87 research outputs found

    The mapping of Europe and ideas of integration: in the new member countries, national meanings of European culture determine debates about the desired European Union's mission

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    With EU enlargement, peculiar Central European ideas and traditions of integration emerged in European politics. In the discussions on a European constitution, the representatives of the new member states surprised the “old” Europe with meanings of Europe that were situated far beyond the canonised Western concepts of pragmatic political integration. Central European politicians and political essayists discussed a canon of cultural and religious European values and the role of the nations in the European Union. Research on the contemporary history of Central Europe brings light into the traditions and the development of Central European meanings of Europe. Before 1989 and East of the “Iron curtain”, Europe rather served as a place of desire than as a concrete concept, a mechanism of integration or an institutional framework. The cases of Poland and the Czech Republic (respectively the former Czechoslovakia) show that the salient feature of their meanings of Europe in history is the high significance of the nation. In the Eastern bloc, Europe was construed along terms of culture and civilisation. Party officials, dissidents and journalists framed Europe nationally. Regarding ideas of integration, 1989 stands for continuity in Central European meanings of Europe. The historical East-West difference in the „thinking of Europe“ and former mappings of Europe in the new member countries re-shape the present new European Union. Exclusive meanings of Europe in Central Europe challenge policies of integration, migration, citizenship and governance. There is a drift towards demarcating a European self and towards defining a collective in cultural terms. This trend strengthens the paradigm of neighbourhood vis-à-vis transnationalisation and unification in the E.U. In the debates on the foreign relations of the Union, exponents of a cultural European identity address questions of self-demarcation and self-delimitation

    A kinesin-13 mutant catalytically depolymerizes microtubules in ADP

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    The kinesin-13 motor protein family members drive the removal of tubulin from microtubules (MTs) to promote MT turnover. A point mutation of the kinesin-13 family member mitotic centromere-associated kinesin/Kif2C (E491A) isolates the tubulin-removal conformation of the motor, and appears distinct from all previously described kinesin-13 conformations derived from nucleotide analogues. The E491A mutant removes tubulin dimers from stabilized MTs stoichiometrically in adenosine triphosphate (ATP) but is unable to efficiently release from detached tubulin dimers to recycle catalytically. Only in adenosine diphosphate (ADP) can the mutant catalytically remove tubulin dimers from stabilized MTs because the affinity of the mutant for detached tubulin dimers in ADP is low relative to lattice-bound tubulin. Thus, the motor can regenerate for further cycles of disassembly. Using the mutant, we show that release of tubulin by kinesin-13 motors occurs at the transition state for ATP hydrolysis, which illustrates a significant divergence in their coupling to ATP turnover relative to motile kinesins

    Communications Biophysics

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    Contains reports on five research projects.National Institutes of Health (Grant 5 P01 GM14940-03)National Institutes of Health (Grant 5 TOl GM01555-03)National Aeronautics and Space Administration (Grant NGL 22-009-304

    Cerebral Amyloid Angiopathy and Parenchymal Amyloid Deposition in Transgenic Mice Expressing the Danish Mutant Form of Human BRI2

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    Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease clinically characterized by the presence of cataracts, hearing impairment, cerebellar ataxia and dementia. Neuropathologically, FDD is characterized by the presence of widespread cerebral amyloid angiopathy (CAA), parenchymal amyloid deposition and neurofibrillary tangles. FDD is caused by a 10-nucleotide duplication-insertion in the BRI2 gene that generates a larger-than-normal precursor protein, of which the Danish amyloid subunit (ADan) comprises the last 34 amino acids. Here, we describe a transgenic mouse model for FDD (Tg-FDD) in which the mouse Prnp (prion protein) promoter drives the expression of the Danish mutant form of human BRI2. The main neuropathological findings in Tg-FDD mice are the presence of widespread CAA and parenchymal deposition of ADan. In addition, we observe the presence of amyloid-associated gliosis, an inflammatory response and deposition of oligomeric ADan. As the animals aged, they showed abnormal grooming behavior, an arched back, and walked with a wide-based gait and shorter steps. This mouse model may give insights on the pathogenesis of FDD and will prove useful for the development of therapeutics. Moreover, the study of Tg-FDD mice may offer new insights into the role of amyloid in neurodegeneration in other disorders, including Alzheimer disease

    Observer weighting of interaural cues in positive and negative envelope slopes of amplitude-modulated waveforms

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    The auditory system can encode interaural delays in highpass-filtered complex sounds by phase locking to their slowly modulating envelopes. Spectrotemporal analysis of interaurally time-delayed highpass waveforms reveals the presence of a concomitant interaural level cue. The current study systematically investigated the contribution of time and concomitant level cues carried by positive and negative envelope slopes of a modified sinusoidally amplitude-modulated (SAM) high-frequency carrier. The waveforms were generated from concatenation of individual modulation cycles whose envelope peaks were extended by the desired interaural delay, allowing independent control of delays in the positive and negative modulation slopes. In experiment 1, thresholds were measured using a 2-interval forced-choice adaptive task for interaural delays in either the positive or negative modulation slopes. In a control condition, thresholds were measured for a standard SAM tone. In experiment 2, decision weights were estimated using a multiple-observation correlational method in a single-interval forced-choice task for interaural delays carried simultaneously by the positive, and independently, negative slopes of the modulation envelope. In experiment 3, decision weights were measured for groups of 3 modulation cycles at the start, middle, and end of the waveform to determine the influence of onset dominance or recency effects. Results were consistent across experiments: thresholds were equal for the positive and negative modulation slopes. Decision weights were positive and equal for the time cue in the positive and negative envelope slopes. Weights were also larger for modulations cycles near the waveform onset. Weights estimated for the concomitant interaural level cue were positive for the positive envelope slope and negative for the negative slope, consistent with exclusive use of time cues.We thank Virginia M. Richards and Bruce G. Berg for helpful discussions. We also thank Brian C. J. Moore and an anonymous reviewer for their insightful comments on an earlier draft of the manuscript. Work supported by grants from the National Science Council, Taiwan NSC 98-2410-H-008-081-MY3 and NIH R01DC009659
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