The inoculum effect (IE) is an increase in the minimum inhibitory concentration (MIC) of an antibiotic as a function of the initial size of a microbial population. The IE has been observed in a wide range of bacteria, implying that antibiotic efficacy may depend on population density. Such density dependence could have dramatic effects on bacterial population dynamics and potential treatment strategies, but explicit measures of per capita growth as a function of density are generally not available. Instead, the IE measures MIC as a function of initial population size, and population density changes by many orders of magnitude on the timescale of the experiment. Therefore, the functional relationship between population density and antibiotic inhibition is generally not known, leaving many questions about the impact of the IE on different treatment strategies unanswered. To address these questions, here we directly measured real-time per capita growth of Enterococcus faecalis populations exposed to antibiotic at fixed population densities using multiplexed computer-automated culture devices. We show that density-dependent growth inhibition is pervasive for commonly used antibiotics, with some drugs showing increased inhibition and others decreased inhibition at high densities. For several drugs, the density dependence is mediated by changes in extracellular pH, a community-level phenomenon not previously linked with the IE. Using a simple mathematical model, we demonstrate how this density dependence can modulate population dynamics in constant drug environments. Then, we illustrate how time-dependent dosing strategies can mitigate the negative effects of density-dependence. Finally, we show that these density effects lead to bistable treatment outcomes for a wide range of antibiotic concentrations in a pharmacological model of antibiotic treatment. As a result, infections exceeding a critical density often survive otherwise effective treatments.

The goal is to evaluate the effect of cover cropping on the population growth of Macrophomina phaseolina in soil. Bulk soil samples were taken 8 weeks after tillage of cover crops into the soil. The relationship between soil microbial diversity and M. phaseolina population growth was assessed.

Tsetse flies are important vectors of human and animal trypanosomiasis. Ability to reduce tsetse populations is an effective means of disease control. Lactation is an essential component of tsetse’s viviparous reproductive physiology and requires a dramatic increase in the expression and synthesis of milk proteins by the milk gland organ in order to nurture larval growth. In between each gonotrophic cycle, tsetse ceases milk production and milk gland tubules undergo a nearly two-fold reduction in width (involution). In this study, we examined the role autophagy plays during tsetse fly milk gland involution and reproductive output. Autophagy genes show elevated expression in tissues associated with lactation, immediately before or within two hours post-parturition, and decline at 24-48h post-parturition. This expression pattern is inversely correlated with that of the milk gland proteins (lactation-specific protein coding genes) and the autophagy inhibitor fk506-bp1. Increased expression of Drosophila inhibitor of apoptosis 1, diap1, was also observed in the milk gland during involution, when it likely prevents apoptosis of milk gland cells. RNAi-mediated knockdown of autophagy related gene 8a (atg8a) prevented rapid milk gland autophagy during involution, prolonging gestation, and reducing fecundity in the subsequent gonotrophic cycle. The resultant inhibition of autophagy reduced the recovery of stored lipids during the dry (non-lactating) periods by 15–20%. Ecdysone application, similar to levels that occur immediately before birth, induced autophagy, and increased milk gland involution even before abortion. This suggests that the ecdysteroid peak immediately preceding parturition likely triggers milk gland autophagy. Population modeling reveals that a delay in involution would yield a negative population growth rate. This study indicates that milk gland autophagy during involution is critical to restore nutrient reserves and allow efficient transition between pregnancy cycles. Targeting post-birth phases of reproduction could be utilized as a novel mechanism to suppress tsetse populations and reduce trypanosomiasis.

