Role of Human Topoisomerase I in DNA Repair and Apoptosis

Human topoisomerase I (htopoI) is an enzyme that up to now was believed to function mainly in the removal of torsional stress generated during transcription and replication. In 1998, it was found that htopoI might play another important role in the cellular response to DNA damage -- the so-called htopoI damage response. Since this initial discovery, many studies have suggested that the htopoI damage response is involved in DNA repair as well as in apoptosis. Here we discuss the earliest as well as the latest results in this field. Combining all of the published and as yet unpublished results, we suggest and discuss a model of how htopoI may function during DNA repair and apoptosis. Furthermore, numerous results show that the htopoI damage response is not a spontaneous event, but is strictly regulated by cellular signalling pathways. We discuss which pathways may be involved and how the htopoI damage response is activated. Although the htopoI damage response was discovered several years ago, research in this area is just beginning. The future will surely bring more clarity regarding the precise mechanism behind the involvement of htopoI in DNA repair and apoptosis, as well as its implications for a broader understanding of how the human organism ensures genomic stability.

The relationship between cannabis outcome expectancies and cannabis refusal self-efficacy in a treatment population

Background and aims Self-efficacy beliefs and outcome expectancies are central to Social Cognitive Theory (SCT). Alcohol studies demonstrate the theoretical and clinical utility of applying both SCT constructs. This study examined the relationship between refusal self-efficacy and outcome expectancies in a sample of cannabis users, and tested formal mediational models. Design Patients referred for cannabis treatment completed a comprehensive clinical assessment, including recently validated cannabis expectancy and refusal self-efficacy scales. Setting A hospital alcohol and drug out-patient clinic. Participants Patients referred for a cannabis treatment [n = 1115, mean age 26.29, standard deviation (SD) 9.39]. Measurements The Cannabis Expectancy Questionnaire (CEQ) and Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ) were completed, along with measures of cannabis severity [Severity of Dependence Scale (SDS)] and cannabis consumption. Findings Positive (β = −0.29, P < 0.001) and negative (β = −0.19, P < 0.001) cannabis outcome expectancies were associated significantly with refusal self-efficacy. Refusal self-efficacy, in turn, fully mediated the association between negative expectancy and weekly consumption [95% confidence interval (CI) = 0.03, 0.17] and partially mediated the effect of positive expectancy on weekly consumption (95% CI = 0.06, 0.17). Conclusions Consistent with Social Cognitive Theory, refusal self-efficacy (a person's belief that he or she can abstain from cannabis use) mediates part of the association between cannabis outcome expectancies (perceived consequences of cannabis use) and cannabis use.

Mathematical investigation of the interactions between the inflammatory response and mechanical aspects of dermal wound repair

Dermal wound repair involves complex interactions between cells, cytokines and mechanics to close injuries to the skin. In particular, we investigate the contribution of fibroblasts, myofibroblasts, TGFβ, collagen and local tissue mechanics to wound repair in the human dermis. We develop a morphoelastic model where a realistic representation of tissue mechanics is key, and a fibrocontractive model that involves a reasonable approximation to the true kinetics of the important bioactive species. We use each of these descriptions to elucidate the mechanisms that generate pathologies such as hypertrophic scars, contractures and keloids. We find that for hypertrophic scar and contracture development, factors regulating the myofibroblast phenotype are critical, with heightened myofibroblast activation, reduced myofibroblast apoptosis or prolonged inflammation all predicted as mediators for scar hypertrophy and contractures. Prevention of these pathologies is predicted when myofibroblast apoptosis is induced, myofibroblast activation is blocked or TGFβ is neutralised. To investigate keloid invasion, we develop a caricature representation of the fibrocontractive model and find that TGFβ spread is the driving factor behind keloid growth. Blocking activation of TGFβ is found to cause keloid regression. Thus, we recommend myofibroblasts and TGFβ as targets for clinicians when developing intervention strategies for prevention and cure of fibrotic scars.

