Interactions of ingested food, beverage, and tobacco components involving human cytochrome P4501A2, 2A6, 2E1, and 3A4 enzymes

Human cytochrome P450 (P450) enzymes are involved in the oxidation of natural products found in foods, beverages, and tobacco products and their catalytic activities can also be modulated by components of the materials. The microsomal activation of aflatoxin B1 to the exo-3,9-epoxide is stimulated by flavone and 7,8-benzoflavone, and attenuated by the flavonoid naringenin, a major component of grapefruit. P4502E1 has been demonstrated to play a potentially major role in the activation of a number of very low-molecular weight cancer suspects, including ethyl carbamate (urethan), which is present in alcoholic beverages and particularly stone brandies. The enzyme (P4502E1) is also known to be inducible by ethanol. Tobacco contains a large number of potential carcinogens. In human liver microsomes a significant role for P4501A2 can be demonstrated in the activation of cigarette smoke condensate. Some of the genotoxicity may be due to arylamines. P4501A2 is also inhibited by components of crude cigarette smoke condensate. The tobacco-specific nitrosamines are activated by a number of P450 enzymes. Of those known to be present in human liver, P4501A2, 2A6, and 2E1 can activate these nitrosamines to genotoxic products.

Cytochrome p450 1b1, a new keystone in gene-environment interactions related to human head and neck cancer?

Alcohol consumption and tobacco smoking are major causes of head and neck cancers, and regional differences point to the importance of research into gene-environment interactions. Much interest has been focused on polymorphisms of CYP1A1 and of GSTM1 and GSTT1, but a number of studies have not demonstrated significant effects. This has mostly been ascribed to small sample sizes. In general, the impact of polymorphisms of metabolic enzymes appears inconsistent, with some reports of weak-to-moderate associations, and with others of no elevation of risks. The classical cytochrome P450 isoenzyme considered for metabolic activation of polycyclic aromatic hydrocarbons (PAH) is CYP1A1. A new member of the CYP1 family, CYP1B1, was cloned in 1994, currently representing the only member of the CYP1B subfamily. A number of single nucleotide polymorphisms of the CYP1B1 gene have been reported. The amino acid substitutions Val432Leu (CYP1B1*3) and Asn453Ser (CYP1B1*4), located in the heme binding domain of CYP1B1, appear as likely candidates to be linked with biological effects. CYP1B1 activates a wide range of PAH, aromatic and heterocyclic amines. Very recently, the CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squamous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has pointed to interactive effects. This provides new molecular evidence that tobacco smoke-specific compounds relevant to head and neck carcinogenesis are metabolically activated through CYP1B1 and is consistent with a major pathogenetic relevance of PAH as ingredients of tobacco smoke.

Exploring the impact of shared domain knowledge on strategic alignment in the Australian public sector

In this age of ever-increasing information technology (IT) driven environments, governments/or public sector organisations (PSOs) are expected to demonstrate the business value of the investment in IT and take advantage of the opportunities offered by technological advancements. Strategic alignment (SA) emerged as a mechanism to bridge the gap between business and IT missions, objectives, and plans in order to ensure value optimisation from investment in IT and enhance organisational performance. However, achieving and sustaining SA remains a challenge requiring even more agility nowadays to keep up with turbulent organisational environments. The shared domain knowledge (SDK) between the IT department and other diverse organisational groups is considered as one of the factors influencing the successful implementation of SA. However, SDK in PSOs has received relatively little empirical attention. This paper presents findings from a study which investigated the influence of SDK on SA within organisations in the Australian public sector. The developed research model examined the relationship of SDK between business and IT domains with SA using a survey of 56 public sector professionals and executives. A key research contribution is the empirical demonstration that increasing levels of SDK between IT and business groups leads to increased SA.

Exploring the usefulness of structural–functional approaches to analyse governance of planning systems

Existing planning theories tend to be limited in their analytical scope and often fail to account for the impact of many interactions between the multitudes of stakeholders involved in strategic planning processes. Although many theorists rejected structural–functional approaches from the 1970s, this article argues that many of structural–functional concepts remain relevant and useful to planning practitioners. In fact, structural–functional approaches are highly useful and practical when used as a foundation for systemic analysis of real-world, multi-layered, complex planning systems to support evidence-based governance reform. Such approaches provide a logical and systematic approach to the analysis of the wider governance of strategic planning systems that is grounded in systems theory and complementary to existing theories of complexity and planning. While we do not propose its use as a grand theory of planning, this article discusses how structural–functional concepts and approaches might be applied to underpin a practical analysis of the complex decision-making arrangements that drive planning practice, and to provide the evidence needed to target reform of poorly performing arrangements.

