Identification of genetic variants contributing to the migraine phenotype in different Australian populations

This project aimed to identify novel genetic risk variants associated with migraine in the Norfolk Island population. Statistical analysis and bioinformatics approaches such as polygenic modeling and gene clustering methods were carried out to explore genotypic and expression data from high-throughput techniques. This project had a particular focus on hormonal genes and other genetic variants and identified a modest effect size on the migraine phenotype.

“There’s nothing standard about standards”: Exploring tensions between two standards documents in higher education

Quality in education at the tertiary level is constantly questioned, and increasingly “professional standards” are offered as the solution to the perceived decline in quality. Foucauldian archaeological analysis of teacher graduate and geography graduate standards in Australia is conducted, revealing tensions between the different document sets. Teacher graduate standards reflect two discourses (one of knowledge and understanding, and one of skills) that are anti-intellectual and based on jargon and formulaic prescriptions. In contrast, disciplinary standards give primacy to geography as an intellectual inquiry such that its knowledge and understanding, skills, and concepts lead to progressively higher order thinking in graduates.

Using genome-Wwide complex trait analysis to quantify 'missing heritability' in Parkinson's disease

Genome-wide association studies (GWASs) have been successful at identifying single-nucleotide polymorphisms (SNPs) highly associated with common traits; however, a great deal of the heritable variation associated with common traits remains unaccounted for within the genome. Genome-wide complex trait analysis (GCTA) is a statistical method that applies a linear mixed model to estimate phenotypic variance of complex traits explained by genome-wide SNPs, including those not associated with the trait in a GWAS. We applied GCTA to 8 cohorts containing 7096 case and 19 455 control individuals of European ancestry in order to examine the missing heritability present in Parkinson's disease (PD). We meta-analyzed our initial results to produce robust heritability estimates for PD types across cohorts. Our results identify 27% (95% CI 17-38, P = 8.08E - 08) phenotypic variance associated with all types of PD, 15% (95% CI -0.2 to 33, P = 0.09) phenotypic variance associated with early-onset PD and 31% (95% CI 17-44, P = 1.34E - 05) phenotypic variance associated with late-onset PD. This is a substantial increase from the genetic variance identified by top GWAS hits alone (between 3 and 5%) and indicates there are substantially more risk loci to be identified. Our results suggest that although GWASs are a useful tool in identifying the most common variants associated with complex disease, a great deal of common variants of small effect remain to be discovered. © Published by Oxford University Press 2012.

Use of part records in Merino breeding programs - The inheritance of wool growth and fibre traits during different times of the year to determine their value in Merino breeding programs

Fibre diameter can vary dramatically along a wool staple, especially in the Mediterranean environment of southern Australia with its dry summers and abundance of green feed in spring. Other research results have shown a very low phenotypic correlation between fibre diameter grown between seasons. Many breeders use short staples to measure fibre diameter for breeding purposes and also to promote animals for sale. The effectiveness of this practice is determined by the relative response to selection by measuring fibre traits on a full 12 months wool staple as compared to measuring them only on part of a staple. If a high genetic correlation exists between the part record and the full record, then using part records may be acceptable to identify genetically superior animals. No information is available on the effectiveness of part records. This paper investigated whether wool growth and fibre diameter traits of Merino wool grown at different times of the year in a Mediterranean environment, are genetically the same trait, respectively. The work was carried out on about 7 dyebanded wool sections/animal.year, on ewes from weaning to hogget age, in the Katanning Merino resource flocks over 6 years. Relative clean wool growth of the different sections had very low heritability estimates of less than 0.10, and they were phenotypically and genetically poorly correlated with 6 or 12 months wool growth. This indicates that part record measurement of clean wool growth of these sections will be ineffective as indirect selection criteria to improve wool growth genetically. Staple length growth as measured by the length between dyebands, would be more effective with heritability estimates of between 0.20 and 0.30. However, these measurements were shown to have a low genetic correlation with wool grown for 12 months which implies that these staple length measurements would only be half as efficient as the wool weight for 6 or 12 months to improve total clean wool weight. Heritability estimates of fibre diameter, coefficient of variation of fibre diameter and fibre curvature were relatively high and were genetically and phenotypically highly correlated across sections. High positive phenotypic and genetic correlations were also found between fibre diameter, coefficient of variation of fibre diameter and fibre curvature of the different sections and similar measurements for wool grown over 6 or 12 months. Coefficient of variation of fibre diameter of the sections also had a moderate negative phenotypic and genetic correlation with staple strength of wool staples grown over 6 months indicating that coefficient of variation of fibre diameter of any section would be as good an indirect selection criterion to improve stable strength as coefficient of variation of fibre diameter for wool grown over 6 or 12 months. The results indicate that fibre diameter, coefficient of variation of fibre diameter and fibre curvature of wool grown over short periods of time have virtually the same heritability as that of wool grown over 12 months, and that the genetic correlation between fibre diameter, coefficient of variation of fibre diameter and fibre curvature on part and on full records is very high (rg > 0.85). This indicates that fibre diameter, coefficient of variation of fibre diameter and fibre curvature on part records can be used as selection criteria to improve these traits. However, part records of greasy and clean wool growth would be much less efficient than fleece weight for wool grown over 6 or 12 months because of the low heritability of part records and the low genetic correlation between these traits on part records and on wool grown for 12 months.

