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Ecological interactions among hosts are critical to consider when predicting disease dynamics. Most theory predicts that intraguild predation (IGP) and cannibalism negatively impact parasite populations, but this is based primarily on assumptions of simple or single‐host life cycles. Here we investigate the effects of cannibalism in a size‐structured host population on two digenean trematodes that have complex, multihost life cycles. A high incidence of cannibalism among paratenic hosts produced higher parasite infection loads and abundance, whereas cannibalism among obligate hosts reduced parasite abundances. We attributed this difference to trophic transmission aggregating parasites in larger, potentially fitter hosts and also to transmission among paratenic hosts via cannibalism. Moreover, we found evidence of indirect competitive interactions between parasites that can also increase infections at small scales. Our results show there are multiple mechanisms through which high cannibalism environments can benefit parasites that use paratenic hosts and trophic transfer to complete their life cycles. [ABSTRACT FROM AUTHOR]

This study employed aerial surveys to quantify the spatial and temporal abundance of the whitespotted eagle ray, Aetobatus narinari, and the giant manta ray, Mobula birostris, in southeast Florida. Aetobatus narinari abundance did not differ along the north-south axis of the coast, whereas M. birostris was more abundant at lower latitudes. Similarly, A. narinari did not exhibit any seasonal difference in abundance, whereas M. birostris was more abundant during December and February. Neither species exhibited a clear trend in abundance over the study period (2014–2021). In addition, the abundance of both species failed to correlate with water temperature, chlorophyll-a concentration, or photoperiod. Both M. birostris and A. narinari are protected species in Florida state waters, and M. birostris is designated as threatened under the US Endangered Species Act. In addition, both species are classified by the IUCN as endangered worldwide. Insufficient data exist to establish critical habitat designations for M. birostris so that the provided information on their distribution and abundance is useful for the development of effective management. [ABSTRACT FROM AUTHOR]

Warming has broad and often nonlinear impacts on organismal physiology and traits, allowing it to impact species interactions like predation through a variety of pathways that may be difficult to predict. Predictions are commonly based on short‐term experiments and models, and these studies often yield conflicting results depending on the environmental context, spatiotemporal scale, and the predator and prey species considered. Thus, the accuracy of predicted changes in interaction strength, and their importance to the broader ecosystems they take place in, remain unclear. Here, we attempted to link one such set of predictions generated using theory, modeling, and controlled experiments to patterns in the natural abundance of prey across a broad thermal gradient. To do so, we first predicted how warming would impact a stage‐structured predator–prey interaction in riverine rock pools between Pantala spp. dragonfly nymph predators and Aedes atropalpus mosquito larval prey. We then described temperature variation across a set of hundreds of riverine rock pools (n = 775) and leveraged this natural gradient to look for evidence for or against our model's predictions. Our model's predictions suggested that warming should weaken predator control of mosquito larval prey by accelerating their development and shrinking the window of time during which aquatic dragonfly nymphs could consume them. This was consistent with data collected in rock pool ecosystems, where the negative effects of dragonfly nymph predators on mosquito larval abundance were weaker in warmer pools. Our findings provide additional evidence to substantiate our model‐derived predictions while emphasizing the importance of assessing similar predictions using natural gradients of temperature whenever possible. [ABSTRACT FROM AUTHOR]