A long-standing question in biology is the effect of growth on cell size. Here, we estimate the effect of Escherichia coli growth rate (r) on population cell size distributions by estimating the coefficient of variation of cell lengths (CVL) from image analysis of fixed cells in DIC microscopy. We find that the CVL is constant at growth rates less than one division per hour, whereas above this threshold, CVL increases with an increase in the growth rate. We hypothesize that stochastic inhibition of cell division owing to replication stalling by a RecA-dependent mechanism, combined with the growth rate threshold of multi-fork replication (according to Cooper and Helmstetter), could form the basis of such a threshold effect. We proceed to test our hypothesis by increasing the frequency of stochastic stalling of replication forks with hydroxyurea (HU) treatment and find that cell length variability increases only when the growth rate exceeds this threshold. The population effect is also reproduced in single-cell studies using agar-pad cultures and ‘mother machine’-based experiments to achieve synchrony. To test the role of RecA, critical for the repair of stalled replication forks, we examine the CVL of E. coli ΔrecA cells. We find cell length variability in the mutant to be greater than wild-type, a phenotype that is rescued by plasmid-based RecA expression. Additionally, we find that RecA-GFP protein recruitment to nucleoids is more frequent at growth rates exceeding the growth rate threshold and is further enhanced on HU treatment. Thus, we find growth rates greater than a threshold result in increased E. coli cell lengths in the population, and this effect is, at least in part, mediated by RecA recruitment to the nucleoid and stochastic inhibition of division.

output from 'lethal' and 'sublethal' modelsThis Zip archive contains 14 netCDF files with the output from the lethal, sublethal, and age-at-maturity models. All file names indicate the time period ['contemp' = 1980-2000; 'future' = 2080-2100], variables ([survival' = embryo survival (percent decimal) 'growth' = population growth (lizards/year), 'maturity' = age at maturity (days), 'minmaxtemp' = minimum and maximum daily temperatures(°C)], and whether the output is from the 'lethal' or 'sublethal' model as described in the manuscript (or in the case of the age-at-maturity model, whether it includes the effect of slowed juvenile growth).Carloetal_EcolLett_model_output.zipCarloetal_EcolLett_labandfield_rearing_data2014and2015This .csv file contains data from the laboratory and field experiments described in the manuscript, including embryonic mortality and development times, maximum daily temperatures, hatchling sizes and body conditions, and juvenile growth rates estimated from von Berta...

1. Large carnivores are expanding in Europe, and their return is associated with conflicts that often result in policies to regulate their population size through culling. Being wide-ranging species, their populations are often distributed across several jurisdictions, which may vary in the extent to which they use lethal control. This creates the conditions for the establishment of source-sink dynamics across borders, which may frustrate the ability of countries to reach their respective management objectives. 2. To explore the consequences of this issue, we constructed a vec-permutation projection model, applied to the case of wolverines in south-central Scandinavia, shared between Norway (where they are culled) and Sweden (where they are protected). We evaluated the effect of compensatory immigration on wolverine population growth rates, and if the effect was influenced by the distance to the national border. We assessed to what extent compensatory immigration had an influence on the number of removals needed to keep the population at a given growth rate. 3. In Norway the model estimated a stable trend, whereas in Sweden it produced a 10% annual increase. The effect of compensatory immigration corresponded to a 0.02 reduction in population growth rate in Sweden and to a similar increase in Norway. This effect was stronger closer to the Norwegian-Swedish border, but weak when moving away from it. An average of 33 wolverines were shot per year in the Norwegian part of the study area. If no compensatory immigration from Sweden had occurred, 28 wolverines shot per year would have been sufficient to achieve the same goal. About 15.5% of all the individuals harvested in Norway between 2005-2012 were compensated for by immigrants, causing a decrease in population growth rate in Sweden. 4. Synthesis and applications. When a population is transboundary, the consequences of management decisions are also transboundary, even though the political bodies in charge of those decisions, the stakeholders who influence them, and the taxpayers who finance them are not. It is important that managers and citizens be informed that a difference in management goals can reduce the efficiency, and increase the costs, of wildlife management.

Lineage and passage are encoded in isolate name in the following way: The first position indicates underlying genotype for each selection experiment (1 = MPAO1-WT; 2 = MPAO1-mutSTn; 3 = PT) followed by the lineage (A–D) and passage number (1–20 for MPAO1-WT and 1–7 for MPAO1-mutSTn and PT strains). (XLSX)