Frailty: A key indicator to minimize inappropriate medication in older people

Older populations are more likely to have multiple co-morbid diseases that require multiple treatments, which make them a large consumer of medications. As a person grows older, their ability to tolerate medications becomes less due to age-related changes in pharmacokinetics and pharmacodynamics often heading along a path that leads to frailty. Frail older persons often have multiple co-morbidities with signs of impairment in activities of daily living. Prescribing drugs for these vulnerable individuals is difficult and is a potentially unsafe activity. Inappropriate prescribing in older population can be detected using explicit (criterion-based) or implicit (judgment-based) criteria. Unfortunately, most current therapeutic guidelines are applicable only to healthy older adults and cannot be generalized to frail patients. These discrepancies should be addressed either by developing new criteria or by refining the existing tools for frail older people. The first and foremost step is to identify the frail patient in clinical practice by applying clinically validated tools. Once the frail patient has been identified, there is a need for specific measures or criteria to assess appropriateness of therapy that consider such factors as quality of life, functional status and remaining life expectancy and thus modified goals of care.

Quantitative methods to measure pigmentation variation in farmed Giant Tiger Prawns, Penaeus monodon, and the effects of different harvest methods on cooked colour

Cooked prawn colour is known to be a driver of market price and a visual indicator of product quality for the consumer. Although there is a general understanding that colour variation exists in farmed prawns, there has been no attempt to quantify this variation or identify where this variation is most prevalent. The objectives of this study were threefold: firstly to compare three different quantitative methods to measure prawn colour or pigmentation, two different colorimeters and colour quantification from digital images. Secondly, to quantify the amount of pigmentation variation that exists in farmed prawns within ponds, across ponds and across farms. Lastly, to assess the effects of ice storage or freeze-thawing of raw product prior to cooking. Each method was able to detect quantitative differences in prawn colour, although conversion of image based quantification of prawn colour from RGB to Lab was unreliable. Considerable colour variation was observed between prawns from different ponds and different farms, and this variation potentially affects product value. Different post-harvest methods prior to cooking were also shown to have a profound detrimental effect on prawn colour. Both long periods of ice storage and freeze thawing of raw product were detrimental to prawn colour. However, ice storage immediately after cooking was shown to be beneficial to prawn colour. Results demonstrated that darker prawn colour was preserved by holding harvested prawns alive in chilled seawater, limiting the time between harvesting and cooking, and avoiding long periods of ice storage or freeze thawing of uncooked product.

