The research described in this thesis mainly focussed on making and refining a model that describes axial patterning during gastrulation in the frog Xenopus laevis. Chapter 2 and 3 describe that... Show moreThe research described in this thesis mainly focussed on making and refining a model that describes axial patterning during gastrulation in the frog Xenopus laevis. Chapter 2 and 3 describe that axial information arises in the mesoderm and subsequently in the neurectoderm. Also is shown that this information, under influence of the Spemann organiser and cellular movements, is translated from a time sequence into a space sequence. The function of the Spemann organiser, important for AP patterning is neural induction. In chapter 4 is described that retinoids, important for axial patterning and formed in the mesoderm, have a patterning effect on neurectoderm. An important conclusion in this chapter is that retinoids are candidates for transfer of axial information from mesoderm to neurectoderm and can, in this way, coordinate the expression of axial information between mesoderm and neurectoderm. In chapter 5 a study is described where the transcriptional targets of Hoxc6 or Antennapedia in the frog Xenopus laevis and the fruitfly Drosophila melanogaster are compared. From this comparison conclusions can be drawn about the processes that are important for the function of Hoxc6/Antp. From this study could be concluded that celldivision, cellmigration, and suppresion of head formation are processes that are important for the function of Hoxc6/Antp. Show less
This thesis examines the effect of developmental care in a tertiary NICU in 2 locations in the Netherlands on preterm infants born < 32 weeks gestational age. Following a pilot study with 22... Show moreThis thesis examines the effect of developmental care in a tertiary NICU in 2 locations in the Netherlands on preterm infants born < 32 weeks gestational age. Following a pilot study with 22 preterm infants and their parents, two consecutive randomized controlled trials (n=179, n=164) in which first basic developmental care (use of incubator covers and positioning aids), and then the comprehensive Newborn Individualized Developmental Care and Assessment Program (NIDCAP), an individual approach in which caregiving is based on the behavior of the infant, was studied in preterm infants born < 32 weeks GA. Basic developmental care had no effect on short-term physical and neurological outcomes; a positive effect on psychomotor development at 1 CA, but no effect on neurological and mental development or growth at 1 and 2 years. NIDCAP showed no effect on short-term physical and neurological outcomes as well as no effect on growth, neurological, mental and psychomotor development at 1 and 2 years CA in infants born < 32 weeks, as compared to basic developmental care. Future research should include not only the effect of developmental care in the neonatal centers but also the effect of continuing the intervention once infants are transferred to regional hospitals. Show less
Caecilians, or Gymnophiona, constitute one of the three extant orders of the Recent Amphibia and are the least known, major living tetrapod clade. Compared to frogs and salamanders, caecilians have... Show moreCaecilians, or Gymnophiona, constitute one of the three extant orders of the Recent Amphibia and are the least known, major living tetrapod clade. Compared to frogs and salamanders, caecilians have an unusual skull morphology. Earlier reports of an unusually high number of individual skull ossifications in Hypogeophis rostratus are addressed and found to be erroneous. Changes in skull morphology and myology at metamorphoses are investigated in representatives of all taxa possessing free-living larvae. It is argued that caecilians are derived from gymno- or zygokrotaphic ancestors and that stegokrotaphy evolved within Recent caecilians. The influence of different life-histories on postembryonic skull development was studied in two direct-developing species. The direct-developing Boulengerula taitanus is characterized by very immature hatchlings, which is correlated with an extended period of post-hatching parental care in this species, during which juveniles feed on the modified skin of their mothers. Direct development in caecilians is characterized by ontogenetic repatterning and heterochronic shifts in certain developmental events. The ontogeny of Scolecomorphus kirkii was studied as a representative of a viviparous form. The emerging picture of available published information, together with observations presented here, suggest a previously unsuspected degree of developmental diversity among caecilians. It is further argued that caecilians are lissamphibians with temnospondyl affinities rather than closely related to lepospondyl microsaurs. Show less
Through evolution the social amoebas have developed mechanisms to adapt to environmental changes and ensure survival. This thesis explores the evolutionary origins of cAMP signalling and regulation... Show moreThrough evolution the social amoebas have developed mechanisms to adapt to environmental changes and ensure survival. This thesis explores the evolutionary origins of cAMP signalling and regulation of developmental decisions in the model organism Dictyostelium discoideum. It also shows the first molecular-based phylogeny of the Dictyostelids. Development in Dictyostelium is characterized by the formation of a multicellular structure, the fruiting body, with a well-defined temporal and spatial pattern. cAMP, normally used as intracellular second messenger, in Dictyostelium is used also as an extracellular signal (chemoattractant) to mediate cell movement and cell differentiation. The study of the different components that control the formation of a multicellular fruiting body at a molecular level and from an evolutionary perspective shows that extracellular cAMP signalling was originally developed to control fruiting body morphogenesis. Furthermore it reinforces the idea that Dictyostelium is a simple but yet robust model to study the origins of multicellularity. Do to cAMP being so prevalent in Dictyostelium development I have studied the regulation of cAMP production during particular developmental stages showing in this thesis novel roles for the adenylyl cyclases that produce cAMP and their specific patters of expression during development. A thorough pharmacological analysis of these enzymes is also present in this work. Show less
