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The skin has a system that can detect light in a fashion similar to the retina. Although its presence was initially reported almost 20 years ago, only in 2011 functional studies started to be reported. The biological clock of the skin has also been reported in the beginning of the century, but its function and relevance still remain unexplored. Thus, this Ph.D. project was designed to explore the functionality of both systems in melanocytes, and whether the disruption of these systems is associated with the development of melanoma cancer. Using in vitro, in vivo, and bioinformatics approaches, we have shown that: 1) the biological clock of malignant melanocytes is more responsive to visible light, UVA radiation, estradiol, and temperature compared to normal cells; 2) UVA radiation is detected by melanopsin (OPN4) and rhodopsin (OPN2), which triggers a cGMP related cascade that leads to immediate pigment darkening (IPD) in normal and malignant melanocytes; 3) in addition to detecting UVA radiation, OPN4 also senses thermal energy, which activates the biological clock of both normal and malignant melanocytes; 4) regarding the biological clock, we have provided several layers of evidence that proves that in melanoma a chronodisruption scenario is established compared to healthy skin and/or normal pigment cells; 5) in vivo tumor samples display a low amplitude circadian rhythm of clock gene expression and an ultradian oscillatory profile in melanin content; 6) a non-metastatic melanoma leads to a systemic chronodisruption, which we suggest that could favor the metastatic process; 7) in human melanoma, we demonstrated the role of BMAL1 as a prognostic marker and a putative marker of immune therapy success. Taken altogether, these results significantly contributed to the literature as it brought to light new and interesting targets and processes, which will be explored in future projects / A pele possui um sistema que pode detectar luz de forma análoga à retina. Embora a presença deste sistema tenha sido inicialmente descrita quase há 20 anos, apenas no ano de 2011 estudos funcionais começaram a ser relatados. Sabe-se que o relógio biológico da pele também foi identificado no início do século, mas sua função e relevância ainda continuam pouco exploradas. Diante deste cenário, este projeto de doutorado foi desenhado para investigar a funcionalidade de ambos os sistemas em melanócitos e se perturbação dos mesmos estaria associada com o desenvolvimento de melanoma. Através do uso de abordagens in vitro, in vivo e de bioinformática, nós demonstramos que: 1) o relógio biológico de melanócitos malignos é mais responsivo à luz visível, radiação UVA, estradiol e temperatura comparado ao de células normais; 2) a radiação UVA é detectada por melanopsina (OPN4) e rodopsina (OPN2), que ativam uma via de sinalização dependente de GMPc, levando ao processo de pigmentação imediata (IPD) em melanócitos normais e malignos; 3) além de detecção de radiação UVA, a OPN4 também detecta energia térmica que, por sua vez, ativa o relógio biológico de melanócitos normais e malignos; 4) relativo ao relógio biológico, provamos por diferentes abordagens que, no melanoma, um cenário de cronoruputura está estabelecido em comparação a pele saudável e/ou melanócitos; 5) tumores in vivo apresentam um ritmo circadiano de baixa amplitude na expressão dos genes de relógio e um ritmo ultradiano oscilatório no conteúdo de melanina; 6) um melanoma não metastático leva a um quadro sistêmico de cronoruptura, o qual sugerimos favorecer o processo de metástase; 7) em melanoma humano, demonstramos o papel do gene BMAL11 como marcador de prognóstico e um possível indicador de sucesso de imunoterapias. Portanto, este projeto contribuiu de forma significante para a literatura científica uma vez que trouxe à luz novos e interessantes alvos terapêuticos e processos, os quais serão explorados em projetos futuros

Despite extensive international acceptance of the critical role of mammalian post-dispersal seed predation in many plant communities, in New Zealand we have limited knowledge of these predators’ influence on plant recruitment in our forests. The principle objective of my thesis was to determine the importance of exotic mammals as post-dispersal seed predators in a New Zealand conifer-broadleaf forest remnant. To address this goal, I used a series of field-based experiments where the actions of different post-dispersal seed predators were separated by wire-mesh exclosures. My study was conducted at Mount Peel Forest Park Scenic Reserve, South Canterbury, New Zealand. Being a human modified conifer forest currently dominated by broadleaf species, it is typical of forest remnants in New Zealand. This presented an opportunity to study a wide range of both potential post-dispersal seed predators and broadleaf tree species. My findings indicate that exotic mammals are not only post-dispersal seed predators at Peel Forest, but are responsible for the majority of post-dispersal predation events observed. Ship rats (Rattus rattus) were the dominant post-dispersal seed predators, while brushtail possums (Trichosurus vulpecula), house mice (Mus musculus) and native invertebrates were also important post-dispersal seed predators for several tree species. Through use of time-lapse video and cafeteria experiments I found that exotic mammalian seed predators, when compared to native invertebrate seed predators, preyed upon larger-seeded plant species and were responsible for considerable seed losses of several tree species. However, exotic mammalian seed predators do share several foraging characteristics with native invertebrate seed predators, as predators foraged in similar habitats and responded in a similar way to changes in seed density. In investigating if post-dispersal seed predation by mammals had a flow-on effect to plant recruitment, I observed natural seedling densities at Peel Forest were significantly higher in the absence of mammalian seed predators, but I found no evidence that the presence of mammals significantly altered the overall species richness. At the community level, I did not find an interaction between habitat and exotic mammals, however I present evidence that for individual plant species a significant mammal : habitat interaction occurred. Consequently, even though my cafeteria experiment implied there was no significant difference in the overall amount of seed preyed upon within different habitats, the less favourable microsite conditions for germination under an intact continuous canopy allows mammals to exacerbate habitat-related patterns of seed mortality and have a noticeable effect on seedling establishment. In an effort to validate the use of manipulative experiments to predict the long-term effect of post-dispersal seed predation on plant dynamics, I attempted to link results of my cafeteria experiment with observed seedling abundance at Peel Forest. Seven tree species were used in this comparison and a strong correlation was observed. This result shows that the level of post-dispersal seed predation determined in the cafeteria experiment provided a good predictor of the effect of mammalian post-dispersal seed predation on seedling establishment. To fully gauge the impact of mammalian post-dispersal seed predators on seedling establishment, the relationship between these seed predators and the type of recruitment limitation experienced by a plant species was also investigated. By using a combination of seed addition, plot manipulations and seed predator exclusion I was able to investigate this relationship. I found evidence that seed limitation at Peel Forest is positively correlated with seed size, and that while mammalian post-dispersal seed predators can further reduce plant recruitment of plant species experiencing seed limitation, the influence of mammals in determining plant recruitment was limited for plant species experiencing microsite limitation. My study has proven that exotic mammals are now the dominant post-dispersal seed predators at Peel Forest, the amount of seed preyed upon varies among plant species, and post-dispersal seed predation by mammalian species can lead to differences in seedling richness and abundance. I proved that the influence of exotic mammals on seedling establishment is also linked to habitat structure and recruitment limitations. When combined these observations suggest that exotic mammalian post-dispersal seed predators may play an important role in determining landscape abundance and distribution of plants at Peel Forest.

