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1.
PLoS One ; 19(3): e0294897, 2024.
Article in English | MEDLINE | ID: mdl-38512960

ABSTRACT

BACKGROUND: SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and viral loads over the course of COVID-19 infection with these sub-variants in otherwise-healthy, vaccinated, non-hospitalised adults, and compared data to infections with the preceding Delta variant of concern (VOC). METHODS: In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive polymerase chain reaction (PCR) or lateral flow test, self-swabbed on alternate weekdays until day 10. We compared participant-reported symptoms and viral load trajectories between infections caused by VOCs Delta and Omicron (sub-variants BA.1, BA.2 or BA.4/5), and tested for relationships between vaccine dose, symptoms and PCR cycle threshold (Ct) as a proxy for viral load using Chi-squared (χ2) and Wilcoxon tests. RESULTS: 563 infection episodes were reported among 491 participants. Across infection episodes, there was little variation in symptom burden (4 [IQR 3-5] symptoms) and duration (8 [IQR 6-11] days). Whilst symptom profiles differed among infections caused by Delta compared to Omicron sub-variants, symptom profiles were similar between Omicron sub-variants. Anosmia was reported more frequently in Delta infections after 2 doses compared with Omicron sub-variant infections after 3 doses, for example: 42% (25/60) of participants with Delta infection compared to 9% (6/67) with Omicron BA.4/5 (χ2 P < 0.001; OR 7.3 [95% CI 2.7-19.4]). Fever was less common with Delta (20/60 participants; 33%) than Omicron BA.4/5 (39/67; 58%; χ2 P = 0.008; OR 0.4 [CI 0.2-0.7]). Amongst infections with an Omicron sub-variants, symptoms of coryza, fatigue, cough and myalgia predominated. Viral load trajectories and peaks did not differ between Delta, and Omicron, irrespective of symptom severity (including asymptomatic participants), VOC or vaccination status. PCR Ct values were negatively associated with time since vaccination in participants infected with BA.1 (ß = -0.05 (CI -0.10-0.01); P = 0.031); however, this trend was not observed in BA.2 or BA.4/5 infections. CONCLUSION: Our study emphasises both the changing symptom profile of COVID-19 infections in the Omicron era, and ongoing transmission risk of Omicron sub-variants in vaccinated adults. TRIAL REGISTRATION: NCT04750356.


Subject(s)
COVID-19 , Adult , Humans , COVID-19/prevention & control , SARS-CoV-2 , Prospective Studies , Vaccination
2.
Science ; 383(6684): 782-788, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38359113

ABSTRACT

Competition, facilitation, and predation offer alternative explanations for successional patterns of migratory herbivores. However, these interactions are difficult to measure, leaving uncertainty about the mechanisms underlying body-size-dependent grazing-and even whether succession occurs at all. We used data from an 8-year camera-trap survey, GPS-collared herbivores, and fecal DNA metabarcoding to analyze the timing, arrival order, and interactions among migratory grazers in Serengeti National Park. Temporal grazing succession is characterized by a "push-pull" dynamic: Competitive grazing nudges zebra ahead of co-migrating wildebeest, whereas grass consumption by these large-bodied migrants attracts trailing, small-bodied gazelle that benefit from facilitation. "Natural experiments" involving intense wildfires and rainfall respectively disrupted and strengthened these effects. Our results highlight a balance between facilitative and competitive forces in co-regulating large-scale ungulate migrations.


Subject(s)
Animal Migration , Antelopes , Equidae , Herbivory , Parks, Recreational , Animals , Antelopes/physiology , Equidae/physiology , Poaceae , Kenya , Tanzania
3.
Nature ; 623(7988): 757-764, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37968390

