908 research outputs found

    Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells

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    Currently, little is known about the evolution of epigenetic regulation in animal stem cells. Here we demonstrate, using the planarian stem cell system to investigate the role of the COMPASS family of MLL3/4 histone methyltransferases that their function as tumor suppressors in mammalian stem cells is conserved over a long evolutionary distance. To investigate the potential conservation of a genome-wide epigenetic regulatory program in animal stem cells, we assess the effects of Mll3/4 loss of function by performing RNA-seq and ChIP-seq on the G2/M planarian stem cell population, part of which contributes to the formation of outgrowths. We find many oncogenes and tumor suppressors among the affected genes that are likely candidates for mediating MLL3/4 tumor suppression function. Our work demonstrates conservation of an important epigenetic regulatory program in animals and highlights the utility of the planarian model system for studying epigenetic regulation

    BIG SHOES TO FILL: THE POTENTIAL OF SEAWALLS TO FUNCTION AS ROCKY SHORE SURROGATES

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    Master'sMASTER OF SCIENC

    A microRNA signature in circulating exosomes is superior to exosomal glypican-1 levels for diagnosing pancreatic cancer

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    Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy that often presents clinically at an advanced stage and that may be confused with chronic pancreatitis (CP). Conversely, CP may be misdiagnosed as PDAC leading to unwarranted pancreas resection. Therefore, early PDAC diagnosis and clear differentiation between PDAC and CP are crucial for improved care. Exosomes are circulating microvesicles whose components can serve as cancer biomarkers. We compared exosomal glypican-1 (GPC1) and microRNA levels in normal control subjects and in patients with PDAC and CP. We report that exosomal GPC1 is not diagnostic for PDAC, whereas high exosomal levels of microRNA-10b, (miR-10b), miR-21, miR-30c, and miR-181a and low miR-let7a readily differentiate PDAC from normal control and CP samples. By contrast with GPC1, elevated exosomal miR levels decreased to normal values within 24 h following PDAC resection. All 29 PDAC cases exhibited significantly elevated exosomal miR-10b and miR-30c levels, whereas 8 cases had normal or slightly increased CA 19-9 levels. Thus, our exosomal miR signature is superior to exosomal GPC1 or plasma CA 19-9 levels in establishing a diagnosis of PDAC and differentiating between PDAC and CP

    Effects of eating rate on satiety:A role for episodic memory?

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    AbstractEating slowly is associated with a lower body mass index. However, the underlying mechanism is poorly understood. Here, our objective was to determine whether eating a meal at a slow rate improves episodic memory for the meal and promotes satiety. Participants (N=40) consumed a 400ml portion of tomato soup at either a fast (1.97ml/s) or a slow (0.50ml/s) rate. Appetite ratings were elicited at baseline and at the end of the meal (satiation). Satiety was assessed using; i) an ad libitum biscuit ‘taste test’ (3h after the meal) and ii) appetite ratings (collected 2h after the meal and after the ad libitum snack). Finally, to evaluate episodic memory for the meal, participants self-served the volume of soup that they believed they had consumed earlier (portion size memory) and completed a rating of memory ‘vividness’. Participants who consumed the soup slowly reported a greater increase in fullness, both at the end of the meal and during the inter-meal interval. However, we found little effect of eating rate on subsequent ad libitum snack intake. Importantly, after 3h, participants who ate the soup slowly remembered eating a larger portion. These findings show that eating slowly promotes self-reported satiation and satiety. For the first time, they also suggest that eating rate influences portion size memory. However, eating slowly did not affect ratings of memory vividness and we found little evidence for a relationship between episodic memory and satiety. Therefore, we are unable to conclude that episodic memory mediates effects of eating rate on satiety

    Area-Independent Effects of Water-Retaining Features on Intertidal Biodiversity on Eco-Engineered Seawalls in the Tropics

