Targeting TNFR2 as a novel therapeutic strategy for Alzheimer's disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. Accumulating experimental evidence shows the important linkage between tumor necrosis factor-α (TNF) and AD, but the exact role of TNF in AD is still not completely understood. Although TNF-inhibitors are successfully used for treating several diseases, total inhibition of TNF can cause side effects, particularly in neurological diseases. This is attributed to the opposing roles of the two TNF receptors. TNF receptor 1 (TNFR1) predominantly mediates inflammatory and pro-apoptotic signaling pathways, whereas TNF receptor 2 (TNFR2) is neuroprotective and promotes tissue regeneration. Therefore, the specific activation of TNFR2 signaling, either by directly targeting TNFR2 via TNFR2 agonists or by blocking TNFR1 signaling with TNFR1-selective antagonists, seems a promising strategy for AD therapy. This mini-review discusses the involvement of TNFR2 and its signaling pathway in AD and outlines its potential application as therapeutic target. A better understanding of the function of TNFR2 may lead to the development of a treatment for AD

Learning intrinsic excitability in medium spiny neurons

We present an unsupervised, local activation-dependent learning rule for intrinsic plasticity (IP) which affects the composition of ion channel conductances for single neurons in a use-dependent way. We use a single-compartment conductance-based model for medium spiny striatal neurons in order to show the effects of parametrization of individual ion channels on the neuronal activation function. We show that parameter changes within the physiological ranges are sufficient to create an ensemble of neurons with significantly different activation functions. We emphasize that the effects of intrinsic neuronal variability on spiking behavior require a distributed mode of synaptic input and can be eliminated by strongly correlated input. We show how variability and adaptivity in ion channel conductances can be utilized to store patterns without an additional contribution by synaptic plasticity (SP). The adaptation of the spike response may result in either "positive" or "negative" pattern learning. However, read-out of stored information depends on a distributed pattern of synaptic activity to let intrinsic variability determine spike response. We briefly discuss the implications of this conditional memory on learning and addiction.Comment: 20 pages, 8 figure

Disequilibrium in development finance: the contested politics of institutional accountability and transparency at the World Bank inspection panel

This article examines the dynamic nature with which independent accountability mechanisms operate. Focusing on the World Bank, the authors argue that its Inspection Panel evolves according to internal and external pressures. In seeking to achieve equilibrium, and protect its authority and independence, the Panel has gone through several distinct phases: negotiation, emergence, protracted resistance, assertion of independence and authority, renewed tension, and contestation. The core novelty of the article is its application of concepts from outside the field of development studies — notably institutional accountability from the governance literature, and judicialization from the legal studies literature — to the topic of the Inspection Panel. Examining the Panel in this way demonstrates that accountability mechanisms represent a hybrid of transnational governance influenced by a range of actors including project-affected peoples, national governments, managers and development donors. Accountability in development finance is about competing interests as well as competing conceptions and expectations of accountability. In such a complex and multi-scalar system, the Panel is not only concerned with delivering well-researched investigation reports; it is also an entity seeking to ensure its own survival, as well as an arbiter of its own brand of legitimacy and accountability. © 2018 The Authors. Development and Change published by John Wiley & Sons Ltd on behalf of Institute of Social Studie

Dyadic Operationalization in Business Relationships: The Empirical Example of Marketing-Purchasing Collaboration

Purpose: The purpose of this paper is to explore whether dyadic operationalization within business relationships is feasible and sensible in a rigorous way. It aims to introduce quantitative operationalizations of business relationship characteristics from both monadic and dyadic datasets, and to introduce aggregation techniques for utilizing the richness of dyadic data. It compares and contrasts the effectiveness of different techniques in terms of explaining business relationship phenomena, using an empirical exemplification. Methodology/Approach: The paper reviews the relevant literature and summarizes various dyadic operationalization and aggregation approaches. It furthermore illustrates such operationalization and aggregation by utilizing an empirical example. A nomological model of marketing-purchasing collaboration is developed and tested based upon internal dyadic data. Using alternative model comparisons, we contrast several different ways of operationalizing dyadic data (combined, dyadic, and dyadic with asymmetry), and compare the outcomes utilizing structural equation modeling. Findings: The study of business relationships typically makes use of a variety of data types, ranging from simple monadic to perceived dyadic, through to rigorous dyadic data. The various aggregation methods include value, asymmetry, and directional asymmetry approaches. Pertinent sub-constructs are developed based on these aggregation methods and relevant hypotheses incorporating and reflecting on the role of the sub-constructs are suggested to develop a more meaningful and rich quantitative analysis of business relationship phenomena. Research Implications: This paper explores the different ways in which data assessing the relationship between two interacting parties can be operationalized. Dyadic operationalization within the context of business relationships is sensible and recommended. Researchers can adopt approaches to conduct dyadic data operationalization including data collection methods such as perceived dyadic and rigorous dyadic. They should benefit from rich dyadic aggregation approaches such as value, asymmetry, and directional asymmetry, noting the strengths and weaknesses of each approach discussed in this paper. Practical Implications: Businesses are recommended to increase customer orientation and marketing-purchasing interaction to improve collaboration between marketing and purchasing departments and thus their overall performance. Businesses should also develop an alignment between the collaboration perceptions of the involved departments, and note that perceptual symmetry improves collaboration. Perception matching in a dyadic relationship plays a role in enhancing the overall firm performance. Managers should note that all involved parties’ perspectives are to be included to ensure a positive and collaborative liaison. An all-encompassing attitude and perspective (as opposed to an asymmetric, unbalanced one) ensures an effective relationship. Originality/Value/Contribution of the paper: The contribution of the research lies in outlining different ways to accomplish more insightful analytics regarding data operationalization, and their different strengths and weaknesses in terms of explaining relationship characteristics, and therefore enriches research on business relationships by making better sense of quantitative dyadic data

