Filtering of false positive microRNA candidates by a clustering-based approach

B M C BioinformaticsBackground: MicroRNAs are small non-coding RNA gene products that play diversified roles from species to species. The explosive growth of microRNA researches in recent years proves the importance of microRNAs in the biological system and it is believed that microRNAs have valuable therapeutic potentials in human diseases. Continual efforts are therefore required to locate and verify the unknown microRNAs in various genomes. As many miRNAs are found to be arranged in clusters, meaning that they are in close proximity with their neighboring miRNAs, we are interested in utilizing the concept of microRNA clustering and applying it in microRNA computational prediction. Results: We first validate the microRNA clustering phenomenon in the human, mouse and rat genomes. There are 45.45%, 51.86% and 48.67% of the total miRNAs that are clustered in the three genomes, respectively. We then conduct sequence and secondary structure similarity analyses among clustered miRNAs, non-clustered miRNAs, neighboring sequences of clustered miRNAs and random sequences, and find that clustered miRNAs are structurally more similar to one another, and the RNAdistance score can be used to assess the structural similarity between two sequences. We therefore design a clustering-based approach which utilizes this observation to filter false positives from a list of candidates generated by a selected microRNA prediction program, and successfully raise the positive predictive value by a considerable amount ranging from 15.23% to 23.19% in the human, mouse and rat genomes, while keeping a reasonably high sensitivity. Conclusion: Our clustering-based approach is able to increase the effectiveness of currently available microRNA prediction program by raising the positive predictive value while maintaining a high sensitivity, and hence can serve as a filtering step. We believe that it is worthwhile to carry out further experiments and tests with our approach using data from other genomes and other prediction software tools. Better results may be achieved with fine-tuning of parameters. © 2008 Leung et al; licensee BioMed Central Ltd.published_or_final_versio

Construction of online catalog topologies using decision trees

Organization of a Web site is important to help users get the most out of the site. A good Web site should help visitors find the information they want easily. Visitors typically find information by searching for selected terms of interest or by following links from one Web page to another. The first approach is more useful if the visitor knows exactly what he is seeking, while the second approach is useful when the visitor has less of a preconceived notion about what he wants. The organization of a Web site is especially important in the latter case. Traditionally, Web site organization is done by hand. In this paper, we introduce the problem of automatic Web site construction and propose a solution for solving a major step of the problem based on decision tree algorithms. The solution is found to be useful in automatic construction of product catalogs.published_or_final_versio

Institutional difference and outward FDI: Evidence from China

This paper investigates the impact of institutional difference on China’s outward foreign direct investment (OFDI) through a gravity model. Our estimations are based on a large panel of 150 countries over the period 2003-2015. The results show that the institutional differences of government effectiveness and control of corruption between China and a host country have a statistically significant negative effect on China’s OFDI. In addition, our empirical evidence suggests that the ‘One Belt One Road’ policy does not have the expected positive effect on China’s OFDI. Consistent results are obtained from a set of robustness tests. Our findings provide a reasonable guideline for countries aiming to attract Chinese OFDI or seeking factors to boost it

Internalisation Theory and outward direct investment by emerging market multinationals

The rise of multinational enterprises from emerging countries (EMNEs) poses an important test for theories of the multinational enterprise such as internalisation theory. It has been contended that new phenomena need new theory. This paper proposes that internalisation theory is appropriate to analyse EMNEs. This paper examines four approaches to EMNEs—international investment strategies, domestic market imperfections, international corporate networks and domestic institutions—and three case studies—Chinese outward FDI, Indian foreign acquisitions and investment in tax havens—to show the enduring relevance and predictive power of internalisation theory. This analysis encompasses many other approaches as special cases of internalisation theory. The use of internalisation theory to analyse EMNEs is to be commended, not only because of its theoretical inclusivity, but also because it has the ability to connect and to explain seemingly desperate phenomena

Blocking Connexin-43 mediated hemichannel activity protects against early tubular injury in experimental chronic kidney disease

Background: Tubulointerstitial fibrosis represents the key underlying pathology of Chronic Kidney Disease (CKD), yet treatment options remain limited. In this study, we investigated the role of connexin43 (Cx43) hemichannel-mediated adenosine triphosphate (ATP) release in purinergic-mediated disassembly of adherens and tight junction complexes in early tubular injury. Methods: Human primary proximal tubule epithelial cells (hPTECs) and clonal tubular epithelial cells (HK2) were treated with Transforming Growth Factor Beta1 (TGFβ1) ± apyrase, or ATPγS for 48h. For inhibitor studies, cells were co-incubated with Cx43 mimetic Peptide 5, or purinergic receptor antagonists Suramin, A438079 or A804598. Immunoblotting, single-cell force spectroscopy and trans-epithelial electrical resistance assessed protein expression, cell-cell adhesion and paracellular permeability. Carboxyfluorescein uptake and biosensing measured hemichannel activity and real-time ATP release, whilst a heterozygous Cx43+/- mouse model with unilateral ureteral obstruction (UUO) assessed the role of Cx43 in vivo. Results: Immunohistochemistry of biopsy material from patients with diabetic nephropathy confirmed increased expression of purinergic receptor P2X7. TGFβ1 increased Cx43 mediated hemichannel activity and ATP release in hPTECs and HK2 cells. The cytokine reduced maximum unbinding forces and reduced cell-cell adhesion, which translated to increased paracellular permeability. Changes were reversed when cells were co-incubated with either Peptide 5 or P2-purinoceptor inhibitors. Cx43+/- mice did not exhibit protein changes associated with early tubular injury in a UUO model of fibrosis. Conclusion: Data suggest that Cx43 mediated ATP release represents an initial trigger in early tubular injury via its actions on the adherens and tight junction complex. Since Cx43 is highly expressed in nephropathy, it represents a novel target for intervention of tubulointerstitial fibrosis in CKD

Home country supportiveness/unfavorableness and outward foreign direct investment from China

What drives the outward foreign direct investments (OFDIs) by emerging market firms (EMFs)? Drawing on a strategy tripod framework, this article proposes a theoretical model to predict OFDI by EMFs from China. Specifically, we use institution- and industry-based views to examine two facets of home country environment, namely the supportiveness from home government and unfavorableness from home industry, as important determinants of OFDI, and compare the relative strength of these effects. Further, we use resource-based view to argue that the effect of the home country environment is contingent on the international experience portfolios of EMFs

Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study

BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group