Rohevintide hematoloogilised tervisenäitajad: individuaalse varieeruvuse põhjused ja vastused immuunsüsteemi manipuleerimisele

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Immuunökoloogia eesmärgiks on välja selgitada mehhanismid, mis seovad immuunsüsteemi teiste elutähtsate funktsioonidega ja seletada selle kaudu looduses esinevat varieeruvust vastuvõtlikkuses haigustele. Kuigi valdavalt nõustutakse, et immuunvastus on organismile kulukas, pole veel kaugeltki selge, milles immuunvastuse hind väljendub ja millised mehhanismid immuunvastuse hinna teiste tunnustega seovad. Minu doktoritöö eesmärkideks oli (1) kontrollida mõne laialt kasutusel oleva meetodi sobivust ning rakendamisvõimalusi immuunökoloogilistes uuringutes ning (2) leida vastuseid teadusharus viimasel ajal kerkinud võtmeküsimustele. Töö esimeses pooles uurisin lindude immuunökoloogias immuunsüsteemi töö hindamiseks laialt kasutusel oleva meetodi (PHA süstimine) pikajalisi mõjusid, erinevate oksüdatiivse staatuse parameetrite ajalist varieeruvust ning omavahelisi korrelatsioone ning vangistuses elavate rohevintide sobivust immuunökoloogiliste uuringute jaoks. Töö teises osas uurisin karotenoidide rolli immuunvastuse reguleerimises, immuunvastuse oksüdatiivset hinda ning karotenoidsetes ja melaniinsetes sulestikuornamentides sisalduvat informatsiooni. Oma töös kasutasin mudelorganismina loodusest püütud rohevinte. Leidsin, et karotenoididel võib tõepoolest olla roll immuunvastuse ja selle hinna kujunemisel, kuid selle rolli uurimise muudavad keerukaks mitmed organismisisesed tegurid. Samuti näitasin, et oksüdatiivsed kahjustused moodustavad tõepoolest osa immuunvastuse hinnast. Linnu võimet tulla toime oksüdatiivse stressiga peegeldavad tema mustad sulestikulaigud, kuid mitte karotenoidsed ornamendid. Oma töö tulemusena veendusin, et rohevinte võib pidada heaks immuunökoloogia mudelorganismiks ning nende abil võib leida vastuseid mitmetele immuunökoloogia võtmeküsimustele. Rohevindid taluvad hästi vangistust ning nende sulestikuornamendid võimaldavad uurida signaaltunnuste ausust tagavaid mehhanisme. Rohevintidel esinev krooniline koktsiidinakkus on kergesti jälgitav ja manipuleeritav, mis võimaldab uurida immuunvastuse hinna probleeme ning immuunsüsteemi seoseid teiste elutähtsate funktsioonidega. On selge, et koos immuunökoloogia võtmeküsimustele vastuste otsimisega peab paralleelselt toimuma ka meedodite väljatöötamine, testimine ja uurimine. Vaid nii on võimalik ühendada üksteisest pealtnäha kaugel asuvad distsipliinid – immunoloogia ja ökoloogia – ning nende teadusharude integreerimise abil leida vastuseid küsimustele, mida kumbki haru eraldi lahendada ei suudaks.The primary goal of immunoecology is to find out the factors, both extrinsic and intrinsic, leading to changes in immune system function, and understand how these changes affect disease susceptibility. Although it has now been accepted that immune responses are costly, the question about the currencies used for paying this cost has remained poorly understood. The main aims of my thesis were (1) to assess the suitability and utility of several widely used methods in ecological research of immunity and oxidative balance systems, and (2) to study some of the most intriguing questions in avian immunoecology. In the first part, I tested the long-term impact of a classic immunoecological technique (PHA skin test), correlations between several indexes of oxidative status and their repeatability in time, and the suitability of wild-caught captive greenfinches for ecophysiological research. In the second part, I studied the association between carotenoids and immune function, oxidative costs of mounting an immune response, and the information content of plumage coloration. Captive greenfinches were used as model organisms. I found that carotenoids may play a role in immune response and in the cost of immune activation, but studying this role is complicated because of several confounding intrinsic factors. I also showed that oxidative damage is a part of the costs of an immune response. According to my results, the bird’s ability to control oxidative stress is signaled with its black plumage ornaments, but not in carotenoid-based ornaments. In conclusion, studying captive greenfinches seems to be a promising approach for answering many intriguing questions in immunoecology. Their good captivity tolerance allows studying a wild species in controlled laboratory conditions. Their plumage ornaments allow studying honesty of signal traits. Their common infection with coccidians is easy to follow and manipulate, making them good models for studying the costs of immune activation and the associations between immune system and other traits. At the same time, although some model systems and methods might seem to be widely accepted and technically completed, work with old and new methods must always continue in order to find possible flaws, better interpretation possibilities and new solutions. Continuous methodological work will eventually help to bind together immunology and ecology, and this synthesis will enable scientists to find solutions to many questions that both disciplines separately would fail to answer

Differences in mutational processes and intratumour heterogeneity between organs: the local selective filter hypothesis.