An adverse early life event is considered a risk factor for stress-related psychiatric disorders in genetically predisposed individuals, probably because of its lasting effect on susceptibility to... Show moreAn adverse early life event is considered a risk factor for stress-related psychiatric disorders in genetically predisposed individuals, probably because of its lasting effect on susceptibility to stress. The objective of this thesis research was to examine in the mouse CD1 strain the immediate and permanent effects of an adverse early experience on the neuroendocrine stress system. For this purpose the hypothalamic-pituitary-adrenal (HPA) axis was examined of mouse pups that were refrained from maternal care, a laboratory model for neglect mimicking aspects of abuse. The data show that the infants__ stress response system readily adapts to daily repeated 8 hours of maternal separation, but that it continues to respond to a novelty stressor. The rapid adaptation to repeated maternal absence seems rather due to the ability to predict return of the mother than to adjust metabolism to episodic food deprivation. If maternal separation was extended to a single episode of 24 hours the immediate outcome was more profound but transient, although subtle effects on stress reactions and cognitive performance did persist. The findings demonstrate the amazing plasticity of the newborn brain and provide a basis to study the mechanistic underpinning of vulnerability or resilience to psychopathology. Show less
Multiple processes are influenced by a protein family named the function of Mitogen Activated Protein Kinases (MAPK), where among tissue morphogenesis, cell-proliferation, cell-differentiation,... Show moreMultiple processes are influenced by a protein family named the function of Mitogen Activated Protein Kinases (MAPK), where among tissue morphogenesis, cell-proliferation, cell-differentiation, cell-survival and immune reactions. A consequence of this broad role of these proteins is that disturbed MAPK signaling possibly leads to severe affects, and could even lead to the development of a disease or disturb embryogenesis. The human genome encodes for 14 mapk genes. One of the best characterized MAPK signaling transductions pathways is the Extracellular signal Regulated Kinase 1 and 2 (ERK1/ERK2). The zebrafish is a relatively new, genetic accessible model organism, which is because of their transparency of the embryos, very suitable to study the role of the MAPKs in embryonic development. The study described in this thesis shows that the zebrafish genome encodes for the same mapk genes, which makes it possible to study the functions of these proteins, using the zebrafish. Further investigations to the roles of ERK1 and ERK2 during embryonic development led to the new insight that ERK1 and ERK2 have distinct roles during crucial developmental cell migration processes and the differentiation of tissues and cell types. In addition, it was found that ERK1 and ERK2 affect the expression of common as well as distinct target genes. Show less
Family businesses are experiencing a revival in the German economy. In the face of the challenges of globalization and the ongoing relocation of production facilities, home base oriented... Show moreFamily businesses are experiencing a revival in the German economy. In the face of the challenges of globalization and the ongoing relocation of production facilities, home base oriented enterprises meet with increasing attention and gain in importance. Family-owned enterprises have indeed been neglected in the past, a fact which shows clearly also in business economics research. But this was also due to the family businesses, or the owner families, respectively, failing to open up. In the present paper, the author succeeded in winning high-ranking representatives of producing family businesses as interview partners. The discussions and the subsequent analyses both of the topics discussed and of the theoretical context serve to provide a new and intriguing picture of family-owned enterprises on their international growth path to world market leaders. Show less
Until recently, the trend in development policy circles has been to focus on the question of poverty, and to suggest that inequality is interesting, but that perhaps it really does not matter. In... Show moreUntil recently, the trend in development policy circles has been to focus on the question of poverty, and to suggest that inequality is interesting, but that perhaps it really does not matter. In the 2007 Wertheim Lecture, Jomo K.S. re-examined the role inequality plays in development and human welfare. Show less
This research describes the quest to create 'super-caffeines', substances that only produce the desired effects of caffeine, and unlike caffeine, substances that should only have to be taken in... Show moreThis research describes the quest to create 'super-caffeines', substances that only produce the desired effects of caffeine, and unlike caffeine, substances that should only have to be taken in measured, minute, controlled amounts to achieve these effects. Unless particular steps are taken to avoid it, caffeine is a very prevalent substance in our society, which almost all of us ingest in some manner on a daily basis. It is an integral part of coffee, tea and chocolate-based products, cola drinks and is even used as a supplement in painkillers. Most people recognise caffeine as a stimulant; however, have you ever wondered how and why we get not only the pick-me-up effect, but also less desirable ones, for example, the need to go to the toilet more often and the racing heart? Caffeine is an example of a ligand (a chemical compound) that acts via certain anchor points in the body, the adenosine receptors. These receptors are located throughout the body in a number of different tissues. There are four different categories of this receptor that respond specifically to a substance called adenosine, which is produced within the body when and where