Prevalence of childhood obesity is increasing. Insulin resistance is a consequence of childhood obesity, and it has a keyrole in the development of cardiometabolic complications, such as... Show more Prevalence of childhood obesity is increasing. Insulin resistance is a consequence of childhood obesity, and it has a keyrole in the development of cardiometabolic complications, such as diabetes mellitus. In the first part of this thesis, the epidemiology of insulin resistance has been described. Since there is no clear definition for insulin resistance, the prevalence of IR remains unclear. In addition, the use of IR in the screening for diabetes mellitus in obese children was evaluated. In the second part of the thesis, treatment of obese children with insulin resistance is discussed. In a randomized controlled trial of 18 months, children were treated with either metformin or placebo in addition to lifestyle intervention. Body mass index in children treated with metformin remained stable during the 18 months, whereas placebo-treated children had an increase in body mass index. Finally, the treatment with metformin under the strict circumstances of the clinical trial was compared to treatment with metformin in daily practice during 18 months. Both groups showed similar results regarding body mass index during metformin treatment. Show less
This publication aims at the analysis of the performance of a corpus of Fongbe stories that I collected in three villages in the south of Benin in 1976 and 1977. The corpus consists of 37 stories ... Show moreThis publication aims at the analysis of the performance of a corpus of Fongbe stories that I collected in three villages in the south of Benin in 1976 and 1977. The corpus consists of 37 stories (57.000 words). The stories aim at children__s education. Seven stories in my corpus are similar, although told by different performers in different villages. These stories stage an identical topic, central participant and pair of agents. However, the plot is different. The analyses give insight in the degree of improvisation. The corpus consists of dramatic and comic stories. The basic topic of the stories is the diviner__s consultation of the __guardian spirit__ through Fa. The statistical analyses of the narrative discourse show a constant speech rate, with the exception of rhetorical highlights and songs. The graphics show that the performers use a pattern of pauses that functions as content marker. The performers use a single particle as the clause-final topic as well as a definite marker of a noun. The framework of the story is rudimentary, although several grammatical functions, lexical markers and rhetorical phenomena obligatorily convey parts of the plot. On the other hand, the performer uses the storyboard technique to structure the performance. __Verbal art of the Fon (Benin)__ is published by Ruediger Koeppe Verlag P.O. Box 45 06 43 50881 Cologne__Germany Show less
The decision to treat elderly patients with cancer aged 70 years or older with chemotherapy is generally based on clinical judgment of the clinician, in combination with the evidence obtained from... Show moreThe decision to treat elderly patients with cancer aged 70 years or older with chemotherapy is generally based on clinical judgment of the clinician, in combination with the evidence obtained from clinical studies performed in younger age groups. The instrument GA might be helpful to detect hidden shortcomings and may aid clinical decision making with regard to the feasibility of treatment with chemotherapy and prediction of survival in the elderly patients with cancer. The following questionnaires and tests were considered appropriate to obtain a practical GA: MNA, GFI, IQCODE, MMSE, and laboratory values of albumin, creatinine, lactate dehydrogenase and hemoglobin. The main questions we tried to answer were firstly to assess the predictive value prior to the start of chemotherapy of the chosen GA with respect to the probability to complete the planned chemotherapy and overall survival and secondly to analyze and determine which elements of the chosen GA were independently predictive to complete chemotherapy and which elements predicted early mortality.This thesis is the result of clinical research on certain elements of GA that might be useful for routine daily oncology practice, in order to select the proper patients and improve the outcome of treatment with chemotherapy. Show less
Phenomenologically, cosmic inflation is a satisfying and well-tested description of the physics of the very early universe. During this epoch, the universe was dominated by high energy phenomena... Show morePhenomenologically, cosmic inflation is a satisfying and well-tested description of the physics of the very early universe. During this epoch, the universe was dominated by high energy phenomena that can only be truly understood in a quantum gravity theory such as string theory. In this thesis we show that the embedding of inflation in a string theoretic framework is very sensitive to the details of the theory. We consider both the low energy supergravity limit as well as a worldsheet set-up. Moreover, we investigate the constraints imposed by supersymmetry and conformal symmetry. Conformal symmetry is important both in the worldsheet theory as well as in a holographic description of inflation. In the latter case we investigate the imprints of conformal invariance on the (observable) statistical correlations in the cosmic microwave background radiation. Show less