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    Over the last decade there has been a global effort to eco-engineer urban artificial shorelines with the aim of increasing their biodiversity and extending their conservation value. One of the most common and viable eco-engineering approaches on seawalls is to use enhancement features that increase habitat structural complexity, including concrete tiles molded with complex designs and precast “flowerpots” that create artificial rock pools. Increases in species diversity in pits and pools due to microhabitat conditions (water retention, shade, protection from waves, and/or biotic refugia) are often reported, but these results can be confounded by differences in the surface area sampled. In this study, we fabricated three tile types (n = 10): covered tile (grooved tile with a cover to retain water), uncovered tile (same grooved tile but without a cover) and granite control. We tested the effects of these tile types on species richness (S), total individual abundance (N), and community composition. All tiles were installed at 0.5 m above chart datum along seawalls surrounding two island sites (Pulau Hantu and Kusu Island) south of Singapore mainland. The colonizing assemblages were sampled after 8 months. Consistent with previous studies, mean S was significantly greater on covered tiles compared to the uncovered and granite tiles. While it is implied in much of the eco-engineering literature that this pattern results from greater niche availability allotted by microhabitat conditions, we further investigated whether there was an underlying species-individual relationship to determine whether increases in S could have simply resulted from covered tiles supporting greater N (i.e., increasing the probability of detecting more species despite a constant area). The species-individual relationship was positive, suggesting that multiple mechanisms are at play, and that biodiversity enhancements may in some instances operate simply by increasing the abundance of individuals, even when microhabitat availability is unchanged. This finding underscores the importance of testing mechanisms in eco-engineering studies and highlights ongoing mechanistic uncertainties that should be addressed to inform the design of more biodiverse seawalls and urban marine environments

    How prepared are pharmacists to provide over-the-counter naloxone? The role of previous education and new training opportunities

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    and Aims: Opioid overdose can be reversed with timely administration of naloxone. In Australia, naloxone was rescheduled from prescription only (S4) to pharmacist only over-the-counter (OTC, S3) in February 2016, increasing access for the general public. A key barrier to naloxone supply by pharmacists is a lack of knowledge, highlighting the role of pharmacist education. Community pharmacists' education, experience, and training preferences related to naloxone provision, overdose, and substance use disorder were examined.Online survey data from a national sample of Australian pharmacists on their educational preferences regarding naloxone and overdose prevention, and prior training on substance use disorder (n = 595) was analyzed using bivariate and multivariate regression analysis. Data from qualitative semi-structured telephone interviews with pharmacists about OTC naloxone provision (n = 21) was analyzed using thematic analysis.Most pharmacists (81%, n = 479) were willing to be trained in opioid overdose prevention, with greater willingness to attend training associated with younger age, being female, fewer years of practice, not having attended previous education on substance use disorder, and higher confidence in issues relating to substance use disorder. Qualitative interviews confirmed community pharmacists' willingness to attend training but analysis revealed low awareness, knowledge, and confidence about naloxone and preventing opioid overdose. Most pharmacists preferred online training or webinars.Most community pharmacists in Australia are willing to attend training on providing naloxone and preventing opioid overdose. There are opportunities to develop and expand the online presence of training, guidelines, and education materials to facilitate the expanded supply of OTC naloxone

    Exploratory study involving observation of traffic behaviour and conflicts in Nigeria using the Traffic Conflict Technique

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    Road traffic crashes are a major public health problem affecting those living in developing countries, exacerbated by the lack of available resources to tackle the issue (WHO, 2015). Whilst crash reduction measures have been developed and implemented, there has been limited success in developing countries and the crash rate keeps increasing. Partly to blame are the lack of empirical research and high quality crash data. Data do exist – but their reliability is questionable, with respect to the data collection methods used and underreporting. This study, undertaken in Nigeria, used surrogate safety measures based on systematic observation of traffic behaviour and conflicts to assess the behaviour of different road users and investigate the role various factors play in determining conflict severity. Data were analysed using the Traffic Conflict Technique and binary logistic regression. Results show that direction of traffic, time of day and the relevant road user’s age, gender and speed are important determinants of conflict severity. This study highlights the applicability of surrogate safety measures in traffic safety assessment in a developing country and demonstrates that quality data needed for road safety assessment in developing countries could be collected over a short period of time by making use of resources which are readily available
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