Using 'sentinel' plants to improve early detection of invasive plant pathogens.

Infectious diseases of plants present an ongoing and increasing threat to international biosecurity, with wide-ranging implications. An important challenge in plant disease management is achieving early detection of invading pathogens, which requires effective surveillance through the implementation of appropriate monitoring programmes. However, when monitoring relies on visual inspection as a means of detection, surveillance is often hindered by a long incubation period (delay from infection to symptom onset) during which plants may be infectious but not displaying visible symptoms. 'Sentinel' plants-alternative susceptible host species that display visible symptoms of infection more rapidly-could be introduced to at-risk populations and included in monitoring programmes to act as early warning beacons for infection. However, while sentinel hosts exhibit faster disease progression and so allow pathogens to be detected earlier, this often comes at a cost: faster disease progression typically promotes earlier onward transmission. Here, we construct a computational model of pathogen transmission to explore this trade-off and investigate how including sentinel plants in monitoring programmes could facilitate earlier detection of invasive plant pathogens. Using Xylella fastidiosa infection in Olea europaea (European olive) as a current high profile case study, for which Catharanthus roseus (Madagascan periwinkle) is a candidate sentinel host, we apply a Bayesian optimisation algorithm to determine the optimal number of sentinel hosts to introduce for a given sampling effort, as well as the optimal division of limited surveillance resources between crop and sentinel plants. Our results demonstrate that including sentinel plants in monitoring programmes can reduce the expected prevalence of infection upon outbreak detection substantially, increasing the feasibility of local outbreak containment.

A synoptic review of plant disease epidemics and outbreaks published in 2022.

This scientometric study reviews the scientific literature and CABI distribution records published in 2022 to find evidence of major disease outbreaks and first reports of pathogens in new locations or on new hosts. This is the second time we have done this, and this study builds on our work documenting and analysing reports from 2021. Pathogens with three or more articles identified in 2022 literature were: Xylella fastidiosa, Bursaphelenchus xylophilus, Meloidogyne species complexes, Candidatus Liberibacter asiaticus, Raffaelea lauricola, Fusarium oxysporum formae specialis and Puccinia graminis f. sp. tritici. Our review of CABI distribution records found 29 pathogens with confirmed first reports in 2022. Pathogens with four or more first reports were: Meloidogyne species complexes, Pantoea ananatis, grapevine red globe virus and Thekopsora minima. Analysis of the proportion of new distribution records from 2022 indicated that grapevine red globe virus, sweet potato chlorotic stunt virus and Ca. Phytoplasma vitis may have been actively spreading. As we saw last year, there was little overlap between the pathogens identified by reviewing scientific literature versus distribution records. Strikingly, too, there was also no overlap between species assessed to be actively spreading in this year's study and those identified last year. In general, introduction of new pathogens and outbreaks of extant pathogens threaten food security and ecosystem services. Continued monitoring of these threats is essential to support phytosanitary measures intended to prevent pathogen introductions and management of threats within a country.

Optimising risk-based surveillance for early detection of invasive plant pathogens.

Emerging infectious diseases (EIDs) of plants continue to devastate ecosystems and livelihoods worldwide. Effective management requires surveillance to detect epidemics at an early stage. However, despite the increasing use of risk-based surveillance programs in plant health, it remains unclear how best to target surveillance resources to achieve this. We combine a spatially explicit model of pathogen entry and spread with a statistical model of detection and use a stochastic optimisation routine to identify which arrangement of surveillance sites maximises the probability of detecting an invading epidemic. Our approach reveals that it is not always optimal to target the highest-risk sites and that the optimal strategy differs depending on not only patterns of pathogen entry and spread but also the choice of detection method. That is, we find that spatial correlation in risk can make it suboptimal to focus solely on the highest-risk sites, meaning that it is best to avoid 'putting all your eggs in one basket'. However, this depends on an interplay with other factors, such as the sensitivity of available detection methods. Using the economically important arboreal disease huanglongbing (HLB), we demonstrate how our approach leads to a significant performance gain and cost saving in comparison with conventional methods to targeted surveillance.

The value of volunteer surveillance for the early detection of biological invaders.

