Institutional change and regional development in China: the case of commodity trading markets

With this paper we explore how institutional changes have influenced the regional development of Yiwu City, East China. The regional development in Yiwu City can be regarded as constituting a specific model in transitional China, which revolves around the establishment, growth, and internationalization of the local commodity trading market. The success of the Yiwu model lies in the interaction between globalization, local institutions, and commodity trading markets. However, we argue that the strategic coupling perspective has its limitations in explaining the development trajectory of the Yiwu model. We develop an integrated paradigm of regional development located between new regionalism and global production networks by synthesizing Scott’s institutional framework. We identify a pronounced and long-established cultural–cognitive element in the entrepreneurial spirit of local people, which led to the establishment of a commodity trading market at the beginning of 1980s. However, the sustainable development of the Yiwu model needs to be supplemented by normative and regulative institutional pillars. We further argue that the developmental local state remains critical to the regional development in developing countries in terms of correcting market failure, encouraging entrepreneurship, and creating a competitive business environment to accommodate globalization

Hepatic microRNA profiles offer predictive and mechanistic insights after exposure to genotoxic and epigenetic hepatocarcinogens.

In recent years, accumulating evidence supports the importance of microRNAs in liver physiology and disease; however, few studies have examined the involvement of these noncoding genes in chemical hepatocarcinogenesis. Here, we examined the liver microRNA profile of male Fischer rats exposed through their diet to genotoxic (2-acetylaminofluorene) and epigenetic (phenobarbital, diethylhexylphthalate, methapyrilene HCL, monuron, and chlorendic acid) chemical hepatocarcinogens, as well as to non-hepatocarcinogenic treatments (benzophenone, and diethylthiourea) for 3 months. The effects of these treatments on liver pathology, plasma clinical parameters, and liver mRNAs were also determined. All hepatocarcinogens affected the expression of liver mRNAs, while the hepatic microRNA profiles were associated with the mode of action of the chemical treatments and corresponded to chemical carcinogenicity. The three nuclear receptor-activating chemicals (phenobarbital, benzophenone, and diethylhexylphthalate) were characterized by the highly correlated induction of the miR-200a/200b/429, which is involved in protecting the epithelial status of cells and of the miR-96/182 clusters. The four non-nuclear receptor-activating hepatocarcinogens were characterized by the early, persistent induction of miR-34, which was associated with DNA damage and oxidative stress in vivo and in vitro. Repression of this microRNA in a hepatoma cell line led to increased cell growth; thus, miR-34a could act to block abnormal cell proliferation in cells exposed to DNA damage or oxidative stress. This study supports the proposal that hepatic microRNA profiles could assist in the earlier evaluation and identification of hepatocarcinogens, especially those acting by epigenetic mechanisms. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved

Time and dose-dependent effects of phenobarbital on the rat liver miRNAome.

In a previous study we had shown that treatment of male Fischer rats with exogenous chemicals for three months resulted in prominent, mode-of-action dependent effects on liver microRNA (miRNA) (Koufaris et al., 2012). Here we investigated how the effects of chemicals on liver miRNA in male Fischer rats relate to the length and dose of exposure to phenobarbital (PB), a drug with multiple established hepatic effects. Importantly, although acute PB treatment (1-7 days) had significant effects on liver mRNA and the expected effects on the liver phenotype (transient hyperplasia, hepatomegaly, cytochrome P450 induction), limited effects on liver miRNA were observed. However, at 14 days of PB treatment clear dose-dependent effects on miRNA were observed. The main effect of PB treatment from days 1 to 90 on liver miRNA was found to be the persistent, progressive, and highly correlated induction of the miR-200a/200b/429 and miR-96/182 clusters, occurring after the termination of the xenobiotic-induced transient hyperplasia. Moreover, in agreement with their reported functions in the literature we found associations between perturbations of miR-29b and miR-200a/200b by PB with global DNA methylation and zeb1/zeb2 proteins respectively. Our data suggest that miRNA are unlikely to play an important role in the acute responses of the adult rodent liver to PB treatment. However, the miRNA responses to longer PB exposures suggest a potential role for maintaining liver homeostasis in response to sub-chronic and chronic xenobiotic-induced perturbations. Similar studies for more chemicals are needed to clarify whether the temporal and dose pattern of miRNA-toxicant interaction identified here for PB are widely applicable to other xenobiotics. © 2013 Elsevier Ireland Ltd

Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis

MicroRNAs (miRNA) are a novel class of small noncoding single-stranded RNA molecules that regulate gene expression. There is increasing evidence of their importance in polycystic ovary syndrome (PCOS). The objective was to determine if miRNA-93 and miRNA-223 are differentially expressed in the circulation of women with PCOS compared to age matched women. A case–control study comparing women with PCOS (n = 25) to age and weight matched controls (n = 24) without PCOS was performed. MiRNA-93 and miRNA-223 were determined by total RNA reverse transcription. Both miRNA-93 and miRNA-223 were significantly increased relative to the control group (p < 0.01, p = 0.029 respectively). In both groups there was no correlation of either miRNA-93 or miRNA-223 with insulin, HOMA-IR, HOMA-β or testosterone levels. The area under the receiver operator characteristic curve for miR-223 and miR-93 was 0.66 and 0.72 respectively, suggesting miR-93 is a more efficient biomarker than miR-223 for diagnosis of PCOS. The combination of the two miRNAs together, tested using multiple logistic regression analysis, did not improve the diagnostic potential. In conclusion, circulating miRNA-93 and miRNA-223 were higher in women with PCOS compared to age and weight matched controls independent of insulin resistance and testosterone levels, and miR-93 may represent a novel diagnostic biomarker for PCOS

Managing human resource management tensions in project-based organisations: evidence from Bangalore

The article analyses the methods used by a large Indian software company to manage HRM tensions with arising from its activities as a project based organisation. These measures are found to be only partially successful

Talent development as an alternative to orthodox career thinking: the Scandinavian case

This chapter argues that orthodox career thinking – which focuses on vertical progression to higher-level managerial positions - is suffering from three shortcomings. First, it is insufficient to explain career dynamics in modern knowledge organizations. Second, it disregards the importance of experiential, lifelong learning on the job. Third, it does not incorporate how career is embedded in the organizational and cultural context, including a wide range of national, institutional features. Based on this, the chapter suggests that we move the focus from narrow career thinking to the more broad-banded concept of talent. The talent concept signifies any kind of outstanding competence of an individual (whether it is managerial or any kind of significant specialist field) which is strategically important to the organization, difficult to achieve, difficult to replace by other types of resources, and difficult to replicate by competitors. Also, a broader definition of how talent can be developed is needed, as it should encompass informal and experiential methods as well as formal education. The broader concept of talent is discussed in relation to the Scandinavian context, as the Scandinavian countries (Denmark, Norway and Sweden) are knowledge intensive economies with a highly educated workforce. This characteristic makes a broader talent paradigm much more appropriate that an orthodox managerial career perception and model

The effect of organizational separation on individuals' knowledge sharing in MNCs

The ability of an organization to apply knowledge globally has been conceptualized as critical for the existence of multinational corporations (MNCs). We argue for an organizational separation effect on knowledge sharing that challenges the view of the MNC as a latent social community. Using a unique data-set of more than 4.000 individual responses from an MNC, Telenor, we test how three types of drivers for individuals’ knowledge sharing –individuals’ motivation, and individuals’ perceptions of organizational values and organizational work practices- work differently within, as opposed to across, business units. Our analysis suggests that while intrinsic motivation, innovative values and job autonomy are relatively important drivers of knowledge sharing within the business units, extrinsic motivation, result-oriented values and participation in corporate employee development are relatively more important for knowledge sharing across business units

Responses of genes involved in cell cycle control to diverse DNA damaging chemicals in human lung adenocarcinoma A549 cells

BACKGROUND: Many anticancer agents and carcinogens are DNA damaging chemicals and exposure to such chemicals results in the deregulation of cell cycle progression. The molecular mechanisms of DNA damage-induced cell cycle alteration are not well understood. We have studied the effects of etoposide (an anticancer agent), cryptolepine (CLP, a cytotoxic alkaloid), benzo [a]pyrene (BaP, a carcinogenic polycyclic aromatic hydrocarbon) and 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP, a cooked-meat derived carcinogen) on the expression of cell cycle regulatory genes to understand the molecular mechanisms of the cell cycle disturbance. RESULTS: A549 cells were treated with DMSO or chemicals for up to 72 h and periodically sampled for cell cycle analysis, mRNA and protein expression. DMSO treated cells showed a dominant G1 peak in cell cycle at all times examined. Etoposide and CLP both induced G2/M phase arrest yet the former altered the expression of genes functioning at multiple phases, whilst the latter was more effective in inhibiting the expression of genes in G2-M transition. Both etoposide and CLP induced an accumulation of p53 protein and upregulation of p53 transcriptional target genes. Neither BaP nor PhIP had substantial phase-specific cell cycle effect, however, they induced distinctive changes in gene expression. BaP upregulated the expression of CYP1B1 at 6–24 h and downregulated many cell cycle regulatory genes at 48–72 h. By contrast, PhIP increased the expression of many cell cycle regulatory genes. Changes in the expression of key mRNAs were confirmed at protein level. CONCLUSION: Our experiments show that DNA damaging agents with different mechanisms of action induced distinctive changes in the expression pattern of a panel of cell cycle regulatory genes. We suggest that examining the genomic response to chemical exposure provides an exceptional opportunity to understand the molecular mechanism involved in cellular response to toxicants

