Time to face the fats : What can mass spectrometry reveal about the structure of lipids and their interactions with proteins?

Since the 1950s, X-ray crystallography has been the mainstay of structural biology, providing detailed atomic-level structures that continue to revolutionize our understanding of protein function. From recent advances in this discipline, a picture has emerged of intimate and specific interactions between lipids and proteins that has driven renewed interest in the structure of lipids themselves and raised intriguing questions as to the specificity and stoichiometry in lipid-protein complexes. Herein we demonstrate some of the limitations of crystallography in resolving critical structural features of ligated lipids and thus determining how these motifs impact protein binding. As a consequence, mass spectrometry must play an important and complementary role in unraveling the complexities of lipid-protein interactions. We evaluate recent advances and highlight ongoing challenges towards the twin goals of (1) complete structure elucidation of low, abundant, and structurally diverse lipids by mass spectrometry alone, and (2) assignment of stoichiometry and specificity of lipid interactions within protein complexes.

Disclosure of documents : by duty, court order, or beyond reach?

The article examines the decision in Erskine v McDowall [2001] QDC 192, where the Court considered an application for an order that the defendant disclose documents to which she had a right of access under the Freedom of Information Act 1982 (Cth).

Australian patent enforcement : a proposal for an expert panel opinion

The Australian Government has been concerned “to find ways of making patent enforcement less of an issue” and to make it “cheaper, simpler and quicker to get fair and appropriate resolution for any dispute”. Major problems relating to patent enforcement in Australia have been identified as: the cost of legal proceedings; the lack of patent owners’ financial capacity to fund enforcement proceedings; delay; and uncertainty as to the outcome and lack of knowledge about the processes of enforcement. This paper considers some of the problems associated with patent enforcement in Australia and proposes an approach to patent litigation which is directed at alleviating some of the difficulties which have been identified. Specifically, it proposes a strategy designed to identify the parties’ risks at an early stage of patent litigation proceeding and facilitate an early resolution of the dispute.

The effect of topical adrenergic and anticholinergic agents on the choroidal thickness of young healthy adults

The human choroid is capable of rapidly changing its thickness in response to a variety of stimuli. However little is known about the role of the autonomic nervous system in the regulation of the thickness of the choroid. Therefore, we investigated the effect of topical parasympatholytic and sympathomimetic agents upon the choroidal thickness and ocular biometrics of young healthy adult subjects. Fourteen subjects (mean age 27.9 ± 4 years) participated in this randomized, single-masked, placebo-controlled study. Each subject had measurements of choroidal thickness (ChT) and ocular biometrics of their right eye taken before, and then 30 and 60 min following the administration of topical pharmacological agents. Three different drugs: 2% homatropine hydrobromide, 2.5% phenylephrine hydrochloride and a placebo (0.3% hydroxypropyl methylcellulose) were tested in all subjects; each on different days (at the same time of the day) in randomized order. Participants were masked to the pharmacological agent being used at each testing session. The instillation of 2% homatropine resulted in a small but significant increase in subfoveal ChT at 30 and 60 min after drug instillation (mean change 7 ± 3 μm and 14 ± 2 μm respectively; both p < 0.0001). The parafoveal choroid also exhibited a similar magnitude, significant increase in thickness with time after 2% homatropine (p < 0.001), with a mean change of 7 ± 0.3 μm and 13 ± 1 μm (in the region located 0.5 mm from the fovea center), 6 ± 1 μm and 12.5 ± 1 μm (1 mm from the fovea center) and 6 ± 2 μm and 12 ± 2 μm (1.5 mm from the fovea center) after 30 and 60 min respectively. Axial length decreased significantly 60 min after homatropine (p < 0.01). There were also significant changes in lens thickness (LT) and anterior chamber depth (ACD) (p < 0.05) associated with homatropine instillation. No significant changes in choroidal thickness, or ocular biometrics were found after 2.5% phenylephrine or placebo at any examination points (p > 0.05). In human subjects, significant increases in subfoveal and parafoveal choroidal thickness occurred after administration of 2% homatropine and this implies an involvement of the parasympathetic system in the control of choroidal thickness in humans.