In this thesis, I investigated the behavioral and neural processes involved in self-concept development in adolescence within the context of future-oriented educational decision-making. The studies... Show moreIn this thesis, I investigated the behavioral and neural processes involved in self-concept development in adolescence within the context of future-oriented educational decision-making. The studies presented in this thesis all highlight that self-concept is a multifaceted and complex construct that not only develops in interaction with the social environment, but can also have an impact on someone’s future environment. For example, results from chapter 2 indicated that the social environment, expressed in the outcomes of social comparisons, can affect the positivity of the self to a different extent across multiple domains and different stages of adolescence. Chapter 3 showed how adolescents’ academic self-concept can influence their motivation to stay committed to goals important for their future educational environment, whereas chapter 4 illustrated differences in self-esteem and self-concept clarity in individuals who differed in their experienced problems with choosing this future educational environment. Finally, chapter 5 demonstrated that in late adolescence, sensitivity to outside influences can be used to stimulate self-concept development through training which can ultimately help adolescents in their educational decision-making and adjustment in higher education. Together, these studies provide a comprehensive view on self-concept development in adolescence that takes place within a broader social, and educational context. Show less
This thesis consists of three parts. Part A describes in chapter 2 the complex diagnosis of asthma in the morbidly obese, and especially focuses on underdiagnosis and overdiagnosis of asthma in... Show moreThis thesis consists of three parts. Part A describes in chapter 2 the complex diagnosis of asthma in the morbidly obese, and especially focuses on underdiagnosis and overdiagnosis of asthma in this patient group. Part B investigates bronchial and systemic inflammation. It starts in chapter 3 with a review on the association between obesity and asthma, where the metabolic syndrome __ as state of systemic inflammation - is mentioned as possible explanation for the association between obesity and asthma. In chapter 4 systemic inflammation and the metabolic syndrome and impaired lung function in morbidly obese subjects are discussed. This is followed by chapter 5, in which the presence and possible relationship between bronchial and systemic inflammation in morbidly obese asthma subjects are discussed. Part C focuses on bariatric surgery, first pulmonary function testing and complications of bariatric surgery are discussed in chapter 6. In chapter 7 the effect of bariatric surgery on asthma is described. And finally, in chapter 8, a summary and general discussion of these studies is presented. Show less
The aim of this dissertation was to investigate whether and how E-health can help to improve health care for individuals with eating disorder symptoms. The main goal was to evaluate two E-health... Show moreThe aim of this dissertation was to investigate whether and how E-health can help to improve health care for individuals with eating disorder symptoms. The main goal was to evaluate two E-health interventions: e-community ‘Proud2Bme’ and fully automated Internet-based intervention ‘Featback’. The effectiveness and cost-effectiveness of Featback with and without therapist support in comparison to a waiting was examined in a randomized controlled trial. Furthermore, potential moderators and mediators were investigated: what works for whom and what is the psychological mechanism that explains how Featback achieves its beneficial effects? Also, all online therapist communication within the Featback intervention was qualitatively examined. What did therapists actually do within the online support sessions as offered in addition to Featback? And can therapist behaviors predict participants’ outcome and satisfaction? Finally, this dissertation includes a systematic review of treating eating disorders over the Internet, as well a chapter about the emerging findings, issues, and opportunities regarding E-health for eating disorders in the past few years (2013-2015). How effective are Internet-based self-help interventions, -treatment, and -relapse prevention programs? What is the potential of Smartphone applications in treating eating disorders? What are the opportunities and challenges for the development and implementation of E-health for eating disorders? Show less
Streptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with... Show moreStreptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with the life cycle. This thesis shows the identification of S. roseifaciens, a novel species with an uncommon, verticillate spore morphology and a unique household of SsgA-like proteins. Analyses of the peptidoglycan composition show that S. coelicolor show a pattern of 3-3 cross-linking befitting a tip-growing organism and change in composition between vegetative mycelium and spores. Kitasatosporae carry meso-DAP in the peptidoglycan of vegetative mycelium and LL-DAP in the peptidoglycan of spores. In line with this difference, the peptidoglycan architecture of these two growth stages undergoes such radical changes that they would seem to be from different species. S. coelicolor is naturally vancomycin resistant, but the addition of D-alanine and disruption in a single gene increases vancomycin sensitivity by a thousandfold. A knockout mutant of the alanine racemase, alr, requires exogenous addition of D-alanine. The Alr crystal structure of S. coelicolor and the D-cycloserine producer S. lavendulae were compared as to look for possible mechanisms for D-cycloserine resistance. Show less
