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Abstract Our understanding of the similarity in trajectories of ecosystem changes during different directions of environmental change is limited. For example, do the dominant organisms exhibit the same responses to different directions of environmental change, that is, do they exhibit symmetric responses? Here, we explore whether such response symmetry is determined and controlled by the symmetry in the features of the underlying biological system (i.e., system symmetry), such as in the network and strength of biotic and abiotic processes, and in symmetry of the environmental change (i.e., environmental symmetry). For this exploration, we developed and used a simple mathematical model of a microbial ecosystem driven by mutual inhibition in which we could vary the amount of system and environmental symmetry. Our results show that perfect system and environmental symmetry indeed produce perfect response symmetry. Moreover, introducing asymmetry in biological systems or in the environment proportionally increases response asymmetry. These findings suggest using symmetries in ecosystem structure and interaction strength to better understand and predict similarities in degradation and restoration phases of environmental change.

Abstract Facing climate change and biodiversity loss, it is critical that ecology advances so that processes, such as species interactions and dynamics, can be correctly estimated and skillfully forecasted. As different processes occur on different time scales, the sampling frequency used to record them should intuitively match these scales. Yet, the effect of data sampling frequency on ecological forecasting accuracy is understudied. Using a simple simulated dataset as a baseline and a more complex high‐frequency plankton dataset, we tested how different sampling frequencies impacted abundance forecasts of different plankton classes and the estimation of their interactions. We then investigated whether plankton growth rates and body sizes could be used to select the most appropriate sampling frequency. The simple simulated dataset showed that the optimal sampling frequency scaled positively with growth rate. This finding was not repeated in the analyses of the plankton time series, however. There, we found that a reduction in sampling frequency worsened forecasts and led us to both over‐ and underestimate plankton interactions. This suggests that forecasting can be used to determine the ideal sampling frequency in scientific and monitoring programs. A better study design will improve theoretical understanding of ecology and advance policy measures dealing with current global challenges.

Microxanox is an R package to simulate a three functional group ecosystem (cyanobacteria, phototrophic sulfur bacteria, and sulfate-reducing bacteria) with four chemical substrates (phosphorus, oxygen, reduced sulfur, and oxidized sulfur) using a set of ordinary differential equations. Simulations can be run individually or over a parameter range. The model can be implemented with different numbers of species per functional group. The package is constructed in such a way that the results contain the input parameter used, so that a saved results can be loaded again and the simulation be repeated. Furthermore, the package framework and code should serve as a useful starting point for making simulation models of other types of ecosystems.

Abstract The insurance effect of biodiversity—that diversity stabilises aggregate ecosystem properties—is mechanistically underlain by inter‐ and intraspecific trait variation in organismal responses to the environment. This variation, termed response diversity, is therefore a potentially critical determinant of ecological stability. However, response diversity has yet to be widely quantified, possibly due to difficulties in its measurement. Even when it has been measured, approaches have varied. Here, we review methods for measuring response diversity and from them distil a methodological framework for quantifying response diversity from experimental and/or observational data, which can be practically applied in laboratory and field settings across a range of taxa. Previous empirical studies on response diversity most commonly invoke response traits as proxies aimed at capturing species' ecological responses to the environment. Our approach, which is based on environment‐dependent ecological responses to any biotic or abiotic environmental variable, is conceptually simple and robust to any form of environmental response, including nonlinear responses. Given its derivation from empirical data on species' ecological responses, this approach should more directly reflect response diversity than the trait‐based approach dominant in the literature. By capturing even subtle inter‐ or intraspecific variation in environmental responses, and environment dependencies in response diversity, we hope this framework will motivate tests of the diversity–stability relationship from a new perspective, and provide an approach for mapping, monitoring and conserving this critical dimension of biodiversity.

The direct relationship between societal development and local ecosystem services breaks down at relatively minor levels of human modification of large river delta landscapes, according to a statistical analysis of 235 deltas.

Abstract Metadata plays an essential role in the long‐term preservation, reuse, and interoperability of data. Nevertheless, creating useful metadata can be sufficiently difficult and weakly enough incentivized that many datasets may be accompanied by little or no metadata. One key challenge is, therefore, how to make metadata creation easier and more valuable. We present a solution that involves creating domain‐specific metadata schemes that are as complex as necessary and as simple as possible. These goals are achieved by co‐development between a metadata expert and the researchers (i.e., the data creators). The final product is a bespoke metadata scheme into which researchers can enter information (and validate it) via the simplest of interfaces: a web browser application and a spreadsheet. We provide the R package dmdScheme (dmdScheme: An R package for working with domain specific MetaData schemes (Version v0.9.22), 2019) for creating a template domain‐specific scheme. We describe how to create a domain‐specific scheme from this template, including the iterative co‐development process, and the simple methods for using the scheme, and simple methods for quality assessment, improvement, and validation. The process of developing a metadata scheme following the outlined approach was successful, resulting in a metadata scheme which is used for the data generated in our research group. The validation quickly identifies forgotten metadata, as well as inconsistent metadata, therefore improving the quality of the metadata. Multiple output formats are available, including XML. Making the provision of metadata easier while also ensuring high quality must be a priority for data curation initiatives. We show how both objectives are achieved by close collaboration between metadata experts and researchers to create domain‐specific schemes. A near‐future priority is to provide methods to interface domain‐specific schemes with general metadata schemes, such as the Ecological Metadata Language, to increase interoperability.

