A review of the pharmacobiotic regulation of gastrointestinal inflammation by probiotics, commensal bacteria and prebiotics.

The idea that microbes induce disease has steered medical research toward the discovery of antibacterial products for the prevention and treatment of microbial infections. The twentieth century saw increasing dependency on antimicrobials as mainline therapy accentuating the notion that bacterial interactions with humans were to be avoided or desirably controlled. The last two decades, though, have seen a refocusing of thinking and research effort directed towards elucidating the critical inter-relationships between the gut microbiome and its host that control health/wellness or disease. This research has redefined the interactions between gut microbes and vertebrates, now recognizing that the microbial active cohort and its mammalian host have shared co-evolutionary metabolic interactions that span millennia. Microbial interactions in the gastrointestinal tract provide the necessary cues for the development of regulated pro- and anti-inflammatory signals that promotes immunological tolerance, metabolic regulation and other factors which may then control local and extra-intestinal inflammation. Pharmacobiotics, using nutritional and functional food additives to regulate the gut microbiome, will be an exciting growth area of therapeutics, developing alongside an increased scientific understanding of gut-microbiome symbiosis in health and disease.

Recombination, decreased host specificity and increased mobility may have driven the emergence of maize streak virus as an agricultural pathogen

Maize streak virus (MSV; family Geminiviridae, genus Mastrevirus), the causal agent of maize streak disease, ranks amongst the most serious biological threats to food security in subSaharan Africa. Although five distinct MSV strains have been currently described, only one of these - MSV-A - causes severe disease in maize. Due primarily to their not being an obvious threat to agriculture, very little is known about the 'grass-adapted' MSV strains, MSV-B, -C, -D and -E. Since comparing the genetic diversities, geographical distributions and natural host ranges of MSV-A with the other MSV strains could provide valuable information on the epidemiology, evolution and emergence of MSV-A, we carried out a phylogeographical analysis of MSVs found in uncultivated indigenous African grasses. Amongst the 83 new MSV genomes presented here, we report the discovery of six new MSV strains (MSV-F to -K). The non-random recombination breakpoint distributions detectable with these and other available mastrevirus sequences partially mirror those seen in begomoviruses, implying that the forces shaping these breakpoint patterns have been largely conserved since the earliest geminivirus ancestors. We present evidence that the ancestor of all MSV-A variants was the recombinant progeny of ancestral MSV-B and MSV-G/-F variants. While it remains unknown whether recombination influenced the emergence of MSV-A in maize, our discovery that MSV-A variants may both move between and become established in different regions of Africa with greater ease, and infect more grass species than other MSV strains, goes some way towards explaining why MSV-A is such a successful maize pathogen. © 2008 SGM.

A highly divergent South African geminivirus species illuminates the ancient evolutionary history of this family

Background. We have characterised a new highly divergent geminivirus species, Eragrostis curvula streak virus (ECSV), found infecting a hardy perennial South African wild grass. ECSV represents a new genus-level geminivirus lineage, and has a mixture of features normally associated with other specific geminivirus genera. Results. Whereas the ECSV genome is predicted to express a replication associated protein (Rep) from an unspliced complementary strand transcript that is most similar to those of begomoviruses, curtoviruses and topocuviruses, its Rep also contains what is apparently a canonical retinoblastoma related protein interaction motif such as that found in mastreviruses. Similarly, while ECSV has the same unusual TAAGATTCC virion strand replication origin nonanucleotide found in another recently described divergent geminivirus, Beet curly top Iran virus (BCTIV), the rest of the transcription and replication origin is structurally more similar to those found in begomoviruses and curtoviruses than it is to those found in BCTIV and mastreviruses. ECSV also has what might be a homologue of the begomovirus transcription activator protein gene found in begomoviruses, a mastrevirus-like coat protein gene and two intergenic regions. Conclusion. Although it superficially resembles a chimaera of geminiviruses from different genera, the ECSV genome is not obviously recombinant, implying that the features it shares with other geminiviruses are those that were probably present within the last common ancestor of these viruses. In addition to inferring how the ancestral geminivirus genome may have looked, we use the discovery of ECSV to refine various hypotheses regarding the recombinant origins of the major geminivirus lineages. © 2009 Varsani et al; licensee BioMed Central Ltd.

