Prion-like propagation of tau aggregation might underlie the stereotyped progression of neurodegenerative tauopathies. True prions stably maintain unique conformations (“strains”) in vivo that link ...structure to patterns of pathology. We now find that tau meets this criterion. Stably expressed tau repeat domain indefinitely propagates distinct amyloid conformations in a clonal fashion in culture. Reintroduction of tau from these lines into naive cells reestablishes identical clones. We produced two strains in vitro that induce distinct pathologies in vivo as determined by successive inoculations into three generations of transgenic mice. Immunopurified tau from these mice recreates the original strains in culture. We used the cell system to isolate tau strains from 29 patients with 5 different tauopathies, finding that different diseases are associated with different sets of strains. Tau thus demonstrates essential characteristics of a prion. This might explain the phenotypic diversity of tauopathies and could enable more effective diagnosis and therapy.
•Tau stably propagates multiple amyloid conformations (strains) in dividing cells•Strains induce unique pathologies in transgenic mice•Strains can be passaged through multiple generations of mice and back to cells•Different tauopathies are associated with different sets of strains
Prions stably propagate unique conformations (strains) that produce different pathologies. Sanders et al. now report that tau acts as a prion in cells and in vivo by this criterion and find that different tauopathies are associated with unique tau strains.
This paper theoretically and empirically analyzes the financing terms that support international trade. The choice of trade finance terms balances the risk that an importer defaults on an exporter ...and the possibility that an exporter does not deliver goods as specified. Analysis of transaction-level data from a US exporter reveals that importers located in countries with weak enforcement of contracts typically finance transactions, but these firms are able to overcome the constraints of such environments if they can establish a relationship with the exporter. Furthermore, the manner in which trade is financed shapes the impact of crises.
US corporations hold significant amounts of cash on their balance sheets. This paper develops and tests the hypothesis that the magnitude of US multinational cash holdings are, in part, a consequence ...of the tax costs associated with repatriating foreign income. Consistent with this hypothesis, firms facing higher repatriation taxes hold higher levels of cash, hold this cash abroad, and hold this cash in affiliates that trigger high tax costs when repatriating earnings. In addition, less financially constrained firms and those that are more technology intensive exhibit a higher sensitivity of affiliate cash holdings to repatriation tax burdens.
WELFARE PAYMENTS AND CRIME Foley, C. Fritz
The review of economics and statistics,
02/2011, Letnik:
93, Številka:
1
Journal Article
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Analysis of daily reported incidents of major crimes in twelve U.S. cities reveals an increase in crime over the course of monthly welfare payment cycles. This increase reflects an increase in crimes ...that are likely to have a direct financial motivation as opposed to other kinds of crime. Temporal patterns in crime are observed in jurisdictions in which disbursements are focused at the beginning of monthly welfare payment cycles and not in jurisdictions in which disbursements are relatively more staggered. These findings indicate that welfare beneficiaries consume welfarerelated income quickly and then attempt to supplement it with criminal income.
Facebook, the most widely used social media platform, has been adopted by public health organisations for health promotion and behaviour change campaigns and activities. However, limited information ...is available on the most effective and efficient use of Facebook for this purpose. This study sought to identify the features of Facebook posts that are associated with higher user engagement on Australian public health organisations' Facebook pages. We selected 20 eligible pages through a systematic search and coded 360-days of posts for each page. Posts were coded by: post type (e.g., photo, text only etc.), communication technique employed (e.g. testimonial, informative etc.) and use of marketing elements (e.g., branding, use of mascots). A series of negative binomial regressions were used to assess associations between post characteristics and user engagement as measured by the number of likes, shares and comments. Our results showed that video posts attracted the greatest amount of user engagement, although an analysis of a subset of the data suggested this may be a reflection of the Facebook algorithm, which governs what is and is not shown in user newsfeeds and appear to preference videos over other post types. Posts that featured a positive emotional appeal or provided factual information attracted higher levels of user engagement, while conventional marketing elements, such as sponsorships and the use of persons of authority, generally discouraged user engagement, with the exception of posts that included a celebrity or sportsperson. Our results give insight into post content that maximises user engagement and begins to fill the knowledge gap on effective use of Facebook by public health organisations.