The cellular toxicology of mitragynine, the dominant alkaloid of the narcotic-like herb, Mitragyna speciosa Korth

Mitragyna speciosa Korth (Kratom), a herb of the Rubiaceae family is indigenous to southeast Asia. The plant and its dominant alkaloid mitragynine (MIT) are narcotic/analgesic and illicit consumption is widespread in Asia; the toxicological consequences of consumption are poorly documented. We determined cytotoxicity of MIT on human cell lines and report dose and time-dependent stimulation and inhibition of proliferation. Since MIT has powerful opiate-like activity, we focussed on human neuronal SH-SY5Y cell line and found the colony forming ability of cells treated with MIT showed a dose-dependent trend for reduced survival. Studies using metabolically competent MCL-5 cells and chemical inhibitors indicated that CYP 2E1 and 2A6 were involved in the cytotoxicity. Cytotoxicity was preceded by cell cycle arrest mainly at G1 and S phase. To assess whether arrest was due to DNA damage or mutation, we examined genotoxic potential using the L5178 TK +/− mouse lymphoma assay and found that MIT was not genotoxic at the TK locus, even at doses that were highly cytotoxic. To investigate mechanisms of MIT cytotoxicity, we used flow cytometry and annexin V with 7-amino-actinomycin D staining and show apoptosis and necrotic activity. Apoptosis was further supported as MIT rapidly induced the activity of executioner caspases 3/7. However, cytotoxicity of MIT was partially reduced by inclusion of the opioid receptor antagonist naloxone, a μ and δ opioid receptor antagonist, suggesting that cytotoxicity depends in part on opioid signalling, consistent with the known toxicity of other opiates. Based on consumption of 20 leaves per day of Mitragyna speciosa, we estimated daily human exposure to MIT to be about 17 mg MIT for regular consumers, potentially giving plasma concentrations in of 10−9 to 10 −7 M. Importantly, fatalities after kratom consumption have been reported to occur in individuals with blood mitragynine concentrations of between 0.45–1.0 μM, substantially lower than the threshold of toxicity predicted from this in vitro report. Clearly the implications of these findings to humans consuming Mitragyna speciosa leaves will require further study, but individuals taking large quantities of these opiate-like materials may be at risk, especially those who have a high CYP2E1 activity, such as heavy alcohol users

Contextualizing AMO explanations of knowledge sharing in MNEs: the role of organizational and national culture

Ability, motivation, and opportunity (AMO) approaches have dominated studies of knowledge sharing in multinational enterprises (MNEs). We argue that there is a need to consider both the national and organizational cultural contexts. Beyond their direct influence on knowledge sharing with colleagues in other business units (BUs), national and organizational culture significantly reinforce the positive relation between individual motivation and knowledge sharing. Thus, our multi-level approach to knowledge sharing in MNEs gives rise to a contextualized AMO approach that provides a novel and more potent understanding of variations in knowledge sharing. At the individual level, our approach includes the degree of ability in the sense of professional competence, intrinsic motivation, and opportunities to interact with colleagues in other BUs. At the organizational and country levels, we examine the direct and indirect effects of a collaborative culture on knowledge sharing. We employ data from an MNE that operates across a variety of regions, including the Nordic countries, Central and Eastern Europe, and Southeast Asia. The sample consists of 11,484 individuals nested in 1,235 departments in 11 countries. As well as confirming the significance of individual competence, intrinsic motivation, and opportunities for interaction for knowledge sharing, our findings reveal that both organizational culture and national culture are important factors for our understanding of knowledge sharing. This suggests that over and above recruiting intrinsically motivated employees, managers can enhance knowledge sharing by developing collaborative organizational cultures at the departmental level