Mechanisms of Mycoplasma-induced inflammation and cellular transformation

There is a growing interest in “medical gasses” for their antibacterial and anti-inflammatory properties. Hydrogen sulfide (H2S), a member of the family of gasotransmitters, is in fact increasingly being recognized as an important signaling molecule, but its precise role in the regulation of the inflammatory response is still not clear. For this reason, the aim of the first part of this thesis was to investigate the effects of H2S on the expression of pro-inflammatory cytokines, such as MCP-1, by using an in vitro model composed by both primary monocytes-derived macrophages cultures and the human monocytic cell line U937 infected with Mycoplasma fermentans, a well-known pro-inflammatory agent. In our experiments, we observed a marked increase in the production of pro-inflammatory cytokines in infected cells. In particular, MCP-1 was induced both at the RNA and at the protein level. To test the effects of H2S on infected cells, we treated the cells with two different H2S donors (NaHS and GYY4137), showing that both H2S treatments had anti-inflammatory effects in Mycoplasma-infected cells: the levels of MCP-1, both mRNA expression and protein production, were reduced. Our subsequent studies aimed at understanding the molecular mechanisms responsible for these effects, focused on two specific molecular pathways, both involved in inflammation: the NF-κB and the Nrf2 pathway. After treatment with pharmacological inhibitors, we demonstrated that Mycoplasma fermentans induces MCP-1 expression through the TLR-NF-κB pathway with the nuclear translocation of its subunits, while treatment with H2S completely blocked the nuclear translocation of NF-κB heterodimer p65/p50. Then, once infected cells were treated with H2S donors, we observed an increased protective effect of Nrf2 and also a decrease in ROS production. These results highlight the importance of H2S in reducing the inflammatory process caused by Mycoplasma fermentans. To this regard, it should be noted that several projects are currently ongoing to develop H2S-releasing compounds as candidate drugs capable of alleviating cell deterioration and to reduce the rate of decline in organ function. In the second part of this study, we investigated the role of Mycoplasma infection in cellular transformation. Infectious agents are involved in the etiology of many different cancers and a number of studies are still investigating the role of microbiota in tumor development. Mycoplasma has been associated with some human cancers, such as prostate cancer and non-Hodgkin’s lymphoma in HIV-seropositive people, and its potential causative role and molecular mechanisms involved are being actively investigated. To this regard, in vitro studies demonstrated that, upon infection, Mycoplasma suppresses the transcriptional activity of p53, key protein in the cancer suppression. As a consequence, infected cells were less susceptible to apoptosis and proliferated more than the uninfected cells. The mechanism(s) responsible for the Mycoplasma-induced inhibitory effect on p53 were not determined. Aim of the second part of this thesis was to better understand the tumorigenic role of the microorganism, by investigating more in details the effect(s) of Mycoplasma on p53 activity in an adenocarcinoma HCT116 cell line. Treatment of Mycoplasma-infected cells with 5FU or with Nutlin, two molecules that induce p53 activity, resulted in cellular proliferation comparable to untreated controls. These results suggested that Mycoplasma infection inhibited p53 activity. Immunoprecipitation of p53 with specific antibodies, and subsequent Gas Chromatography and Mass Spectroscopy (GC-MS) assays, allowed us to identify several Mycoplasma-specific proteins interacting with p53, such as DnaK, a prokaryotic heat shock protein and stress inducible chaperones. In cells transfected with DnaK we observed i) reduced p53 protein levels; ii) reduced activity and expression of p21, Bax and PUMA, iii) a marked increase in cells leaving G1 phase. Taken together, these data show an interaction between the human p53 and the Mycoplasma protein DnaK, with the consequent decreased p53 activity and decreased capability to respond to DNA damage and prevent cell proliferation. Our data indicate that Mycoplasma could be involved in cancer formation and the mechanism(s) has the potential to be a target for cancer diagnosis and treatment(s).