Mast cells and basophils have long been implicated in the pathogenesis of IgE-mediated hypersensitivity reactions. They express the high-affinity IgE receptor, FcϵRI, on their surface. Antigen-induced crosslinking of IgE antibodies bound to that receptor triggers a signaling cascade that results in activation, leading to the release of an array of preformed vasoactive mediators and rapidly synthesized lipids, as well as the de novo production of inflammatory cytokines. In addition to bearing activating receptors like FcεRI, these effector cells of allergy express inhibitory ones including FcγR2b, an IgG Fc receptor with a cytosolic inhibitory motif that activates protein tyrosine phosphatases that suppress IgE-mediated activation. We and others have shown that food allergen-specific IgG antibodies strongly induced during the course of oral immunotherapy (OIT), signal via FcγR2b to suppress IgE-mediated mast cell and basophil activation triggered by food allergen challenge. However, the potential inhibitory effects of IgA antibodies, which are also produced in response to OIT and are present at high levels at mucosal sites, including the intestine where food allergens are encountered, have not been well studied. Here we uncover an inhibitory function for IgA. We observe that IgA binds mouse bone marrow-derived mast cells (BMMCs) and peritoneal mast cells. Binding to BMMCs is dependent on calcium and sialic acid. We also found that IgA antibodies inhibit IgE-mediated mast cell degranulation in an allergen-specific fashion. Antigen-specific IgA inhibits IgE-mediated mast cell activation early in the signaling cascade, suppressing the phosphorylation of Syk, the proximal protein kinase mediating FcεRI signaling, and suppresses mast cell production of cytokines. Furthermore, using basophils from a peanut allergic donor we found that IgA binds to basophils and that activation by exposure to peanuts is effectively suppressed by IgA. We conclude that IgA serves as a regulator of mast cell and basophil degranulation, suggesting a physiologic role for IgA in the maintenance of immune homeostasis at mucosal sites.

Abstract Understanding how microbial communities of aquatic ecosystems respond to environmental change remains a critical challenge in microbial ecology. In this study, we used light‐dependent oxic–anoxic micro‐ecosystems to understand how the functioning and diversity of aerobic and anaerobic lake analog communities are affected by a pulse light deprivation. Continuous measurements of oxygen concentration were made and a time series of full‐length 16S rRNA sequencing was used to quantify changes in alpha‐ and beta diversity. In the upper oxic layer, oxygen concentration decreased significantly under light reduction, but showed resilience in daily mean, minimum, and maximum after light conditions were restored to control level. Only the amplitude of diurnal fluctuations in oxygen concentrations did not recover fully, and instead tended to remain lower in treated ecosystems. Alpha diversity of the upper oxic layer communities showed a delayed increase after light conditions were restored, and was not resilient in the longer term. In contrast, alpha diversity of the anoxic lower layer communities increased during the light reduction, but was resilient in the longer term. Community composition changed significantly during light reduction, and showed resilience in the oxic layer and lack of resilience in the anoxic layer. Alpha diversity and the amplitude of daily oxygen fluctuations within and among treatments were strongly correlated, suggesting that higher diversity could lead to less variable oxygen concentrations, or vice versa. Our experiment showed that light deprivation induces multifaceted responses of community function (oxygen respiration) and structure, hence focusing on a single stability component could potentially be misleading.

Habitat loss is a significant driver of biodiversity loss, causing fragmentation into small, isolated patches of suitable land cover. This reduces the permeability of landscapes to the movement of individuals and reduces the likelihood of metapopulation persistence. Quantifying functional connectivity, the ability of a focal species to move between resource patches, is therefore essential for conservation management. There is substantial evidence supporting a technique based on ‘population synchrony’- the degree of correlation in time-series of annual population growth rates between different long-term monitoring sites, to provide a measure of functional connectivity. However, synchronised population dynamics are not only driven by the movement of individuals between sites, but also shared environmental conditions which must be accounted for. Here, we use species survey data from over four decades to investigate average levels and temporal trends in population synchrony for 58 British bird and butterfly species. We first show that population synchrony is significantly associated with synchrony in some seasonal climatic variables. Once we accounted for spatiotemporal climatic patterns, we found that synchrony in butterflies declined over time by 71% between 1985 and 2000 but increased by 64% in recent years. Synchrony in birds showed some decline between 1999 and 2005, after which there appears to being recovery, however most species (74%) show no significant overall change in synchrony. Our proposed indicator provides a ‘species-eye-view’ of functional connectivity using widely available abundance data. Developing such indicators of functional connectivity, which can be updated annually, is crucial to improve the effectiveness of land management strategies for conservation under increasing environmental change.