Medical negligence, causation and liability for non-disclosure of risk : a post-wallace framework and critique

Through an examination of Wallace v Kam, this article considers and evaluates the law of causation in the specific context of a medical practitioner’s duty to provide information to patients concerning material risks of treatment. To supply a contextual background for the analysis which follows, Part II summarises the basic principles of causation law, while Part III provides an overview of the case and the reasoning adopted in the decisions at first instance and on appeal. With particular emphasis upon the reasoning in the courts of appeal, Part IV then examines the implications of the case in the context of other jurisprudence in this field and, in so doing, provides a framework for a structured consideration of causation issues in future non-disclosure cases under the Australian civil liability legislation. As will become clear, Wallace was fundamentally decided on the basis of policy reasoning centred upon the purpose behind the legal duty violated. Although the plurality in Rogers v Whitaker rejected the utility of expressions such as ‘the patient’s right of self-determination’ in this context, some Australian jurisprudence may be thought to frame the practitioner’s duty to warn in terms of promoting a patient’s autonomy, or right to decide whether to submit to treatment proposed. Accordingly, the impact of Wallace upon the protection of this right, and the interrelation between it and the duty to warn’s purpose, is investigated. The analysis in Part IV also evaluates the courts’ reasoning in Wallace by questioning the extent to which Wallace’s approach to liability and causal connection in non-disclosure of risk cases: depends upon the nature and classification of the risk(s) in question; and can be reconciled with the way in which patients make decisions. Finally, Part V adopts a comparative approach by considering whether the same decision might be reached if Wallace was determined according to English law.

Characterization of acyl chain position in unsaturated phosphatidylcholines using differential mobility-mass spectrometry

Glycerophospholipids (GPs) that differ in the relative position of the two fatty acyl chains on the glycerol backbone (i.e., sn-positional isomers) can have distinct physicochemical properties. The unambiguous assignment of acyl chain position to an individual GP represents a significant analytical challenge. Here we describe a workflow where phosphatidylcholines (PCs) are subjected to ESI for characterization by a combination of differential mobility spectrometry and MS (DMS-MS). When infused as a mixture, ions formed from silver adduction of each phospholipid isomer {e.g., [PC (16:0/18:1) + Ag]+ and [PC (18:1/16:0) + Ag]+} are transmitted through the DMS device at discrete compensation voltages. Varying their relative amounts allows facile and unambiguous assignment of the sn-positions of the fatty acyl chains for each isomer. Integration of the well-resolved ion populations provides a rapid method (< 3 min) for relative quantification of these lipid isomers. The DMS-MS results show excellent agreement with established, but time-consuming, enzymatic approaches and also provide superior accuracy to methods that rely on MS alone. The advantages of this DMS-MS method in identification and quantification of GP isomer populations is demonstrated by direct analysis of complex biological extracts without any prior fractionation.

The potential availability of roosting sites for lesser short-tailed bats (Mystacina tuberculata) on Kapiti Island, New Zealand: Implications for a translocation

Lesser short-tailed bats (Mystacina tuberculata) have recently been translocated to Kapiti Island in an attempt to form a new population of this threatened species. However, the island's vegetation is regenerating, and there was doubt that the forests provided enough large trees with cavities for bats to roost in. This study measured the availability of tree-trunk cavities of the right size for potential roost sites on Kapiti Island, and assessed if habitat restoration would be required to increase the translocation's chance of success. First, trees with cavities accessible to us were sampled in six of Kapiti Island's forest types. Size variables known to affect roost site selection by lesser short-tailed bats at the tree and cavity level were measured. Trees were classified as containing cavities that could potentially provide suitable roosts if their values for all variables measured fell within the range of roosts used by lesser short-tailed bats in natural populations. Roosts were classified as suitably sized for solitary bats or for colonies, using measurements from both types of roosts in natural populations. Second, the density of these potential roost cavities was calculated. Cavities of a size potentially suitable for colonies were found in four of the six forest types at densities ranging from 3.2 +/- 3.2 SE to 52.4 +/- 14.0 trees per ha. Density of potential solitary roosts was much higher. Not all potential cavities will be suitable because they may be damp, poorly insulated, or have an unsuitable microclimate. Nevertheless, our estimates indicated that the two most extensive forest types each contained thousands of potential cavities of a size suitable for colonies of lesser short-tailed bats. In addition, there were tens of thousands of cavities large enough to shelter solitary bats. Roost habitat restoration appears unnecessary to assist translocated Mystacina tuberculata on Kapiti Island.

