extracellular milieu, which corresponded to bacteriophage production. We also employed a plasmid system that does not require antibiotic in the growth medium for plasmid maintenance. Collectively, these data provide new avenues to exploit native prophages to deliver therapeutic molecules.IMPORTANCELactic acid bacteria (LAB) have been explored as potential biotherapeutic vehicles for the past 20 years. To secrete a therapeutic in the extracellular milieu, one typically relies on the bacterial secretion pathway, i.e., the Sec pathway. Overexpression of a secreted protein can overload the secretory pathway and impact the organism’s fitness, and optimization of the signal peptide is also required to maximize the efficiency of the release of mature protein. Here, we describe a previously unexplored approach to release therapeutics from the probioticLactobacillus reuteri. We demonstrate that an intracellularly accumulated recombinant protein is released following prophage activation. Since we recently demonstrated that prophages are activated during gastrointestinal transit, we propose that this method will provide a straightforward and efficient approach to deliver therapeuticsin vivo.

A new framework for time-cost trade-off considering float loss impact

2017 ◽  
Vol 22 (1) ◽  
pp. 20-36 ◽  
Author(s):  
Sameh Monir El-Sayegh ◽  
Rana Al-Haj
Keyword(s):  
Optimization Technique ◽  
Time Cost ◽  
Trade Off ◽  
Deterministic Optimization ◽  
Content Type ◽  
Project Duration ◽  
Trade Offs ◽  
Project Objectives ◽  
The Impact ◽  
New Framework

Purpose The purpose of this paper is to propose a new framework for time–cost trade-off. The new framework provides the optimum time–cost value taking into account the float loss impact. Design/methodology/approach The stochastic framework uses Monte Carlo Simulation to calculate the effect of float loss on risk. This is later translated into an added cost to the trade-off problem. Five examples, from literature, are solved using the proposed framework to test the applicability of the developed framework. Findings The results confirmed the research hypothesis that the new optimum solution will be at a higher duration and cost but at a lower risk compared to traditional methods. The probabilities of finishing the project on time using the developed framework in all five cases were better than those using the classical deterministic optimization technique. Originality/value The objective of time–cost trade-off is to determine the optimum project duration corresponding to the minimum total cost. Time–cost trade-off techniques result in reducing the available float for noncritical activities and thus increasing the schedule risks. Existing deterministic optimization technique does not consider the impact of the float loss within the noncritical activities when the project duration is being crashed. The new framework allows project managers to exercise new trade-offs between time, cost and risk which will ultimately improve the chances of achieving project objectives.

scholarly journals The transformative service paradox: the dilemma of wellbeing trade-offs

2020 ◽  
Vol 31 (4) ◽  
pp. 637-663
Author(s):  
Rebekah Russell–Bennett ◽  
Rory Mulcahy ◽  
Kate Letheren ◽  
Ryan McAndrew ◽  
Uwe Dulleck
Keyword(s):  
Laboratory Experiment ◽  
Qualitative Interviews ◽  
Implicit Assumption ◽  
Trade Off ◽  
Content Type ◽  
Individual Level ◽  
Trade Offs ◽  
Physical Wellbeing ◽  
The Individual ◽  
Future Implication

PurposeA transformative service aims to improve wellbeing; however, current approaches have an implicit assumption that all wellbeing dimensions are equal and more dimensions led to higher wellbeing. The purpose of this paper is to present evidence for a new framework that identifies the paradox of competing wellbeing dimensions for both the individual and others in society – the transformative service paradox (TSP).Design/methodology/approachData is drawn from a mixed-method approach using qualitative (interviews) and quantitative data (lab experiment) in an electricity service context. The first study involves 45 household interviews (n = 118) and deals with the nature of trade-offs at the individual level to establish the concept of the TSP. The second study uses a behavioral economics laboratory experiment (n = 110) to test the self vs. other nature of the trade-off in day-to-day use of electricity.FindingsThe interviews and experiment identified that temporal (now vs. future) and beneficiary-level factors explain why individuals make wellbeing trade-offs for the transformative service of electricity. The laboratory experiment showed that when the future implication of the trade-off is made salient, consumers are more willing to forego physical wellbeing for environmental wellbeing, whereas when the “now” implication is more salient consumers forego financial wellbeing for physical wellbeing.Originality/valueThis research introduces the term “Transformative Service Paradox” and identifies two factors that explain why consumers make wellbeing trade-offs at the individual level and at the societal level; temporal (now vs. future) and wellbeing beneficiary.