Abstract Understanding the effects of temperature on ecological and evolutionary processes is crucial for generating future climate adaptation scenarios. Using experimental evolution, we evolved the model ciliate Tetrahymena thermophila in an initially novel high temperature environment for more than 35 generations, closely monitoring population dynamics and morphological changes. We observed initially long lag phases in the high temperature environment that over about 26 generations reduced to no lag phase, a strong reduction in cell size and modifications in cell shape at high temperature. When exposing the adapted populations to their original temperature, most phenotypic traits returned to the observed levels in the ancestral populations, indicating phenotypic plasticity is an important component of this species thermal stress response. However, persistent changes in cell size were detected, indicating possible costs related to the adaptation process. Exploring the molecular basis of thermal adaptation will help clarify the mechanisms driving these phenotypic responses.

Abstract Theory predicts that organism–environment feedbacks play a central role in how ecological communities respond to environmental change. Strong feedback causes greater nonlinearity between environmental change and ecosystem state, increases the likelihood of hysteresis in response to environmental change, and augments the possibility of alternative stable regimes. To illustrate these predictions and their dependence on a temporal scale, we simulated a minimal ecosystem model. To test the predictions, we manipulated the feedback strength between the metabolism and the dissolved oxygen concentration in an aquatic heterotrophic tri‐trophic community in microecosystems. The manipulation consisted of five levels, ranging from low to high feedback strength by altering the oxygen diffusivity: free gas exchange between the microcosm atmosphere and the external air (metabolism not strongly affecting environmental oxygen), with the regular addition of 200, 100, or 50 ml of air and no gas exchange. To test for nonlinearity and hysteresis in response to environmental change, all microecosystems experienced a gradual temperature increase from 15 to 25°C and then back to 15°C. We regularly measured the dissolved oxygen concentration, total biomass, and species abundance. Nonlinearity and hysteresis were higher in treatments with stronger organism–environment feedbacks. There was no evidence that stronger feedback increased the number of observed ecosystem states. These empirical results are in broad agreement with the theory that stronger feedback increases nonlinearity and hysteresis. They therefore represent one of the first direct empirical tests of the importance of feedback strength. However, we discuss several limitations of the study, which weaken confidence in this interpretation. Research demonstrating the causal effects of feedback strength on ecosystem responses to environmental change should be placed at the core of efforts to plan for sustainable ecosystems.

Abstract Alternative and non-opioid options for pain management are necessary in perioperative patient care. Opioids are no longer touted as cure-all medications, and furthermore, there have been tremendous advances in alternative therapies such as in interventional pain, physical therapy, exercise, and nutritional counseling that have proven benefits to combat pain. The center for disease control now strongly recommends the use of multimodal analgesia and multidisciplinary approaches based on the individual needs of patients: personalized medicine. In this manuscript, the specifics of non-opioid pharmacological and non-pharmacological analgesic approaches will be discussed as well as their possible indications and uses to reduce the need for excessive use of opioids for adequate pain control.

Abstract Aquatic ecosystems are often stratified, with cyanobacteria in oxic layers and phototrophic sulfur bacteria in anoxic zones. Changes in stratification caused by the global environmental change are an ongoing concern. Increasing understanding of how such aerobic and anaerobic microbial communities, and associated abiotic conditions, respond to multifarious environmental changes is an important endeavor in microbial ecology. Insights can come from observational and experimental studies of naturally occurring stratified aquatic ecosystems, theoretical models of ecological processes, and experimental studies of replicated microbial communities in the laboratory. Here, we demonstrate a laboratory‐based approach with small, replicated, and liquid‐dominated Winogradsky columns, with distinct oxic/anoxic strata in a highly replicable manner. Our objective was to apply simultaneous global change scenarios (temperature, nutrient addition) on this micro‐ecosystem to report how the microbial communities (full‐length 16S rRNA gene seq.) and the abiotic conditions (O2, H2S, TOC) of the oxic/anoxic layer responded to these environmental changes. The composition of the strongly stratified microbial communities was greatly affected by temperature and by the interaction of temperature and nutrient addition, demonstrating the need of investigating global change treatments simultaneously. Especially phototrophic sulfur bacteria dominated the water column at higher temperatures and may indicate the presence of alternative stable states. We show that the establishment of such a micro‐ecosystem has the potential to test global change scenarios in stratified eutrophic limnic systems.

Spatial proteomics allows studying cellular protein localisations at system-wide scale. Here, the authors show that combining the previously developed hyperLOPIT method with differential centrifugation yields protein localisation maps at suborganellar resolution while reducing analysis time and input material.