Early detection of invaders requires finding small numbers of individuals across large landscapes. It has been argued that the only feasible way to achieve the sampling effort needed for early detection of an invader is to involve volunteer groups (citizen scientists, passive surveyors, etc.). A key concern is that volunteers may have a considerable false-positive and false-negative rate. The question then becomes whether verification of a report from a volunteer is worth the effort. This question is the topic of this paper. Since we are interested in early detection we calculate the Z% upper limit of the one sided confidence interval of the incidence (fraction infected) and use the term maximum expected plausible incidence for this. We compare the maximum plausible incidence when the expert samples on their own, qE∼, and the maximum plausible incidence when the expert only verifies cases reported by the volunteer surveyor to be infected, qV∼. The maximum plausible incidences qE∼ and qV∼. are related as, qV∼=θfp1-θfnqE∼ where θfp and θfn are the false positive and false negative rate of the volunteer surveyor, respectively. We also show that the optimal monitoring programme consists of verifying only the cases reported by the volunteer surveyor if, TXTN<θfp1-θfn, where TN is the time needed for a sample taken by the expert and TX is the time needed for an expert to verify a case reported by a volunteer surveyor. Our results can be used to calculate the maximum plausible incidence of a plant disease based on reports of passive surveyors that have been verified by experts and data from experts sampling on their own. The results can also be used in the development phase of a surveillance project to assess whether including passive surveyor reports is useful in the early detection of exotic invaders.

What Can Be Learned by a Synoptic Review of Plant Disease Epidemics and Outbreaks Published in 2021?

A synoptic review of plant disease epidemics and outbreaks was made using two complementary approaches. The first approach involved reviewing scientific literature published in 2021, in which quantitative data related to new plant disease epidemics or outbreaks were obtained via surveys or similar methodologies. The second approach involved retrieving new records added in 2021 to the CABI Distribution Database, which contains over a million global geographic records of organisms from over 50,000 species. The literature review retrieved 186 articles, describing studies in 62 categories (pathogen species/species complexes) across more than 40 host species on six continents. Pathogen species with more than five articles were Bursaphelenchus xylophilus, 'Candidatus Liberibacter asiaticus', cassava mosaic viruses, citrus tristeza virus, Erwinia amylovora, Fusarium spp. complexes, F. oxysporum f. sp. cubense, Magnaporthe oryzae, maize lethal necrosis co-infecting viruses, Meloidogyne spp. complexes, Pseudomonas syringae pvs., Puccinia striiformis f. sp. tritici, Xylella fastidiosa, and Zymoseptoria tritici. Automated searches of the CABI Distribution Database identified 617 distribution records new in 2021 of 283 plant pathogens. A further manual review of these records confirmed 15 pathogens reported in new locations: apple hammerhead viroid, apple rubbery wood viruses, Aphelenchoides besseyi, Biscogniauxia mediterranea, 'Ca. Liberibacter asiaticus', citrus tristeza virus, Colletotrichum siamense, cucurbit chlorotic yellows virus, Erwinia rhapontici, Erysiphe corylacearum, F. oxysporum f. sp. cubense Tropical race 4, Globodera rostochiensis, Nothophoma quercina, potato spindle tuber viroid, and tomato brown rugose fruit virus. Of these, four pathogens had at least 25% of all records reported in 2021. We assessed two of these pathogens-tomato brown rugose fruit virus and cucurbit chlorotic yellows virus-to be actively emerging in/spreading to new locations. Although three important pathogens-'Ca. Liberibacter asiaticus', citrus tristeza virus, and F. oxysporum f. sp. cubense-were represented in the results of both our literature review and our interrogation of the CABI Distribution Database, in general, our dual approaches revealed distinct sets of plant disease outbreaks and new records, with little overlap. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Kidney stone formation in a novel murine model of polycystic kidney disease.

