NESH Regulates Dendritic Spine Morphology and Synapse Formation

Background: Dendritic spines are small membranous protrusions on the neuronal dendrites that receive synaptic input from axon terminals. Despite their importance for integrating the enormous information flow in the brain, the molecular mechanisms regulating spine morphogenesis are not well understood. NESH/Abi-3 is a member of the Abl interactor (Abi) protein family, and its overexpression is known to reduce cell motility and tumor metastasis. NESH is prominently expressed in the brain, but its function there remains unknown. Methodology/Principal Findings: NESH was strongly expressed in the hippocampus and moderately expressed in the cerebral cortex, cerebellum and striatum, where it co-localized with the postsynaptic proteins PSD95, SPIN90 and F-actin in dendritic spines. Overexpression of NESH reduced numbers of mushroom-type spines and synapse density but increased thin, filopodia-like spines and had no effect on spine density. siRNA knockdown of NESH also reduced mushroom spine numbers and inhibited synapse formation but it increased spine density. The N-terminal region of NESH co-sedimented with filamentous actin (F-actin), which is an essential component of dendritic spines, suggesting this interaction is important for the maturation of dendritic spines. Conclusions/Significance: NESH is a novel F-actin binding protein that likely plays important roles in the regulation o

SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism

Genetic mutations of SHANK3 have been reported in patients with intellectual disability, autism spectrum disorder (ASD) and schizophrenia. At the synapse, Shank3/ProSAP2 is a scaffolding protein that connects glutamate receptors to the actin cytoskeleton via a chain of intermediary elements. Although genetic studies have repeatedly confirmed the association of SHANK3 mutations with susceptibility to psychiatric disorders, very little is known about the neuronal consequences of these mutations. Here, we report the functional effects of two de novo mutations (STOP and Q321R) and two inherited variations (R12C and R300C) identified in patients with ASD. We show that Shank3 is located at the tip of actin filaments and enhances its polymerization. Shank3 also participates in growth cone motility in developing neurons. The truncating mutation (STOP) strongly affects the development and morphology of dendritic spines, reduces synaptic transmission in mature neurons and also inhibits the effect of Shank3 on growth cone motility. The de novo mutation in the ankyrin domain (Q321R) modifies the roles of Shank3 in spine induction and morphology, and actin accumulation in spines and affects growth cone motility. Finally, the two inherited mutations (R12C and R300C) have intermediate effects on spine density and synaptic transmission. Therefore, although inherited by healthy parents, the functional effects of these mutations strongly suggest that they could represent risk factors for ASD. Altogether, these data provide new insights into the synaptic alterations caused by SHANK3 mutations in humans and provide a robust cellular readout for the development of knowledge-based therapies

Service Systems in Changing Paradigms: An Inquiry Through the Systems Sciences

For professionals at the beginning of the 21st century, much of the conventional wisdom on business management and engineering is founded in the 20th century industrial / manufacturing paradigm. In developed economies, however, the service sector now dominates the manufacturing sector, just as manufacturing prevailed over the agricultural sector after the industrial revolution.\ud This chapter proposes the development of a body of knowledge on services systems, based on foundations in the systems sciences. The approach includes the design of\ud the systems of inquiry, acknowledging that body of knowledge on 21st century service systems is relatively nascent. A program of action science is proposed, with an\ud emphasis on multiple realities and knowledge development through dialectic. The outcome pursued is an increased number of T-shaped people with depth and breadth\ud in service systems, in communities of inquiry of researchers and practitioners

Service Interaction Design: A Hawk-Dove Game Based Approach to Managing Customer Expectations for Oligopoly Service Providers

[[abstract]]In the “experience economy”, effectively delivering memorable and exciting customer experiences has become a key issue for service providers. Service experience delivery involves service encounters through which interactions between service providers and customers can be shaped into interactive artifacts managing customer expectations and dynamically delivering suitable services. Service interaction design aims to optimize customer interactions with services to match customer expectations and yield satisfactory service experiences. On the other hand, service providers typically make profits and cost the priority, despite knowing that high service quality can maximize satisfaction, particularly in markets served by an oligopoly, resulting in customers only accepting existing limited-value services. Hence, the oligopoly market can be regarded as a value-bounded context. Additionally, understanding customer expectations regarding a wide range of interactions is crucial to service providers selecting and designing services that match customer expectations. Therefore, this paper presents a service interaction design mechanism to help oligopoly service providers systematically and effectively manage customer expectations in dynamic interactions, even in value-bounded contexts. The proposed mechanism models this service interaction design problem as a series of Hawk-Dove games that approach an evolutionary stable state. The evaluation results suggest that oligopoly service providers should change their mindsets and design service interactions to manage customer expectations associated with service delivery, not only to ensure high satisfaction and profit but also to engage customers in co-creating value.[[notice]]補正完畢[[journaltype]]國外[[incitationindex]]SCI[[ispeerreviewed]]

Introduction to tactical management research

The first chapter outlines the research context—starting with what tactical management is, defining tactical management, and clarifying tactical management managerial and information system distinctiveness and needs. The outlining of the research context continues with reference to the manager as our subject of interest, but also incorporating the questions of what is being managed—a complex adaptive system, and in what kind of environment—complex, dynamic, turbulent. These constructs define the course of the research and its goal. The theoretical positioning of the research follows. The research methodology, named “methodological kaleidoscope” (due to its assembled nature of Design Science Research, Action Design Research, nested problem solving, and CIMO logic), is presented along with visualizations of how the research implements it