Introduction:Endothelial dysfunction is a major risk factor for several of the vascular complications of diabetes, including ischemic stroke. Nitroxyl (HNO), the one electron reduced and protonated form of nitric oxide (NO•), is resistant to scavenging by superoxide, but the role of HNO in diabetes mellitus associated endothelial dysfunction in the carotid artery remains unknown.Aim: To assess how diabetes affects the role of endogenous NO• and HNO in endothelium-dependent relaxation in rat isolated carotid arteries.Methods: Male Sprague Dawley rats were fed a high-fat-diet (HFD) for 2 weeks prior to administration of low dose streptozotocin (STZ; 35 mg/kg i. p./day) for 2 days. The HFD was continued for a further 12 weeks. Sham rats were fed standard chow and administered with citrate vehicle. After 14 weeks total, rats were anesthetized and carotid arteries collected to assess responses to the endothelium-dependent vasodilator, acetylcholine (ACh) by myography. The combination of calcium-activated potassium channel blockers, TRAM-34 (1 μmol/L) and apamin (1 μmol/L) was used to assess the contribution of endothelium-dependent hyperpolarization to relaxation. The corresponding contribution of NOS-derived nitrogen oxide species to relaxation was assessed using the combination of the NO• synthase inhibitor, L-NAME (200 μmol/L) and the soluble guanylate cyclase inhibitor ODQ (10 μmol/L). Lastly, L-cysteine (3 mmol/L), a selective HNO scavenger, and hydroxocobalamin (HXC; 100 μmol/L), a NO• scavenger, were used to distinguish between NO• and HNO-mediated relaxation.Results: At study end, diabetic rats exhibited significantly retarded body weight gain and elevated blood glucose levels compared to sham rats. The sensitivity and the maximal relaxation response to ACh was significantly impaired in carotid arteries from diabetic rats, indicating endothelial dysfunction. The vasorelaxation evoked by ACh was abolished by L-NAME plus ODQ, but not affected by the apamin plus TRAM-34 combination, indicating that NOS-derived nitrogen oxide species are the predominant endothelium-derived vasodilators in sham and diabetic rat carotid arteries. The maximum relaxation to ACh was significantly decreased by L-cysteine in both sham and diabetic rats, whereas HXC attenuated ACh-induced relaxation only in sham rats, suggesting that diabetes impaired the contribution of NO•, whereas HNO-mediated vasorelaxation remained intact.Conclusion: Both NO• and HNO contribute to endothelium-dependent relaxation in carotid arteries. In diabetes, NO•-mediated relaxation is impaired, whereas HNO-mediated relaxation was preserved. The potential for preserved HNO activity under pathological conditions that are associated with oxidative stress indicates that HNO donors may represent a viable therapeutic approach to the treatment of vascular dysfunction.

Non-alcoholic steatohepatitis (NASH) develops from non-alcoholic fatty liver disease (NAFLD). Currently, around 25% of the population is estimated to have NAFLD, and 25% of NAFLD patients are estimated to have NASH. NASH is typically characterized by liver steatosis inflammation, and fibrosis driven by metabolic disruptions such as obesity, diabetes, and dyslipidemia. NASH patients with significant fibrosis have increased risk of developing cirrhosis and liver failure. Currently, NASH is the second leading cause for liver transplant in the United States. More importantly, the risk of developing hepatocellular carcinoma from NASH has also been highlighted in recent studies. Patients may have NAFLD for years before progressing into NASH. Although the pathogenesis of NASH is not completely understood, the current “multiple-hits” hypothesis suggests that in addition to fat accumulation, elevated oxidative and ER stress may also drive liver inflammation and fibrosis. The development of clinically relevant animal models and pharmacological treatments for NASH have been hampered by the limited understanding of the disease mechanism and a lack of sensitive, non-invasive diagnostic tools. Currently, most pre-clinical animal models are divided into three main groups which includes: genetic models, diet-induced, and toxin + diet-induced animal models. Although dietary models mimic the natural course of NASH in humans, the models often only induce mild liver injury. Many genetic and toxin + diet-induced models rapidly induce the development of metabolic disruption and serious liver injury, but not without their own shortcomings. This review provides an overview of the “multiple-hits” hypothesis and an evaluation of the currently existing animal models of NASH. This review also provides an update on the available interventions for managing NASH as well as pharmacological agents that are currently undergoing clinical trials for the treatment of NASH.

Food allergy is a major health issue, affecting the lives of 8% of U.S. children and their families. There is an urgent need to identify the environmental and endogenous signals that induce and sustain allergic responses to ingested allergens. Acute reactions to foods are triggered by the activation of mast cells and basophils, both of which release inflammatory mediators that lead to a range of clinical manifestations, including gastrointestinal, cutaneous, and respiratory reactions as well as systemic anaphylaxis. Both of these innate effector cell types express the high affinity IgE receptor, FcϵRI, on their surface and are armed for adaptive antigen recognition by very-tightly bound IgE antibodies which, when cross-linked by polyvalent allergen, trigger degranulation. These cells also express inhibitory receptors, including the IgG Fc receptor, FcγRIIb, that suppress their IgE-mediated activation. Recent studies have shown that natural resolution of food allergies is associated with increasing food-specific IgG levels. Furthermore, oral immunotherapy, the sequential administration of incrementally increasing doses of food allergen, is accompanied by the strong induction of allergen-specific IgG antibodies in both human subjects and murine models. These can deliver inhibitory signals via FcγRIIb that block IgE-induced immediate food reactions. In addition to their role in mediating immediate hypersensitivity reactions, mast cells and basophils serve separate but critical functions as adjuvants for type 2 immunity in food allergy. Mast cells and basophils, activated by IgE, are key sources of IL-4 that tilts the immune balance away from tolerance and towards type 2 immunity by promoting the induction of Th2 cells along with the innate effectors of type 2 immunity, ILC2s, while suppressing the development of regulatory T cells and driving their subversion to a pathogenic pro-Th2 phenotype. This adjuvant effect of mast cells and basophils is suppressed when inhibitory signals are delivered by IgG antibodies signaling via FcγRIIb. This review summarizes current understanding of the immunoregulatory effects of mast cells and basophils and how these functions are modulated by IgE and IgG antibodies. Understanding these pathways could provide important insights into innovative strategies for preventing and/or reversing food allergy in patients.

