Heterologous microarray experiments used to identify the early gene response to heat stress in a coral reef fish

Coral reef fishes are expected to experience rising sea surface temperatures due to climate change. How well tropical reef fishes will respond to these increased temperatures and which genes are important in the response to elevated temperatures is not known. Microarray technology provides a powerful tool for gene discovery studies, but the development of microarrays for individual species can be expensive and time-consuming. In this study, we tested the suitability of a Danio rerio oligonucleotide microarray for application in a species with few genomic resources, the coral reef fish Pomacentrus moluccensis. Results from a comparative genomic hybridization experiment and direct sequence comparisons indicate that for most genes there is considerable sequence similarity between the two species, suggesting that the D. rerio array is useful for genomic studies of P. moluccensis. We employed this heterologous microarray approach to characterize the early transcriptional response to heat stress in P. moluccensis. A total of 111 gene loci, many of which are involved in protein processing, transcription, and cell growth, showed significant changes in transcript abundance following exposure to elevated temperatures. Changes in transcript abundance were validated for a selection of candidate genes using quantitative real-time polymerase chain reaction. This study demonstrates that heterologous microarrays can be successfully employed to study species for which specific microarrays have not yet been developed, and so have the potential to greatly enhance the utility of microarray technology to the field of environmental and functional genomics.

Systematic review of randomised controlled trials of sildenafil (Viagra®) in the treatment of male erectile dysfunction.

Background: Sildenafil (Viagra®), a new oral drug for the treatment of erectile dysfunction, was licensed for use across Europe in 1998. Aim: To examine the effectiveness and safety of sildenafil as an oral treatment for erectile dysfunction. Design of study: Systematic review and meta-analysis.
Setting: All published or unpublished randomised controlled trials comparing sildenafil with a placebo or alternative therapies. Method: Published studies were sought by computerised searches of electronic databases using the keywords ‘sildenafil’ and ‘Viagra’. A hand search was also done of the British Medical Journal, Lancet, Journal of the American
Medical Association, New England Journal of Medicine, British Journal of General Practice, Drug, Inpharma and Scrip. An assessment of quality of all identified studies and data extraction was undertaken independently by two researchers. Results were combined in a meta-analysis where appropriate, using RevMan version 3. Results: Twenty-one trials were identified. All trials showed a statistically significant improvement in erectile or sexual function in patients using sildenafil compared with a placebo. A meta-analysis of 16 trials reporting a global efficacy response showed that men were 3.57 (95% CI = 2.93–4.43) times as likely to have improved erections on sildenafil compared with those on a placebo. The number needed to treat to have one man with improved erections was two. The drug has a relatively safe side-effect profile. Conclusions: Available research shows that sildenafil is an effective treatment for male erectile dysfunction. Many trial participants had some baseline erectile function and it is probable that in clinical practice, where the erectile function tends to be more impaired, the number needed to treat may be higher.

Global and threshold-free transcriptional regulatory networks reconstruction through integrating ChIP-Chip and expression data

Inferring transcriptional regulatory networks from high-throughput biological data is a major challenge to bioinformatics today. To address this challenge, we developed TReNGO (Transcriptional Regulatory Networks reconstruction based on Global Optimization), a global and threshold-free algorithm with simulated annealing for inferring regulatory networks by the integration of ChIP-chip and expression data. Superior to existing methods, TReNGO was expected to find the optimal structure of transcriptional regulatory networks without any arbitrary thresholds or predetermined number of transcriptional modules (TMs). TReNGO was applied to both synthetic data and real yeast data in the rapamycin response. In these applications, we demonstrated an improved functional coherence of TMs and TF (transcription factor)- target predictions by TReNGO when compared to GRAM, COGRIM or to analyzing ChIP-chip data alone. We also demonstrated the ability of TReNGO to discover unexpected biological processes that TFs may be involved in and to also identify interesting novel combinations of TFs.

Preparing students for a world which is global in its outlook and influences: the rhetoric, reality and response

The imperative for schools and teachers to understand and teach with a global perspective has been reiterated in Victoria recently with the release of the Victorian Curriculum Reform Consultation Paper (VCAA, 2004). This paper states that, "the purposes of schooling are to prepare students for a world which is global in its outlook and influences." (p.4).

The introductory paragraphs of selected states' and territories' Studies of Society and Environment (SOSE) curriculum statements include and reiterate 'global' in the rationale for teaching and learning. Teaching in SOSE is charged with responsibility for incorporating 'global' into classroom practice. What is the role and place of SOSE in this teaching and how can SOSE teachers be better equipped to teach in a time of internationalisation and globalisation? Are teachers prepared to meet this challenge?