Duchenne muscular dystrophy (DMD) is a severe, lethal neuromuscular disorder caused by reading frame disrupting mutations (mostly deletions) in the dystrophin gene. This results in the complete... Show moreDuchenne muscular dystrophy (DMD) is a severe, lethal neuromuscular disorder caused by reading frame disrupting mutations (mostly deletions) in the dystrophin gene. This results in the complete absence of dystrophin and leads to the continuous loss of muscle fibers and fibrosis. As a consequence, DMD patients are wheelchair dependent before the age of 12 and often die in the third decade of the life (or earlier) due to respiratory- or heart failure. Deletions in the dystrophin gene that keep the reading frame intact allow the generation of internally deleted, partly functional dystrophins and are associated with the milder Becker muscular dystrophy (BMD). Becker patients often remain ambulant until later in life and have near normal life expectancies. Normal dystrophin consists of an N-terminal actin-binding domain, a central rod domain (containing 24 spectrin-like repeat units and 4 hinge regions) a cysteine-rich and a C-terminal domain. Dystrophin is thought to fulfill a bridge function between the cytoskeleton and the extracellular matrix, since the actin binding domain binds to cytoskeletal actin, while the C-terminal domain is involved with the transmembranal dystrophin glycoprotein complex (DGC) that is connected to the extracellular matrix via laminin 2. In DMD patients this bridge function is completely lost, since the C-terminal bridgehead is lacking due to a truncating mutation. In BMD patients on the other hand, an internal deletion results in a shorter, but still semi-functional bridge that contains both the N-terminal and C-terminal bridgeheads. As yet there is no clinically applicable therapy for DMD patients, despite extensive research for a variety of different approaches. Currently, one of the most promising strategies is the antisense-mediated reading frame restoration. The aim of this approach is to induce specific exon skipping to convert an out of frame DMD transcript into its nearest in frame BMD-like counterpart. This would allow the generation of an internally deleted but partly functional dystrophin and should convert DMD into a milder BMD phenotype. The skipping of a specific exon can be induced by antisense oligoribonucleotides (AONs), which are small synthetic RNAs. Upon binding of the AONs to the pre-mRNA the splicing machinery does not recognize the exon as such anymore, and as a result the targeted exon is spliced out with its flanking introns (i.e. the exon is "skipped"). The broad mutation spectrum found for DMD would require the skipping of a series of exons to restore the reading frame for several patients. Fortunately, designing efficient DMD specific AONs has proven relatively easy, and we can currently induce the specific skipping of 20 different exons in human control myotube cultures after PEI-mediated AON delivery (Chapter 2). This would restore the reading frame for over 40% of all DMD patients. The broad therapeutic applicability of this technique was confirmed in myotube cultures derived from 8 different patients (Chapter 3). For each patient skipping of the specific exons could be induced on RNA level and dystrophin synthesis was restored in over 75% of treated myotubes. Time course experiments revealed that dystrophin was detectable as early as 16 hours post transfection and increasing levels were found for up to 7 days. In addition, expression of DGC proteins was restored in treated myotube cultures, further confirming the functionality of the BMD-like dystrophins. Since a significant part of DMD patients carries a mutation that requires the skipping of two exons, we also tested the feasibility of double-exon skipping in two patients (Chapter 4). After treatment with a mix of the respective AONs, double exon skipping was detected on RNA level and dystrophin synthesis was restored for over 70% of treated myotube cultures for both patients. Furthermore, when we treated control myotubes with AONs targeting exons 45 and 51 we observed multi-exon skipping of exon 45 through 51. Multi-exon skipping not only increases the applicability of this technique, it also reduces the mutation specificity, since it allows for the generation of a BMD-like deletion that covers the majority of DMD mutations. The skipping of exon 45 through 51 would already be applicable to 15% of all patients and its feasibility was confirmed in myotubes derived from a patient carrying an exon 48-50 deletion. Subsequent experiments aiming at the skipping of a larger number of exons seem to indicate that the number of exons that can be skipped is limited due to hitherto unknown processes. Thus far we have used AONs containing 2'-O-methyl RNA with a full-length phosphorothioate backbone (2OMePS), which are cytotoxic at high concentrations. For future clinical applications the optimal AON induces high levels of specific exon skipping at low levels of cytotoxicity. We thus compared the efficacy and efficiency of our most efficient exon 46 2OMePS AON to those of a morpholino, a locked nucleic acid (LNA) and a peptide nucleic acid (PNA) AON (Chapter 5). Only the LNA induced higher levels of exon skipping than 2OMePS in patient and control myotube cultures. However, when we compared the sequence specificity of these analogues we observed that LNAs appear to be much less sequence specific than 2OMePS