Individuals with autosomal dominant polycystic kidney disease have a higher incidence of stone formation than the general population. However, there are no cystic animal models known to develop stones. Cystic mice compound heterozygous for hypomorphic Pkd1V and Pkd1RC alleles develop cystic kidneys within a few weeks of birth but live beyond 20 wk of age, allowing for the study of cystic comorbidities including stone formation. Cystic Pkd1V/RC mice were euthanized at 3, 13, or 26 wk of age, and their kidneys were analyzed by microcomputed tomography (µCT) for stone formation. Mice had occasional mineral aggregates that could be detected by µCT analysis at 3 wk of age. At 13 or 26 wk of age, numerous white masses were visible beneath the kidney surface. µCT analysis confirmed the masses to be large mineral stone deposits throughout the renal cortex, with mineral content increasing with age. Staining of histological sections with alizarin red and von Kossa suggested that the stone deposits were composed primarily of calcium and phosphate. Microdissection confirmed stones localized within cyst lumens. Analysis of individual stones by µCT and infrared spectroscopy confirmed apatite mineral composition. Urinalysis revealed elevated levels of phosphate and citrate at 3 wk of age and lower pH and elevated levels of calcium and citrate at 13 wk of age, suggesting altered phosphate and calcium homeostasis as a potential cause of mineralization and renal stone formation. This is the first animal model exhibiting overt kidney stone formation in the context of cystic kidney disease.NEW & NOTEWORTHY Compound heterozygous Pkd1V/RC mice were found to form calcium phosphate-containing stones within cysts of the renal cortex by 13 wk of age. This is the first polycystic kidney disease animal model exhibiting spontaneous stone formation. A growing body of evidence suggests a link between renal stone formation and cystic kidney disease. This mouse model may be useful for studying the interplay between stone and cyst formation and the functional role of polycystins in mineral homeostasis.

Expression of active B-Raf proto-oncogene in kidney collecting ducts induces cyst formation in normal mice and accelerates cyst growth in mice with polycystic kidney disease.

Polycystic kidney disease (PKD) is characterized by the formation and progressive enlargement of fluid-filled cysts due to abnormal cell proliferation. Cyclic AMP agonists, including arginine vasopressin, stimulate ERK-dependent proliferation of cystic cells, but not normal kidney cells. Previously, B-Raf proto-oncogene (BRAF), a MAPK kinase kinase that activates MEK-ERK signaling, was shown to be a central intermediate in the cAMP mitogenic response. However, the role of BRAF on cyst formation and enlargement in vivo had not been demonstrated. To determine if active BRAF induces kidney cyst formation, we generated transgenic mice that conditionally express BRAFV600E, a common activating mutation, and bred them with Pkhd1-Cre mice to express active BRAF in the collecting ducts, a predominant site for cyst formation. Collecting duct expression of BRAFV600E (BRafCD) caused kidney cyst formation as early as three weeks of age. There were increased levels of phosphorylated ERK (p-ERK) and proliferating cell nuclear antigen, a marker for cell proliferation. BRafCD mice developed extensive kidney fibrosis and elevated blood urea nitrogen, indicating a decline in kidney function, by ten weeks of age. BRAFV600E transgenic mice were also bred to Pkd1RC/RC and pcy/pcy mice, well-characterized slowly progressive PKD models. Collecting duct expression of active BRAF markedly increased kidney weight/body weight, cyst number and size, and total cystic area. There were increased p-ERK levels and proliferating cells, immune cell infiltration, interstitial fibrosis, and a decline in kidney function in both these models. Thus, our findings demonstrate that active BRAF is sufficient to induce kidney cyst formation in normal mice and accelerate cystic disease in PKD mice.

What makes or breaks a campaign to stop an invading plant pathogen?

Diseases in humans, animals and plants remain an important challenge in our society. Effective control of invasive pathogens often requires coordinated concerted action of a large group of stakeholders. Both epidemiological and human behavioural factors influence the outcome of a disease control campaign. In mathematical models that are frequently used to guide such campaigns, human behaviour is often ill-represented, if at all. Existing models of human, animal and plant disease that do incorporate participation or compliance are often driven by pay-offs or direct observations of the disease state. It is however very well known that opinion is an important driving factor of human decision making. Here we consider the case study of Citrus Huanglongbing disease (HLB), which is an acute bacterial disease that threatens the sustainability of citrus production across the world. We show how by coupling an epidemiological model of this invasive disease with an opinion dynamics model we are able to answer the question: What makes or breaks the effectiveness of a disease control campaign? Frequent contact between stakeholders and advisors is shown to increase the probability of successful control. More surprisingly, we show that informing stakeholders about the effectiveness of control methods is of much greater importance than prematurely increasing their perceptions of the risk of infection. We discuss the overarching consequences of this finding and the effect on human as well as plant disease epidemics.