This paper will position the importance of teachers' lived experiences, their capacity to reflect upon these experiences, to their preparedness and competency in teaching 'global education' both within a SOSE classroom and beyond. How can personal critical reflection sharpen the focus for teaching in and to this global world? What are the place of narrative and the lived experiences of teachers in sharpening this focus? The data for this paper is drawn from a self study of the author who is studying a Masters by Research and teaches Social Education and Education Studies at Deakin University.

The paper argues that pedagogy around teaching global education in the classroom cannot be isolated from the teacher's identities, background experiences, which influence and shape their approaches to teaching in a global education curriculum. The methodology in teaching global education needs to be further aligned to teacher narratives and the lived experiences of teachers in order to link local, national and global domains.

The paper will describe how teaching for a 'world which is global in outlook and influences' can be researched by examining a selection of personal stories and lived experiences. The paper will conclude with a draft framework of global education that acknowledges reflection on lived experiences and narratives.

Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis.

Deregulated glucose metabolism fulfills the energetic and biosynthetic requirements for tumor growth driven by oncogenes. Because inhibition of oncogenic BRAF causes profound reductions in glucose uptake and a strong clinical benefit in BRAF-mutant melanoma, we examined the role of energy metabolism in responses to BRAF inhibition. We observed pronounced and consistent decreases in glycolytic activity in BRAF-mutant melanoma cells. Moreover, we identified a network of BRAF-regulated transcription factors that control glycolysis in melanoma cells. Remarkably, this network of transcription factors, including hypoxia-inducible factor-1α, MYC, and MONDOA (MLXIP), drives glycolysis downstream of BRAF(V600), is critical for responses to BRAF inhibition, and is modulated by BRAF inhibition in clinical melanoma specimens. Furthermore, we show that concurrent inhibition of BRAF and glycolysis induces cell death in BRAF inhibitor (BRAFi)-resistant melanoma cells. Thus, we provide a proof-of-principle for treatment of melanoma with combinations of BRAFis and glycolysis inhibitors.

Global review of permian Tyloplecta muir-wood and cooper, 1960 (Brachiopoda): morphology, palaeobiogeographical and palaeogeographical implications

A global review of the stratigraphical and geographical distribution of Tyloplecta reveals that the genus ranges in age from Kungurian to Changhsingian (Middle to Late Permian). Tyloplecta first evolved in South China in the Kungurian (late Early Permian). The genus went through its first diversification in the Guadalupian, suffered a major extinction at the end of the Guadalupian, and re-diversified in the Wuchiapingian. T. yangtzeensis persisted into the Changhsingian as the only survivor of the genus involved in the end-Permian mass extinction. Palaeogeographically, South China is not only the centre of origin for the genus but also an area of diversification and evolution. In addition to South China, Tyloplecta has also been recorded from the Far East Russia, Japan, central Thailand, Laos, Cambodia, Qiangtang Terrane of Tibet, Salt Range, Iran, Armenia, Hungary, Yugoslavia, and Slovenia. This geographic spread suggests that Tyloplecta was primarily restricted to the Palaeotethys and is indicative of warm-water palaeoequatorial conditions. Its presence in some of the northeast Asian terranes (e.g., parts of Japan and Far East Russia) and in the Salt Range (Pakistan) and central and north Iran (part of the Cimmerian microcontinents) demonstrate that the genus invaded the middle palaeolatitudinal regions in both hemispheres during the late Middle Permian in response to increased shallow marine biotic communications between Cathaysia in the eastern Palaeotethys and southern Angaraland, and between Cathaysia and Peri-Gondwanaland. The invasion of Tyloplecta (and some other taxa) into the southern shore waters of Angaraland may be explained by assuming ocean surface current connections and close palaeogeographical proximities between the South China, Sino-Korea and Bureya blocks. In comparison, the invasion of Tyloplecta into the Peri-Gondwanaland region is more likely a result of reduced palaeogeographical distance between South China and Peri-Gondwanaland and the appearance of the Cimmerian microcontinents as migratory stepping stones.

