Data and code associated with “Supporting Adaptive Management with Ecological Forecasting: Chronic Wasting Disease in the Jackson Elk Herd”

Final_Data.zip contains several spreadsheets representing data collected by both the Wyoming Game and Fish Department and the US Fish and Wildlife Service for elk management: Jackson feedground census, 1998-2016; Harvest data, 1997-2015; Hunt area census, 1998-2016; Chronic wasting disease test results, 1998-2015. Final_Code.zip contains several Program R scripts written for data analysis and model fitting as described in the full associated article.Adaptive management has emerged as the prevailing approach for combining environmental research and management to advance science and policy. Adaptive management, as originally formulated by Carl Walters in 1986, depends on the use of Bayesian models to provide a framework to accumulate knowledge. The emergence of ecological forecasting using the Bayesian framework has provided robust tools and supports a new approach to informing adaptive management, which can be particularly useful in developing policy for managing infectious disease in wildlife. We used the potential infection of elk populations with chronic wasting disease in the Jackson Valley of Wyoming and the National Elk Refuge as a model system to show how Bayesian forecasting can support adaptive management in anticipation of management challenges. The core of our approach resembles the sex- and age-structured, discrete time models used to support management decisions on elk harvest throughout western North America. Our model differs by including stages for CWD infected and unaffected animals. We used data on population counts, sex and age classification, and CWD testing, as well as results from prior research, in a Bayesian statistical framework to predict model parameters and the number of animals in each age, sex, and disease stage over time. Initial forecasts suggested CWD may reach a mean prevalence in the population of 12%, but uncertainty in this forecast is large and we cannot rule out a mean forecasted prevalence as high as 20%. Using recruitment rates observed during the last two decades, the model predicted that a CWD prevalence of 7% in females would cause the population growth rate (l) to drop below 1, resulting in population declines even when female harvest was zero. The primary value of this ecological forecasting approach is to provide a framework to assimilate data with understanding of disease processes to enable continuous improvement in understanding the ecology of CWD and its management.Data collection was funded as part of management efforts by the Wyoming Game and Fish Department and the US Fish and Wildlife Service. Data analysis and work for publication was funded by the US Fish and Wildlife Service and the National Park Service

Reimmunization increases contraceptive effectiveness of gonadotropin-releasing hormone vaccine (GonaCon-Equine) in freeranging horses (\u3ci\u3eEquus caballus\u3c/i\u3e): Limitations and side effects

Wildlife and humans are increasingly competing for resources worldwide, and a diverse, innovative, and effective set of management tools is needed. Controlling abundance of wildlife species that are simultaneously protected, abundant, competitive for resources, and in conflict with some stakeholders but beloved by others, is a daunting challenge. Free-ranging horses (Equus caballus) present such a conundrum and managers struggle for effective tools for regulating their abundance. Controlling reproduction of female horses presents a potential alternative. During 2009±2017, we determined the long-term effectiveness of GnRH vaccine (GonaCon-Equine) both as a single immunization and subsequent reimmunization on reproduction and side effects in free-ranging horses. At a scheduled management roundup in 2009, we randomly assigned 57 adult mares to either a GonaCon-Equine treatment group (n = 29) or a saline control group (n = 28). In a second roundup in 2013, we administered a booster vaccination to these same mares. We used annual ground observations to estimate foaling proportions, social behaviors, body condition, and injection site reactions. We found this vaccine to be safe for pregnant females and neonates, with no overt deleterious behavioral side effects during the breeding season. The proportion of treated mares that foaled following a single vaccination was lower than that for control mares for the second (P = 0.03) and third (P = 0.08) post-treatment foaling seasons but was similar (P = 0.67) to untreated mares for the fourth season, demonstrating reversibility of the primary vaccine treatment. After two vaccinations, however, the proportion of females giving birth was lower (

The N-Myc Down Regulated Gene1 (NDRG1) Is a Rab4a Effector Involved in Vesicular Recycling of E-Cadherin

Cell to cell adhesion is mediated by adhesion molecules present on the cell surface. Downregulation of molecules that form the adhesion complex is a characteristic of metastatic cancer cells. Downregulation of the N-myc down regulated gene1 (NDRG1) increases prostate and breast metastasis. The exact function of NDRG1 is not known. Here by using live cell confocal microscopy and in vitro reconstitution, we report that NDRG1 is involved in recycling the adhesion molecule E-cadherin thereby stabilizing it. Evidence is provided that NDRG1 recruits on recycling endosomes in the Trans Golgi network by binding to phosphotidylinositol 4-phosphate and interacts with membrane bound Rab4aGTPase. NDRG1 specifically interacts with constitutively active Rab4aQ67L mutant protein and not with GDP-bound Rab4aS22N mutant proving NDRG1 as a novel Rab4a effector. Transferrin recycling experiments reveals NDRG1 colocalizes with transferrin during the recycling phase. NDRG1 alters the kinetics of transferrin recycling in cells. NDRG1 knockdown cells show a delay in recycling transferrin, conversely NDRG1 overexpressing cells reveal an increase in rate of transferrin recycling. This novel finding of NDRG1 as a recycling protein involved with recycling of E-cadherin will aid in understanding NDRG1 role as a metastasis suppressor protein

The ABC130 barrel module prototyping programme for the ATLAS strip tracker

For the Phase-II Upgrade of the ATLAS Detector, its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100 % silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-25) and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.Comment: 82 pages, 66 figure

Molecular ecology and hierarchical models elucidate chronic wasting disease dynamics

2018 Summer.Includes bibliographical references.Prions present a unique evolutionary scenario because a single gene codes for both a disease agent and a functionally constrained native protein. The prion precursor gene, Prnp, codes for the prion precursor protein, PrP, which is constitutively expressed as a native isoform within all mammals. Upon misfolding to the disease isoform, known as prions, the same protein causes fatal neurodegenerative diseases known as transmissible spongiform encephalopathies. We review the literature and available data for the genetics of Prnp in order to examine its molecular evolutionaryhistory, and the likely force of natural selection acting on it, by analyzing genetic diversity both within and between species within Class Mammalia. We accessed Prnp nucleotide sequences of a large number of mammalian species from GenBank. We undertook three distinct analyses of these molecular data to characterize the force of selection acting on Prnp through comparisons of gene sequences and allele frequencies within and between species. Our analyses include: 1.) comparisons of genetic and amino acid polymorphisms across protein domains within Prnp, 2.) a within and between species comparison of nucleotide diversity within Prnp to characterize natural selection acting on the gene, and 3.) observed frequencies of genetic and amino acid polymorphisms from natural populations of animals. We show that amino acid substitutions reported to correlate with prion disease risk within species do not aggregate within particular protein structural domains, but rather are disparately located throughout. Branch model estimates using Phylogenetic Analysis by Maximum Likelihood across mammals show that Prnp undergoes strong purifying selection at the broad scale, that purifying selection is stronger between species than it is within species but no evidence that species orally susceptible to prion disease experience unique positive selection. We do show, however, that amino acid substitutions occur at higher frequencies than synonymous substitutions within Prnp, in direct conflict with the expectations for purifying selection. This evidence suggests that Prnp is experiencing balancing selection in opposition to the purifying selection observed at the large scale; this unique selective pressure may be due to the presence of prion disease. Ecological processes such as reproduction, habitat use, and disease epizootiology contribute to the growth or decline of wildlife populations, but many of these processes go directly unobserved. We set out to describe gene flow and disease transmission to better understand the ecological role of chronic wasting disease (CWD) in a northern Colorado population of mule deer (Odocoileus hemionus). CWD, a fatal prion disease, has been affecting this population for many decades. It has not caused extirpation of the deer, but may play an important limiting role in population growth and resilience. We employed genetic methods to analyze neutral genetic markers, which provide information about gene flow. Further, we examined allelic variation in the functional prion precursor gene, Prnp, which codes for the disease-causative prion of CWD and has alternative alleles with one (225F) that confers some resistance to prion disease within individual deer. The study in northern Colorado included sampling across four winter ranges. Genetic analysis identified four genetic lineages of deer, but lineages were distributed throughout the study area and did not correspond with winter ranges used annually with high fidelity by groups of females. Further, we show that males drive gene flow across genetic lineages. In contrast, CWD prevalence was spatially segregated: CWD-positive female deer were located in two of the winter ranges and absent from the others. This suggests that neither breeding sites nor natal dispersal are the primary means of disease spread in females across the winter ranges. Furthermore, we found, as previously reported, that an individual deer's Prnp genotype predicts the likelihood of a positive disease test. Even so, the frequency of the Prnp 225F allele was similar across winter ranges, and was notably higher than that reported in neighboring populations a decade earlier. Thus, it appears that gene flow spreads the favored allele across the study area despite different selective regimes in winter ranges. Our work shows the benefit of using population genetics to gain insight into ecological processes that go directly unobserved, such as the epizootiology of chronic wasting disease. Chronic wasting disease is a fatal neurodegenerative prion disease that infects members of the deer family in North America and Scandinavia. We conducted a five-year mark recapture study of a northern Colorado population of mule deer (Odocoileus hemionus) with endemic disease, including 217 females. All study animals were also genotyped at the prion precursor gene, Prnp, which has alternative alleles in many species to express amino acid differences that alter prion disease dynamics. Mark-recapture analysis revealed decreased disease incidence for individuals expressing genotypes with at least one copy of the minor allele, including heterozygotes, Prnp 225SF (expressing both a serine and phenylalanine at amino acid position 225) , and rare homozygotes, 225FF.We found no evidence for an evolutionary trade-off of decreased survival of CWD-negative deer for this group but emphasize the difficulty in estimating dynamic rates for the rare homozygotes alone. We employed estimates of annual disease risk and survival from this study as well as recruitment estimates from the literature, to forecast the expected future minor allele frequency in the population under the observed disease risk. This forecast revealed a clear expected evolutionary increase in the Prnp minor allele (225F) frequency given our model and field data