The introduction and spread of non‐native species restructure native ecosystems and can be particularly impactful when invaders are ecosystem engineers or habitat‐forming species. In coastal, estuarine, and marine systems, submerged aquatic vegetation (SAV), like macroalgae and seagrasses, form key habitats for nekton, serving as nurseries, foraging grounds, and reproduction sites. If non‐native ecosystem engineers can provide sufficient structure and/or resources, they may exert a neutral or positive effect on organisms occupying higher trophic positions. As such, we hypothesized that nekton response to non‐native SAV species may be neutral or positive. We performed a quantitative meta‐analysis to quantify impacts of non‐native SAV on native crabs, fishes, and shrimps. We extracted data from 35 studies and evaluated 11 response metrics related to facilitation (e.g., habitat use and foraging), restricting our analysis to studies that compared at least one of these metrics in nekton from co‐occurring native and non‐native SAV habitats in marine, coastal, or estuarine systems. We found that nekton abundance, species richness, and biomass were the most assessed metrics of nekton performance. Our pooled data revealed differential results among response metrics, with nekton growth and reproduction enhanced in non‐native habitats and species richness enhanced in a native setting. The mean effect sizes for all other nekton response metrics, including abundance, had 95% CIs that overlapped zero, indicating no difference in response between native and non‐native SAV. For many endpoints, limited sample sizes prevented robust inferences, but they also highlighted areas where more research is needed in future studies. Non‐native species have the potential to restructure the systems they invade. Our results lend support to the relative trophic position hypothesis, indicating that non‐native habitat formers may facilitate native organisms in higher trophic levels. We identify research gaps that may guide future studies and allow for a more comprehensive understanding of responses to non‐native ecosystem engineers. [ABSTRACT FROM AUTHOR]

Peripheral artery disease (PAD) is an occlusive disease of limb arteries. Critical limb ischemia (CLI) is an advanced form of PAD that is prognostically worse in subjects with diabetes and can result in limb loss, gangrene, and death, although the underlying signaling mechanisms that contribute to its development remain poorly understood. By comparing plasma samples from diabetic humans with PAD and mouse models of PAD, we identified miR-375 to be significantly downregulated in humans and mice during progression to CLI. Overexpression of miR-375 was pro-angiogenic in endothelial cells in vitro and induced endothelial migration, proliferation, sprouting, and vascular network formation, whereas miR-375 inhibition conferred anti-angiogenic effects. Intramuscular delivery of miR-375 improved blood flow recovery to diabetic mouse hindlimbs following femoral artery ligation (FAL) and improved neovessel growth and arteriogenesis in muscle tissues. Using RNA-sequencing and prediction algorithms, Kruppel-like factor 5 (KLF5) was identified as a direct target of miR-375 and siRNA knockdown of KLF5 phenocopied the effects of miR-375 overexpression in vitro and in vivo through regulatory changes in NF-kB signaling. Together, a miR-375-KLF5-NF-kB signaling axis figures prominently as a potential therapeutic pathway in the development CLI in diabetes. [ABSTRACT FROM AUTHOR]

To predict the impacts of environmental change on species, we must first understand the factors that limit the present-day ranges of species. Most anuran amphibians cannot survive at elevated salinities, which may drive their distribution in coastal locations. Previous research showed that coastal Hyla cinerea are locally adapted to brackish habitats in North Carolina, USA. Although Hyla squirella and Hyla chrysoscelis both inhabit coastal wetlands nearby, they have not been observed in saline habitats. We take advantage of naturally occurring microgeographic variation in coastal wetland occupancy exhibited by these congeneric tree frog species to explore how salt exposure affects oviposition site choice, hatching success, early tadpole survival, plasma osmolality and tadpole body condition across coastal and inland locations. We observed higher survival among coastal H. cinerea tadpoles than inland H. cinerea, which corroborates previous findings. But contrary to expectations , coastal H. cinerea had lower survival than H. squirella and H. chrysoscelis , indicating that all three species may be able to persist in saline wetlands. We also observed differences in tadpole plasma osmolality across species, locations and salinities, but these differences were not associated with survival rates in salt water. Instead, coastal occupancy may be affected by stage-specific processes like higher probability of total clutch loss as shown by inland H. chrysoscelis or maladaptive egg deposition patterns as shown by inland H. squirella. Although we expected salt water to be the primary filter driving species distributions along a coastal salinity gradient, it is likely that the factors dictating anuran ranges along the coast involve stage-, species- and location-specific processes that are mediated by ecological processes and life history traits. [ABSTRACT FROM AUTHOR]