A mutation affecting polycystin-1 mediated heterotrimeric G-protein signaling causes PKD.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of renal cysts that ultimately destroy kidney function. Mutations in the PKD1 and PKD2 genes cause ADPKD. Their protein products, polycystin-1 (PC1) and polycystin-2 (PC2) have been proposed to form a calcium-permeable receptor-channel complex; however the mechanisms by which they function are almost completely unknown. Most mutations in PKD1 are truncating loss-of-function mutations or affect protein biogenesis, trafficking or stability and reveal very little about the intrinsic biochemical properties or cellular functions of PC1. An ADPKD patient mutation (L4132Δ or ΔL), resulting in a single amino acid deletion in a putative G-protein binding region of the PC1 C-terminal cytosolic tail, was found to significantly decrease PC1-stimulated, G-protein-dependent signaling in transient transfection assays. Pkd1ΔL/ΔL mice were embryo-lethal suggesting that ΔL is a functionally null mutation. Kidney-specific Pkd1ΔL/cond mice were born but developed severe, postnatal cystic disease. PC1ΔL protein expression levels and maturation were comparable to those of wild type PC1, and PC1ΔL protein showed cell surface localization. Expression of PC1ΔL and PC2 complexes in transfected CHO cells failed to support PC2 channel activity, suggesting that the role of PC1 is to activate G-protein signaling to regulate the PC1/PC2 calcium channel.

Eco-Epidemiological Uncertainties of Emerging Plant Diseases: The Challenge of Predicting Xylella fastidiosa Dynamics in Novel Environments.

In order to prevent and control the emergence of biosecurity threats such as vector-borne diseases of plants, it is vital to understand drivers of entry, establishment, and spatiotemporal spread, as well as the form, timing, and effectiveness of disease management strategies. An inherent challenge for policy in combatting emerging disease is the uncertainty associated with intervention planning in areas not yet affected, based on models and data from current outbreaks. Following the recent high-profile emergence of the bacterium Xylella fastidiosa in a number of European countries, we review the most pertinent epidemiological uncertainties concerning the dynamics of this bacterium in novel environments. To reduce the considerable ecological and socio-economic impacts of these outbreaks, eco-epidemiological research in a broader range of environmental conditions needs to be conducted and used to inform policy to enhance disease risk assessment, and support successful policy-making decisions. By characterizing infection pathways, we can highlight the uncertainties that surround our knowledge of this disease, drawing attention to how these are amplified when trying to predict and manage outbreaks in currently unaffected locations. To help guide future research and decision-making processes, we invited experts in different fields of plant pathology to identify data to prioritize when developing pest risk assessments. Our analysis revealed that epidemiological uncertainty is mainly driven by the large variety of hosts, vectors, and bacterial strains, leading to a range of different epidemiological characteristics further magnified by novel environmental conditions. These results offer new insights on how eco-epidemiological analyses can enhance understanding of plant disease spread and support management recommendations.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Human-Specific Abnormal Alternative Splicing of Wild-Type PKD1 Induces Premature Termination of Polycystin-1.

