Human handedness is likely related to brain lateralization and major cognitive innovations in human evolution. Identifying handedness in the archaeological record is, therefore, an important step in understanding our cognitive evolution. This thesis reports on experiments in identifying knapper handedness in lithic debitage. I conducted a blind study on flakes (n=631) from Acheulean handaxes replicated by right- and left-handed flintknappers. Several flake characteristics significantly indicated handedness, with a binary logistic regression correctly predicting handedness for 71.7% of the flakes. However, other characteristics were not associated with handedness. This is a result of personal knapping styles, as additional analyses show that individual knappers associate with some attributes better than handedness does. Continued work on these methodologies will enable analysis of Paleolithic assemblages in the future, with the ultimate goal of tracking population-level hominid handedness rates through time and using them as a proxy for cognitive evolution and language acquisition. / Includes bibliography. / Thesis (M.A.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

Brain injury is a serious clinical problem. The success of recovery from brain injury involves functional compensation in the affected brain area. We are interested in general mechanisms that underlie compensatory plasticity after brain damage, particularly when multiple brain areas or multiple modalities are included. In this thesis, I studied the function of auditory cortex after recovery from neonatal midbrain damage as a model system that resembles patients with brain damage or sensory dysfunction. I addressed maladaptive changes of auditory cortex after invasion by ectopic visual inputs. I found that auditory cortex contained auditory, visual, and multisensory neurons after it recovered from neonatal midbrain damage (Mao et al. 2011). The distribution of these different neuronal responses did not show any clustering or segregation. As might be predicted from the fact that auditory neurons and visual neurons were intermingled throughout the entire auditory cortex, I found that residual auditory tuning and tonotopy in the rewired auditory cortex were compromised. Auditory tuning curves were broader and tonotopic maps were disrupted in the experimental animals. Because lateral inhibition is proposed to contribute to refinement of sensory maps and tuning of receptive fields, I tested whether loss of inhibition is responsible for the compromised auditory function in my experimental animals. I found an increase rather than a decrease of inhibition in the rewired auditory cortex, suggesting that broader tuning curves in the experimental animals are not caused by loss of lateral inhibition. These results suggest that compensatory plasticity can be maladaptive and thus impair the recovery of the original sensory cortical function. The reorganization of brain areas after recovery from brain damage may require stronger inhibition in order to process multiple sensory modalities simultaneously. These findings provide insight into compensatory plasticity after sensory dysfunction and brain damage and new information about the role of inhibition in cross-modal plasticity. This study can guide further research on design of therapeutic strategies to encourage adaptive changes and discourage maladaptive changes after brain damage, sensory/motor dysfunction, and deafferentation.

<p>Fossil taxa are crucial to studies of brain evolution, as they allow us to identify evolutionary trends in relative brain size and brain shape that may not otherwise be identifiable in comparative studies using only extant taxa, owing to multiple events of parallel encephalization among primate clades. This thesis combines indirect and direct approaches to understanding primate evolution, by evaluating variation in the endocranial morphology of extant primates and their fossil representatives. I use a comparative approach to examine the relationships between interspecific adult endocranial volume and shape, and brain evolution and cranial form among extant primate clades and their fossil representatives. The associations are evaluated via phylogenetically informed statistics perfomed on volumetric measurements and three-dimensional geometric morphometric analyses of virtual endocasts constructed from micro-CT scans of primate crania. Fossil taxa included in these analyses are: 1) anthropoids Parapithecus, Aegyptopithecus (Early Oligocene, Egypt), Homunculus and Tremacebus (Early Miocene, Argentina), and 2) Eocene euprimates Adapis and Leptadapis (Eocene adapoids, France), and the Rooneyia (Eocene omomyoid, Texas). </p><p>The first part of this work (Chapter 2) explores variation in residual mass of brain components (taken from the literature) among primates, and evaluates the correlated evolution of encephalization and brain proportions with endocast shape, quantified via three-dimensional geometric morphometric techniques. Analyses reveal a broad range of variation in endocast shape among primates. Endocast shape is influenced by a complex array of factors, including phylogeny, body size, encephalization, and brain proportions (residual mass of brain components). The analysis supports previous research, which concludes that anthropoids and tarsiers (Haplorhini) share the enlargement of several key brain regions including the neocortex and visual systems, and a reduction of the olfactory system. Anthropoids further differ from strepsirrhines in endocranial features associated with encephalization--a more flexed brain base, an inferiorly deflected olfactory fossa--and those associated with brain proportions--a small olfactory fossa, and a more caudally extended cerebrum that extends posteriorly past the cerebellar