β-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some... Show moreβ-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some compounds, β-lactamase inhibitors, can block these enzymes allowing for possible treatments using a combination of antibiotic and inhibitor. BlaC is the β-lactamase of Mycobacterium tuberculosis, the bacteria that cause tuberculosis, and is used as a model for protein evolution. To understand if and how BlaC can develop resistance against certain inhibitors we studied the evolutionary adaptability of this enzyme. We used laboratory evolution and various biochemical techniques to characterize several mutations in BlaC and subsequently tested the effect of combining mutations. One of the findings is that BlaC can easily become less sensitive to the inhibitor sulbactam by partially blocking the entrance to the active site. Interestingly, this was accompanied by increased sensitivity to another inhibitor, avibactam, that could not be compensated for by other mutations.Generally, Escherichia coli bacteria are used to test the effects of BlaC variants in cells, as they are easy and safe to use in the lab. We show that results obtained for E. coli can be extrapolated to conditions that resemble tuberculosis disease in humans: the M. marinum infection model of zebrafish. All these findings are of interest for the future development of combination therapies to treat tuberculosis. Show less
The explosive radiation and diversification of the advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared venom system. Morphological changes included... Show moreThe explosive radiation and diversification of the advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared venom system. Morphological changes included the partitioning of the mixed ancestral glands into two discrete glands devoted for production of venom ormucous respectively, as well as changes in the location, size and structural elements of the venom-delivering teeth. Evidence also exists for homology among venom gland toxins expressed across the advanced snakes. However, despite the evolutionary novelty of snake venoms, in-depth toxin molecular evolutionary history reconstructions have been mostly limited to those types present in only two front-fanged snake families, Elapidae and Viperidae. To have a broader understanding of toxins shared among extant snakes, here we first sequenced the transcriptomes of eight taxonomically diverse rear-fanged species and four key viperid species and analysed major toxin types shared across the advanced snakes. Show less
The thesis is about the study of shell evolution of the Hydrocenidae of the genus Georissa. This thesis started with a general overview on the evolutionary process of animals due to ecological... Show moreThe thesis is about the study of shell evolution of the Hydrocenidae of the genus Georissa. This thesis started with a general overview on the evolutionary process of animals due to ecological changes. This study has revealed that the Bornean Georissa are more diverse than previously anticipated. I did the taxonomic revision of the genus Georissa, and discussed the morphological features, phylogenetic relationships, and the biogeographic distribution of the genus in Malaysian Borneo. Also, I studied the shell character evolution of the Bornean Georissa in a phylogenetic framework. Based on the phylogeny, I found convergence in the formation of scales. Additionally, I discussed the differentiation of size and coloration of the Bornean Georissa in dependence on different habitats. Show less
Taxonomy as a science has accumulated data and knowledge for more than 250 years. The quality and usefulness of the facts recorded in taxonomic literature has greatly improved from the early... Show moreTaxonomy as a science has accumulated data and knowledge for more than 250 years. The quality and usefulness of the facts recorded in taxonomic literature has greatly improved from the early descriptive texts to the modern data-rich, hypothesis-driven works. Our work illustrates the application of some of the “e-taxonomic” tools and the “New Taxonomy” thinking explored in the introduction. Here, we analyzed specimen data contained in legacy taxonomic literature in Chapters 2 and 3—to observe species distribution of one spider group and genital evolution, respectively—and also explored an integrative perspective that involves describing new taxa and testing phylogenetic hypotheses using molecular and morphological data, as done in Chapter 4 and 5. Show less
Radio observations provide a unique view of black holes in the Universe. This thesis presents low frequency radio images and uses the radio sources in those images to study the evolution of black... Show moreRadio observations provide a unique view of black holes in the Universe. This thesis presents low frequency radio images and uses the radio sources in those images to study the evolution of black holes and galaxies through the age of the Universe. Show less
