scholarly journals The emergence, maintenance and demise of diversity in a spatially variable antibiotic regime

2017 ◽  
Author(s):  
Alanna M. Leale ◽  
Rees Kassen
Keyword(s):  
Drug Delivery ◽  
Spatial Variation ◽  
Trade Offs ◽  
New Antibiotics ◽  
Changing Patterns ◽  
Protected Polymorphism ◽  
Antibiotic Regime ◽  
Negative Frequency Dependent Selection ◽  
Global Threat ◽  
Spatially Varying

Antimicrobial resistance (AMR) is a growing global threat that, in the absence of new antibiotics, requires effective management of existing drugs. Here, we explore how changing patterns of drug delivery modulates the spread of resistance in a population. Resistance evolves readily under both temporal and spatial variation in drug delivery and fixes rapidly under temporal, but not spatial, variation. Resistant and sensitive genotypes coexist in spatially varying conditions due to a resistance-growth rate trade-off which, when coupled to dispersal, generates negative frequency-dependent selection and a quasi-protected polymorphism. Coexistence is ultimately lost, however, because resistant types with improved growth rates in the absence of drug spread through the population. These results suggest that spatially variable drug prescriptions can delay but not prevent the spread of resistance and provide a striking example of how the emergence and eventual demise of biodiversity is underpinned by evolving fitness trade-offs.

Sample size determination in geotechnical site investigation considering spatial variation and correlation

2019 ◽  
Vol 56 (7) ◽  
pp. 992-1002 ◽  
Author(s):  
Yu Wang ◽  
Zheng Guan ◽  
Tengyuan Zhao
Keyword(s):  
Spatial Variation ◽  
Sample Size ◽  
Test Data ◽  
Site Investigation ◽  
Sample Size Determination ◽  
Engineering Practice ◽  
Size Determination ◽  
Penetration Test ◽  
Cone Penetration ◽  
Spatially Varying

Site investigation is a fundamental element in geotechnical engineering practice, but only a small portion of geomaterials is sampled and tested during site investigation. This leads to a question of sample size determination: how many samples are needed to achieve a target level of accuracy for the results inferred from the samples? Sample size determination is a well-known topic in statistics and has many applications in a wide variety of areas. However, conventional statistical methods, which mainly deal with independent data, only have limited applications in geotechnical site investigation because geotechnical data are not independent, but spatially varying and correlated. Existing design codes around the world (e.g., Eurocode 7) only provide conceptual principles on sample size determination. No scientific or quantitative method is available for sample size determination in site investigation considering spatial variation and correlation of geotechnical properties. This study performs an extensive parametric study and develops a statistical chart for sample size determination with consideration of spatial variation and correlation using Bayesian compressive sensing or sampling. Real cone penetration test data and real laboratory test data are used to illustrate application of the proposed statistical chart, and the method is shown to perform well.

scholarly journals Crumbling the Castle: Targeting DNABII Proteins for Collapsing Bacterial Biofilms as a Therapeutic Approach to Treat Disease and Combat Antimicrobial Resistance

Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
James V. Rogers ◽  
Veronica L. Hall ◽  
Charles C. McOsker
Keyword(s):  
Antimicrobial Resistance ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Defense Mechanism ◽  
Treatment Options ◽  
Bacterial Biofilms ◽  
Host Immune System ◽  
New Antibiotics ◽  
Financial Burdens ◽  
Global Threat

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.

scholarly journals Poisson-Gamma Mixture Spatially Varying Coefficient Modeling of Small-Area Intestinal Parasites Infection

2019 ◽  
Vol 16 (3) ◽  
pp. 339 ◽  
Author(s):  
Frank Osei ◽  
Alfred Stein ◽  
Anthony Ofosu
Keyword(s):  
Drinking Water ◽  
Spatial Variation ◽  
Waste Disposal ◽  
Intestinal Parasites ◽  
Liquid Waste ◽  
Public Health Intervention ◽  
Demographic Factors ◽  
Exceedance Probability ◽  
Varying Coefficient ◽  
Spatially Varying

