| 1. |
- Burza, Maria Antonella, 1980, et al.
(författare)
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DEPDC5 variants increase fibrosis progression in Europeans with chronic HCV infection.
- 2016
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Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 63:2, s. 418-427
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Tidskriftsartikel (refereegranskat)abstract
- Chronic hepatitis C virus (HCV) infection may progress to cirrhosis and hepatocellular carcinoma (HCC). Recently, two genetic variants, DEPDC5 rs1012068 and MICA rs2596542, were associated with the onset of HCC in Asian subjects with chronic HCV infection. The aim of the present study was to analyze whether DEPDC5 and MICA genetic variants were associated with liver disease progression in Europeans with chronic HCV infection. In a Northern Italian discovery cohort (n=477), neither DEPDC5 rs1012068 nor MICA rs2596542 were associated with HCC (n=150). However, DEPDC5 rs1012068 was independently associated with cirrhosis (n=300; p=0.049). The association of rs1012068 with moderate-severe fibrosis was confirmed in an independent cross-sectional German cohort (n=415; p=0.006). Furthermore, DEPDC5 rs1012068 predicted faster fibrosis progression in a prospective cohort (n=247; p=0.027). Next, we examined the distribution of non-synonymous DEPDC5 variants in the overall cross-sectional cohort (n=912). The presence of at least one variant increased the risk of moderate/severe fibrosis by 54% (p=0.040). To understand the molecular mechanism underlying the genetic association of DEPDC5 variants with fibrosis progression, we performed in vitro studies on immortalized hepatic stellate cells (LX-2). In these cells, down-regulation of DEPDC5 resulted in increased expression of β-catenin and production of its target matrix metallopeptidase 2 (MMP2), a secreted enzyme involved in fibrosis progression.
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| 2. |
- Peterlongo, Paolo, et al.
(författare)
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FANCM c.5791C>T nonsense mutation (rs144567652) induces exon skipping, affects DNA repair activity and is a familial breast cancer risk factor.
- 2015
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:18, s. 5345-5355
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Tidskriftsartikel (refereegranskat)abstract
- Numerous genetic factors that influence breast cancer risk are known. However, approximately two-thirds of the overall familial risk remain unexplained. To determine whether some of the missing heritability is due to rare variants conferring high to moderate risk, we tested for an association between the c.5791C>T nonsense mutation (p.Arg1931*; rs144567652) in exon 22 of FANCM gene and breast cancer. An analysis of genotyping data from 8635 familial breast cancer cases and 6625 controls from different countries yielded an association between the c.5791C>T mutation and breast cancer risk [odds ratio (OR) = 3.93 (95% confidence interval (CI) = 1.28-12.11; P = 0.017)]. Moreover, we performed two meta-analyses of studies from countries with carriers in both cases and controls and of all available data. These analyses showed breast cancer associations with OR = 3.67 (95% CI = 1.04-12.87; P = 0.043) and OR = 3.33 (95% CI = 1.09-13.62; P = 0.032), respectively. Based on information theory-based prediction, we established that the mutation caused an out-of-frame deletion of exon 22, due to the creation of a binding site for the pre-mRNA processing protein hnRNP A1. Furthermore, genetic complementation analyses showed that the mutation influenced the DNA repair activity of the FANCM protein. In summary, we provide evidence for the first time showing that the common p.Arg1931* loss-of-function variant in FANCM is a risk factor for familial breast cancer.
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| 3. |
- Aghasi, Keivan, et al.
(författare)
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Antecedents of target CEO departure in post-acquisitions : The leading role of founder
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This study investigates on firm specific human capital of target CEOs in small high-tech firms as the antecedent of their retention after the acquisition. The main finding of the paper is that acquirers are willing to keep the founder-CEOs because of their valuable embedded human capital. This value is to the extent that founder-CEOs compare to professional CEOs have a higher chance of retention when relatedness between acquirer and target is high or when the acquirer structurally integrates the target after the acquisition; the two conditions that general managerial skills and industry specific skills of the CEOs are not of interest for the acquirers. Also the value of firm specific human capital depends on the maturity of the target. The value diminishes as the target is more mature at the time of acquisition. This research is based on empirical analysis of acquisition of small high-tech firms between 2001 and 2005.
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| 4. |
- Aghasi, Keivan, et al.
(författare)
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Post-acquisition implementation of small high-tech firms : Looking beyond the surface
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In post-acquisition, the main challenge for the acquirer is choosing the right coordination mechanism with respect to the required level of coordination and associated costs of implementation of the mechanism. In acquisition of small high-tech firms, the challenge is exacerbated as technology and knowledge transfer requires high level of coordination while the costs related such as loss of autonomy and organizational disruptions are also higher. In this paper, we showed that acquirer’s choice of coordination mechanisms is determined by the cost-benefit trade-off. In particular, we found that, component technology as a form of task interdependency necessitates higher level of coordination and justifies choosing mechanisms to provide high level of coordination at higher cost. On the contrary, technological relatedness and prior alliance between acquirer and target provide coordination capacity, which in turn reduce the benefits of choosing mechanisms to provide high level of coordination with respect to the associated costs. This study is based on empirical analysis of 403 acquisitions of small high-tech firms between 2001 and 2005.
