Ethyl-Iophenoxic acid as a serum marker for oral baiting of carnivorous marsupials

Context: Ethyl-Iophenoxic acid (Et-IPA) has been widely used as a bait biomarker to determine oral bait consumption by vertebrate wildlife species. Oral bait vaccines have been delivered to numerous wildlife species to protect them from disease. The Tasmanian devil (Sarcophilis harrisii), the largest extant carnivorous marsupial species, is threatened by the transmissible cancers known as devil facial tumour disease (DFTD). Development of a protective DFTD vaccine is underway, and an oral bait has been proposed to deliver the vaccine in the wild. The bait delivery system requires a biomarker that can be detected for several months post-consumption in Tasmanian devils. Aim: To determine the suitability of Et-IPA as a bait biomarker in the Tasmanian devil. Method: Two Tasmanian devils were fed 50 mg Et-IPA (4.5 to 7.1 mg Et-IPA/kg bodyweight). Liquid chromatography with tandem mass spectrometry (LC-MS/-MS) was used to directly measure Et-IPA in baseline serum samples and samples collected on days 1, 14, 26 and 56 post-baiting. Key results: Both devils retained serum Et-IPA concentrations at two orders of magnitude above negative control sera when this study concluded. Conclusions: Et-IPA is a useful bait biomarker for Tasmanian devils and can be included in future DFTD bait vaccine field trials to determine bait vaccine uptake.

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Are any populations 'safe'? Unexpected reproductive decline in a population of Tasmanian devils free of devil facial tumour disease

Wildlife Research ◽

10.1071/wr16234 ◽

2018 ◽

Vol 45 (1) ◽

pp. 31 ◽

Cited By ~ 7

Author(s):

K. A. Farquharson ◽

R. M. Gooley ◽

S. Fox ◽

S. J. Huxtable ◽

K. Belov ◽

...

Keyword(s):

Conservation Management ◽

Southern Oscillation ◽

Demographic Data ◽

Management Strategies ◽

Natural Populations ◽

Significant Decline ◽

Tasmanian Devil ◽

Devil Facial Tumour Disease ◽

In The Wild ◽

Reproductive Rates

Context Conservation management relies on baseline demographic data of natural populations. For Tasmanian devils (Sarcophilus harrisii), threatened in the wild by two fatal and transmissible cancers (devil facial tumour disease DFTD: DFT1 and DFT2), understanding the characteristics of healthy populations is crucial for developing adaptive management strategies to bolster populations in the wild. Aims Our analysis aims to evaluate contemporary reproductive rates for wild, DFTD-free Tasmanian devil populations, and to provide a baseline with which to compare the outcome of current translocation activities. Methods We analysed 8 years of field-trapping data, including demographics and reproductive rates, across 2004–16, from the largest known DFTD-free remnant population at Woolnorth, Tasmania. Key results Surprisingly, we found a dramatic and statistically significant decline in female breeding rate when comparing data collected from 2004–2009 with data from 2014–2016. Unfortunately we do not have any data from the intermediate years. This decline in breeding rate was accompanied by a subtle but statistically significant decline in litter sizes. These changes were not associated with a change in body condition over the same period. Furthermore, we could not attribute the decline in breeding to a change in population size or sex ratio. Preliminary analysis suggested a possible association between annual breeding rate and coarse measures of environmental variation (Southern Oscillation Index), but any mechanistic associations are yet to be determined. Conclusions The decline in breeding rates was unexpected, so further monitoring and investigation into potential environmental and/or biological reasons for the decline in breeding rate are recommended before the arrival of DFTD at Woolnorth. Implications Our results provide valuable data to support the conservation management of Tasmanian devils in their native range. They also highlight the importance of continued monitoring of ‘safe’ populations, in the face of significant threats elsewhere.

