Striving for the Impossible : The Hegelian background of Judith Butler

This study analyses the Hegelian roots of the subject-theory and the political theory of Judith Butler. Butler can be seen as the author of "gender performativity". Butler claims that subject's identities are linquistic "terms". Linquistic identities are performative and normative: they produce, according to cultural rules, the identities which they just claim to describe. Butler's theory of the performativity of identities is based on her theory of identities as "ek-static" constructions. This means that there is a relation between the self and the Other in the heart of identities. It is claimed in this study that Butler's theory of the relation between the self and the Other, or, between the subject and the constitutive outside, is based on G.W.F. Hegel's theory of the dialectics of recognition in The Phenomenology of Spirit. Especially the sections dealing with the relation between "Lord" and "Bondsman" set the theoretical base for Butler's theory. Further, it is claimed that Hegel's own solution for the enslaving and instrumentalizing relation between the self and the Other, reciprocal recognition, remains an important alternative to the postmodernist conception supported by political theorists like Butler. Chapter 2, on Hegel, goes through the dialectics of recognition between the self and the Other in The Phenomenology of Spirit up until the ideal of reciprocal recognition and absolute knowledge. Chapter 3 introduces two French interpretations of Hegel, by Alexandre Kojéve and Louis Althusser. Both of these interpretations, especially the Kojevian one, have deeply influenced the contemporary understanding of Hegel as well as the contemporary thought - presented e.g. in the postmodern political thought - on the relations between the self and the Other. The Kojévian Marxist utopia with its notion of "the End of History" as well as the Althusserian theory of the Interpellative formation of subjects have influenced how Hegel's theory of the self and the Other have travelled into Butler's thought. In chapter 5 these influences are analyzed in detail. According to the analysis, Butler, like numerous other poststructuralist theorists, accepts Kojéve's interpretation as basically correct, but rejects his vision of "the End of History" as static and totalitarian. Kojéve's utopian philosophy of history is replaced by the paradoxical idea of an endless striving towards emancipation which, however, could not and should not be reached. In chapter 6 Butler's theory is linked to another postmodern political theory, that of Chantal Mouffe. It is argued that Mouffe's theory is based on a similar view of the relation of the self and the other as Butler's theory. The former, however, deals explicitly with politics. Therefore, it makes the central paradox of striving for the impossible more visible; such a theory is unable to guide political action. Hegel actually anticipated this kind of theorizing in his critique of "Unhappy Consciousness" in the Phenomenology of Spirit. Keywords: Judith Butler, G.W.F. Hegel, Chantal Mouffe, Alexandre Kojéve, Postmodernism, Politics, Identities, Performativity, Self-consciousness, Other

Democratic Legitimacy and the Politics of Rights : A comparative analysis of the conceptual relationship between democracy and rights in contemporary political theories

Democratic Legitimacy and the Politics of Rights is a research in normative political theory, based on comparative analysis of contemporary democratic theories, classified roughly as conventional liberal, deliberative democratic and radical democratic. Its focus is on the conceptual relationship between alternative sources of democratic legitimacy: democratic inclusion and liberal rights. The relationship between rights and democracy is studied through the following questions: are rights to be seen as external constraints to democracy or as objects of democratic decision making processes? Are individual rights threatened by public participation in politics; do constitutionally protected rights limit the inclusiveness of democratic processes? Are liberal values such as individuality, autonomy and liberty; and democratic values such as equality, inclusion and popular sovereignty mutually conflictual or supportive? Analyzing feminist critique of liberal discourse, the dissertation also raises the question about Enlightenment ideals in current political debates: are the universal norms of liberal democracy inherently dependent on the rationalist grand narratives of modernity and incompatible with the ideal of diversity? Part I of the thesis introduces the sources of democratic legitimacy as presented in the alternative democratic models. Part II analyses how the relationship between rights and democracy is theorized in them. Part III contains arguments by feminists and radical democrats against the tenets of universalist liberal democratic models and responds to that critique by partly endorsing, partly rejecting it. The central argument promoted in the thesis is that while the deconstruction of modern rationalism indicates that rights are political constructions as opposed to externally given moral constraints to politics, this insight does not delegitimize the politics of universal rights as an inherent part of democratic institutions. The research indicates that democracy and universal individual rights are mutually interdependent rather than oppositional; and that democracy is more dependent on an unconditional protection of universal individual rights when it is conceived as inclusive, participatory and plural; as opposed to robust majoritarian rule. The central concepts are: liberalism, democracy, legitimacy, deliberation, inclusion, equality, diversity, conflict, public sphere, rights, individualism, universalism and contextuality. The authors discussed are e.g. John Rawls, Jürgen Habermas, Seyla Benhabib, Iris Young, Chantal Mouffe and Stephen Holmes. The research focuses on contemporary political theory, but the more classical work of John S. Mill, Benjamin Constant, Isaiah Berlin and Hannah Arendt is also included.

Human genetic variation in the Baltic Sea region: Features of population history and natural selection

In this thesis, the genetic variation of human populations from the Baltic Sea region was studied in order to elucidate population history as well as evolutionary adaptation in this region. The study provided novel understanding of how the complex population level processes of migration, genetic drift, and natural selection have shaped genetic variation in North European populations. Results from genome-wide, mitochondrial DNA and Y-chromosomal analyses suggested that the genetic background of the populations of the Baltic Sea region lies predominantly in Continental Europe, which is consistent with earlier studies and archaeological evidence. The late settlement of Fennoscandia after the Ice Age and the subsequent small population size have led to pronounced genetic drift, especially in Finland and Karelia but also in Sweden, evident especially in genome-wide and Y-chromosomal analyses. Consequently, these populations show striking genetic differentiation, as opposed to much more homogeneous pattern of variation in Central European populations. Additionally, the eastern side of the Baltic Sea was observed to have experienced eastern influence in the genome-wide data as well as in mitochondrial DNA and Y-chromosomal variation – consistent with linguistic connections. However, Slavic influence in the Baltic Sea populations appears minor on genetic level. While the genetic diversity of the Finnish population overall was low, genome-wide and Y-chromosomal results showed pronounced regional differences. The genetic distance between Western and Eastern Finland was larger than for many geographically distant population pairs, and provinces also showed genetic differences. This is probably mainly due to the late settlement of Eastern Finland and local isolation, although differences in ancestral migration waves may contribute to this, too. In contrast, mitochondrial DNA and Y-chromosomal analyses of the contemporary Swedish population revealed a much less pronounced population structure and a fusion of the traces of ancient admixture, genetic drift, and recent immigration. Genome-wide datasets also provide a resource for studying the adaptive evolution of human populations. This study revealed tens of loci with strong signs of recent positive selection in Northern Europe. These results provide interesting targets for future research on evolutionary adaptation, and may be important for understanding the background of disease-causing variants in human populations.

Novel CDNF/MANF protein family : Molecular structure, expression and neurotrophic activity