Finance, Development, and Remittances: Extending the Scale of Accumulation in Migrant Labour Regimes

The last decade has seen a heightened level of interest in the relationship between remittances and development, driven by the World Bank and other Bretton Woods Institutions. This has materialised in a global agenda to incorporate migrants and their households in commercial banking. The double significance of this policy rests in the financial incorporation of migrants and their households, and in the deepening entrenchment of the historical labour migration dynamic between sending communities and centres of capital. The central role of labour power in the advance of money forms the core of this analysis of a contemporary market-building strategy. This article presents a threefold critique of the global remittance agenda, based on (1) its transformative profit-driven development ideology, (2) its detachment of remittances from the political economy of migrant labour regimes, and (3) its dismissal of existing modes of remitting and uses of the funds

Entrepreneurs’ mental health and well-being:A review and research agenda

Interest in entrepreneurs’ mental health and well-being (MWB) is growing in recognition of the role of MWB in entrepreneurs’ decision making, motivation, and action. Yet relevant knowledge is dispersed across disciplines, which makes what we currently understand about entrepreneurs’ MWB unclear. In this systematic review I integrate insights from 144 empirical studies. These studies show that research is focused on three research questions: (1) Do different types of entrepreneurs differ in their MWB? What are the (2) antecedents and (3) consequences of entrepreneurs’ MWB? The review systematizes evidence on known antecedents and consequences of entrepreneurs’ MWB but also reveals overlooked and undertheorized sources and outcomes of entrepreneurs’ MWB. The review provides a mapping and framework that advance research on entrepreneurs’ MWB and help to position entrepreneurs’ MWB more centrally in management and entrepreneurship research. It calls for researchers to go beyond applying models developed for employees to understand entrepreneurs. Instead, the findings point the way to developing a dedicated theory of entrepreneurial work and MWB that is dynamic, socialized, and open to considering context and acknowledges variability and fluidity across entrepreneurs’ life domains, as well as the centrality of work for entrepreneurs’ identity

Measuring regional creative capacity: A literature review for rural-specific approaches

Recent theories on regional creative capacity often focus on urban regions without taking into account rural regions. In addition, the application of such analyses to rural regions may lead to misrepresentation or misunderstanding of rural creative capacity. Against this background, the aim of the present study is to integrate the existing literature on different components of creative capacity, namely, knowledge, innovation, entrepreneurship and networks, in order to build a more comprehensive framework for rural creative capacity and its evaluation. In the light of the perspective from the empirical literature review on the evaluation of creative capacity in rural regions, various empirical measurements seem to misrepresent or underestimate the creative capacity of rural regions. Therefore, there is a clear need to use the locality in relation to its dynamics, i.e. tacit knowledge, cultural heritage and social and physical environment as the main and basic measurement unit for creative capacity analysis. 2010 Taylor & Francis

A Cross-Cultural Comparison of Business Complaint Management Expectations

This paper is in closed access until 9th Dec 2016.Copyright © Taylor and Francis Group, LLC. This study explores the complaint management expectations of 72 British and 74 German organizational buyers using automated online means-end laddering and a Hierarchical Value Map presentation. It conceptualizes the links between expected complaint resolution attributes by the buyer (i.e., means) and the buyer's value perceptions (i.e., ends). Unlike previous research, we highlight similarities and differences in the drivers behind and attributes of complaint management expectations across two countries (Germany and the United Kingdom). Even in countries appearing to be similar economically and culturally, we find differences in the desired attributes. British buyers, for example, emphasize softer complaint resolution attributes compared to Germans. Our study is the first to present a model of complaint management expectations incorporating the role of culture, and it provides managerial directions on standardization and adaption of complaint resolution attributes. Furthermore, it evaluates justice dimensions (especially interactional justice) and their impact on perceptions of complaint management

The entrepreneurial ladder, gender, and regional development

Gender differences at five levels of entrepreneurial engagement are explained using country effects while controlling for individual-level variables. We distinguish between individuals who have never considered starting up a business, those who are thinking about it, and nascent, young, and established entrepreneurs. We use a large international dataset that includes respondents from 32 European countries, three Asian countries, and the United States. Findings show that cross-country gender differences are largest in the first and final transitions of the entrepreneurial process. In par