RATIONALE:The human genome harbors a large number of sequences encoding for RNAs that are not translated but control cellular functions by distinct mechanisms. The expression and function of the ...longer transcripts namely the long noncoding RNAs in the vasculature are largely unknown.
OBJECTIVE:Here, we characterized the expression of long noncoding RNAs in human endothelial cells and elucidated the function of the highly expressed metastasis-associated lung adenocarcinoma transcript 1 (MALAT1).
METHODS AND RESULTS:Endothelial cells of different origin express relative high levels of the conserved long noncoding RNAs MALAT1, taurine upregulated gene 1 (TUG1), maternally expressed 3 (MEG3), linc00657, and linc00493. MALAT1 was significantly increased by hypoxia and controls a phenotypic switch in endothelial cells. Silencing of MALAT1 by small interfering RNAs or GapmeRs induced a promigratory response and increased basal sprouting and migration, whereas proliferation of endothelial cells was inhibited. When angiogenesis was further stimulated by vascular endothelial growth factor, MALAT1 small interfering RNAs induced discontinuous sprouts indicative of defective proliferation of stalk cells. In vivo studies confirmed that genetic ablation of MALAT1 inhibited proliferation of endothelial cells and reduced neonatal retina vascularization. Pharmacological inhibition of MALAT1 by GapmeRs reduced blood flow recovery and capillary density after hindlimb ischemia. Gene expression profiling followed by confirmatory quantitative reverse transcriptase-polymerase chain reaction demonstrated that silencing of MALAT1 impaired the expression of various cell cycle regulators.
CONCLUSIONS:Silencing of MALAT1 tips the balance from a proliferative to a migratory endothelial cell phenotype in vitro, and its genetic deletion or pharmacological inhibition reduces vascular growth in vivo.
RATIONALE:Increasing evidence indicates the presence of lncRNAs in various cell types. Airn is an imprinting gene transcribed from the paternal chromosome. It is in antisense orientation to the ...imprinted, but maternally derived, Igf2r gene, on which Airn exerts its regulation in cis. Although Airn is highly expressed in the heart, functions aside from imprinting remain unknown.
OBJECTIVE:Here, we studied the functions of Airn in the heart, especially cardiomyocytes.
METHODS AND RESULTS:Silencing of Airn via siRNAs augmented cell death, vulnerability to cellular stress, and reduced cell migration. To find the cause of such phenotypes, the potential binding partners of Airn were identified via RNA pull-down followed by mass spectrometry, which indicated Igf2bp2 (insulin-like growth factor 2 mRNA-binding protein 2) and Rpa1 (replication protein A1) as potential binding partners. Further experiments showed that Airn binds to Igf2bp2 to control the translation of several genes. Moreover, silencing of Airn caused less binding of Igf2bp2 to other mRNAs and reduced translation of Igf2bp2 protein.
CONCLUSIONS:Our study uncovers a new function of Airn and demonstrates that Airn is important for the physiology of cardiomyocytes.
Abstract
Myogenesis is a complex process required for skeletal muscle formation during embryonic development and for regeneration and growth of myofibers in adults. Accumulating evidence suggests ...that long non-coding RNAs (lncRNAs) play key roles in regulating cell fate decision and function in various tissues. However, the role of lncRNAs in the regulation of myogenesis remains poorly understood. In this study, we identified a novel muscle-enriched lncRNA called ‘Myolinc (AK142388)’, which we functionally characterized in the C2C12 myoblast cell line. Myolinc is predominately localized in the nucleus, and its levels increase upon induction of the differentiation. Knockdown of Myolinc impairs the expression of myogenic regulatory factors and formation of multi-nucleated myotubes in cultured myoblasts. Myolinc also regulates the expression of Filip1 in a cis-manner. Similar to Myolinc, knockdown of Filip1 inhibits myogenic differentiation. Furthermore, Myolinc binds to TAR DNA-binding protein 43 (TDP-43), a DNA/RNA-binding protein that regulates the expression of muscle genes (e.g. Acta1 and MyoD). Knockdown of TDP-43 inhibits myogenic differentiation. We also show that Myolinc−TDP-43 interaction is essential for the binding of TDP-43 to the promoter regions of muscle marker genes. Finally, we show that silencing of Myolinc inhibits skeletal muscle regeneration in adult mice. Altogether, our study identifies a novel lncRNA that controls key regulatory networks of myogenesis.
Provides a diverse but integrated set of opinion pieces, analyses and cases about Russian business, covering markets and macro perspectives, strategy and governance, innovation and entrepreneurship, ...internationalization and leadership. The book illustrates the under reported and multifaceted nature of the life of Russian business.
Building on research within corporate governance and strategic management, this paper explores how managerial discretion stemming from managerial task environment influences the balance between ...controlling and enabling managerial decision-making. Two sets of alternative hypotheses about the moderating effects of managerial discretion on the performance effects of board monitoring and CEO human capital were formulated. The results indicate partial support for governance-driven explanation showing that the association between board monitoring and market-based performance is strongest in environments characterized by high levels of managerial discretion. The findings also show that CEO human capital is positively associated with market-based performance in low-discretion environments, while in high-discretion environments this relationship turns negative. The central contribution of this paper is to demonstrate that managerial discretion is a useful tool to explain the balance between controlling and enabling managerial decision making.