<p>Home cage aggression in male laboratory mice continues to challenge preclinical researchers. It reduces animal welfare and can alter research parameters, potentially reducing the validity and reliability of study data. While simply reducing aggression would be beneficial, promoting socio-positive, affiliative behaviors would greatly improve mouse welfare as mice are a social species. Mice also use olfaction to communicate, so this sensory modality could be used as a tool to improve social interactions in the home cage. A scoping review of the literature on how mammalian odor signals impact same sex social behavior found that studies are dominated by rodent subjects, treatments from urine, and aggression measures (Chapter 1). As a whole, urine treatments had a variable effect on aggression. This review highlights that treatments from non-urinary sources are not often tested, and affiliative behavior is rarely measured.</p> <p>One murine odor source worth exploring is found in used nesting material. Mice build complex nests for insulation and it has been speculated that the nest holds odor signals that appease home cage aggression, particularly aggression triggered by cage cleaning. It has been suggested that the nest contains secretions from plantar sweat glands, but the chemical content of neither nesting material nor plantar sweat have been examined. The main goals of this dissertation are to identify the odors stored in used nesting material, determine the sources of those odors, and test them for a behavioral role.</p> <p>Samples of used nesting material were collected from cages of group housed male mice. Further, plantar sweat, saliva, and urine were collected from the dominant and subordinate mouse in each cage as plausible odor sources. All samples were analyzed for protein and volatile organic compound content. Home cage aggression and affiliative behavior were also recorded to compare to odor profiles. Protein profiles showed that used nesting material contains a variety of proteins that primarily originate from plantar sweat, saliva, and urine sources (Chapter 2). A large proportion of these proteins contain messages about individual identity and bind volatile compounds that further contribute to identity cues. This suggests that the nest aids in maintaining a familiar odor environment. Analysis of volatile content showed that small compounds in the nest are also traced back to plantar sweat, saliva, and urine sources (Chapter 3). Few of the compounds have a known behavior role. However, one compound detected in nest, sweat, and saliva samples had a negative correlation with home cage aggression and three compounds (two from sweat and one from urine) had a positive correlation with affiliative behaviors, making them potential candidates for controlled studies on social behavior.</p> <p>Before testing the four candidate compounds, a challenge from the correlation study needed to be addressed. Body fluid samples were collected from individual mice based on social status, as this factor impacts production of known murine pheromones. Further, aggression is typically directed from a dominant to a subordinate mouse for territorial reasons. An aggression appeasement signal is likely to be produced by a subordinate to mitigate the dominant mouse’s perceived threat. Data from the correlation study showed no odor profile differences based on social status, and the pheromones that are known to vary with social status did not differ between dominant and subordinate mice. Therefore, Chapter 4 assesses the convergent validity of several dominance measures. Over one week, home cage interactions were observed in group housed male mice. For every aggression occurrence, the aggressor and target mouse was recorded to calculate individual dominance rankings in each cage. Then, individual mice were evaluated for the following measures known to correlate with dominance: levels of urinary darcin (a murine pheromone); scores from three rounds of the tube test; and ratio of preputial gland weight to body length. Postmortem wounding was also compared. Results showed that urinary darcin and preputial gland ratio have strong convergent validity with dominance ranking based on home cage aggression.</p> <p>Finally, the four candidate compounds (identified in Chapter 3) were developed into treatment solutions to assess their effect on home cage social behavior (Chapter 5). Cages of group housed male mice were randomly assigned one of five treatments (four compounds + control) and home cage aggression and affiliative behavior were recorded for one week. Postmortem wounding was recorded as a secondary aggression measure and social stress was measured through fecal corticosterone metabolites from each cage’s dominant and subordinate mouse (rank based on preputial gland ratio). Treatment did not predict changes in most measures. This may be due to limitations in application or from the original correlation study, which are further discussed.</p> <p>Although the final study showed null results, future research is still warranted to fine tune application methods and gain a better understanding of how odor signals impact interactions other than aggression. The relationship between olfaction and affiliative behaviors is largely unexamined and this dissertation is a first step in filling that gap.</p>

