Dioctadecyldimethylammonium:monoolein nanocarriers for efficient in vitro gene silencing

This study describes a novel liposomal formulation for siRNA delivery, based on the mixture of the neutral lipid monoolein (MO) and cationic lipids of the dioctadecyldimethylammonium (DODA) family. The cationic lipids dioctadecyldimethylammonium bromide (DODAB) and chloride (DODAC) were compared in order to identify which one will most efficiently induce gene silencing. MO has a fluidizing effect on DODAC and DODAB liposomes, although it was more homogeneously distributed in DODAC bilayers. All MO-based liposomal formulations were able to efficiently encapsulate siRNA. Stable lipoplexes of small size (100-160 nm) with a positive surface charge (>+45 mV) were formed. A more uniform MO incorporation in DODAC:MO may explain an increase of the fusogenic potential of these liposomes. The siRNA-lipoplexes were readily internalized by human nonsmall cell lung carcinoma (H1299) cells, in an energy dependent process. DODAB:MO nanocarriers showed a higher internalization efficiency in comparison to DODAC:MO lipoplexes, and were also more efficient in promoting gene silencing. MO had a similar gene silencing ability as the commonly used helper lipid 1,2-dioleyl-3-phosphatidylethanolamine (DOPE), but with much lower cytotoxicity. Taking in consideration all the results presented, DODAB:MO liposomes are the most promising tested formulation for systemic siRNA delivery.This work was supported by FEDER through POFC - COMPETE and by national funds from FCT through the projects PEst-C/BIA/UI4050/2011 (CBM.A), PEst-C/FIS/UI0607/2011 (CFUM), and PTDC/QUI/69795/2006, while Ana Oliveira holds scholarship SFRH/BD/68588/2010. Eloi Feitosa thanks FAPESP (2011/03566-0) and CNPq (303030/2012-7), and Renata D. Adati thanks FAPESP for scholarship (2011/07414-0). K. Raemdonck is a postdoctoral fellow of the Research Foundation - Flanders (FWO-Vlaanderen). We acknowledge NanoDelivery-I&D em Bionanotecnologia, Lda. for access to their equipment

Physicochemical and Biological Evaluation of siRNA Polyplexes Based on PEGylated Poly(amido amine)s

PURPOSE: Use of RNA interference as novel therapeutic strategy is hampered by inefficient delivery of its mediator, siRNA, to target cells. Cationic polymers have been thoroughly investigated for this purpose but often display unfavorable characteristics for systemic administration, such as interactions with serum and/or toxicity. METHODS: We report the synthesis of a new PEGylated polymer based on biodegradable poly(amido amine)s with disulfide linkages in the backbone. Various amounts of PEGylated polymers were mixed with their unPEGylated counterparts prior to polyplex formation to alter PEG content in the final complex. RESULTS: PEGylation effectively decreased polyplex surface charge, salt- or serum-induced aggregation and interaction with erythrocytes. Increasing amount of PEG in formulation also reduced its stability against heparin displacement, cellular uptake and subsequent silencing efficiency. Yet, for polyplexes with high PEG content, significant gene silencing efficacy was found, which was combined with almost no toxicity. CONCLUSIONS: PEGylated poly(amido amine)s are promising carriers for systemic siRNA delivery in vivo

National and firm-level drivers of the devolution of HRM decision making to line managers

Multinational companies must understand the influences on responsibility for managing people so that they can manage talent consistently thus ensuring that it is transferable across locations. We examine the impact of firm and national level characteristics on the devolution of HRM decision making to line managers. Our analysis draws on data from 2335 indigenous organizations in 21 countries. At the firm level, we found that where the HR function has higher power, devolution is less likely. At the national level, devolution of decision making to line management is more likely in societies with more stringent employment laws and lower power distance

Muziek en natievorming in België: het muziekleven te Brussel 1830-1850

Koen Buyens, Music and nation building in BelgiumThe article examines the Brussels music scene (1830-1850) in relation to the efforts made at the time with regard to nation building after the Belgian Revolution of 1830. The first part focuses on François-Joseph Fétis, who was appointed director of the Brussels conservatorium in 1832. In this capacity, Fétis intended to model both the Brussels music scene and the national music scene according to his own clear-cut ideas. In the second part it is argued that musical life in Brussels was suffused with a military spirit. The music of military bands was probably the core element of the urban soundscape. The third part concentrates on the obstacles that hampered the country’s musical development. The crushing preponderance of Paris reduced the Belgian capital to a place of servile imitation. From 1840 onwards this provoked heated reactions among the early advocates of the Flemish case, who soon fell under the spell of German music

Linking behavioral control to frontline employee commitment and performance: a test of two alternative explanations using motivation theories

We propose and empirically test a model in which behavioral control is linked to frontline employee commitment and performance. We test two alternative explanations by examining the intermediate role of job autonomy and situational learning orientation. The hypotheses are tested using multiple-source survey data from a sample of 1184 frontline employees and their supervisors. Results indicate that situational learning orientation is an important construct in linking behavioral control to performance. Job autonomy shows to be important in explaining employee outcomes but is only marginally related to behavioral control. Theoretical and managerial implications are discussed.

Managerial learning from on-the-job experiences: An integrative framework to guide future research

Both scholars and practitioners increasingly attest to the importance of developmental on-the-job (OTJ) experiences as the primary source of managerial learning. However, there is no single theory of managerial OTJ learning; several elements are missing in the conceptualization of the developmental OTJ experience construct, no comprehensive nomological network of the construct has been developed so far, and the underlying mechanisms explaining the relationship with relevant learning outcomes have not been examined in depth. In response to these shortcomings, current paper proposes an integrative framework of managerial learning from developmental OTJ experiences. First, we suggest developing a better understanding of the developmental OTJ experience construct by considering it from a scope beyond the managers’ job assignments, by also including more quantitative measures of OTJ experience and by looking further than the current job. Next, the central variable of interest is linked to individual and situational variables that influence directly the extent to which managers are confronted with developmental OTJ experiences as well as involve conditions that enhance or inhibit managerial learning (i.e. moderating mechanisms). Finally, our model emphasizes the importance to take into account relevant mediating mechanisms in order to fully understand the impact of OTJ experiences on managerial learning. Building on our model, we conclude with a discussion of promising avenues for future research.

Psychological Empowerment in the Workplace: Reviewing the Empowerment Effects on Critical Work Outcomes

This paper reviews theory and empirical findings on the effects of empowerment in the workplace. Data from existing studies is used to assess the effects of the four empowerment dimensions on affective and behavioral employee responses. Data is reanalyzed using hierarchical regression analysis. Confirming growing skepticism among practitioners and academics, this study indicates that empowerment practices result in more satisfied and committed, but not necessarily better performing employees. Furthermore, it is shown that there is a differential impact of the distinct empowerment dimensions on employee performance levels. Theoretical and practical implications are discussed.Employee Empowerment; Employee Performance