A conceptual analysis of strategic capability development within product innovation projects

Strategic capability development refers to the renewal of the organisational capabilities which are sources of competitive advantage. The aim of this paper is to examine how strategic capability and competitive advantage build up over time. Recent literature points to the integration of dynamic capability and ambidexterity perspectives in explaining organisational capability development. Literature analysis reveals the role of knowledge integration and product innovation in integrating dynamic capability and ambidexterity. However, little attention has yet been paid to knowledge integration within innovation projects as a context for capability development. Accordingly, this paper aims to develop a conceptual framework for strategic capability development focusing on the role of knowledge integration within product innovation projects. This framework contributes to identifying and emphasising the role of micro processes in capability renewal which in turn enhances our understanding of strategic capability development.

Epigenetics and migraine; complex mitochondrial interactions contributing to disease susceptibility

Migraine is a common neurological disorder classified by the World Health Organisation (WHO) as one of the top twenty most debilitating diseases in the developed world. Current therapies are only effective for a proportion of sufferers and new therapeutic targets are desperately needed to alleviate this burden. Recently the role of epigenetics in the development of many complex diseases including migraine has become an emerging topic. By understanding the importance of acetylation, methylation and other epigenetic modifications, it then follows that this modification process is a potential target to manipulate epigenetic status with the goal of treating disease. Bisulphite sequencing and methylated DNA immunoprecipitation have been used to demonstrate the presence of methylated cytosines in the human D-loop of mitochondrial DNA (mtDNA), proving that the mitochondrial genome is methylated. For the first time, it has been shown that there is a difference in mtDNA epigenetic status between healthy controls and those with disease, especially for neurodegenerative and age related conditions. Given co-morbidities with migraine and the suggestive link between mitochondrial dysfunction and the lowered threshold for triggering a migraine attack, mitochondrial methylation may be a new avenue to pursue. Creative thinking and new approaches are needed to solve complex problems and a systems biology approach, where multiple layers of information are integrated is becoming more important in complex disease modelling.

Effect of rod-cone interactions on mesopic visual performance mediated by chromatic and luminance pathways

We studied the effect of rod–cone interactions on mesopic visual reaction time (RT). Rod and cone photoreceptor excitations were independently controlled using a four-primary photostimulator. It was observed that (1) lateral rod–cone interactions increase the cone-mediated RTs; (2) the rod–cone interactions are strongest when rod sensitivity is maximal in a dark surround, but weaker with increased rod activity in a light surround; and (3) the presence of a dark surround nonselectively increased the mean and variability of chromatic (+L-M, S-cone) and luminance (L+M+S) RTs independent of the level of rod activity. The results demonstrate that lateral rod–cone interactions must be considered when deriving mesopic luminous efficiency using RT.

Strategic supply chain management factors influencing agribusiness innovation utilization