The Comparative Functional Response Approach (CFRA) was developed to provide a practical methodology by which short-term experiments can be used to forecast the longer-term impacts of a potential invading consumer. The CFRA makes inferences about potential invader impact based on comparisons of the functional responses of invader and native consumers on native resources in a common experimental venue. Application of the CFRA and derivative approaches have proliferated since it was introduced in 2014. Here we examine the conceptual foundations of the CFRA within the context of basic Lotka–Volterra consumer-resource theory. Our goals are to assess whether core predictions of the CFRA hold within this framework, to consider the relative importance of background mortality and consumer assimilation efficiency in determining predator impact, and to leverage this conceptual framework to expand the discussion regarding stability and long term consumer and resource dynamics. The CFRA assertion that consumers with a higher functional response will have larger impacts on resources only holds as long as all other parameters are equal, but basic theory indicates that predator impacts on prey abundance and stability will depend more on variation in conversion efficiency and background mortality. While examination of the CFRA within this framework highlights limitations about its current application, it also points to potential strengths that are only revealed when a theoretical context is identified, in this case the implications for stability and conceptual links to competition theory. [ABSTRACT FROM AUTHOR]

Focusing on Cumberland County, Pennsylvania, this article considers the standard of living among 408 rural laboring men and their families, asking three questions: what were the costs of a typical household budget; did households earn enough to meet their needs; and did they achieve a minimal level of material comfort? The article answers these questions through two means: (1) it constructs a household budget and tests the degree to which households could afford the necessities; and (2) it measures the material conditions of working men and families by constructing an index of basic household goods against which to compare the personal possessions of the working poor. Together, these measures suggest that the region's working poor struggled to achieve and maintain an often-austere standard of living. This examination sheds light on the conditions of the rural working class in the Age of Jackson. [ABSTRACT FROM AUTHOR]

Perturbations in striatal dopamine (DA) homeostasis might underlie the behavioral and pathobiological consequences of METH use disorder in humans. To identify potential consequences of long-term METH exposure, we modeled the adverse consequence DSM criterion of substance use disorders by giving footshocks to rats that had escalated their intake of METH during a drug self-administration procedure. Next, DA D1 receptor antagonist, SCH23390 was injected. Thereafter, rats were euthanized to measure several indices of the striatal dopaminergic system. Footshocks split the METH rats into two phenotypes: (i) shock-sensitive that decreased their METH-intake and (ii) shock-resistant that continued their METH intake. SCH23390 caused substantial dose-dependent reduction of METH taking in both groups. Stopping SCH23390 caused re-emergence of compulsive METH taking in shock-resistant rats. Compulsive METH takers also exhibited greater incubation of METH seeking than non-compulsive rats during withdrawal from METH SA. Analyses of DA metabolism revealed non-significant decreases (about 35%) in DA levels in resistant and sensitive rats. However, striatal contents of the deaminated metabolites, DOPAL and DOPAC, were significantly increased in sensitive rats. VMAT2 and DAT protein levels were decreased in both phenotypes. Moreover, protein expression levels of the D1-like DA receptor, D5R, and D2-like DA receptors, D3R and D4R, were significantly decreased in the compulsive METH takers. Our results parallel findings in post-mortem striatal tissues of human METH users who develop Parkinsonism after long-term METH intake and support the use of this model to investigate potential therapeutic interventions for METH use disorder. [ABSTRACT FROM AUTHOR]

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Predicting the combined effects of predators on shared prey has long been a focus of community ecology, yet quantitative predictions often fail. Failure to account for nonlinearity is one reason for this. Moreover, prey depletion in multiple predator effects (MPE) studies generates biased predictions in applications of common experimental and quantitative frameworks. Here, we explore additional sources of bias stemming from nonlinearities in prey predation risk. We show that in order to avoid bias, predictions about the combined effects of independent predators must account for nonlinear size-dependent risk for prey as well as changes in prey risk driven by nonlinear predator functional responses and depletion. Historical failure to account for biases introduced by well-known nonlinear processes that affect predation risk suggest that we may need to reevaluate the general conclusions that have been drawn about the ubiquity of emergent MPEs over the past three decades. [ABSTRACT FROM AUTHOR]