AON. Therefore, we conclude that 2OMePS currently seem the favorable compounds to establish clinical trials. To study exon skipping in vivo we injected PEI-coupled 2OMePS AONs specific for murine exon 46 into the gastrocnemius muscle of normal mice (Chapter 6). Relatively low levels of exon 46 skipping could be detected on RNA level and persisted for over four weeks post injection. Furthermore, we have previously engineered a mouse model that contains the entire human DMD gene (2.6 Mb) integrated into the murine genome (hDMD mouse). These transgenic mice uniquely allow for the preclinical testing of human-specific AONs in vivo. We have injected AONs targeting human exons 44, 46 and 49 into the musculus. gastrocnemicus of hDMD mice, and showed that the skipping of the human exons (but not the murine exons) was indeed specifically induced. Based on pre-clinical data obtained by our group and others, we are currently setting up a clinical trial aiming at local dystrophin restoration following intramuscular injections of exon 46 and 51 specific AONs. For future application, however, we aim at systemic delivery of AONs. Therefore, we are currently investigating delivery methods that will allow systemic delivery of AONs. Show less
Approximately 35% of colorectal cancer (CRC) risk is attributed to heritable factors, with 5 to 10% linked to dominant or recessive inherited syndromes. Known high-risk genes like POLE, POLD1,... Show moreApproximately 35% of colorectal cancer (CRC) risk is attributed to heritable factors, with 5 to 10% linked to dominant or recessive inherited syndromes. Known high-risk genes like POLE, POLD1, NTHL1 and APC contribute to a portion of this risk. However, the genetic basis for 20%-30% of inherited CRC remains unclear. This thesis explores the roles of POLE, POLD1, APC and NTHL1 in CRC and polyposis. While screening for pathogenic variants in POLE and POLD1, remarkably POLE L424V variants were found to induce Lynch syndrome-like features due to somatic mismatch repair gene mutations. Biallelic NTHL1 variants predisposing to CRC and polyposis were studied in a collaborative effort, describing a broad tumor spectrum and a high risk of extracolonic cancers associated with NTHL1 deficiency. For monoallelic NTHL1 variant carriers, no significant evidence link was found with increased polyposis or CRC risk, as supported by mutational signature analysis on colorectal tumors. Show less
This dissertation argues that civil society actors have engaged in Eastern Nile politics despite the dominance of states and intergovernmental organisations. There are different characteristics of... Show moreThis dissertation argues that civil society actors have engaged in Eastern Nile politics despite the dominance of states and intergovernmental organisations. There are different characteristics of civil engagement in Nile politics. There are structured organisations including non-governmental organisations and think tanks, others act through initiatives and loosely structured arrangements such as diaspora groups and youth-based initiatives. The analysis of this dissertation focuses on transnational activities of civil society actors in the Eastern Nile Basin countries: Egypt, Sudan and Ethiopia. It investigates how an intergovernmental organisation (the Nile Basin Initiative) interacts with different civil society actors (e.g. the Nile Basin Discourse). Network analysis has been applied to understand interconnections among civil society actors on the one hand and relations with national governments and donor agencies on the other hand. Several interviews have been conducted in Egypt, Sudan and Ethiopia with a variety of actors to discern their positions on the issues and connections with other actors. The research findings show a clustered network as civil society actors operating in small groups rather than covering the whole Eastern Nile Basin. The network has this feature because the majority of organised civil society actors employ depoliticized activities, such as capacity building programs, water service provision and awareness raising. Nevertheless, unstructured civil society activism (e.g. diaspora groups and anti-dam movements) has been able to contest water policies and projects as determined on national levels. The research shows civil society actors often take similar positions as their respective governments regarding contested politics (e.g. water shares), despite the fact that they may conduct joint activities with other civil society actors in transnational networks across the Eastern Nile Basin. But enhanced patterns of civil society engagement and transnational patterns of collaboration could constitute a counterweight to nationally determined agendas that often lead to clashing visions on water governance in the region and among the riparian communities. Show less
Geometric phases lead to a nontrivial interference result when an electron's different quantum mechanical paths choices encircle a magnetic coil in an Aharonov-Bohm experiment. They are also... Show moreGeometric phases lead to a nontrivial interference result when an electron's different quantum mechanical paths choices encircle a magnetic coil in an Aharonov-Bohm experiment. They are also responsible for the daily precession of a Foucault pendulum in Paris. A dynamical shape change induces a geometric phase, which, for instance, cats use to rotate when falling and swimmers use to swim forward.A modern application of such geometric phases has led to the notion of topological phases, which are described by a global property of the system. These phases are very different from the classical phases of matter, which are characterized by a local order parameter. A topological phase transition is therefore a fundamentally different process compared to a classical one as in a liquid-gas transition, because the former requires a change of a global topological index of the system. Topological phases can, for example, lead to the presence of traveling electronic modes which are robust against being backscattered by obstacles at the boundary of an insulator.This thesis describes some applications of geometric and topological phases in soft-matter systems. Show less