Astrocytic control of synaptic function Papouin, Thomas; Dunphy, Jaclyn; Tolman, Michaela ...
Philosophical transactions - Royal Society. Biological sciences,
03/2017, Letnik:
372, Številka:
1715
Journal Article
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Astrocytes intimately interact with synapses, both morphologically and, as evidenced in the past 20 years, at the functional level. Ultrathin astrocytic processes contact and sometimes enwrap the ...synaptic elements, sense synaptic transmission and shape or alter the synaptic signal by releasing signalling molecules. Yet, the consequences of such interactions in terms of information processing in the brain remain very elusive. This is largely due to two major constraints: (i) the exquisitely complex, dynamic and ultrathin nature of distal astrocytic processes that renders their investigation highly challenging and (ii) our lack of understanding of how information is encoded by local and global fluctuations of intracellular calcium concentrations in astrocytes. Here, we will review the existing anatomical and functional evidence of local interactions between astrocytes and synapses, and how it underlies a role for astrocytes in the computation of synaptic information.
This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.
This paper analyzes the capital structures of foreign affiliates and internal capital markets of multinational corporations. Ten percent higher local tax rates are associated with 2.8% higher ...debt/asset ratios, with internal borrowing being particularly sensitive to taxes. Multinational affiliates are financed with less external debt in countries with underdeveloped capital markets or weak creditor rights, reflecting significantly higher local borrowing costs. Instrumental variable analysis indicates that greater borrowing from parent companies substitutes for three-quarters of reduced external borrowing induced by capital market conditions. Multinational firms appear to employ internal capital markets opportunistically to overcome imperfections in external capital markets.
This paper examines how technology transfer within U.S. multinational firms changes in response to a series of IPR reforms undertaken by sixteen countries over the 1982-1999 period. Analysis of ...detailed firm-level data reveals that royalty payments for technology transferred to affiliates increase at the time of reforms, as do affiliate R&D expenditures and total levels of foreign patent applications. Increases in royalty payments and R&D expenditures are concentrated among affiliates of parent companies that use U.S. patents extensively prior to reform and are therefore expected to value IPR reform most. For this set of affiliates, increases in royalty payments exceed 30 percent. PUBLICATION ABSTRACT
Amyloidoses (misfolded polypeptide accumulation) are among the most debilitating diseases our aging societies face. Amyloidogenesis can be catalyzed by hydrophobic–hydrophilic interfaces (e.g., ...air–water interface in vitro AWI). We recently demonstrated hydrogelation of the amyloidogenic type II diabetes-associated islet amyloid polypeptide (IAPP), a hydrophobic–hydrophilic interface-dependent process with complex kinetics. We demonstrate that human IAPP undergoes AWI-catalyzed liquid–liquid phase separation (LLPS), which initiates hydrogelation and aggregation. Insulin modulates these processes but does not prevent them. Using nonamyloidogenic rat IAPP, we show that, whereas LLPS does not require the amyloidogenic sequence, hydrogelation and aggregation do. Interestingly, both insulin and rat sequence delayed IAPP LLPS, which may reflect physiology. By developing an experimental setup and analysis tools, we show that, within the whole system (beyond the droplet stage), macroscopic interconnected aggregate clusters form, grow, fuse, and evolve via internal rearrangement, leading to overall hydrogelation. As the AWI-adsorbed gelled layer matures, its microviscosity increases. LLPS-driven aggregation may be a common amyloid feature and integral to pathology.
This paper studies the impact that ethnic innovators have on the global activities of U.S. firms by analyzing detailed data on patent applications and on the operations of the foreign affiliates of ...U.S. multinational firms. The results indicate that increases in the share of a firm's innovation performed by inventors of a particular ethnicity are associated with increases in the share of that firm's affiliate activity in countries related to that ethnicity. Ethnic innovators also appear to facilitate the disintegration of innovative activity across borders and to allow U.S. multinationals to form new affiliates abroad without the support of local joint venture partners.
This paper was accepted by Bruno Cassiman, business strategy.