On the need for a new playing die

We model the rolling of a standard die, using a Markov matrix. Though a die may be called ‘fair’, its initial position influences a roll’s outcome. This being undesirable, a simple solution is proposed

Liposomal delivery of hydrophobic RAMBAs provides good bioavailability and significant enhancement of retinoic acid signalling in neuroblastoma tumour cells

Retinoid treatment is employed during residual disease treatment in neuroblastoma, where the aim is to induce neural differentiation or death in tumour cells. However, although therapeutically effective, retinoids have only modest benefits and suffer from poor pharmacokinetic properties. In vivo, retinoids induce CYP26 enzyme production in the liver, enhancing their own rapid metabolic clearance, while retinoid resistance in tumour cells themselves is considered to be due in part to increased CYP26 production. Retinoic acid metabolism blocking agents (RAMBAs), which inhibit CYP26 enzymes, can improve retinoic acid pharmacokinetics in pre-clinical neuroblastoma models. Here we demonstrate that in cultured neuroblastoma tumour cells, RAMBAs enhance retinoic acid action as seen by morphological differentiation, AKT signalling and suppression of MYCN protein. Although active as retinoid enhancers, these RAMBAs are highly hydrophobic and their effective delivery in humans will be very challenging. Here we demonstrate that such RAMBAs can be loaded efficiently into cationic liposomal particles, where the RAMBAs achieve good bioavailability and activity in cultured tumour cells. This demonstrates the efficacy of RAMBAs in enhancing retinoid signaling in neuroblastoma cells and shows for the first time that liposomal delivery of hydrophobic RAMBAs is a viable approach, providing novel opportunities for their delivery and application in humans

Imaging through turbid media with a nonlinear-optical correlation time gate

Experiments directed towards a clinically useful optical imaging system use long-pulse near-infrared lasers and a correlation time gate based on degenerate four-wave mixing in a nonlinear medium

Sustained low-dose treatment with the histone deacetylase inhibitor LBH589 induces terminal differentation of osteosarcoma cells

Histone deacetylase inhibitors (HDACi) were identified nearly four decades ago based on their ability to induce cellular differentiation. However, the clinical development of these compounds as cancer therapies has focused on their capacity to induce apoptosis in hematologic and lymphoid malignancies, often in combination with conventional cytotoxic agents. In many cases, HDACi doses necessary to induce these effects result in significant toxicity. Since osteosarcoma cells express markers of terminal osteoblast differentiation in response to DNA methyltransferase inhibitors, we reasoned that the epigenetic reprogramming capacity of HDACi might be exploited for therapeutic benefit. Here, we show that continuous exposure of osteosarcoma cells to low concentrations of HDACi LBH589 (Panobinostat) over a three-week period induces terminal osteoblast differentiation and irreversible senescence without inducing cell death. Remarkably, transcriptional profiling revealed that HDACi therapy initiated gene signatures characteristic of chondrocyte and adipocyte lineages in addition to marked upregulation of mature osteoblast markers. In a mouse xenograft model, continuous low dose treatment with LBH589 induced a sustained cytostatic response accompanied by induction of mature osteoblast gene expression. These data suggest that the remarkable capacity of osteosarcoma cells to differentiate in response to HDACi therapy could be exploited for therapeutic benefit without inducing systemic toxicity

Asymmetric patterns of recovery in two habitat forming seagrass species following simulated overgrazing by urchins

The persistence of seagrass meadows reflects variation in factors that influence their productivity and consumption. Sea urchins (Amblypneustes pallidus) can over-graze seagrass (Amphibolis antarctica) to create sparse meadows in South Australia, but this effect is not observed in adjacent Posidonia sinuosa meadows despite greater densities of inhabiting urchins. To test the effect of urchin grazing on seagrass biomass, we elevated the density of urchins in meadows of A. antarctica and P. sinuosa and quantified seagrass decline. Urchins removed similar amounts of biomass from both seagrass species, but the loss of leaf meristems was 11-times greater in A. antarctica than in P. sinuosa. In a second experiment to assess the recovery of seagrass, we simulated urchin grazing by clipping seagrass to mimic impacts measured in the first experiment, as well as completely removing all above ground biomass in one treatment. Following simulated grazing, P. sinuosa showed a rapid trajectory toward recovery, while A. antarctica meadows continued to decline relative to control treatments. While both A. antarctica and P. sinuosa were susceptible to heavy grazing loss, consumption of the exposed meristems of A. antarctica appears to reduce its capacity to recover, which may increase its vulnerability to long-term habitat phase-shifts and associated cascading ecosystem changes. © 2013 Elsevier B.V.Owen W. Burnell, Sean D. Connell, Andrew D. Irving, Bayden D. Russel