Quantitative evaluation of matching methods and validity measures for stereo vision

The authors present a qualitative and quantitative comparison of various similarity measures that form the kernel of common area-based stereo-matching systems. The authors compare classical difference and correlation measures as well as nonparametric measures based on the rank and census transforms for a number of outdoor images. For robotic applications, important considerations include robustness to image defects such as intensity variation and noise, the number of false matches, and computational complexity. In the absence of ground truth data, the authors compare the matching techniques based on the percentage of matches that pass the left-right consistency test. The authors also evaluate the discriminatory power of several match validity measures that are reported in the literature for eliminating false matches and for estimating match confidence. For guidance applications, it is essential to have and estimate of confidence in the three-dimensional points generated by stereo vision. Finally, a new validity measure, the rank constraint, is introduced that is capable of resolving ambiguous matches for rank transform-based matching.

mCOPA: analysis of heterogeneous features in cancer expression data

Background Cancer outlier profile analysis (COPA) has proven to be an effective approach to analyzing cancer expression data, leading to the discovery of the TMPRSS2 and ETS family gene fusion events in prostate cancer. However, the original COPA algorithm did not identify down-regulated outliers, and the currently available R package implementing the method is similarly restricted to the analysis of over-expressed outliers. Here we present a modified outlier detection method, mCOPA, which contains refinements to the outlier-detection algorithm, identifies both over- and under-expressed outliers, is freely available, and can be applied to any expression dataset. Results We compare our method to other feature-selection approaches, and demonstrate that mCOPA frequently selects more-informative features than do differential expression or variance-based feature selection approaches, and is able to recover observed clinical subtypes more consistently. We demonstrate the application of mCOPA to prostate cancer expression data, and explore the use of outliers in clustering, pathway analysis, and the identification of tumour suppressors. We analyse the under-expressed outliers to identify known and novel prostate cancer tumour suppressor genes, validating these against data in Oncomine and the Cancer Gene Index. We also demonstrate how a combination of outlier analysis and pathway analysis can identify molecular mechanisms disrupted in individual tumours. Conclusions We demonstrate that mCOPA offers advantages, compared to differential expression or variance, in selecting outlier features, and that the features so selected are better able to assign samples to clinically annotated subtypes. Further, we show that the biology explored by outlier analysis differs from that uncovered in differential expression or variance analysis. mCOPA is an important new tool for the exploration of cancer datasets and the discovery of new cancer subtypes, and can be combined with pathway and functional analysis approaches to discover mechanisms underpinning heterogeneity in cancers

Signaling of receptor tyrosine kinases in the nucleus

Since the discovery of the first receptor tyrosine kinase (RTK) proteins in the late 1970s and early 1980s, many scientists have explored the functions of these important cell signaling molecules. The finding that these proteins are often deregulated or mutated in diseases such as cancers and diabetes, together with their potential as clinical therapeutic targets, has further highlighted the necessity for understanding the signaling functions of these important proteins. The mechanisms of RTK regulation and function have been recently reviewed by Lemmon & Schlessinger (2010) but in this review we instead focus on the results of several recent studies that show receptor tyrosine kinases can function from subcellular localisations, including in particular the nucleus, in addition to their classical plasma membrane location. Nuclear localisation of receptor tyrosine kinases has been demonstrated to be important for normal cell function but is also believed to contribute to the pathogenesis of several human diseases.

Phylodynamic analysis of the emergence and epidemiological impact of transmissible defective dengue viruses

Intra-host sequence data from RNA viruses have revealed the ubiquity of defective viruses in natural viral populations, sometimes at surprisingly high frequency. Although defective viruses have long been known to laboratory virologists, their relevance in clinical and epidemiological settings has not been established. The discovery of long-term transmission of a defective lineage of dengue virus type 1 (DENV-1) in Myanmar, first seen in 2001, raised important questions about the emergence of transmissible defective viruses and their role in viral epidemiology. By combining phylogenetic analyses and dynamical modelling, we investigate how evolutionary and ecological processes at the intra-host and inter-host scales shaped the emergence and spread of the defective DENV-1 lineage. We show that this lineage of defective viruses emerged between June 1998 and February 2001, and that the defective virus was transmitted primarily through co-transmission with the functional virus to uninfected individuals. We provide evidence that, surprisingly, this co-transmission route has a higher transmission potential than transmission of functional dengue viruses alone. Consequently, we predict that the defective lineage should increase overall incidence of dengue infection, which could account for the historically high dengue incidence reported in Myanmar in 2001-2002. Our results show the unappreciated potential for defective viruses to impact the epidemiology of human pathogens, possibly by modifying the virulence-transmissibility trade-off, or to emerge as circulating infections in their own right. They also demonstrate that interactions between viral variants, such as complementation, can open new pathways to viral emergence.

