Three-dimensional analysis of budding sites and released virus suggests a revised model for HIV-1 morphogenesis

Current models of HIV-1 morphogenesis hold that newly synthesized viral Gag polyproteins traffic to and assemble at the cell membrane into spherical protein shells. The resulting late-budding structure is thought to be released by the cellular ESCRT machinery severing the membrane tether connecting it to the producer cell. Using electron tomography and scanning transmission electron microscopy, we find that virions have a morphology and composition distinct from late-budding sites. Gag is arranged as a continuous but incomplete sphere in the released virion. In contrast, late-budding sites lacking functional ESCRT exhibited a nearly closed Gag sphere. The results lead us to propose that budding is initiated by Gag assembly, but is completed in an ESCRT-dependent manner before the Gag sphere is complete. This suggests that ESCRT functions early in HIV-1 release-akin to its role in vesicle formation-and is not restricted to severing the thin membrane tether.

Loss of neuronatin expression is associated with promoter hypermethylation in pituitary adenoma

The imprinted gene, neuronatin (NNAT), is one of the most abundant transcripts in the pituitary and is thought to be involved in the development and maturation of this gland. In a recent whole-genome approach, exploiting a pituitary tumour cell line, we identified hypermethylation associated loss of NNAT. In this report, we determined the expression pattern of NNAT in individual cell types of the normal gland and within each of the different pituitary adenoma subtypes. In addition, we determined associations between expression and CpG island methylation and used colony forming efficiency assays (CFE) to gain further insight into the tumour-suppressor function of this gene. Immunohistochemical (IHC) co-localization studies of normal pituitaries showed that each of the hormone secreting cells (GH, PRL, ACTH, FSH and TSH) expressed NNAT. However, 33 out of 47 adenomas comprising, 11 somatotrophinomas, 10 prolactinomas, 12 corticotrophinomas and 14 non-functioning tumours, irrespective of subtype failed to express either NNAT transcript or protein as determined by quantitative real-time RT-PCR and IHC respectively. In normal pituitaries and adenomas that expressed NNAT the promoter-associated CpG island showed characteristics of an imprinted gene where approximately 50% of molecules were densely methylated. However, in the majority of adenomas that showed loss or significantly reduced expression of NNAT, relative to normal pituitaries, the gene-associated CpG island showed significantly increased methylation. Induced expression of NNAT in transfected AtT-20 cells significantly reduced CFE. Collectively, these findings point to an important role for NNAT in the pituitary and perhaps tumour development in this gland.

Spatial-temporal epidemiological analyses of two sympatric, co-endemic alphaviral diseases in Queensland, Australia

Background: The two most reported mosquito-borne diseases in Queensland, a northern state of Australia, are Ross River virus (RRV) disease and Barmah Forest virus (BFV) disease. Both diseases are endemic in Queensland and have similar clinical symptoms and comparable transmission cycles involving a complex inter-relationship between human hosts, various mosquito vectors, and a range of nonhuman vertebrate hosts, including marsupial mammals that are unique to the Australasian region. Although these viruses are thought to share similar vectors and vertebrate hosts, RRV is four times more prevalent than BFV in Queensland. Methods: We performed a retrospective analysis of BFV and RRV human disease notification data collected from 1995 to 2007 in Queensland to ascertain whether there were differences in the incidence patterns of RRV and BFV disease. In particular, we compared the temporal incidence and spatial distribution of both diseases and considered the relationship between their disease dynamics. We also investigated whether a peak in BFV incidence during spring was indicative of the following RRV and BFV transmission season incidence levels. Results: Although there were large differences in the notification rates of the two diseases, they had similar annual temporal patterns, but there were regional variations between the length and magnitude of the transmission seasons. During periods of increased disease activity, however, there was no association between the dynamics of the two diseases. Conclusions: The results from this study suggest that while RRV and BFV share similar mosquito vectors, there are significant differences in the ecology of these viruses that result in different epidemic patterns of disease incidence. Further investigation is required into the ecology of each virus to determine which factors are important in promoting RRV and BFV disease outbreaks.

Writing and the disappearance of architecture theory

One of the first architects to write a book was Vitruvius, the Roman architect who published De Architectura in the 1st century BC, a book that would become the foundation for Western Architectural Thought. When I was an undergraduate, the history of architecture was taught via a series of books by architects that were at least, if not more significant than the buildings. From De Architectura to Alberti’s rejoinder De re aedificatoria (On the Art of Building) in the fifteenth century, Palladio’s Quattro Libri (The Four Books of Architecture) 1570, and Laugier’s Essai sur l'Architecture 1753. In the 1990s, we treasured the heroic architecture books of the 20th century from Le Corbusier, Vers une Architecture, to Aldo Rossi’s the Architecture of the City, Rem Koolhaas’s Delirious New York, and of course Robert Venturi’s Learning from Las Vegas which for me was the very starting point for the postmodern movement.

