Determining the Relationship between Delivery Parameters and Ablation Distribution for Novel Gel Ethanol Percutaneous Therapy in Ex Vivo Swine Liver.

Ethyl cellulose-ethanol (ECE) is emerging as a promising formulation for ablative injections, with more controllable injection distributions than those from traditional liquid ethanol. This study evaluates the influence of salient injection parameters on forces needed for infusion, depot volume, retention, and shape in a large animal model relevant to human applications. Experiments were conducted to investigate how infusion volume (0.

DNA superhelicity.

Closing each strand of a DNA duplex upon itself fixes its linking number L. This topological condition couples together the secondary and tertiary structures of the resulting ccDNA topoisomer, a constraint that is not present in otherwise identical nicked or linear DNAs. Fixing L has a range of structural, energetic and functional consequences.

Non-equilibrium structural dynamics of supercoiled DNA plasmids exhibits asymmetrical relaxation.

Many cellular processes occur out of equilibrium. This includes site-specific unwinding in supercoiled DNA, which may play an important role in gene regulation. Here, we use the Convex Lens-induced Confinement (CLiC) single-molecule microscopy platform to study these processes with high-throughput and without artificial constraints on molecular structures or interactions.

Restoration of marine ecosystems: Understanding possible futures for optimal outcomes.

Accelerating declines in the extent, quality and functioning of the world's marine ecosystems have generated an upsurge in focus on practical solutions, with ecosystem restoration becoming an increasingly attractive mitigation strategy for systems as diverse as coral reefs, mangroves and tidal flats. While restoration is popular because it promises positive outcomes and a return to something approaching unimpacted condition and functioning, it involves substantial public and private investment, both for the initial restoration activity and for on-going maintenance of the restored asset. This investment often affords one big chance to get things right before irretrievable damage is done.

FUBP1 and FUBP2 enforce distinct epigenetic setpoints for MYC expression in primary single murine cells.

Physiologically, MYC levels must be precisely set to faithfully amplify the transcriptome, but in cancer MYC is quantitatively misregulated. Here, we study the variation of MYC amongst single primary cells (B-cells and murine embryonic fibroblasts, MEFs) for the repercussions of variable cellular MYC-levels and setpoints. Because FUBPs have been proposed to be molecular "cruise controls" that constrain MYC expression, their role in determining basal or activated MYC-levels was also examined.

Dysregulation of TRPV4, eNOS and caveolin-1 contribute to endothelial dysfunction in the streptozotocin rat model of diabetes.

Endothelial dysfunction is a common complication in diabetes in which endothelium-dependent vasorelaxation is impaired. The aim of this study was to examine the involvement of the TRPV4 ion channel in type 1 diabetic endothelial dysfunction and the possible association of endothelial dysfunction with reduced expression of TRPV4, endothelial nitric oxide synthase (eNOS) and caveolin-1. Male Wistar rats (350-450 g) were injected with 65 mg/kg i.

Identification and validation of the mode of action of the chalcone anti-mycobacterial compounds.

Objectives: The search for new TB drugs has become one of the great challenges for modern medicinal chemistry. An improvement in the outcomes of TB chemotherapy can be achieved by the development of new, shorter, cheap, safe and effective anti-TB regimens.

Methods: Chalcones (-) were synthesized and evaluated for their antimycobacterial activity against BCG using growth inhibition assays.

Emerging roles for R-loop structures in the management of topological stress.

R-loop structures are a prevalent class of alternative non-B DNA structures that form during transcription upon invasion of the DNA template by the nascent RNA. R-loops form universally in the genomes of organisms ranging from bacteriophages, bacteria, and yeasts to plants and animals, including mammals. A growing body of work has linked these structures to both physiological and pathological processes, in particular to genome instability.

Our Environmental Value Orientations Influence How We Respond to Climate Change.

People variably respond to global change in their beliefs, behaviors, and grief (associated with losses incurred). People that are less likely to believe in climate change, adopt pro-environmental behaviors, or report ecological grief are assumed to have different psycho-cultural orientations, and do not perceive changes in environmental condition or any impact upon themselves. We test these assumptions within the context of the Great Barrier Reef (GBR), a region currently experiencing significant climate change impacts in the form of coral reef bleaching and increasingly severe cyclones.

