Applicability of Chronic Multiple Linear Regression Models for Predicting Zinc Toxicity in Australian and New Zealand Freshwaters.

Bioavailability models, for example, multiple linear regressions (MLRs) of water quality parameters, are increasingly being used to develop bioavailability-based water quality criteria for metals. However, models developed for the Northern Hemisphere cannot be adopted for Australia and New Zealand without first validating them against local species and local water chemistry characteristics. We investigated the applicability of zinc chronic bioavailability models to predict toxicity in a range of uncontaminated natural waters in Australia and New Zealand.

Role of endothelial CXCR4 in the development of aortic valve stenosis.

Background: CXCL12/CXCR4 signaling is essential in cardiac development and repair, however, its contribution to aortic valve stenosis (AVS) remains unclear. In this study, we tested the role of endothelial CXCR4 on the development of AVS.

Materials And Methods: We generated CXCR4 endothelial cell-specific knockout mice (EC CXCR4 KO) by crossing CXCR4 mice with Tie2-Cre mice to study the role of endothelial cell CXCR4 in AVS.

The essential role for endothelial cell sprouting in coronary collateral growth.

Rationale: Coronary collateral growth is a natural bypass for ischemic heart diseases. It offers tremendous therapeutic benefit, but the process of coronary collateral growth isincompletely understood due to limited preclinical murine models that would enable interrogation of its mechanisms and processes via genetic modification and lineage tracing. Understanding the processes by which coronary collaterals develop can unlock new therapeutic strategies for ischemic heart disease.

Mechanism of the switch from NO to HO in endothelium-dependent vasodilation in diabetes.

Coronary microvascular dysfunction is prevalent among people with diabetes and is correlated with cardiac mortality. Compromised endothelial-dependent dilation (EDD) is an early event in the progression of diabetes, but its mechanisms remain incompletely understood. Nitric oxide (NO) is the major endothelium-dependent vasodilatory metabolite in the healthy coronary circulation, but this switches to hydrogen peroxide (HO) in coronary artery disease (CAD) patients.

Metal forms and dynamics in urban stormwater runoff: New insights from diffusive gradients in thin-films (DGT) measurements.

Stormwater runoff typically contains significant quantities of metal contaminants that enter urban waterways over short durations and represent a potential risk to water quality. The origin of metals within the catchment and processes that occur over the storm can control the partitioning of metals between a range of different forms. Understanding the fraction of metals present in a form that is potentially bioavailable to aquatic organisms is useful for environmental risk assessment.

Probabilistic risk assessment of mine-derived copper in the Ok Tedi/Fly River, Papua New Guinea.

The Ok Tedi mine discharges waste rock and tailings into the Ok Tedi River in Papua New Guinea. This has resulted in elevated copper concentrations throughout the Ok Tedi/Fly River system, which can potentially impact aquatic biota. Ten years of measured copper and toxicity monitoring data were used to assess the risk of chronic effects from the mine-derived copper.

Application of Bioavailability Models to Derive Chronic Guideline Values for Nickel in Freshwaters of Australia and New Zealand.

There has been an increased emphasis on incorporating bioavailability-based approaches into freshwater guideline value derivations for metals in the Australian and New Zealand water quality guidelines. Four bioavailability models were compared: the existing European biotic ligand model (European Union BLM) and a softwater BLM, together with 2 newly developed multiple linear regressions (MLRs)-a trophic level-specific MLR and a pooled MLR. Each of the 4 models was used to normalize a nickel ecotoxicity dataset (combined tropical and temperate data) to an index condition of pH 7.

Towards Sustainable Environmental Quality: Priority Research Questions for the Australasian Region of Oceania.

Environmental challenges persist across the world, including the Australasian region of Oceania, where biodiversity hotspots and unique ecosystems such as the Great Barrier Reef are common. These systems are routinely affected by multiple stressors from anthropogenic activities, and increasingly influenced by global megatrends (e.g.

The neuronal metabolite NAA regulates histone H3 methylation in oligodendrocytes and myelin lipid composition.

The neuronal mitochondrial metabolite N-acetylaspartate (NAA) is decreased in the multiple sclerosis (MS) brain. NAA is synthesized in neurons by the enzyme N-acetyltransferase-8-like (NAT8L) and broken down in oligodendrocytes by aspartoacylase (ASPA) into acetate and aspartate. We have hypothesized that NAA links the metabolism of axons with oligodendrocytes to support myelination.

Single-molecule fluorescence quantification with a photobleached internal standard.

In cellular and molecular biology, fluorophores are employed to aid in tracking and quantifying molecules involved in cellular function. We previously developed a sensitive single-molecule quantification technique to count the number of proteins and the variation of the protein number over the population of individual subcellular organelles. However, environmental effects on the fluorescent intensity of fluorophores can make it difficult to accurately quantify proteins using these sensitive techniques.