Structuring time and questioning to achieve tactical awareness in games lessons

Background: A paradigm shift in educational policy to create problem solvers and critical thinkers produced the games concept approach (GCA) in Singapore's Revised Syllabus for Physical Education (1999). A pilot study (2001) conducted on 11 primary school student teachers (STs) using this approach identified time management and questioning as two of the major challenges faced by novice teachers. Purpose: To examine the GCA from three perspectives: structure—lesson form in terms of teacher-time and pupil-time; product—how STs used those time fractions; and process—the nature of their questioning (type, timing, and target). Participants and setting: Forty-nine STs from three different PETE cohorts (two-year diploma, four-year degree, two-year post-graduate diploma) volunteered to participate in the study conducted during the penultimate week of their final practicum in public primary and secondary schools. Intervention: Based on the findings of the pilot study, PETE increased the emphasis on GCA content specific knowledge and pedagogical procedures. To further support STs learning to actualise the GCA, authentic micro-teaching experiences that were closely monitored by faculty were provided in schools nearby. Research design: This is a descriptive study of time-management and questioning strategies implemented by STs on practicum. Each lesson was segmented into a number of sub-categories of teacher-time (organisation, demonstration and closure) and pupil-time (practice time and game time). Questions were categorised as knowledge, technical, tactical or affective. Data collection: Each ST was video-taped teaching a GCA lesson towards the end of their final practicum. The STs individually determined the timing of the data collection and the lesson to be observed. Data analysis: Each lesson was segmented into a number of sub-categories of both teacher- and pupil-time. Duration recording using Noldus software (Observer 4.0) segmented the time management of different lesson components. Questioning was coded in terms of type, timing and target. Separate MANOVAs were used to measure the difference between programmes and levels (primary and secondary) in relation to time-management procedures and questioning strategies. Findings: No differences emerged between the programmes or levels in their time-management or questioning strategies. Using the GCA, STs generated more pupil time (53%) than teacher time (47%). STs at the primary level provided more technical practice, and those in secondary schools more small-sided game play. Most questions (58%) were asked during play or practice but were substantially low-order involving knowledge or recall (76%) and only 6.7% were open-ended or divergent and capable of developing tactical awareness. Conclusions: Although STs are delivering more pupil time (practice and game) than teacher-time, the lesson structure requires further fine-tuning to extend the practice task beyond technical drills. Many questions are being asked to generate knowledge about games but lack sufficient quality to enhance critical thinking and tactical awareness, as the GCA intends.

Genome-wide DNA methylation profiling of CD8+ T cells shows a distinct epigenetic signature to CD4+ T cells in multiple sclerosis patients

Background Multiple sclerosis (MS) is thought to be a T cell-mediated autoimmune disorder. MS pathogenesis is likely due to a genetic predisposition triggered by a variety of environmental factors. Epigenetics, particularly DNA methylation, provide a logical interface for environmental factors to influence the genome. In this study we aim to identify DNA methylation changes associated with MS in CD8+ T cells in 30 relapsing remitting MS patients and 28 healthy blood donors using Illumina 450K methylation arrays. Findings Seventy-nine differentially methylated CpGs were associated with MS. The methylation profile of CD8+ T cells was distinctive from our previously published data on CD4+ T cells in the same cohort. Most notably, there was no major CpG effect at the MS risk gene HLA-DRB1 locus in the CD8+ T cells. Conclusion CD8+ T cells and CD4+ T cells have distinct DNA methylation profiles. This case–control study highlights the importance of distinctive cell subtypes when investigating epigenetic changes in MS and other complex diseases.

An algorithm to find distant repeats in a pair of protein sequences

Distant repeats between a pair of protein sequences can be exploited to study the various aspects of proteins such as structure-function relationship, disorders due to protein malfunction, evolutionary analysis, etc. An in-depth analysis of the distant repeats would facilitate to establish a stable evolutionary relation of the repeats with respect to their three-dimensional structure. To this effect, an algorithm has been devised to identify the distant repeats in a pair of protein sequences by essentially using the scores of PAM (Percent Accepted Mutation) matrices. The proposed algorithm will be of much use to researchers involved in the comparative study of various organisms based on the amino-acid repeats in protein sequences. (C) 2010 Elsevier B.V. All rights reserved.