Purpose – The purpose of this paper is to examine empirically, an industry development paradox, using embryonic literature in the area of strategic supply chain management, together with innovation management literature. This study seeks to understand how, forming strategic supply chain relationships, and developing strategic supply chain capability, influences beneficial supply chain outcomes expected from utilizing industry-led innovation, in the form of electronic business solutions using the internet, in the Australian beef industry. Findings should add valuable insights to both academics and practitioners in the fields of supply chain innovation management and strategic supply chain management, and expand knowledge to current literature. Design/methodology/approach – This is a quantitative study comparing innovative and non-innovative supply chain operatives in the Australian beef industry, through factor analysis and structural equation modeling using PAWS Statistical V18 and AMOS V18 to analyze survey data from 412 respondents from the Australian beef supply chain. Findings – Key findings are that both innovative and non-innovative supply chain operators attribute supply chain synchronization as only a minor indicator of strategic supply chain capability, contrary to the literature; and they also indicate strategic supply chain capability has a minor influence in achieving beneficial outcomes from utilizing industry-led innovation. These results suggest a lack of coordination between supply chain operatives in the industry. They also suggest a lack of understanding of the benefits of developing a strategic supply chain management competence, particularly in relation to innovation agendas, and provides valuable insights as to why an industry paradox exists in terms of the level of investment in industry-led innovation, vs the level of corresponding benefit achieved. Research limitations/implications – Results are not generalized due to the single agribusiness industry studied and the single research method employed. However, this provides opportunity for further agribusiness studies in this area and also studies using alternate methods, such as qualitative, in-depth analysis of these factors and their relationships, which may confirm results or produce different results. Further, this study empirically extends existing theoretical contributions and insights into the roles of strategic supply chain management and innovation management in improving supply chain and ultimately industry performance while providing practical insights to supply chain practitioners in this and other similar agribusiness industries. Practical implications – These findings confirm results from a 2007 research (Ketchen et al., 2007) which suggests supply chain practice and teachings need to take a strategic direction in the twenty-first century. To date, competence in supply chain management has built up from functional and process orientations rather than from a strategic perspective. This study confirms that there is a need for more generalists that can integrate with various disciplines, particularly those who can understand and implement strategic supply chain management. Social implications – Possible social implications accrue through the development of responsible government policy in terms of industry supply chains. Strategic supply chain management and supply chain innovation management have impacts to the social fabric of nations through the sustainability of their industries, especially agribusiness industries which deal with food safety and security. If supply chains are now the competitive weapon of nations then funding innovation and managing their supply chain competitiveness in global markets requires a strategic approach from everyone, not just the industry participants. Originality/value – This is original empirical research, seeking to add value to embryonic and important developing literature concerned with adopting a strategic approach to supply chain management. It also seeks to add to existing literature in the area of innovation management, particularly through greater understanding of the implications of nations developing industry-wide, industry-led innovation agendas, and their ramifications to industry supply chains.

A study of the informal interactions between audit committees and internal auditors in Australia

This paper finds evidence for the growing importance of informal interactions between the internal audit function and the audit committee (AC) in Australia – a relatively unexplored topic in the literature – using a survey of Chief Audit Executives (CAEs). It also describes the nature of these informal interactions. The most innovative elements of this paper are the findings that certain personal characteristics of CAEs, the specific knowledge and expertise of the AC chair, as well as some of the AC chair’s personal characteristics are associated with the existence (and increase) of informal interactions.

Informal interactions between audit committees and internal audit functions : exploratory evidence and directions for future research

Purpose – This paper aims to recognise the importance of informal processes within corporate governance and complement existing research in this area by investigating factors associated with the existence of informal interactions between audit committees and internal audit functions and in providing directions for future research. Design/methodology/approach – To examine the existence and drivers of informal interactions between audit committees and internal audit functions, this paper relies on a questionnaire survey of chief audit executives (CAEs) in the UK from listed and non-listed, as well as financial and non-financial, companies. While prior qualitative research suggests that informal interactions do take place, most of the evidence is based on particular organisational setting or on a very small range of interviews. The use of a questionnaire enabled the examination of the existence of internal interactions across a relatively larger number of entities. Findings – The paper finds evidence of audit committees and internal audit functions engaging in informal interactions in addition to formal pre-scheduled regular meetings. Informal interactions complement formal meetings with the audit committee and as such represent additional opportunities for the audit committees to monitor internal audit functions. Audit committees’ informal interactions are significantly and positively associated with audit committee independence, audit chair’s knowledge and experience, and internal audit quality. Originality/value – The results demonstrate the importance of the background of the audit committee chair for the effectiveness of the governance process. This is possibly the first paper to examine the relationship between audit committee quality and internal audit, on the existence and driver of informal interactions. Policy makers should recognize that in addition to formal mechanisms, informal processes, such as communication outside of formal pre-scheduled meetings, play a significant role in corporate governance.

The co-transcriptome of uropathogenic Escherichia coli-infected mouse macrophages reveals new insights into host-pathogen interactions

Urinary tract infections (UTI) are among the most common infections in humans. Uropathogenic Escherichia coli (UPEC) can invade and replicate within bladder epithelial cells, and some UPEC strains can also survive within macrophages. To understand the UPEC transcriptional program associated with intramacrophage survival, we performed host–pathogen co-transcriptome analyses using RNA sequencing. Mouse bone marrow-derived macrophages (BMMs) were challenged over a 24 h time course with two UPEC reference strains that possess contrasting intramacrophage phenotypes: UTI89, which survives in BMMs, and 83972, which is killed by BMMs. Neither of these strains caused significant BMM cell death at the low multiplicity of infection that was used in this study. We developed an effective computational framework that simultaneously separated, annotated, and quantified the mammalian and bacterial transcriptomes. BMMs responded to the two UPEC strains with a broadly similar gene expression program. In contrast, the transcriptional responses of the UPEC strains diverged markedly from each other. We identified UTI89 genes upregulated at 24 h post-infection, and hypothesized that some may contribute to intramacrophage survival. Indeed, we showed that deletion of one such gene (pspA) significantly reduced UTI89 survival within BMMs. Our study provides a technological framework for simultaneously capturing global changes at the transcriptional level in co-cultures, and has generated new insights into the mechanisms that UPEC use to persist within the intramacrophage environment.

