Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Computational Drug Resistomes Analyses of Mycobacteroides Abscessus Complex

Mycobacteroides abscessus complex (MABC) is an emerging pathogen that causes human infections and resistance to multiple antibiotics. In this study, the genome data of 1,581 MABC strains were downloaded from NCBI Genome database for resistome analysis. The MABC strains were classified based on phylogenomic analysis and examined to identify the differences in antibiotic resistance proteins (ARPs) distribution among MABC subspecies. In addition, evolutionary analysis was performed on resistomes to evaluate the impact of evolution on the resistance of MABC. Multiple Biopython and Bash scripts were coded to handle and manage the genomes big data. A total of 395 putative ARPs, distributed among 28 antibiotic classes in accordance with CARD and ARG-ANNOT were predicted. The ARPs most frequently identified in MABC were those associated with resistance to multiple antibiotic classes, beta-lactams, and aminoglycosides. After excluding ARPs that had undergone recombination, two ARPs were predicted to be influenced by diversifying selection and 202 experienced purifying selection. The wide occurrence of purifying selection suggested that the amino acid diversity of commonly shared ARPs in MABC may have been reduced to achieve protein stability. The unequal distribution of ARPs in members of the MABC complex could be due to horizontal gene transfer or ARPs pseudogenization events. Most (81.5%) of the ARPs were observed in the accessory genome and 72.2% ARPs were highly homologous to proteins associated with mobile genetic elements such as plasmids, prophages, and viruses. On the other hand, with TBLASTN search, only 18 of the ARPs were identified as pseudogenes. Altogether, this study suggested an important role of horizontal gene transfer in shaping the resistome of MABC. The present study provides insights into the antibiotic resistomes in MABC and the evolutionary forces exerted on the resistomes. These findings would be useful in designing new therapeutic strategies and potential discovery of new antibiotics

The perception of households about solid waste management issues in Malaysia

With the aim being to have an integrated and efficient management system, Malaysia is currently facing a remarkable waste issue with a massive increase in waste generated per day. This study collected 400 survey responses to assess the satisfaction and awareness of households about various issues of solid waste management. This study revealed that the majority of the respondents were satisfied with their waste management services. However, there was concern about providing a more diverse waste management facility. This study found a strong positive relationship between age and waste reduction behaviours. The majority of the respondents agreed that their lifestyle affected waste minimisation. Almost half of the respondents indicated that they lacked knowledge to practise waste sorting. Age and education were positively correlated to reuse and recycling behaviours. Overall, a holistic waste management education is vital for Malaysia to build an efficient waste management system

Digitalisation and financial inclusion of lower middle-income ASEAN

Recent studies reasoned that digitalising business processes support financial inclusion, resulting in greater economic activities and growth. Digital financial inclusion is argued to be accessible to some privileged and digitally savvy individuals. However, digitalised financial services do not always guarantee financial inclusion. This study examines how the digitalisation of business processes might instil financial inclusion in lower-middle-income ASEAN economies. Based on the Diffusion of Innovation (DOI) theory, the digitalisation of business processes is modelled by fixed high-speed broadband, mobile and cellular subscriptions as a predictor of financial inclusion. The pooled mean group estimation of the autoregressive distributed lag (ARDL) model is employed to determine the effect of digitalisation on the financial inclusion of Cambodia, Indonesia, Laos, Myanmar, the Philippines and Vietnam economies. The key finding is the significance of digitalisation in inducing the financial inclusion of lower-middle-income ASEAN economies. The digitalisation of business processes significantly affects the accessibility of private businesses to domestic credit provided by their banks

The resistomes of Mycobacteroides abscessus complex and their possible acquisition from horizontal gene transfer

Background Mycobacteroides abscessus complex (MABC), an emerging pathogen, causes human infections resistant to multiple antibiotics. In this study, the genome data of 1,581 MABC strains were downloaded from NCBI database for phylogenetic relatedness inference, resistance profile identification and the estimation of evolutionary pressure on resistance genes in silico. Results From genes associated with resistance to 28 antibiotic classes, 395 putative proteins (ARPs) were identified, based on the information in two antibiotic resistance databases (CARD and ARG-ANNOT). The ARPs most frequently identified in MABC were those associated with resistance to multiple antibiotic classes, beta-lactams and aminoglycosides. After excluding ARPs that had undergone recombination, two ARPs were predicted to be under diversifying selection and 202 under purifying selection. This wide occurrence of purifying selection suggested that the diversity of commonly shared ARPs in MABC have been reduced to achieve stability. The unequal distribution of ARPs in members of the MABC could be due to horizontal gene transfer or ARPs pseudogenization events. Most (81.5%) of the ARPs were observed in the accessory genome and 72.2% ARPs were highly homologous to proteins associated with mobile genetic elements such as plasmids, prophages and viruses. On the other hand, with TBLASTN search, only 18 of the ARPs were identified as pseudogenes. Conclusion Altogether, our results suggested an important role of horizontal gene transfer in shaping the resistome of MABC