scholarly journals Magnesium Sensing Regulates Intestinal Colonization of Enterohemorrhagic Escherichia coli O157:H7

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Yutao Liu ◽  
Runhua Han ◽  
Junyue Wang ◽  
Pan Yang ◽  
Fang Wang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Large Intestine ◽  
Intestinal Tract ◽  
Regulatory System ◽  
Regulatory Pathway ◽  
Content Type ◽  
E Coli ◽  
Low Magnesium ◽  
Enterocyte Effacement

ABSTRACT The large intestinal pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 detects host cues to regulate virulence gene expression during colonization and infection. However, virulence regulatory mechanisms of EHEC O157:H7 in the human large intestine are not fully understood. Herein, we identified a virulence-regulating pathway where the PhoQ/PhoP two-component regulatory system senses low magnesium levels and signals to the O island 119-encoded Z4267 (LmiA; low magnesium-induced regulator A), directly activating loci of enterocyte effacement genes to promote EHEC O157:H7 adherence in the large intestine. Disruption of this pathway significantly decreased EHEC O157:H7 adherence in the mouse intestinal tract. Moreover, feeding mice a magnesium-rich diet significantly reduced EHEC O157:H7 adherence in vivo. This LmiA-mediated virulence regulatory pathway is also conserved among several EHEC and enteropathogenic E. coli serotypes; therefore, our findings support the use of magnesium as a dietary supplement and provide greater insights into the dietary cues that can prevent enteric infections. IMPORTANCE Sensing specific gut metabolites is an important strategy for inducing crucial virulence programs by enterohemorrhagic Escherichia coli (EHEC) O157:H7 during colonization and infection. Here, we identified a virulence-regulating pathway wherein the PhoQ/PhoP two-component regulatory system signals to the O island 119-encoded low magnesium-induced regulator A (LmiA), which, in turn, activates locus of enterocyte effacement (LEE) genes to promote EHEC O157:H7 adherence in the low-magnesium conditions of the large intestine. This regulatory pathway is widely present in a range of EHEC and enteropathogenic E. coli (EPEC) serotypes. Disruption of this pathway significantly decreased EHEC O157:H7 adherence in the mouse intestinal tract. Moreover, mice fed a magnesium-rich diet showed significantly reduced EHEC O157:H7 adherence in vivo, indicating that magnesium may help in preventing EHEC and EPEC infection in humans.

Australian customer willingness to pay and wait for mass-customised products

2018 ◽  
Vol 30 (1) ◽  
pp. 106-120 ◽  
Author(s):  
Hassan Daronkola Kalantari ◽  
Lester Johnson
Keyword(s):  
Cluster Analysis ◽  
Design Methodology ◽  
Additional Time ◽  
Market Segments ◽  
Trade Off ◽  
Content Type ◽  
Mass Customisation ◽  
Product Categories ◽  
Trade Offs ◽  
To Receive

Purpose The purpose of this paper is to find out how consumers constantly trade off the potential extra cost of mass customisation with the additional time they have to wait to receive their customised products. Design/methodology/approach The authors examine this issue by using conjoint analysis to estimate the trade-offs using a sample of Australian consumers. The authors use cluster analysis to form market segments in the three product categories examined. Findings The segments demonstrate that there are groups of customers who are quite willing to trade-off price with waiting time. The results have significant implications for Australian manufacturers who are contemplating moving into mass customisation. Originality/value Many researchers have investigated the issue of a customer’s readiness to buy a customised product. In particular, they have examined whether customers are willing to pay extra for a mass-customised product, whether they would spend some time to design it, as well as wait to receive it. There has been no study that has examined all three factors simultaneously. The results of this study can help manufacturers form a better understanding of customer willingness for purchasing mass-customised products.

scholarly journals Lactobacillus reuteri 100-23 Modulates Urea Hydrolysis in the Murine Stomach

2014 ◽  
Vol 80 (19) ◽  
pp. 6104-6113 ◽  
Author(s):  
Charlotte M. Wilson ◽  
Diane Loach ◽  
Blair Lawley ◽  
Tracey Bell ◽  
Ian M. Sims ◽  
...  
Keyword(s):  
Stable Isotope ◽  
Lactobacillus Reuteri ◽  
Urine Analysis ◽  
Acid Tolerance ◽  
Laboratory Culture ◽  
Urea Hydrolysis ◽  
Content Type ◽  
Urease Production

