Biochemical markers of bone turnover allow inference of the events occurring at the bone tissue level and may detect changes in bone cell activity earlier than densitometric technologies. Serum concentrations of receptor activator for nuclear factor kappa-beta ligand (RANKL), osteoprotegerin (OPG), osteocalcin, and N-telopeptide (NTx) were measured in women aged 20 + 1.5 years (mean + SD) who underwent 32 weeks of unilateral isokinetic concentric or eccentric muscular strength training. Changes in serum biomarkers were compared with changes in arm and leg flexor and extensor muscle strength. Dual X-ray absorptiometry (DXA) measures of bone mineral density (BMD) and bone mineral content (BMC) of the total forearm, total tibia, and total body also were assessed. The mean serum OPG concentration increased from 4.6 + 1.9 pmol/L to 5.2 + 2.1 pmol/L (â 14.9 %, mean + SD; p = 0.05, n = 20) following long-term isokinetic exercise training that also increased elbow extensor and knee flexor muscular strength (p < 0.05) and total forearm BMD (p = 0.04). The ratio of OPG/RANKL also increased over the course of the study (p = 0.045). Serum concentrations of other measured bone biomarkers did not change during training. Serum concentrations of OPG, a suppressor of osteoclastogenesis, increased with high-load muscular strength training that led to local increases in muscle strength and BMD. These adaptations may represent an exercise-mediated suppression of osteoclast differentiation and activity. The central role of the RANKL-OPG cytokine system in the regulation of bone cell biology is well established. Further research is needed to confirm the efficacy of using serum OPG and RANKL as biomarkers of bone cell metabolism in healthy populations undergoing long-term exercise interventions. / Master of Science

The "Mystery'" sonatas for scordato violin and continuo by H. I. F. Biber (1644-1704) had been largely ignored until 1905, when they were included in the collection of Austrian masterpieces, Denkmäler der Tonkunst der 0sterreich. Even then, they were the cause of some confusion which was later corrected in an addenda to the volume which included this series of sonatas. In the baroque period, scordatura was used by a few of Biber's contemporaries, but the technique is not commonly used today. In order to fully understand and to appreciate the " mystery" sonatas, a knowledge of scordatura is necessary, and this technique is discussed in Chapter II. Because the 17th century violins differed slightly from those used today, and the resources of the instrument had not yet been fully developed, a discussion of these aspects has been included. A comparison of the works of Biber with those of his contemporaries shows him to be an innovator who contributed greatly to the growing technique of the violin.

Speciation, the formation of new species, is an essential evolutionary process that causes species diversity on the Earth. At the beginning of this process is the separation of two populations by a reproductive barrier that prevents gene flow between these populations. One of the mechanisms, which enable reproductive isolation, is hybrid sterility (HS). It is a mechanism of postzygotic isolation that is described in a number of eukaryotes. The first discovered gene of hybrid sterility in vertebrates is the mice gene Hst1, later identified as gene Prdm9. By genetic and molecular analysis the locus on the X chromosome was determined, whose interaction with Prdm9 causes sterility or reduced fitness in male hybrids. This locus contains two genetic factors: Hstx1, causing an abnormal morphology of spermatozoa, and Hstx2, causing an arrest in spermatogenesis in pachytene spermatocytes and sterility. In my thesis I focus on the effect of deletion of a candidate hybrid sterility gene Fmr1nb on the X chromosome. The analysis of males B6N.Fmr1nbmut with deletion variants of the Fmr1nb gene showed that Fmr1nb is one of the factors influencing spermatogenesis. An increase in morphologic abnormalities in spermatozoa occurred in males with Fmr1nb gene deletion. This phenotype is identical with Hstx1. The effect...