Understanding the spatially varying effects of demographic factors on the spatio-temporal variation of intestinal parasites infections is important for public health intervention and monitoring. This paper presents a hierarchical Bayesian spatially varying coefficient model to evaluate the effects demographic factors on intestinal parasites morbidities in Ghana. The modeling relied on morbidity data collected by the District Health Information Management Systems. We developed Poisson and Poisson-gamma spatially varying coefficient models. We used the demographic factors, unsafe drinking water, unsafe toilet, and unsafe liquid waste disposal as model covariates. The models were fitted using the integrated nested Laplace approximations (INLA). The overall risk of intestinal parasites infection was estimated to be 10.9 per 100 people with a wide spatial variation in the district-specific posterior risk estimates. Substantial spatial variation of increasing multiplicative effects of unsafe drinking water, unsafe toilet, and unsafe liquid waste disposal occurs on the variation of intestinal parasites risk. The structured residual spatial variation widely dominates the unstructured component, suggesting that the unaccounted-for risk factors are spatially continuous in nature. The study concludes that both the spatial distribution of the posterior risk and the associated exceedance probability maps are essential for monitoring and control of intestinal parasites.

Substock variation in reproductive traits in North Sea cod (Gadus morhua)

2010 ◽  
Vol 67 (5) ◽  
pp. 866-876 ◽  
Author(s):  
Marion Harrald ◽  
Peter J. Wright ◽  
Francis C. Neat
Keyword(s):  
Spatial Variation ◽  
North Sea ◽  
Gadus Morhua ◽  
Atlantic Cod ◽  
Liver Weight ◽  
Adaptive Divergence ◽  
Female Size ◽  
Common Environment ◽  
Relative Liver Weight ◽  
Trade Offs

The North Sea stock of Atlantic cod ( Gadus morhua ) is comprised of a number of subcomponents that differ both genetically and phenotypically. A potential cause for such spatial variability is adaptive divergence, which may be linked to differences in thermal environment and (or) historical fishing pressure. Here we present evidence that spatial variation in maturity–size relationships in the wild has a significant intrinsic component. Using a common-environment experiment on wild-caught juveniles raised through to maturity, we demonstrate that cod from the southern North Sea (SNS) mature at larger sizes than those from the northwestern North Sea (NWNS) despite broadly similar growth rates. Consistent with these experimental results, year-class-specific maturity ogives for recent maturing year classes (1999–2001) suggested that the length at which 50% of females reached maturity was 11 cm greater for SNS than for NWNS cod. Under a common environment, smaller female size at maturity partly reflected higher relative liver weight, with NWNS females having a higher relative liver weight than SNS females. By investigating maturation under controlled conditions, our study provides evidence for life history trade-offs in energy allocation between growth, energy storage, and reproduction that may underlie the spatial variation observed in the field.

scholarly journals Determination of spatially varying Van der Burgh's coefficient from estuarine parameter to describe salt transport in an estuary

2010 ◽  
Vol 7 (6) ◽  
pp. 8781-8808
Author(s):  
D. C. Shaha ◽  
Y.-K. Cho
Keyword(s):  
Spatial Variation ◽  
Salinity Gradient ◽  
Spring Tide ◽  
Vertical Mixing ◽  
River Estuary ◽  
Relative Strength ◽  
Salt Transport ◽  
K Value ◽  
Relative Contribution ◽  
Spatially Varying

Abstract. The estuarine parameter ν is widely accepted as describing the relative contribution of the tide-driven and density-driven mixing mechanism of salt transport in estuaries. Van der Burgh's coefficient K is another parameter that also determines the relative strength of two mechanisms. However, a single value of K, which has been considered in previous studies, can not represent the spatial variation of these mechanisms in an estuary. In this study, the spatially varying K has been determined from the ν value calculated using intensively observed longitudinal salinity transects of the Sumjin River Estuary with exponential shape. The spatially varying K describes the spatial variation of these mechanisms reasonably well and is independent of the river discharge downstream of the estuary during spring tide where the strong tides cause well mixed conditions. However, K values increase upstream and are found to depend on the freshwater discharge, with suppressing vertical mixing. The K value has been scaled on the basis of the ν value and ranges between 0 and 1. If K is <0.4, the up-estuary salt transport is entirely dominated by tide-driven mixing during spring tide near the mouth. If 0.4 < K < 0.8, both tide-driven and density-driven mixing contribute to transporting salt in the central regimes. If K > 0.8, the salt transport is almost entirely by density-driven circulation in the upper most regimes during both spring and neap tides. In addition, another K-based dispersion equation has been solved by using this spatially varying K. The spatially varying K demonstrates density-driven circulation more prominently at the strong salinity gradient location compared with a single K value.

scholarly journals Upregulation of gluconeogenesis leads to increased tolerance to antibiotics targeting the MreB elongosome in E. coli

