Role of (R)-9-hydroxystearic acid in zebrafish development

9-hydroxystearic acid (9-HSA) belongs to a class of lipid peroxidation products identified in several human and murine cell lines. These products are greatly diminished in tumors compared to normal tissues and their amount is inversely correlated with the malignancy of the tumor. 9-HSA activity has been tested in cancer cell lines, where it showed to act as a histone deacetylase 1 (HDAC1) inhibitor. In particular, in a colon cancer cell line (HT29), its administration resulted in an inhibition of proliferation together with an induction of differentiation. In this thesis the effect of (R)-9-hydroxystearic acid has been tested in vivo on cell proliferation and differentiation processes, in the early stages of zebrafish development. The final aim of this work was to elucidate the role of (R)-9-HSA in the control of cell differentiation and proliferation during normal development, in order to better understand its molecular control of cancerogenesis. The molecule has been administered via injection in the yolk of zebrafish embryos. The analysis of the histone acetylation pattern showed a hyperacetilation of histone H4 after treatment with the molecule, as detectable in HDAC1 mutants. (R)-9-HSA was also demonstrated to interfere with the signaling pathways that regulate proliferation and differentiation in zebrafish retina and hindbrain. This resulted in a reduction of proliferation in the hindbrain at 24 hours post injection (hpi), and in a hyperproliferation at 48 and 72 hpi in the retina, with a concomitant inhibition of differentiation. Finally, (R)-9-HSA effects were evident on proliferation of stem cell located in the ciliary marginal zone (CMZ) of the retina. The presence of ROS and 4-hydroxynoneal in the CMZ of wild-type embryos supports the hypothesis that oxidative stress could regulate stem cells fate in zebrafish retina.

The role of the BMP signaling antagonist noggin in the development of prostate cancer osteolytic bone metastasis

Members of the BMP and Wnt protein families play a relevant role in physiologic and pathologic bone turnover. Extracellular antagonists are crucial for the modulation of their activity. Lack of expression of the BMP antagonist noggin by osteoinductive, carcinoma-derived cell lines is a determinant of the osteoblast response induced by their bone metastases. In contrast, osteolytic, carcinoma-derived cell lines express noggin constitutively. We hypothesized that cancer cell-derived noggin may contribute to the pathogenesis of osteolytic bone metastasis of solid cancers by repressing bone formation. Intra-osseous xenografts of PC-3 prostate cancer cells induced osteolytic lesions characterized not only by enhanced osteoclast-mediated bone resorption, but also by decreased osteoblast-mediated bone formation. Therefore, in this model, uncoupling of the bone remodeling process contributes to osteolysis. Bone formation was preserved in the osteolytic lesions induced by noggin-silenced PC-3 cells, suggesting that cancer cell-derived noggin interferes with physiologic bone coupling. Furthermore, intra-osseous tumor growth of noggin-silenced PC-3 cells was limited, most probably as a result of the persisting osteoblast activity. This investigation provides new evidence for a model of osteolytic bone metastasis where constitutive secretion of noggin by cancer cells mediates inhibition of bone formation, thereby preventing repair of osteolytic lesions generated by an excess of osteoclast-mediated bone resorption. Therefore, noggin suppression may be a novel strategy for the treatment of osteolytic bone metastases.

Role of the environment in the development of canine atopic dermatitis in Labrador and golden retrievers

Canine and human atopic dermatitis are multifaceted diseases whose clinical development may be influenced by several factors, such as genetic background, environment, secondary infections, food and psychological effects. The role of the environment has been extensively examined in humans but remains unclear in dogs. The aim of this study was to examine environmental factors in two genetically close breeds, Labrador and golden retrievers. Using standard criteria, atopic dogs in Switzerland and Germany were selected and compared with healthy individuals. Information on environmental factors was collected using a 46-question survey encompassing date and place of birth, way of life at the breeder's and owner's home, food and treatments. Univariate and multivariate logistic regression were used to assess the association between potential risk factors and disease status. The following parameters were associated with an increased risk of disease development: living in a shed during puppyhood, adoption at the age of 8-12 weeks and washing the dog regularly. In contrast, the following factors were associated with a lower risk: living in a rural environment, living in a household with other animals and walking in a forest. These associations do not prove causality but support the primary hypothesis that certain environmental factors may influence the development of canine atopic dermatitis. Further studies are warranted to confirm these results and conclusions.