it is needed. Once a substance like caffeine enters the body the majority of its effects are as a result of blocking these receptors, thereby not allowing the body's own chemical compound, adenosine, to occupy the receptors. The often welcome stimulatory effects of caffeine have been found to be as a consequence of blocking a particular adenosine receptor, known as the adenosine A1 receptor. The unwelcome sideeffects mentioned earlier are often a result of caffeine's interaction with one or more of the other three adenosine receptors. The therapeutic potential for new __super-caffeines__ (so called adenosine A1 receptor antagonists) are great, for instance as cognition enhancers in the elderly. This thesis describes the design and development of several series of new compounds which help us to define, understand and further the research into adenosine receptor antagonists. The substances themselves are novel in chemical structure, have excellent affinity for the adenosine A1 receptor (very much better than that measured for caffeine) and are selective for this particular receptor above the rest of the adenosine receptor family. Show less
Simultaneous with the improved survival of very preterm and low birth weight infants, the awareness increased that not all survive without sequelae. Mild developmental disturbances that interfere... Show moreSimultaneous with the improved survival of very preterm and low birth weight infants, the awareness increased that not all survive without sequelae. Mild developmental disturbances that interfere with the acquisition of everyday skills and normal learning appeared to be very frequent and were not detected until at school age. The expectation was that such developmental disabilities were temporary side effects and would diminish with increasing perinatal knowledge and experience. The data in this thesis show that impairments, disabilities and handicaps remain invariably high, with the exception of the decreased incidence of visual problems. The increased incidence of cerebral palsy of children born in 1993, compared to 1983, is worrisome. Factors that are responsible for a decreased mortality such as antenatal steroids, artificial ventilation and surfactant, do not decrease these developmental problems in the surviving children. The use of dexamethasone in the neonatal period is a serious extra risk factor for developmental problems. Severe developmental problems are mostly diagnosed at the age oaf two years. Diagnosis of mild motor problems, learning disabilities and problem behaviour however, is mostly delayed until school age. When with advancing age the demands imposed by society increase, the problem rate increases even further. Singularly, these deficits may be subtle, but combined, without compensation in other domains, they may pose a lifelong burden. Therefore, long term longitudinal follow up of these children is necessary. Paediatricians who assess very preterm and low birth weight infants with assessments that include structured elements from the Touwen examination, Denver Development Screening Test, Dutch Language Screening Test and a shortlist from the Child behaviour Checklist overlook developmental motor coordination disorders and learning and behavioural problems. As the movement ABC is an accurate and widely used instrument to detect these motor coordination disorders, the movement ABC should be included in the follow up of very preterm and low birth weight infants at the age of five. To detect all neurological problems a neurological assessment is also necessary. Cognitive problems are indicated by the appearance of learning difficulties at school. As the presence of learning difficulties in very preterm and low birth weight infants is an alarm-signal for cognitive delay, referral and formal cognitive assessment by a child psychologist is indicated. Repeating the school year may not be a good solution. To identify cognitive delays that may interfere with learning before school age, formal cognitive assessment before six years of age should be incorporated in a systematic follow up program. As over one half of all very preterm and low birth weight infants show these developmental problems, routine assessment of all very preterm and low birth weight infants before school age is necessary. Standardised and normalised test instruments that cover all developmental domains must have a rigid structure for managing the test process and calculating the results General judgement by paediatricians in a routine outpatient clinic, even when these paediatricians are well trained, is insufficient. Follow up studies that do not include detailed standardised tests for several domains will underestimate developmental problems in survivors of neonatal intensive care. There is no simple way to identify children in need of extra help or to enable a true evaluation of neonatal intensive care. This thesis deals with problems in very preterm and low birth weight infants. It also documented, however, that modern intensive care saves the lives of many children 'born to soon or born too small' 56 and that many of them grow up without any problem at all. Although modern neonatal intensive care will not restore complete integrity of all preterm born infants, it certainly is worthwhile. Show less
This paper discusses the concept of social security and criticizes the ILO definition of the concept as too limited to analyse non-Western social security systems. It develops an alternative... Show moreThis paper discusses the concept of social security and criticizes the ILO definition of the concept as too limited to analyse non-Western social security systems. It develops an alternative definition which includes, firstly, the protection by society of individuals or social groups against a fall in their standards of living as a result of temporary adversities, and, secondly, the promotion by society of the standards of living of those individuals or groups that are below an acceptable minimum level. This wider definition is justified by arguing that social security is a universal necessity. The paper further discusses principles and forms of social security systems, methods of redistribution, and determinants of social security systems. Show less
