Identifying optimal lipid raft characteristics required to promote nanoscale protein-protein interactions on the plasma membrane

The dynamic lateral segregation of signaling proteins into microdomains is proposed to facilitate signal transduction, but the constraints on microdomain size, mobility, and diffusion that might realize this function are undefined. Here we interrogate a stochastic spatial model of the plasma membrane to determine how microdomains affect protein dynamics. Taking lipid rafts as representative microdomains, we show that reduced protein mobility in rafts segregates dynamically partitioning proteins, but the equilibrium concentration is largely independent of raft size and mobility. Rafts weakly impede small-scale protein diffusion but more strongly impede long-range protein mobility. The long-range mobility of raft-partitioning and raft-excluded proteins, however, is reduced to a similar extent. Dynamic partitioning into rafts increases specific interprotein collision rates, but to maximize this critical, biologically relevant function, rafts must be small (diameter, 6 to 14 nm) and mobile. Intermolecular collisions can also be favored by the selective capture and exclusion of proteins by rafts, although this mechanism is generally less efficient than simple dynamic partitioning. Generalizing these results, we conclude that microdomains can readily operate as protein concentrators or isolators but there appear to be significant constraints on size and mobility if microdomains are also required to function as reaction chambers that facilitate nanoscale protein-protein interactions. These results may have significant implications for the many signaling cascades that are scaffolded or assembled in plasma membrane microdomains.

Book review : "Carbon Capture and Storage Emerging Legal and Regulatory Issues" edited by Ian Havercroft, Richard Macrory, Richard B Stewart, Oxford, Hart Publishing, 2011

As the international community struggles to find a cost-effective solution to mitigate climate change and reduce greenhouse gas emissions, carbon capture and storage (CCS) has emerged as a project mechanism with the potential to assist in transitioning society towards its low carbon future. Being a politically attractive option, legal regimes to promote and approve CCS have proceeded at an accelerated pace in multiple jurisdictions including the European Union and Australia. This acceleration and emphasis on the swift commercial deployment of CCS projects has left the legal community in the undesirable position of having to advise on the strengths and weaknesses of the key features of these regimes once they have been passed and become operational. This is an area where environmental law principles are tested to their very limit. On the one hand, implementation of this new technology should proceed in a precautionary manner to avoid adverse impacts on the atmosphere, local community and broader environment. On the other hand, excessive regulatory restrictions will stifle innovation and act as a barrier to the swift deployment of CCS projects around the world. Finding the balance between precaution and innovation is no easy feat. This is an area where lawyers, academics, regulators and industry representatives can benefit from the sharing of collective experiences, both positive and negative, across the jurisdictions. This exemplary book appears to have been collated with this philosophy in mind and provides an insightful addition to the global dialogue on establishing effective national and international regimes for the implementation of CCS projects...

Legal liability for carbon capture and storage in Australia : where should the losses fall?

This article presents a critical analysis of the current and proposed CCS legal frameworks across a number of jurisdictions in Australia in order to examine the legal treatment of the risks of carbon leakage from CCS operations. It does so through an analysis of the statutory obligations and liability rules established under the offshore Commonwealth and Victorian regimes, and onshore Queensland and Victorian legislative frameworks. Exposure draft legislation for CCS laws in Western Australia is also examined. In considering where the losses will fall in the event of leakage, the potential tortious and statutory liabilities of private operators and the State are addressed alongside the operation of statutory protections from liability. The current legal treatment of CCS under the new Australian Carbon Pricing Mechanism is also critiqued.

Cytokine secretion via cholesterol-rich lipid raft-associated SNAREs at the phagocytic cup

Lipopolysaccharide-activated macrophages rapidly synthesize and secrete tumor necrosis factor α (TNFα) to prime the immune system. Surface delivery of membrane carrying newly synthesized TNFα is controlled and limited by the level of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins syntaxin 4 and SNAP-23. Many functions in immune cells are coordinated from lipid rafts in the plasmamembrane, and we investigated a possible role for lipid rafts in TNFα trafficking and secretion. TNFα surface delivery and secretion were found to be cholesterol- dependent. Upon macrophage activation, syntaxin 4 was recruited to cholesterol-dependent lipid rafts, whereas its regulatory protein, Munc18c, was excluded from the rafts. Syntaxin 4 in activated macrophages localized to discrete cholesterol-dependent puncta on the plasmamembrane, particularly on filopodia. Imaging the early stages of TNFα surface distribution revealed these puncta to be the initial points of TNFα delivery. During the early stages of phagocytosis, syntaxin 4 was recruited to the phagocytic cup in a cholesterol dependent manner. Insertion of VAMP3-positive recycling endosome membrane is required for efficient ingestion of a pathogen. Without this recruitment of syntaxin 4, it is not incorporated into the plasma membrane, and phagocytosis is greatly reduced. Thus, relocation of syntaxin 4 into lipid rafts in macrophages is a critical and rate-limiting step in initiating an effective immune response.