La naissance est l'une des étapes les plus délicates à laquelle les nouveau-nés mammifères doivent faire face. Le nouveau-né doit opérer des changements physiologiques et comportementaux pour s'adapter à l'environnement aérien, et l'un des premiers défis est d'ingérer du colostrum et du lait. Il est surprenant que la nature des stimuli et les mécanismes impliqués dans le déclenchement de la tétée soient encore mal connus, alors que la survie du nouveau-né est conditionnée par le succès de la première tétée. Par conséquent, cette étude a pour but de comprendre comment un nouveau-né immature et inexpérimenté réussit à s'orienter vers une tétine, à la saisir et à la téter de façon efficace? Cette question générale est posée chez la souris en focalisant sur : i) la nature des substrats chimiques utilisés par les souriceaux pour atteindre les tétines maternelles ; ii) la variation de la puissance attractive de ces substrats au cours du développement ; et iii) l'implication des effets de l'expérience dans l'établissement des réponses adaptatives précoces. Premièrement, nos résultats mettent en lumière que les odeurs mammaires de femelles allaitantes induisent plus d'approches et de saisies de la tétine chez les souriceaux que celles émanant de femelles non allaitantes. Deuxièmement, les odeurs de liquide amniotique et de lait déclenchent la première saisie orale de la tétine chez des souriceaux à la naissance, alors que les odeurs de salives maternelle et infantile n'induisent ce comportement qu'après une brève expérience de tétée. Troisièmement, les souriceaux âgés de 0, 2 et 6 jours postnatals (P), ayant eu une expérience de tétée, affichent une attraction sélective envers des odeurs de laits collectés en début de lactation plutôt qu'en fin de lactation, alors que les souriceaux plus âgés P15 ne montrent aucune réponse sélective envers ces odeurs. En résumé, certains substrats biologiques présents sur les tétines de femelles allaitantes sont immédiatement attractifs après la naissance, tandis que d'autres ont besoin d'être appris pour être réactogènes. Par conséquent, la réponse initiale de recherche de la tétine chez le souriceau est contrôlée par des processus d'apprentissage postnatal. A ce stade, l'implication de l'apprentissage prénatal et de processus prédisposés n'a pu être prouvée, bien qu'elle ne soit pas exclue. Ces résultats montrent des capacités d'apprentissage sophistiquées chez le souriceau nouveau-né

L'incessant augment del nombre de seqüències genòmiques, juntament amb l'increment del nombre de tècniques experimentals de les que es disposa, permetrà obtenir el catàleg complet de les funcions cel.lulars de diferents organismes, incloent-hi la nostra espècie. Aquest catàleg definirà els fonaments sobre els que es podrà entendre millor com els organismes funcionen a nivell molecular. Al mateix temps es tindran més pistes sobre els canvis que estan associats amb les malalties. Per tant, la seqüència en brut, tal i com s'obté dels projectes de seqüenciació de genomes, no té cap valor sense les anàlisis i la subsegüent anotació de les característiques que defineixen aquestes funcions. Aquesta tesi presenta la nostra contribució en tres aspectes relacionats de l'anotació dels gens en genomes eucariotes. Primer, la comparació a nivell de seqüència entre els genomes humà i de ratolí es va dur a terme mitjançant un protocol semi-automàtic. El programa de predicció de gens SGP2 es va desenvolupar a partir d'elements d'aquest protocol. El concepte al darrera de l'SGP2 és que les regions de similaritat obtingudes amb el programa TBLASTX, es fan servir per augmentar la puntuació dels exons predits pel programa geneid, amb el que s obtenen conjunts d'anotacions més acurats d'estructures gèniques. SGP2 té una especificitat que és prou gran com per que es puguin validar experimentalment via RT-PCR. La validació de llocs d'splicing emprant la tècnica de la RT-PCR és un bon exemple de com la combinació d'aproximacions computacionals i experimentals produeix millors resultats que per separat. S'ha dut a terme l'anàlisi descriptiva a nivell de seqüència dels llocs d'splicing obtinguts sobre un conjunt fiable de gens ortòlegs per humà, ratolí, rata i pollastre. S'han explorat les diferències a nivell de nucleòtid entre llocs U2 i U12, pel conjunt d'introns ortòlegs que se'n deriva d'aquests gens. S'ha trobat que els senyals d'splicing ortòlegs entre humà i rossegadors, així com entre rossegadors, estan més conservats que els llocs no relacionats. Aquesta conservació addicional pot ser explicada però a nivell de conservació basal dels introns. D'altra banda, s'ha detectat més conservació de l'esperada entre llocs d'splicing ortòlegs entre mamífers i pollastre. Els resultats obtinguts també indiquen que les classes intròniques U2 i U12 han evolucionat independentment des de l'ancestre comú dels mamífers i les aus. Tampoc s'ha trobat cap cas convincent d'interconversió entre aquestes dues classes en el conjunt d'introns ortòlegs generat, ni cap cas de substitució entre els subtipus AT-AC i GT-AG d'introns U12. Al contrari, el pas de GT-AG a GC-AG, i viceversa, en introns U2 no sembla ser inusual. Finalment, s'han implementat una sèrie d'eines de visualització per integrar anotacions obtingudes pels programes de predicció de gens i per les anàlisis comparatives sobre genomes. Una d'aquestes eines, el gff2ps, s'ha emprat en la cartografia dels genomes humà, de la mosca del vinagre i del mosquit de la malària, entre d'altres. El programa gff2aplot i els filtres associats, han facilitat la tasca d'integrar anotacions de seqüència amb els resultats d'eines per la cerca d'homologia, com ara el BLAST. S'ha adaptat també el concepte de pictograma a l'anàlisi comparativa de llocs d splicing ortòlegs, amb el desenvolupament del programa compi. / El aumento incesante del número de secuencias genómicas, junto con el incremento del número de técnicas experimentales de las que se dispone, permitirá la obtención del catálogo completo de las funciones celulares de los diferentes organismos, incluida nuestra especie. Este catálogo definirá las bases sobre las que se pueda entender mejor el funcionamiento de los organismos a nivel molecular. Al mismo tiempo, se obtendrán más pistas sobre los cambios asociados a enfermedades. Por tanto, la secuencia en bruto, tal y como se obtiene en los proyectos de