2020 ◽  
Author(s):  
Brody Barton ◽  
Addison Grinnell ◽  
Randy M. Morgenstein
Keyword(s):  
Antibiotic Resistance ◽  
Minimal Inhibitory Concentration ◽  
Bacterial Infections ◽  
Inhibitory Concentration ◽  
Resistance Mechanism ◽  
Tca Cycle ◽  
Resistant Bacteria ◽  
Antibiotic Development ◽  
New Antibiotics ◽  
Global Threat

AbstractAntibiotic resistant bacteria are a global threat to human health. One way to combat the rise of antibiotic resistance is to make new antibiotics that target previously ignored proteins. The bacterial actin homolog, MreB, is highly conserved among rod-shaped bacteria and essential for growth, making MreB a good focus for antibiotic targeting. Therefore, it is imperative to understand mechanisms that can give rise to resistance to MreB targeting drugs. Using the MreB targeting drug, A22, we show that changes to central metabolism through deletion of TCA cycle genes, leads to the upregulation of gluconeogenesis resulting in cells with an increased minimal inhibitory concentration to A22. This phenotype can be recapitulated through the addition of glucose to the media. Finally, we show that this increase in minimal inhibitory concentration is not specific to A22 but can be seen in other cell wall targeting antibiotics, such as mecillinam.ImportanceThe spread of antibiotic resistance has made bacterial infections harder to treat. Finding new targets for antibiotic development is critical to overcoming the variety of resistance mechanism that are already crippling our ability to treat infections with current antibiotics. The bacterial actin homolog MreB is a good target for new antibiotic development because it is essential for growth and highly conserved among rod-shaped pathogens. The significance of this research is in understanding the mechanisms cells can develop toward the inhibition of MreB to better understand how to make MreB targeting antibiotics in the future.

scholarly journals Life history variation is maintained by fitness trade-offs and negative frequency-dependent selection

2018 ◽  
Vol 115 (17) ◽  
pp. 4441-4446 ◽  
Author(s):  
Mark R. Christie ◽  
Gordon G. McNickle ◽  
Rod A. French ◽  
Michael S. Blouin
Keyword(s):  
Life History ◽  
Reproductive Success ◽  
Life History Strategies ◽  
Lifetime Reproductive Success ◽  
Life History Variation ◽  
Additional Energy ◽  
Frequency Dependent ◽  
Frequency Dependent Selection ◽  
Trade Offs ◽  
Negative Frequency Dependent Selection

The maintenance of diverse life history strategies within and among species remains a fundamental question in ecology and evolutionary biology. By using a near-complete 16-year pedigree of 12,579 winter-run steelhead (Oncorhynchus mykiss) from the Hood River, Oregon, we examined the continued maintenance of two life history traits: the number of lifetime spawning events (semelparous vs. iteroparous) and age at first spawning (2–5 years). We found that repeat-spawning fish had more than 2.5 times the lifetime reproductive success of single-spawning fish. However, first-time repeat-spawning fish had significantly lower reproductive success than single-spawning fish of the same age, suggesting that repeat-spawning fish forego early reproduction to devote additional energy to continued survival. For single-spawning fish, we also found evidence for a fitness trade-off for age at spawning: older, larger males had higher reproductive success than younger, smaller males. For females, in contrast, we found that 3-year-old fish had the highest mean lifetime reproductive success despite the observation that 4- and 5-year-old fish were both longer and heavier. This phenomenon was explained by negative frequency-dependent selection: as 4- and 5-year-old fish decreased in frequency on the spawning grounds, their lifetime reproductive success became greater than that of the 3-year-old fish. Using a combination of mathematical and individual-based models parameterized with our empirical estimates, we demonstrate that both fitness trade-offs and negative frequency-dependent selection observed in the empirical data can theoretically maintain the diverse life history strategies found in this population.

scholarly journals Spatial variation in egg size and egg number reflects trade-offs and bet-hedging in a freshwater fish

2012 ◽  
Vol 81 (4) ◽  
pp. 806-817 ◽  
Author(s):  
John R. Morrongiello ◽  
Nicholas R. Bond ◽  
David A. Crook ◽  
Bob B. M. Wong
Keyword(s):  
Spatial Variation ◽  
Freshwater Fish ◽  
Egg Size ◽  
Bet Hedging ◽  
Trade Offs ◽  
Egg Number
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