ABSTRACTComparisons ofin vivo(mouse stomach) andin vitro(laboratory culture) transcriptomes ofLactobacillus reuteristrain 100-23 were made by microarray analysis. These comparisons revealed the upregulation of genes associated with acid tolerance, including urease production, in the mouse stomach. Inactivation of theureCgene reduced the acid tolerance of strain 100-23in vitro, and the mutant was outcompeted by the wild type in the gut of ex-Lactobacillus-free mice. Urine analysis showed that stable isotope-labeled urea, administered by gavage, was metabolized to a greater extent inLactobacillus-free mice than animals colonized by strain 100-23. This surprising observation was associated with higher levels of urease activity and fecal-type bacteria in the stomach digesta ofLactobacillus-free mice. Despite the modulation of urea hydrolysis in the stomach, recycling of urea nitrogen in the murine host was not affected since the essential amino acid isoleucine, labeled with a stable isotope, was detected in the livers of bothLactobacillus-free and 100-23-colonized animals. Therefore, our experiments reveal a new and unexpected impact ofLactobacilluscolonization on urea hydrolysis in the murine gut.

scholarly journals Optimal maintenance scheduling for local public purpose buildings

2016 ◽  
Vol 34 (2) ◽  
pp. 120-135 ◽  
Author(s):  
Arnt O. Hopland ◽  
Sturla F. Kvamsdal
Keyword(s):  
Local Governments ◽  
Formal Model ◽  
Maintenance Scheduling ◽  
Trade Off ◽  
Content Type ◽  
Maintenance Schedule ◽  
Public Purpose ◽  
Trade Offs ◽  
Optimal Maintenance ◽  
The Cost

Purpose – The purpose of this paper is to set up and analyze a formal model for maintenance scheduling for local government purpose buildings. Design/methodology/approach – The authors formulate the maintenance scheduling decision as a dynamic optimization problem, subject to an accelerating decay. This approach offers a formal, yet intuitive, weighting of an important trade-off when deciding a maintenance schedule. Findings – The optimal maintenance schedule reflects a trade-off between the interest rate and the rate at which the decay accelerates. The prior reflects the alternative cost, since the money spent on maintenance could be saved and earn interests, while the latter reflects the cost of postponing maintenance. Importantly, it turns out that it is sub-optimal to have a cyclical maintenance schedule where the building is allowed to decay and then be intensively maintained before decaying again. Rather, local governments should focus the maintenance either early in the building’s life-span and eventually let it decay toward replacement/abandonment or first let it decay to a target level and then keep it there until replacement/abandonment. Which of the two is optimal depends on the trade-off between the alternative cost and the cost of postponing maintenance. Originality/value – The paper provides a first formal inquiry into important trade-offs that are important for maintenance scheduling of local public purpose buildings.

scholarly journals Population Pharmacokinetic and Pharmacodynamic Modeling of Amodiaquine and Desethylamodiaquine in Women with Plasmodium vivax Malaria during and after Pregnancy

2012 ◽  
Vol 56 (11) ◽  
pp. 5764-5773 ◽  
Author(s):  
Joel Tarning ◽  
Palang Chotsiri ◽  
Vincent Jullien ◽  
Marcus J. Rijken ◽  
Martin Bergstrand ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Plasmodium Vivax ◽  
Plasma Concentrations ◽  
Inhibitory Effect ◽  
Biologically Active ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Content Type ◽  
Plasmodium Vivax Malaria

ABSTRACTAmodiaquine is effective for the treatment ofPlasmodium vivaxmalaria, but there is little information on the pharmacokinetic and pharmacodynamic properties of amodiaquine in pregnant women with malaria. This study evaluated the population pharmacokinetic and pharmacodynamic properties of amodiaquine and its biologically active metabolite, desethylamodiaquine, in pregnant women withP. vivaxinfection and again after delivery. Twenty-seven pregnant women infected withP. vivaxmalaria on the Thai-Myanmar border were treated with amodiaquine monotherapy (10 mg/kg/day) once daily for 3 days. Nineteen women, with and withoutP. vivaxinfections, returned to receive the same amodiaquine dose postpartum. Nonlinear mixed-effects modeling was used to evaluate the population pharmacokinetic and pharmacodynamic properties of amodiaquine and desethylamodiaquine. Amodiaquine plasma concentrations were described accurately by lagged first-order absorption with a two-compartment disposition model followed by a three-compartment disposition of desethylamodiaquine under the assumption of completein vivoconversion. Body weight was implemented as an allometric function on all clearance and volume parameters. Amodiaquine clearance decreased linearly with age, and absorption lag time was reduced in pregnant patients. Recurrent malaria infections in pregnant women were modeled with a time-to-event model consisting of a constant-hazard function with an inhibitory effect of desethylamodiaquine. Amodiaquine treatment reduced the risk of recurrent infections from 22.2% to 7.4% at day 35. In conclusion, pregnancy did not have a clinically relevant impact on the pharmacokinetic properties of amodiaquine or desethylamodiaquine. No dose adjustments are required in pregnancy.