Contractile dysfunction and nitrergic dysregulation in small intestine of a primate model of Parkinson's disease.

Bowel dysfunction is a common non-motor symptom in Parkinson's disease (PD). The main contractile neurotransmitter in the GI tract is acetylcholine (ACh), while nitric oxide (NO) causes the relaxation of smooth muscle in addition to modulating ACh release. The aim of this study was to characterise functional and neurochemical changes in the isolated ileum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmoset, an established model of PD motor dysfunction.

Single-molecule visualization of the effects of ionic strength and crowding on structure-mediated interactions in supercoiled DNA molecules.

DNA unwinding is an important cellular process involved in DNA replication, transcription and repair. In cells, molecular crowding caused by the presence of organelles, proteins, and other molecules affects numerous internal cellular structures. Here, we visualize plasmid DNA unwinding and binding dynamics to an oligonucleotide probe as functions of ionic strength, crowding agent concentration, and crowding agent species using single-molecule CLiC microscopy.

Interplay between DNA sequence and negative superhelicity drives R-loop structures.

R-loops are abundant three-stranded nucleic-acid structures that form during transcription. Experimental evidence suggests that R-loop formation is affected by DNA sequence and topology. However, the exact manner by which these factors interact to determine R-loop susceptibility is unclear.

Dysfunction in nitric oxide synthesis in streptozotocin treated rat aorta and role of methylglyoxal.

Diabetic vascular dysfunction is a major complication of diabetes. Methylglyoxal (MGO) is a dicarbonyl metabolite elevated in diabetic plasma that reacts with interstitial molecules to form advanced glycation end products (AGE). We investigated whether MGO affects the release of nitric oxide (NO) from rat aortic smooth muscle cells (ASMCs), and if L-arginine can prevent these effects of MGO.

Social capital plays a central role in transitions to sportfishing tourism in small-scale fishing communities in Papua New Guinea.

Growing concerns about pressures of global change on small-scale fishing communities have resulted in a proliferation of livelihood diversification initiatives linked to tourism. Where the focus is often on the role of financial, physical, and human capital in influencing the uptake of new opportunities, we argue for more consideration of the role of social capital. We implemented 157 household-level surveys in small-scale fishing communities in Papua New Guinea and modelled the influence of social and other capital assets on people's perceptions of how easy it would be to become involved in sportfishing tourism.

Visualizing structure-mediated interactions in supercoiled DNA molecules.

We directly visualize the topology-mediated interactions between an unwinding site on a supercoiled DNA plasmid and a specific probe molecule designed to bind to this site, as a function of DNA supercoiling and temperature. The visualization relies on containing the DNA molecules within an enclosed array of glass nanopits using the Convex Lens-induced Confinement (CLiC) imaging method. This method traps molecules within the focal plane while excluding signal from out-of-focus probes.

Diabetic dyslipidaemia is associated with alterations in eNOS, caveolin-1, and endothelial dysfunction in streptozotocin treated rats.

Background: Diabetes is a complex progressive disease characterized by chronic hyperglycaemia and dyslipidaemia associated with endothelial dysfunction. Oxidized LDL (Ox-LDL) is elevated in diabetes and may contribute to endothelial dysfunction. The aim of this study was to relate the serum levels of Ox-LDL with endothelial dysfunction in streptozotocin (STZ)-diabetic rats and to further explore the changes in endothelial nitric oxide synthase (eNOS) and caveolin-1 (CAV-1) expression in primary aortic endothelial cells.

Altered detrusor contractility in MPTP-treated common marmosets with bladder hyperreflexia.

Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We now report on the contractility of the isolated primate detrusor strips devoid of nerve input and show that following MPTP, the amplitude and frequency of spontaneous contraction was increased. These responses were unaffected by dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively.

Permanganate/S1 Nuclease Footprinting Reveals Non-B DNA Structures with Regulatory Potential across a Mammalian Genome.