La tortue verte (Chelonia mydas) constitue l‘un des espèces emblématiques de la vie marine, pourtant de nombreuses menaces pèsent de nos jours encore sur sa survie (braconnage, captures accidentelles). Ainsi, malgré l‘essor de mesures de protection menées à travers pour sa sauvegarde, la tortue verte constitue une espèce ‗en danger d‘extinction‘ et figure dans l‘Annexe I de la Convention de Washington (CITES). Afin d‘élaborer des plans de gestion et de conservation qui soient efficaces, il est important d‘avoir une parfaite connaissance de la biologie de la tortue verte, mais aussi de la structure de ses populations et de leurs caractéristiques. C‘est dans ce cadre que s‘inscrit la présente étude. L‘objectif de cette étude était d‘acquérir des connaissances sur la structure des populations de tortues vertes dans le sud-ouest de l‘océan Indien grâce à l‘utilisation de l‘outil génétique. Au total, 1551 échantillons de tissu ont été collectés dans la zone d‘étude et dans notre site témoin la Polynésie française (37 échantillons). Toutes les catégories d‘individus ont été échantillonnées (excepté les mâles en phase de reproduction) et les 15 sites d‘échantillonnage comprennent à la fois des sites de ponte, d‘alimentation et de développement pour les immatures. Deux types de marqueurs ont été utilisés : la région contrôle de l‘ADN mitochondrial et 6 loci microsatellites, afin d‘appréhender au mieux l‘apport des lignées maternelles et paternelles. Nous avons pu mettre en évidence la présence dans le sud-ouest de l‘océan Indien de 29 haplotypes distincts, appartenant à trois clades fortement divergents dont l‘un constitué d‘haplotypes originaires de l‘océan Atlantique. Parmi ces haplotypes, 7 ont été détectés pour la première fois dans la zone d‘étude, et 15 autres n‘ont jamais été précédemment décrits chez cette espèce. Ils sont présents dans chacun des 3 clades d‘haplotypes. Ces nouveaux haplotypes semblent spécifiques à la région, et en font une zone originale. On observe par ailleurs une grande richesse allélique dans les effectifs analysés. Ces résultats montrent que le sud-ouest de l‘océan Indien est une zone riche et très diversifiée. Cette région joue un rôle important dans la diversité génétique globale de l‘espèce. Le sud-ouest de l‘océan Indien constitue l‘une des deux seules zones connues à l‘heure actuelle de contact entre les deux métapopulations de tortues vertes (Atlantique-Méditerranée et Indo-Pacifique). Ce contact a entraîné la formation d‘un cline génétique portant principalement sur les fréquences relatives des haplotypes CM8 (Atlantique) et C3 (Indo-Pacifique). Les résultats obtenus lors de l‘analyse microsatellite de la différenciation entre les individus originaires des deux métapopulations montrent que le sud-ouest de l‘océan Indien constitue une zone d‘échanges génétiques entre les deux métapopulations, participant au brasage génétique de l‘espèce. L‘étude de facteurs, intrinsèques et extrinsèques, pouvant influencer la structuration des populations apportent de nombreuses informations qui pourraient s‘avérer utiles lors de l‘élaboration de plans de gestion. La structure des femelles et des mâles en alimentation ne diffère pas, contrairement à celle des immatures qui semble s‘organiser en ‗pools régionaux‘ qui seraient le fruit de l‘interaction d‘un comportement de philopatrie et d‘une influence des courants océaniques. La forte différenciation mitochondriale des femelles en ponte et la très faible différenciation microsatellite observée à l‘échelle de la région, indiquent l‘existence de flux de gènes via les mâles. La composition génétique d‘un site ne varie pas de manière significative au cours de l‘année. Par contre, elle peut varier d‘une année à l‘autre, signifiant l‘alternance dans certains sites de ponte de plusieurs populations distinctes. L‘évolution de la composition génétique d‘un groupe, au cours de 10 ou 20 ans, diffère selon le site considéré. La distance ne semble pas influencer de manière significative la structuration des populations au niveau microsatellite. Les femelles en ponte sur la plage de Saziley (Mayotte) diffèrent génétiquement de celles pondant sur les deux autres plages de l‘île. La structure observée des populations est en accord avec l‘organisation des courants océanique dans la région.

Sertoli cells (SCs) are somatic cells of testicular tissue that are involved in spermatogenesis and maturation of germ cells. They are currently being extensively studied for their immunomodulatory abilities, and recent studies have shown that they share some properties with mesenchymal stromal cells (MSCs). Detailed characterization of SCs and clarification of their role in testicular tissue is crucial for potential use of SCs as a therapeutic tool in regenerative medicine. Cell culture of Xenopus tropicalis immature Sertoli cells (XtiSCs) and Mus musculus (mSCs) Sertoli cells were established in the Laboratories of Developmental Biology and Immunoregulations, Faculty of Science, Charles University. Previous research has characterized XtiSCs and demonstrated their multipotent potential by in vitro differentiation into a mesodermal line. Following this research, one of the goals of the diploma project was the induction of in vitro differentiation of XtiSC into other cell types, which would verify the differentiation potential of XtiSCs. The mSC expression profile confirmed the somatic origin of this culture as well as the transcription of Sertoli cell gene markers. Differentiation of mSCs along the mesodermal line into osteoblasts, chondrocytes and adipocytes has been successfully induced in vitro....