Social Media Sites as Online Information Grounds : An exploratory study of the ways in which Information Technology (IT) professionals experience social media

Social media tools are often the result of innovations in Information Technology and developed by IT professionals and innovators. Nevertheless, IT professionals, many of whom are responsible for designing and building social media technologies, have not been investigated on how they themselves use or experience social media for professional purposes. This study will use Information Grounds Theory (Pettigrew, 1998) as a framework to study IT professionals’ experience in using social media for professional purposes. Information grounds facilitates the opportunistic discovery of information within social settings created temporarily at a place where people gather for a specific purpose (e.g., doctors’ waiting rooms, office tea rooms etc.), but the social atmosphere stimulates spontaneous sharing of information (Pettigrew, 1999). This study proposes that social media has the qualities that make it a rich information grounds; people participate from separate “places” in cyberspace in a synchronous manner in real-time, making it almost as dynamic and unplanned as physical information grounds. There is limited research on how social media platforms are perceived as a “place,” (a place to go to, a place to gather, or a place to be seen in) that is comparable to physical spaces. There is also no empirical study on how IT professionals use or “experience” social media. The data for this study is being collected through a study of IT professionals who currently use Twitter. A digital ethnography approach is being taken wherein the researcher uses online observations and “follows” the participants online and observes their behaviours and interactions on social media. Next, a sub-set of participants will be interviewed on their experiences with and within social media and how social media compares with traditional methods of information grounds, information communication, and collaborative environments. An Evolved Grounded Theory (Glaser, 1992) approach will be used to analyse tweets data and interviews and to map the findings against the Information Ground Theory. Findings from this study will provide foundational understanding of IT professionals’ experiences within social media, and can help both professionals and researchers understand this fast-evolving method of communications.

The search for migraine genes : an overview of current knowledge

Migraine is a complex familial condition that imparts a significant burden on society. There is evidence for a role of genetic factors in migraine, and elucidating the genetic basis of this disabling condition remains the focus of much research. In this review we discuss results of genetic studies to date, from the discovery of the role of neural ion channel gene mutations in familial hemiplegic migraine (FHM) to linkage analyses and candidate gene studies in the more common forms of migraine. The success of FHM regarding discovery of genetic defects associated with the disorder remains elusive in common migraine, and causative genes have not yet been identified. Thus we suggest additional approaches for analysing the genetic basis of this disorder. The continuing search for migraine genes may aid in a greater understanding of the mechanisms that underlie the disorder and potentially lead to significant diagnostic and therapeutic applications.

A data mining framework for relevance feature discovery

This thesis is a study for automatic discovery of text features for describing user information needs. It presents an innovative data-mining approach that discovers useful knowledge from both relevance and non-relevance feedback information. The proposed approach can largely reduce noises in discovered patterns and significantly improve the performance of text mining systems. This study provides a promising method for the study of Data Mining and Web Intelligence.

The importance of individual difference : examining anthropomorphic tendency and responses to spokes-characters

Anthropomorphism is a cognitive bias, which occurs when individuals see human characteristics in a non-human agent, object or animal. Anthropomorphism is especially interesting to marketers, because once anthropomorphic bias has been triggered, it can lead to a greater feeling of connectedness to a non-human agent (Tam, Lee and Chao, 2013), the emulation of behaviours (Aggarwal and McGill, 2012) or greater attribution of brand personality and brand liking (Delbaere, McQuarrie and Phillips, 2011). Importantly, research now shows that levels of this tendency vary between individuals (Waytz, Cacioppo and Epley, 2010), but research to date has failed to focus on how anthropomorphic tendency influences individual responses to marketing communications messages. Spokes-characters present an ideal context through which to examine this gap, given that they function as personified brands, designed to trigger consumer anthropomorphic tendency. Further, little is understood about how spokes-characters operate and which consumers will prefer them to their human counterparts. Like anthropomorphic research, much empirical work to date has focused on design and outcomes, examining the sender’s encoding process and the feedback generated, but ignoring the individual decoding process that is so important to understanding individual differences and message effectiveness. The current research employs three experiments using an online survey with stimulus exposure to show that anthropomorphic tendency, personality similarity and spokes-character type all have relevance to the understanding of this complex relationship. Study one and two indicate that while a human spokesperson is still preferred by many, higher levels of anthropomorphic tendency increase likeability of cartoon spokes characters. Study three highlights the importance of personality similarity, which further increases likability. Additional analyses provide key findings concerning the nature of anthropomorphic tendency as an individual difference and trait. This research contributes to a greater understanding of anthropomorphism theory and fills existing gaps in the consumer psychology and marketing communications literature.

