Early evidence on how Industry 4.0 reshapes MNEs' global value chains: The role of value creation versus value capturing by headquarters and foreign subsidiaries.

In anticipation of the upcoming changes and turbulence caused by Industry 4.0, in which digital integration connects all value chain members, managers at leading multinational enterprises (MNEs) are scrambling to predict the associated changes in the market. This pioneering study advances our understanding by investigating the impact of an MNE's Industry 4.0 orientation on the globalization of its value chain network. Identifying two types of value-generation activities as potential moderators, namely value creation and value capturing, we compare the moderation effects when these activities are conducted by headquarters versus foreign subsidiaries. We test the proposed model using a panel dataset comprising 5572 subsidiary-year observations from 358 Korean MNEs from 2011 to 2019. The results show that an MNE's Industry 4.0 orientation leads to a more rapid expansion of its distribution network than of its supplier network. Furthermore, value creation by headquarters has a stronger positive impact on the globalization of its distribution network than that of its supplier network, whereas value creation by subsidiaries has a stronger positive impact on the globalization of its supplier network than that of its distribution network. However, value capturing has a stronger impact on the globalization of the MNE's distribution network than that of its supplier network when performed by both locations. This study concludes by discussing the theoretical and managerial implications.

En prévision des turbulences et des changements à venir causés par l'Industrie 4.0 dans laquelle l'intégration numérique relie tous les membres de la chaîne de valeur, les managers des grandes entreprises multinationales (Multinational Enterprises - MNEs) s'efforcent de prévoir les changements associés sur le marché. Cette recherche pionnière fait progresser notre connaissance en étudiant l'impact de l'orientation vers l'Industrie 4.0 des MNEs sur la globalisation de leurs réseaux de chaîne de valeur. En identifiant deux types d'activités génératrices de valeur comme modérateurs potentiels, à savoir la création de valeur et la capture de valeur, nous comparons les effets modérateurs lorsque ces activités sont menées par le siège social versus les filiales étrangères. Nous testons le modèle proposé à l'aide d'un ensemble de données de panel comprenant 5 572 observations d'année-filiale de 358 MNEs coréennes durant la période 2011 - 2019. Les résultats montrent que l'orientation vers l'Industrie 4.0 d'une MNE conduit à une expansion de son réseau de distribution plus rapide que celle de son réseau de fournisseurs. En outre, la création de valeur par le siège social a un impact positif plus fort sur la globalisation de son réseau de distribution que sur celle de son réseau de fournisseurs, tandis que la création de valeur par les filiales exerce un impact positif plus fort sur la globalisation de son réseau de fournisseurs que sur celle de son réseau de distribution. Néanmoins, la capture de valeur a un impact plus fort sur la globalisation du réseau de distribution d'une MNE que sur celle de son réseau de fournisseurs lorsqu'elle est réalisée par les deux sites. Cette recherche se termine par une discussion des implications théoriques et managériales.

Anticipándose a los próximos cambios y turbulencias causadas por la Industria 4.0, en la cual la integración digital conecta a todos los miembros de la cadena de valor, los gerentes de las principales empresas multinacionales (EMN) se esfuerzan por predecir los cambios asociados en el mercado. Este estudio pionero avanza en nuestra comprensión investigando el impacto de la orientación de la Industria 4.0 de una EMN en la globalización de su red de cadena de valor. Al identificar dos tipos de actividades de generación de valor como moderadores potenciales, es decir, la creación de valor y la captura de valor, comparamos los efectos moderadores cuando estas actividades son llevadas a cabo por la casa matriz frente a las filiales extranjeras. Pusimos a prueba el modelo propuesto utilizando un conjunto de datos de panel que comprende 5.572 observaciones de años subsidiarios de 358 empresas multinacionales coreanas de 2011 a 2019. Los resultados muestran que la orientación a la Industria 4.0 de una empresa multinacional lleva a una expansión más rápida de su red de distribución que de su red de proveedores. Adicionalmente, la creación de valor por parte de la casa matriz tiene un impacto positivo más fuerte en la globalización de su red de distribución que en la de su red de proveedores, mientras que la creación de valor por parte de las filiales tiene un impacto positivo más fuerte en la globalización de su red de proveedores que en la de su red de distribución. Sin embargo, la captura de valor tiene un impacto más fuerte en la globalización de la red de distribución de la empresa multinacional que en la de su red de proveedores cuando es realizada en ambos lugares. El estudio concluye con un análisis de las implicaciones teóricas y gerenciales.