Diabetes-associated atherosclerosis involves excessive immune cell recruitment and plaque formation. However, the mechanisms remain poorly understood. Transcriptomic analysis of the aortic intima in Ldlr −/− mice on a high-fat, high-sucrose-containing (HFSC) diet identifies a macrophage-enriched nuclear long noncoding RNA (lncRNA), MERRICAL (macrophage-enriched lncRNA regulates inflammation, chemotaxis, and atherosclerosis). MERRICAL expression increases by 249% in intimal lesions during progression. lncRNA-mRNA pair genomic mapping reveals that MERRICAL positively correlates with the chemokines Ccl3 and Ccl4. MERRICAL -deficient macrophages exhibit lower Ccl3 and Ccl4 expression, chemotaxis, and inflammatory responses. Mechanistically, MERRICAL guides the WDR5-MLL1 complex to activate CCL3 and CCL4 transcription via H3K4me3 modification. MERRICAL deficiency in HFSC diet-fed Ldlr −/− mice reduces lesion formation by 74% in the aortic sinus and 86% in the descending aorta by inhibiting leukocyte recruitment into the aortic wall and pro-inflammatory responses. These findings unveil a regulatory mechanism whereby a macrophage-enriched lncRNA potently inhibits chemotactic responses, alleviating lesion progression in diabetes. [Display omitted] • Macrophage-enriched lncRNA MERRICAL increased in diabetes-associated atherosclerosis • MERRICAL in cis regulated chemokines CCL3 and CCL4 by guiding WDR5-MLL1 and H3K4me3 • MERRICAL KD macrophages had reduced CCL3 and CCL4 expression and chemotactic responses • MERRICAL KD abrogated pro-inflammatory macrophage recruitment and lesion formation Diabetes-associated atherosclerosis involves excessive immune cell recruitment and plaque formation that is more resistant to standard therapy. Chen et al. discovered a macrophage-enriched long noncoding RNA named MERRICAL in diabetes-associated atherosclerosis. MERRICAL regulated chemotaxis and inflammatory responses, and systemic deficiency of MERRICAL markedly reduced lesion formation in a diabetes-associated atherosclerosis mouse model. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) use disorder (MUD) is characterized by compulsive and repeated drug taking despite negative life consequences. Large intake of METH in humans and animals is accompanied by dysfunctions in learning and memory processes. The endocannabinoid system (ECS) is known to modulate synaptic plasticity and cognitive functions. In addition, the ECS has been implicated in some of the manifestations of substance use disorders (SUDs). We therefore sought to identify potential changes in the expression of various enzymes and of the receptors (CB1 and CB2) that are members of that system. Herein, we used a model of METH self-administration (SA) that includes a punishment phase (footshocks) that helps to separate rats into a compulsive METH phenotype (compulsive) that continues to take METH and a non-compulsive METH (abstinent) group that suppressed or stopped taking METH. Animals were euthanized 2 h after the last METH SA session and their hippocampi were used to measure mRNA levels of cannabinoid receptors (CB/Cnr), as well as those of synthesizing (DAGL-A, DAGL-B, NAPEPLD) and metabolizing (MGLL, FAAH, PTGS2) enzymes of the endocannabinoid cascade. Non-compulsive rats exhibited significant increased hippocampal expression of CB1/Cnr1 and CB2/Cnr2 mRNAs. mRNA levels of the synthesizing enzyme, DAGL-A, and of the metabolic enzymes, MGLL and FAAH, were also increased. Non-compulsive rats also exhibited a significant decrease in hippocampal Ptgs2 mRNA levels. Taken together, these observations implicate the hippocampal endocannabinoid system in the suppression of METH intake in the presence of adverse consequences. [ABSTRACT FROM AUTHOR]

This essay draws on an uninterrupted stretch of indictment records from 1827 to 1846 to consider the relationship between hard times and property crimes in rural Pennsylvania. Focusing on working poor defendants, the piece illustrates how struggling men and women used petty crime as a makeshift response to material hardship and how such a strategy often led to more hard times. By examining the ways in which economic conditions and crime together shaped the lives of laboring people in a rural setting, this essay adds to the rich historiographies of working- class experience and crime in Pennsylvania. Demonstrating that rural crime was born of the same struggle for survival as it was in the Jacksonian city, the essay ultimately suggests that, amid capitalist transformation, the material lives of Urban and rural working people--if they were ever that different--grew increasingly uniform. [ABSTRACT FROM AUTHOR]