A Shapley Value-Based Approach to Discover Influential Nodes in Social Networks

Our study concerns an important current problem, that of diffusion of information in social networks. This problem has received significant attention from the Internet research community in the recent times, driven by many potential applications such as viral marketing and sales promotions. In this paper, we focus on the target set selection problem, which involves discovering a small subset of influential players in a given social network, to perform a certain task of information diffusion. The target set selection problem manifests in two forms: 1) top-k nodes problem and 2) lambda-coverage problem. In the top-k nodes problem, we are required to find a set of k key nodes that would maximize the number of nodes being influenced in the network. The lambda-coverage problem is concerned with finding a set of k key nodes having minimal size that can influence a given percentage lambda of the nodes in the entire network. We propose a new way of solving these problems using the concept of Shapley value which is a well known solution concept in cooperative game theory. Our approach leads to algorithms which we call the ShaPley value-based Influential Nodes (SPINs) algorithms for solving the top-k nodes problem and the lambda-coverage problem. We compare the performance of the proposed SPIN algorithms with well known algorithms in the literature. Through extensive experimentation on four synthetically generated random graphs and six real-world data sets (Celegans, Jazz, NIPS coauthorship data set, Netscience data set, High-Energy Physics data set, and Political Books data set), we show that the proposed SPIN approach is more powerful and computationally efficient. Note to Practitioners-In recent times, social networks have received a high level of attention due to their proven ability in improving the performance of web search, recommendations in collaborative filtering systems, spreading a technology in the market using viral marketing techniques, etc. It is well known that the interpersonal relationships (or ties or links) between individuals cause change or improvement in the social system because the decisions made by individuals are influenced heavily by the behavior of their neighbors. An interesting and key problem in social networks is to discover the most influential nodes in the social network which can influence other nodes in the social network in a strong and deep way. This problem is called the target set selection problem and has two variants: 1) the top-k nodes problem, where we are required to identify a set of k influential nodes that maximize the number of nodes being influenced in the network and 2) the lambda-coverage problem which involves finding a set of influential nodes having minimum size that can influence a given percentage lambda of the nodes in the entire network. There are many existing algorithms in the literature for solving these problems. In this paper, we propose a new algorithm which is based on a novel interpretation of information diffusion in a social network as a cooperative game. Using this analogy, we develop an algorithm based on the Shapley value of the underlying cooperative game. The proposed algorithm outperforms the existing algorithms in terms of generality or computational complexity or both. Our results are validated through extensive experimentation on both synthetically generated and real-world data sets.

A Huber-loss-driven clustering technique and its application to robust cell detection in confocal microscopy images

We address the problem of detecting cells in biological images. The problem is important in many automated image analysis applications. We identify the problem as one of clustering and formulate it within the framework of robust estimation using loss functions. We show how suitable loss functions may be chosen based on a priori knowledge of the noise distribution. Specifically, in the context of biological images, since the measurement noise is not Gaussian, quadratic loss functions yield suboptimal results. We show that by incorporating the Huber loss function, cells can be detected robustly and accurately. To initialize the algorithm, we also propose a seed selection approach. Simulation results show that Huber loss exhibits better performance compared with some standard loss functions. We also provide experimental results on confocal images of yeast cells. The proposed technique exhibits good detection performance even when the signal-to-noise ratio is low.

A multi-level multi-scale approach to study essential genes in Mycobacterium tuberculosis

Background: The set of indispensable genes that are required by an organism to grow and sustain life are termed as essential genes. There is a strong interest in identification of the set of essential genes, particularly in pathogens, not only for a better understanding of the pathogen biology, but also for identifying drug targets and the minimal gene set for the organism. Essentiality is inherently a systems property and requires consideration of the system as a whole for their identification. The available experimental approaches capture some aspects but each method comes with its own limitations. Moreover, they do not explain the basis for essentiality in most cases. A powerful prediction method to recognize this gene pool including rationalization of the known essential genes in a given organism would be very useful. Here we describe a multi-level multi-scale approach to identify the essential gene pool in a deadly pathogen, Mycobacterium tuberculosis. Results: The multi-level workflow analyses the bacterial cell by studying (a) genome-wide gene expression profiles to identify the set of genes which show consistent and significant levels of expression in multiple samples of the same condition, (b) indispensability for growth by using gene expression integrated flux balance analysis of a genome-scale metabolic model, (c) importance for maintaining the integrity and flow in a protein-protein interaction network and (d) evolutionary conservation in a set of genomes of the same ecological niche. In the gene pool identified, the functional basis for essentiality has been addressed by studying residue level conservation and the sub-structure at the ligand binding pockets, from which essential amino acid residues in that pocket have also been identified. 283 genes were identified as essential genes with high-confidence. An agreement of about 73.5% is observed with that obtained from the experimental transposon mutagenesis technique. A large proportion of the identified genes belong to the class of intermediary metabolism and respiration. Conclusions: The multi-scale, multi-level approach described can be generally applied to other pathogens as well. The essential gene pool identified form a basis for designing experiments to probe their finer functional roles and also serve as a ready shortlist for identifying drug targets.