Antisocial behaviour orders : Unanticipated directions in social network site development

Abstract: Social network technologies, as we know them today have become a popular feature of everyday life for many people. As their name suggests, their underlying premise is to enable people to connect with each other for a variety of purposes. These purposes however, are generally thought of in a positive fashion. Based on a multi-method study of two online environments, Habbo Hotel and Second Life, which incorporate social networking functionality, we she light on forms of what can be conceptualized as antisocial behaviours and the rationales for these. Such behaviours included: scamming, racist/homophobic attacks, sim attacks, avatar attacks, non-conformance to contextual norms, counterfeiting and unneighbourly behaviour. The rationales for sub behaviours included: profit, fun, status building, network disruption, accidental acts and prejudice. Through our analysis we are able to comment upon the difficulties of defining antisocial behaviour in such environments, particularly when such environments are subject to interpretation vis their use and expected norms. We also point to the problems we face in conducting our public and private lives given the role ICTs are playing in the convergence of these two spaces and also the convergence of ICTs themselves.

Intellectual Property – What Went Wrong!

In its simplest form the patent system is designed to encourage the disclosure of innovative thought in exchange for a period of exclusivity in which the grantee of the rights may profit from such knowledge. I will attempt in this paper to show that patentees seeking to enforce their patents in Australia will face great difficulty through a number of potentially fatal pitfalls. I also submit that as a result of the decisions in Australia in reported patent cases in the last ten years, legal advisers should place their clients on notice that if they are trying to enforce their patents they are unlikely to succeed...

Studying upper-limb kinematic using inertial sensors embedded in smartphones

Background: In recent years, there have been investigations concerning upper-limbs kinematics by various devices. The latest generation of smartphones often includes inertial sensors with subunits which can detect inertial kinematics. The use of smartphones is presented as a convenient and portable analysis method for studying kinematics in terms of angular mobility and linear acceleration Objective: The aim of this study was to study humerus kinematics through six physical properties that correspond to angular mobility and acceleration in the three axes of space, obtained by a smartphone. Methods: This cross-sectional study recruited healthy young adult subjects. Descriptive and anthropometric independent variables related to age, gender, weight, size, and BMI were included. Six physical properties were included corresponding to two dependent variables for each of three special axes: mobility angle (degrees) and lineal acceleration (meters/seconds2), which were obtained thought the inertial measurement sensor embedded in the iPhone4 smartphone equipped with three two elements for the detection of kinematic variables: a gyroscope and an accelerometer. Apple uses an LIS302DL accelerometer in the iPhone4. The application used to obtain kinematic data was xSensor Pro, Crossbow Technology, Inc., available at the Apple AppStore. The iPhone4 has storage capacity of 20MB. The data-sampling rate was set to 32 Hz, and the data for each analytical task was transmitted as email for analysis and postprocessing The iPhone4 was placed in the right half of the body of each subject located in the middle third of the humerus slightly posterior snugly secured by a neoprene fixation belt. Tasks were explained concisely and clearly. The beginning and the end were decided by a verbal order by the researcher. Participants were placed standing, starting from neutral position, performing the following analytical tasks: 180º right shoulder abduction (eight repetitions) and, after a break of about 3 minutes, 180º right shoulder flexion (eight repetitions). Both tasks were performed with the elbow extended, wrist in neutral position and the palmar area of the hand toward the midline at the beginning and end of the movement. Results: A total of 11 subjects (8 men, 3 woman) were measured, whose mean of age was 24.7 years (SD = 4.22 years) and their average BMI was 22.64 Kg/m2 (SD = 2.29 Kg/m2). The mean of angular mobility collected by the smartphone was bigger in pitch axis for flexion (= 157.28°, SD= 12.35°) and abduction (= 151.71°, SD= 9.70°). With regard to acceleration, the highest peak mean value was shown in the Y motion axis during flexion (= 19.5°/s2, SD = 0.8°/s2) and abduction (= 19.4°/s2, SD = 0.8°/s2). Also, descriptive graphics of analytical tasks performed were obtained. Conclusions: This study shows how humerus contributes to upper-limb motion and it identified movement patterns. Therefore, it supports smartphone as a useful device to analyze upper-limb kinematics. Thanks to this study it´s possible to develop a simple application that facilitates the evaluation of the patient.