Purpose: This paper examines the problems of changing the systems of the structures of governance in the first years of the existence of Soviet rule using the example of the armed forces, the ...redistribution of powers between them, the strengthening of the administrative influence of individual departments on the most important decisions in this area. Methodology: The basis of scientific research is the dialectical materialist method, which allows revealing the patterns of development of the relevant legal industry and suggesting the most likely options for the development of legislation and law enforcement practice. In addition, the authors use the historical-chronological method, the historical-systemic method, the formal-logical method, the method of comparative law, the system-structural method, the technical-legal method, etc. Result: a dramatic change in internal political line with the advent of the Bolsheviks predetermined the sweeping changes in the approaches to public administration. Having no experience in organizing public authority, the leaders of the revolutionary movement proposed and approved numerous ideas related to improving the efficiency of the management of uniformed services, which was very important in the conditions of the civil war and foreign intervention. Applications: This research can be used for universities, teachers, and students. Novelty/Originality: In this research, the model of the development of the Soviet state system in 1918-1940 is presented in a comprehensive and complete manner.
•Despite its growing social and business relevance, research on top management teams (TMTs) cultural diversity remains sparse and fragmented.•This semi-structured literature review provides a ...comprehensive overview and synthesis of current knowledge about cultural diversity in TMTs, and proposes an agenda for theoretical, methodological, and conceptual development.•Research on TMT cultural diversity would benefit from more explicit definitions and measures, which go beyond measures of nationality and racioethnicity.•Current research is moving from a focus on whether TMTs cultural diversity influences organizations towards how and why it matters.•With national institutional context shaping both definition and influence of TMT cultural diversity, there is a need for further research in non-western contexts.
Despite its growing social relevance, research on cultural diversity in top management teams (TMTs) has been sparse and fragmented. To build a firm foundation and facilitate the development of this field, we review and synthesize 106 key articles published between 1997 and 2021. Our study provides a comprehensive field map explicating the antecedents and influence of TMT cultural diversity, showing that cultural diversity constitutes a distinct and important aspect of TMT diversity that has significant implications for a variety of outcomes. By critically assessing the field, we identify key research gaps and promising areas for future research.
While it has long been recognized that boards of directors perform two primary functions – monitoring and resource provision – little research has systematically examined the relationship between ...these two functions in public corporations. Given the growing external emphasis on the monitoring function by investors and advocates of corporate governance reforms, it is important to understand how such an emphasis impacts the resource provision function. In addition to identifying the composition of the nominating committee as a key to understanding the relationship, we propose two mechanisms through which the formation of an independent nominating committee in response to the external emphasis on monitoring leads to a decline in board resource provision. One mechanism is through a decline in information sharing between top managers and the nominating committee in new director selection, which results in a divergence between board capital and the firm's specific resource needs. The other is through decreased trust between the CEO and the board, which results in a less collaborative CEO-board relationship. To alleviate this negative impact that an external emphasis on monitoring has on resource provision, we propose that boards can bring non-CEO executives back onto nominating committees as inside directors. Our theoretical analysis contributes to the understanding of how the composition of the nominating committee influences board monitoring and resource provision, and has important implications for corporate governance research and practices.
Research Question/Issue
How does organizational context influence the impact of board control over managerial decisions on shareholder wealth?
Research Findings/Insights
We introduce a new ...theoretical concept—organizational discretion—to characterize the upper limit of managers' latitude of actions presented by their organizational context and propose that it moderates the impact of board control on shareholder wealth. Specifically, we first argue that strategic control by boards over managerial decisions reduces managers' latitude of actions and leads to trade‐offs between the containment of managerial opportunism and the pursuit of strategic opportunities, which consequently influence the relationship between strategic control and shareholder wealth. We then suggest that the trade‐offs incurred by strategic control over managerial decisions are more prominent in firms with high organizational discretion. Because of the trade‐offs, we propose that boards are likely to decide whether to rely more on strategic control or financial control in internal corporate governance based on their firms' level of organizational discretion.
Theoretical/Academic Implications
By introducing the concept of organizational discretion and highlighting the trade‐offs caused by boards' strategic control over managerial decisions, we advance a contingency perspective to enhance the understanding about the impact of board control on shareholder wealth. It also bridges the strategic management and corporate governance research on managerial discretion that has largely evolved separately in the literature.
Practitioner/Policy Implications
Boards should attend to the trade‐offs between the containment of managerial opportunism and the pursuit of strategic opportunities when exercising strategic control over managerial decisions. Moreover, considering the trade‐offs involved, boards should carefully design and implement internal corporate governance mechanisms based on their firms' level of organizational discretion.
Abstract
Family firms often opt for a combined CEO and board chair positions, yet the implications of such leadership structure on firm performance remain a subject of scholarly debate. We introduce ...the socioemotional wealth (SEW) perspective as a unifying framework that bridges the divergent views of stewardship and agency theories. We argue that the effects of CEO duality on performance are contingent upon the balance between extended and restricted SEW priorities. Drawing on a sample of listed companies on the Milan Stock Exchange between 2003 and 2015, our empirical analysis reveals that listed family firms derive greater benefits from CEO duality compared to their non‐family counterparts. Moreover, our findings demonstrate that such leadership structure renders the highest performance benefits in listed family firms when the CEO–chair is not a family member, particularly during periods of economic crisis.
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