Investigating relationships between relationship quality, customer loyalty and cooperation : an empirical study of convenience stores' franchise chain systems

Franchising has become a way to minimise the risks of small business management. There has been little research into the factors that promote franchise relationship success. This study attempts to empirically examine the important elements (relationship quality, customer loyalty and cooperation), which might promote a successful long-term franchising relationship between franchisors and franchisees within the context of convenience stores in Taiwan. A model of these relationships was developed and tested. A total of 500 surveys were mailed to a random sample of convenience stores’ franchisee owners among the four main franchisors in Taiwan. The results show that relationship quality positively influences the cooperation between franchisors and franchisees and is positively correlated with franchisee loyalty. Additionally, the cooperative behaviour between franchisees and franchisors is significantly associated with franchisees’ loyalty.

Time as the critical factor in the investigation of the relationship between pollutant wash-off and rainfall characteristics

The approach adopted for investigating the relationship between rainfall characteristics and pollutant wash-off process is commonly based on the use of parameters which represent the entire rainfall event. This does not permit the investigation of the influence of rainfall characteristics on different sectors of the wash-off process such as first flush where there is a high pollutant wash-off load at the initial stage of the runoff event. This research study analysed the influence of rainfall characteristics on the pollutant wash-off process using two sets of innovative parameters by partitioning wash-off and rainfall characteristics. It was found that the initial 10% of the wash-off process is closely linked to runoff volume related rainfall parameters including rainfall depth and rainfall duration while the remaining part of the wash-off process is primarily influenced by kinetic energy related rainfall parameters, namely, rainfall intensity. These outcomes prove that different sectors of the wash-off process are influenced by different segments of a rainfall event.

Crucial roles for olfactory ensheathing cells and olfactory mucosal cells in the repair of damaged neural tracts

Olfactory ensheathing cells, the glial cells of the olfactory nervous system, exhibit unique growth-promoting and migratory properties that make them interesting candidates for cell therapies targeting neuronal injuries such as spinal cord injury. Transplantation of olfactory cells is feasible and safe in humans; however, functional outcomes are highly variable with some studies showing dramatic improvements and some no improvements at all. We propose that the reason for this is that the identity and purity of the cells is different in each individual study. We have shown that olfactory ensheathing cells are not a uniform cell population and that individual subpopulations of OECs are present in different regions of the olfactory nervous system, with strikingly different behaviors. Furthermore, the presence of fibroblasts and other cell types in the transplant can dramatically alter the behavior of the transplanted glial cells. Thus, a thorough characterization of the differences between olfactory ensheathing cell subpopulations and how the behavior of these cells is affected by the presence of other cell types is highly warranted.

Psychological services under Medicare : broken but not beyond repair

How well is the Better Access scheme for the provision of affordable, effective psychological services to the Australian public working? Robert King identifies important weaknesses in the system that have adverse impacts on clients, providers and public policy objectives. These weaknesses are explored and options to remedy the problems are outlined.

Mesenchymal stromal cells and the repair of cartilage tissue

Articular cartilage has a limited intrinsic repair capacity, and thus defects are more likely to further degrade rather than undergo spontaneous self-repair. Whilst a number of surgical techniques have been developed to repair cartilage defects, their efficacy is generally poor and total joint replacement remains the gold standard, albeit last resort, treatment option. Cell-based therapies hold the greatest promise, as they appear uniquely capable of generating de novo cartilage tissue. Two approved therapies (ACI and MACI) are based on the premise that the transplantation of ex vivo expanded autologous chondrocyte populations, harvested from a non-load bearing region of the same joint, could be utilized to effectively regenerate cartilage tissue in the primary defect site. These therapeutic strategies are partially limited by our inability to harvest and expand adequate numbers of autologous chondrocytes that retain the appropriate phenotype. By contrast, the harvest and expansion of large numbers of mesenchymal stem/stromal cells (MSC) derived from tissues such as bone marrow and adipose is comparatively straightforward and has become routine in laboratories worldwide. Additionally, our understanding of the biochemical and biophysical signals required to drive the chondrogenic differentiation of MSC is rapidly increasing. It is conceivable that in the near future MSC expansion and differentiation technologies will offer a means to generate sufficient cell numbers, of an appropriate phenotype, for use in cartilage defect repair. In this chapter we review the relative potential of MSC and their likely contribution to cartilage regeneration.