Antecipando as próximas mudanças e turbulências causadas pela Indústria 4.0, na qual integração digital conecta todos os membros da cadeia de valor, gerentes de principais empresas multinacionais (MNEs) estão se esforçando para prever as mudanças associadas no mercado. Este estudo pioneiro avança nosso entendimento ao investigar o impacto da orientação de uma MNE na Indústria 4.0 na globalização de sua rede de cadeia de valor. Ao identificar dois tipos de atividades de geração de valor como potenciais moderadores, a saber, criação de valor e captura de valor, comparamos os efeitos moderadores quando essas atividades são conduzidas pela matriz versus subsidiárias estrangeiras. Testamos o modelo proposto usando um conjunto de dados em painel compreendendo 5.572 observações subsidiária-ano de 358 MNEs coreanas de 2011 a 2019. Os resultados mostram que uma orientação para a Indústria 4.0 por uma MNE leva a uma expansão mais rápida de sua rede de distribuição do que de sua rede de fornecedores. Além disso, a criação de valor pela matriz tem um impacto positivo mais forte na globalização de sua rede de distribuição do que na rede de fornecedores, enquanto a criação de valor pelas subsidiárias tem um impacto positivo mais forte na globalização de sua rede de fornecedores do que na rede de distribuição. No entanto, a captura de valor tem um impacto mais forte na globalização da rede de distribuição da MNE do que na rede de fornecedores quando realizada por ambas as localidades. Este estudo conclui discutindo as implicações teóricas e gerenciais.

Rad51 Regulates Reprogramming Efficiency through DNA Repair Pathway.

Rad51 is a key component of homologous recombination (HR) to repair DNA double-strand breaks and it forms Rad51 recombinase filaments of broken single-stranded DNA to promote HR. In addition to its role in DNA repair and cell cycle progression, Rad51 contributes to the reprogramming process during the generation of induced pluripotent stem cells. In light of this, we performed reprogramming experiments to examine the effect of co-expression of Rad51 and four reprogramming factors, Oct4, Sox2, Klf4, and c-Myc, on the reprogramming efficiency. Co-expression of Rad51 significantly increased the numbers of alkaline phosphatase-positive colonies and embryonic stem cell-like colonies during the process of reprogramming. Co-expression ofRad51 significantly increased the expression of epithelial markers at an early stage of reprogramming compared with control cells. Phosphorylated histone H2AX (γH2AX), which initiates the DNA double-strand break repair system, was highly accumulated in reprogramming intermediates upon co-expression of Rad51. This study identified a novel role of Rad51 in enhancing the reprogramming efficiency, possibly by facilitating mesenchymal-to-epithelial transition and by regulating a DNA damage repair pathway during the early phase of the reprogramming process.

Novel Function of Lysine Methyltransferase G9a in the Regulation of Sox2 Protein Stability.

G9a is a lysine methyltransferase (KMTase) for histone H3 lysine 9 that plays critical roles in a number of biological processes. Emerging evidence suggests that aberrant expression of G9a contributes to tumor metastasis and maintenance of a malignant phenotype in cancer by inducing epigenetic silencing of tumor suppressor genes. Here, we show that G9a regulates Sox2 protein stability in breast cancer cells. When G9a lysine methyltransferase activity was chemically inhibited in the ER(+) breast cancer cell line MCF7, Sox2 protein levels were decreased. In addition, ectopic overexpression of G9a induced accumulation of Sox2. Changes in cell migration, invasion, and mammosphere formation by MCF7 cells were correlated with the activity or expression level of G9a. Ectopic expression of G9a also increased Sox2 protein levels in another ER(+) breast cancer cell line, ZR-75-1, whereas it did not affect Sox2 expression in MDA-MB-231 cells, an ER(-) breast cancer cell line, or in glioblastoma cell lines. Furthermore, treatment of mouse embryonic stem cells with a KMT inhibitor, BIX-01294, resulted in a rapid reduction in Sox2 protein expression despite increased Sox2 transcript levels. This finding suggests that G9a has a novel function in the regulation of Sox2 protein stability in a cell type-dependent manner.

Rad51 regulates cell cycle progression by preserving G2/M transition in mouse embryonic stem cells.

Homologous recombination (HR) maintains genomic integrity against DNA replication stress and deleterious lesions, such as double-strand breaks (DSBs). Rad51 recombinase is critical for HR events that mediate the exchange of genetic information between parental chromosomes in eukaryotes. Additionally, Rad51 and HR accessory factors may facilitate replication fork progression by preventing replication fork collapse and repair DSBs that spontaneously arise during the normal cell cycle. In this study, we demonstrated a novel role for Rad51 during the cell cycle in mouse embryonic stem cells (mESCs). In mESCs, Rad51 was constitutively expressed throughout the cell cycle, and the formation of Rad51 foci increased as the cells entered S phase. Suppression of Rad51 expression caused cells to accumulate at G2/M phase and activated the DNA damage checkpoint, but it did not affect the self-renewal or differentiation capacity of mESCs. Even though Rad51 suppression significantly inhibited the proliferation rate of mESCs, Rad51 suppression did not affect the replication fork progression and speed, indicating that Rad51 repaired DNA damage and promoted DNA replication in S phase through an independent mechanism. In conclusion, Rad51 may contribute to G2/M transition in mESCs, while preserving genomic integrity in global organization of DNA replication fork.

Lefty1 and lefty2 control the balance between self-renewal and pluripotent differentiation of mouse embryonic stem cells.