poles. Tarsiers are unique in having a mediolaterally broad and rostro-caudally short endocast with an attenuated anterior and middle cranial fossae. This morphology is likely related to the extreme orbital enlargement in this taxon, which limits anterior expansion of the endocranium. Finally, despite the correlation between residual endocranial volume and endocast shape among modern primates, early anthropoid fossils demonstrate a disconnect between these factors in sharing key features of endocast shape with extant anthropoids at a relatively small brain size. </p><p>The second part of this thesis (Chapter 3) explores the relationship between craniofacial organization--cranial base angle, facial size, facial hafting--and encephalization via the lens of the Spatial Constraints and Facial Packing Hypotheses. These hypotheses predict that interspecific adult variation in encephalization correlates with endocranial shape such that a larger brain for a given body size will be more "globular" or spherical in shape. These hypotheses futher predict that basicranial angle covaries with encephalization and that the relative size of the endocranium and facial skeleton will have an antagonistic effect on basicranial angle and facial hafting. Results show that various measures of globularity have inconsistent and weak relationships to phylogeny, encephalization, and basicranial flexion, owing to a diversity of clade-specific scaling patterns between the maximum length, breadth, and width of the endocast. Among extant primates, there is weak but significant evidence to suggest that both facial size and encephalization influence variation in basicranial flexion. Considering the fossil specimens in isolation, their relative ranks in encephalization, basicranial flexion, and midline facial size and shape follow the pattern expected from the Spatial and Facial Packing Hypotheses outlined above; however, relative to modern species, the early fossil anthropoids have more flexed cranial bases and shorter facial skeletons at much smaller level of encephalization than seen in modern anthropoids. </p><p>Together, the extant data suggest a moderately conserved pattern of correlated evolution among endocranial size, endocranial shape, brain proportions, and craniofacial organization, which may explain differences in endocranial and facial shape between extant strepsirrhine and anthropoid primates; however, the fossil record for early anthropoid evolution demonstrates that a shift towards key anthropoid-like traits of the endocranium, basicranium, and facial skeleton were initiated early in anthropoid evolution, with subsequent encephalization occurring within and among members of this clade. Thus, these anthropoid cranial traits evolved in tandem with changes in the relative size of brain components, rather than absolute or relative brain size alone. Basicranial flexion, facial length and orientation are influenced by both: 1) shifts in endocranial shape associated with changes in brain proportion--accounting for the initiation of the anthropoid-like craniofacial plan early in the evolution of the clade--and 2) encephalization, which influenced subsequent morphological divergence among extant anthropoid groups.</p> / Dissertation

The social brain hypothesis predicts that larger group size and greater social complexity select for increased brain size. In ants, social complexity is associated with large colony size, emergent collective action, and division of labor among workers. The great diversity of social organization in ants offers numerous systems to test social brain theory and examine the neurobiology of social behavior. My studies focused on the Australasian weaver ant, Oecophylla smaragdina, a polymorphic species, as a model of advanced social organization. I critically analyzed how biogenic amines modulate social behavior in ants and examined their role in worker subcaste-related territorial aggression. Major workers that naturally engage in territorial defense showed higher levels of brain octopamine in comparison to more docile, smaller minor workers, whose social role is nursing. Through pharmacological manipulations of octopaminergic action in both subcastes, octopamine was found to be both necessary and sufficient for aggression, suggesting subcaste-related task specialization results from neuromodulation. Additionally, I tested social brain theory by contrasting the neurobiological correlates of social organization in a phylogenetically closely related ant species, Formica subsericea, which is more basic in social structure. Specifically, I compared brain neuroanatomy and neurometabolism in respect to the neuroecology and degree of social complexity of O. smaragdina major and minor workers and F. subsericea monomorphic workers. Increased brain production costs were found in both O. smaragdina subcastes, and the collective action of O. smaragdina majors appeared to compensate for these elevated costs through decreased ATP usage, measured from cytochrome oxidase activity, an endogenous marker of neurometabolism. Macroscopic and cellular neuroanatomical analyses of brain development showed that higher-order sensory processing regions in workers of O. smaragdina, but not F. subsericea, had age-related synaptic reorganization and increased volume. Supporting the social brain hypothesis, ecological and social challenges associated with large colony size were found to contribute to increased brain size. I conclude that division of labor and collective action, among other components of social complexity, may drive the evolution of brain structure and function in compensatory ways by generating anatomically and metabolically plastic mosaic brains that adaptively reflect cognitive demands of worker task specialization and colony-level social organization.