The cell is compartmentalised into complex micro-environments allowing an array of specialised biological processes to be carried out in synchrony. Determining a protein's sub-cellular localisation to one or more of these compartments can therefore be a first step in determining its function. High-throughput and high-accuracy mass spectrometry-based sub-cellular proteomic methods can now shed light on the localisation of thousands of proteins at once. Machine learning algorithms are then typically employed to make protein-organelle assignments. However, these algorithms are limited by insufficient and incomplete annotation. We propose a semi-supervised Bayesian approach to novelty detection, allowing the discovery of additional, previously unannotated sub-cellular niches. Inference in our model is performed in a Bayesian framework, allowing us to quantify uncertainty in the allocation of proteins to new sub-cellular niches, as well as in the number of newly discovered compartments. We apply our approach across 10 mass spectrometry based spatial proteomic datasets, representing a diverse range of experimental protocols. Application of our approach to hyperLOPIT datasets validates its utility by recovering enrichment with chromatin-associated proteins without annotation and uncovers sub-nuclear compartmentalisation which was not identified in the original analysis. Moreover, using sub-cellular proteomics data from Saccharomyces cerevisiae, we uncover a novel group of proteins trafficking from the ER to the early Golgi apparatus. Overall, we demonstrate the potential for novelty detection to yield biologically relevant niches that are missed by current approaches.

Diabetes is associated with an increased mortality risk due to cardiovascular complications. Hyperglycemia-induced oxidative stress underlies these complications, leading to an impairment in endogenous nitric oxide (NO•) generation, together with reductions in NO• bioavailability and NO• responsiveness in the vasculature, platelets and myocardium. The latter impairment of responsiveness to NO•, termed NO• resistance, compromises the ability of traditional NO•-based therapeutics to improve hemodynamic status during diabetes-associated cardiovascular emergencies, such as acute myocardial infarction. Whilst a number of agents can ameliorate (e.g. angiotensin converting enzyme [ACE] inhibitors, perhexiline, statins and insulin) or circumvent (e.g. nitrite and sGC activators) NO• resistance, nitroxyl (HNO) donors offer a novel opportunity to circumvent NO• resistance in diabetes. With a suite of vasoprotective properties and an ability to enhance cardiac inotropic and lusitropic responses, coupled with preserved efficacy in the setting of oxidative stress, HNO donors have intact therapeutic potential in the face of diminished NO• signaling. This review explores the major mechanisms by which hyperglycemia-induced oxidative stress drives NO• resistance, and the therapeutic potential of HNO donors to circumvent this to treat cardiovascular complications in type 2 diabetes mellitus.

Volume phase transitions in polyeletrolyte gels play important roles in many biophysical processes such as DNA packaging, nerve excitation, and cellular secretion. The swelling and deswelling of these charged polymer gels depend strongly on their ionic environment. In this paper, we present an extension to our previous two-fluid model for ion-binding-mediated gel swelling. The extended model eliminates the assumptions about the size similarity between the network and solvent particles, which makes it suitable for investigating of a large family of biologically relevant problems. The model treats the polyeletrolyte gel as a mixture of two materials, the network and the solvent. The dynamics of gel swelling is governed by the balance between the mechanical and chemical forces on each of these two materials. Simulations based on the model illustrate that the chemical forces are significantly influenced by the binding/unbinding reactions between the ions and the network, as well as the resulting distribution of charges within the gel. The dependence of the swelling rate on ionic bath concentrations is analyzed and this analysis highlights the importance of the electromigration of ions and the induced electric field in regulating gel swelling.

As remote sensing technology improves, it is now possible to map fine-scale variation in plant functional traits. Schneider et al. remotely sense tree functional diversity, validate with field data, and reveal patterns of plant adaptation to the environment previously not retrievable from plot data

We aimed to determine whether tocomin, an extract from palm oil that has a high tocotrienol content, was able to prevent diabetes-induced endothelial dysfunction. To induce type 1 diabetes streptozotocin (50 mg/kg) was injected into the tail vein of Wistar rats. Six weeks later the diabetic rats, and normal rats injected with citrate buffer, commenced treatment with tocomin (40 mg/kg/day sc) or its vehicle (peanut oil) for a further 4 weeks. Aortae isolated from diabetic rats had impaired acetylcholine (ACh)-induced endothelium-dependent relaxation compared to normal rat aortae but there was no change in endothelium-independent relaxation in response to sodium nitroprusside. By contrast, responses to ACh in aortae from diabetic rats treated with tocomin were not different to normal rats. In addition to impaired endothelium-dependent relaxation the diabetic aortae had increased expression of the NADPH oxidase Nox2 subunit, increased generation of superoxide and decreased expression of eNOS and all of these effects were prevented by tocomin treatment. Tocomin did not affect plasma glucose levels. The impaired response to ACh in vitro was maintained in the presence of TRAM-34 and apamin, selective inhibitors of calcium-activated potassium (KCa) channels, indicating diabetes impaired the contribution of NO to endothelium-dependent relaxation. By contrast, neither diabetes nor tocomin treatment influenced EDH-type relaxation as, in the presence of L-NNA, an inhibitor of eNOS, and ODQ, to inhibit soluble guanylate cyclase, responses to ACh were similar in all treatment groups. Thus tocomin treatment improves NO mediated endothelium dependent relaxation in aortae from diabetic rats associated with a decrease in vascular oxidant stress but without affecting hyperglycaemia.