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Cathelicidin-3 associated with serum extracellular vesicles enables early diagnosis of a transmissible cancer

10.1101/2021.12.06.471373 ◽

2021 ◽

Author(s):

Camila Espejo ◽

Richard Wilson ◽

Ruth J. Pye ◽

Julian C. Ratcliffe ◽

Manuel Ruiz-Aravena ◽

...

Keyword(s):

Early Diagnosis ◽

Biomarker Discovery ◽

Extracellular Vesicle ◽

Conservation Strategies ◽

Tasmanian Devil ◽

Serum Samples ◽

Visual Identification ◽

Devil Facial Tumour Disease ◽

Transmissible Cancer ◽

One Year

AbstractThe identification of practical early diagnosis biomarkers is a cornerstone of improved prevention and treatment of cancers. Such a case is devil facial tumour disease (DFTD), a highly lethal transmissible cancer afflicting virtually an entire species, the Tasmanian devil (Sarcophilus harrisii). Despite a latent period that can exceed one year, to date DFTD diagnosis requires visual identification of tumour lesions. To enable earlier diagnosis, which is essential for the implementation of effective conservation strategies, we analysed the extracellular vesicle (EV) proteome of 87 Tasmanian devil serum samples. The antimicrobial peptide cathelicidin-3 (CATH3) was enriched in serum EVs of both devils with clinical DFTD (87.9% sensitivity and 94.1% specificity) and devils with latent infection (i.e., collected while overtly healthy, but 3-6 months before subsequent DFTD diagnosis; 93.8% sensitivity and 94.1% specificity). As antimicrobial peptides can play a variety of roles in the cancer process, our results suggest that the specific elevation of serum EV-associated CATH3 may be mechanistically involved in DFTD pathogenesis. This EV-based approach to biomarker discovery is directly applicable to improving understanding and diagnosis of a broad range of diseases in other species, and these findings directly enhance the capacity of conservation strategies to ensure the viability of the imperilled Tasmanian devil population.

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A Tasmanian devil breeding program to support wild recovery

Reproduction Fertility and Development ◽

10.1071/rd18152 ◽

2019 ◽

Vol 31 (7) ◽

pp. 1296 ◽

Cited By ~ 7

Author(s):

C. E. Grueber ◽

E. Peel ◽

B. Wright ◽

C. J. Hogg ◽

K. Belov

Keyword(s):

Genetic Diversity ◽

Reproductive Success ◽

Genetic Research ◽

Breeding Program ◽

Natural Environments ◽

Tasmanian Devil ◽

Strategic Approach ◽

Devil Facial Tumour Disease ◽

Transmissible Cancer ◽

In The Wild

Tasmanian devils are threatened in the wild by devil facial tumour disease: a transmissible cancer with a high fatality rate. In response, the Save the Tasmanian Devil Program (STDP) established an ‘insurance population’ to enable the preservation of genetic diversity and natural behaviours of devils. This breeding program includes a range of institutions and facilities, from zoo-based intensive enclosures to larger, more natural environments, and a strategic approach has been required to capture and maintain genetic diversity, natural behaviours and to ensure reproductive success. Laboratory-based research, particularly genetics, in tandem with adaptive management has helped the STDP reach its goals, and has directly contributed to the conservation of the species in the wild. Here we review this work and show that the Tasmanian devil breeding program is a powerful example of how genetic research can be used to understand and improve reproductive success in a threatened species.

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Lessons from the Looming Extinction of the Tasmanian Devil

Pacific Conservation Biology ◽

10.1071/pc080151 ◽

2008 ◽

Vol 14 (3) ◽

pp. 151 ◽

Cited By ~ 3

Author(s):

D. Lunney ◽

M. Jones ◽

H. McCullum

Keyword(s):