The advantages of a proactive business response to human rights reporting

In a globalizing world, with shifting production, labor and consumer markets and increased competitiveness, human rights are gaining new practical relevance. The UN Global Compact presented by UN Secretary-General Kofi Annan to the World Economic Forum at Davos in 1999, sought to create a voluntary international corporate citizenship network to bring together private-sector and other social actors. Its central aim is to advance responsible corporate citizenship and universal social and environmental principles to meet the challenges of globalization. The business (and ethical) case for corporate engagement in human rights reporting is strengthening, although much still needs to be done. The Danish Human Rights and Business Project launched its 2006 educational project on company codes of conduct aimed at developing models for business in the pharmaceutical, steel, agricultural, logging, lumber, paper and cardboard, and apparel and textile industries, assessing company codes against international human rights standards.

Educational partnerships on-line: global collaborative learning through an on-line student exchange programme

Deakin University and the University of Calgary have used the internet to provide workplace-based learners with the possibility of a student exchange programme which does not disrupt their careers, lives or families.  The programmes involved in this on-line exchange were both developed in response to the needs of workplace learners and are representative of the role of universities in the field of life-long learning.  This paper describes the first phase of the exchange and discusses the shared pedagogical philosophies and shared implementation of on-line groupware which provided a rationale for the exchange.  The paper will explore the cross-cultural implications of the educational experience and the possibilities such an exchange opens up for life-long learners.

The global biopharma industry and the rise of Indian drug multinationals: implication for Australian generics policy

This article provides a synopsis of the new dynamics of the global biopharma industry. The emergence of global generics companies with capabilities approximating those of 'big pharma' has accelerated the blurring of boundaries between the innovator and generics sectors. Biotechnology-based products form a large and growing segment of prescription drug markets and regulatory pathways for biogenerics are imminent. Indian biopharma multinationals with large-scale efficient manufacturing plants and growing R&D capabilities are now major suppliers of Active Pharmaceutical Ingredients (APIs) and generic drugs across both developed and developing countries. In response to generic competition, innovator companies employ a range of life cycle management techniques, including the launch of 'authorised generics'. The generics segment in Australia will see high growth rates in coming years but the prospect for local manufacturing is bleak. The availability of cheap generics in international markets has put pressure on Pharmaceutical Benefits Scheme (PBS) pricing arrangements, and a new policy direction was announced in November 2006. Lower generics prices will have a negative impact on some incumbent suppliers but industrial renewal policies for the medicines industry in Australia are better focused on higher value R&D activities and niche manufacturing of sophisticated products.

Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation

Creatine monohydrate (CrM) supplementation has been shown to increase fat-free mass and muscle power output possibly via cell swelling. Little is known about the cellular response to CrM. We investigated the effect of short-term CrM supplementation on global and targeted mRNA expression and protein content in human skeletal muscle. In a randomized, placebo-controlled, crossover, double-blind design, 12 young, healthy, nonobese men were supplemented with either a placebo (PL) or CrM (loading phase, 20 g/day x 3 days; maintenance phase, 5 g/day x 7 days) for 10 days. Following a 28-day washout period, subjects were put on the alternate supplementation for 10 days. Muscle biopsies of the vastus lateralis were obtained and were assessed for mRNA expression (cDNA microarrays + real-time PCR) and protein content (Kinetworks KPKS 1.0 Protein Kinase screen). CrM supplementation significantly increased fat-free mass, total body water, and body weight of the participants (P < 0.05). Also, CrM supplementation significantly upregulated (1.3- to 5.0-fold) the mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodeling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival. We are the first to report this large-scale gene expression in the skeletal muscle with short-term CrM supplementation, a response that suggests changes in cellular osmolarity.

Teacher education in a global context : towards a defensible theory of teacher education

This paper examines some of the effects of globalisation on education and teacher education. In particular it considers the contradictory demands of economic and cultural forms of globalisation, and between globalisation and localisation. Attempts to construct an 'education space' in Europe and Asia are considered and various responses of teacher education systems are outlined. A defensible theory of teacher education is presented around the transformation of curriculum, pedagogy, assessment and the practicum: one that might allow a creative response to the contradictions of globalisation.