secuenciación masiva, no tiene ningún valor sin los análisis y la posterior anotación de las características que definen estas funciones. Esta tesis presenta nuestra contribución a tres aspectos relacionados de la anotación de los genes en genomas eucariotas. Primero, la comparación a nivel de secuencia entre el genoma humano y el de ratón se llevó a cabo mediante un protocolo semi-automático. El programa de predicción de genes SGP2 se desarrolló a partir de elementos de dicho protocolo. El concepto sobre el que se fundamenta el SGP2 es que las regiones de similaridad obtenidas con el programa TBLASTX, se utilizan para aumentar la puntuación de los exones predichos por el programa geneid, con lo que se obtienen conjuntos más precisos de anotaciones de estructuras génicas. SGP2 tiene una especificidad suficiente como para validar esas anotaciones experimentalmente vía RT-PCR. La validación de los sitios de splicing mediante el uso de la técnica de la RT-PCR es un buen ejemplo de cómo la combinación de aproximaciones computacionales y experimentales produce mejores resultados que por separado. Se ha llevado a cabo el análisis descriptivo a nivel de secuencia de los sitios de splicing obtenidos sobre un conjunto fiable de genes ortólogos para humano, ratón, rata y pollo. Se han explorado las diferencias a nivel de nucleótido entre sitios U2 y U12 para el conjunto de intrones ortólogos derivado de esos genes. Se ha visto que las señales de splicing ortólogas entre humanos y roedores, así como entre roedores, están más conservadas que las no ortólogas. Esta conservación puede ser explicada en parte a nivel de conservación basal de los intrones. Por otro lado, se ha detectado mayor conservación de la esperada entre sitios de splicing ortólogos entre mamíferos y pollo. Los resultados obtenidos indican también que las clases intrónicas U2 y U12 han evolucionado independientemente desde el ancestro común de mamíferos y aves. Tampoco se ha hallado ningún caso convincente de interconversión entre estas dos clases en el conjunto de intrones ortólogos generado, ni ningún caso de substitución entre los subtipos AT-AC y GT-AG en intrones U12. Por el contrario, el paso de GT-AG a GC-AG, y viceversa, en intrones U2 no parece ser inusual. Finalmente, se han implementado una serie de herramientas de visualización para integrar anotaciones obtenidas por los programas de predicción de genes y por los análisis comparativos sobre genomas. Una de estas herramientas, gff2ps, se ha utilizado para cartografiar los genomas humano, de la mosca del vinagre y del mosquito de la malaria. El programa gff2aplot y los filtros asociados, han facilitado la tarea de integrar anotaciones a nivel de secuencia con los resultados obtenidos por herramientas de búsqueda de homología, como BLAST. Se ha adaptado también el concepto de pictograma al análisis comparativo de los sitios de splicing ortólogos, con el desarrollo del programa compi. / The constantly increasing amount of available genome sequences, along with an increasing number of experimental techniques, will help to produce the complete catalog of cellular functions for different organisms, including humans. Such a catalog will define the base from which we will better understand how organisms work at the molecular level. At the same time it will shed light on which changes are associated with disease. Therefore, the raw sequence from genome sequencing projects is worthless without the complete analysis and further annotation of the genomic features that define those functions. This dissertation presents our contribution to three related aspects of gene annotation on eukaryotic genomes. First, a comparison at sequence level of human and mouse genomes was performed by developing a semi-automatic analysis pipeline. The SGP2 gene-finding tool was developed from procedures used in this pipeline. The concept behind SGP2 is that similarity regions obtained by TBLASTX are used to increase the score of exons predicted by geneid, in order to produce a more accurate set of gene structures. SGP2 provides a specificity that is high enough for its predictions to be experimentally verified by RT-PCR. The RT-PCR validation of predicted splice junctions also serves as example of how combined computational and experimental approaches will yield the best results. Then, we performed a descriptive analysis at sequence level of the splice site signals from a reliable set of orthologous genes for human, mouse, rat and chicken. We have explored the differences at nucleotide sequence level between U2 and U12 for the set of orthologous introns derived from those genes. We found that orthologous splice signals between human and rodents and within rodents are more conserved than unrelated splice sites. However, additional conservation can be explained mostly by background intron conservation. Additional conservation over background is detectable in orthologous mammalian and chicken splice sites. Our results also indicate that the U2 and U12 intron classes have evolved independently since the split of mammals and birds. We found neither convincing case of interconversion between these two classes in our sets of orthologous introns, nor any single case of switching between AT-AC and GT-AG subtypes within U12 introns. In contrast, switching between GT-AG and GC-AG U2 subtypes does not appear to be unusual. Finally, we implemented visualization tools to integrate annotation features for gene- finding and comparative analyses. One of those tools, gff2ps, was used to draw the whole genome maps for human, fruitfly and mosquito. gff2aplot and the accompanying parsers facilitate the task of integrating sequence annotations with the output of homologybased tools, like BLAST.We have also adapted the concept of pictograms to the comparative analysis of orthologous splice sites, by developing compi.