Cancer Cells ◽

Captive Breeding ◽

Active Management ◽

Tasmanian Devil ◽

Population Bottlenecks ◽

Low Genetic Diversity ◽

Devil Facial Tumour Disease ◽

In The Wild ◽

Breeding Programmes ◽

Infectious Cancer

Extinction in the wild is now regarded as likely for the Tasmanian Devil Sarcophilus harrissi. In 1996, a disease, Devil Facial Tumour Disease (DFTD), was seen in a Devil in the wild. By mid-2008, the population had declined by about 70%, and the disease was spreading rapidly from east to west across Tasmania. DFTD is an infectious cancer, passed from one Devil to another principally, or entirely, by biting. The bite implants the cancer cells; the low genetic diversity in the Tasmanian Devil population from previous population bottlenecks or selective sweeps means that those cancer cells are not recognized by the immune system and the cancer grows in the infected Devil. Estimates of the time to extinction in the wild range from about 20 to 35 years. If, however, there are resistant genotypes within the Devil population then extinction in the wild may be averted, with numbers augmented through captive breeding programmes and active management to spread these genotypes in the wild.

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FRI0596 NOVEL AUTOANTIBODY BIOMARKERS FOR THE PREDICTION OF THERAPY RESPONSE IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4184 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 904.1-904

Author(s):

P. Vandormael ◽

A. Pues ◽

E. Sleurs ◽

P. Verschueren ◽

V. Somers

Keyword(s):

Rheumatoid Arthritis ◽

Therapy Response ◽

Autoimmune Disorder ◽

First Line ◽

Research Support ◽

Serum Samples ◽

Glucocorticoid Treatment ◽

Baseline Serum ◽

Disease Remission ◽

Antibody Reactivity

Background:Rheumatoid arthritis (RA) is an autoimmune disorder that is characterized by chronic inflammation of the joint synovium and presence of autoantibodies in most patients. For RA, many treatments are currently available but each treatment will only induce disease remission in a subset of patients. Moreover, finding out which patients respond well to first-line therapy with classical synthetic disease modifying anti-rheumatic drugs (csDMARDs), still largely depends on trial and error.Objectives:In this study, we aim to find novel RA autoantibody biomarkers that predict therapy response to csDMARDs before the initiation of treatment.Methods:In the CareRA trial, a Flemish multicenter study of different treatment regimes, serum samples were collected from RA patients that did or did not show disease remission (DAS28(CRP)<2.6) in response to csDMARDs, combined with a step down glucocorticoid treatment. In our study, baseline samples, collected before the start of treatment, were used to determine predictive antibody reactivity. A cDNA phage display library, representing the antigens from RA synovial tissue, was constructed and screened for antibody reactivity in baseline serum samples of RA patients that failed to reach remission at week 16. Using enzyme-linked immunosorbent assays (ELISA), antibody reactivity against the identified antigens was initially determined in pooled baseline serum samples of RA patients that did (n=50) or did not (n=40) reach disease remission at week 16. Antigenic targets that showed increased antibody reactivity in pools from patients that did not reach disease remission, were further validated in individual serum samples of 69 RA patients that did not reach DAS28(CRP) remission at week 16, and 122 RA patients that did.Results:Screening and validation of antibody reactivity resulted in 41 novel antigens. The retrieved antigenic sequences correspond to (parts of) known proteins and to randomly formed peptides. A panel of 3 of these peptide antigens could be composed, whose baseline antibody reactivity correlated with lack of therapy response at week 16. Presence of antibodies against at least one of these 3 antigens was significantly higher in individual samples of RA patients that did not reach DAS28(CRP) remission (43 vs. 29%, p=0.041), or that failed to reach ACR 70 (42 vs. 26%, p=0.029) response criteria at week 16, compared to RA patients that did reach these respective criteria. In addition, RA patients which were positive for this antibody panel at baseline, also showed less DAS(CRP) remission at week 4 and week 8.Conclusion:We have identified a set of 3 antibody biomarkers that can predict failure of early disease remission after first-line RA therapy, which might contribute to personalized medicine decisions.Disclosure of Interests:Patrick Vandormael: None declared, Astrid Pues: None declared, Ellen Sleurs: None declared, Patrick Verschueren Grant/research support from: Pfizer unrestricted chair of early RA research, Speakers bureau: various companies, Veerle Somers Grant/research support from: Research grant from Pfizer and BMS