DNA in cells is predominantly B-form double helix. Though certain DNA sequences in vitro may fold into other structures, such as triplex, left-handed Z form, or quadruplex DNA, the stability and prevalence of these structures in vivo are not known. Here, using computational analysis of sequence motifs, RNA polymerase II binding data, and genome-wide potassium permanganate-dependent nuclease footprinting data, we map thousands of putative non-B DNA sites at high resolution in mouse B cells.

Long-range correlations in the mechanics of small DNA circles under topological stress revealed by multi-scale simulation.

It is well established that gene regulation can be achieved through activator and repressor proteins that bind to DNA and switch particular genes on or off, and that complex metabolic networks determine the levels of transcription of a given gene at a given time. Using three complementary computational techniques to study the sequence-dependence of DNA denaturation within DNA minicircles, we have observed that whenever the ends of the DNA are constrained, information can be transferred over long distances directly by the transmission of mechanical stress through the DNA itself, without any requirement for external signalling factors. Our models combine atomistic molecular dynamics (MD) with coarse-grained simulations and statistical mechanical calculations to span three distinct spatial resolutions and timescale regimes.

Synthesis and Spectral Characterization of Benzo-[6,7][1,5]diazocino[2,1-a]isoindol-12-(14H)-one Derivatives.

A simple synthetic route affording 27%-85% yields of benzo[6,7][1,5]diazocino[2,1-a]isoindol-12(14H)-one ring systems from readily available 3-(2-oxo-2-phenylethyl) isobenzofuran-1(3H)-ones and 2-(aminomethyl)aniline starting materials in toluene and catalysed by p-toluene-sulfonic acid is developed. The ¹H- and (13)C-NMR spectra of the final products were assigned using a variety of one and two-dimensional NMR experiments. The distinction between the two potential isomers of the final products was made on the basis of heteronuclear multiple bond connectivity (HMBC) NMR spectra.

Growth effects of shading and sedimentation in two tropical seagrass species: Implications for port management and impact assessment.

Seagrass meadows in many parts of the globe are threatened by a range of processes including port development, dredging and land clearing in coastal catchments, which can reduce water clarity and increase sedimentation pressure. As rates of seagrass loss increase, there is an urgent need to understand the potential impacts of development on these critical species. This research compares the effects of shading and burial by fine sand on two seagrass species Zostera muelleri and Halophila ovalis in Port Curtis Bay, an industrial harbour located on the continental margin adjacent to the Great Barrier Reef Heritage Area, Australia.

Methylglyoxal, A Metabolite Increased in Diabetes is Associated with Insulin Resistance, Vascular Dysfunction and Neuropathies.

Background: Diabetes mellitus (DM) is a pandemic metabolic disease characterized by a chronically elevated blood glucose concentration (hyperglycemia) due to insulin dysfunction. Approximately 50% of diabetics show diabetes complications by the time they are diagnosed. Vascular dysfunction, nephropathy and neuropathic pain are common diabetes complications.

Inter-annual patterns of aggression and pair bonding in captive American flamingos (Phoenicopterus ruber).

Because zoos typically house animals for extended periods of time, longitudinal studies can play an important role in evaluating and optimizing animal care and management. For example, information on patterns of aggression and mating behavior across years can be used to monitor well-being, assess response to changes to group composition, and promote successful reproduction. Here, we report on patterns of aggression and pair bonding by American flamingos (Phoenicopterus ruber) at the Audubon Zoo, New Orleans USA across 4 years (2012-2015), a period that included a simultaneous introduction and removal of individuals in 2014.

Selective inhibition of NADPH oxidase reverses the over contraction of diabetic rat aorta.

Abnormal vascular responsiveness in diabetes has been attributed to a number of changes in contractile pathways, affected in part by the overproduction of reactive oxygen species (ROS). It has been reported that NADPH oxidase (NOX) is increased in diabetic (streptozotocin treated; STZ) rat arteries; however the pharmacological agents used to inhibit NOX activity are known to be unsuitable for in vitro studies and have a high level of non-selectivity. Here we have used the highly selective NOX inhibitor VAS2870 in diabetic rat aorta and compared its effects with apocynin, SOD, and allopurinol on phenylephrine and U46619 induced contraction.