Hidden hot springs likely impact rural water supplies in Malawi’s Rift Valley with excess dissolved fluoride leading to localised endemic severe dental fluorosis. Predicting their occurrence is a challenge; Malawi’s groundwater data archive is sporadic and incomplete which prevents the application of standard modelling techniques. A creative alternative method to predict hidden hot spring locations was developed using a synthesis of proxy indicators (geological, geochemical, dental) and is shown to be at least 75% effective. An exciting collaboration between geoscientists and dentists allowed corroboration of severe dental fluorosis with hydrogeological vulnerability. Thirteen hidden hot springs were identified based on synthesised proxy indicators. A vulnerability prediction map for the region was developed and is the first of its kind in Malawi. It allows improved groundwater fluoride prediction in Malawi’s rift basin which hosts the majority of hot springs. Moreover, it allows dentists to recognise geological control over community oral health. Collaborative efforts have proven mutually beneficial, allowing both disciplines to conduct targeted research to improve community wellbeing and health and inform policy development in their respective areas. This work contributes globally in developing nations where incomplete groundwater data and vulnerability to groundwater contamination from hydrothermal fluoride exist in tandem.

Abstract Understanding and quantifying the temperature dependence of population parameters, such as intrinsic growth rate and carrying capacity, is critical for predicting the ecological responses to environmental change. Many studies provide empirical estimates of such temperature dependencies, but a thorough investigation of the methods used to infer them has not been performed yet. We created artificial population time series using a stochastic logistic model parameterized with the Arrhenius equation, so that activation energy drives the temperature dependence of population parameters. We simulated different experimental designs and used different inference methods, varying the likelihood functions and other aspects of the parameter estimation methods. Finally, we applied the best performing inference methods to real data for the species Paramecium caudatum. The relative error of the estimates of activation energy varied between 5% and 30%. The fraction of habitat sampled played the most important role in determining the relative error; sampling at least 1% of the habitat kept it below 50%. We found that methods that simultaneously use all time series data (direct methods) and methods that estimate population parameters separately for each temperature (indirect methods) are complementary. Indirect methods provide a clearer insight into the shape of the functional form describing the temperature dependence of population parameters; direct methods enable a more accurate estimation of the parameters of such functional forms. Using both methods, we found that growth rate and carrying capacity of Paramecium caudatum scale with temperature according to different activation energies. Our study shows how careful choice of experimental design and inference methods can increase the accuracy of the inferred relationships between temperature and population parameters. The comparison of estimation methods provided here can increase the accuracy of model predictions, with important implications in understanding and predicting the effects of temperature on the dynamics of populations.

Urban development is rapidly expanding across the globe and is a major driver of environmental change. Despite considerable improvements in our understanding of how species richness responds to urbanization, there is still insufficient knowledge of how other measures of assemblage composition and structure respond to urban development. Functional diversity metrics provide a useful approach for quantifying ecological function. We compare avian functional diversity in 25 urban areas, located across the globe, with paired non-urban assemblages using a database of 27 functional traits that capture variation in resource use (amount and type of resources and how they are acquired) across the 529 species occurring across these assemblages. Using three standard functional diversity metrics (FD, MNTD, and convex hull) we quantify observed functional diversity and, using standardized effect sizes, how this diverges from that expected under random community assembly null models. We use regression trees to investigate whether human population density, amount of vegetation and city size (spatial extent of urban land), bio-region and use of semi-natural or agricultural assemblages as a baseline modulate the effect of urbanization on functional diversity. Our analyses suggest that observed functional diversity of urban avian assemblages is not consistently different from that of non-urban assemblages. After accounting for species richness avian functional diversity is higher in cities than areas of semi-natural habitat. This creates a paradox as species responses to urban development are determined by their ecological traits, which should generate assemblages clustered within a narrow range of trait space. Greater habitat diversity within cities compared to semi-natural areas dominated by a single habitat may enhance functional diversity in cities and explain this paradox. Regression trees further suggest that smaller urban areas, lower human population densities and increased vegetation all enhance the functional diversity of urban areas. A city's attributes can thus influence the functional diversity of its biological assemblages, and their associated ecological functions. This has important implications for the debate regarding how we should grow the world's cities whilst maintaining their ecological function.