The incredible complexity of biological processes across temporal and spatial scales hampers defining common underlying mechanisms driving the patterns of life. However, recent advances in sequencing, big data analysis, machine learning, and molecular dynamics simulation have renewed the hope and urgency of finding potential hidden rules of life. There currently exists no framework to develop such synoptic investigations. Some efforts aim to identify unifying rules of life across hierarchical levels of time, space, and biological organization, but not all phenomena occur across all the levels of these hierarchies. Instead of identifying the same parameters and rules across levels, we posit that each level of a temporal and spatial scale and each level of biological organization has unique parameters and rules that may or may not predict outcomes in neighboring levels. We define this neighborhood, or the set of levels, across which a rule functions as the zone of influence. Here, we introduce the zone of influence framework and explain using three examples: (a) randomness in biology, where we use a Poisson process to describe processes from protein dynamics to DNA mutations to gene expressions, (b) island biogeography, and (c) animal coloration. The zone of influence framework may enable researchers to identify which levels are worth investigating for a particular phenomenon and reframe the narrative of searching for a unifying rule of life to the investigation of how, when, and where various rules of life operate. [ABSTRACT FROM AUTHOR]

Connectivity and patch size are important landscape characteristics that drive patterns of abundance and diversity across scales. However, responses to connectivity and patch size are dependent on species traits. Riverine landscapes are highly dynamic both spatially and temporally, with hydrologic connectivity being a major driver of abundance and diversity. Here we modeled the densities of 2 taxa that differ in life history and dispersal ability, the Virginia River Snail (Elimia virginica) and skimmer dragonfly larvae (Pantala spp.), as a function of flooding, patch area, and season in >300 riverine rock pools. We found key differences in how each taxon responded to these predictors. Specifically, increasing pool flood height had a strong negative effect on snail densities, whereas dragonfly nymph densities increased as pools became isolated from the river channel for longer durations of time. Increasing pool surface area had a positive effect on snail densities, whereas dragonfly nymph densities showed no such relationship. Dragonfly nymph densities were greater in summer and autumn than in spring, but snails showed no difference in their temporal distribution across seasons. Our study highlights how differential responses to landscape characteristics are dependent on organism traits. These findings give insight into patterns of abundance and diversity across spatiotemporal scales. [ABSTRACT FROM AUTHOR]

Salinization is a global phenomenon affecting ecosystems and forcing freshwater organisms to deal with increasing levels of ionic stress. However, our understanding of mechanisms that permit salt tolerance in amphibians is limited. This study investigates mechanisms of salt tolerance in locally adapted, coastal populations of a treefrog, Hylacinerea. Using a common garden experiment, we (i) determine the extent that environment (i.e., embryonic and larval saltwater exposure) or genotype (i.e., coastal vs. inland) affects developmental benchmarks and transcriptome expression, and (ii) identify genes that may underpin differences in saltwater tolerance. Differences in gene expression, survival, and plasma osmolality were most strongly associated with genotype. Population genetic analyses on expressed genes also delineated coastal and inland groups based on genetic similarity. Coastal populations differentially expressed osmoregulatory genes including ion transporters (atp1b1, atp6V1g2, slc26a), cellular adhesion components (cdh26, cldn1, gjb3, ocln), and cytoskeletal components (odc1‐a, tgm3). Several of these genes are the same genes expressed by euryhaline fish after exposure to freshwater, which is a novel finding for North American amphibians and suggests that these genes may be associated with local salinity adaptation. Coastal populations also highly expressed glycerol‐3‐phosphate dehydrogenase 1 (gpd1), which indicates they use glycerol as a compatible osmolyte to reduce water loss – another mechanism of saltwater tolerance previously unknown in frogs. These data signify that Hylacinerea inhabiting coastal, brackish wetlands have evolved a salt‐tolerant ecotype, and highlights novel candidate pathways that can lead to salt tolerance in freshwater organisms facing habitat salinization. [ABSTRACT FROM AUTHOR]