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Low major histocompatibility complex diversity in the Tasmanian devil predates European settlement and may explain susceptibility to disease epidemics

Biology Letters ◽

10.1098/rsbl.2012.0900 ◽

2013 ◽

Vol 9 (1) ◽

pp. 20120900 ◽

Cited By ~ 36

Author(s):

Katrina Morris ◽

Jeremy J. Austin ◽

Katherine Belov

Keyword(s):

Major Histocompatibility Complex ◽

Tasmanian Devil ◽

Major Histocompatibility ◽

European Settlement ◽

Low Genetic Diversity ◽

Histocompatibility Complex ◽

Devil Facial Tumour Disease ◽

History Of ◽

Mhc Diversity ◽

Disease Epidemics

The Tasmanian devil ( Sarcophilus harrisii ) is at risk of extinction owing to the emergence of a contagious cancer known as devil facial tumour disease (DFTD). The emergence and spread of DFTD has been linked to low genetic diversity in the major histocompatibility complex (MHC). We examined MHC diversity in historical and ancient devils to determine whether loss of diversity is recent or predates European settlement in Australia. Our results reveal no additional diversity in historical Tasmanian samples. Mainland devils had common modern variants plus six new variants that are highly similar to existing alleles. We conclude that low MHC diversity has been a feature of devil populations since at least the Mid-Holocene and could explain their tumultuous history of population crashes.

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BAFF Predicts Immunogenicity in Older Patients With Rheumatoid Arthritis Treated With TNF Inhibitors

10.21203/rs.3.rs-74233/v1 ◽

2020 ◽

Author(s):

Borja Hernández-Breijo ◽

Victoria Navarro-Compán ◽

Chamaida Plasencia-Rodríguez ◽

Ioannis Parodis ◽

Johanna E. Gehin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Older Patients ◽

Operating Characteristic ◽

Certolizumab Pegol ◽

Positive Likelihood Ratio ◽

Characteristic Analysis ◽

Serum Samples ◽

Chi Square ◽

Baseline Serum ◽

Logistic Regression Models

Abstract Background: Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum BAFF with immunogenicity after 6 months of TNFi treatment.Methods: A total of 139 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association.Results: At 6 months, 39 patients (28%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value=5.30; p=0.02); therefore, subsequent results were stratified according to mean age (≤/>55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR=1.55; 95% CI: 1.03-2.12). Baseline serum BAFF≥1034pg/mL predicted the presence of ADA at 6 months (positive likelihood ratio=3.7).Conclusions: Our results suggest that the association of BAFF concentration and immunogenicity depends on the patient’s age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.

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The effects of season and devil facial tumour disease on the reproductive physiology of the male Tasmanian devil (Sarcophilus harrisii)

Reproduction Fertility and Development ◽

10.1071/rd11134 ◽

2012 ◽

Vol 24 (7) ◽

pp. 999 ◽

Cited By ~ 7

Author(s):

T. Keeley ◽

P. D. McGreevy ◽

J. K. O'Brien

Keyword(s):