Proceedings of the International Workshop responding to HIV and AIDS in the fishery sector in Africa, Lusaka, Zambia, 21-22 February 2006

The purpose of the workshop was to enable professionals and organizations working with fishing communities in response to HIV and AIDS in Africa to share experiences, appraise the efficacy of their approaches and identify actions in research and development that will further improve their impact. The workshop pursued and achieved the following objectives: 1)Review and compare research findings and approaches applied in response to HIV and AIDS in fishing communities and the wider fishery sector. 2)Identify good practice examples for wider application. 3)Identify next steps in development and research to scale up these examples. 4)Initiate a network of practitioners in Africa for capacity building, scaling-up and further development of approaches. The range of papers presented at the conference reveals the diversity of responses to HIV and AIDS in the fishery sector at all levels. The papers discussed a range of issues within this broad remit, from community level impacts of disease to policy implementation, from spatial mapping to theatre as a mode of communication. (Document contains 92 pages)

Donut-Shaped Fingerprint In Homologous Polypeptide Relationships-A Topological Feature Related To Pathogenic Structural Changes In Conformational Disease

Features of homologous relationship of proteins can provide us a general picture of protein universe, assist protein design and analysis, and further our comprehension of the evolution of organisms. Here we carried Out a Study of the evolution Of protein molecules by investigating homologous relationships among residue segments. The motive was to identify detailed topological features of homologous relationships for short residue segments in the whole protein universe. Based on the data of a large number of non-redundant Proteins, the universe of non-membrane polypeptide was analyzed by considering both residue mutations and structural conservation. By connecting homologous segments with edges, we obtained a homologous relationship network of the whole universe of short residue segments, which we named the graph of polypeptide relationships (GPR). Since the network is extremely complicated for topological transitions, to obtain an in-depth understanding, only subgraphs composed of vital nodes of the GPR were analyzed. Such analysis of vital subgraphs of the GPR revealed a donut-shaped fingerprint. Utilization of this topological feature revealed the switch sites (where the beginning of exposure Of previously hidden "hot spots" of fibril-forming happens, in consequence a further opportunity for protein aggregation is Provided; 188-202) of the conformational conversion of the normal alpha-helix-rich prion protein PrPC to the beta-sheet-rich PrPSc that is thought to be responsible for a group of fatal neurodegenerative diseases, transmissible spongiform encephalopathies. Efforts in analyzing other proteins related to various conformational diseases are also introduced. (C) 2009 Elsevier Ltd. All rights reserved.

Mugilid Fish Are Sentinels of Exposure to Endocrine Disrupting Compounds in Coastal and Estuarine Environments

Effects on fish reproduction can result from a variety of toxicity mechanisms first operating at the molecular level. Notably, the presence in the environment of some compounds termed endocrine disrupting chemicals (EDCs) can cause adverse effects on reproduction by interfering with the endocrine system. In some cases, exposure to EDCs leads to the animal feminization and male fish may develop oocytes in testis (intersex condition). Mugilid fish are well suited sentinel organisms to study the effects of reproductive EDCs in the monitoring of estuarine/marine environments. Up-regulation of aromatases and vitellogenins in males and juveniles and the presence of intersex individuals have been described in a wide array of mullet species worldwide. There is a need to develop new molecular markers to identify early feminization responses and intersex condition in fish populations, studying mechanisms that regulate gonad differentiation under exposure to xenoestrogens. Interestingly, an electrophoresis of gonad RNA, shows a strong expression of 5S rRNA in oocytes, indicating the potential of 5S rRNA and its regulating proteins to become useful molecular makers of oocyte presence in testis. Therefore, the use of these oocyte markers to sex and identify intersex mullets could constitute powerful molecular biomarkers to assess xenoestrogenicity in field conditions.