The development of video-based monitoring methods allows for rapid, dynamic and accurate monitoring of individuals or communities, compared to slower traditional methods, with far reaching ecological and evolutionary applications. Large amounts of data are generated using video-based methods, which can be effectively processed using machine learning (ML) algorithms into meaningful ecological information. ML uses user defined classes (e.g. species), derived from a subset (i.e. training data) of video-observed quantitative features (e.g. phenotypic variation), to infer classes in subsequent observations. However, phenotypic variation often changes due to environmental conditions, which may lead to poor classification, if environmentally induced variation in phenotypes is not accounted for. Here we describe a framework for classifying species under changing environmental conditions based on the random forest classification. A sliding window approach was developed that restricts temporal and environmentally conditions to improve the classification. We tested our approach by applying the classification framework to experimental data. The experiment used a set of six ciliate species to monitor changes in community structure and behavior over hundreds of generations, in dozens of species combinations and across a temperature gradient. Differences in biotic and abiotic conditions caused simplistic classification approaches to be unsuccessful. In contrast, the sliding window approach allowed classification to be highly successful, as phenotypic differences driven by environmental change, could be captured by the classifier. Importantly, classification using the random forest algorithm showed comparable success when validated against traditional, slower, manual identification. Our framework allows for reliable classification in dynamic environments, and may help to improve strategies for long-term monitoring of species in changing environments. Our classification pipeline can be applied in fields assessing species community dynamics, such as eco-toxicology, ecology and evolutionary ecology.

We present encube—a qualitative, quantitative and comparative visualisation and analysis system, with application to high-resolution, immersive three-dimensional environments and desktop displays. encube extends previous comparative visualisation systems by considering: (1) the integration of comparative visualisation and analysis into a unified system; (2) the documentation of the discovery process; and (3) an approach that enables scientists to continue the research process once back at their desktop. Our solution enables tablets, smartphones or laptops to be used as interaction units for manipulating, organising, and querying data. We highlight the modularity of encube, allowing additional functionalities to be included as required. Additionally, our approach supports a high level of collaboration within the physical environment. We show how our implementation of encube operates in a large-scale, hybrid visualisation and supercomputing environment using the CAVE2 at Monash University, and on a local desktop, making it a versatile solution. We discuss how our approach can help accelerate the discovery rate in a variety of research scenarios.

Gastric mucus gel is known to exhibit dramatic and unique swelling behaviors in response to the ionic composition of the hydrating solution. This swelling behavior is important in the maintenance of the mucus layer lining the stomach wall, as the layer is constantly digested by enzymes in the lumen, and must be replenished by new mucus that swells as it is secreted from the gastric wall. One hypothesis suggests that the condensed state of mucus at secretion is maintained by transient bonds with calcium that form crosslinks. These crosslinks are lost as monovalent cations from the environment displace divalent crosslinkers, leading to a dramatic change in the energy of the gel and inducing the swelling behavior. Previous modeling work has characterized the equilibrium behavior of polyelectrolyte gels that respond to calcium crosslinking. Here, we present an investigation of the dynamic swelling behavior of a polyelectrolytic gel model of mucus. In particular, we quantified the rate at which a globule of initially crosslinked gel swells when exposed to an ionic bath. The dependence of this swelling rate on several parameters was characterized. We observed that swelling rate has a non-monotone dependence on the molarity of the bath solution, with moderate concentrations of available sodium inducing the fastest swelling.

Recent advances in tracking technologies such as GPS or video tracking systems describe the movement paths of individuals in unprecedented details and are increasingly used in different fields, including ecology. However, extracting information from raw movement data requires advanced analysis techniques, for instance to infer behaviors expressed during a certain period of the recorded trajectory, or gender or species identity in case data is obtained from remote tracking. In this paper, we address how different movement features affect the ability to automatically classify the species identity, using a dataset of unicellular microbes (i.e., ciliates). Previously, morphological attributes and simple movement metrics, such as speed, were used for classifying ciliate species. Here, we demonstrate that adding advanced movement features, in particular such based on discrete wavelet transform, to morphological features can improve classification. These results may have practical applications in automated monitoring of waste water facilities as well as environmental monitoring of aquatic systems.

The aim of the study was to investigate the effect of the DPP-4 inhibitor linagliptin on the mechanism(s) of endothelium-dependent relaxation in mesenteric arteries from STZ-induced diabetic rats. Both normal and diabetic animals received linagliptin (2 mg/kg) daily by oral gavage for a period of 4 weeks. To measure superoxide generation in mesenteric arteries, lucigenin-enhanced chemiluminescence was used. ACh-induced relaxation of mesenteric arteries was assessed using organ bath techniques and Western blotting was used to investigate protein expression. Pharmacological tools (1 μM TRAM-34, 1 μM apamin, 100 nM Ibtx, 100 μM L-NNA, 10 μM ODQ) were used to distinguish between NO and EDH-mediated relaxation. Linagliptin did not affect plasma glucose, but did decrease vascular superoxide levels. Diabetes reduced responses to ACh but did not affect endothelium-independent responses to SNP. Linagliptin improved endothelial function indicated by a significant increase in responses to ACh. Diabetes impaired the contribution of both nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) to endothelium-dependent relaxation and linagliptin treatment significantly enhanced the contribution of both relaxing factors. Western blotting demonstrated that diabetes also increased expression of Nox2 and decreased expression and dimerization of endothelial NO synthase, effects that were reversed by linagliptin. These findings demonstrate treatment of type 1 diabetic rats with linagliptin significantly reduced vascular superoxide levels and preserved both NO and EDH-mediated relaxation indicating that linagliptin can improve endothelial function in diabetes independently of any glucose lowering activity.

