Distinct Early Molecular Responses to Mutations Causing vLINCL and JNCL Presage ATP Synthase Subunit C Accumulation in Cerebellar Cells

Variant late-infantile neuronal ceroid lipofuscinosis (vLINCL), caused by CLN6 mutation, and juvenile neuronal ceroid lipofuscinosis (JNCL), caused by CLN3 mutation, share clinical and pathological features, including lysosomal accumulation of mitochondrial ATP synthase subunit c, but the unrelated CLN6 and CLN3 genes may initiate disease via similar or distinct cellular processes. To gain insight into the NCL pathways, we established murine wild-type and CbCln6nclf/nclf cerebellar cells and compared them to wild-type and CbCln3Δex7/8/Δex7/8 cerebellar cells. CbCln6nclf/nclf cells and CbCln3Δex7/8/Δex7/8 cells both displayed abnormally elongated mitochondria and reduced cellular ATP levels and, as cells aged to confluence, exhibited accumulation of subunit c protein in Lamp 1-positive organelles. However, at sub-confluence, endoplasmic reticulum PDI immunostain was decreased only in CbCln6nclf/nclf cells, while fluid-phase endocytosis and LysoTracker® labeled vesicles were decreased in both CbCln6nclf/nclf and CbCln3Δex7/8/Δex7/8 cells, though only the latter cells exhibited abnormal vesicle subcellular distribution. Furthermore, unbiased gene expression analyses revealed only partial overlap in the cerebellar cell genes and pathways that were altered by the Cln3Δex7/8 and Cln6nclf mutations. Thus, these data support the hypothesis that CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival

The science of organizational design: fit between structure and coordination

Abstract Organization design is a major factor determining an organization’s performance and how the people work together in these organizations. In the paper, we argue that designing organizations should be scientific-based and forward-looking. This raises challenges in designing organizations in contexts and situations that are new and have not been seen before. Experimentation of what is and what might be is the basis for exploring and examining what makes a good science for organizational design. Experimentation permits us to examine what might be for organization designs, which are not well understood or may not exist yet. Collaborative communities, new ventures, agile organizations, and temporary organizations are examples; experimentation permits us explore and examine what is and what might be and to examine the organizational design problem and perform experiments to understand the relationship between structure and coordination mechanisms of information, communications, decisions, trust, and incentives—the basis for the multi-contingency theory of organizational design. An organizational design must specify the fit between the structure of division of tasks in the organization with its coordination, or how to make these tasks work in concert. These tasks can be interdependent and uncertain. To design good organizations, we need empirical evidence about what is and exploration about what might be; we need a good theoretical basis for being able to generalize our knowledge. To illustrate our point, we examine two experiments on the classic M-form hypothesis—a computer simulation that examines coordination, organization structure, and interdependency and a laboratory experiment that examines the effect of incentives on opportunism and performance. Together, we find that the M-form is a robust organizational design, but with contingent conditions. Finally, we discuss how observation and experimentation together is the foundation for the development of scientific-based theory of organizational design

Do synergies exist in related acquisitions? - A meta-analysis of acquisition studies

Mergers and Acquisitions (M&A) aim to increase wealth for shareholders of the acquiring company, in particular by creating synergies. It is often assumed that relatedness is a source of synergies. Our study distinguishes between business, cultural, technological and size relatedness. It discusses the reasons why these different forms of relatedness can lead to an acquisition success and conducts a meta-analysis of 67 prior M&A studies. Results indicate that positive effects can be expected under specific conditions only and have a limited overall impact on acquisition success. A moderator analysis finds that synergies stemming from relatedness depend on industry-, country-, and investor-characteristics

Collaborative organizational forms: on communities, crowds, and new hybrids

Abstract In this article, I examine collaborative organizational forms in terms of their institutional properties and the mechanisms by which they solve the universal problems of organizing. Based on three ideal forms—markets, hierarchies, and communities—I propose a framework for analyzing and mapping organizational forms. The framework expands our understanding of the ideal forms and derives a set of analytically distinct hybrids at the intersection of the ideal types. The framework also specifies the main conditions that drive organizations to change form and move toward another hybrid or ideal form. The theoretical review of collaborative organizational forms is illustrated and informed by three empirical cases of new forms within the domains of drug discovery, software development, as well as professional services. Further, I discuss plural forms and the role of hierarchy in collaborative forms. Finally, I outline implications for research and practice in terms of comparative analysis of organizational forms, the role of crowds, as well as the interplay between new technologies and new organizational forms

Revisiting the trustworthiness-performance-governance nexus in international joint ventures

This paper contributes to the research on international joint ventures (IJV) in the following ways: (1) by identifying different patterns of governance that partners in the post-formation period exercise and examining how contrasting patterns relate to variations in perceived partner’s trustworthiness, as well as to IJV performance; (2) by empirically testing the extent to which partners emphasize or even renegotiate and change different elements of governance; and (3) by complementing existing studies that have examined only unidirectional links among trustworthiness, performance and governance by considering possible simultaneous relationships that may exist among these variables. The findings from a survey and follow-up interviews with international joint ventures located in Taiwan reveal that levels of partners’ trustworthiness and performance satisfaction each, by itself, may lead to the deployment of different governance measures. However, it is the combinations of extreme (high or low) variants on both partners’ trustworthiness and performance satisfaction that seem to generate clearer patterns of governance. Low satisfaction and partners’ trustworthiness seem to encourage intensification of control or the deployment of more aggressive governance measures. In contrast, high performance satisfaction and partners’ trustworthiness may foster a combination of soft and routine forms of control