ABSTRACT

Extreme weather events perturb ecosystems and increasingly threaten biodiversity1. Ecologists emphasize the need to forecast and mitigate the impacts of these events, which requires knowledge of how risk is distributed among species and environments. However, the scale and unpredictability of extreme events complicate risk assessment1-4-especially for large animals (megafauna), which are ecologically important and disproportionately threatened but are wide-ranging and difficult to monitor5. Traits such as body size, dispersal ability and habitat affiliation are hypothesized to determine the vulnerability of animals to natural hazards1,6,7. Yet it has rarely been possible to test these hypotheses or, more generally, to link the short-term and long-term ecological effects of weather-related disturbance8,9. Here we show how large herbivores and carnivores in Mozambique responded to Intense Tropical Cyclone Idai, the deadliest storm on record in Africa, across scales ranging from individual decisions in the hours after landfall to changes in community composition nearly 2 years later. Animals responded behaviourally to rising floodwaters by moving upslope and shifting their diets. Body size and habitat association independently predicted population-level impacts: five of the smallest and most lowland-affiliated herbivore species declined by an average of 28% in the 20 months after landfall, while four of the largest and most upland-affiliated species increased by an average of 26%. We attribute the sensitivity of small-bodied species to their limited mobility and physiological constraints, which restricted their ability to avoid the flood and endure subsequent reductions in the quantity and quality of food. Our results identify general traits that govern animal responses to severe weather, which may help to inform wildlife conservation in a volatile climate.


Subject(s)
Body Size , Cyclonic Storms , Mammals , Animals , Altitude , Biodiversity , Carnivory , Conservation of Natural Resources , Diet/veterinary , Ecosystem , Extreme Weather , Floods , Forecasting , Herbivory , Mammals/anatomy & histology , Mammals/physiology , Mozambique
4.
Curr Biol ; 33(11): R584-R610, 2023 06 05.
Article in English | MEDLINE | ID: mdl-37279691

ABSTRACT

Large herbivores play unique ecological roles and are disproportionately imperiled by human activity. As many wild populations dwindle towards extinction, and as interest grows in restoring lost biodiversity, research on large herbivores and their ecological impacts has intensified. Yet, results are often conflicting or contingent on local conditions, and new findings have challenged conventional wisdom, making it hard to discern general principles. Here, we review what is known about the ecosystem impacts of large herbivores globally, identify key uncertainties, and suggest priorities to guide research. Many findings are generalizable across ecosystems: large herbivores consistently exert top-down control of plant demography, species composition, and biomass, thereby suppressing fires and the abundance of smaller animals. Other general patterns do not have clearly defined impacts: large herbivores respond to predation risk but the strength of trophic cascades is variable; large herbivores move vast quantities of seeds and nutrients but with poorly understood effects on vegetation and biogeochemistry. Questions of the greatest relevance for conservation and management are among the least certain, including effects on carbon storage and other ecosystem functions and the ability to predict outcomes of extinctions and reintroductions. A unifying theme is the role of body size in regulating ecological impact. Small herbivores cannot fully substitute for large ones, and large-herbivore species are not functionally redundant - losing any, especially the largest, will alter net impact, helping to explain why livestock are poor surrogates for wild species. We advocate leveraging a broad spectrum of techniques to mechanistically explain how large-herbivore traits and environmental context interactively govern the ecological impacts of these animals.


Subject(s)
Ecosystem , Herbivory , Animals , Humans , Herbivory/physiology , Biomass , Biodiversity , Plants
5.
Article in English | MEDLINE | ID: mdl-36800396

ABSTRACT

Due to allergy concerns, it is mandatory under EU law to declare in food products all ingredients derived from fish. Gelatine is prepared from the waste collagen of animal carcasses, including piscine, bovine and porcine materials, and is an ingredient in a wide range of foods. The Elliott Review into the integrity and assurance of food supply networks highlighted requirements for analytical surveillance methods to support due diligence, food safety and authenticity. We present the development of a method to extract gelatine from foods and determine the presence of piscine gelatine by liquid chromatography-tandem mass spectrometry using a suite of sixteen piscine marker peptides. The method has been successfully applied to gelatine granules, capsules and composite retail food products. While a study is required to determine parameters including the limit of detection of this method, the data indicate the method is reproducible between replicates of sub-samples and applies to a range of piscine gelatines collected over 16 years. Once validation studies are complete, there is potential for enforcement officers to apply the technology to verify the authenticity of fish products to support consumers in ensuring food safety and also food provenance relating to animal origin.