International audienceExtensive diversity (genetic, cytogenetic, epigenetic and phenotypic) exists within and between tumors, but reasons behind these variations, as well as their consistent hierarchical pattern between organs, are poorly understood at the moment. We argue that these phenomena are, at least partially, explanable by the evolutionary ecology of organs’ theory, in the same way that environmental adversity shapes mutation rates and level of polymophism in organisms. Organs in organisms can be considered as specialized ecosystems that are, for ecological and evolutionary reasons, more or less efficient at supressing tumours. When a malignancy does arise in an organ applying strong selection pressure on tumours, its constituent cells are expected to display a large range of possible surviving strategies, from hyper mutator phenotypes relying on bet-hedging to persist (high mutation rates and high diversity), to few poorly variable variants that become invisible to natural defences. In contrast, when tumour suppression is weaker, selective pressure favouring extreme surviving strategies is relaxed, and tumours are moderately variable as a result. We provide a comprehensive overview of this hypothesis

Differences on the level of hepatic transcriptome between two flatfish species in response to liver cancer and environmental pollution levels

Environmental factors can cause cancer in both wild animals and humans. In ecological settings, genetic variation and natural selection can sometimes produce resilience to the negative impacts of environmental change. An increase in oncogenic substances in natural habitats has therefore, unintentionally, created opportunities for using polluted habitats to study cancer defence mechanisms. The Baltic and North Sea are among the most contaminated marine areas, with a long history of pollution. Two flatfish species (flounder, Platichthys flesus and dab, Limanda limanda) are used as ecotoxicological indicator species due to pollution-induced liver cancer. Cancer is more prevalent in dab, suggesting species-specific differences in vulnerability and/or defence mechanisms. We conducted gene expression analyses for 30 flatfishes. We characterize between- and within-species patterns in potential cancer-related mechanisms. By comparing cancerous and healthy fishes, and noncancerous fishes from clean and polluted sites, we suggest also genes and related physiological mechanisms that could contribute to a higher resistance to pollution-induced cancer in flounders. We discovered changes in transcriptome related to elevated pollutant metabolism, alongside greater tumour suppression mechanisms in the liver tissue of flounders compared to dabs. This suggests either hormetic upregulation of tumour suppression or a stronger natural selection pressure for higher cancer resistance for flounders in polluted environment. Based on gene expression patterns seen in cancerous and healthy fish, for liver cancer to develop in flounders, genetic defence mechanisms need to be suppressed, while in dabs, analogous process is weak or absent. We conclude that wild species could offer novel insights and ideas for understanding the nature and evolution of natural cancer defence mechanisms.We are grateful to the crew of RW Walther Herwig III for all-round help during the fieldwork. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 951963.We are grateful to the crew of RW Walther Herwig III for all-round help during the fieldwork. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 951963

Data sharing practices and data availability upon request differ across scientific disciplines

Data sharing is one of the cornerstones of modern science that enables large-scale analyses and reproducibility. We evaluated data availability in research articles across nine disciplines in Nature and Science magazines and recorded corresponding authors' concerns, requests and reasons for declining data sharing. Although data sharing has improved in the last decade and particularly in recent years, data availability and willingness to share data still differ greatly among disciplines. We observed that statements of data availability upon (reasonable) request are inefficient and should not be allowed by journals. To improve data sharing at the time of manuscript acceptance, researchers should be better motivated to release their data with real benefits such as recognition, or bonus points in grant and job applications. We recommend that data management costs should be covered by funding agencies; publicly available research data ought to be included in the evaluation of applications; and surveillance of data sharing should be enforced by both academic publishers and funders. These cross-discipline survey data are available from the plutoF repository.Peer reviewe

