The Molecular Genetics of Wilms Tumour And The Wilms Tumour Predisposition Syndromes

A molecular genetic analysis of Wilms tumour and the Wilms tumour predisposition syndromes. Genetic analysis of Wilms tumour (WT) and WT predisposition syndromes has revealed that a complex set of genetic events are associated with the development of this tumour. This thesis analyses specific genetic loci in a series of patients and tumours in order to gain a greater understanding of the molecular aetiology of this tumour. Sporadic Wilms tumours are the most common type and constitute the bulk of the analysis presented. The WT1 gene in 11p13 was analysed using SSCP and DNA sequencing in 36 tumours. Mutations were only found in 1 of 32 sporadic Wilms tumours, strongly suggesting that WT1 has only a limited role to play in the development of sporadic WT. Karyotypic analysis and Loss of Heterozygosity (LOH) studies have implicated loci on chromosome arms 7p and 16q in Wilms tumourigenesis. Paired constitutional and tumour DNA from sporadic WT were studied for LOH using polymorphic microsatellite repeats from both these chromosomes. 15% showed LOH for 16q and there was evidence for a worse outcome in this small group. LOH for 7p was found in 10% of cases and in one tumour a homozygous deletion was detected, this finding suggests the locaton of a tumour suppressor gene on 7p. Previous analysis of Beckwith-Wiedemann syndrome (BWS) patients has suggested another WT predisposition gene lies in 11p15. Two patients with constitutional translocations were analysed using fluoresence in situ hybridisation (FISH) and trisomy for the 11p15 region was identified. Analysis of the extent of the triplication was studied using 11p15-specific cosmids. The importance of these observations in the development of WT are discussed. Perlman syndrome (PS) is another WT predisposition syndrome and cytogenetic analysis in two patients with this syndrome suggested rearrangements of 11p15. Detailed FISH and molecular analysis has been used to characterise the nature of these rearrangments. The data presented in this thesis adds to the body of evidence demonstrating the complex nature of the molecular mechanisms underlying Wilms tumorigenesis

Expression alterations define unique molecular characteristics of spinal ependymomas

Ependymomas are glial tumors that originate in either intracranial or spinal regions. Although tumors from different regions are histologically similar, they are biologically distinct. We therefore sought to identify molecular characteristics of spinal ependymomas (SEPN) in order to better understand the disease biology of these tumors. Using gene expression profiles of 256 tumor samples, we identified increased expression of 1,866 genes in SEPN when compared to intracranial ependymomas. These genes are mainly related to anterior/posterior pattern specification, response to oxidative stress, glial cell differentiation, DNA repair, and PPAR signalling, and also significantly enriched with cellular senescence genes (P = 5.5 × 10-03). In addition, a high number of significantly down-regulated genes in SEPN are localized to chromosome 22 (81 genes from chr22: 43,325,255 – 135,720,974; FDR = 1.77 × 10-23 and 22 genes from chr22: 324,739 – 32,822,302; FDR = 2.07 × 10-09) including BRD1, EP300, HDAC10, HIRA, HIC2, MKL1, and NF2. Evaluation of NF2 co-expressed genes further confirms the enrichment of chromosome 22 regions. Finally, systematic integration of chromosome 22 genes with interactome and NF2 co-expression data identifies key candidate genes. Our results reveal unique molecular characteristics of SEPN such as altered expression of cellular senescence and chromosome 22 genes

150 YEARS OF HIGHER AGRICULTURAL EDUCATION IN TRANSYLVANIA, 1869 – 2019

The University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca, ranked today among the most prestigious universities in the country and in Europe, celebrates this year, 2019, 150 years of productive existence!The School of Agronomy of Cluj laid its foundations in 1869, when the Institute of Agronomic Studies was established, during the reign of Emperor Franz Joseph (1830-1916) as Transylvania belonged at the time to the Austrian-Hungarian Empire. The new higher school counted on a dowry consisting in 730 acres (420 hectares) of land taken from the Roman Catholic status and from the buildings around the old Benedictine Monastery on ″Dealul Craiului″ (nowadays the location belonging to the university)

Antiangiogenic Therapy and Mechanisms of Tumor Resistance in Malignant Glioma

Despite advances in surgery, radiation therapy, and chemotherapeutics, patients with malignant glioma have a dismal prognosis. The formations of aberrant tumour vasculature and glioma cell invasion are major obstacles for effective treatment. Angiogenesis is a key event in the progression of malignant gliomas, a process involving endothelial cell proliferation, migration, reorganization of extracellular matrix and tube formation. Such processes are regulated by the homeostatic balance between proangiogenic and antiangiogenic factors, most notably vascular endothelial growth factors (VEGFs) produced by glioma cells. Current strategies targeting VEGF-VEGF receptor signal transduction pathways, though effective in normalizing abnormal tumor vasculature, eventually result in tumor resistance whereby a highly infiltrative and invasive phenotype may be adopted. Here we review recent anti-angiogenic therapy for malignant glioma and highlight implantable devices and nano/microparticles as next-generation methods for chemotherapeutic delivery. Intrinsic and adaptive modes of glioma resistance to anti-angiogenic therapy will be discussed with particular focus on the glioma stem cell paradigm