Restoring Coastal Plants to Improve Global Carbon Storage: Reaping What We Sow

Long-term carbon capture and storage (CCS) is currently considered a viable strategy for mitigating rising levels of atmospheric CO2 and associated impacts of global climate change. Until recently, the significant below-ground CCS capacity of coastal vegetation such as seagrasses, salt marshes, and mangroves has largely gone unrecognized in models of global carbon transfer. However, this reservoir of natural, free, and sustainable carbon storage potential is increasingly jeopardized by alarming trends in coastal habitat loss, totalling 30–50% of global abundance over the last century alone. Human intervention to restore lost habitats is a potentially powerful solution to improve natural rates of global CCS, but data suggest this approach is unlikely to substantially improve long-term CCS unless current restoration efforts are increased to an industrial scale. Failure to do so raises the question of whether resources currently used for expensive and time-consuming restoration projects would be more wisely invested in arresting further habitat loss and encouraging natural recovery

Assessing Seagrass Restoration Actions through a Micro-Bathymetry Survey Approach (Italy, Mediterranean Sea)

Underwater photogrammetry provides a means of generating high-resolution products such as dense point clouds, 3D models, and orthomosaics with centimetric scale resolutions. Underwater photogrammetric models can be used to monitor the growth and expansion of benthic communities, including the assessment of the conservation status of seagrass beds and their change over time (time lapse micro-bathymetry) with OBIA classifications (Object-Based Image Analysis). However, one of the most complex aspects of underwater photogrammetry is the accuracy of the 3D models for both the horizontal and vertical components used to estimate the surfaces and volumes of biomass. In this study, a photogrammetry-based micro-bathymetry approach was applied to monitor Posidonia oceanica restoration actions. A procedure for rectifying both the horizontal and vertical elevation data was developed using soundings from high-resolution multibeam bathymetry. Furthermore, a 3D trilateration technique was also tested to collect Ground Control Points (GCPs) together with reference scale bars, both used to estimate the accuracy of the models and orthomosaics. The root mean square error (RMSE) value obtained for the horizontal planimetric measurements was 0.05 m, while the RMSE value for the depth was 0.11 m. Underwater photogrammetry, if properly applied, can provide very high-resolution and accurate models for monitoring seagrass restoration actions for ecological recovery and can be useful for other research purposes in geological and environmental monitoring

Aeolianite and barrier dune construction spanning the last two glacial-interglacial cycles from the southern Cape coast, South Africa

The southern Cape region of South Africa has extensive coastal aeolianites and barrier dunes. Whilst previously reported, limited knowledge of their age has precluded an understanding of their relationship with the climatic and sea-level fluctuations that have taken place during the Late Quaternary. Sedimentological and geomorphological studies combined with an optical dating programme reveal aeolianite development and barrier dune construction spanning at least the last two glacial–interglacial cycles. Aeolianite deposition has occurred on the southern Cape coast at ca 67–80, 88–90, 104–128, 160–189 and >200 ka before the present. Using this and other published data coupled with a better understanding of Late Quaternary sea-level fluctuations and palaeocoastline configurations, it is concluded that these depositional phases appear to be controlled by interglacial and subsequent interstadial sea-level high stands. These marine transgressions and regressions allowed onshore carbonate-rich sediment movement and subsequent aeolian reworking to occur at similar points in the landscape on a number of occasions. The lack of carbonates in more recent dunes (Oxygen Isotope Stages 1/2 and 4/5) is attributed not to leaching but to changes to carbonate production in the sediment source area caused by increased terrigenous material and/or changes in the balance between the warm Agulhas and nutrient-rich Benguela ocean current

Imprinted Gene Expression and Function of the Dopa Decarboxylase Gene in the Developing Heart

Dopa decarboxylase (DDC) synthesizes serotonin in the developing mouse heart where it is encoded by Ddc_exon1a, a tissue-specific paternally expressed imprinted gene. Ddc_exon1a shares an imprinting control region (ICR) with the imprinted, maternally expressed (outside of the central nervous system) Grb10 gene on mouse chromosome 11, but little else is known about the tissue-specific imprinted expression of Ddc_exon1a. Fluorescent immunostaining localizes DDC to the developing myocardium in the pre-natal mouse heart, in a region susceptible to abnormal development and implicated in congenital heart defects in human. Ddc_exon1a and Grb10 are not co-expressed in heart nor in brain where Grb10 is also paternally expressed, despite sharing an ICR, indicating they are mechanistically linked by their shared ICR but not by Grb10 gene expression. Evidence from a Ddc_exon1a gene knockout mouse model suggests that it mediates the growth of the developing myocardium and a thinning of the myocardium is observed in a small number of mutant mice examined, with changes in gene expression detected by microarray analysis. Comparative studies in the human developing heart reveal a paternal expression bias with polymorphic imprinting patterns between individual human hearts at DDC_EXON1a, a finding consistent with other imprinted genes in human