UHT milk contains multiple forms of αS1-casein that undergo degradative changes during storage

Milk proteins are susceptible to chemical changes during processing and storage. We used proteomic tools to analyse bovine αS1-casein in UHT milk. 2-D gels of freshly processed milk αS1-casein was presented as five or more spots due to genetic polymorphism and variable phosphorylation. MS analysis after phosphopeptide enrichment allowed discrimination between phosphorylation states and genetic variants. We identified a new alternatively-spliced isoform with a deletion of exon 17, producing a new C-terminal sequence, K164SQVNSEGLHSYGL177, with a novel phosphorylation site at S174. Storage of UHT milk at elevated temperatures produced additional, more acidic αS1-casein spots on the gels and decreased the resolution of minor forms. MS analysis indicated that non-enzymatic deamidation and loss of the N-terminal dipeptide were the major contributors to the changing spot pattern. These results highlight the important role of storage temperature in the stability of milk proteins and the utility of proteomic techniques for analysis of proteins in food.

Implications of lipid biology for the pathogenesis of schizophrenia

Objective: Preclinical and clinical data suggest that lipid biology is integral to brain development and neurodegeneration. Both aspects are proposed as being important in the pathogenesis of schizophrenia. The purpose of this paper is to examine the implications of lipid biology, in particular the role of essential fatty acids (EFA), for schizophrenia. Methods: Medline databases were searched from 1966 to 2001 followed by the crosschecking of references. Results: Most studies investigating lipids in schizophrenia described reduced EFA, altered glycerophospholipids and an increased activity of a calcium-independent phospholipase A2 in blood cells and in post-mortem brain tissue. Additionally, in vivo brain phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS) demonstrated lower phosphomonoesters (implying reduced membrane precursors) in first- and multi-episode patients. In contrast, phosphodiesters were elevated mainly in first-episode patients (implying increased membrane breakdown products), whereas inconclusive results were found in chronic patients. EFA supplementation trials in chronic patient populations with residual symptoms have demonstrated conflicting results. More consistent results were observed in the early and symptomatic stages of illness, especially if EFA with a high proportion of eicosapentaenoic acid was used. Conclusion: Peripheral blood cell, brain necropsy and 31P-MRS analysis reveal a disturbed lipid biology, suggesting generalized membrane alterations in schizophrenia. 31P-MRS data suggest increased membrane turnover at illness onset and persisting membrane abnormalities in established schizophrenia. Cellular processes regulating membrane lipid metabolism are potential new targets for antipsychotic drugs and might explain the mechanism of action of treatments such as eicosapentaenoic acid.

Capping computation time and storage requirements for appearance-based localization with CAT-SLAM

Appearance-based localization is increasingly used for loop closure detection in metric SLAM systems. Since it relies only upon the appearance-based similarity between images from two locations, it can perform loop closure regardless of accumulated metric error. However, the computation time and memory requirements of current appearance-based methods scale linearly not only with the size of the environment but also with the operation time of the platform. These properties impose severe restrictions on longterm autonomy for mobile robots, as loop closure performance will inevitably degrade with increased operation time. We present a set of improvements to the appearance-based SLAM algorithm CAT-SLAM to constrain computation scaling and memory usage with minimal degradation in performance over time. The appearance-based comparison stage is accelerated by exploiting properties of the particle observation update, and nodes in the continuous trajectory map are removed according to minimal information loss criteria. We demonstrate constant time and space loop closure detection in a large urban environment with recall performance exceeding FAB-MAP by a factor of 3 at 100% precision, and investigate the minimum computational and memory requirements for maintaining mapping performance.

A security architecture for cloud storage combining proofs of retrievability and fairness

We investigate existing cloud storage schemes and identify limitations in each one based on the security services that they provide. We then propose a new cloud storage architecture that extends CloudProof of Popa et al. to provide availability assurance. This is accomplished by incorporating a proof of storage protocol. As a result, we obtain the first secure storage cloud computing scheme that furnishes all three properties of availability, fairness and freshness.