Reimmunization increases contraceptive effectiveness of gonadotropin-releasing hormone vaccine (GonaCon-Equine) in freeranging horses (\u3ci\u3eEquus caballus\u3c/i\u3e): Limitations and side effects

Wildlife and humans are increasingly competing for resources worldwide, and a diverse, innovative, and effective set of management tools is needed. Controlling abundance of wildlife species that are simultaneously protected, abundant, competitive for resources, and in conflict with some stakeholders but beloved by others, is a daunting challenge. Free-ranging horses (Equus caballus) present such a conundrum and managers struggle for effective tools for regulating their abundance. Controlling reproduction of female horses presents a potential alternative. During 2009±2017, we determined the long-term effectiveness of GnRH vaccine (GonaCon-Equine) both as a single immunization and subsequent reimmunization on reproduction and side effects in free-ranging horses. At a scheduled management roundup in 2009, we randomly assigned 57 adult mares to either a GonaCon-Equine treatment group (n = 29) or a saline control group (n = 28). In a second roundup in 2013, we administered a booster vaccination to these same mares. We used annual ground observations to estimate foaling proportions, social behaviors, body condition, and injection site reactions. We found this vaccine to be safe for pregnant females and neonates, with no overt deleterious behavioral side effects during the breeding season. The proportion of treated mares that foaled following a single vaccination was lower than that for control mares for the second (P = 0.03) and third (P = 0.08) post-treatment foaling seasons but was similar (P = 0.67) to untreated mares for the fourth season, demonstrating reversibility of the primary vaccine treatment. After two vaccinations, however, the proportion of females giving birth was lower (

Anaplasma phagocytophilum APH0032 is exposed on the cytosolic face of the pathogen-occupied vacuole and co-opts host cell SUMOylation