Until a few years ago, only two human polyomaviruses (JC and BK) were known to infect humans and cause severe illness in immunocompromised hosts. Since 2007, at least eleven new polyomaviruses... Show moreUntil a few years ago, only two human polyomaviruses (JC and BK) were known to infect humans and cause severe illness in immunocompromised hosts. Since 2007, at least eleven new polyomaviruses became known that infect humans. Among them is the polyomavirus associated with trichodysplasia spinulosa (TSPyV). In Chapter 1 of this dissertation, the main focus is on the recent developments in studying the newly identified human polyomaviruses until mid-2014. This introductory chapter sets the stage for further investigation into TSPyV infection, pathogenesis, evolution and host adaptation, which is detailed in Chapter 2. To study causality between TSPyV infection and TS disease, in Chapter 3, the prevalence, load and localization of this virus is described. In Chapter 4, the cellular mechanisms behind disruption of cellular proliferation and TS spicule formation by TSPyV Large T-antigen is investigated. By In-silico analysis, in Chapter 5, the identification of a polyomavirus evolution and adaptation mechanism called COCO-VA is highlighted. Subsequently, in Chapter 6, TSPyV genome sequences are tested to gain more insight into this COCO-VA mechanism. Finally, in Chapter 7, the findings described in this dissertation are discussed with regard to several TSPyV aspects, and compared to existing knowledge about polyomaviruses in a broader context. Show less
The evolution of ageing is a field flush with misconceptions, misunderstandings, and hiatuses. In this thesis I address the most important misunderstanding and misconceptions, and develop new... Show moreThe evolution of ageing is a field flush with misconceptions, misunderstandings, and hiatuses. In this thesis I address the most important misunderstanding and misconceptions, and develop new theory to fill the gaps. This work directly leads to the restatement of the central question in the evolutionary theory of ageing. Rather than evaluating evolutionary forces in models that are at best weakly rooted in (patho-) physiological mechanisms, usually phrased in terms of __age-specific genes__ that are not further specified, as is the current practice, the most pressing question becomes why an organism cannot, or does not, do in itself what it is perfectly capable of doing outside itself in the form of reproduction, namely producing a perfectly healthy __young__ organism. Evolutionary forces cannot answer this question. If anything, this is a mechanistic question. I suggest investigating __the evolution of unretainability__: why and how has our form of life evolved, in which it is mechanistically impossible to bring ageing to a halt, and what are the responsible mechanistic constraints? Show less
Diplomatiek onderhandelen is een moeilijk te begrijpen en te beheersen proces. Toch is het onderhandelen tussen staten en in internationale organisaties van levensbelang voor het functioneren van... Show moreDiplomatiek onderhandelen is een moeilijk te begrijpen en te beheersen proces. Toch is het onderhandelen tussen staten en in internationale organisaties van levensbelang voor het functioneren van het internationale bestel. Het Handvest van de Verenigde Naties noemt onderhandelen dan ook als het eerste instrument bij het vreedzaam oplossen van conflicten. De wetenschap is nog altijd op zoek naar methoden om de uitkomst van een onderhandeling te verklaren uit de processen waaruit zij is voortgekomen. Dit proefschrift benadert het diplomatiek onderhandelingsproces van verschillende kanten en tracht daarmee aan de hand van gevalstudies in verleden en heden de essentie en de evolutie van het proces beter in beeld te krijgen. Een goed begrip daarvan zal, zo wordt gehoopt, bijdragen tot een effectiever gebruik van het diplomatieke geven en nemen, om daarmee geweldsgebruik terug te dringen. Dat neemt niet weg dat onderhandelen een belangenstrijd blijft, het is een vorm van oorlog met vreedzame middelen. Kernpunt van dit boek is de stelling dat onderhandelen tussen staten pas een werkelijk alternatief voor oorlogvoering kan zijn, als het kan worden gevoerd binnen een kader van regels en procedures om het onderhandelingsproces in goede banen te leiden en gebrek aan vertrouwen tussen partijen te verminderen. Daarin ligt het belang van internationale regimes die de concrete vorm kunnen aannemen van internationale organisaties, met de potentie de uitvoering van genomen besluiten af te dwingen. Uit de voortdurende pogingen de internationale betrekkingen beter te organiseren blijkt dat de diplomatie allang tot dit inzicht is gekomen. Het blijkt echter al even duidelijk uit het falen van onderhandelingen als middel tot conflictbeheersing in gebieden waar een overkoepelende onderhandelingsstructuur ontbreekt, zoals nu in het Midden-Oosten. Diplomatic Negotiation is difficult to grasp, both in practice and in theory. Yet it is important to get to grips with this process, as negotiations between states and in international organizations are the lifeblood of the international body politic. The Charter of the United Nations, for obvious reasons, ranks negotiation as the foremost instrument in the peaceful settlement of inter-state conflicts. Scholars