Exploring the trade-off between liquidity, risk and return under sectoral diversification across distinct economic settings

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Carla Henriques ◽  
Elisabete Neves
Keyword(s):  
Economic Crisis ◽  
Liquidity Risk ◽  
Investment Strategies ◽  
Objective Functions ◽  
Cardinality Constraints ◽  
Risk And Return ◽  
Trade Off ◽  
Content Type ◽  
Risk Increase ◽  
Trade Offs

PurposeThis paper aims to explore the trade-off between liquidity, risk and return under sectoral diversification across distinct economic settings and investment strategies.Design/methodology/approachA novel multi-objective portfolio model is proposed to assess investment decisions under sectoral diversification, where the objective functions and constraints are interval-valued. The objective functions used are risk minimization (through the semi-absolute deviation measure of risk), maximization of liquidity (using turnover as a proxy) and the maximization of logarithmic return. Besides coherence constraints (imposing that the sum of the percentages of investment assigned to each stock should be equal to 100%), constraints regarding the maximum proportion of capital that can be invested (ensuring a minimum level of diversification) and cardinality constraints (to account for transaction costs) are also imposed.FindingsBesides the trade-off between return and risk, the study findings highlight a trade-off between liquidity and return and a positive relationship between risk and liquidity. Under an economic crisis scenario, the trade-off between return and liquidity is reduced. With the economic recovery, the levels of risk increase when contrasted with the setting of the economic crisis. The highest liquidity levels are reached with the economic boom, whereas the highest returns are obtained with the economic recession.Originality/valueThis paper suggests a new modeling approach for assessing the trade-offs between liquidity, risk and return under different scenarios and investment strategies. A new interactive procedure inspired on the reference point approach is also proposed to obtain possibly efficient portfolios according to the investor's preferences. Regarding previous approaches suggested in the literature, this new procedure allows obtaining both supported and unsupported efficient solutions when cardinality constraints are included.

Sorry, no carnitas: balancing “Food with Integrity” and growth at Chipotle

2015 ◽  
Vol 11 (3) ◽  
pp. 369-371 ◽  
Author(s):  
Rebecca J. Morris
Keyword(s):  
Strategic Management ◽  
Competitive Advantage ◽  
Stakeholder Analysis ◽  
Primary Sources ◽  
Annual Reports ◽  
Content Type ◽  
Mba Students ◽  
Secondary Sources ◽  
News Reports ◽  
Trade Offs

Synopsis In January, 2015, Chipotle stopped serving pork at a third of its 1,800 restaurants due to its discovery that a pork supplier was not meeting Chipotle's “Food with Integrity” standards. This case examines the trade-offs Chipotle faced in maintaining its focus on sustainable ingredients as the chain grew rapidly. Demand for healthier ingredients by others in the industry and scalability problems in sustainable agricultural production suggested that supply shortages and higher prices were likely threats to Chipotle's continued rapid growth. Could Chipotle maintain its commitment to “Food with Integrity” when the supply of sustainable foods failed to meet demand or should the company just buy available ingredients regardless of farming methods? Research methodology This case was developed from both secondary and primary sources. The secondary sources included industry reports, company annual reports, news reports, social media sites and company websites. Primary sources included video interviews with Chipotle executives (available on the company's website) and visits to Chipotle restaurants in several cities. This case has been classroom tested with MBA students in a capstone course and with undergraduates in a strategic management course. Relevant courses and levels This case was written for use in Strategic Management classes at the undergraduate and MBA levels. The focus of the case aligns well with discussions of competitive advantage, firm performance and business level strategy. The case also has application in discussions regarding implementation of strategy. Instructors that choose to emphasize sustainability strategies could assign this case to explore trade-offs between profitability, sustainability and growth. Additionally, the case could be used in supply chain management courses. Theoretical bases This case utilizes a stakeholder analysis approach to examine the trade-offs between sustainability initiatives, growth and performance. The resource-based model of VRIO is used to analyze the firm's competitive advantage.

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