No description available.

L'objectif de mon projet de recherche était de faire le lien entre structures cérébrales et fonctions, pour mieux comprendre les bases de la cognition. La première partie de ma thèse a été de développer des tests comportementaux pour analyser la cognition et ses fondamentaux. Les résultats suggèrent fortement que les téléostéens possèdent des fonctions exécutives semblables à celles des mammifères. J’ai par la suite cherché le substrat anatomique de ces capacités cognitives nouvellement mises à jour chez cette espèce, notamment dans le pallium (équivalent du cortex cérébral des mammifères). Cependant la neuroanatomie du poisson zèbre adulte est mal connue, car il est souvent utilisé au stade larvaire. Une seconde partie de mon travail a cherché à analyser et identifier l'origine développementale des structures cérébrales adultes. Nous avons découvert que certaines structures considérées jusqu'ici comme faisant partie du cerveau antérieur (prosencéphale) font en fait partie du cerveau médian (mésencéphale) chez le poisson zèbre. L’une de ces structures est le lobe inférieur, précédemment considéré comme hypothalamique. Une autre structure est le noyau préglomérulaire, le noyau sensoriel relais majeur et analogue fonctionnel du thalamus. Cette voie sensorielle contient la principale voie visuelle vers le pallium. Ainsi, même si certaines structures ont la même fonction, elles peuvent avoir une origine évolutive et développementale différente des structures connues chez les mammifères. En résumé, des fonctions similaires ont évolué indépendamment chez les amniotes et les téléostéens. Ce travail élargit ainsi les champs d'application pour la recherche en neurosciences, et permet d'approcher les fondamentaux de la cognition de manière nouvelle par l'identification des structures essentielles à l'émergence d'une cognition de haut niveau telle qu'elle est observée dans l'espèce humaine. / The aim of my research project was to link brain structures and functions, to better understand the fundamental bases of cognition. The first part of my thesis consisted in the development of behavioral tests to analyze the essential principles of cognition. The results strongly suggest the existence of executive functions in teleosts similar to those of mammals. Then I looked for the anatomical structures responsible for these cognitive capacities, in particular in the pallium (equivalent of the mammalian cerebral cortex). However, little is known about adult zebrafish neuroanatomy. Indeed, zebrafish is often studied at larval stage. A second part of my work aimed at studying adult structures in more detail through their developmental origin. This has redefined some parts of the brain. We have discovered that some of the structures that were considered as part of the forebrain (prosencephalon) are actually part of the midbrain (mesencephalon) in zebrafish. This includes the inferior lobe, previously classified as hypothalamus. Another structure is the major sensory relay nucleus, the preglomerular nucleus, functional analogue of the thalamus (part of the forebrain) in amniotes. This sensory pathway contains the main visual pathway to the pallium. Thus, even if some structures have the same function, they may have an evolutionary and developmental origin different from structures known in mammals. In summary, similar functions have independently evolved in amniotes and teleosts. This comparative work adds new perspectives for neuroscience research. It also allows us to approach the fundamentals of cognition in a new way: what are the essential building blocks for a higher level of cognition like the human one?