of international relations, however, are still searching for methodologies and theories to explain the outcomes of negotiations by the processes that produce them. This doctoral dissertation approaches the process of diplomatic negotiation from different angles, while applying a multi-faceted qualitative analysis of case studies from the past and present. It is hoped that a better understanding of negotiation as one of the main tools of diplomacy will help to enhance the effectiveness of this process as an alternative to warfare. Still, negotiation is basically a struggle in the promotion and defence of state interests. It is war by peaceful means. The central proposition of this book is that negotiations between states can only be a viable replacement of the use of violence if they are conducted within a framework of international regimes that set the rules and procedures for negotiation behaviour and mitigate lack of trust. International regimes may take the shape of international organizations, which can force countries to live up to their agreements. Diplomats and political leaders have come to recognize this, as the evolution of diplomacy in the last 400 years testifies. Diplomatic negotiation may be taken as a ceaseless series of attempts to bring more order to the international system. The current demise of the negotiation processes in the Middle East thus demonstrates the failure of the international community to build overarching negotiation structures. Show less
The purpose of this thesis is to articulate a theological metaethic which accepts the nature of ethics as understood under the rubric of evolutionary theory. It will be argued that such a... Show moreThe purpose of this thesis is to articulate a theological metaethic which accepts the nature of ethics as understood under the rubric of evolutionary theory. It will be argued that such a theological methaethic can be interpreted as hopeful and optimistic given the apparent evolution of the moral from the amoral. The relationship between theology and evolutionary theory is presented here not as dichotomic but as dialectic – this is not to suggest that the two fields are mutually communicative, but rather that both can contribute to a cohesive, overarching worldview. In this respect, this thesis threads together the theological presupposition of a God of values with the naturalistic and material presuppositions of the modern scientific worldview (being cognizant of the fact that science may not necessarily be presented with these presuppositions). This dialectic occurs between two different but intertwined levels. One is the level of ethical systems; in this work, a particular understanding of Western Christian ethics. This level is framed by another, broader level of metaethics; in this thesis, an overarching understanding of the character of ethics will emerge from reflections on evolutionary theory and its naturalistic context. This will be a naturalistic view, though one which is understood to fit within a theological framework. Show less
The northwest corner of South America harbours a region of spectacular and mysterious landscapes called Pantepui. Due to its ancient age and fragmented topography Pantepui has been assumed to be an... Show moreThe northwest corner of South America harbours a region of spectacular and mysterious landscapes called Pantepui. Due to its ancient age and fragmented topography Pantepui has been assumed to be an ideal nursery of speciation, and tepuis (table mountains) have been seen as potential inland counterparts to oceanic islands. Tepuis are often called __islands in the sky__ and their summits seem indeed ideal candidates to harbour relict species, isolated from the rest of the world for millions of years. However our knowledge about the origin and diversification of the Pantepui biota is at least as fragmentary as the tepui physiography itself. This led some authors to consider the origin of local biodiversity and endemism a still-unresolved evolutionary enigma. This work aims to (1) better understand the species diversity, the evolutionary history, the dynamics of biotic interchanges between tepui summits, and the patterns of endemism of the fauna in the Pantepui region, using morphological analyses and molecular phylogenies of six amphibian and reptile taxa; (2) provide new insights in the timing of the geomorphological evolution of the tepuis in the light of amphibian and reptile species diversification inferred from molecular phylogeny reconstructions and estimates of divergence time. Show less
Natural zebra finch song contains heterogeneity in the relative distribution of element types across 13 populations worldwide, but compared between individuals it contains relatively little... Show moreNatural zebra finch song contains heterogeneity in the relative distribution of element types across 13 populations worldwide, but compared between individuals it contains relatively little structural constraints or rules in the order of elements. In contrast, from a perception point of view, zebra finches are able to detect differences in song structure and are able to learn rules to generalize these regularities to new element types in some instances, a hallmark of human language. This ability might seem conflicting with the absences of clear structural rules in their own natural songs, but it might be that these rule learning/detection mechanisms operate in a more general cognitive context, which has also been suggested for some mechanisms found in human artificial language learning. Show less
The evolution of Acehnese kingship is examined against the background of its relations with European traders and the tradingports in the region of the Malacca Straits. There are two defining... Show moreThe evolution of Acehnese kingship is examined against the background of its relations with European traders and the tradingports in the region of the Malacca Straits. There are two defining moments in the history of Aceh: first the arrival of the Portuguese in Malacca in 1511 which gave impetus to Aceh's rise as a local power. The dispelling of the Portuguese from Malacca was the constante in Aceh's policy. The second moment was the arrival of the northern Europen traders from 1599 onwards.European presence in the Straits and beyond profoundly impacted on the region's development.Fusion and fission were part of the changing geo-political scene of the period of this study.Aceh's dominance in politics and trade was the marked feature of the period 1599-1641. A military partnership with the Dutch,later the VOC,was a marked feature of the period examined. Although the two partners failed to meet their obligations and they quarrelled,ther relations continued. The conquest of Malacca in 1641 by the VOC happened without the actual help of Aceh. Aceh's powerful role diminished. Show less
Evolution and Interaction are two processes in Computer Science that are used in many algorithms to create, shape, find and optimize solutions to real world problems. Evolution has been very... Show moreEvolution and Interaction are two processes in Computer Science that are used in many algorithms to create, shape, find and optimize solutions to real world problems. Evolution has been very successfully applied as a pow-erful tool to solve complex search problems in fields ranging from physics, chemistry and biology all the way to commercial application such as aircraft fuselage design and civil engineering grading plans. Defining interaction is a big part of algorithm design. Not only defining the inputs and outputs of an algorithm but for a complex algorithm the interactions inside of an al- gorithm are as important. This thesis will concentrate on where Evolution overlaps Interaction. It will show how evolution can be used to evolve in- teraction, how the interaction inside an evolutionary algorithm impacts its performance and how an evolutionary algorithm can interact with humans. By touching on these three forms of overlap this thesis tries to give insight into the world of evolution and interaction 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
De negentiende eeuw was de eeuw van de vooruitgang. Vertegenwoordigers van het Nederlandse modernisme, een vrijzinnig-protestantse stroming, kozen ervoor het christelijk geloof aan de natuur- en... Show moreDe negentiende eeuw was de eeuw van de vooruitgang. Vertegenwoordigers van het Nederlandse modernisme, een vrijzinnig-protestantse stroming, kozen ervoor het christelijk geloof aan de natuur- en bijbelwetenschappelijke ontwikkelingen aan te passen. Ze vreesden dat het christendom anders voor veel mensen snel een gepasseerd station zou worden. God van vooruitgang laat zien hoe de modernen geloof en wetenschap met elkaar verenigden door bijvoorbeeld een __evolutietheologie__ te ontwerpen. Ook worden hun standpunten in maatschappelijke kwesties geanalyseerd. Daarbij staat het materiaal centraal dat zij voor een breed publiek gemaakt hebben, zoals romans, gedichten, prekenbundels en almanakken. Ook de problemen waarmee de modernen te kampen kregen worden besproken: de tegenstand van rechtzinnigen en vrijdenkers, het vertrek van vooraanstaande predikanten als Conrad Busken Huet en Allard Pierson en de praktische invulling van het moderne geloof. Show less
This thesis comprises elementary work on the evolution of ageing. The issue of ageing, and especially of starvation resistance, has been approached from both the environmental and the genetic sides... Show moreThis thesis comprises elementary work on the evolution of ageing. The issue of ageing, and especially of starvation resistance, has been approached from both the environmental and the genetic sides that are of relevance to the issue. Therewith, this study has a broad orientation, varying from ecophysiology to selection experiments, mutant analysis and sate of the art microarray gene expression analysis. All this work was performed on Drosophila melnogaster, the fruit fly, and was put in an integrative context with human ageing. Show less