BACKGROUND: The major form of autosomal dominant polycystic kidney disease is caused by heterozygous mutations in PKD1, the gene that encodes polycystin-1 (PC1). Unlike PKD1 genes in the mouse and most other mammals, human PKD1 is unusual in that it contains two long polypyrimidine tracts in introns 21 and 22 (2.5 kbp and 602 bp, respectively; 97% cytosine and thymine). Although these polypyrimidine tracts have been shown to form thermodynamically stable segments of triplex DNA that can cause DNA polymerase stalling and enhance the local mutation rate, the efficiency of transcription and splicing across these cytosine- and thymine-rich introns has been unexplored. METHODS: We used RT-PCR and Western blotting (using an mAb to the N terminus) to probe splicing events over exons 20-24 in the mouse and human PKD1 genes as well as Nanopore sequencing to confirm the presence of multiple splice forms. RESULTS: Analysis of PC1 indicates that humans, but not mice, have a smaller than expected protein product, which we call Trunc_PC1. The findings show that Trunc_PC1 is the protein product of abnormal differential splicing across introns 21 and 22 and that 28.8%-61.5% of PKD1 transcripts terminate early. CONCLUSIONS: The presence of polypyrimidine tracts decreases levels of full-length PKD1 mRNA from normal alleles. In heterozygous individuals, low levels of full-length PC1 may reduce polycystin signaling below a critical "cystogenic" threshold.

Periostin overexpression in collecting ducts accelerates renal cyst growth and fibrosis in polycystic kidney disease.

In polycystic kidney disease (PKD), persistent activation of cell proliferation and matrix production contributes to cyst growth and fibrosis, leading to progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is overexpressed by cystic epithelial cells of PKD kidneys. Periostin binds αVß3-integrins and activates integrin-linked kinase (ILK), leading to Akt/mammalian target of rapamycin (mTOR)-mediated proliferation of human PKD cells. By contrast, periostin does not stimulate the proliferation of normal human kidney cells. This difference in the response to periostin is due to elevated expression of αVß3-integrins by cystic cells. To determine whether periostin accelerates cyst growth and fibrosis, we generated mice with conditional overexpression of periostin in the collecting ducts (CDs). Ectopic CD expression of periostin was not sufficient to induce cyst formation or fibrosis in wild-type mice. However, periostin overexpression in pcy/pcy ( pcy) kidneys significantly increased mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis; and accelerated the decline in renal function. Moreover, CD-specific overexpression of periostin caused a decrease in the survival of pcy mice. These pathological changes were accompanied by increased renal expression of vimentin, α-smooth muscle actin, and type I collagen. We also found that periostin increased gene expression of pathways involved in repair, including integrin and growth factor signaling and ECM production, and it stimulated focal adhesion kinase, Rho GTPase, cytoskeletal reorganization, and migration of PKD cells. These results suggest that periostin stimulates signaling pathways involved in an abnormal tissue repair process that contributes to cyst growth and fibrosis in PKD.

A method of determining where to target surveillance efforts in heterogeneous epidemiological systems.

The spread of pathogens into new environments poses a considerable threat to human, animal, and plant health, and by extension, human and animal wellbeing, ecosystem function, and agricultural productivity, worldwide. Early detection through effective surveillance is a key strategy to reduce the risk of their establishment. Whilst it is well established that statistical and economic considerations are of vital importance when planning surveillance efforts, it is also important to consider epidemiological characteristics of the pathogen in question-including heterogeneities within the epidemiological system itself. One of the most pronounced realisations of this heterogeneity is seen in the case of vector-borne pathogens, which spread between 'hosts' and 'vectors'-with each group possessing distinct epidemiological characteristics. As a result, an important question when planning surveillance for emerging vector-borne pathogens is where to place sampling resources in order to detect the pathogen as early as possible. We answer this question by developing a statistical function which describes the probability distributions of the prevalences of infection at first detection in both hosts and vectors. We also show how this method can be adapted in order to maximise the probability of early detection of an emerging pathogen within imposed sample size and/or cost constraints, and demonstrate its application using two simple models of vector-borne citrus pathogens. Under the assumption of a linear cost function, we find that sampling costs are generally minimised when either hosts or vectors, but not both, are sampled.