Insgesamt 1746 Kleinsäuger aus den Familien Muridae (Murinae, Arvicolinae) und Soricidae aus dem Naturschutzgebiet ”Großer Hakel” (Sachsen-Anhalt) und der Tagebaufolgelandschaft ”Phönix-Ost und Rusendorf” Meuselwitz (Thüringen) wurden auf einen Befall mit Capillaria hepatica und Metazestoden von Bandwürmern (Cyclophyllida) untersucht. Das Tiermaterial stammte aus genehmigten faunistischen Untersuchungen aus den Jahren 1993 bis 1997 in Zusammenarbeit mit der Universität Halle und dem Naturkundemuseum "Mauritianum" Altenburg. Alle Mäuse wurden seziert und der Brust- und Bauchraum einschließlich aller Organoberflächen, der Subkutis, des Gehirns und der Leber untersucht. Eine Altersbestimmung der Wirte erfolgte bei den untersuchten Rötelmäusen (Clethrionomys glareolus). Erstmals in Deutschland konnte im Hakel ein stabiles Endemiegebiet von Capillaria hepatica bei Wildmäusen nachgewiesen werden. Die aus dem ”Großen Hakel” stammenden Gelbhals- (Apodemus flavicollis) und Rötelmäuse wiesen Befallshäufigkeiten von 8,5 bzw. 15,1 % auf, die Eizahlen pro Leber lagen zwischen 67 und 3 600 000. Weibliche Mäuse zeigten eine höhere Befallshäufigkeit als männliche Mäuse. Bei den Rötelmäusen konnte ein Anstieg der Befallshäufigkeit von 5,8 % der bis zu 3 Monate alten bis auf 28,6 % der bis zu einem Jahr alten Tiere beobachtet werden. Patente Infektionen waren erst in der Altersgruppe 3-6 Monate nachzuweisen. In dem Untersuchungsgebiet Meuselwitz war Capillaria hepatica bei den untersuchten 1069 Muridae und Soricidae nicht nachweisbar. Eine aktuelle Übersicht der weltweit in 53 Ländern festgestellten 137 Wirtsarten aus 25 Säugetierfamilien von Capillaria hepatica wurde zusammengestellt. Die Familie Muridae stellt mit 83 Arten die bedeutendste Wirtsgruppe dar. Bisher wurde über 56 Capillaria-hepatica-Infektionen beim Menschen (davon 39 Kinder) aus 18 Ländern berichtet. Die Leitsymptome der Erkrankung beim Menschen sind intermittierendes Fieber, Hepatomegalie, Leukozytose mit hochgradiger, persistierender Eosinophilie, Anämie, Hypergammaglobulinämie und Hypoalbuminämie. Die Serumaktivitäten von AST, ALT und LDH sind erhöht. Die Diagnose der zum Teil tödlich verlaufenden Erkrankung ist intra vitam bisher nur durch Leberbiopsie oder Laparotomie möglich. Einzelne Versuche mit serologischen Tests scheinen erfolgversprechend. Die Einzelnachweise von Capillaria hepatica bei Mensch, Hase und Sumpfbiber in Deutschland (Bayern, Sachsen und Sachsen-Anhalt) sind als Hinweise auf bestehende Endemiegebiete zu werten. Aufgrund der weiteren Verbreitung und der diagnostischen Probleme kann von einer höheren Gefährdung des Menschen (insbesondere Kleinkinder) und der Haustiere durch den Zoonoseerreger Capillaria hepatica ausgegangen werden. Bei 10,5 % aller untersuchten Mäuse wurden Metazestoden gefunden. Die Rötelmaus wies insgesamt mit durchschnittlich 23,5 % (Meuselwitz 30,2 %, Hakel 15,1 %) die signifikant höchsten Befallshäufigkeiten mit Metazestoden auf. Insgesamt konnten bei Muridae und Soricidae in Sachsen-Anhalt und Thüringen Metazestoden von 8 Bandwurmgattungen bzw. -arten (Cladotaenia globifera, Mesocestoides spp., T. crassiceps, T. martis martis, T. martis americana, T. mustelae, T. polyacantha, T. taeniaeformis) nachgewiesen werden. Die breiteste Metazestodenfauna mit insgesamt 7 Arten wurde bei der Feldmaus (Microtus arvalis), nur jeweils eine Metazestodenart dagegen bei Brandmaus (Apodemus agrarius), Zwergmaus (Micromys minutus), Feldspitzmaus (Crocidura leucodon) und Waldspitzmaus (Sorex araneus) gefunden. Die Zwergspitzmaus (Sorex minutus) war nicht von Metazestoden befallen. Eine deutliche Wirtsspezifität (Feldmaus) konnte für T.-crassiceps- und T.-polyacantha-Metazestoden festgestellt werden. Im Gebiet Meuselwitz dominierten bei Muridae Metazestoden von T. mustelae (Befallshäufigkeit 9,3 %) sowie von T. martis martis (Befallshäufigkeit 6,4 %), im Hakel von T. martis martis (Befallshäufigkeit 2,5 %) sowie T. mustelae (Befallshäufigkeit 2,2 %). Während in Meuselwitz die höchsten Befallshäufigkeiten mit Metazestoden von T. mustelae (24,7 %) bei der Rötelmaus und von T. martis martis (13 %) bei der Gelbhalsmaus vorlagen, waren im Hakel die Rötelmäuse am häufigsten mit T.-mustelae- (8,2 %) und T.-martis-martis- Metazestoden (4,8 %) befallen. Mit zunehmendem Alter der Rötelmäuse stieg die Befallshäufigkeit mit Metazestoden bei dieser Tierart an. Rötelmäuse unter einem Alter von 2 Monaten waren noch nicht von Metazestoden befallen. Infektionen mit 2 Metazestodenarten traten erstmals bei 4 Monate alten Rötelmäusen auf, bei zwei Tieren im Alter von 9 bzw. 12 Monaten wurden Infektionen mit 3 Metazestodenarten (Cladotaenia globifera + T. martis americana + T. mustelae; Cladotaenia globifera + T. martis martis + T. mustelae) nachgewiesen. Bei insgesamt 10 Muriden konnten Mischinfektionen mit Capillaria hepatica und Metazestoden von Bandwürmern festgestellt werden. Bei Mäusen der Familie Soricidae sind ausschließlich Metazestoden von Cladotaenia globifera gefunden worden. Erstnachweise für Deutschland stellen Funde der Metazestoden von Cladotaenia globifera bei der Feldspitzmaus, T. martis americana bei der Rötelmaus, T. mustelae bei Erd- und Zwergmaus und T. polyacantha bei der Waldmaus dar. Das erste Mal in Europa konnten T.