The development of one-stop wide-awake dupuytren's fasciectomy service: a retrospective review.

Objectives: To detail the transition to a totally one-stop wide-awake (OSWA) Dupuytren's contracture surgical service.

Design: Retrospective review of Dupuytren's component of last 1000 OSWA cases.

Setting: The UK's first totally one-stop wide-awake orthopaedic service.

High-throughput fluorescence-activated nanoscale subcellular sorter with single-molecule sensitivity.

Recent single-cell and single-molecule studies have shown that a variety of subpopulations exist within biological systems, such as synaptic vesicles, that have previously been overlooked in common bulk studies. By isolating and enriching these various subpopulations, detailed analysis with a variety of analytical techniques can be done to further understand the role that various subpopulations play in cellular dynamics and how alterations to these subpopulations affect the overall function of the biological system. Previous sorters lack the sensitivity, sorting speed, and efficiency to isolate synaptic vesicles and other nanoscale systems.

Probing the interior of synaptic vesicles with internalized nanoparticles.

Synaptic vesicles are subcellular organelles that are found in the synaptic bouton and are responsible for the propagation of signals between neurons. Synaptic vesicles undergo endo- and exocytosis with the neuronal membrane to load and release neurotransmitters. Here we discuss how we utilize this property to load nanoparticles as a means of probing the interior of synaptic vesicles.

Determining the number of specific proteins in cellular compartments by quantitative microscopy.

This protocol describes a method for determining both the average number and variance of proteins, in the few to tens of copies, in isolated cellular compartments such as organelles and protein complexes. Other currently available protein quantification techniques either provide an average number, but lack information on the variance, or they are not suitable for reliably counting proteins present in the few to tens of copies. This protocol entails labeling of the cellular compartment with fluorescent primary-secondary antibody complexes, total internal reflection fluorescence microscopic imaging of the cellular compartment, digital image analysis and deconvolution of the fluorescence intensity data.

Synaptosomes as a platform for loading nanoparticles into synaptic vesicles.

Synaptosomes are intact, isolated nerve terminals that contain the necessary machinery to recycle synaptic vesicles via endocytosis and exocytosis upon stimulation. Here we use this property of synaptosomes to load quantum dots into synaptic vesicles. Vesicles are then isolated from the synaptosomes, providing a method to probe isolated, individual synaptic vesicles where each vesicle contains a single, encapsulated nanoparticle.

Intracellular delivery of bioactive molecules using light-addressable nanocapsules.

This paper describes a method by which molecules that are impermeable to cells are encapsulated in dye-sensitized lipid nanocapsules for delivery into cells via endocytosis. Once inside the cells, the molecules are released from the lipid nanocapsules into the cytoplasm with a single nanosecond pulse from a laser in the far red (645 nm). We demonstrate this method with the intracellular release of the second messenger IP(3) in CHO-M1 cells and report that calcium responses from the cells changed from a sustained increase to a transient spike when the average number of IP(3) released is decreased below 50 molecules per nanocapsule.

Passive secondary biological treatment systems reduce estrogens in dairy shed effluent.

Steroid estrogens are found at high concentrations in untreated dairy shed effluents. Reduction of estrogenic activity and steroid estrogen concentrations was assessed in two systems used to treat dairy shed effluents: the two-pond system and the advanced pond system. Both include anaerobic and aerobic treatment stages.

Steroid estrogens, conjugated estrogens and estrogenic activity in farm dairy shed effluents.

Agricultural wastes are a source of steroid estrogens and, if present, conjugated estrogens may add to the estrogen load released to soil and aquatic environments. Dairy shed effluent samples were collected from 18 farms for analysis of steroid estrogens by GC-MS, conjugated estrogens by LC-MS-MS, and estrogenic activity by E-screen in vitro bioassay. 17alpha-estradiol was found at highest concentrations (median 730 ng l(-1)), followed by estrone (100 ng l(-1)) and 17beta-estradiol (24 ng l(-1)).

Sizing subcellular organelles and nanoparticles confined within aqueous droplets.

This article describes two complementary techniques, single-particle tracking and correlation spectroscopy, for accurately sizing nanoparticles confined within picoliter volume aqueous droplets. Single-particle tracking works well with bright particles that can be continuously illuminated and imaged, and we demonstrated this approach for sizing single fluorescent beads. Fluorescence correlation spectroscopy detects small intensity bursts from particles or molecules diffusing through the confocal probe volume, which works well with dim and rapidly diffusing particles or molecules; we demonstrated FCS for sizing synaptic vesicles confined in aqueous droplets.

Phase III pilot study of dose escalation using conformal radiotherapy in prostate cancer: PSA control and side effects.

Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin.

High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity.