On the Thermodynamic Solvation of Biomolecules in Solution

The topic solvation thermodynamics is an important aspect of chemistry, dealing with the effects introduced by solvents onto solutes. In particular, biological systems are highly heterogeneous in their choice of solvent typically characterized by either being in a polar or non-polar environment. For example, the cytoplasm of cells constituting the internal environment of cells is an aqueous solvent, whereas the membrane, being the boundary separating the cells from its surroundings, is an example of a lipid solvent. In addition to the main solvent, the majority of biological solvents also contain co-solvents such as ions, including ATP which can be found to be on the ~10 mM cellular concentration scale, or monovalent ions such as potassium, sodium, chloride, and not to forget free amino acids. While the previously mentioned examples are important in their own regards for oxidative phosphorylation, nerve cell communication, and construction of proteins respectively, to mention a few examples, their role as co-solvents can also greatly affect the stability and solubility of molecular matter.In this work, we will investigate the properties underlying the solvation of molecular matter utilizing statistical thermodynamics and molecular simulations. In specific by using molecular simulations we can determine atomistic properties for systems of interest, and via statistical thermodynamics relate these properties to experimental observables. These observables may either be mechanical properties addressing the behavior of molecular matter at a given state, or they may be state functions that describe the changes in energetics and entropy for the molecular matter changing. Within solvation thermodynamics, one of the most important state functions is the chemical potential and highly related solvation free energy describing the free energy of adding a solute particle to the system and thus quantifies the reversible work between the solute and solvent upon introducing the particle, and thus multiple methods are discussed how to obtain this quantity.The findings of the presented research include among others reflections upon the solubility of salt bridges in proteins, and counter-intuitive cation-cation enthalpic attraction due to changes in ion solvations induced via a host molecule. Furthermore, the research also addresses the regulation of co-solvent-induced aggregation. Last, but not least, the total thermodynamic decomposition of caffeine solvation in electrolyte solutions, utilizing energy-representation theory of solvation to unveil the mechanism of anion-specific processes, and demonstrating the capabilities of the method to unlock solvation properties to optimize and rationally design future systems

Changes in Purkinje cell firing and gene expression precede behavioral pathology in a mouse model of SCA2.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited disorder, which is caused by a pathological expansion of a polyglutamine (polyQ) tract in the coding region of the ATXN2 gene. Like other ataxias, SCA2 most overtly affects Purkinje cells (PCs) in the cerebellum. Using a transgenic mouse model expressing a full-length ATXN2(Q127)-complementary DNA under control of the Pcp2 promoter (a PC-specific promoter), we examined the time course of behavioral, morphologic, biochemical and physiological changes with particular attention to PC firing in the cerebellar slice. Although motor performance began to deteriorate at 8 weeks of age, reductions in PC number were not seen until after 12 weeks. Decreases in the PC firing frequency first showed at 6 weeks and paralleled deterioration of motor performance with progression of disease. Transcription changes in several PC-specific genes such as Calb1 and Pcp2 mirrored the time course of changes in PC physiology with calbindin-28 K changes showing the first small, but significant decreases at 4 weeks. These results emphasize that in this model of SCA2, physiological and behavioral phenotypes precede morphological changes by several weeks and provide a rationale for future studies examining the effects of restoration of firing frequency on motor function and prevention of future loss of PCs

Building Eurafrica: Reviving Colonialism through European Integration, 1920-1960

This paper examines the history of the ‘Eurafrican project’ as it evolved from the Pan‐ European movement in the 1920s to its institutionalization in the European Economic Community (EEC) (i.e. today’s EU) in the late 1950s. As we show, practically all of the visions, movements and concrete institutional arrangements working towards European integration during this period placed Africa’s incorporation into the European enterprise as a central objective. As so much of the scholarly, political and journalistic accounts at the time testify to, European integration was inextricably bound up with a Eurafrican project. According to the intellectual, political and institutional discourse on Eurafrica—or the fate of Europe’s colonial enterprise—a future European community presupposed the transformation of the strictly national colonial projects into a joint European colonization of Africa. There is strong evidence to support that this project was instrumental in the actual, diplomatic and political constitution of the EEC, or of Europe as a political subject. According to our thesis, the origins of the EU cannot be separated from the perceived necessity to preserve and reinvigorate the colonial system. On a second level the paper also introduces a broader historiographic problematic in which we position Eurafrica as the wider but by now forgotten formation that shaped Europe and Africa and their relations to one another in the greater part of the twentieth century. Eurafrica conditioned both the integration of Europe and the political landscape in postcolonial Africa. We are thus able to shift the terrain upon which most if not all scholarly analyses of the political, economic and ideological developments on the two continents have taken place up until now. Eurafrica is the forgotten geopolitical context that must be reconstructed in order for us to resolve a set of crucial historical and political problems. Questioning the historical framework usually employed in EU studies, our intervention emphasizes the radically different geopolitical designs for the postwar world order that was encoded in the Eurafrican project. Finally, we also show how these Eurafrican designs continue to influence current relations between Europe and Africa

Eurafrica

This book is available as open access through the Bloomsbury Open Access programme and is available on www.bloomsburycollections.com. In order to think theoretically about our global age it is important to understand how the global has been conceived historically. 'Eurafrica' was an intellectual endeavor and political project that from the 1920s saw Europe's future survival - its continued role in history - as completely bound up with Europe's successful merger with Africa. In its time the concept of Eurafrica was tremendously influential in the process of European integration. Today the project is largely forgotten, yet the idea continues to influence EU policy towards its African 'partner'. The book will recover a critical conception of the nexus between Europe and Africa - a relationship of significance across the humanities and social sciences. In assessing this historical concept the authors shed light on the process of European integration, African decolonization and the current conflictual relationship between Europe and Africa