Neurotrophic factors (NTFs) are secreted proteins which promote the survival of neurons, formation and maintenance of neuronal contacts and regulate synaptic plasticity. NTFs are also potential drug candidates for the treatment of neurodegenerative diseases. Parkinson’s disease (PD) is mainly caused by the degeneration of midbrain dopaminergic neurons. Current therapies for PD do not stop the neurodegeneration or repair the affected neurons. Thus, search of novel neurotrophic factors for midbrain dopaminergic neurons, which could also be used as therapeutic proteins, is highly warranted. In the present study, we identified and characterized a novel protein named conserved dopamine neurotrophic factor (CDNF), a homologous protein to mesencephalic astrocyte-derived neurotrophic factor (MANF). Others have shown that MANF supports the survival of embryonic midbrain dopaminergic neurons in vitro, and protects cultured cells against endoplasmic reticulum (ER) stress. CDNF and MANF form a novel evolutionary conserved protein family with characteristic eight conserved cysteine residues in their primary structure. The vertebrates have CDNF and MANF encoding genes, whereas the invertebrates, including Drosophila and Caenorhabditis have a single homologous CDNF/MANF gene. In this study we show that CDNF and MANF are secreted proteins. They are widely expressed in the mammalian brain, including the midbrain and striatum, and in several non-neuronal tissues. We expressed and purified recombinant human CDNF and MANF proteins, and tested the neurotrophic activity of CDNF on midbrain dopaminergic neurons using a 6-hydroxydopamine (6-OHDA) rat model of PD. In this model, a single intrastriatal injection of CDNF protected midbrain dopaminergic neurons and striatal dopaminergic fibers from the 6-OHDA toxicity. Importantly, an intrastriatal injection of CDNF also restored the functional activity of the nigrostriatal dopaminergic system when given after the striatal 6-OHDA lesion. Thus, our study shows that CDNF is a potential novel therapeutic protein for the treatment of PD. In order to elucidate the molecular mechanisms of CDNF and MANF activity, we resolved their crystal structure. CDNF and MANF proteins have two domains; an amino (N)-terminal saposin-like domain and a presumably unfolded carboxy (C)-terminal domain. The saposin-like domain, which is formed by five α-helices and stabilized by three intradomain disulphide bridges, may bind to lipids or membranes. The C-terminal domain contains an internal cysteine bridge in a CXXC motif similar to that of thiol/disulphide oxidoreductases and isomerases, and may thus facilitate protein folding in the ER. Our studies suggest that CDNF and MANF are novel potential therapeutic proteins for the treatment of neurodegenerative diseases. Future studies will reveal the neurotrophic and cytoprotective mechanisms of CDNF and MANF in more detail.

Golgi proteomics : Identification of a novel cartilage-specific Golgi protein GoPro49

The Golgi complex is a central organelle of the secretory pathway, responsible for a range of post-translational modifications, as well as for membrane traffic to the plasma membrane and to the endosomal-lysosomal pathway. In addition, this organelle has roles in cell migration, in the regulation of traffic, and as a mitotic check point. The structure of the Golgi complex is highly dynamic and able to respond to the amount of cargo being transported and the stage of the cell cycle. The Golgi proteome reflects the functions and structure of this organelle, and can be divided into three major groups: the Golgi resident proteins (e.g. modification enzymes), the Golgi matrix proteins (involved in structure and tethering events), and trafficking proteins (e.g. vesicle coat proteins and Rabs). The Golgi proteome has been studied on several occasions, from both rat liver and mammary gland Golgi membranes using proteomic approaches, but still little more than half of the estimated Golgi proteome is known. Nevertheless, methodological improvements and introduction of shotgun proteomics have increased the number of identified proteins, and especially the number of identified transmembrane proteins. Cartilage, even though not a typical tissue in which to study membrane traffic, secretes large amounts of extracellular matrix proteins that are extensively modified, especially by amino acid hydroxylation, glycosylation and sulfation. Furthermore, the cartilage ECM contains several, large oligomeric proteins (such as collagen II) that are difficult to assemble and transport. Indeed, cartilage has been shown to be susceptible to changes both in secretory pathway (e.g. the COPII coat assembly) and in post-translational modifications (e.g. heparan sulfate formation). Dental follicle, and the periodontal ligament (PDL) that it forms, are another type of connective tissue, and they have a role in anchoring teeth to bone. This anchorage is achieved by numerous matrix fibres that connect the bone matrix with the cementum. These tissues have in common the secretion of large matrix molecules. In this study the Golgi proteome was analysed from purified, stacked Golgi membranes isolated from rat liver. The identified, extensive proteome included a protein similar to Ab2-095, or Golgi protein 49kDa (GoPro49), which was shown to localise to the Golgi complex as an EGFP fusion protein. Surprisingly, in situ hybridisation showed the GoPro49 expression to be highly restricted to different mesenchymal tissues, especially in cartilage, and this expression pattern was clearly developmentally regulated. In addition to cartilage, GoPro49 was also expressed in the dental follicle, but was not observed in the mature PDL. Importantly, GoPro49 is the first specific marker for the dental follicle. Endogenous GoPro49 protein co-localised with β-COP in both chondrosarcoma and primary dental follicle cell lines. The COPI staining in these cells was highly dynamic, showing a number of tubules. This may reflect the type of secretory cargo they secrete. Currently GoPro49 is the only Golgi protein with such a restricted expression pattern.