Exercise-induced histone modifications in human skeletal muscle

Skeletal muscle adaptations to exercise confer many of the health benefits of physical activity and occur partly through alterations in skeletal muscle gene expression. The exact mechanisms mediating altered skeletal muscle gene expression in response to exercise are unknown. However, in recent years, chromatin remodelling through epigenetic histone modifications has emerged as a key regulatory mechanism controlling gene expression in general. The purpose of this study was to examine the effect of exercise on global histone modifications that mediate chromatin remodelling and transcriptional activation in human skeletal muscle in response to exercise. In addition, we sought to examine the signalling mechanisms regulating these processes. Following 60 min of cycling, global histone 3 acetylation at lysine 9 and 14, a modification associated with transcriptional initiation, was unchanged from basal levels, but was increased at lysine 36, a site associated with transcriptional elongation. We examined the regulation of the class IIa histone deacetylases (HDACs), which are enzymes that suppress histone acetylation and have been implicated in the adaptations to exercise. While we found no evidence of proteasomal degradation of the class IIa HDACs, we found that HDAC4 and 5 were exported from the nucleus during exercise, thereby removing their transcriptional repressive function. We also observed activation of the AMP-activated protein kinase (AMPK) and the calcium–calmodulin-dependent protein kinase II (CaMKII) in response to exercise, which are two kinases that induce phosphorylation-dependent class IIa HDAC nuclear export. These data delineate a signalling pathway that might mediate skeletal muscle adaptations in response to exercise.

Late palaeozoic global changes affecting high-latitude environments and biotas : an introduction

The Late Palaeozoic Ice Age (LPIA), spanning approximately from ~320 Ma (Serpukhovian, late Mississippian) to 290 Ma (mid-Sakmarian, Early Permian), represents the vegetated Earth’s largest and most long-lasting regime of severe and multiple glaciations, involving processes and patterns probably comparable to those of the Last Ice Age. Accompanying the LPIA occurred a number of broadly synchronous global environmental and biotic changes. These global changes, as briefly reviewed and summarized in this introductory paper, comprised (but are not limited to) the following: massive continental reorganization in the lead up to the final assembly of Pangea resulting in profound changes in global palaeogeography, palaeoceanography and palaeobiogeogarphy; substantially lowered global atmospheric carbon dioxide concentrations (pCO₂), coupled with an unprecedented increase in atmospheric oxygen concentrations reaching Earth's all-time high in its last 600 million year history; sharp global temperature and sea-level drops (albeit with considerable spatial and temporal variability throughout the ice age); and apparently a prolonged period of global sluggish macro-evolution with both low extinction and origination rates compared to other times. In the aftermath of the LPIA, the world's climate entered into a transitional climate phase through the late Early to Middle Permian before its transformation into a greenhouse state towards the end-Permian. In recent years, considerable amount of data and interpretations have been published concerning the physical evidence in support of the LPIA, its broad timeframe and eustatic and ecosystem responses from the lower latitudes, but relatively less attention has been drawn to the impact of the ice age on late Palaeozoic high-latitude environments and biotas. It is with this mission in mind that we have organized this special issue, with the central focus on late Palaeozoic high latitude regions of both hemispheres, that is, Gondwana and northern Eurasia. Our aim is to gather a set of papers that not only document the physical environmental changes that had occurred in the polar regions of Gondwana and northern Eurasia during the LPIA, but also review on the biotic responses at different taxonomic, ecological and spatial scales to these physical changes in a refined chronological timeframe.

This introductory paper is designed to provide a global context for the special issue, with a brief review of key late Palaeozoic global environmental changes (including: changes in global land-sea configurations, atmospheric chemistry, global climate regimes, global ocean circulation patterns and sea levels) and large -scale biotic (biogeographic and evolutionary) responses, followed by a summary of what we see as unresolved scientific issues and various working hypotheses concerning late Palaeozoic global changes and, in particular, the LPIA, as a possible reference to future research.

Regular exercise participation mediates the affective response to acute bouts of vigorous exercise

Physical inactivity is a leading factor associated with cardiovascular disease and a major contributor to the global burden of disease in developed countries. Subjective mood states associated with acute exercise are likely to influence future exercise adherence and warrant further investigation. The present study examined the effects of a single bout of vigorous exercise on mood and anxiety between individuals with substantially different exercise participation histories. Mood and anxiety were assessed one day before an exercise test (baseline), 5 minutes before (pre-test) and again 10 and 25 minutes post-exercise. Participants were 31 university students (16 males, 15 females; Age M = 20), with 16 participants reporting a history of regular exercise with the remaining 15 reporting to not exercise regularly. Each participant completed an incremental exercise test on a Monark cycle ergometer to volitional exhaustion. Regular exercisers reported significant post-exercise improvements in mood and reductions in state anxiety. By contrast, non-regular exercisers reported an initial decline in post-exercise mood and increased anxiety, followed by an improvement in mood and reduction in anxiety back to pre-exercise levels. Our findings suggest that previous exercise participation mediates affective responses to acute bouts of vigorous exercise. We suggest that to maximise positive mood changes following exercise, practitioners should carefully consider the individual's exercise participation history before prescribing new regimes.