Although the human brain has been studied over past decades at morphological and histological levels, much remains unknown about its molecular and genetic mechanisms. Furthermore, when compared with our closest relative the chimpanzee, the human brain strikingly shows great morphological changes that have been often associated with our cognitive specializations and skills. Nevertheless, such drastic changes in the human brain may have arisen not only through morphological changes but also through changes in the expression levels of genes and transcripts. Gene regulatory networks are complex and large-scale sets of protein interactions that play a fundamental role at the core of cellular and tissue functions. Among the most important players of such regulatory networks are transcription factors (TFs) and the transcriptional circuitries in which TFs are the central nodes. Over past decades, several studies have focused on the functional characterization of brain-specific TFs, highlighting their pathways, interactions, and target genes implicated in brain development and often disorders. However, one of the main limitations of such studies is the data collection which is generally based on an individual experiment using a single TF. To understand how TFs might contribute to such human-specific cognitive abilities, it is necessary to integrate the TFs into a system level network to emphasize their potential pathways and circuitry. This thesis proceeds with a novel systems biology approach to infer the evolution of these networks. Using human, chimpanzee, and rhesus macaque, we spanned circa 35 million years of evolution to infer ancestral TF networks and the TF-TF interactions that are conserved or shared in important brain regions. Additionally, we developed a novel method to integrate multiple TF networks derived from human frontal lobe next-generation sequencing data into a high confidence consensus network. In this study, we also integrated a manually curated list of TFs important for brain function and disorders. Interestingly, such “Brain-TFs” are important hubs of the consensus network, emphasizing their biological role in TF circuitry in the human frontal lobe. This thesis describes two major studies in which DNA microarray and RNA-sequencing (RNA-seq) datasets have been mined, directing the TFs and their potential target genes into co-expression networks in human and non-human primate brain genome-wide expression datasets. In a third study we functionally characterized ZEB2, a TF implicated in brain development and linked with Mowat-Wilson syndrome, using human, chimpanzee, and orangutan cell lines. This work introduces not only an accurate analysis of ZEB2 targets, but also an analysis of the evolution of ZEB2 binding sites and the regulatory network controlled by ZEB2 in great apes, spanning circa 16 million years of evolution. In summary, those studies demonstrated the critical role of TFs on the gene regulatory networks of human frontal lobe evolution and functions, emphasizing the potential relationships between TF circuitries and such cognitive skills that make humans unique.

During the last years, important progress has been made in modeling early brain development using 3-dimensional in vitro systems, so-called cerebral organoids. These can be grown from pluripotent stem cells of different species such as our closest living relatives, the chimpanzees and from patients carrying disease mutations that affect brain development. This offers the possibility to study uniquely human features of brain development as well as to identify gene networks altered in neurological diseases. Profiling the transcriptional landscape of cells provides insights into how gene expression programs have changed during evolution and are affected by disease. Previously, studies of this kind were realized using bulk RNA-sequencing, essentially measuring ensemble signals of genes across potentially heterogeneous populations and thus obscured subtle changes with respect to transient cell states or cellular subtypes. However, remarkable advances during the last years have enabled researchers to profile the transcriptomes of single cells in high throughput. This thesis demonstrates how single-cell transcriptomics can be used to dissect human-specific features of the developing and adult brain as well as cellular subpopulations dysregulated in a malformation of the cortex.