-martis-americana-Metazestoden bei der Feldmaus gefunden werden. Eine wichtige Einflußgröße auf die Metazestodenfauna war das Aufeinandertreffen von End- und Zwischenwirt in bestimmten Biotopen. / The occurrence of Capillaria hepatica and metacestodes of Cyclophillida was investigated in 1746 small mammals of the families Muridae (Murinae, Arvicolinae) and Soricidae from the nature reserve ”Grosser Hakel” (Saxony-Anhalt) and the former open-cast mining area "Phoenix-Ost and Rusendorf" Meuselwitz (Thuringia). The animals came from approved faunistic surveys in co-operation with the University of Halle and the natural history museum ”Mauritianum” Altenburg. All mice were sectioned and the thoracic as well as the abdominal cavity including all organ surfaces, subcutaneous tissue, brain and liver were examined. The age of all bank voles (Clethrionomys glareolus) was determined. In the nature reserve "Grosser Hakel"an stable endemic area of Capillaria hepatica in wild mice could be detected for the first time in Germany. The percentage of yellow-necked mice (Apodemus flavicollis) infected with Capillaria hepatica in that area was 8.5 %, the percentage of bank voles infected with Capillaria hepatica in that area reached 15.1 % respectively. The number of eggs per liver ranged from 67 to 3,600,000. The proportion of infected mice was higher in female than in male mice. In bank voles the frequency of infection increased with age (from 5.8 % in the age of 3 months to 28.6 % in the age of one year). Patent infections were first detected in the age group of 3 to 6 month. No Capillaria hepatica could be found in 1069 Muridae and Soricidae examined in the Meuselwitz area. A current survey of the world-wide occurrence of Capillaria hepatica in 137 hosts of 25 mammal families was prepared. The family of Muridae (with 83 species) is the most important host group. Up to now 56 Capillaria-hepatica-infections in humans (including 39 children) from 18 different countries were reported. Major symptoms in humans are intermittent fever, hepatomegaly, leucocytosis with severe, persistent eosinophilia, anaemia, hypergammaglobulinaemia and hypoalbuminaemia. The serum activities of AST, ALT and LDH are elevated. Intra-vitam diagnosis of this partly lethal disease is only possible by liver biopsy or laparatomy. First serological tests are promising. Sporadic detection of Capillaria hepatica in humans, hares and nutria in Germany (Bavaria, Saxony and Saxony-Anhalt) can be regarded as an indication of existing endemic areas. A higher risk of Capillaria-hepatica-infection in humans (especially in small children) and domestic animals can be assumed on the basis of the wide distribution and the diagnostic problems. Metacestodes were found in 10.5 % of all examined mice. The bank voles showed the significantly highest rate of infection with 23.5 % (Meuselwitz 30.2 % and Hakel 15.1 %). Altogether metacestodes of 8 tapeworm genuses (Cladotaenia globifera, Mesocestoides spp., T. crassiceps, T. martis martis, T. martis americana, T. mustelae, T. polyacantha, T. taeniaeformis) could be detected in Muridae and Soricidae in Saxony-Anhalt and Thuringia. The broadest metacestode-fauna (with 7 species) was found in the common vole (Microtus arvalis). Only one metacestode-species was detected in the stripped field mouse (Apodemus agrarius), the harvest mouse (Micromys minutus), the bicoloured whitetoothed shrew (Crocidura leucodon) and the eurasion common shrew (Sorex araneus). The pygmy shrew (Sorex minutus) was not infected by metacestodes. A distinct host specificity (in the common vole) could be established for T. crassiceps and T. polyacantha. Metacestodes of T. mustelae (infection rate 9.3 %) and T. martis martis (infection rate 6.4 %) dominated in Muridae of the Meuselwitz area. In the Hakel area T. martis martis (infection rate 2.5 %) and T. mustelae (infection rate 2.2 %) dominated as well. Whereas metacestodes of T. mustelae occurred in the bank vole with an infection rate of 24.7 % and T. martis martis in yellow-necked mice with an infection rate of 13.0 % in the Meuselwitz area, T. mustelae occurred in bank voles with an infection rate of 8.2 % and T. martis martis in yellow-necked mice with an infection rate of 4.8 % in the Hakel area. The infection rate of bank voles with metacestodes increased with age. No metacestodes were found in bank voles younger than 2 month of age. Infection with 2 different metacestode-species occurred in bank voles for the first time at the age of 4 month. 3 metacestode-species were found in 2 animals at the age of 9 to 12 months (Cladotaenia globifera + T. martis americana + T. mustelae; Cladotaenia globifera + T. martis martis + T. mustelae). In 10 Muridae occurred a mixed infection with Capillaria hepatica and metacestodes of tapeworms. In mice of the Soricidae-family only metacestodes from Cladotaenia globifera could be found. For the first time in Germany were detected metacestodes of Cladotaenia globifera in the bicoloured whitetoothed shrew, of T. martis americana in bank voles, of T. mustelae in the common field vole and the harvest mouse and of T. polyacantha in the wood mouse. For the first time in Europe T. martis americana-metacestodes could be detected in the common vole. Of high importance to the metacestode-fauna was the encounter of final host and intermediate host in certain biotopes.