Subject(s)
Food , Gelatin , Animals , Cattle , Swine , Gelatin/chemistry , Peptides/analysis , Food Security , Biomarkers/analysis
6.
J Matern Fetal Neonatal Med ; 36(1): 2167074, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36642443

ABSTRACT

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a multifactorial disease with neurodevelopmental implications. This study aims to quantify the risks of adverse neurodevelopmental outcomes for each BPD grade among preterm infants born at less than 30 weeks' gestation. METHODS: We retrospectively studied infants who received care in our institution until at least 36 weeks postmenstrual age and had a formal neurodevelopmental assessment in our infant follow-up clinic using the Bayley Scales for Infant and Toddler Development (BSID). We assessed the association between BPD grade and adverse neurodevelopmental outcomes using descriptive statistics and regression models. RESULTS: Two hundred and fifty infants, including 89 (35.6%), 87 (34.8%), 65 (20.6%), and 9 (3.6%) with No BPD, Grade 1, Grade 2, and Grade 3 BPD, were included in the study. Small for gestational age, late pulmonary hypertension, dexamethasone administration, and adverse neurodevelopmental outcomes were more common as BPD grade increased. In a logistic regression analysis, Grades 2 and 3, but not Grade 1, BPD were associated with increased odds of a composite adverse neurodevelopmental outcome by 2.7 and 7.2 folds, respectively. A BSID domain-specific analysis showed that higher grades were associated with lower scores in the cognitive, gross motor, and fine motor domains. CONCLUSIONS: Grades 2 and 3 BPD, but not Grade 1, correlate with risks of adverse neurodevelopmental outcomes at a grade-dependent manner in our single-center cohort retrospective study. Further validation using a multi-center large cohort is warranted.


Subject(s)
Bronchopulmonary Dysplasia , Hypertension, Pulmonary , Infant , Female , Infant, Newborn , Humans , Infant, Premature , Bronchopulmonary Dysplasia/epidemiology , Bronchopulmonary Dysplasia/complications , Retrospective Studies , Gestational Age , Hypertension, Pulmonary/complications
7.
Hip Int ; 33(2): 207-213, 2023 Mar.
Article in English | MEDLINE | ID: mdl-34424781

ABSTRACT

INTRODUCTION: There is conflicting evidence as to whether or not patients undergoing total hip arthroplasty (THA) via the direct anterior approach (DAA) have increased risk of component malposition. The aim of this study was to investigate whether specific preoperative radiographic features were predictive of postoperative component malposition in DAA THA. PATIENTS AND METHODS: We examined 204 THA operations performed for osteoarthritis via the DAA at a single institution. Preoperative radiographs were analysed with numerous pre-specified measurements and classifications being recorded. Postoperative radiographs were analysed to determine if any of these preoperative radiographic factors correlated with component malposition in regard to cup inclination, cup version, femoral stem coronal alignment, leg-length discrepancy (LLD) and femoral offset discrepancy. RESULTS: Numerous preoperative factors were associated with component malposition. Coxa profunda was found to be a significant predictor of cup anteversion being outside of the target range (p = 0.0089) and an increased centre-edge angle was a significant predictor for a postoperative LLD (p = 0.0134). A decreased neck-shaft angle (p = 0.0007) and a lower preoperative LLD (p = 0.0019) were both predictive of femoral stem coronal malalignment. CONCLUSIONS: Preoperative radiographs can be a valuable tool for surgeons in predicting patients at risk of component malposition in DAA THA.


Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Humans , Arthroplasty, Replacement, Hip/adverse effects , Hip Prosthesis/adverse effects , Radiography , Leg Length Inequality/diagnostic imaging , Leg Length Inequality/etiology
8.
Ecology ; 104(2): e3921, 2023 02.
Article in English | MEDLINE | ID: mdl-36415899