Externality effects of information and communication technologies across country Borders

As information and communications technology (ICT) involves both traditional capital and knowledge capital, potential spillovers through various mechanisms can occur. We posit that ICT capital may boost productivity growth, not only in the home country, but also in other countries. In this paper, we provide empirical evidence of such spillovers using panel data on 37 countries from 1996 to 2004. Our results support the existence of ICT spillovers across country borders. Furthermore, we find that developing countries could reap more benefits from ICT spillovers than developed countries. This is particularly important for policy decisions regarding national trade liberalization and economic integration. Developing economies that are more open to foreign trade may have an economic advantage and may develop knowledge-intensive activities, which will lead to economic development in the long run.

Meta-analytic model comparisons of surface- and deep-level relational diversity effects on social integration and individual effectiveness

While diversity might give an organization a competitive advantage, individuals have a tendency to prefer homogenous group settings. Prior research suggests that group members who are dissimilar (vs. similar) to their peers in terms of a given diversity attribute (e.g. demographics, attitudes, values or traits) feel less attached to their work group, experience less satisfying and more conflicted relationships with their colleagues, and consequently are less effective. However, prior empirical findings tend to be weak and inconsistent, and it remains unclear when, how and to what extent such differences affect group members’ social integration (i.e. attachment with their work group, satisfaction and conflicted relationships with their peers) and effectiveness. To address these issues the current study conducted a meta-analysis and integrated the empirical results of 129 studies. For demographic diversity attributes (such as gender, ethnicity, race, nationality, age, functional background, and tenure) the findings support the idea that demographic dissimilarity undermines individual member performance via lower levels of social integration. These negative effects were more pronounced in pseudo teams – i.e. work groups in which group members pursue individual goals, work on individual tasks, and are rewarded for their individual performance. These negative effects were however non-existent in real teams - i.e. work groups in which groups members pursue group goals, work on interdependent tasks, and are rewarded (at least partially) based on their work group’s performance. In contrast, for underlying psychological diversity attributes (such as attitudes, personality, and values), the relationship between dissimilarity and social integration was more negative in real teams than in pseudo teams, which in return translated into even lower individual performance. At the same time however, differences in underlying psychological attributes had an even stronger positive effect on dissimilar group member’s individual performance, when the negative effects of social integration were controlled for. This implies that managers should implement real work groups to overcome the negative effects of group member’s demographic dissimilarity. To harness the positive effects of group members’ dissimilarity on underlying psychological attributes, they need to make sure that dissimilar group members become socially integrated.

Factors affecting the durability of 5.25 inch floppy diskette media and its mechanisms of wear

This project is targeted towards establishing the durability and mechanisms of wear involved in the use of 5.25 inch magnetic floppy diskettes with particular reference to the media manufactured by the Minnesota Mining and Manufacturing Company, 3M Center, St. Paul, Minnesota, USA. In the present work most stress has been laid on the presentation of the conclusions drawn from the results obtained using samples produced specifically for this project. These samples were produced on the pilot plant at 3MTM, St. Paul, USA and are identified by the code 58759-4 with sample numbers SR1 to SR4 each with different lubrication conditions. All of the categories have been produced with four different surface roughnesses by varying the degree of burnishing. It has been found that the mechanisms of wear are related to a fatigue process. Some surprises have been noted in respect of the value of burnishing compared to the observations made elsewhere. Good reasons for these observed differences have been noted, however, and it will be shown that these are merely superficial and not concerned with wear of any real type. The present work reports the effects of the changes in the media's lubrication status and its surface topography as well as presenting evidence for the suggested wear mechanisms.

The Great Slump of 2008–9 and Ukraine's integration with the European Union

For a number of years following the Orange revolution of 2004, Ukraine aspired to join the European Union. Although full integration was never a short-term prospect, European integration, through the Association Agreement and the Deep and Comprehensive Free Trade Area, offers considerable benefits to Ukraine. However, the country was severely affected by the Great Slump of 2008–9 in the global economy, and this profoundly negative experience has shaped Ukrainian domestic and foreign policy in the subsequent period, putting paid to aspirations to EU membership and influencing the Ukrainian government's decision to seek a closer relationship with Russia immediately following the presidential election of 2010. Nevertheless, closer relations with Russia should not adversely affect Ukraine's efforts at EU integration.