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| 5. |
- Aghasi, Keivan, 1983-
(författare)
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Predicting who stays or leaves after the acquisition: : Target’s top manager turnover
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In acquisition of high-tech and knowledge intensive firms, scholars have paid special attention to top managers’ status after the deal. Literature suggests that these managers in particular CEOs if kept in post-acquisition provide coordination capacity for the acquirer to transfer the knowledge and technology from the target to the acquirer while minimizing the disruptive effect of post-acquisition integration process. In addition, the acquirer benefits from human capital embedded in target’s managerial resources; especially in high-tech and knowledge intensive firms where top managers are founders or patent holders. Although the above mentioned argument have been validated by empirical studies showing that top manager’s turnover reduces the post-acquisition performance for the acquirers, multiple empirical studies have reported abnormal managerial turnover shortly after the acquisition. This thesis made an attempt to explain this puzzling phenomenon by investigating on the determinants of the top manager’s turnover of the target in the post-acquisition period. The study finds that in case of CEOs, acquirers do not rely always on coordinating capacity provided by them in post-acquisition. Indeed, the acquirer’s choice of provision of coordination is beyond the target’s CEO retention. The choice of coordination depends on the existing level of coordination capacities and the acquisition’s motivation. In addition, founder-CEOs are more likely to stay after the acquisition because of their valuable firm-specific human capital for the acquirer. However, this value diminishes by the maturity of the target. In addition, similarity in demographic characteristics of the two CEOs (of the acquirer and target) causes social attraction, collaboration and cooperation which ultimately increases the chance that the target’s CEO retention. Finally, diversity within the target’s top management team (TMT) directly increases their chance of departure after the deal. The diversity engenders social frictions, conflicts and coordination inefficiencies.
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| 6. |
- Aghasi, Keivan, et al.
(författare)
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Why diverse top managementteams break up in post-acquisition periods
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- This paper proposes a complementary explanation behind the turnover of target’s top managers in post-acquisition periods. Although human capital and acquisition implementation literature describe managerial retention as desirable, empirical studies have reported significant managerial turnover in acquisition of high-tech and knowledge intensive firms. Borrowing some insights from the team diversity literature, the paper examines the ex-ante diversity among top managers of knowledge-intensive and high-tech firms as an antecedent of their turnover in post-acquisition. We argue that diversity reduces the coordination efficiency necessary to transfer knowledge and facilitate post-acquisition organizational integration, and managers belonging to such teams are more likely to be replaced. Empirical analysis drawing on 2164 top managers in 297 Swedish firms shows that managerial position diversity as a separation, pay disparity and industrial tenure diversity as a variety indeed are associated with managerial exit in three years after the acquisition.
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| 7. |
- Bettiga, Arianna, et al.
(författare)
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Bladder cancer cell growth and motility implicate cannabinoid 2 receptor-mediated modifications of sphingolipids metabolism
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- The inhibitory effects demonstrated by activation of cannabinoid receptors (CB) on cancer proliferation and migration may also play critical roles in controlling bladder cancer (BC). CB expression on human normal and BC specimens was tested by immunohistochemistry. Human BC cells RT4 and RT112 were challenged with CB agonists and assessed for proliferation, apoptosis, and motility. Cellular sphingolipids (SL) constitution and metabolism were evaluated after metabolic labelling. CB1-2 were detected in BC specimens, but only CB2 was more expressed in the tumour. Both cell lines expressed similar CB2. Exposure to CB2 agonists inhibited BC growth, down-modulated Akt, induced caspase 3-activation and modified SL metabolism. Baseline SL analysis in cell lines showed differences linked to unique migratory behaviours and cytoskeletal re-arrangements. CB2 activation changed the SL composition of more aggressive RT112 cells by reducing (p amp;lt; 0.01) Gb3 ganglioside (-50 +/- 3%) and sphingosine 1-phosphate (S1P, -40 +/- 4%), which ended up to reduction in cell motility (-46 +/- 5%) with inhibition of p-SRC. CB2-selective antagonists, gene silencing and an inhibitor of SL biosynthesis partially prevented CB2 agonist-induced effects on cell viability and motility. CB2 activation led to ceramide-mediated BC cell apoptosis independently of SL constitutive composition, which instead was modulated by CB2 agonists to reduce cell motility.
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| 10. |
- Colombo, Massimo G., et al.
(författare)
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Introduction : Small Business and Networked Innovation: Organizational and Managerial Challenges
- 2012
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Ingår i: Journal of small business management (Print). - 0047-2778 .- 1540-627X. ; 50:2, s. 181-190
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this article is to provide an introduction to the special issue. We briefly consider the organizational and managerial challenges that small and medium-sized enterprises encounter in networked innovation, thereby building a background to the articles included in the special issue. We then present the main findings of these articles and highlight their novel contributions.
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