ABSTRACT

Many populations of consumers consist of relatively specialized individuals that eat only a subset of the foods consumed by the population at large. Although the ecological significance of individual-level diet variation is recognized, such variation is difficult to document, and its underlying mechanisms are poorly understood. Optimal foraging theory provides a useful framework for predicting how individuals might select different diets, positing that animals balance the "opportunity cost" of stopping to eat an available food item against the cost of searching for something more nutritious; diet composition should be contingent on the distribution of food, and individual foragers should be more selective when they have greater energy reserves to invest in searching for high-quality foods. We tested these predicted mechanisms of individual niche differentiation by quantifying environmental (resource heterogeneity) and organismal (nutritional condition) determinants of diet in a widespread browsing antelope (bushbuck, Tragelaphus sylvaticus) in an African floodplain-savanna ecosystem. We quantified individuals' realized dietary niches (taxonomic richness and composition) using DNA metabarcoding of fecal samples collected repeatedly from 15 GPS-collared animals (range 6-14 samples per individual, median 12). Bushbuck diets were structured by spatial heterogeneity and constrained by individual condition. We observed significant individual-level partitioning of food plants by bushbuck both within and between two adjacent habitat types (floodplain and woodland). Individuals with home ranges that were closer together and/or had similar vegetation structure (measured using LiDAR) ate more similar diets, supporting the prediction that heterogeneous resource distribution promotes individual differentiation. Individuals in good nutritional condition had significantly narrower diets (fewer plant taxa), searched their home ranges more intensively (intensity-of-use index), and had higher-quality diets (percent digestible protein) than those in poor condition, supporting the prediction that animals with greater endogenous reserves have narrower realized niches because they can invest more time in searching for nutritious foods. Our results support predictions from optimal foraging theory about the energetic basis of individual-level dietary variation and provide a potentially generalizable framework for understanding how individuals' realized niche width is governed by animal behavior and physiology in heterogeneous landscapes.


Subject(s)
Ecosystem , Herbivory , Animals , Diet/veterinary , Forests , Food
9.
Proc Natl Acad Sci U S A ; 119(35): e2204400119, 2022 08 30.
Article in English | MEDLINE | ID: mdl-35994662

ABSTRACT

Ecological niche differences are necessary for stable species coexistence but are often difficult to discern. Models of dietary niche differentiation in large mammalian herbivores invoke the quality, quantity, and spatiotemporal distribution of plant tissues and growth forms but are agnostic toward food plant species identity. Empirical support for these models is variable, suggesting that additional mechanisms of resource partitioning may be important in sustaining large-herbivore diversity in African savannas. We used DNA metabarcoding to conduct a taxonomically explicit analysis of large-herbivore diets across southeastern Africa, analyzing ∼4,000 fecal samples of 30 species from 10 sites in seven countries over 6 y. We detected 893 food plant taxa from 124 families, but just two families-grasses and legumes-accounted for the majority of herbivore diets. Nonetheless, herbivore species almost invariably partitioned food plant taxa; diet composition differed significantly in 97% of pairwise comparisons between sympatric species, and dissimilarity was pronounced even between the strictest grazers (grass eaters), strictest browsers (nongrass eaters), and closest relatives at each site. Niche differentiation was weakest in an ecosystem recovering from catastrophic defaunation, indicating that food plant partitioning is driven by species interactions, and was stronger at low rainfall, as expected if interspecific competition is a predominant driver. Diets differed more between browsers than grazers, which predictably shaped community organization: Grazer-dominated trophic networks had higher nestedness and lower modularity. That dietary differentiation is structured along taxonomic lines complements prior work on how herbivores partition plant parts and patches and suggests that common mechanisms govern herbivore coexistence and community assembly in savannas.


Subject(s)
Diet , Grassland , Herbivory , Mammals , Plants , Africa , Animals , Competitive Behavior , DNA Barcoding, Taxonomic , Diet/statistics & numerical data , Diet/veterinary , Fabaceae/classification , Fabaceae/genetics , Feces , Mammals/classification , Mammals/physiology , Plants/classification , Plants/genetics , Poaceae/classification , Poaceae/genetics , Rain
10.
Am Nat ; 199(6): 855-868, 2022 06.
Article in English | MEDLINE | ID: mdl-35580221