Integrin-Linked Kinase Signaling Promotes Cyst Growth and Fibrosis in Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by innumerous fluid-filled cysts and progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is markedly overexpressed by cyst epithelial cells. Periostin promotes cell proliferation, cyst growth, interstitial fibrosis, and the decline in renal function in PKD mice. Here, we investigated the regulation of these processes by the integrin-linked kinase (ILK), a scaffold protein that links the extracellular matrix to the actin cytoskeleton and is stimulated by periostin. Pharmacologic inhibition or shRNA knockdown of ILK prevented periostin-induced Akt/mammalian target of rapamycin (mTOR) signaling and ADPKD cell proliferation in vitro Homozygous deletion of ILK in renal collecting ducts (CD) of Ilkfl/fl ;Pkhd1-Cre mice caused tubule dilations, apoptosis, fibrosis, and organ failure by 10 weeks of age. By contrast, Ilkfl/+ ;Pkhd1-Cre mice had normal renal morphology and function and survived >1 year. Reduced expression of ILK in Pkd1fl/fl ;Pkhd1-Cre mice, a rapidly progressive model of ADPKD, decreased renal Akt/mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis, and significantly improved renal function and animal survival. Additionally, CD-specific knockdown of ILK strikingly reduced renal cystic disease and fibrosis and extended the life of pcy/pcy mice, a slowly progressive PKD model. We conclude that ILK is critical for maintaining the CD epithelium and renal function and is a key intermediate for periostin activation of signaling pathways involved in cyst growth and fibrosis in PKD.

Integrating regulatory surveys and citizen science to map outbreaks of forest diseases: acute oak decline in England and Wales.

The number of emerging tree diseases has increased rapidly in recent times, with severe environmental and economic consequences. Systematic regulatory surveys to detect and establish the distribution of pests are crucial for successful management efforts, but resource-intensive and costly. Volunteers who identify potential invasive species can form an important early warning network in tree health; however, what these data can tell us and how they can be best used to inform and direct official survey effort is not clear. Here, we use an extensive dataset on acute oak decline (AOD) as an opportunity to ask how verified data received from the public can be used. Information on the distribution of AOD was available as (i) systematic regulatory surveys conducted throughout England and Wales, and (ii) ad hoc sightings reported by landowners, land managers and members of the public (i.e. 'self-reported' cases). By using the available self-reported cases at the design stage, the systematic survey could focus on defining the boundaries of the affected area. This maximized the use of available resources and highlights the benefits to be gained by developing strategies to enhance volunteer efforts in future programmes.

Risk-based management of invading plant disease.

Effective control of plant disease remains a key challenge. Eradication attempts often involve removal of host plants within a certain radius of detection, targeting asymptomatic infection. Here we develop and test potentially more effective, epidemiologically motivated, control strategies, using a mathematical model previously fitted to the spread of citrus canker in Florida. We test risk-based control, which preferentially removes hosts expected to cause a high number of infections in the remaining host population. Removals then depend on past patterns of pathogen spread and host removal, which might be nontransparent to affected stakeholders. This motivates a variable radius strategy, which approximates risk-based control via removal radii that vary by location, but which are fixed in advance of any epidemic. Risk-based control outperforms variable radius control, which in turn outperforms constant radius removal. This result is robust to changes in disease spread parameters and initial patterns of susceptible host plants. However, efficiency degrades if epidemiological parameters are incorrectly characterised. Risk-based control including additional epidemiology can be used to improve disease management, but it requires good prior knowledge for optimal performance. This focuses attention on gaining maximal information from past epidemics, on understanding model transferability between locations and on adaptive management strategies that change over time.

Bayesian inference for an emerging arboreal epidemic in the presence of control.

The spread of Huanglongbing through citrus groves is used as a case study for modeling an emerging epidemic in the presence of a control. Specifically, the spread of the disease is modeled as a susceptible-exposed-infectious-detected-removed epidemic, where the exposure and infectious times are not observed, detection times are censored, removal times are known, and the disease is spreading through a heterogeneous host population with trees of different age and susceptibility. We show that it is possible to characterize the disease transmission process under these conditions. Two innovations in our work are (i) accounting for control measures via time dependence of the infectious process and (ii) including seasonal and host age effects in the model of the latent period. By estimating parameters in different subregions of a large commercially cultivated orchard, we establish a temporal pattern of invasion, host age dependence of the dispersal parameters, and a close to linear relationship between primary and secondary infectious rates. The model can be used to simulate Huanglongbing epidemics to assess economic costs and potential benefits of putative control scenarios.

Monitoring invasive pathogens in plant nurseries for early-detection and to minimise the probability of escape.