Interspecific competition in bacteria governs colony growth dynamics and pattern formation. Here, we demonstrate an interesting phenomenon of interspecific competition between Bacillus cereus MSM-S1 and Pseudomonas sp. MSM-M1, where secretion of an inhibitor by Pseudomonas sp. is used as a strategy for survival. Although B. cereus grows faster than Pseudomonas sp., in the presence of Pseudomonas sp. the population of B. cereus reduces significantly, whereas Pseudomonas sp. do not show any marked alteration in their population growth. Appearance of a zone of inhibition between growing colonies of two species on nutrient agar prevents the expanding front of the MSM-S1 colony from accessing and depleting nutrients in the region occupied by MSM-M1, thereby aiding the survival of the slower growing MSM-M1 colonies. To support our experimental results, we present simulations, based on a chemotactic model of colony growth dynamics. We demonstrate that the chemical(s) secreted by Pseudomonas sp. is responsible for the observed inhibition of growth and spatial pattern of the B. cereus MSM-S1 colony. Our experimental results are in excellent agreement with the numerical results and confirm that secreted inhibitors enable Pseudomonas sp. to survive and coexist in the presence of faster growing B. cereus, in a common niche.

Population aging has become a social issue of concern to the whole world, and as the world’s most populous country, how to cope with population aging will be a hot issue that all sectors of Chinese society must think about. This paper uses provincial panel data from 30 provinces in China from 2000 to 2021 to study the relationship between population aging and economic development based on the perspective of health expenditure. The DIFF-GMM model, the fixed effect model (FE), and fixed effect instrumental variable model (FE-IV) are used to test this study. The following two conclusions are drawn from the empirical study: (1) population aging has a significant inhibitory effect on economic development, while health expenditures have a significant promotional effect on economic development; and (2) increased health expenditures help to alleviate the negative impact of population aging on economic development. However, the deepening of population aging will likewise inhibit the positive effect of health expenditure on economic growth. Based on the conclusions of the study, it is recommended that the government and society should continue to increase spending in the field of health protection, encourage and guide residents to carry out self-care, and moderately increase personal health expenditure, to promote economic development with healthy bodies and realize the goal of "Healthy China".

Shrubs have expanded in Arctic ecosystems over the past century, resulting in significant changes to albedo, ecosystem function, and plant community composition. Willow and rock ptarmigan (Lagopus lagopus, L. muta) and moose (Alces alces) extensively browse Arctic shrubs, and may influence their architecture, growth, and reproduction. Furthermore, these herbivores may alter forage plants in such a way as to increase the quantity and accessibility of their own food source. We estimated the effect of winter browsing by ptarmigan and moose on an abundant, early-successional willow (Salix alaxensis) in northern Alaska by comparing browsed to unbrowsed branches. Ptarmigan browsed 82–89% of willows and removed 30–39% of buds, depending on study area and year. Moose browsed 17–44% of willows and browsed 39–55% of shoots. Browsing inhibited apical dominance and activated axillary and adventitious buds to produce new vegetative shoots. Ptarmigan- and moose-browsed willow branches produced twice the volume of shoot growth but significantly fewer catkins the following summer compared with unbrowsed willow branches. Shoots on browsed willows were larger and produced 40–60% more buds compared to unbrowsed shoots. This process of shoot production at basal parts of the branch is the mechanism by which willows develop a highly complex “broomed” architecture after several years of browsing. Broomed willows were shorter and more likely to be re-browsed by ptarmigan, but not moose. Ptarmigan likely benefit from the greater quantity and accessibility of buds on previously browsed willows and may increase the carrying capacity of their own habitat. Despite the observed tolerance of willows to browsing, their vertical growth and reproduction were strongly inhibited by moose and ptarmigan. Browsing by these herbivores therefore needs to be considered in future models of shrub expansion in the Arctic.

Population aging has become a social issue of concern to the whole world, and as the world’s most populous country, how to cope with population aging will be a hot issue that all sectors of Chinese society must think about. This paper uses provincial panel data from 30 provinces in China from 2000 to 2021 to study the relationship between population aging and economic development based on the perspective of health expenditure. The DIFF-GMM model, the fixed effect model (FE), and fixed effect instrumental variable model (FE-IV) are used to test this study. The following two conclusions are drawn from the empirical study: (1) population aging has a significant inhibitory effect on economic development, while health expenditures have a significant promotional effect on economic development; and (2) increased health expenditures help to alleviate the negative impact of population aging on economic development. However, the deepening of population aging will likewise inhibit the positive effect of health expenditure on economic growth. Based on the conclusions of the study, it is recommended that the government and society should continue to increase spending in the field of health protection, encourage and guide residents to carry out self-care, and moderately increase personal health expenditure, to promote economic development with healthy bodies and realize the goal of "Healthy China".