ABSTRACT

AbstractNiche packing is one of the prevailing mechanisms underlying the increase in the number of co-occurring species and the extraordinary diversity of tropical ecosystems. However, it is not yet understood whether niche packing is facilitated by higher specialization and reduced niche overlap or, rather, by diffuse competition and increased niche overlap. We combined highly resolved bird-plant interaction networks, bird phylogenies, and plant functional traits to compare dietary niche overlap and foraging frequencies among frugivorous birds at seven sites in the tropical Andes. We quantified niche overlap on the basis of the traits of the plants used by each bird and related it to the degree of niche packing at the different sites. Niche complementarity decreased with increasing niche packing, suggesting that increasingly dense niche packing is facilitated by increased niche overlap. Pairwise niche overlap was mediated by shifts in foraging frequencies away from shared resources, and it decreased with decreasing phylogenetic relatedness and increasing dependence on fruit as resource. Our findings suggest that foraging choices are a key axis of diversification in frugivorous birds and that differences in resource use frequencies are already sufficient to reduce potential competition between ecologically similar species and facilitate niche packing, especially if species differ in their dependence on particular resources.


Subject(s)
Biodiversity , Birds , Animals , Diet , Ecosystem , Feeding Behavior , Fruit , Phylogeny
11.
Proc Biol Sci ; 289(1974): 20212702, 2022 05 11.
Article in English | MEDLINE | ID: mdl-35538775

ABSTRACT

Amidst global shifts in the distribution and abundance of wildlife and livestock, we have only a rudimentary understanding of ungulate parasite communities and parasite-sharing patterns. We used qPCR and DNA metabarcoding of fecal samples to characterize gastrointestinal nematode (Strongylida) community composition and sharing among 17 sympatric species of wild and domestic large mammalian herbivore in central Kenya. We tested a suite of hypothesis-driven predictions about the role of host traits and phylogenetic relatedness in describing parasite infections. Host species identity explained 27-53% of individual variation in parasite prevalence, richness, community composition and phylogenetic diversity. Host and parasite phylogenies were congruent, host gut morphology predicted parasite community composition and prevalence, and hosts with low evolutionary distinctiveness were centrally positioned in the parasite-sharing network. We found no evidence that host body size, social-group size or feeding height were correlated with parasite composition. Our results highlight the interwoven evolutionary and ecological histories of large herbivores and their gastrointestinal nematodes and suggest that host identity, phylogeny and gut architecture-a phylogenetically conserved trait related to parasite habitat-are the overriding influences on parasite communities. These findings have implications for wildlife management and conservation as wild herbivores are increasingly replaced by livestock.


Subject(s)
Nematoda , Parasites , Animals , Animals, Wild/parasitology , Herbivory , Host-Parasite Interactions , Livestock , Mammals , Phylogeny
12.
Ecol Lett ; 25(4): 992-1008, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34967090

ABSTRACT

Diet composition is among the most important yet least understood dimensions of animal ecology. Inspired by the study of species abundance distributions (SADs), we tested for generalities in the structure of vertebrate diets by characterising them as dietary abundance distributions (DADs). We compiled data on 1167 population-level diets, representing >500 species from six vertebrate classes, spanning all continents and oceans. DADs near-universally (92.5%) followed a hollow-curve shape, with scant support for other plausible rank-abundance-distribution shapes. This strong generality is inherently related to, yet incompletely explained by, the SADs of available food taxa. By quantifying dietary generalisation as the half-saturation point of the cumulative distribution of dietary abundance (sp50, minimum number of foods required to account for 50% of diet), we found that vertebrate populations are surprisingly specialised: in most populations, fewer than three foods accounted for at least half the diet. Variation in sp50 was strongly associated with consumer type, with carnivores being more specialised than herbivores or omnivores. Other methodological (sampling method and effort, taxonomic resolution), biological (body mass, frugivory) and biogeographic (latitude) factors influenced sp50 to varying degrees. Future challenges include identifying the mechanisms underpinning the hollow-curve DAD, its generality beyond vertebrates, and the biological determinants of dietary generalisation.