Public space for street-scape theatrics : guerrilla spatial tactics and methods of urban hacking in Brisbane, Australia

It could be argued that architecture has an inherent social responsibility to enrich the urban and spatial environments for the city’s occupants. However how we define quality, and how ‘places’ can be designed to be fair and equitable, catering for individuals on a humanistic and psychological level, is often not clearly addressed. Lefebvre discusses the idea of the ‘right to the city’; the belief that public space design should facilitate freedom of expression and incite a sense of spatial ownership for its occupants in public/commercial precincts. Lefebvre also points out the importance of sensory experience in the urban environment. “Street-scape theatrics” are performative activities that summarise these two concepts, advocating the ‘right to the city’ by way of art as well as providing sensual engagement for city users. Literature discusses the importance of Street-scape Theatrics however few sources attempt to discuss this topic in terms of how to design these spaces/places to enhance the city on both a sensory and political level. This research, grounded in political theory, investigates the case of street music, in particular busking, in the city of Brisbane, Australia. Street culture is a notion that already exists in Brisbane, but it is heavily controlled especially in central locations. The study discusses how sensory experience of the urban environment in Brisbane can be enriched through the design for busking; multiple case studies, interviews, observations and thematic mappings provide data to gather an understanding of how street performers see and understand the built form. Results are sometime surprisingly incongruous with general assumptions in regards to street artist as well as the established political and ideological framework, supporting the idea that the best and most effective way of urban hacking is working within the system. Ultimately, it was found that the Central Business District in Brisbane, Australia, could adopt certain political and design tactics which attempt to reconcile systematic quality control with freedom of expression into the public/commercial sphere, realism upheld. This can bridge the gap between the micro scale of the body and the macro of the political economy through freedom of expression, thus celebrating the idiosyncratic nature of the city.

Imaginging the good Indigenous citizen : race war and the pathology of partiarchal white sovereignty

In June 2007, the Australian federal government sent military and policy into Indigenous communities in the Northern Territory on the premise that sexual abuse of children was rampant and a national crisis. This article draws on Foucault’s work on sovereignty and rights to argue that patriarchal white sovereignty as a regime of power deploys a discourse of pathology in the exercising of sovereign right to subjugate and discipline Indigenous people as good citizens.

Insertions in the OCL1 locus of Acinetobacter baumannii lead to shortened lipooligosaccharides

Genomes of 82 Acinetobacter baumannii global clones 1 (GC1) and 2 (GC2) isolates were sequenced and different forms of the locus predicted to direct synthesis of the outer core (OC) of the lipooligosaccharide were identified. OCL1 was in all GC2 genomes, whereas GC1 isolates carried OCL1, OCL3 or a new locus, OCL5. Three mutants in which an insertion sequence (ISAba1 or ISAba23) interrupted OCL1 were identified. Isolates with OCL1 intact produced only lipooligosaccharide, while the mutants produced lipooligosaccharide of reduced molecular weight. Thus, the assignment of the OC locus as that responsible for the synthesis of the OC is correct.

Unspeakably present: The (un)acknowledgment of diverse sexuality and gender human rights in Australian youth justice systems

A number of international human rights frameworks protect the rights of young people in contact with the criminal justice system in states parties, including Australia. These frameworks inform youth justice policy in Australia’s jurisdictions. While the frameworks protect young people’s right to non-discrimination on the grounds of ‘race’, religion and political opinion, the rights of young people to non-discrimination on the grounds of sexuality and gender diversity are not explicitly protected. This is problematic given that lesbian, gay, bisexual, trans, intersex and queer (LGBTIQ) young people appear over-represented in youth justice systems. This article argues that the exclusion of this group from human rights frameworks has an important flow-on effect: the marginalisation of the right of LGBTIQ young people to non-discrimination in policy and discourse that is informed by international human rights frameworks. After outlining the relevant frameworks, this article examines the evidence about LGBTIQ young people’s interactions with youth justice agencies, particularly police. The evidence indicates that the human rights of LGBTIQ young people are frequently breached in these interactions. We conclude by arguing that it is timely to consider how best to protect the human rights of LBGTIQ young people and keep their rights on the agenda.

