This collection showcases a multivalent approach to the study of literary multilingualism, embodied in contemporary Nordic literature. While previous approaches to literary multilingualism have ...tended to take a textual or authorship focus, this book advocates for a theoretical perspective which reflects the multiplicity of languages in use in contemporary literature emerging from increased globalization and transnational interaction. Drawing on a multimodal range of examples from contemporary Nordic literature, these eighteen chapters illustrate the ways in which multilingualism is dynamic rather than fixed, resulting from the interactions between authors, texts, and readers as well as between literary and socio-political institutions. The book highlights the processes by which borders are formed within the production, circulation, and reception of literature and in turn, the impact of these borders on issues around cultural, linguistic, and national belonging. Introducing an innovative approach to the study of multilingualism in literature, this collection will be of particular interest to students and researchers in literary studies, cultural studies, and multilingualism.
V-ATPases constitute a ubiquitous family of heteromultimeric, proton translocating proteins. According to their localization in a multitude of eukaryotic endomembranes and plasma membranes, they ...energize many different transport processes. Currently, a handful of specific inhibitors of the V-ATPase are known, which represent valuable tools for the characterization of transport processes on the level of tissues, single cells or even purified proteins. The understanding of how these inhibitors function may provide a basis to develop new drugs for the benefit of patients suffering from diseases such as osteoporosis or cancer. For this purpose, it appears absolutely essential to determine the exact inhibitor binding site in a target protein on the one side and to uncover the crucial structural elements of an inhibitor on the other side. However, even for some of the most popular and long known V-ATPase inhibitors, such as bafilomycin or concanamycin, the authentic structures of their binding sites are elusive. The aim of this review is to summarize the recent advances for the old players in the inhibition game, the plecomacrolides bafilomycin and concanamycin, and to introduce some of the new players, the macrolacton archazolid, the benzolactone enamides salicylihalamide, lobatamide, apicularen, oximidine and cruentaren, and the indolyls.
Scandinavian societies have historically, and problematically, been understood as homogeneous, when in fact they have a long history of ethnic and cultural pluralism due to colonialism and ...territorial conquest. After World War II, Sweden, Denmark, and Norway all became destinations for an increasingly diverse stream of migrants and asylum seekers from war-torn countries around the globe, culminating in the 2015-16 "refugee crisis." This multidisciplinary volume opens with an overview of how the three countries' current immigration policies developed and evolved, then expands to address how we might understand the current contexts and the social realities of immigration and diversity on the ground. Drawing from personal experiences and theoretical perspectives in such varied fields as sociology, political science, literature, and media studies, nineteen scholars assess recent shifts in Scandinavian societies and how they intertwine with broader transformations in Europe and beyond. Chapters explore a variety of topics, including themes of belonging and identity in Norway, the experiences and activism of the Nordic countries' Indigenous populations, and parallels between the racist far-right resurgence in Sweden and the United States. Contributors: Ellen A. Ahlness, Julie K. Allen, Grete Brochmann, Eric Einhorn, Sherrill Harbison, Anne Heith, Markus Huss, Peter Leonard, Barbara Mattsson, Kelly McKowen, Andreas Önnerfors, Elisabeth Oxfeldt, Tony Sandset, Carly Elizabeth Schall, Ryan Thomas Skinner, Admir Skodo, Benjamin R. Teitelbaum, Sayaka Osanami Törngren, Ethelene Whitmire.
The vacuolar (H+)-ATPases (V-ATPases) are a family of ATP-driven proton pumps that couple ATP hydrolysis with translocation of protons across membranes. Previous studies have implicated V-ATPases in ...cancer cell invasion. It has been proposed that V-ATPases participate in invasion by localizing to the plasma membrane and causing acidification of the extracellular space. To test this hypothesis, we utilized two separate approaches to specifically inhibit plasma membrane V-ATPases. First, we stably transfected highly invasive MDA-MB231 cells with a V5-tagged construct of the membrane-embedded c subunit of the V-ATPase, allowing for extracellular expression of the V5 epitope. We evaluated the effect of addition of a monoclonal antibody directed against the V5 epitope on both V-ATPase-mediated proton translocation across the plasma membrane and invasion using an in vitro Matrigel assay. The addition of anti-V5 antibody resulted in acidification of the cytosol and a decrease in V-ATPase-dependent proton flux across the plasma membrane in transfected but not control (untransfected) cells. These results demonstrate that the anti-V5 antibody inhibits activity of plasma membrane V-ATPases in transfected cells. Addition of the anti-V5 antibody also inhibited in vitro invasion of transfected (but not untransfected) cells. Second, we utilized a biotin-conjugated form of the specific V-ATPase inhibitor bafilomycin. When bound to streptavidin, this compound cannot cross the plasma membrane. Addition of this compound to MDA-MB231 cells also inhibited in vitro invasion. These studies suggest that plasma membrane V-ATPases play an important role in invasion of breast cancer cells.