Art therapy is an often provided but little studied treatment option in mental health care.The effectiveness of art therapy in the treatment of anxiety was studied and its working mechanisms were... Show moreArt therapy is an often provided but little studied treatment option in mental health care.The effectiveness of art therapy in the treatment of anxiety was studied and its working mechanisms were explored. Outcomes of a randomised controlled trial (n=59) showed preliminary evidence of the effectiveness of art therapy. The treatment, consisting of three months of anthroposophic art therapy, showed major reduction of anxiety symptom severity in women, compared to a wait list condition. The therapy also improved quality of life and various aspects of self-regulation: higher HRV at rest (which may indicate an overall lower stress level), improvements in emotion regulation and improvements in daily executive functioning.The second part of this PhD research focused on case report methodology and the development of tools for research within this field, with and for therapists in clinical practice, and for education. A publication guideline for case reports was developed and positively evaluated in practice. An exemplary case report of a female client with anxiety was provided.The outcomes of this research support the indication of art therapy in the treatment of anxiety and justify further studying of the effectiveness and mechanisms of art therapy. Show less
This book provides an overview of the conditions facing the urban poor in Khartoum, Sudan and explores the opportunities and constraints people of different genders, ages, wealth and social origins... Show moreThis book provides an overview of the conditions facing the urban poor in Khartoum, Sudan and explores the opportunities and constraints people of different genders, ages, wealth and social origins face in the pursuant of their livelihoods. Using an in-depth analysis, it argues that the livelihoods of poor people have been severely constrained by both formal and informal institutions that have not allowed them to access capitals and choose the way they utilize those they have. Show less
It has been shown by this thesis that plant metabolomics is a promising tool for studying the interaction between B. rapa and pathogenic fungi. It gives a picture of the plant metabolites during... Show moreIt has been shown by this thesis that plant metabolomics is a promising tool for studying the interaction between B. rapa and pathogenic fungi. It gives a picture of the plant metabolites during the interaction. Brassica rapa has many defense related compounds such as glucosinolates, IAA, phenylpropanoids and flavonoids and even some primary metabolites including amino and organic acids which might play role in resistance against pathogens. These metabolic pathways undergo rerouting during the infection and the required precursors for the defense compounds might be formed. The rerouting of fluxes at the level of chorismate seems to play a role in resistance of B. rapa to pathogenic fungi. Resistance involves a very high level of complexity. Understanding resistance thus requires studies of different combinations of cultivars and microorganisms. By taking a systems biology approach and measuring on the level of transcriptome, proteome and metabolome and analyzing the large data sets from interactions of different cultivars with different fungi in combination with data on susceptibility by means of multivariate analysis might give a better insight in the defense response of the plant. As we used different cultivars in our study, the fungal infection and also treatment with signal molecules induced secondary metabolites that branch from the chorismate pathway including phenylpropanoids, flavonoids, IAA and indole glucosinolates. Even with using different cultivars from B. rapa, all cultivars showed enhanced accumulation of secondary metabolites derived from the chorismate pathway. Phenylpropanoids, benzoyl glucosinolates, flavonoids and indole glucosinolates should be the target compounds for genetic engineering research. By using genetic engineering techniques, one can breed new cultivars that are characterized by higher levels of these secondary metabolites. Show less
Evidence is accumulating that infliction of DNA damage can lead to spatial repositioning of chromatin. Mitomycin C (MMC)-induced interchanges between homologous chromosomes have been taken as... Show moreEvidence is accumulating that infliction of DNA damage can lead to spatial repositioning of chromatin. Mitomycin C (MMC)-induced interchanges between homologous chromosomes have been taken as cytological evidence for somatic pairing of human chromosomes. Pairing of specific chromosomal regions might differ dependent on biological states or activities, i.e. cell type, cell cycle phase, differentiation stage and diseases. However, the biological relevance of pairing is unclear. The aim of this thesis was to dissect the mechanisms that underlie the interaction between homologous chromosomes observed in metaphase and the interphase of the cell cycle. To reach this goal, we assessed the effect of genotoxic agents such as X-rays, UV radiation and MMC on the positioning of homologous chromosomal regions within the nucleus of human cells. Moreover, we examined the relationship between interphase pairing and processing of DNA damage that leads to exchange formation. We found that: (i) pairing of heterochromatic regions is a general response to genotoxic stress, (ii) pairing is correlated with exchanges between homologous chromosomes after exposure to the anticancer drug mitomycin C (MMC), (iii) pairing is genetically controlled by genes involved in the DNA damage response and (iv) processing of MMC-induced DNA damage is initiated in non-dividing cells. Show less
