Effects of ecological factors on dominance and immune defence in crayfish

Both the ability to gain a high dominance status and having an efficient immune defence are favourable qualities that typically increase fitness in social and host-parasite interactions. Individuals with a high dominance status are predicted to gain fitness-related benefits from prior access to limited, defensible resources, such as food and matings. Immune defence mechanisms, on the other hand, have evolved to minimize the fitness costs of parasitic infections. The relative significance of a high dominance status and strong immune defence for individual fitness is, however, affected by the quality of the environment. The aim of this thesis is to improve the understanding of environmentally determined variation in dominance status, immune defence and their consequences for individual fitness. I use the native noble crayfish (Astacus astacus), the invasive signal crayfish (Pacifastacus leniusculus) and the highly virulent, invasive Aphanomyces astaci, the causative agent of the crayfish plague, as my study models. I first experimentally test theoretical predictions on how major ecological factors, including food availability, predation risk and population density, influence behavioural decision-making in fight contests, especially with regard to the maintenance of dominance hierarchies between size-matched crayfish. Using natural noble crayfish subpopulations with different crayfish plague history, I then explore whether variation in immune defence and crayfish plague resistance is potentially explained by local adaptation to the disease, or alternatively by geographical divergence. By keeping noble crayfish experimentally under constant environmental conditions, I finally determine whether seasonal variation in immune defence is endogenously regulated. My results show that individuals that had achieved dominant status in non-resource fight contests have an advantage in monopolising a limited, defendable food resource in a future contest. Furthermore, I find evidence that as population density increases, the division of the resource between dominants and subdominants becomes more unequal. Generally, my results suggest that due to ecological factors the dominance status of individuals can be more dynamic than theory predicts, especially when the contestants have similar fighting ability. For example, in line with the asset-protection principle, individuals having achieved dominant status in a non-predation risk contest increase their submissive behaviours in the presence of a predation threat, giving subdominants the opportunity to win a larger percentage of bouts in the predation risk contest. My results also reveal evidence for geographical variation in resistance to the crayfish plague and immune defence that is, however, independent of historical disease outbreaks in the study subpopulations. Furthermore, for the first time in invertebrates, my results demonstrate reproduction-related endogenous seasonal variation in the immune defence of noble crayfish. Overall, my results suggest that ecological factors, such as population density, predation risk and disease history, have to be taken in to account to better understand the causes and consequences of dominance status and immune defence in any individual species.Korkea dominanssistatus sekä tehokas immuunipuolustus ovat ominaisuuksia, jotka tyypillisesti parantavat yksilön kelpoisuutta sosiaalisissa tilanteissa ja isäntä-loissuhteissa. Teoria ennustaa, että yksilöt joilla on korkea dominanssistatus pääsevät paremmin käsiksi kelpoisuutta lisääviin, rajallisiin ja puolustettaviin resursseihin, kuten ruokaan ja parittelukumppaneihin. Toisaalta, immuunipuolustuksen mekanismien ajatellaan kehittyneen pienentämään loisinfektioiden kustannuksia. Korkean dominanssistatuksen ja tehokkaan immuunipuolustuksen suhteellinen merkitys yksilön kelpoisuuteen riippuu ympäristön laadusta. Väitöskirjani tavoitteena on parantaa ymmärrystä siitä, miten ympäristö vaikuttaa dominanssistatuksessa ja immuunipuolustuksessa havaittavaan vaihteluun, ja näiden piirteiden vaikutuksiin yksilön kelpoisuudelle. Työssäni käytän Suomen luontoon kuuluvaa alkuperäislajia, jokirapua (Astacus astacus), sekä vieraslajia, täplärapua (Pacifastacus lenisculus), ja hyvin virulenttia rapuruttoa aiheuttavaa oomykeettiä (Aphanomyces astaci). Ensimmäiseksi testaan teorioita siitä, miten ekologiset tekijät (esim. ravinnon saatavuus, saalistusriski, populaatiotiheys) vaikuttavat yksilön päätöksentekoon taistelutilanteissa, etenkin suhteessa dominanssihierarkioiden säilyvyyteen silloin, kun vastustajat ovat samankokoisia. Toiseksi tutkin rapuruttohistorialtaan eroavilla jokiravun luonnonpopulaatioilla, voiko immuunipuolustuksessa ja rapuruton vastustamisessa olevaa variaatiota selittää paikallisella sopeutumisella tautia vastaan tai maantieteellisillä eroavaisuuksilla. Pitämällä jokirapuja kontrolloidussa ympäristössä selvitin onko kausiluonteinen vaihtelevuus immuunipuolustuksessa sisäisen kellon säätelemää. Tulokseni osoittavat, että yksilöt, jotka saavuttivat korkeamman dominanssistatuksen taisteluissa ilman resurssia, pystyivät monopolisoimaan rajoitetun, puolustettavan resurssin seuraavissa taisteluissa. Lisäksi osoitin, että populaatiotiheyden kasvaessa erot resurssien jaossa dominanttien ja subdominanttien yksilöiden kesken kasvavat. Yleisesti tulokseni osoittavat, että ekologisten tekijöiden vaikutuksesta yksilön dominanssistatus voi muuttua dynaamisemmin kuin perusteoria ennustaa etenkin, kun vastustajilla on samankaltaiset taistelukyvyt. Esimerkiksi asset-protection teorian mukaisesti yksilöt, joilla oli korkea dominanssistatus saalistajien puuttuessa, lisäsivät subdominanttia käyttäytymistä saalistajien läsnäollessa. Tällöin saalistusriskikokeissa alhaisemman dominanssistatuksen yksilöt saivat paremmat mahdollisuudet voittaa taisteluita. Tulokseni osoittavat myös, että rapuruton vastustamisessa ja immuunipuolustuksessa on maantieteellistä vaihtelua, jota ei voitu selittää tutkittujen osapopulaatioiden rapuruttohistorialla. Lisäksi osoitan ensimmäistä kertaa selkärangattomilla, että immuunipuolustuksen vaihtelu on kausiluonteista sisäisesti säädeltyä ja mahdollisesti kytköksissä lisääntymiseen. Yleisesti, tulokseni osoittavat, että ekologiset tekijät, kuten populaatiotiheys, saalistusriski ja tautihistoria, on otettava huomioon, jotta ymmärtäisimme dominanssistauksen ja immuunipuolustuksen yksilöllisiä syitä ja seurauksia paremmin