Bakgrund En stor del av de patienter som frekvent söker vård lider av psykosomatiska sjukdomar (MUPS) och somatiseringssyndrom (MUS). Båda dessa tillstånd grundar sig i psykiska påfrestningar men yttrar sig i form av fysiska symptom. Stress är en psykisk påfrestning som är mycket utbredd i vårt samhälle idag. När människan utsätts för stress startar en rad olika fysiska processer i kroppen, som en del av vår överlevnadsinstinkt. Trots det är det många som stressar sig sjuka. Då kroppen inte får chans till återhämtning ökar risken för ohälsa med risk för psykosomatiska sjukdomar och somatiseringssyndrom som följd. Syfte Studiens syfte var att belysa upplevelser hos patienter med psykosomatiska sjukdomar och somatiseringssyndrom i den somatiska vården. Metod En litteraturöversikt valdes som metod, där 16 artiklar inkluderades. Artiklarna var av kvantitativ eller kvalitativ metod och analyserades enligt metoden integrerad analys. Resultat Patienter med MUPS/MUS lider av ohälsa och remitteras runt till olika vårdenheter utan att få den hjälp de behöver. Detta innebär ytterligare påfrestning på hälsan hos dessa patienter. Starka känslor såsom utanförskap, oro, skam och rädsla för sin egna ohälsan genomsyrar dessa patienters upplevelser. Kunskapen för dessa sjukdomstillstånd är bristfällig och det saknas tydliga riktlinjer och behandlingsmetoder inom vården. Slutsats Stigmatisering kring psykisk ohälsa skapar skam och utanförskap, vilket patienter med MUPS/MUS i stor utsträckning upplever. Bristande kunskap har visat på ineffektiv behandling vilket dessutom medför enorma kostnad för samhället. Sambandet mellan kropp och själ får inte förbises. Sjukvårdspersonal bör därför utbildas i att se den psykologiska faktorn bakom de fysiologiska symptomen. / Background A large proportion of patients who frequently seek health care suffer from psychophysiologic disorders (MUPS) and somatoform disorders (MUS). Both of these conditions derive from mental illness yet they manifest as physical symptoms. Stress is a psychological phenomenon which is widely spread in our society today. When a person is exposed to stress, a variety of physical reactions commence within our body, due to our survival instinct. In spite of this, a lot of people become physically and mentally ill from stress. When our body is deprived of recovery, there is a higher probability for lack of health and therefore the risk of developing psychophysiologic disorder and somatoform syndromes increases. Aim The purpose of the study was to illuminate patients with psychophysiologic disorders and somatoform disorders and their experiences within the somatic healthcare. Method A literature review has been conducted with an including total of 16 articles. The chosen articles consisted of quantitative or qualitative methods, analyzed according to the integrated analysis method. Results Patients with MUPS/MUS suffer from lack of health and are often referred to various care units without getting the help they need. This leads to further distress with a decreased health experience. Strong emotions such as exclusion, anxiety, shame and fear of lacking health permeate these patients' experiences. The knowledge regarding these conditions are insufficient and no distinct guidelines nor clear treatments exist within the healthcare system. Conclusions The stigmatization regarding mental illness leads to feelings of shame and exclusion for these patients. The lack of knowledge leads to ineffective treatment, which also entails an increased economic burden for the society. The relationship between the body and the soul must not be overlooked. Healthcare professionals need to be educated in the ability to recognize the underlying psychological factors behind the physiological symptoms.

<p> The age at which a juvenile female reaches sexual maturity can be modulated by a variety of environmental and social factors. Experiments described in this thesis were designed to enhance the current understanding of the relationships among three variables that influence the onset of sexual maturation in female mice (Mus musculus), including: [1] exposure to dietary phytoestrogens during development, [2] variations in prenatal androgens, and [3] the presence or absence of genetically-unrelated males after weaning. For the first time, age at onset of male-induced female puberty was investigated using non-invasive behavioural and fertility measures. Through enzyme immunoassay procedures, daily output of urinary creatinine, 17P-estradiol, and progesterone was profiled in developing females that were either isolated or exposed to adult males. Uterine and ovarian tissue was also measured in such females, and male exposure was observed to increase reproductive tissue mass and was influenced by prior androgen exposure in interaction with diet and male presence. Male-exposed females fed a diet containing phytoestrogens immediately became sexually receptive when housed directly with males, and they conceived earlier than females in other conditions. Females with longer anogenital distance, which reflects higher in utero androgen exposure, displayed more escape attempts and aggressive posturing in the direct presence of males, especially when they had been housed near males and fed the phytoestrogen-containing diet. Urinary 17P-estradiol was substantially reduced in females raised on the phytoestrogenfree diet. Urinary output of progesterone was not strongly influenced by diet. Maleexposed females ' output of progesterone and 17P-estradiol was more dynamic in comparison to that of isolated females. The size of this effect depended on diet, prior androgen exposure, and whether urinary steroid measures were adjusted by urinary creatinine. Urinary creatinine was elevated by the low phytoestrogen diet and reduced by male exposure. These data suggest that dietary phytoestrogens and in utero androgen exposure interact with presence or absence of males in determining the age at onset of sexual maturity in developing females. </p> <p> A final experiment was designed to examine two components of adult male urine, preputial gland emissions and unconjugated estrogens, that have been posited to act on females to advance reproductive maturation. Intact and preputialectomized males were compared in their output of urinary creatinine, 17~-estradiol, and testosterone, and in their influence on reproductive tissue in juvenile females. Lack of preputial glands did not hinder the capacity of males to induce uterine and ovarian growth in females. Male urinary creatinine was reduced by exposure to juvenile females. Creatinine-adjusted 17~estradiol and testosterone were greater in female-exposed males, regardless of whether the preputial glands were present. Based on these findings and those reported elsewhere, it is probable that male excreted urinary steroids are important in regulating reproductive changes in developing females exposed to males. </p> / Thesis / Doctor of Philosophy (PhD)

No description available.

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.