Lefty expression has been recognized as a stemness marker because Lefty is enriched both in undifferentiated embryonic stem cells (ESCs) and in blastocysts. Here, we examined the function of Lefty1 and Lefty2 in the maintenance of self-renewal and pluripotency of mouse ESCs (mESCs). Suppression of Lefty1 or Lefty2 expression in mESCs did not alter the self-renewal properties of mESCs under nondifferentiating conditions, but suppression of these genes did affect Smad2 phosphorylation and differentiation. Lefty1 knockdown mESCs showed enhanced phosphorylation of Smad2 and increased differentiation potential, whereas Lefty2 knockdown mESCs exhibited reduced phosphorylation of Smad2 and enhanced self-renewal in the presence of a differentiation signal. In vivo, teratomas developed from Lefty2 knockdown mESCs contained massive expansions of immature neuroepithelium, a marker of malignant teratomas. Taken together, these results suggest that optimal expression of Lefty1 and Lefty2 is critical for the balanced differentiation of mESCs into three germ layers.

TCEA3 binds to TGF-beta receptor I and induces Smad-independent, JNK-dependent apoptosis in ovarian cancer cells.

TFIIS is a transcription elongation factor conserved in frog, mouse and human. Recently, knockdown of TCEA1, the most well-characterized isoform of TFIIS, by RNA silencing was reported to inhibit cancer cell proliferation and induce apoptosis in breast, lung and pancreatic cancer cell lines through activation of p53 (Hubbard et al., 2008 [1]). However, the functions of other TFIIS isoforms are poorly defined. The present study shows that TCEA3, an isoform of TFIIS, can trigger ovarian cancer-specific cell death by activating the JNK signaling pathway. TCEA3 expression is low in ovarian cancer cell lines compared to noncancerous ovarian epithelial cells. Suppression of TCEA3 in noncancerous ovarian epithelial cells promotes cell growth whereas ectopic expression of TCEA3 in ovarian cancer cell lines induces the caspase-dependent mitochondrial cell death pathway. Molecular and chemical inhibition assays show that the interaction of TCEA3 with TGFß receptor I induces cell death in ovarian cancer cell through Smad-independent activation of the JNK pathway. These results reveal that TCEA3 induces a novel apoptotic mechanism in OEC, which provides TCEA3 as a novel target to develop therapeutics of ovarian cancer.

PI3K/Akt and Stat3 signaling regulated by PTEN control of the cancer stem cell population, proliferation and senescence in a glioblastoma cell line.

Malignant gliomas are the most common primary brain tumor in adults. A number of genes have been implicated in glioblastoma including mutation and deletion of PTEN. PTEN is a regulator of PI3K-mediated Akt signaling pathways and has been recognized as a therapeutic target in glioblastoma. To achieve potent therapeutic inhibition of the PI3K-Akt pathway in glioblastoma, it is essential to understand the interplay between the regulators of its activation. Here, ectopic expression of PTEN in the U-87MG human glioblastoma-astrocytoma cell line is shown to result in the depletion of glioblastoma stem cells (GSCs) and to cause growth retardation and senescence. These effects are likely to be associated with PTEN-mediated cooperative perturbation of Akt and Stat3 signals. Using an in vivo rat model of glioblastoma, we showed that PTEN-overexpressing U-87MG cells failed to induce tumor formation, while untreated U-87MG cells did so. Furthermore, cells expressing the phosphorylated form of Stat3 were completely absent from the brain of rats implanted with PTEN-overexpressing U-87MG cells. Based on these results, PTEN appears to function as a crucial inhibitor of GSCs and as an inducer of senescence, suggesting that functional enhancement of the PTEN pathway will be useful to provide a therapeutic strategy for targeting glioblastoma.

Sprouty1 regulates neural and endothelial differentiation of mouse embryonic stem cells.

Fibroblast growth factor (FGF) signaling is implicated in the control of pluripotency and lineage differentiation of both human and mouse embryonic stem cells (mESCs). FGF4 dependent stimulation of ERK1/2 signaling triggers transition of pluripotent ESCs from self-renewal and lineage commitment. In this study, Sprouty 1 (Spry1) expression was observed in undifferentiated mESCs, where it modulated ERK1/2 activity. Spry1 was confirmed as dispensable for the maintenance of self-renewal. However, suppression of Spry1 expression and subsequent activation of ERK1/2 signaling promoted neural differentiation and inhibited endothelial differentiation of mESCs. Moreover, evidence is presented which indicates that SHP2, a major determinant of balance between mESC self-renewal and differentiation, directly regulates Spry1 activity to modulate ERK1/2 signaling and lineage-specific differentiation in mESCs. Our results show that Spry1 has an essential role in the lineage specific differentiation of mESCs.

Price sensitivity and innovativeness for fashion among Korean consumers.

Price sensitivity is how consumers react to price levels and to price changes. Consumer innovativeness is a tendency to welcome and to adopt new products. Researchers (e.g., R. E. Goldsmith & S. J. Newell, 1997) consider innovative consumers relatively more price insensitive than other consumers, so there should be a negative correlation between measures of these constructs. The results of the present study supported the psychometric soundness of a self-report measure of price sensitivity among 860 Korean consumers and replicated earlier findings of the negative correlation between the 2 constructs.