Behavioural variation in the field cricket (Gryllus integer), what is the role of heritable components?

Eines der bekanntesten Verhaltenssyndrome ist das Aggressions-/Aktivitätssyndrome. In meiner Diplomarbeit untersuchte ich Verhaltensvariationen und deren erbliche Komponenten bei adulten Feldgrillen (G. integer). Ich prüfte, ob intrasexuelle Aggression mit der generellen Aktivität in einem unbekannten, möglicherweise sogar gefährlichen Umfeld korreliert. Dazu wurden die Latenzzeiten der ersten Bewegung sowie des Verlassens eines sicheren Versteckes gemessen und anschließend wurde die Anzahl der gewonnenen Kämpfe während eines intrasexellen Aggressionstests notiert. Mittels Eltern-Nachkommen-Regression und Verwandtschaftsanalyse ermittelte ich die Heritabilität der getesteten Verhaltensweisen. Entgegen meiner Erwartungen konnte ich kein Verhaltenssyndrom nachweisen. Es existiert allerdings immer noch wenig Theorie, die das Auftreten dieser Syndrome ausreichend erklärt. Mögliche Gründe für die Abwesenheit des Syndroms können z.B. das Fehlen von Prädatoren, das Nahrungsüberangebot und die über mehrere Generationen bestehende Laborhaltung sein. Sowohl die Erkundungsbereitschaft als auch die Krampfkraft weisen geringe erbliche Komponenten auf. Diese Verhaltensweisen können sich somit im Laufe eines Evolutionsprozesses verändern, wodurch Anpassungen (Adaptation) der Lebewesen an ihre Umwelt ermöglicht werden. Des weiteren konnte ich meinen Daten entnehmen, dass mutige bzw. erkundungsfreudige Individuen ein geringeres Körpergewicht und dabei zudem eine längere Entwicklung bis zur Geschlechtsreife aufweisen. Weniger offensive Individuen waren im Vergleich zu Erkundungsfreudigen schwerer und entwickelten sich darüber hinaus schneller zu adulten Tieren. Außerdem konnten aggressive, intrasexuell dominante Männchen gegenüber weniger aggressiven, nicht mehr Kopulationsversuche erzielen, in der Tat wurden kleinere Männchen von den Weibchen bevorzugt, wobei es allerdings keinen Zusammenhang zwischen Größe und Kampfkraft gab.One of the most familiar behavioural linkages is the aggressiveness-activity behavioural syndrome. In this study I used sexually mature field crickets (Gryllus integer) from a laboratory stock as model animals to explore experimentally the relationship between individual variation in exploration activity and intrasexual aggression as well as to estimate if behavioural traits are heritable. I measured individual willingness to exit from a shelter into an unfamiliar, potentially dangerous environment and afterwards the individual’s fighting success and the resultant dominance rank of males in male-male competition. Further, I used full-sib-half-sib analysis and parent-offspring-regression to study the heritability of the examined behaviours. My study could not confirm the previous observations of a aggressiveness–activity behavioural syndrome in the G. integer. However, there is still relatively little theory and data to explain the causes of behavioural correlations. There is evidence that behavioural syndromes may not be universal, even within a species. It is possible that because of the lack of predation pressure, competition for food or other natural stimuli, the syndrome will break apart. My results suggest that latency to emerge and fighting success seem to have small heritable components, which make them susceptible to evolutionary changes and facilitate behavioural adaptation to varying environments. In addition, I found that shy individuals were both heavier and gain maturation faster than bold ones and that aggressive, intrasexually dominant males did not obtain a higher mounting rate, i.e. female preference, than less dominant males