Subject(s)
Ecology , Herbivory , Animals , Diet , Vertebrates
13.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Article in English | MEDLINE | ID: mdl-34580170

ABSTRACT

African savannas are the last stronghold of diverse large-mammal communities, and a major focus of savanna ecology is to understand how these animals affect the relative abundance of trees and grasses. However, savannas support diverse plant life-forms, and human-induced changes in large-herbivore assemblages-declining wildlife populations and their displacement by livestock-may cause unexpected shifts in plant community composition. We investigated how herbivory affects the prevalence of lianas (woody vines) and their impact on trees in an East African savanna. Although scarce (<2% of tree canopy area) and defended by toxic latex, the dominant liana, Cynanchum viminale (Apocynaceae), was eaten by 15 wild large-herbivore species and was consumed in bulk by native browsers during experimental cafeteria trials. In contrast, domesticated ungulates rarely ate lianas. When we experimentally excluded all large herbivores for periods of 8 to 17 y (simulating extirpation), liana abundance increased dramatically, with up to 75% of trees infested. Piecewise exclusion of different-sized herbivores revealed functional complementarity among size classes in suppressing lianas. Liana infestation reduced tree growth and reproduction, but herbivores quickly cleared lianas from trees after the removal of 18-y-old exclosure fences (simulating rewilding). A simple model of liana contagion showed that, without herbivores, the long-term equilibrium could be either endemic (liana-tree coexistence) or an all-liana alternative stable state. We conclude that ongoing declines of wild large-herbivore populations will disrupt the structure and functioning of many African savannas in ways that have received little attention and that may not be mitigated by replacing wildlife with livestock.


Subject(s)
Cynanchum/growth & development , Ecosystem , Food Preferences , Herbivory/physiology , Trees/growth & development , Africa , Animals , Animals, Wild , Elephants , Environmental Restoration and Remediation , Giraffes , Humans , Livestock
14.
PLoS One ; 16(7): e0255056, 2021.
Article in English | MEDLINE | ID: mdl-34293065

ABSTRACT

Grassy biomes such as savannas are maintained by an interacting suite of ecosystem processes from herbivory to rainfall to fire. Many studies have examined the impacts of large mammalian herbivores on herbaceous plant communities, but few of these studies have been conducted in humid, fertile savannas. We present the findings of a short-term experiment that investigated the effects of herbivory in a fertile, humid, and semi-managed savanna. We erected large-herbivore exclosures in Alas Purwo National Park, Java, Indonesia where rainfall is high and fire is suppressed to test how herbivores impact plant community development across the growing season. Where large mammalian herbivores were excluded, herbaceous plant communities contained more non-grasses and were less similar; diverging in their composition as the growing season progressed. Effects of herbivore exclusion on plant species richness, evenness, and biomass per quadrat were generally weak. Notably, however, two weedy plant species (one native, Imperata cylindrica and one introduced, Senna cf. tora) appeared to benefit most from herbivore release. Our results suggest that heavy grazing pressure by native large mammalian herbivores controlled the composition of the herbaceous plant community. Moreover, exclusion of large mammalian herbivores led to divergence in the plant species composition of exclosures; compositional dissimilarity between herbivore-exclusion plots was higher than between plots exposed to large mammalian herbivores. Our findings suggest that, at this high-rainfall site, large mammalian herbivores constrained the developmental trajectory of plant communities across the growing season.


Subject(s)
Grassland , Herbivory/physiology , Mammals/physiology , Plants , Animals , Geography , Indonesia , Seasons , Species Specificity
15.
Curr Biol ; 31(13): 2964-2971.e5, 2021 07 12.
Article in English | MEDLINE | ID: mdl-34004144

ABSTRACT

Pollination by animals is a key ecosystem service1,2 and interactions between plants and their pollinators are a model system for studying ecological networks,3,4 yet plant-pollinator networks are typically studied in isolation from the broader ecosystems in which they are embedded. The plants visited by pollinators also interact with other consumer guilds that eat stems, leaves, fruits, or seeds. One such guild, large mammalian herbivores, are well-known ecosystem engineers5-7 and may have substantial impacts on plant-pollinator networks. Although moderate herbivory can sometimes promote plant diversity,8 potentially benefiting pollinators, large herbivores might alternatively reduce resource availability for pollinators by consuming flowers,9 reducing plant density,10 and promoting somatic regrowth over reproduction.11 The direction and magnitude of such effects may hinge on abiotic context-in particular, rainfall, which modulates the effects of ungulates on vegetation.12 Using a long-term, large-scale experiment replicated across a rainfall gradient in central Kenya, we show that a diverse assemblage of native large herbivores, ranging from 5-kg antelopes to 4,000-kg African elephants, limited resource availability for pollinators by reducing flower abundance and diversity; this in turn resulted in fewer pollinator visits and lower pollinator diversity. Exclusion of large herbivores increased floral-resource abundance and pollinator-assemblage diversity, rendering plant-pollinator networks larger, more functionally redundant, and less vulnerable to pollinator extinction. Our results show that species extrinsic to plant-pollinator interactions can indirectly and strongly alter network structure. Forecasting the effects of environmental change on pollination services and interaction webs more broadly will require accounting for the effects of extrinsic keystone species.