An investigation into physiognomic perception : accurate judgments of psychopathic traits and criminality from facial photographs

Research has shown that some aspects of personality can be accurately read from the permanent features of a person's face. This accuracy has been explained through reference to actual relationships between underlying traits and facial appearance. These could be caused through a self-fulfilling prophecy that arises from the effect of facial stereotypes on personality development, from habitual expressions leaving permanent traces on the face, or from common biological or environmental causes of both facial appearance and character. The latter two explanations are associated with physiognomy, the direct perception of underlying character through reading faces. An attempt was made to find support for the validity of physiognomy by controlling those physical characteristics of faces that have been linked to processes of over-generalisation, and thus might lead to self-fulfilling prophecies. Other potential cues to underlying character that were irrelevant to physiognomy were also controlled. It was predicted that participants would accurately perceive psychopathic traits and criminal propensity from facial photographs of sexual serial killers and non-criminals. This prediction was supported. However, the accuracy found may have resulted from a failure to control differences between the sexual serial killers and non-criminals relating to certain physical characteristics of the photographs and their subjects. These variables were found to correlate with participants' judgments regarding psychopathic traits and criminality. It was concluded that the results were consistent with processes of over-generalisation, but that the occurrence of direct physiognomic perception could not be ruled out. Suggestions were made regarding future research that might isolate the direct perception of character from accuracy due to self-fulfilling prophecies. The importance of controlling confounding features such as grooming and transient facial expression was emphasised

Life-course partnership history and midlife health behaviours in a population-based birth cohort

The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ ERC grant agreement n° 324055.Background:  Marital and partnership history is strongly associated with health in midlife and later life. However, the role of health behaviours as an explanatory mechanism remains unclear. The aim of this study was to investigate prospective associations between life-course partnership trajectories (taking into account timing, non-marital cohabitation, remarriage and marital transitions) and health behaviours measured in midlife. Methods:  We analysed data from the British National Child Development Study, a prospective cohort study that includes all people born in 1 week of March 1958 (N=10 226). This study included men and women with prospective data on partnership history from age 23 to 42–44 and health behaviours collected at ages 42–46 (2000–2004). Latent class analysis was used to derive longitudinal trajectories of partnership history. We used multivariable regression models to estimate the association between midlife health behaviours and partnership trajectory, adjusting for various early and young adult characteristics. Results:  After adjustment for a range of potential selection factors in childhood and early adulthood, we found that problem drinking, heavy drinking and smoking were more common in men and women who experienced divorce or who had never married or cohabited. Women who married later had a lower prevalence of smoking and were less likely to be overweight than those who married earlier. Overall marriage was associated with a higher body mass index. Individuals who never married or cohabited spent less time exercising. Conclusions:  Some aspects of partnership history such as remaining unpartnered and experiencing divorce are associated with more smoking and drinking in midlife, whereas marriage is associated with midlife weight gain. Despite these offsetting influences, differences in health behaviours probably account for much of the association between partnership trajectories and health found in previous studies.Publisher PDFPeer reviewe

From reaching every district to reaching every community: analysis and response to the challenge of equity in immunization in Cambodia

Background An international review of the Cambodian Expanded Programme on Immunization (EPI) in 2010 and other data show that despite immunization coverage increases and vaccine preventable diseases incidence reductions, inequities in access to immunization services exist. Utilizing immunization and health systems literature, analysis of global health databases and the EPI review findings, this paper examines the characteristics of immunization access and outcome inequities, and describes proposed longer-term strategic and operational responses to these problems. Findings The national programme has evolved from earlier central and provincial level planning to strengthening routine immunization coverage through the District level ‘Reaching Every District Strategy'. However, despite remarkable improvements, the review found over 20% of children surveyed were not fully immunized, primarily from communities where inequities of both access and impact persist. These inequities relate mainly to socio-economic exposures including wealth and education level, population mobility and ethnicity. To address these problems, a shift in strategic and operational response is proposed that will include (a) a re-focus of planning on facility level to detect disadvantaged communities, (b) establishment of monitoring systems to provide detailed information on community access and utilization, (c) development of communication strategies and health networks that enable providers to adjust service delivery according to the needs of vulnerable populations, and (d) securing financial, management and political commitment for ‘reaching every community'. Conclusions For Cambodia to achieve its immunization equity objectives and disease reduction goals, a shift of emphasis to health centre and community is needed. This approach will maximize the benefits of new vaccine introduction in the coming ‘Decade of Vaccines', plus potentially extend the reach of other life-saving maternal and child health interventions to the socially disadvantaged, both in Cambodia and in other countries with a similar level of developmen