Do You Plead Connected? - Understanding How Lawyers Deal With Constant Connectivity

Being available and responsive has become an imperative to accomplish the complex work of knowledge workers and to adequately satisfy today’s business needs. As a consequence, individuals are required to adopt strategies to cope with increasing connectivity levels. We conducted a Q methodological study among 34 lawyers from Switzerland and Austria to examine the adoption of different strategies for dealing with constant connectivity. Our findings reveal four ICT user types, whereof three types successfully deploy a coping strategy while one type fails. We observe that specific determinants such as the work environment, the hierarchical position, the perceived autonomy as well as personality traits have substantial influence on the adoption of a coping strategy

Die Bedeutung von Weiterbildung für das Arbeitsfeld Kindertageseinrichtung. Eine Studie der Weiterbildungsinitiative Frühpädagogische Fachkräfte (WiFF)

Weiterbildung zählt in der Frühen Bildung zu den wichtigsten Instrumenten der Professionalisierung. Dies gilt umso mehr, da frühpädagogische Fachkräfte im Vergleich zu anderen Berufsgruppen besonders weiterbildungsaffin sind. Doch welche Gründe hat das Weiterbildungsverhalten der Kita-Fachkräfte? Und wie reagiert das Weiterbildungssystem auf die enormen Veränderungsprozesse im Arbeitsfeld? Diesen und weiteren Fragen ist die WiFF systematisch nachgegangen. Die Studie dokumentiert die Ergebnisse dieser Forschungsarbeit: Sie bündelt und erweitert die bisherigen Erkenntnisse zur berufsbezogenen Weiterbildung frühpädagogischer Fachkräfte, macht die Positionen der unterschiedlichen Akteure aus Kindertageseinrichtung und Weiterbildung transparent und formuliert Entwicklungsbedarfe beider Systeme. (DIPF/Verlag

TGFβ-signaling in Squamous Cell Carcinoma Occurring in Recessive Dystrophic Epidermolysis Bullosa