What selective forces and molecular mechanisms govern the integration of worker body size and morphology, brain architecture, and behavior in insect societies? Workers of the remarkably polyphenic and socially complex fungus-growing leafcutter ant Atta cephalotes exhibit a striking agricultural division of labor. The number of morphologically distinct and behaviorally differentiated worker groups, adaptive mosaic neural phenotypes, and brain transcriptomes have not been examined and the influences of socioecological challenges on behavioral performance, cognition, and brain evolution are unclear. We quantified worker morphological and behavioral variation to assess the number of worker size classes and characterized their social roles. We discriminated multiple worker size groups using a Gaussian mixture model: mid-sized workers (“medias”) had the most diverse task repertories and serve dominant roles in leaf harvesting, whereas workers of other size classes performed fewer, more specialized behaviors. We used variation among tasks in sensorimotor functions and task performance frequencies to create an estimate of sensory integration and processing demands across worker size groups. This metric predicted that medias require the greatest neural investment due to the high diversity of sensory inputs and motor functions associated with their task set. We quantified the volumes of key neuropils in brains of workers of different sizes and determined their allometries, finding that our estimate corresponded to proportional investment in the mushroom bodies, a brain compartment responsible for learning, memory, and sensory integration, and identifying allometric scaling patterns in other brain centers. Additionally, we measured whole-brain gene expression and identified significant differences in expression levels for numerous genes likely to underpin behavior. Differences were most pronounced between the smallest (fungal gardener “minims”) and largest (defensive “majors”), although not all expression differences were driven by worker size. Overrepresented gene functional categories included those related to sensory processing (enriched in genes upregulated in medias and minims) and metabolism (enriched in genes upregulated in majors). These results identify the nature of selective forces favoring differentiation along morphological, neuroanatomical, behavioral, and molecular axes among A. cephalotes workers and the impact of advanced division of labor on brain evolution. / 2023-03-01T00:00:00Z

Modern humans, archaic humans and great apes are genetically closely related and share many behavioral and anatomical similarities. However, modern humans differ from the others by a fast development of complex culture and technologies, that rely on complex cognitive abilities. Cognition is directly linked to brain structure and neuronal function. In this thesis, I study neuronal differences between humans and chimpanzees and bonobos as well as morphological differences of “ancestralized” and “modernized” human neurons, that could possibly contribute to cognitive differences among the different hominid species. The comparison of human and ape induced pluripotent stem cell-derived neurons (iNeurons) revealed that the human neurons mature transcriptionally, morphologically and functionally slower than their ape counterparts. By injecting the mRNA of 16 genes that are relevant for neuronal function and carry amino acid substitutions on the modern human lineage, I could show that the 16 proteins are able to increase the total neurite length and suggest a potential slower development of neurons injected with the modern human variants. In a single gene approach, I investigated the effect of modern and ancestral human SSH2 variants on neurite outgrowth and found differences in neurite length and branching pattern, making SSH2 a promising candidate for being involved in human neuron-specific morphology. I