Anaplasma phagocytophilum, a member of the family Anaplasmataceae and the obligate intracellular bacterium that causes granulocytic anaplasmosis, resides in a host cell-derived vacuole. Bacterial proteins that localize to the A. phagocytophilum-occupied vacuole membrane (AVM) are critical host-pathogen interfaces. Of the few bacterial AVM proteins that have been identified, the domains responsible for AVM localization and the host cell pathways that they co-opt are poorly defined. APH0032 is an effector that is expressed and localizes to the AVM late during the infection cycle. Herein, the APH0032 domain that is essential for associating with host cell membranes was mapped. Immunofluorescent labeling of infected cells that had been differentially permeabilized confirmed that APH0032 is exposed on the AVM’s cytosolic face, signifying its potential to interface with host cell processes. SUMOylation is the covalent attachment of a member of the small ubiquitin-like modifier (SUMO) family of proteins to lysines in target substrates. Previous work from our laboratory determined that SUMOylation is important for A. phagocytophilum survival and that SUMOylated proteins decorate the AVM. Algorithmic prediction analyses identified APH0032 as a candidate for SUMOylation. Endogenous APH0032 was precipitated from infected cells using a SUMO affinity matrix, confirming that the effector co-opts SUMOylation during infection. APH0032 pronouncedly colocalized with SUMO1, but not SUMO2/3 moieties on the AVM. Ectopic expression of APH0032 in A. phagocytophilum infected host cells significantly boosted the bacterial load. This study delineates the first domain of any Anaplasmataceae protein that is essential for associating with the pathogen-occupied vacuole membrane, demonstrates the importance of APH0032 to infection, and identifies it as the second A. phagocytophilum effector that co-opts SUMOylation, thus underscoring the relevance of this post-translational modification to infection

Differentiating research from management in welfare review of wildlife activities

Abstract A common understanding and clear process to apply the Animal Welfare Act (AWA) to wildlife‐related activities is crucial to promote animal welfare when conducting wildlife research and for streamlining review by an Institutional Animal Care and Use Committee (IACUC). Current interpretation of the AWA and United States government policies advise that wildlife research activities be reviewed for compliance by an IACUC; however, guidance regarding which wildlife activities are categorized as research and therefore subject to review and oversight is limited. In our opinion and experience, this lack of clarity creates a challenge, particularly for natural resource agencies that conduct a range of wildlife activities, to ensure that research is properly identified for IACUC review and differentiated from management activities that are exempt from review. To fill the gap in current guidance, we propose a decision‐making model that clarifies research and management activities. We apply our model to case studies involving wildlife to highlight nuanced differences between the 2 types of activities. Wildlife agencies conducting potentially regulated activities could use this adaptable model, which has been successfully employed by the National Park Service IACUC, to clarify when the AWA might apply, streamline IACUC reviews, and promote welfare of wildlife

Intra-host mathematical model of chronic wasting disease dynamics in deer (<i>Odocoileus</i>)

<p>Bioassays of native cervid hosts have established the presence of infectious chronic wasting disease (CWD) prions in saliva, blood, urine, and feces of clinically diseased and pre-clinical infected deer. The intra-host trafficking of prions from the time of initial infection to shedding has been less well defined. We created a discrete-time compartmentalized model to simulate the misfolding catalysis, trafficking, and shedding of infectious prions throughout the organ systems of CWD-infected cervids. Using parameter values derived from experimental infections of North American deer (<i>Odocoileus spp</i>.), the exponential-based model predicts prion deposition over time with: 1) nervous tissues containing the highest deposition of prions at 20 months post-infection and 2) excreted fluids containing low levels of prions throughout infection with the highest numbers of prions predicted to be shed in saliva and feces (as high as 10 lethal doses (1.34 × 10²⁹ prions) in 11–15 months). These findings are comparable to prion deposition described in literature as assayed by conventional and ultrasensitive amplification assays. The comparison of our model to published data suggests that highly sensitive assays (sPMCA, RT-QuIC, and bioassay) are appropriate for early prion detection in bodily fluids and secretions. The model provides a view of intra-host prion catalysis leading to pre-clinical shedding and provides a framework for continued development of antemortem diagnostic methods.</p