Where the Ground Answers the Foot: Kerstin Ekman, Ecology, and the Sense of Place in a Globalized World

Kerstin Ekman has emerged as one of the important literary voices in Northern Europe challenging facile definitions of nature and inviting readers to reconsider conceptions of the local. She accomplishes this by using ecological models in her fiction that explore how human subjects exist in interdependent relationships with their environments intertwining space with experience and memory to produce constellations of significance and meaning. The materiality of the space combines with human discourse to create a sense of place situated between immediate and the distant and between the constructed and the found. In particular, her 1993 work, Händelser vid vatten [Blackwater] explores an ecological model of ontology in which all elements are intricately interconnected in myriad ways that question, among other things, the construction of place and the role of both materiality and place in an increasingly mobile, technologically mediated, and globalized world. My purpose is to consider Ekman's model(s) of ecological interdependence in dialogue with the theoretical discussions of space and place that have emerged in recent decades, particularly within the field of ecocriticism. In Ekman's work, the decidedly human propensities for naming, narrating, manipulating, and constructing space are counterbalanced by an experience of materiality and the natural environment's ultimate ambivalence to anthropocentrism. The novel's network of competing narratives, memories, definitions, and confrontation with materiality tend to frustrate the classical modernist epistemological project by lacking clear linearity, diverging, converging, and doubling back on themselves. The effect is to focus readers' attention on how space is produced as a means of understanding the diffuse subject's being in the world as part of complex material and discursive networks as well as between the constructed and the found, the subjective and the objective, the embodied and the abstract, and the local and the global

Where the Ground Answers the Foot: Kerstin Ekman, Ecology, and the Sense of Place in a Globalized World

Kerstin Ekman has emerged as one of the important literary voices in Northern Europe challenging facile definitions of nature and inviting readers to reconsider conceptions of the local. She accomplishes this by using ecological models in her fiction that explore how human subjects exist in interdependent relationships with their environments intertwining space with experience and memory to produce constellations of significance and meaning. The materiality of the space combines with human discourse to create a sense of place situated between immediate and the distant and between the constructed and the found. In particular, her 1993 work, Händelser vid vatten [Blackwater] explores an ecological model of ontology in which all elements are intricately interconnected in myriad ways that question, among other things, the construction of place and the role of both materiality and place in an increasingly mobile, technologically mediated, and globalized world. My purpose is to consider Ekman's model(s) of ecological interdependence in dialogue with the theoretical discussions of space and place that have emerged in recent decades, particularly within the field of ecocriticism. In Ekman's work, the decidedly human propensities for naming, narrating, manipulating, and constructing space are counterbalanced by an experience of materiality and the natural environment's ultimate ambivalence to anthropocentrism. The novel's network of competing narratives, memories, definitions, and confrontation with materiality tend to frustrate the classical modernist epistemological project by lacking clear linearity, diverging, converging, and doubling back on themselves. The effect is to focus readers' attention on how space is produced as a means of understanding the diffuse subject's being in the world as part of complex material and discursive networks as well as between the constructed and the found, the subjective and the objective, the embodied and the abstract, and the local and the global

Exploring functional pairing between surface glycoconjugates and human galectins using programmable glycodendrimersomes

Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3′-O-sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity

Helicobacter pylori Adapts to Chronic Infection and Gastric Disease via pH-Responsive BabA-Mediated Adherence

International audienceThe BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease

Exploring functional pairing between surface glycoconjugates and human galectins using programmable glycodendrimersomes

Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3′-O-sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity

Candidate gene case-control association studies: advantages and potential pitfalls

There is increasing information on the importance of genetic polymorphisms in human genes. Polymorphisms occur on average once every 500–1000 base pairs in the human genome and are useful in the identification of genes involved in human disease. Some genetic polymorphisms have functionally significant effects on the gene product and are the most useful type of polymorphism in disease association studies while others are simply useful markers. There are two main approaches using polymorphisms in the identification of genes involved in polygenic diseases. The first involves examining inheritance patterns for genetic polymorphisms in family studies and the second case-control studies which compare genotype frequencies for candidate disease genes in unrelated individuals with the disease and healthy controls. Use of family studies is generally the preferred approach but this is only feasible if the genetic component of the disease is relatively strong, DNA samples are available from other family members and the disease is relatively easy to diagnose and is not stigmatized. Population case-control studies are useful both as an alternative and an adjunct to family studies. When performing case-control studies factors such as study design, methods for recruitment of cases and controls, functional significance of polymorphisms chosen for study and statistical analysis of data require close attention to ensure that only genuine associations are detected. To illustrate some potential problems in the design and interpretation of association studies, some specific examples of association studies on drug response and on disease susceptibility involving receptor genes, cytochrome P450 and other xenobiotic metabolizing enzyme genes and immune system genes including TNF-α, IL-10 and the IL-4 receptor are discussed