A review of current statistical methodologies for in storage sampling and surveillance in the grains industry

Effective, statistically robust sampling and surveillance strategies form an integral component of large agricultural industries such as the grains industry. Intensive in-storage sampling is essential for pest detection, Integrated Pest Management (IPM), to determine grain quality and to satisfy importing nation’s biosecurity concerns, while surveillance over broad geographic regions ensures that biosecurity risks can be excluded, monitored, eradicated or contained within an area. In the grains industry, a number of qualitative and quantitative methodologies for surveillance and in-storage sampling have been considered. Primarily, research has focussed on developing statistical methodologies for in storage sampling strategies concentrating on detection of pest insects within a grain bulk, however, the need for effective and statistically defensible surveillance strategies has also been recognised. Interestingly, although surveillance and in storage sampling have typically been considered independently, many techniques and concepts are common between the two fields of research. This review aims to consider the development of statistically based in storage sampling and surveillance strategies and to identify methods that may be useful for both surveillance and in storage sampling. We discuss the utility of new quantitative and qualitative approaches, such as Bayesian statistics, fault trees and more traditional probabilistic methods and show how these methods may be used in both surveillance and in storage sampling systems.

Drugs for cardiac arrhythmmias, antithrombotic drugs and lipid modulating drugs

13.1 Drugs for cardiac arrhythmias 13.1.1 Introduction to cardiac arrhythmias 13.1.2 Cardiac action potentials 13.1.3 Mechanisms of cardiac arrhythmias 13.1.3 Class I 13.1.4 Class II 13.1.5 Class III 12.1.6 Class IV 13.1.7 Amiodarone 13.1.8 Adenosine 13.2 Antithrombotic drugs 13.2.1 Thrombus formation 13.2.2 Platelet aggregation and anti-platelet drugs 13.2.3 Coagulation 13.2.4 Anticoagulants 13.2.5 Fibrinolysis and fibrinolytics 13.3. Lipid modulating drugs 13.3.1 Cholesterol 13.3.2 Statins 13.3.3 Fibric acid derivatives 13.3.4 Ezetimibe

Stability studies of HIV-1 Pr55gag virus-like particles made in insect cells after storage in various formulation media

Background: HIV-1 Pr55gag virus-like particles (VLPs) expressed by baculovirus in insect cells are considered to be a very promising HIV-1 vaccine candidate, as they have been shown to elicit broad cellular immune responses when tested in animals, particularly when used as a boost to DNA or BCG vaccines. However, it is important for the VLPs to retain their structure for them to be fully functional and effective. The medium in which the VLPs are formulated and the temperature at which they are stored are two important factors affecting their stability. FINDINGS We describe the screening of 3 different readily available formulation media (sorbitol, sucrose and trehalose) for their ability to stabilise HIV-1 Pr55gag VLPs during prolonged storage. Transmission electron microscopy (TEM) was done on VLPs stored at two different concentrations of the media at three different temperatures (4[degree sign]C, --20[degree sign]C and -70[degree sign]C) over different time periods, and the appearance of the VLPs was compared. VLPs stored in 15% trehalose at -70[degree sign]C retained their original appearance the most effectively over a period of 12 months. VLPs stored in 5% trehalose, sorbitol or sucrose were not all intact even after 1 month storage at the temperatures tested. In addition, we showed that VLPs stored under these conditions were able to be frozen and re-thawed twice before showing changes in their appearance. Conclusions Although the inclusion of other analytical tools are essential to validate these preliminary findings, storage in 15% trehalose at -70[degree sign]C for 12 months is most effective in retaining VLP stability.

Simulation of phosphine flow in vertical grain storage : a preliminary numerical study

To fumigate grain stored in a silo, phosphine gas is distributed by a combination of diffusion and fan-forced advection. This initial study of the problem mainly focuses on the advection, numerically modelled as fluid flow in a porous medium. We find satisfactory agreement between the flow predictions of two Computational Fluid Dynamics packages, Comsol and Fluent. The flow predictions demonstrate that the highest velocity (>0.1 m/s) occurs less than 0.2m from the inlet and reduces drastically over one metre of silo height, with the flow elsewhere less than 0.002 m/s or 1% of the velocity injection. The flow predictions are examined to identify silo regions where phosphine dosage levels are likely to be too low for effective grain fumigation.