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a hereditary skin disorder characterized by mechanical fragility of the skin, resulting in blistering and chronic wounds. The causative mutations lie in the COL7A1 gene. Patients suffering from RDEB have a high risk to develop aggressive, rapidly metastasizing squamous cell carcinomas (SCCs). Cutaneous RDEB SCCs develop preferentially in long-term skin wounds or cutaneous scars. Albeit being well differentiated, they show a more aggressive behavior than UV-induced SCCs. These findings suggest other contributing factors in SCC tumorigenesis in RDEB. Objective: To analyze factors contributing to RDEB tumorigenesis, we conducted a comprehensive gene expression study comparing a non-malignant RDEB (RDEB-CL) to a RDEB SCC cell line (SCCRDEB4) to achieve an overview on the changes of the gene expression levels in RDEB related skin cancer. Methods: We applied cDNA arrays comprising 9738 human expressed sequence tags (EST) with various functions. Selected results were verified by Real-time RT PCR. Results: Large-scale gene expression analysis revealed changes in the expression level of transforming growth factor β1 (TGFβ1) and several genes under the control of TGFβ for RDEB and SCCRDEB4 cell lines. Even untransformed RDEB keratinocytes show elevated levels of TGFβ1. Conclusion: Our findings demonstrate a prominent role of TGFβ-signaling in RDEB-related skin cancer. Once activated, TGFβ signaling either in response to wounding or in order to influence type VII collagen expression levels could facilitate cancer development and progression. Moreover, TGFβ signaling might also represent a potentially useful therapeutic target in this disease

Amlexanox Enhances Premature Termination Codon Read-Through in COL7A1 and Expression of Full Length Type VII Collagen: Potential Therapy for Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder caused by the lack of functional type VII collagen, leading to skin fragility and subsequent trauma-induced separation of the epidermis from the underlying dermis. A total of 46% of patients with RDEB harbor at least one premature termination codon (PTC) mutation in COL7A1, and previous studies have shown that aminoglycosides are able to overcome RDEB PTC mutations by inducing read-through and incorporation of an amino acid at the PTC site. However, aminoglycoside toxicity will likely prevent widespread clinical application. Here the FDA-approved drug amlexanox was tested for its ability to read-through PTC mutations in cells derived from patients with RDEB. Eight of 12 different PTC alleles responded to treatment and produced full length protein, in some cases more than 50% relative to normal controls. Read-through type VII collagen was readily detectable in cell culture media and also localized to the dermal-epidermal junction in organotypic skin culture. Amlexanox increased COL7A1 transcript and the phosphorylation of UPF-1, an RNA helicase associated with nonsense-mediated mRNA decay, suggesting that amlexanox inhibits nonsense-mediated mRNA decay in cells from patients with RDEB that respond to read-through treatment. This preclinical study demonstrates the potential of repurposing amlexanox for the treatment of patients with RDEB harboring PTC mutation in COL7A1

Targeting class I histone deacetylases by the novel small molecule inhibitor 4SC-202 blocks oncogenic hedgehog-GLI signaling and overcomes smoothened inhibitor resistance

Aberrant activation of Hedgehog (HH)/GLI signaling is causally involved in numerous human malignancies, including basal cell carcinoma (BCC) and medulloblastoma. HH pathway antagonists targeting smoothened (SMO), an essential effector of canonical HH/GLI signaling, show significant clinical success in BCC patients and have recently been approved for the treatment of advanced and metastatic BCC. However, rapid and frequent development of drug resistance to SMO inhibitors (SMOi) together with severe side effects caused by prolonged SMOi treatment call for alternative treatment strategies targeting HH/GLI signaling downstream of SMO. In this study, we report that 4SC-202, a novel clinically validated inhibitor of class I histone deacetylases (HDACs), efficiently blocks HH/GLI signaling. Notably, 4SC-202 treatment abrogates GLI activation and HH target gene expression in both SMOi-sensitive and -resistant cells. Mechanistically, we propose that the inhibition of HDACs 1/2/3 is crucial for targeting oncogenic HH/GLI signaling, and that class I HDAC inhibitors either in combination with SMOi or as second-line therapy may improve the treatment options for HH-associated malignancies with SMOi resistance

Cord Blood Derived CD4+CD25high T Cells Become Functional Regulatory T Cells upon Antigen Encounter

Background: Upon antigen exposure, cord blood derived T cells respond to ubiquitous environmental antigens by high proliferation. To date it remains unclear whether these “excessive” responses relate to different regulatory properties of the putative T regulatory cell (Treg) compartment or even expansion of the Treg compartment itself