showed that iNeurons can serve as a model system for evolutionary neurobiology. I gained insights into features of neurons that are unique to modern humans in comparison to their closest relatives, the great apes and archaic humans.:BIBLIOGRAPHISCHE DARSTELLUNG 2 TABLE OF CONTENTS 3 1. THESIS SUMMARY 6 COMPARISON OF HUMAN AND APE INDUCED NEURONS 7 MICROINJECTION AS A TOOL TO STUDY RECENT HUMAN HISTORY 8 MODELING THE EFFECT OF A SINGLE GENE BY USING TRANSFECTION OF PRIMARY NEURONS 9 CONCLUSION 10 2. ZUSAMMENFASSUNG 11 VERGLEICH VON NERVENZELLEN VON MENSCHEN UND MENSCHENAFFEN 12 MIKROINJEKTION ZUR UNTERSUCHUNG DER JÜNGSTEN MENSCHLICHEN VERGANGENHEIT 14 MODELLIERUNG DES EFFEKTS EINES EINZELNEN GENS AUF DAS NEURITEN WACHSTUM VON PRIMÄREN NEURONEN 15 FAZIT 16 3. INTRODUCTION 17 3.1 THE HOMINID FAMILY 17 3.2 THE HOMINID BRAIN 19 3.3 THE INEURON MODEL SYSTEM 23 3.4 MICROINJECTION OF INS: A TOOL TO STUDY ANCIENT AND MODERN HUMAN NEURONS 24 4. MATERIAL AND METHODS 27 4.1 METHODS 27 4.1.1 GENERATION OF RTTA/NGN2-POSITIVE PLURIPOTENT STEM CELL LINES 27 4.1.2 CULTURING OF PLURIPOTENT STEM CELL LINES 27 4.1.3 CRYOPRESERVATION OF PLURIPOTENT STEM CELLS 28 4.1.4 DIFFERENTIATION OF RTTA/NGN2-POSITIVE PLURIPOTENT STEM CELLS TO INEURONS 28 4.1.5 SINGLE CELL TRANSCRIPTOMIC ANALYSIS 29 4.1.5.1 SINGLE CELL RNA-SEQ DATA GENERATION 29 4.1.5.2 DATA PROCESSING 30 4.1.5.3 IDENTIFICATION OF NEURONAL CELLS AND DIFFERENTIALLY EXPRESSED GENES 30 4.1.5.4 GENE ONTOLOGY ENRICHMENT ANALYSIS 31 4.1.6 ELECTROPHYSIOLOGY 32 4.1.6.1 RECORDINGS 33 4.1.6.2 ANALYSIS 33 4.1.7 LIPOFECTION OF INEURONS 34 4.1.8 IMMUNOSTAINING OF INEURONS 34 4.1.8.1 PREPARATION OF PARAFORMALDEHYDE FIXATIVE 34 4.1.8.2 FIXATION OF GFP-LABELLED INEURONS 34 4.1.8.3 QUENCHING AND IMMUNOSTAINING OF GFP-LABELLED INEURONS 35 4.1.9 IMAGE ACQUISITION 35 4.1.10 IMAGE QUANTIFICATION 35 4.1.10.1 QUANTIFICATION OF NEURONAL MORPHOLOGY. 35 4.1.10.2 QUANTIFICATION OF TUJI SIGNAL. 36 4.1.11 ASSIGNMENT OF CELL IDENTITY. 36 4.1.12 MICROINJECTION 36 4.13 TRANSFECTION OF PRIMARY NEURONS WITH SSH2 PLASMIDS 40 4.1.3.1 CELL CULTURE 40 4.1.3.2 TRASFECTION 40 4.2 MATERIALS 41 5. RESULTS 48 5.1 COMPARISON OF INDUCED NEURONS REVEALS A SLOWER STRUCTURAL AND FUNCTIONAL MATURATION IN HUMANS THAN IN APES 48 5.1.1 ABSTRACT 49 5.1.2 INTRODUCTION 49 5.1.3 RESULTS 51 5.1.3.1 MATURATION OF HUMAN AND APE INDUCED NEURONS IN VITRO 51 5.1.3.2 MORPHOLOGICAL HETEROGENEITY IN IN POPULATIONS 53 5.1.3.3 MORPHOLOGICAL MATURATION OF APE AND HUMAN INS 55 5.1.3.4 SCRNASEQ REVEALED THAT NGN2 INDUCES CORTICAL AND SENSORY NEURON FATES 56 5.1.3.5 NGN2 ALSO INDUCES CORTICAL SENSORY NEURON FATE 59 5.1.3.6 TRANSCRIPTIONAL MATURATION OF HUMAN AND CHIMPANZEE INS 60 5.1.3.7 INTRINSIC PASSIVE ELECTROPHYSIOLOGICAL PROPERTIES OF HUMAN AND APE INS 62 5.1.3.8 ACTIVE ELECTROPHYSIOLOGICAL PROPERTIES OF APE AND HUMAN INS 63 5.1.4 DISCUSSION 65 5.1.4.1 NGN2 INDUCES HETEROGENEOUS NEURONAL FATES 65 5.1.4.2 EVOLUTIONARY ASPECTS OF NEURONAL MATURATION 65 5.5. SUPPLEMENTARY INFORMATION 68 5.5.1 SUPPLEMENTARY FIGURES 68 5.5.2 SUPPLEMENTARY TABLES 81 5.2 MRNA MICROINJECTION AS A TOOL TO STUDY RECENT HUMAN BRAIN EVOLUTION 88 5.2.1 ABSTRACT 89 5.2.2 INTRODUCTION 89 5.2.3 RESULTS 91 5.2.3.1 NEURONAL GENES CARRYING AMINO ACID SUBSTITUTIONS BETWEEN MODERN AND ARCHAIC HUMANS 91 5.2.3.2 SCREEN OF DISTINCT TRANSCRIPTOME DATASETS FOR EXPRESSION ANALYSES OF THE 16 NEURONAL GENES 94 5.2.3.3 TRANSCRIPTIONAL ANALYSES OF THE 16 NEURONAL GENES IN INEURONS 97 5.2.3.4 MICROINJECTION OF THE 16 NEURONAL GENES INTO INEURONS 99 5.2.3.5 EFFECT OF SSH2 GENE VARIANTS ON HUMAN PRIMARY NEURONS 101 5.2.4. DISCUSSION 103 6. DISCUSSION 108 6.1 COMPARISON OF HUMAN AND APE INDUCED NEURONS 108 6.2 EXPERIMENTAL SYSTEMS TO MODEL RECENT HUMAN HISTORY 109 6.3 MRNA MICROINJECTION TO MODEL MULTIGENIC HUMAN TRAITS 110 6.4 MODELING THE EFFECT OF A SINGLE GENE BY USING TRANSFECTION OF PRIMARY NEURONS 111 6.5 CONCLUDING REMARKS 111 INDEX OF FIGURES 113 SUPPLEMENTARY FIGURES 113 INDEX OF TABLES 114 SUPPLEMENTARY TABLES 114 REFERENCES 115 SOFTWARE AND SCRIPTS 128 ACKNOWLEDGEMENTS 129 CURRICULUM VITAE 130 PUBLICATIONS 133 SELECTED TALKS 134 POSTER PRESENTATIONS 134 SELBSTÄNDIGKEITSERKLÄRUNG 135