Background: The V-ATPase has been proposed to function at the plasma membrane in tumor cell invasion.
Results: Inhibition of plasma membrane V-ATPases prevented invasion of MDA-MB-231 cells.
Conclusion: Activity of plasma membrane V-ATPases is critical for breast cancer cell invasion.
Significance: Plasma membrane V-ATPases are a possible therapeutic target to limit metastasis.
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Vacuolar-type proton pumps in insect epithelia Wieczorek, Helmut; Beyenbach, Klaus W; Huss, Markus ...
Journal of experimental biology,
06/2009, Volume:
212, Issue:
Pt 11
Journal Article
Peer reviewed
Open access
Active transepithelial cation transport in insects was initially discovered in Malpighian tubules, and was subsequently also found in other epithelia such as salivary glands, labial glands, midgut ...and sensory sensilla. Today it appears to be established that the cation pump is a two-component system of a H(+)-transporting V-ATPase and a cation/nH(+) antiporter. After tracing the discovery of the V-ATPase as the energizer of K(+)/nH(+) antiport in the larval midgut of the tobacco hornworm Manduca sexta we show that research on the tobacco hornworm V-ATPase delivered important findings that emerged to be of general significance for our knowledge of V-ATPases, which are ubiquitous and highly conserved proton pumps. We then discuss the V-ATPase in Malpighian tubules of the fruitfly Drosophila melanogaster where the potential of post-genomic biology has been impressively illustrated. Finally we review an integrated physiological approach in Malpighian tubules of the yellow fever mosquito Aedes aegypti which shows that the V-ATPase delivers the energy for both transcellular and paracellular ion transport.
Autophagy is a catabolic lysosomal degradation process essential for cellular homeostasis and cell survival. Dysfunctional autophagy has been associated with a wide range of human diseases, e.g., ...cancer and neurodegenerative diseases. A large number of small molecules that modulate autophagy have been widely used to dissect this process and some of them, e.g., chloroquine (CQ), might be ultimately applied to treat a variety of autophagy-associated human diseases. Here we found that vacuolin-1 potently and reversibly inhibited the fusion between autophagosomes and lysosomes in mammalian cells, thereby inducing the accumulation of autophagosomes. Interestingly, vacuolin-1 was less toxic but at least 10-fold more potent in inhibiting autophagy compared with CQ. Vacuolin-1 treatment also blocked the fusion between endosomes and lysosomes, resulting in a defect in general endosomal-lysosomal degradation. Treatment of cells with vacuolin-1 alkalinized lysosomal pH and decreased lysosomal Ca
2+
content. Besides marginally inhibiting vacuolar ATPase activity, vacuolin-1 treatment markedly activated RAB5A GTPase activity. Expression of a dominant negative mutant of RAB5A or RAB5A knockdown significantly inhibited vacuolin-1-induced autophagosome-lysosome fusion blockage, whereas expression of a constitutive active form of RAB5A suppressed autophagosome-lysosome fusion. These data suggest that vacuolin-1 activates RAB5A to block autophagosome-lysosome fusion. Vacuolin-1 and its analogs present a novel class of drug that can potently and reversibly modulate autophagy.