The investigation of form-function relationships requires a detailed understanding of anatomical systems. Here we document the 3-dimensional morphology of the cranial musculoskeletal anatomy in the Australian Laughing Kookaburra Dacelo novaeguineae, with a focus upon the geometry and attachments of the jaw muscles in this species. The head of a deceased specimen was CT scanned, and an accurate 3D representation of the skull and jaw muscles was generated through manual segmentation of the CT scan images, and augmented by dissection of the specimen. We identified 14 major jaw muscles: 6 in the temporal group (M. adductor mandibulae and M. pseudotemporalis), 7 in the pterygoid group (M. pterygoideus dorsalis and M. pterygoideus ventralis), and the single jaw abductor M. depressor mandibulae. Previous descriptions of avian jaw musculature are hindered by limited visual representation and inconsistency in the nomenclature. To address these issues, we: (1) present the 3D model produced from the segmentation process as a digital, fully interactive model in the form of an embedded 3D image, which can be viewed from any angle, and within which major components can be set as opaque, transparent, or hidden, allowing the anatomy to be visualised as required to provide a detailed understanding of the jaw anatomy; (2) provide a summary of the nomenclature used throughout the avian jaw muscle literature. The approach presented here provides considerable advantages for the documentation and communication of detailed anatomical structures in a wide range of taxa.

Researchers contribute to the scientific peer review system by providing reviews, and "withdraw" from it by submitting manuscripts that are subsequently reviewed. So far as we are aware, there has been no quantification of the balance of individual's contributions and withdrawals. We compared the number of reviews provided by individual researchers (i.e., their contribution) to the number required by their submissions (i.e. their withdrawals) in a large and anonymised database provided by the British Ecological Society. The database covered the Journal of Ecology, Journal of Animal Ecology, Journal of Applied Ecology, and Functional Ecology from 2003-2010. The majority of researchers (64%) did not have balanced contributions and withdrawals. Depending on assumptions, 12% to 44% contributed more than twice as much as required; 20% to 52% contributed less than half as much as required. Balance, or lack thereof, varied little in relation to the number of years a researcher had been active (reviewing or submitting). Researchers who contributed less than required did not lack the opportunity to review. Researchers who submitted more were more likely to accept invitations to review. These finding suggest overall that peer review of the four analysed journals is not in crisis, but only due to the favourable balance of over- and under-contributing researchers. These findings are limited to the four journals analysed, and therefore cannot include researcher's other peer review activities, which if included might change the proportions reported. Relatively low effort was required to assemble, check, and analyse the data. Broader analyses of individual researcher's peer review activities would contribute to greater quality, efficiency, and fairness in the peer review system.

Background3',4'-Dihydroxyflavonol (DiOHF) is an effective antioxidant that acutely preserves nitric oxide (NO) activity in the presence of elevated reactive oxygen species (ROS). We hypothesized that DiOHF treatment (7 days, 1 mg/kg per day s.c.) would improve relaxation in mesenteric arteries from diabetic rats where endothelial dysfunction is associated with elevated oxidant stress.Methodology/principal findingsIn mesenteric arteries from diabetic rats there was an increase in ROS, measured by L-012 and 2',7'-dichlorodihydrofluorescein diacetate fluorescence. NADPH oxidase-derived superoxide levels, assayed by lucigenin chemiluminescence, were also significantly increased in diabetic mesenteric arteries (diabetes, 4892±946 counts/mg versus normal 2486±344 counts/mg, n = 7-10, pConclusions/significanceDiOHF improves NO activity in diabetes by reducing Nox2-dependent superoxide production and preventing eNOS uncoupling to improve endothelial function.

BackgroundDiabetic cardiomyopathy (DCM) is an increasingly recognized cause of chronic heart failure amongst diabetic patients. Both increased reactive oxygen species (ROS) generation and impaired ROS scavenging have been implicated in the pathogenesis of hyperglycemia-induced left ventricular dysfunction, cardiac fibrosis, apoptosis and hypertrophy. We hypothesized that 3',4'-dihydroxyflavonol (DiOHF), a small highly lipid soluble synthetic flavonol, may prevent DCM by scavenging ROS, thus preventing ROS-induced cardiac damage.Methodology/principal findingsSix week old homozygous Ren-2 rats were randomized to receive either streptozotocin or citrate buffer, then further randomized to receive either DiOHF (1 mg/kg/day) by oral gavage or vehicle for six weeks. Cardiac function was assessed via echocardiography and left ventricular cardiac catheterization before the animals were sacrificed and hearts removed for histological and molecular analyses. Diabetic Ren-2 rats showed evidence of diastolic dysfunction with prolonged deceleration time, reduced E/A ratio, and increased slope of end-diastolic pressure volume relationship (EDPVR) in association with marked interstitial fibrosis and oxidative stress (all PConclusionsInhibition of ROS production and action by DiOHF improved diastolic function and reduced myocyte hypertrophy as well as collagen deposition. These findings suggest the potential clinical utility of antioxidative compounds such as flavonols in the prevention of diabetes-associated cardiac dysfunction.