Insgesamt 1746 Kleinsäuger aus den Familien Muridae (Murinae, Arvicolinae) und Soricidae aus dem Naturschutzgebiet ”Großer Hakel” (Sachsen-Anhalt) und der Tagebaufolgelandschaft ”Phönix-Ost und Rusendorf” Meuselwitz (Thüringen) wurden auf einen Befall mit Capillaria hepatica und Metazestoden von Bandwürmern (Cyclophyllida) untersucht. Das Tiermaterial stammte aus genehmigten faunistischen Untersuchungen aus den Jahren 1993 bis 1997 in Zusammenarbeit mit der Universität Halle und dem Naturkundemuseum "Mauritianum" Altenburg. Alle Mäuse wurden seziert und der Brust- und Bauchraum einschließlich aller Organoberflächen, der Subkutis, des Gehirns und der Leber untersucht. Eine Altersbestimmung der Wirte erfolgte bei den untersuchten Rötelmäusen (Clethrionomys glareolus). Erstmals in Deutschland konnte im Hakel ein stabiles Endemiegebiet von Capillaria hepatica bei Wildmäusen nachgewiesen werden. Die aus dem ”Großen Hakel” stammenden Gelbhals- (Apodemus flavicollis) und Rötelmäuse wiesen Befallshäufigkeiten von 8,5 bzw. 15,1 % auf, die Eizahlen pro Leber lagen zwischen 67 und 3 600 000. Weibliche Mäuse zeigten eine höhere Befallshäufigkeit als männliche Mäuse. Bei den Rötelmäusen konnte ein Anstieg der Befallshäufigkeit von 5,8 % der bis zu 3 Monate alten bis auf 28,6 % der bis zu einem Jahr alten Tiere beobachtet werden. Patente Infektionen waren erst in der Altersgruppe 3-6 Monate nachzuweisen. In dem Untersuchungsgebiet Meuselwitz war Capillaria hepatica bei den untersuchten 1069 Muridae und Soricidae nicht nachweisbar. Eine aktuelle Übersicht der weltweit in 53 Ländern festgestellten 137 Wirtsarten aus 25 Säugetierfamilien von Capillaria hepatica wurde zusammengestellt. Die Familie Muridae stellt mit 83 Arten die bedeutendste Wirtsgruppe dar. Bisher wurde über 56 Capillaria-hepatica-Infektionen beim Menschen (davon 39 Kinder) aus 18 Ländern berichtet. Die Leitsymptome der Erkrankung beim Menschen sind intermittierendes Fieber, Hepatomegalie, Leukozytose mit hochgradiger, persistierender Eosinophilie, Anämie, Hypergammaglobulinämie und Hypoalbuminämie. Die Serumaktivitäten von AST, ALT und LDH sind erhöht. Die Diagnose der zum Teil tödlich verlaufenden Erkrankung ist intra vitam bisher nur durch Leberbiopsie oder Laparotomie möglich. Einzelne Versuche mit serologischen Tests scheinen erfolgversprechend. Die Einzelnachweise von Capillaria hepatica bei Mensch, Hase und Sumpfbiber in Deutschland (Bayern, Sachsen und Sachsen-Anhalt) sind als Hinweise auf bestehende Endemiegebiete zu werten. Aufgrund der weiteren Verbreitung und der diagnostischen Probleme kann von einer höheren Gefährdung des Menschen (insbesondere Kleinkinder) und der Haustiere durch den Zoonoseerreger Capillaria hepatica ausgegangen werden. Bei 10,5 % aller untersuchten Mäuse wurden Metazestoden gefunden. Die Rötelmaus wies insgesamt mit durchschnittlich 23,5 % (Meuselwitz 30,2 %, Hakel 15,1 %) die signifikant höchsten Befallshäufigkeiten mit Metazestoden auf. Insgesamt konnten bei Muridae und Soricidae in Sachsen-Anhalt und Thüringen Metazestoden von 8 Bandwurmgattungen bzw. -arten (Cladotaenia globifera, Mesocestoides spp., T. crassiceps, T. martis martis, T. martis americana, T. mustelae, T. polyacantha, T. taeniaeformis) nachgewiesen werden. Die breiteste Metazestodenfauna mit insgesamt 7 Arten wurde bei der Feldmaus (Microtus arvalis), nur jeweils eine Metazestodenart dagegen bei Brandmaus (Apodemus agrarius), Zwergmaus (Micromys minutus), Feldspitzmaus (Crocidura leucodon) und Waldspitzmaus (Sorex araneus) gefunden. Die Zwergspitzmaus (Sorex minutus) war nicht von Metazestoden befallen. Eine deutliche Wirtsspezifität (Feldmaus) konnte für T.-crassiceps- und T.-polyacantha-Metazestoden festgestellt werden. Im Gebiet Meuselwitz dominierten bei Muridae Metazestoden von T. mustelae (Befallshäufigkeit 9,3 %) sowie von T. martis martis (Befallshäufigkeit 6,4 %), im Hakel von T. martis martis (Befallshäufigkeit 2,5 %) sowie T. mustelae (Befallshäufigkeit 2,2 %). Während in Meuselwitz die höchsten Befallshäufigkeiten mit Metazestoden von T. mustelae (24,7 %) bei der Rötelmaus und von T. martis martis (13 %) bei der Gelbhalsmaus vorlagen, waren im Hakel die Rötelmäuse am häufigsten mit T.-mustelae- (8,2 %) und T.-martis-martis- Metazestoden (4,8 %) befallen. Mit zunehmendem Alter der Rötelmäuse stieg die Befallshäufigkeit mit Metazestoden bei dieser Tierart an. Rötelmäuse unter einem Alter von 2 Monaten waren noch nicht von Metazestoden befallen. Infektionen mit 2 Metazestodenarten traten erstmals bei 4 Monate alten Rötelmäusen auf, bei zwei Tieren im Alter von 9 bzw. 12 Monaten wurden Infektionen mit 3 Metazestodenarten (Cladotaenia globifera + T. martis americana + T. mustelae; Cladotaenia globifera + T. martis martis + T. mustelae) nachgewiesen. Bei insgesamt 10 Muriden konnten Mischinfektionen mit Capillaria hepatica und Metazestoden von Bandwürmern festgestellt werden. Bei Mäusen der Familie Soricidae sind ausschließlich Metazestoden von Cladotaenia globifera gefunden worden. Erstnachweise für Deutschland stellen Funde der Metazestoden von Cladotaenia globifera bei der Feldspitzmaus, T. martis americana bei der Rötelmaus, T. mustelae bei Erd- und Zwergmaus und T. polyacantha bei der Waldmaus dar. Das erste Mal in Europa konnten T.