Identification of the bovine Arachnomelia mutation by massively parallel sequencing implicates sulfite oxidase (SUOX) in bone development

Arachnomelia is a monogenic recessive defect of skeletal development in cattle. The causative mutation was previously mapped to a approximately 7 Mb interval on chromosome 5. Here we show that array-based sequence capture and massively parallel sequencing technology, combined with the typical family structure in livestock populations, facilitates the identification of the causative mutation. We re-sequenced the entire critical interval in a healthy partially inbred cow carrying one copy of the critical chromosome segment in its ancestral state and one copy of the same segment with the arachnomelia mutation, and we detected a single heterozygous position. The genetic makeup of several partially inbred cattle provides extremely strong support for the causality of this mutation. The mutation represents a single base insertion leading to a premature stop codon in the coding sequence of the SUOX gene and is perfectly associated with the arachnomelia phenotype. Our findings suggest an important role for sulfite oxidase in bone development.

[Complement--a phylogenetically old system as a new player in the development of atherosclerosis]

Atherosclerotic diseases such as coronary artery disease and ischaemic stroke are caused by chronic inflammation in arterial vessel walls. The complement system is part of the innate immune system. It is involved in many processes contributing to onset and development of atherosclerotic plaques up to the final stage of acute thrombotic events. This is due to its prominent role in inflammatory processes. In addition, there is increasing evidence that interactions between complement and coagulation provide a link between inflammation and thrombosis. On the other hand, the complement system also has an atheroprotective function through the clearance of apoptotic material. The knowledge of these complex mechanisms will become increasingly important, also for clinicians, since it may lead to novel therapeutic and diagnostic options. Therapies targeting the complement system have the potential to reduce tissue damage caused by acute ischaemic events. Whether early anti-inflammatory and anti-complement therapy may be able to prevent atherosclerosis, remains a hot topic for research.

Rwandan youth in the development of music industry

In this days for ever, the Rwandan youth are more active in the development of music industry, the recording studio are created every day, and the number of musician is increasing from one day to another day, it is too early to get the statistic; some of the youth are dropped out their studies to develop their career of music; the question was how many of them are developing their career to become the Professional? WHY IN THESE DAYS, RWANDAN YOUTH ARE WORKING HARDLY IN THE DEVELOPMENT OF MUSIC INDUSTRY?” it was not easy for me to get the accurate answers; some questions remains in my mind like -Are they working for money-music as a job (professional)? -Are they willing to become célèbre-stars? -Is it for the entertainment/Relaxing? -Is it because they love music? -Are they escaping the problems-Music as an escape domain? -Are they exploring their free time? -Are they using the music as the way of expressing their views? Those questions require analysing each question deeply, and getting the answers from the singers and listeners of music or DJ, in order to confirm the causes of being more active in music industry for the Rwandan youth. I am not interesting to make a deep research but to analyze and I hope this article will help the students and many researchers to develop and find out the exact causes. As my aim is to open the door for the researchers, briefly let us analyze all those above questions one to one based on the main causes as the motivation of forcing the Rwandan youth to be in the industry music.

Perceptions of Social Mobility in Community College Scholars at Bucknell University

While national leaders have joined the discussion more recently, scholars in the fields of education, psychology, and sociology, have been exploring the ways in which students? socioeconomic background affects the outcomes they experience as a result of their education (Lareau, Unequal Childhoods: Class, Race, and Family Life, 2003).Furthermore, the role played by the education system in creating or diminishing socioeconomic disparity has also been studied in depth (Bourdieu, 1977; Boudon, 1977). However, the journeys of students from low-income families that begin their education at community colleges and continue it, through careful planning or chance, at elite four-year institutions, has not been the subject of much attention. This thesis explores these students? perceptions of social mobility as they have been shaped by their experiences so far in life. This includes the exploration of changes in their perceptions as the contexts for their lives have been changed. Quantitative analysis of survey results and qualitative analysis of participant interviews serve as the data set for this study. The implications ofthe findings for student affairs practitioners are also explored.