Warming can impact consumer–resource interactions through multiple mechanisms. For example, warming can both alter the rate at which predators consume prey and the rate prey develop through vulnerable life stages. Thus, the overall effect of warming on consumer–resource interactions will depend upon the strength and asymmetry of warming effects on predator and prey performance.Here, we quantified the temperature dependence of both (a) density‐dependent predation rates for two dragonfly nymph predators on a shared mosquito larval prey, via the functional response, and (b) the development rate of mosquito larval prey to a predator‐invulnerable adult stage. We united the results of these two empirical studies using a temperature‐ and density‐dependent stage‐structured predation model to predict the effects of temperature on the number of larvae that survive to adulthood.Warming accelerated both larval mosquito development and increased dragonfly consumption. Model simulations suggest that differences in the magnitude and rate of predator and prey responses to warming determined the change in magnitude of the overall effect of predation on prey survival to adulthood. Specifically, we found that depending on which predator species prey were exposed to in the model, the net effect of warming was either an overall reduction or no change in predation strength across a temperature gradient.Our results highlight a need for better mechanistic understanding of the differential effects of temperature on consumer–resource pairs to accurately predict how warming affects food web dynamics. A free plain language summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

Some industrial crane control panels were historically equipped with chrysotile-containing arc chutes. Because of the paucity of data regarding potential exposure from such equipment, we used a simulation approach to quantify the release of chrysotile from arc chutes in two functional 1970s-era industrial crane control panels during operation and maintenance. Two experienced operators separately simulated operation of crane controls under load; one of these operators then simulated two arc chute maintenance protocols: sanding (protocol 1) and scraping, sanding, and blowing (protocol 2). The original arc chutes contained approximately 36% chrysotile. Personal breathing zone (PBZ) (n = 8) and area samples (n = 8) were collected and analyzed using phase contrast microscopy (PCM) and transmission electron microscopy. PCM-equivalent (PCME) concentrations were derived, from which 8-h time-weighted averages (TWA) were calculated. During operation, chrysotile was identified in one of the four PBZ samples, equivalent to a PCME concentration of 0.012 f/cm3 (8-h TWA: 0.011 f/cm3). During protocols 1 and 2, chrysotile was identified in all PBZ samples (n = 4); PCME concentrations (and corresponding 8-h TWA) were <0.013 and 0.021 f/cm3 (0.001 and 0.004 f/cm3) and 0.013 and 0.017 f/cm3 (0.003 f/cm3), respectively. Many of the airborne chrysotile fibers had matrix attached, supporting the low exposure potential during this work. These data indicate very low, if any, exposures to chrysotile asbestos during the simulated scenarios. In addition, these data could assist with refining assumptions in exposure reconstruction and inform the state-of-the science on low-level chrysotile exposure. [ABSTRACT FROM AUTHOR]

Widespread adoption of evidence-based new healthcare practice guidelines can take years to occur. Policy leaders frequently make decisions based on incomplete and often incorrect information. These policy decisions can result in wasteful healthcare spending and poor health outcomes. Proponents of a medicolegal policy, Communication-and-Resolution Program (CRP), were successful in their endeavor to get hospitals to implement CRP, state legislators to pass state laws to encourage CRP adoption by hospitals, and national medical societies to endorse CRP to their members. The purpose of this paper is to explain the methods used by nine teams in their efforts to accomplish these goals. We identify reasons for the successes, failures, and obstacles faced by the teams in their effort to advance CRP. Our hope is to educate groups on a potentially more expeditious method to advance evidence-based policy than other methods. We propose that advocates of an innovation determine the concerns and goals of all stakeholder groups impacted by the policy. The specific concerns of each group should be the focus of the message to that group. Teams should identify the opinion leaders of each stakeholder group who can champion the new policy to their peers. Teams can aid the opinion leaders in their communication efforts to their peer group. National groups should be organized to help teams in their endeavor to advance evidence-based policies. [ABSTRACT FROM AUTHOR]