Subject(s)
Grassland , Herbivory , Plants , Pollination , Africa , Animals , Flowers
16.
Mol Cancer Ther ; 20(3): 589-601, 2021 03.
Article in English | MEDLINE | ID: mdl-33298589

ABSTRACT

Oncolytic viruses (OV) have been shown to activate the antitumor functions of specific immune cells like T cells. Here, we show OV can also reprogram tumor-associated macrophage (TAM) to a less immunosuppressive phenotype. Syngeneic, immunocompetent mouse models of primary breast cancer were established using PyMT-TS1, 4T1, and E0771 cell lines, and a metastatic model of breast cancer was established using the 4T1 cell line. Tumor growth and overall survival was assessed following intravenous administration of the OV, HSV1716 (a modified herpes simplex virus). Infiltration and function of various immune effector cells was assessed by NanoString, flow cytometry of dispersed tumors, and immunofluorescence analysis of tumor sections. HSV1716 administration led to marked tumor shrinkage in primary mammary tumors and a decrease in metastases. This was associated with a significant increase in the recruitment/activation of cytotoxic T cells, a reduction in the presence of regulatory T cells and the reprograming of TAMs towards a pro-inflammatory, less immunosuppressive phenotype. These findings were supported by in vitro data demonstrating that human monocyte-derived macrophages host HSV1716 replication, and that this led to immunogenic macrophage lysis. These events were dependent on macrophage expression of proliferating cell nuclear antigen (PCNA). Finally, the antitumor effect of OV was markedly diminished when TAMs were depleted using clodronate liposomes. Together, our results show that TAMs play an essential role in support of the tumoricidal effect of the OV, HSV1716-they both host viral replication via a novel, PCNA-dependent mechanism and are reprogramed to express a less immunosuppressive phenotype.


Subject(s)
Macrophages/metabolism , Oncolytic Viruses/pathogenicity , Animals , Disease Models, Animal , Female , Humans , Mammary Neoplasms, Animal , Mice , Transfection
17.
Physiol Rep ; 8(13): e14482, 2020 07.
Article in English | MEDLINE | ID: mdl-32643289

ABSTRACT

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) begins with steatosis, where a mixed macrovesicular pattern of large and small lipid droplets (LDs) develops. Since in vitro models recapitulating this are limited, the aims of this study were to develop mixed macrovesicular steatosis in immortalized hepatocytes and investigate effects on intracellular metabolism by altering nutritional substrates. METHODS: Huh7 cells were cultured in 11 mM glucose and 2% human serum (HS) for 7 days before additional sugars and fatty acids (FAs), either with 200 µM FAs (low fat low sugar; LFLS), 5.5 mM fructose + 200 µM FAs (low fat high sugar; LFHS), or 5.5 mM fructose + 800 µM FAs (high fat high sugar; HFHS), were added for 7 days. FA metabolism, lipid droplet characteristics, and transcriptomic signatures were investigated. RESULTS: Between the LFLS and LFHS conditions, there were few notable differences. In the HFHS condition, intracellular triacylglycerol (TAG) was increased and the LD pattern and distribution was similar to that found in primary steatotic hepatocytes. HFHS-treated cells had lower levels of de novo-derived FAs and secreted larger, TAG-rich lipoprotein particles. RNA sequencing and gene set enrichment analysis showed changes in several pathways including those involved in metabolism and cell cycle. CONCLUSIONS: Repeated doses of HFHS treatment resulted in a cellular model of NAFLD with a mixed macrovesicular LD pattern and metabolic dysfunction. Since these nutrients have been implicated in the development of NAFLD in humans, the model provides a good physiological basis for studying NAFLD development or regression in vitro.