In this dissertation we developed a number of automatic methods for multi-modal data registration, mainly between mass spectrometry imaging, imaging microscopy, and the Allen Brain Atlas. We... Show moreIn this dissertation we developed a number of automatic methods for multi-modal data registration, mainly between mass spectrometry imaging, imaging microscopy, and the Allen Brain Atlas. We have shown the importance of these methods for performing large scale preclinical biomarker discovery investigations for neurological disorders. We have also proposed a data-driven approach to stratify patients’ tumor tissues into molecularly distinct tumor subpopulations and automatically identify those tumor subpopulations that drive patient outcome. Show less
This thesis describes clinical and fundamental studies addressing clinical challenges in patients with differentiated thyroid carcinoma (DTC). The diagnosis of DTC is hampered by the fact that... Show moreThis thesis describes clinical and fundamental studies addressing clinical challenges in patients with differentiated thyroid carcinoma (DTC). The diagnosis of DTC is hampered by the fact that although the incidence is low thyroid nodules are prevalent. In this thesis, the diagnostic value of a potential marker for DTC has been studied. Unfortunately, in a high proportion of patients with metastases of DTC, the tumor has become resistant to RAI therapy. We have performed fundamental studies into the mechanisms of the regulation of the sodium iodide symporter (NIS) that may have implications for restoring susceptibility to RAI therapy. Furthermore, the long-term efficacy of a new treatment with the multi kinase inhibitor (MKI) sorafenib for DTC patients with metastases that are unresponsive to RAI has been evaluated. Therapy with MKI has numerous adverse effects, including hypothyroidism. We have evaluated a potential mechanism of sorafenib associated hypothyroidism. Finally, DTC patients have traditionally been treated with TSH suppressive levothyroxine substitution. However, high thyroid hormone concentrations may have adverse effects on various organ systems, including the heart. In this thesis, we studied the effects of various thyroid hormone concentrations on cardiac function in DTC, using dedicated cardiac ultrasound. Show less
The glioma microenvironment harbors a variety of immune cells including innate immune cells such as monocytes, macrophages and microglia. Microglia are the major innate immune cells present in the... Show moreThe glioma microenvironment harbors a variety of immune cells including innate immune cells such as monocytes, macrophages and microglia. Microglia are the major innate immune cells present in the glioma microenvironment. Communication between glioma and these immune cells is crucial to maintain a tumor-promoting environment. In this thesis the role of a specific type of communication is described. In detail, the consequence of extracellular communication from glioma to the innate immune cells is studied, this includes the transferring of messages (including miRNAs) through extracellular vesicles. In addition, the changes that these cells undergo in the presence of a tumor is documented. Show less
Glomerulosclerosis is a general term describing the process of scarring of the glomeruli, the functional units in the kidney that filter urine from the blood. This severe, irreversible complication... Show moreGlomerulosclerosis is a general term describing the process of scarring of the glomeruli, the functional units in the kidney that filter urine from the blood. This severe, irreversible complication can occur secondary to various already established systemic or local diseases. However, not all patients with renal diseases show progression to end stage renal disease (ESRD). Thus renal patients can be subdivided into progressors and non-progressors based on clinical parameters1. Why patients with renal diseases become progressors or non-progressors is unclear, and better insight into the pathogenesis of glomerulosclerosis may improve our understanding of the process towards progression. However, the pathogenesis of glomerulosclerosis is complex and still poorly understood, although genetic factors probably play a role, given the considerable variation among individuals in both the risk of developing glomerulosclerosis and the rate of progression. Therefore, the first aim of the work described in this thesis was to identify genes involved in the progression and repair of glomerulosclerosis, using an animal model that allows a clear distinction between progression and repair after renal injury. The second aim was to gain better insight into the pathogenesis of glomerulosclerosis by investigating the expression and activity of fibrosis-related molecules in an animal model and in patients with renal diseases. Show less