Early Stage ◽

Reproductive Function ◽

Serum Testosterone ◽

Serum Cortisol ◽

Disease Stage ◽

Rapid Decline ◽

Tasmanian Devil ◽

Early Stage Disease ◽

Devil Facial Tumour Disease ◽

Disease Free

Devil facial tumour disease (DFTD) is the cause of the rapid decline of wild Tasmanian devils. Female devils are seasonal breeders with births peaking during autumn (i.e. March) but the degree of reproductive seasonality in male devils is unknown. The objective of this study was to examine the potential effects of season and DFTD on reproductive function in male devils (n = 55). Testicular (1.90 ± 0.23 g) and epididymal (0.90 ± 0.06 g) weights were maximal during autumn and spring (P < 0.05), whereas prostate (3.71 ± 0.74 g) and Cowper’s gland (0.68 ± 0.22; 0.52 ± 0.21 g) weights peaked during autumn (P < 0.001). The motility of spermatozoa from the cauda epididymides extracted post-mortem was similar (P > 0.05) across season and disease state (31.5 ± 13.1% total motility). Testicular and epididymal weights were no different between animals displaying late or early-stage DTFD signs or disease-free animals (P > 0.1). The accessory sex glands were larger in late-stage DFTD animals than in animals with early-stage disease signs or which were disease-free (P < 0.01) but effects of season on this result can’t be excluded. Serum testosterone concentrations peaked during summer (0.25 ± 0.18 ng mL–1) but values were not different from the preceding and subsequent seasons (P > 0.05), nor influenced by disease stage (P > 0.1). Seasonal and DFTD-related changes in serum cortisol concentrations were not evident (P > 0.1). Male devil reproduction does not appear to be restricted by season nor inhibited by DFTD.

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Evidence for a genetic basis of urogenital carcinoma in the wild California sea lion

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2014.0240 ◽

2014 ◽

Vol 281 (1796) ◽

pp. 20140240 ◽

Cited By ~ 16

Author(s):

Helen M. Browning ◽

Karina Acevedo-Whitehouse ◽

Frances M. D. Gulland ◽

Ailsa J. Hall ◽

Jeanie Finlayson ◽

...

Keyword(s):

California Sea Lions ◽

California Sea Lion ◽

Gene Encoding ◽

Sea Lions ◽

Wildlife Species ◽

Large Gene ◽

In The Wild ◽

Urogenital Carcinoma ◽

Control Study ◽

Individual Locus

Although neoplasia is a major cause of mortality in humans and domestic animals, it has rarely been described in wildlife species. One of the few examples is a highly prevalent urogenital carcinoma in California sea lions (CSLs). Although the aetiology of this carcinoma is clearly multifactorial, inbreeding depression, as estimated using levels of microsatellite multilocus heterozygosity, is identified as predictive for this neoplasia. On further analysis, this relationship appears to be largely driven by one marker, suggesting that a single locus might be associated with the occurrence of this disease in CSLs. In a case–control study, carcinoma was significantly associated with homozygosity at the Pv11 microsatellite locus. Pv11 was mapped to intron 9 of the heparanase 2 gene ( HPSE2 ) locus, a very large gene encoding heparanase 2, which in humans is associated with multiple carcinomas. Correspondingly, immunohistochemical labelling in tissues was present in carcinoma cases within a single homozygous Pv11 genotype. To our knowledge, this is the first report of an individual locus being associated with cancer in any wildlife species. This adds emphasis to the study of HPSE2 in other species, including humans and will guide future studies on this sentinel species that shares much of its diet and environment with humans

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An Agent-Based Model of the Spread of Devil Facial Tumor Disease in an Isolated Population of Tasmanian Devils

International Journal of Agent Technologies and Systems ◽

10.4018/jats.2012100101 ◽

2012 ◽

Vol 4 (4) ◽

pp. 1-16

Author(s):

Charles E. Knadler

Keyword(s):

Life History ◽

Cancer Cells ◽

Tasmanian Devil ◽

Isolated Population ◽

Agent Based Model ◽

Disease Mechanism ◽

Agent Based ◽

In The Wild ◽

Devil Facial Tumor Disease

The Tasmanian devil population is being reduced in the wild at an alarming rate due to an epidemic, which is the result of an unusual disease mechanism. Infected animals “inject” cancer cells into other devils, which then clone the cells, developing tumors. These tumors are invariably fatal. Field observers have developed hypotheses that include a life- history change for the species. It is hypothesized that this change has the potential to improve the population’s survivability. An agent-based model of Tasmanian devils is used to evaluate these hypotheses. The model results suggest that the devils’ intra-gender aggression as well as their aggressive mating practices render the life-history change hypotheses’ correctness improbable.

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