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Primary active proton transport by eukaryotic V-ATPases (vacuolar ATPases) is regulated via the reversible disassembly of the V1Vo holoenzyme into its peripheral catalytic V1 complex and its ...membrane-bound proton-translocating Vo complex. This nutrient-dependent phenomenon had been first detected in the midgut epithelium of non-feeding moulting tobacco hornworms (Manduca sexta) and in glucose-deprived yeast cells (Saccharomyces cerevisiae). Since reversible disassembly to date had been investigated mostly in vitro, we wanted to test this phenomenon under in vivo conditions. We used living yeast cells with V-ATPase subunits fused to green, yellow or cyan fluorescent protein and found that only the V1 subunit C (Vma5) was released into the cytosol after substitution of extracellular glucose with galactose, whereas the other V1 subunits remained at or near the membrane. FRET analysis demonstrated close proximity between V1 and Vo even under glucose-starvation conditions. Disassembly, but not reassembly, depended on functional microtubules. Results from overlay blots, pull-down assays and bimolecular fluorescence complementation support the assumption that subunit C interacts directly with microtubules without involvement of linker proteins.
The vacuolar H
+-ATPase (V-ATPase) is an ATP-driven rotary molecular motor that is a transmembrane proton pump in all eukaryotic cells. Although its activity is fundamental to many physiological ...processes, our understanding of the structure and mechanism of the V-ATPase is poor. Using cryo-electron microscopy of the tobacco hornworm (
Manduca sexta) enzyme, we have calculated the first 3D reconstruction of the intact pump in its native state. The resolution of 16.5 Å is significantly higher than that of previous cryo-electron microscopy models of either V-ATPase or the related F
1F
0-ATPase. A network of four stalk structures connecting the V
1 catalytic domain and the V
0 membrane domain is now fully resolved, demonstrating substantially greater complexity than that found in the F-ATPase. Three peripheral stator stalks connect these domains to a horizontal collar that partly encircles the region between V
1 and V
0. The fourth stalk is a central axle that connects to V
0 but makes minimal contact with V
1. Several subunit crystal structures can be fit accurately into the reconstruction. The model thus provides new insights into the organisation of key components involved in mechanical coupling between the domains and regulation of activity.
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The macrolactone archazolid is a novel, highly specific V-ATPase inhibitor with an IC50 value in the low nanomolar range. The binding site of archazolid is presumed to overlap with the binding site ...of the established plecomacrolide V-ATPase inhibitors bafilomycin and concanamycin in subunit c of the membrane-integral VO complex. Using a semi-synthetic derivative of archazolid for photoaffinity labeling of the V1VO holoenzyme we confirmed binding of archazolid to the VO subunit c. For the plecomacrolide binding site a model has been published based on mutagenesis studies of the c subunit of Neurospora crassa, revealing 11 amino acids that are part of the binding pocket at the interface of two adjacent c subunits (Bowman, B. J., McCall, M. E., Baertsch, R., and Bowman, E. J. (2006) J. Biol. Chem. 281, 31885–31893). To investigate the contribution of these amino acids to the binding of archazolid, we established in Saccharomyces cerevisiae mutations that in N. crassa had changed the IC50 value for bafilomycin 10-fold or more and showed that out of the amino acids forming the plecomacrolide binding pocket only one amino acid (tyrosine 142) contributes to the binding of archazolid. Using a fluorescent derivative of N,N′-dicyclohexylcarbodiimide, we found that the binding site for archazolid comprises the essential glutamate within helix 4 of subunit c. In conclusion the archazolid binding site resides within the equatorial region of the VO rotor subunit c. This hypothesis was supported by an additional subset of mutations within helix 4 that revealed that leucine 144 plays a role in archazolid binding.
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How can sign language be rendered in written literary form? What can such a literary rendering teach us about the social dimensions and aesthetic productivity of a language, which in this case ...demands intermedial translation? How does the thematisation and use of sign language play into the vernacular-cosmopolitan dynamic of world literature? The essay addresses these questions by turning to the German author and ethnographer Michael Roes's Die Laute (2012). In this novel, a young Yemenite musical genius, Aziz, loses his hearing and is forced to learn the local variety of sign language in the city of Aden. The characterisation of sign language is shown to oscillate between two poles: as a uniform linguistic entity, beyond any specific international, national or subnational framework, and as a variety of vernacular practices, linked to specific socio-geographical spaces. The analysis displays how the novel's metalinguistic reflections on the specificities of sign language on part of the protagonist prompts the reader to consider the text as a translation of a sign language original. Sign language in terms of a vernacular, ritualized practice, is shown to be used as a tool for aesthetic renewal, inviting the reader to imagine sign language as poetic practice.
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