Subject(s)
Fatty Acids/metabolism , Glucose/metabolism , Hepatocytes/metabolism , Lipid Droplets/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Cell Line, Tumor , Cells, Cultured , Hepatocytes/pathology , Humans , Lipid Droplets/pathology , Non-alcoholic Fatty Liver Disease/genetics , Transcriptome
18.
Diabetes Care ; 43(5): 1134-1141, 2020 05.
Article in English | MEDLINE | ID: mdl-32165444

ABSTRACT

OBJECTIVE: Debate continues regarding the influence of dietary fats and sugars on the risk of developing metabolic diseases, including insulin resistance and nonalcoholic fatty liver disease (NAFLD). We investigated the effect of two eucaloric diets, one enriched with saturated fat (SFA) and the other enriched with free sugars (SUGAR), on intrahepatic triacylglycerol (IHTAG) content, hepatic de novo lipogenesis (DNL), and whole-body postprandial metabolism in overweight males. RESEARCH DESIGN AND METHODS: Sixteen overweight males were randomized to consume the SFA or SUGAR diet for 4 weeks before consuming the alternate diet after a 7-week washout period. The metabolic effects of the respective diets on IHTAG content, hepatic DNL, and whole-body metabolism were investigated using imaging techniques and metabolic substrates labeled with stable-isotope tracers. RESULTS: Consumption of the SFA diet significantly increased IHTAG by mean ± SEM 39.0 ± 10.0%, while after the SUGAR diet IHTAG was virtually unchanged. Consumption of the SFA diet induced an exaggerated postprandial glucose and insulin response to a standardized test meal compared with SUGAR. Although whole-body fat oxidation, lipolysis, and DNL were similar following the two diets, consumption of the SUGAR diet resulted in significant (P < 0.05) decreases in plasma total, HDL, and non-HDL cholesterol and fasting ß-hydroxybutyrate plasma concentrations. CONCLUSIONS: Consumption of an SFA diet had a potent effect, increasing IHTAG together with exaggerating postprandial glycemia. The SUGAR diet did not influence IHTAG and induced minor metabolic changes. Our findings indicate that a diet enriched in SFA is more harmful to metabolic health than a diet enriched in free sugars.


Subject(s)
Blood Glucose/drug effects , Dietary Carbohydrates/pharmacology , Dietary Fats/pharmacology , Fatty Acids , Liver/drug effects , Postprandial Period/drug effects , Adult , Blood Glucose/metabolism , Cross-Over Studies , Diet , Diet, High-Fat/adverse effects , Fatty Acids/metabolism , Fatty Acids/pharmacology , Humans , Insulin Resistance , Lipid Metabolism/drug effects , Lipids/blood , Liver/metabolism , Male , Meals , Middle Aged , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Risk Factors
19.
Nat Ecol Evol ; 4(5): 712-724, 2020 05.
Article in English | MEDLINE | ID: mdl-31932702

ABSTRACT

Trophic rewilding seeks to rehabilitate degraded ecosystems by repopulating them with large animals, thereby re-establishing strong top-down interactions. Yet there are very few tests of whether such initiatives can restore ecosystem structure and functions, and on what timescales. Here we show that war-induced collapse of large-mammal populations in Mozambique's Gorongosa National Park exacerbated woody encroachment by the invasive shrub Mimosa pigra-considered one of the world's 100 worst invasive species-and that one decade of concerted trophic rewilding restored this invasion to pre-war baseline levels. Mimosa occurrence increased between 1972 and 2015, a period encompassing the near extirpation of large herbivores during the Mozambican Civil War. From 2015 to 2019, mimosa abundance declined as ungulate biomass recovered. DNA metabarcoding revealed that ruminant herbivores fed heavily on mimosa, and experimental exclosures confirmed the causal role of mammalian herbivory in containing shrub encroachment. Our results provide mechanistic evidence that trophic rewilding has rapidly revived a key ecosystem function (biotic resistance to a notorious woody invader), underscoring the potential for restoring ecological health in degraded protected areas.


Subject(s)
Conservation of Natural Resources , Ecosystem , Animals , Herbivory , Introduced Species , Mammals
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