The relationship between BCOM1 gene variants and macular pigment optical density in persons with and without age-related macular degeneration

Background: Recent evidence indicates that gene variants related to carotenoid metabolism play a role in the uptake of macular pigments lutein (L) and zeaxanthine (Z). Moreover, these pigments are proposed to reduce the risk for advanced age-related macular degeneration (AMD). This study provides the initial examination of the relationship between the gene variants related to carotenoid metabolism, macular pigment optical density (MPOD) and their combined expression in healthy humans and patients with AMD. Participants and Methods: Forty-four participants were enrolled from a general population and a private practice including 20 healthy participants and 24 patients with advanced (neovascular) AMD. Participants were genotyped for the three single nucleotide polymorphisms (SNPs) upstream from BCMO1, rs11645428, rs6420424 and rs6564851 that have been shown to either up or down regulate beta-carotene conversion efficiency in the plasma. MPOD was determined by heterochromatic flicker photometry. Results: Healthy participants with the rs11645428 GG genotype, rs6420424 AA genotype and rs6564851 GG genotype all had on average significantly lower MPOD compared to those with the other genotypes (p < 0.01 for all three comparisons). When combining BCMO1 genotypes reported to have “high” (rs11645428 AA/rs6420424 GG/rs6564851 TT) and “low” (rs11645428 GG/rs6420424 AA/rs6564851 GG) beta-carotene conversion efficiency, we demonstrate clear differences in MPOD values (p<0.01). In patients with AMD there were no significant differences in MPOD for any of the three BCMO1 gene variants. Conclusion: In healthy participants MPOD levels can be related to high and low beta-carotene conversion BCMO1 genotypes. Such relationships were not found in patients with advanced neovascular AMD, indicative of additional processes influencing carotenoid uptake, possibly related to other AMD susceptibility genes. Our findings indicate that specific BCMO1 SNPs should be determined when assessing the effects of carotenoid supplementation on macular pigment and that their expression may be influenced by retinal disease.

An analysis for the causes of accidents of repair, maintenance, alteration and addition works in Hong Kong

This study unveils causes of accidents in repair, maintenance, alteration and addition (RMAA) work. RMAA work is playing an increasingly important role in developed societies, including Hong Kong. Safety problems associated with RMAA work in Hong Kong has reached an alarming level. In view of rapid expansion of the RMAA sector and rising proportion of accidents in the construction industry, there is a pressing need to investigate causes of RMAA accidents. Structured interviews were conducted with RMAA contractors to explore causes of accidents in the RMAA sector. A two-round Delphi method with 13 safety experts was subsequently employed to verify the interview findings and rank the relative degree of importance for various causes of accidents. Accidents happen in RMAA work due to intersection of reasons. One of the root causes of accidents in RMAA works is low safety awareness of RMAA workers; however, wider organizational and industrial factors are not negligible. This study sheds light on why accidents happen in the RMAA sector. Only when the factors leading to accidents are identified can effective measures be made.

Empirical study to investigate the difficulties of implementing safety practices in the repair and maintenance sector in Hong Kong

Repair, maintenance, minor alteration, and addition work (RMAA) has become more and more important in developed societies, but its safety performance is alarming. For example, RMAA projects accounted for 53.2% of the total construction market and the percentage of RMAA accidents to all construction accidents in the Hong Kong Special Administrative Region (HKSAR) increased considerably in 2007. The RMAA sector has a huge potential for safety improvement. This study aims to explore and evaluate the difficulties of implementing safety practices in RMAA work. The mixed methods approach was adopted, and semistructured interviews and a two-round Delphi survey were conducted for the data collection. Major difficulties were identified, including limited safety resources for small and medium enterprises (SMEs), difficulty in changing the mindset of RMAA workers, and difficulty in performing safety supervision. These obstacles for implementing safety practices in the RMAA sector, if successfully removed, could significantly improve the safety performance of the RMAA sector and the construction industry as a whole.