-martis-americana-Metazestoden bei der Feldmaus gefunden werden. Eine wichtige Einflußgröße auf die Metazestodenfauna war das Aufeinandertreffen von End- und Zwischenwirt in bestimmten Biotopen. / The occurrence of Capillaria hepatica and metacestodes of Cyclophillida was investigated in 1746 small mammals of the families Muridae (Murinae, Arvicolinae) and Soricidae from the nature reserve ”Grosser Hakel” (Saxony-Anhalt) and the former open-cast mining area "Phoenix-Ost and Rusendorf" Meuselwitz (Thuringia). The animals came from approved faunistic surveys in co-operation with the University of Halle and the natural history museum ”Mauritianum” Altenburg. All mice were sectioned and the thoracic as well as the abdominal cavity including all organ surfaces, subcutaneous tissue, brain and liver were examined. The age of all bank voles (Clethrionomys glareolus) was determined. In the nature reserve "Grosser Hakel"an stable endemic area of Capillaria hepatica in wild mice could be detected for the first time in Germany. The percentage of yellow-necked mice (Apodemus flavicollis) infected with Capillaria hepatica in that area was 8.5 %, the percentage of bank voles infected with Capillaria hepatica in that area reached 15.1 % respectively. The number of eggs per liver ranged from 67 to 3,600,000. The proportion of infected mice was higher in female than in male mice. In bank voles the frequency of infection increased with age (from 5.8 % in the age of 3 months to 28.6 % in the age of one year). Patent infections were first detected in the age group of 3 to 6 month. No Capillaria hepatica could be found in 1069 Muridae and Soricidae examined in the Meuselwitz area. A current survey of the world-wide occurrence of Capillaria hepatica in 137 hosts of 25 mammal families was prepared. The family of Muridae (with 83 species) is the most important host group. Up to now 56 Capillaria-hepatica-infections in humans (including 39 children) from 18 different countries were reported. Major symptoms in humans are intermittent fever, hepatomegaly, leucocytosis with severe, persistent eosinophilia, anaemia, hypergammaglobulinaemia and hypoalbuminaemia. The serum activities of AST, ALT and LDH are elevated. Intra-vitam diagnosis of this partly lethal disease is only possible by liver biopsy or laparatomy. First serological tests are promising. Sporadic detection of Capillaria hepatica in humans, hares and nutria in Germany (Bavaria, Saxony and Saxony-Anhalt) can be regarded as an indication of existing endemic areas. A higher risk of Capillaria-hepatica-infection in humans (especially in small children) and domestic animals can be assumed on the basis of the wide distribution and the diagnostic problems. Metacestodes were found in 10.5 % of all examined mice. The bank voles showed the significantly highest rate of infection with 23.5 % (Meuselwitz 30.2 % and Hakel 15.1 %). Altogether metacestodes of 8 tapeworm genuses (Cladotaenia globifera, Mesocestoides spp., T. crassiceps, T. martis martis, T. martis americana, T. mustelae, T. polyacantha, T. taeniaeformis) could be detected in Muridae and Soricidae in Saxony-Anhalt and Thuringia. The broadest metacestode-fauna (with 7 species) was found in the common vole (Microtus arvalis). Only one metacestode-species was detected in the stripped field mouse (Apodemus agrarius), the harvest mouse (Micromys minutus), the bicoloured whitetoothed shrew (Crocidura leucodon) and the eurasion common shrew (Sorex araneus). The pygmy shrew (Sorex minutus) was not infected by metacestodes. A distinct host specificity (in the common vole) could be established for T. crassiceps and T. polyacantha. Metacestodes of T. mustelae (infection rate 9.3 %) and T. martis martis (infection rate 6.4 %) dominated in Muridae of the Meuselwitz area. In the Hakel area T. martis martis (infection rate 2.5 %) and T. mustelae (infection rate 2.2 %) dominated as well. Whereas metacestodes of T. mustelae occurred in the bank vole with an infection rate of 24.7 % and T. martis martis in yellow-necked mice with an infection rate of 13.0 % in the Meuselwitz area, T. mustelae occurred in bank voles with an infection rate of 8.2 % and T. martis martis in yellow-necked mice with an infection rate of 4.8 % in the Hakel area. The infection rate of bank voles with metacestodes increased with age. No metacestodes were found in bank voles younger than 2 month of age. Infection with 2 different metacestode-species occurred in bank voles for the first time at the age of 4 month. 3 metacestode-species were found in 2 animals at the age of 9 to 12 months (Cladotaenia globifera + T. martis americana + T. mustelae; Cladotaenia globifera + T. martis martis + T. mustelae). In 10 Muridae occurred a mixed infection with Capillaria hepatica and metacestodes of tapeworms. In mice of the Soricidae-family only metacestodes from Cladotaenia globifera could be found. For the first time in Germany were detected metacestodes of Cladotaenia globifera in the bicoloured whitetoothed shrew, of T. martis americana in bank voles, of T. mustelae in the common field vole and the harvest mouse and of T. polyacantha in the wood mouse. For the first time in Europe T. martis americana-metacestodes could be detected in the common vole. Of high importance to the metacestode-fauna was the encounter of final host and intermediate host in certain biotopes.