Coccidian Infection Causes Oxidative Damage in Greenfinches

The main tenet of immunoecology is that individual variation in immune responsiveness is caused by the costs of immune responses to the hosts. Oxidative damage resulting from the excessive production of reactive oxygen species during immune response is hypothesized to form one of such costs. We tested this hypothesis in experimental coccidian infection model in greenfinches Carduelis chloris. Administration of isosporan coccidians to experimental birds did not affect indices of antioxidant protection (TAC and OXY), plasma triglyceride and carotenoid levels or body mass, indicating that pathological consequences of infection were generally mild. Infected birds had on average 8% higher levels of plasma malondialdehyde (MDA, a toxic end-product of lipid peroxidation) than un-infected birds. The birds that had highest MDA levels subsequent to experimental infection experienced the highest decrease in infection intensity. This observation is consistent with the idea that oxidative stress is a causative agent in the control of coccidiosis and supports the concept of oxidative costs of immune responses and parasite resistance. The finding that oxidative damage accompanies even the mild infection with a common parasite highlights the relevance of oxidative stress biology for the immunoecological research

Urban evolutionary physiology

International audienc

Telomere shortening as a mechanism of long-term cost of infectious diseases in natural animal populations

International audiencePathogens are potent selective forces that can reduce the fitness of their hosts. While studies of the short-term energetic costs of infections are accumulating, the long-term costs have only just started to be investigated. Such delayed costs may, at least in part, be mediated by telomere erosion. This hypothesis is supported by experimental investigations conducted on laboratory animals which show that infection accelerates telomere erosion in immune cells. However, the generalizability of such findings to natural animal populations and to humans remains debatable. First, laboratory animals typically display long telomeres relative to their wild counterparts. Second, unlike humans and most wild animals, laboratory small-bodied mammals are capable of telomerase-based telomere maintenance throughout life. Third, the effect of infections on telomere shortening and ageing has only been studied using single pathogen infections, yet hosts are often simultaneously confronted with a range of pathogens in the wild. Thus, the cost of an infection in terms of telomere-shortening-related ageing in natural animal populations is likely to be strongly underestimated. Here, we discuss how investigations into the links between infection, immune response and tissue ageing are now required to improve our understanding of the long-term impact of disease

Data from: Carotenoid coloration is related to fat digestion efficiency in a wild bird

Some of the most spectacular visual signals found in the animal kingdom are based on dietarily derived carotenoid pigments (which cannot be produced de novo), with a general assumption that carotenoids are limited resources for wild organisms, causing trade-offs in allocation of carotenoids to different physiological functions and ornamentation. This resource trade-off view has been recently questioned, since the efficiency of carotenoid processing may relax the trade-off between allocation toward condition or ornamentation. This hypothesis has so far received little exploratory support, since studies of digestive efficiency of wild animals are limited due to methodological difficulties. Recently, a method for quantifying the percentage of fat in fecal samples to measure digestive efficiency has been developed in birds. Here, we use this method to test if the intensity of the carotenoid-based coloration predicts digestive efficiency in a wild bird, the house finch (Haemorhous mexicanus). The redness of carotenoid feather coloration (hue) positively predicted digestion efficiency, with redder birds being more efficient at absorbing fats from seeds. We show for the first time in a wild species that digestive efficiency predicts ornamental coloration. Though not conclusive due to the correlative nature of our study, these results strongly suggest that fat extraction might be a crucial but overlooked process behind many ornamental traits

Urban environment and cancer in wildlife: available evidence and future research avenues

International audienceWhile it is generally known that the risk of several cancers in humans is higher in urban areas compared with rural areas, cancer is often deemed a problem of human societies with modern lifestyles. At the same time, more and more wild animals are affected by urbanization processes and are faced with the need to adapt or acclimate to urban conditions. These include, among other things, increased exposure to an assortment of pollutants (e.g. chemicals, light and noise), novel types of food and new infections. According to the abundant literature available for humans, all of these factors are associated with an increased probability of developing cancerous neoplasias; however, the link between the urban environment and cancer in wildlife has not been discussed in the scientific literature. Here, we describe the available evidence linking environmental changes resulting from urbanization to cancer-related physiological changes in wild animals. We identify the knowledge gaps in this field and suggest future research avenues, with the ultimate aim of understanding how our modern lifestyle affects cancer prevalence in urbanizing wild populations. In addition, we consider the possibilities of using urban wild animal populations as models to study the association between environmental factors and cancer epidemics in humans, as well as to understand the evolution of cancer and defence mechanisms against it