Normal reference values of strength in pelvic floor muscle of women: A descriptive and inferential study

Background To describe the clinical, functional and quality of life characteristics in women with Stress Urinary Incontinence (SUI). In addition, to analyse the relationship between the variables reported by the patients and those informed by the clinicians, and the relationship between instrumented variables and the manual pelvic floor strength assessment. Methods Two hundred and eighteen women participated in this observational, analytical study. An interview about Urinary Incontinence and the quality of life questionnaires (EuroQoL-5D and SF-12) were developed as outcomes reported by the patients. Manual muscle testing and perineometry as outcomes informed by the clinician were assessed. Descriptive and correlation analysis were carried out. Results The average age of the subjects was (39.93?±?12.27 years), (24.49?±?3.54 BMI). The strength evaluated by manual testing of the right levator ani muscles was 7.79?±?2.88, the strength of left levator ani muscles was 7.51?±?2.91 and the strength assessed with the perineometer was 7.64?±?2.55. A positive correlation was found between manual muscle testing and perineometry of the pelvic floor muscles (p?of quality of life reported by the patients and outcomes of functional capacity informed by the physiotherapist. Conclusion A stratification of the strength of pelvic floor muscles in a normal distribution of a large sample of women with SUI was done, which provided the clinic with a baseline. There is a relationship between the strength of the pelvic muscles assessed manually and that obtained by a perineometer in women with SUI. There was no relationship between these values of strength and quality of life perceived.

A Bayesian model of source monitoring

The Source Monitoring Framework is a promising model of constructive memory, yet fails because it is connectionist and does not allow content tagging. The Dual-Process Signal Detection Model is an improvement because it reduces mnemic qualia to a single memory signal (or degree of belief), but still commits itself to non-discrete representation. By supposing that ‘tagging’ means the assignment of propositional attitudes to aggregates of anemic characteristics informed inductively, then a discrete model becomes plausible. A Bayesian model of source monitoring accounts for the continuous variation of inputs and assignment of prior probabilities to memory content. A modified version of the High-Threshold Dual-Process model is recommended to further source monitoring research.

Cosmo, Cosmolino: Patent law and nanotechnology

Patent law has a significant instrumental and symbolic role in regulating nanotechnology. A 2011 report of the United States Federal Trade Commission noted that ‘the patent system plays a critical role in promoting innovation across industries from biotechnology to nanotechnology, and by entities from large corporations to independent inventors’. This chapter considers the much contested legal, ethical and social issues involved with regulating the patenting of nanotechnology. Section I considers the efforts of patent offices to classify nanotechnology and the empirical evidence about patent filing rates. Section II examines whether there is a ‘tragedy of the anticommons’ emerging in respect of nanotechnology. It contemplates access mechanisms – such as the defence of experimental use, patent pools, open innovation models and technology transfer. Section III explores ethical and social concerns associated with nanotechnology – in particular, issues about the impact upon human health and the environment.

23andMe Inc.: Patent law and lifestyle genetics

The venture, 23andMe Inc., raises a host of issues in respect of patent law, policy, and practice in respect of lifestyle genetics and personalised medicine. The company observes: ‘We recognize that the availability of personal genetic information raises important issues at the nexus of ethics, law, and public policy’. 23andMe Inc. has tested the boundaries of patent law, with its patent applications, which cut across information technology, medicine, and biotechnology. The company’s research raises fundamental issues about patentability, especially in light of the litigation in Bilski v. Kappos, Mayo Collaborative Services v. Prometheus Laboratories Inc. and Association for Molecular Pathology v. United States Patent and Trademark Office and Myriad Genetics Inc. There has been much debate and controversy over 23andMe Inc. filing patent applications – particularly in respect of its granted patent on ‘Polymorphisms associated with Parkinson’s Disease’. The direct-to-consumer marketing of genetic testing by 23andMe Inc. has also raised important questions of bioethics and human rights. It is queried whether the terms of service for 23andMe Inc. provide adequate recognition of the concepts of informed consent and benefit-sharing, especially in light of litigation in this area in the United States. Given the patent thickets surrounding genetic testing, the case study of 23andMe Inc. also highlights questions about patent infringement and patent exceptions. The future reform of patent law, policy, and practice needs to take into account new developments in lifestyle genetics and personalised medicine – as exemplified by 23andMe Inc.