The global increase in the movement of plant products in recent years has triggered an increase in the number of introduced plant pathogens. Plant nurseries importing material from abroad may play an important role in the introduction and spread of diseases such as ash dieback and sudden oak death which are thought to have been introduced through trade. The economic, environmental and social costs associated with the spread of invasive pathogens become considerably larger as the incidence of the pathogen increases. To control the movement of pathogens across the plant trade network it is crucial to develop monitoring programmes at key points of the network such as plant nurseries. By detecting the introduction of invasive pathogens at low incidence, the control and eradication of an epidemic is more likely to be successful. Equally, knowing the likelihood of having sold infected plants once a disease has been detected in a nursery can help designing tracing plans to control the onward spread of the disease. Here, we develop an epidemiological model to detect and track the movement of an invasive plant pathogen into and from a plant nursery. Using statistical methods, we predict the epidemic incidence given that a detection of the pathogen has occurred for the first time, considering that the epidemic has an asymptomatic period between infection and symptom development. Equally, we calculate the probability of having sold at least one infected plant during the period previous to the first disease detection. This analysis can aid stakeholder decisions to determine, when the pathogen is first discovered in a nursery, the need of tracking the disease to other points in the plant trade network in order to control the epidemic. We apply our method to high profile recent introductions including ash dieback and sudden oak death in the UK and citrus canker and Huanglongbing disease in Florida. These results provide new insight for the design of monitoring strategies at key points of the trade network.

The Effect of Farmers' Decisions on Pest Control with Bt Crops: A Billion Dollar Game of Strategy.

A farmer's decision on whether to control a pest is usually based on the perceived threat of the pest locally and the guidance of commercial advisors. Therefore, farmers in a region are often influenced by similar circumstances, and this can create a coordinated response for pest control that is effective at a landscape scale. This coordinated response is not intentional, but is an emergent property of the system. We propose a framework for understanding the intrinsic feedback mechanisms between the actions of humans and the dynamics of pest populations and demonstrate this framework using the European corn borer, a serious pest in maize crops. We link a model of the European corn borer and a parasite in a landscape with a model that simulates the decisions of individual farmers on what type of maize to grow. Farmers chose whether to grow Bt-maize, which is toxic to the corn borer, or conventional maize for which the seed is cheaper. The problem is akin to the snow-drift problem in game theory; that is to say, if enough farmers choose to grow Bt maize then because the pest is suppressed an individual may benefit from growing conventional maize. We show that the communication network between farmers' and their perceptions of profit and loss affects landscape scale patterns in pest dynamics. We found that although adoption of Bt maize often brings increased financial returns, these rewards oscillate in response to the prevalence of pests.

Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease.

In renal cystic diseases, sustained enlargement of fluid-filled cysts is associated with severe interstitial fibrosis and progressive loss of functioning nephrons. Periostin, a matricellular protein, is highly overexpressed in cyst-lining epithelial cells of autosomal-dominant polycystic disease kidneys (ADPKD) compared with normal tubule cells. Periostin accumulates in situ within the matrix subjacent to ADPKD cysts, binds to αVß3 and αVß5 integrins, and stimulates the integrin-linked kinase to promote cell proliferation. We knocked out periostin (Postn) in pcy/pcy mice, an orthologous model of nephronophthisis type 3, to determine whether periostin loss reduces PKD progression in a slowly progressive model of renal cystic disease. At 20 weeks of age, pcy/pcy:Postn(-/-) mice had a 34% reduction in kidney weight/body weight, a reduction in cyst number and total cystic area, a 69% reduction in phosphorylated S6, a downstream component of the mTOR pathway, and fewer proliferating cells in the kidneys compared with pcy/pcy:Postn(+/+) mice. The pcy/pcy Postin knockout mice also had less interstitial fibrosis with improved renal function at 20 weeks and significantly longer survival (51.4 compared with 38.0 weeks). Thus, periostin adversely modifies the progression of renal cystic disease by promoting cyst epithelial cell proliferation, cyst enlargement, and interstitial fibrosis, all contributing to the decline in renal function and premature death.