The several hundred species of cichlid fish endemic to Lake Victoria (East-Africa) are textbook examples of explosive speciation. This thesis evaluates the hypothesis that sexual selection by... Show moreThe several hundred species of cichlid fish endemic to Lake Victoria (East-Africa) are textbook examples of explosive speciation. This thesis evaluates the hypothesis that sexual selection by female mate choice has contributed to this process of divergence, by investigating the mechanisms that drive the evolution and divergence of mating preferences for colour patterns. I studied two representative model systems, the highly polymorphic species Neochromis omnicaeruleus and the species pair Pundamilia nyererei and P. pundamilia. I used observational and experimental approaches in both laboratory and field. My work indicates that the interaction between sexual selection and habitat heterogeneity, in terms of photic environment and parasite exposure, can promote population divergence in male nuptial coloration and female preferences. In contrast, predation pressure and water turbidity may constrain the evolution and persistence of conspicuously coloured morphs and species. Show less
The aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs... Show moreThe aim of the studies described in this thesis was to investigate the genome organization of rodent malaria parasites (RMPs) and compare the organization and gene content of the genomes of RMPs and the human malaria parasite P. falciparum. The release of the complete genome sequence of P. falciparum and partial genome sequences of three RMPs (Plasmodium yoelii - Chapter 3; Plasmodium berghei and Plasmodium chabaudi - Chapter 4) enabled us to expand the analysis to a genome-wide survey. By aligning the RMP contigs against the P. falciparum genome, a composite RMP genome was constructed, which was subsequently compared in detail with the P. falciparum genome (Chapter 5). These comparative analyses showed high levels of conservation in both genome organization and gene content (~85%), supporting the use of RMPs as models for human malaria infection. P. falciparum-specific genes located in both subtelomeric and core regions of the chromosomes were also found and included many genes involved in host-parasite interactions, such as host cell invasion and evasion of the human immune response. Finally, reverse genetics approaches were used to study the function of certain genes that are conserved between the rodent and human malaria parasites (Chapters 6 & 7). Show less
Research described in this thesis focused on biological, ecological and evolutionary aspects of Arbuscular Mycorrhizal Fungi (AMF), and in particular of the family Gigasporaceae (Gigaspora and... Show moreResearch described in this thesis focused on biological, ecological and evolutionary aspects of Arbuscular Mycorrhizal Fungi (AMF), and in particular of the family Gigasporaceae (Gigaspora and Scutellospora, genera). This study had two major objectives. The first objective was to obtain better knowledge about the life history strategies (LHS) of Gigasporaceae, and the second objective was to study the intragenomic polymorphism of the ribosomal rDNA copies in order to understand its origin and to test the use of such polymorphism to discriminate between closely related species. The LHS patterns observed for the Gigasporaceae species studied suggests that they behave like K-strategists, i.e. organisms adapted to live at stable and predictable environments, as compared to Glomeraceae species that form single spores in the soil. Based on LHS patterns of Gigasporaceae an hypotheses that those species will be negatively selected in disturbed ecosystems have been formulated. Although intraspecific rDNA polymorphism in Gigasporaceae has been previously reported, this study, for the first time, systematically describes this heterogeneity and analyses this phenomenon with respect to Gigasporaceae phylogeny and evolution. It has been demonstrated that the intragenomic polymorphism of the rDNA copies can be used to differentiate species and in the case of Gigaspora even isolates. The phylogenetic analysis of inter and intragenomic rDNA polymorphism of closely related Gigaspora species strongly suggested that reticulated evolution, characterized by occasional hybridization or horizontal gene transfer between two species, played a significant role in evolution of this asexual group of fungi, via parasexual recombination. In addition, a molecular method was developed to assess Gigasporaceae diversity in environmental samples. Show less
The thesis describes the design and evolution of echolocation in the South and Southeast Asian Swiftlets. It starts explaining the molecular phylogenetics of Swiftlets, which is used in subsequent... Show moreThe thesis describes the design and evolution of echolocation in the South and Southeast Asian Swiftlets. It starts explaining the molecular phylogenetics of Swiftlets, which is used in subsequent chapters. Echolocation calls and social vocalisations of Swifts are compared between species and with non-echolocating Swifts and Swiftlets. The following chapters treat potential morphological adaptations in the echolocation system, i.e. in the syrinx, ear, and brain. The final chapters discuss the biogeography of the Swiftlets and integrate the results into an overall hypothesis on the evolution of Swiftlets and their echolocation system. Show less