Anti-fibrotic potential of Tomentosenol A, a constituent of cerumen from the Australian native stingless bee, Tetragonula carbonaria

Bioactivity-guided fractionation was used to isolate two compounds, tomentosenol A (1) and torellianone A (2), from a cerumen extract from Tetragonula carbonaria. The anti-fibrotic activity of these compounds was examined using human cultured neonatal foreskin fibroblasts (NFF) and immortalised keratinocytes (HaCaTs). Tomentosenol A (1), inhibited NFF and HaCaT cell proliferation and prevented NFF and HaCaT scratch wound repopulation at 12.5−25 µM concentrations. These inhibitory effects were associated with reduced cell viability, determined by tetrazolium dye (MTT) and sulforhodamine B (SRB) assays. Compound 1 further inhibited transforming growth factor-β1 (TGF-β1)-stimulated, NFF-myofibroblast differentiation and soluble collagen production; and was an effective scavenger of the model oxidant, 2,2-diphenyl-1-picrylhydrazyl (DPPH·), with an EC50 value of 44.7 ± 3.1 µM. These findings reveal significant anti-fibrotic potential for cerumen-derived tomentosenol A (1)

Ecological and Cultural Understanding as a Basis for Management of a Globally Significant Island Landscape

Islands provide the opportunity to explore management regimes and research issues related to the isolation, uniqueness, and integrity of ecological systems. K’gari (Fraser Island) is an Australian World Heritage property listed based on its outstanding natural value, specifically, the unique wilderness characteristics and the diversity of ecosystem types. Our goal was to draw on an understanding of the natural and cultural environment of K’gari as a foundation on which to build a management model that includes First Nations Peoples in future management and research. Our research involved an analysis of papers in the peer-reviewed scientific literature, original reports, letters, and other manuscripts now housed in the K’gari Fraser Island Research Archive. The objectives of the research were: (1) to review key historical events that form the cultural, social, and environmental narrative; (2) review the major natural features of the island and threats; (3) identify the gaps in research; (4) analyse the management and conservation challenges associated with tourism, biosecurity threats, vegetation management practices, and climate change and discuss whether the requirements for sustaining island ecological integrity can be met in the future; and (5) identify commonalities and general management principles that may apply globally to other island systems and other World Heritage sites listed on the basis of their unique natural and cultural features. We found that the characteristics that contribute to island uniqueness are also constraints for research funding and publication; however, they are important themes that warrant more investment. Our review suggests that K’gari is a contested space between tourist visitation and associated environmental impacts, with an island that has rich First Nations history, extraordinary ecological diversity, and breathtaking aesthetic beauty. This juxtaposition is reflected in disparate views of custodianship and use, and the management strategies are needed to achieve multiple objectives in an environmentally sustainable way whilst creating cultural equity in modern times. We offer a foundation on which to build a co-management model that includes First Nations Peoples in governance, management, research, and monitoring

Characterisation of PAUSE-1, a powerful silencer in the human plasminogen activator inhibitor type 2 gene promoter

Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor traditionally regarded as a regulator of fibrinolysis and extracellular matrix degradation. More recently, PAI-2 has been implicated in diverse processes such as keratinocyte differentiation, cell death and viral pathogenesis. The PAI-2 promoter tightly regulates PAI-2 gene expression in a cell-specific manner and this control is mediated, in part, by the upstream silencer element, PAUSE-1. Here we have defined PAUSE-1 and investigated its activity as a silencer. A series of mutations were generated within the PAUSE-1 element and analysed for transcription factor binding and transcriptional silencing activity. These studies have defined the minimal functional PAUSE-1 element as TCTN(x)AGAN(3)T(4), where x = 0, 2 or 4. Examination of related elements present in other promoters, such as the human IFNβ promoter, suggests that PAUSE-1 is a member of a family of universal silencers with the consensus sequence TCTN(x)AGA. UV crosslinking analyses determined that the PAUSE-1 binding protein was ∼67 kDa. Insertion of PAUSE-1 into the heterologous (SV40) or the minimal PAI-2 promoters silenced transcription by 2.5-fold. These data show that PAUSE-1 acts as a powerful silencer of PAI-2 gene transcription and is likely to be important in the silencing of other genes as well

Glyphosate: Environmental contamination, toxicity and potential risks to human health via food contamination