Retaining skilled workers through motivation: The Malaysian case

Skill drain is a loss of human capital, investment in education and training. This study examines if motivated, skilled workers at the firm level can retain skilled workers and mitigate the loss of human capital. A survey was conducted in Iskandar city to gather skilled workers’ feedback on their current working conditions in Malaysia. Completed responses were tested for data adequacy, reliability, factor analysis and multiple-regression analysis. The findings of this study suggest that skilled workers perceive instrumentality as their primary motivating factor, to be followed by expectancy and valence. Instrumentality in intrinsic and monetary rewards is vital in retaining skilled workers. The practical implication of this study suggests that monetary rewards and non-monetary recognition are effective in motivating and retaining skilled workers. Firms in other developing countries may consider implementing instrumental strategies in the workplace to retain skilled workers

More than cultural celebrations Indigenous identities in school settings

Australian research on Indigenous education has been based on deficit notions of cultural difference as the inhibitor to educational parity between Indigenous and non-Indigenous young people. Research from the 1970s focused on ‘why’ Indigenous young people were not succeeding in conventional school settings, and ‘how’ schools could engage and improve outcomes for Indigenous young people. In the following four decades, there has been limited research on the types of learning within which Indigenous young people have subsequently re-engaged after being disengaged. The research presented in this chapter focuses on the specific Australian schooling site termed ‘flexi schools’. The term describes a model of schooling outside conventional education addressing the needs of disenfranchised young people. There is an array of flexible schooling programs operating in Australia with the distinct aim of re-engagement (te Riele, 2007). Given the high numbers of Indigenous young people disengaging from conventional schooling and the disparity in educational outcomes between Indigenous and non-Indigenous young people (Australian Government, 2013), it is not surprising that there are high numbers of Indigenous young people engaged in flexi schools (Shay, 2013)

DISTRIBUTED MARITIME OPERATIONS AND UNMANNED SYSTEMS TACTICAL EMPLOYMENT

The concept of Distributed Maritime Operations intends to enable a force that is capable of winning a fleet-on-fleet engagement through the integration of manned and unmanned systems, execution of deceptive tactics, and emboldening of units to conduct offensive strikes. This report contributes to the concept of DMO in the 2030-2035 timeframe through the development of an operational simulation that examines the ability for various compositions of multi-domain fleet assets to perform tactical operations in a naval combat environment. This project studies the impact of the friendly force employment of deception and tactics against an enemy force, and the resulting impact on the adversary’s ability to progress through the various stages of a kill chain. Through the development and analysis of a discrete event simulation, this research investigates the ability for naval forces in the air, surface, and electromagnetic warfare domains to contribute to DMO through the performance of tactical offensive operations and employment of deceptive tactics. The analysis resulted in two major findings. In terms of force composition, an increased number of missile carrying assets had the largest impact on operational effectiveness and survivability. Tactically, the utilization of electronic jamming, coupled with the utilization of unmanned deceptive swarms, provided a significant improvement in the survivability of friendly force assets as well as the attrition of enemy forces.OPNAV N9Ihttp://archive.org/details/distributedmarit1094559587Lieutenant, United States NavyLieutenant, United States NavyMajor, Singapore ArmyCivilian, Other, SingaporeMajor, Singapore ArmyMajor, Singapore Air ForceCaptain, United States Marine CorpsLieutenant Commander, Singapore NavyCivilian, Other, SingaporeMajor, Singapore Air ForceCivilian, Other, SingaporeMajor, Singapore Air ForceCaptain, Israel ArmyCaptain, United States Marine CorpsMajor, Singapore ArmyMajor, Singapore ArmyLieutenant, United States NavyLieutenant, United States NavyCaptain, Singapore ArmyApproved for public release; distribution is unlimited