Safety management in repair, maintenance, minor alteration, and addition works : knowledge management perspective

Safety of repair, maintenance, alteration, and addition (RMAA) works have long been neglected because RMAAworks are often minute and only last for a short period of time. With rising importance of the RMAA sector in many developed societies, safety of RMAA works has begun to draw attention. Many RMAA contracting companies are small- and medium-sized enterprises (SMEs) that do not have comprehensive safety management systems. Existing safety legislation and regulations for new construction sites are not fully applicable to RMAAworks. Instead of relying on explicit and well-established safety systems, tacit safety knowledge plays an extremely important role in RMAA projects. To improve safety of RMAAworks, safety knowledge should be better managed. However, safety knowledge is difficult to capture in RMAA works. This study aims to examine safety management practices of RMAA contracting companies to see how safety knowledge of RMAA projects is managed. Findings show that RMAA contracting companies undertaking large-scale RMAA projects have more initiatives of safety management. Safety management of small-scale RMAA works relies heavily on the motivation of site supervisors and self-regulation of workers. Better tacit knowledge management improves safety performance. To enhance safety capability of RMAA contracting companies, a knowledge sharing culture should be cultivated. The government should provide assistance to SMEs to implement proper safety management practices in small-sized projects. Potentials of applying computer software technology in RMAA projects to capture, store, and retrieve safety information should be explored. Employees should be motivated to share safety knowledge by giving proper recognition to those who are willing to share.

Safety climate and injury occurrence of repair, maintenance, minor alteration and addition works : a comparison of workers, supervisors and managers

Purpose The repair, maintenance, minor alteration and addition (RMAA) sector has been expanding in many developed cities. Safety problems of the RMAA sector have attracted the attention of many governments. This study has the objectives of comparing the level of safety climate of workers, supervisors and managers in the RMAA sector; and explaining/ predicting the impact of safety climate on injury occurrence of workers, supervisors and managers. Design/methodology/approach A questionnaire survey was administered to RMAA contracting companies in Hong Kong. Findings When comparing the safety climate perception of workers, supervisors and managers in the RMAA sector, the supervisors group had the lowest mean safety climate score. Results showed that a positive workforce safety attitude and acceptance of safety rules and regulations reduced the workers’ likelihood of having injuries. A reasonable production schedule led to a lower probability of supervisors being injured. Management commitment and effective safety management reduced the probability of managers being injured. Originality/value This study revealed variations of safety climate at the different levels in the organizational hierarchy and their varying influence on safety performance of the RMAA sector. Safety of RMAA works could be improved by promulgating specific safety measures at the different hierarchy levels.

Fatalities of repair, maintenance, minor alteration, and addition works in Hong Kong

This study examines fatalities of repair, maintenance, minor alteration, and addition (RMAA) works which occurred in Hong Kong between January 2000 and October 2011. A total of 119 RMAA fatalities were recorded. Particular emphasis was placed on fall from height accidents as they accounted for the vast majority of RMAA fatal accidents for the period. A cluster analysis was conducted on fall from height fatal cases. The cluster analysis clearly identified three groups of fall from height fatalities: (1) bamboo scaffolders aged between 25 and 34 who fell from external wall/facade in the beginning of weekdays; (2) miscellaneous workers aged between 45 and 54 who fell from other/unknown places in the end of weekdays; and (3) manual labour aged between 35 and 44 who fell at floor level/from floor openings in weekends. Unsafe process and improper procedures were the main unsafe condition leading to fatalities whereas safety belt not properly used was the main unsafe action leading to fatalities. Specific safety interventions were recommended for each of these groups to help avoid these fatalities.