Pedestrian-cyclist interactions at bus stops along segregated bike paths : a case study of Montreal

Safety is one of the major world health issues, and is even more acute for “vulnerable” road users, pedestrians and cyclists. At the same time, public authorities are promoting the active modes of transportation that involve these very users for their health benefits. It is therefore important to understand the factors and designs that provide the best safety for vulnerable road users and encourage more people to use these modes. Qualitative and quantitative shortcomings of collisions make it necessary to use surrogate measures of safety in studying these modes. Some interactions without a collision such as conflicts can be good surrogates of collisions as they are more frequent and less costly. To overcome subjectivity and reliability challenges, automatic conflict analysis using video cameras and deriving users’ trajectories is a solution to overcome shortcomings of manual conflict analysis. The goal of this paper is to identify and characterize various interactions between cyclists and pedestrians at bus stops along bike paths using a fully automated process. Three conflict severity indicators are calculated and adapted to the situation of interest to capture those interactions. A microscopic analysis of users’ behavior is proposed to explain interactions more precisely. Eventually, the study aims to show the capability of automatically collecting and analyzing data for pedestrian-cyclist interactions at bus stops along segregated bike paths in order to better understand the actual and perceived risks of these facilities.

Cryptic marketing : strategic targeting of subculture markets

This research aims to understand what factors influence consumers' behaviour to subculture marketing and how companies can strategically overcome potential brand alienation. Findings validate cryptic marketing as a strategy for organizations to communicate effectively with their chosen market through the use of cryptic cues, symbols and messages while circumventing negative responses from non-target audiences. The thesis contributes to extending current understanding of marketing communication through the use of covert strategies, employing covert tactics on the non-target, wider market instead of the target, subculture market.

Subsurface imaging of vegetation, climate, and root-zone moisture interactions

Changes in global climate and land use affect important prolesses from evapotranspiration and groundwater recharge to carbon storage and biochemical cycling. Near surface soil moisture is pivotal to understand the consequences of these changes. However, the dynamic interactions between vegetation and soil moisture remain largely unresolved because it is difficult to monitor and quantify subsurface hydrologic fluxes at relevant scales. Here we use electrical resistivity to monitor the influence of climate and vegetation on root-zone moisture, bridging the gap between remotely-sensed and in-situ point measurements. Our research quantifies large seasonal differences in root-zone moisture dynamics for a forest-grassland ecotone. We found large differences in effective rooting depth and moisture distributions for the two vegetation types. Our results highlight the likely impacts of land transformations on groun ter recharge, streamflow, and land-atmosphere exchanges.

Parent feeding interactions and practices during childhood cancer treatment: A qualitative investigation

In the general population it is evident that parent feeding practices can directly shape a child’s life long dietary intake. Young children undergoing childhood cancer treatment may experience feeding difficulties and limited food intake, due to the inherent side effects of their anti-cancer treatment. What is not clear is how these treatment side effects are influencing the parent–child feeding relationship during anti-cancer treatment. This retrospective qualitative study collected telephone based interview data from 38 parents of childhood cancer patients who had recently completed cancer treatment (child’s mean age: 6.98 years). Parents described a range of treatment side effects that impacted on their child’s ability to eat, often resulting in weight loss. Sixty-one percent of parents (n = 23) reported high levels of stress in regard to their child’s eating and weight loss during treatment. Parents reported stress, feelings of helplessness, and conflict and/or tension between parent and the child during feeding/eating interactions. Parents described using both positive and negative feeding practices, such as: pressuring their child to eat, threatening the insertion of a nasogastric feeding tube, encouraging the child to eat and providing home cooked meals in hospital. Results indicated that parent stress may lead to the use of coping strategies such as positive or negative feeding practices to entice their child to eat during cancer treatment. Future research is recommended to determine the implication of parent feeding practice on the long term diet quality and food preferences of childhood cancer survivors.