The biology of the glutamatergic system and potential role in migraine

Migraine is a common genetically linked neurovascular disorder. Approximately ~12% of the Caucasian population are affected including 18% of adult women and 6% of adult men (1, 2). A notable female bias is observed in migraine prevalence studies with females affected ~3 times more than males and is credited to differences in hormone levels arising from reproductive achievements. Migraine is extremely debilitating with wide-ranging socioeconomic impact significantly affecting people's health and quality of life. A number of neurotransmitter systems have been implicated in migraine, the most studied include the serotonergic and dopaminergic systems. Extensive genetic research has been carried out to identify genetic variants that may alter the activity of a number of genes involved in synthesis and transport of neurotransmitters of these systems. The biology of the Glutamatergic system in migraine is the least studied however there is mounting evidence that its constituents could contribute to migraine. The discovery of antagonists that selectively block glutamate receptors has enabled studies on the physiologic role of glutamate, on one hand, and opened new perspectives pertaining to the potential therapeutic applications of glutamate receptor antagonists in diverse neurologic diseases. In this brief review, we discuss the biology of the Glutamatergic system in migraine outlining recent findings that support a role for altered Glutamatergic neurotransmission from biochemical and genetic studies in the manifestation of migraine and the implications of this on migraine treatment.

Storytelling beyond the anthropocene : a quest through the crises of ecocide toward new ecological paradigms

This project is a passionate and sometimes enraged thrust toward a biodiverse future. Weaving stories with deep thinking beyond the limits of the anthropocene, I am trying to recall myself in a more-than-human world. Our planet is suffering human induced ecocide which is a global crisis threatening the existence of multiple life forms. The alchemical mix of storytelling and ecological thinking could be part remedy for humanity's adaptation: a transformational mix to re-pattern the crisis into an opportunity and shift anthropocentric structures toward networks of dynamic relationships. The purpose of this project is to explore this cultural remedy. This is a quest, a search for tools that can germinate the hypothesis: storytelling in relation to ecological thinking manifests human potential in a more-than-human world. The practice-led research is guided by the philosophy and practice of Mythology, Deep ecology and Transdisciplinarity. Further navigation is sourced from Systems Thinking, Indigenous Methodologies, Biomimicry, and Quantum Physics. The journey unfolds by reawakening the Artist's function as caretaker of Mythology and pattern inciter for the collective. The resounding discovery of this adventure is Quantum Narratives: a storytelling tool for today's world, a method to connect multiple ways of knowing and diverse languages with the purpose of engaging, relating and working with living knowledge. Quantum Narratives are used to test the field study research into the Future of Water in context of Coal Seam Gas Mining in the Murray-Darling Basin and to materialise the collaborative results as the Water Stories. This thesis is a Living Script, full of imagination and complexity. Within its folds are strategies for systemic change ready to be adapted by policy and planning brokers and those who hold power for widespread remedial action.

Understanding and measuring information security culture in developing countries : case of Saudi Arabia

The purpose of the current study was to develop a measurement of information security culture in developing countries such as Saudi Arabia. In order to achieve this goal, the study commenced with a comprehensive review of the literature, the outcome being the development of a conceptual model as a reference base. The literature review revealed a lack of academic and professional research into information security culture in developing countries and more specifically in Saudi Arabia. Given the increasing importance and significant investment developing countries are making in information technology, there is a clear need to investigate information security culture from developing countries perspective such as Saudi Arabia. Furthermore, our analysis indicated a lack of clear conceptualization and distinction between factors that constitute information security culture and factors that influence information security culture. Our research aims to fill this gap by developing and validating a measurement model of information security culture, as well as developing initial understanding of factors that influence security culture. A sequential mixed method consisting of a qualitative phase to explore the conceptualisation of information security culture, and a quantitative phase to validate the model is adopted for this research. In the qualitative phase, eight interviews with information security experts in eight different Saudi organisations were conducted, revealing that security culture can be constituted as reflection of security awareness, security compliance and security ownership. Additionally, the qualitative interviews have revealed that factors that influence security culture are top management involvement, policy enforcement, policy maintenance, training and ethical conduct policies. These factors were confirmed by the literature review as being critical and important for the creation of security culture and formed the basis for our initial information security culture model, which was operationalised and tested in different Saudi Arabian organisations. Using data from two hundred and fifty-four valid responses, we demonstrated the validity and reliability of the information security culture model through Exploratory Factor Analysis (EFA), followed by Confirmatory Factor Analysis (CFA.) In addition, using Structural Equation Modelling (SEM) we were further able to demonstrate the validity of the model in a nomological net, as well as provide some preliminary findings on the factors that influence information security culture. The current study contributes to the existing body of knowledge in two major ways: firstly, it develops an information security culture measurement model; secondly, it presents empirical evidence for the nomological validity for the security culture measurement model and discovery of factors that influence information security culture. The current study also indicates possible future related research needs.

Molecular approaches to diagnosis and management of ovarian cancer

The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.