Hosseini Bai, S ORCiD: 0000-0001-8646-6423Glyphosate has been the most widely used herbicide during the past three decades. The US Environmental Protection Agency (EPA) classifies glyphosate as ‘practically non-toxic and not an irritant’ under the acute toxicity classification system. This classification is based primarily on toxicity data and due to its unique mode of action via a biochemical pathway that only exists in a small number of organisms that utilise the shikimic acid pathway to produce amino acids, most of which are green plants. This classification is supported by the majority of scientific literature on the toxic effects of glyphosate. However, in 2005, the Food and Agriculture Organisation (FAO) reported that glyphosate and its major metabolite, aminomethylphosphonic acid (AMPA), are of potential toxicological concern, mainly as a result of accumulation of residues in the food chain. The FAO further states that the dietary risk of glyphosate and AMPA is unlikely if the maximum daily intake of 1 mg kg−1body weight (bw) is not exceeded. Research has now established that glyphosate can persist in the environment, and therefore, assessments of the health risks associated with glyphosate are more complicated than suggested by acute toxicity data that relate primarily to accidental high-rate exposure. We have used recent literature to assess the possible risks associated with the presence of glyphosate residues in food and the environment. © 2016, Springer-Verlag Berlin Heidelberg

A multidisciplinary approach to inform assisted migration of the restricted rainforest tree, Fontainea rostrata.

Assisted migration can aid in the conservation of narrowly endemic species affected by habitat loss, fragmentation and climate change. Here, we employ a multidisciplinary approach by examining the population genetic structure of a threatened, dioecious rainforest tree of the subtropical notophyll vine forests of eastern Australia, Fontainea rostrata, and its potential requirements for population enhancement and translocation to withstand the effects of anthropogenic fragmentation and climate change. We used microsatellite markers to gain an understanding of the way genetic diversity is partitioned within and among the nine extant populations of F. rostrata identified in this study. We combined the results with species distribution modelling to identify populations vulnerable to possible future range shifts based on climate change projections. We found regional differences between the species' main distribution in the south and a disjunct northern population cluster (FRT = 0.074, FSR = 0.088, FST = 0.155), in mean allelic richness (AR = 2.77 vs 2.33, p < 0.05), expected heterozygosity (HE = 0.376 vs 0.328), and inbreeding (F = 0.116 vs 0.219). Species distribution models predicted that while southern populations of F. rostrata are likely to persist for the next 50 years under the RCP6.0 climate change scenario, with potential for a small-scale expansion to the south-east, the more highly inbred and less genetically diverse northern populations will come under increasing pressure to expand southwards as habitat suitability declines. Given the species' genetic structure and with the aim to enhance genetic diversity and maximise the likelihood of reproductive success, we recommend that plant reintroductions to supplement existing populations should be prioritised over translocation of the species to new sites. However, future conservation efforts should be directed at translocation to establish new sites to increase population connectivity, focussing particularly on habitat areas identified as persisting under conditions of climate change

Natural products isolated from Tetragonula carbonaria cerumen modulate free radical-scavenging and 5-lipoxygenase activities in vitro

Abstract Background Propolis and cerumen are plant-derived products found in honeybees and stingless bees, respectively. Although propolis is an ancient folk medicine, the bioactivities of cerumen obtained from Australian native stingless bees (Tetragonula carbonaria) have not been widely studied. Therefore, we investigated selected anti-oxidant and anti-inflammatory properties of T. carbonaria cerumen. Methods A methanolic extract was prepared from the combined cerumen of 40 T. carbonaria hives, and HPLC was used to screen for chemical constituents that scavenged 2,2-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The ability of cerumen extracts to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and to interfere with leukotriene B4 (LTB4) production in ionomycin-stimulated human neutrophils was also examined. Results The extract dose-dependently scavenged DPPH (EC50 = 27.0 ± 2.3 μg/mL); and inhibited the 5-lipoxygenase (5-LOX)-mediated oxidation of linoleic acid (IC50 = 67.1 ± 9.6 μg/mL). Pre-treatment of isolated human neutrophils with the methanolic cerumen extract additionally inhibited the ionomycin-stimulated production of LTB4 from these cells (IC50 = 13.3 ± 5.3 μg/mL). Following multi-solvent extraction, the free radical-scavenging and 5-LOX-inhibiting activities of the initial cerumen extract were retained in a polar, methanol-water extract, which contained gallic acid and a range of flavonone and phenolic natural products. Conclusions The findings identify free radical scavenging activity, and interference by extracts of T. carbonaria cerumen in 5-LOX–LTB4 signaling. Further investigation is needed to determine whether the extracts will provide therapeutic benefits for medical conditions in which oxidative stress and inflammation are implicated, including cardiovascular disease and impaired wound healing