To identify signaling pathways activated by oxycodone self-administration (SA), Sprague–Dawley rats self-administered oxycodone for 20 days using short—(ShA, 3 h) and long-access (LgA, 9 h) paradigms. Animals were euthanized 2 h after SA cessation and dorsal striata were used in post-mortem molecular analyses. LgA rats escalated their oxycodone intake and separated into lower (LgA-L) or higher (LgA-H) oxycodone takers. LgA-H rats showed increased striatal protein phosphorylation of ERK1/2 and MSK1/2. Histone H3, phosphorylated at serine 10 and acetylated at lysine 14 (H3S10pK14Ac), a MSK1/2 target, showed increased abundance only in LgA-H rats. RT-qPCR analyses revealed increased AMPA receptor subunits, GluA2 and GluA3 mRNAs, in the LgA-H rats. GluA3, but not GluA2, mRNA expression correlated positively with changes in pMSK1/2 and H3S10pK14Ac. These findings suggest that escalated oxycodone SA results in MSK1/2-dependent histone phosphorylation and increases in striatal gene expression. These observations offer potential avenues for interventions against oxycodone addiction. [ABSTRACT FROM AUTHOR]

A shared Toll for innate immunity: Toll-like receptor 2 (TLR2) is found in various tissues but is best known for its role in the innate immune system of activating sentinel immune cells in response to infection. Using conditional knockout mice, McCoy et al. found that TLR2 also mediated innate immune signaling within the endothelium. TLR2 in endothelial cells activated proinflammatory signaling that promoted angiogenesis and immune cell recruitment in response to various "danger" signals, such as those produced during infection or tissue damage. Endothelial TLR2 also supported tumor growth in a mouse model of prostate cancer. These findings show that the endothelium contributes to innate immune responses and that TLR2 may be a therapeutic target in cancer (see also the Focus by Mahfoud and Petrova). Toll-like receptor 2 (TLR2) is implicated in various pathologies, mainly in terms of its function within innate immune cells. However, TLR2 is also present in endothelial cells. Here, we explored the physiological and pathophysiological roles of endothelial TLR2 signaling. We found that TLR2 was highly abundant in the endothelium within various tissues using TLR2-IRES-EGFP reporter mice and was required for proinflammatory endothelial cell function. Endothelial cells lacking TLR2 exhibited reduced proinflammatory potential at the protein, cell, and tissue levels. Loss of endothelial TLR2 blunted the inflammatory response to both exogenous and endogenous danger signals in endothelial cells in culture and in vivo. Endothelial TLR2 promoted tumor growth, angiogenesis, and protumorigenic immune cell recruitment in a mouse model of prostate cancer. Furthermore, the cell surface localization of P-selectin and the subsequent production of other critical cell adhesion molecules (such as E-selectin, ICAM-1, and VCAM-1) that recruit immune cells required endothelial TLR2. Our findings demonstrate that endothelial cells actively contribute to innate immune pathways and propose that endothelial TLR2 has a pathological role in proinflammatory conditions. [ABSTRACT FROM AUTHOR]

Fertilization studies have elucidated basic principles of the role of nutrients in shaping plant communities and demonstrated the potential effects of anthropogenic nutrient deposition. Yet less is known about how these effects are mediated by interacting ecological factors, particularly in nutrient‐poor wetland habitats. In a long‐term experiment in a coastal plain wetland, we examined how fertilization and mowing affected the diversity and composition of a plant community as it reestablished after major disturbance. A drainage ditch in proximity to the experimental plots allowed us also to consider the influence of hydrology and its interactions with nutrient addition. Fertilization decreased species richness, with wetland specialist species showing especially great losses, and several lines of evidence suggest that the effect was mediated by competition for light. Altered hydrology via ditch drainage had effects that were similar to fertilization, with more rapidly draining plots showing lower diversity and decreased abundance of wetland species. Plant community diversity and dynamics were influenced by complex interactions between fertilization, disturbance, and hydrology. The negative effect of fertilization on species richness was initially mitigated by mowing, but in later years was more evident in mowed than in unmowed plots. In the absence of disturbance, nutrient addition increased the rate of transition to primarily woody communities. Similarly, drained plots experienced increased rates of succession compared to wetter plots. Our results suggest that these interactions need to be considered to understand the potential effects of anthropogenic nutrient addition and hydrologic alterations to wetland ecosystems. [ABSTRACT FROM AUTHOR]