Influence of visible work activity on drivers’ speed choice at roadworks

Vehicle traffic through roadwork sites creates a hazardous work environment, with speed limit noncompliance a major contributor to the high risk and high severity of roadwork crashes. This paper examines responses to an online survey to better understand the factors underlying drivers’ work zone speed choices. Drivers’ stated speed choice was compared between two photographs of the same work zone section – one with workers and machinery present and another with no visible activity. Drivers also provided comments on any aspect of roadwork safety they thought was important. A paired t-test of stated speed choice revealed that significantly lower mean speeds were nominated when workers and machinery were clearly present and active (41.7 vs 53.5 km/h, p<0.01). Participants expressed concern about roadwork signage and reduced speed limits being left in place when there was no apparent work activity. Driver perceptions, and thus compliance, may be improved through technological and operational changes.

Activation of forkhead box O transcription factors by oncogenic BRAF promotes p21cip1-dependent senescence

Oncogene-induced senescence (OIS) is a potent tumor-suppressive mechanism that is thought to come at the cost of aging. The Forkhead box O (FOXO) transcription factors are regulators of life span and tumor suppression. However, whether and how FOXOs function in OIS have been unclear. Here, we show a role for FOXO4 in mediating senescence by the human BRAFV600E oncogene, which arises commonly in melanoma. BRAFV600E signaling through mitogen-activated protein kinase/extracellular signal-regulated kinase kinase resulted in increased reactive oxygen species levels and c-Jun NH 2 terminal kinase-mediated activation of FOXO4 via its phosphorylation on Thr223, Ser226, Thr447, and Thr451. BRAFV600E-induced FOXO4 phosphorylation resulted in p21cip1-mediated cell senescence independent of p16 ink4a or p27kip1. Importantly, melanocyte-specific activation of BRAFV600E in vivo resulted in the formation of skin nevi expressing Thr223/Ser226-phosphorylated FOXO4 and elevated p21cip1. Together, these findings support a model in which FOXOs mediate a trade-off between cancer and aging.

KRAB zinc-finger proteins localise to novel KAP1-containing foci that are adjacent to PML nuclear bodies

The KRAB-zinc finger proteins (KRAB-ZFPs) represent a very large, but poorly understood, family of transcriptional regulators in mammals. They are thought to repress transcription via their interaction with KRAB-associated protein 1 (KAP1), which then assembles a complex of chromatin modifiers to lay down histone marks that are associated with inactive chromatin. Studies of KRAB-ZFP/KAP1-mediated gene silencing, using reporter constructs and ectopically expressed proteins, have shown colocalisation of both KAP1 and repressed reporter target genes to domains of constitutive heterochromatin in the nucleus. However, we show here that although KAP1 does indeed become recruited to pericentric heterochromatin during differentiation of mouse embryonic stem (ES) cells, endogenous KRAB-ZFPs do not. Rather, KRAB-ZFPs and KAP1 relocalise to novel nucleoplasmic foci that we have termed KRAB- and KAP1-associated (KAKA) foci. HP1s can also concentrate in these foci and there is a close spatial relationship between KAKA nuclear foci and PML nuclear bodies. Finally, we reveal differential requirements for the recruitment of KAP1 to pericentric heterochromatin and KAKA foci, and suggest that KAKA foci may contain sumoylated KAP1 - the form of the protein that is active in transcriptional repression.

A loss of bioscience knowledge in nursing students

Background: Knowledge of the human biosciences is fundamental to the development of competent nurse practitioners (Smales, 2010) with the requisite knowledge and skills, necessary for high quality patient care and good patient outcomes (Logan and Angel, 2011). Many of these students study bioscience units which cover topics in anatomy, physiology, pathophysiology and microbiology. Studies of science recall in general and medical education, report up to 33% loss of knowledge in the first year which declines to 50% in the subsequent year (Custers, 2010). Objectives: The objectives were to test the recall of bioscience knowledge by nursing students and to ascertain their perceptions of the testing. Questions explored: What would the results be for multiple choice questions in fundamental microbiology and gastrointestinal anatomy and physiology (A&P) undertaken by nursing students 4, 9 and 16 months after their first bioscience exam on these topics? Would pre-warning the students of a microbiology quiz and not a gastrointestinal A&P quiz affect the findings? How would the students respond to the testing when surveyed? Recall results: The nursing students performed better in the final exam on gastrointestinal A&P than on fundamental microbiology. There was an approximate 20% loss in knowledge of gastrointestinal A&P after 4 months and this did not change significantly over the next 12 months. Although there was an improved performance in microbiology quizzes after 4 months, there was no significant difference in results over the next 12 months. Survey results: More than 50% of students thought the testing helped them focus for the lectures and made them aware they had some pre-knowledge of the lecture topics. Discussion: Although there was a loss of knowledge of gastrointestinal A&P, it appears that warning the students about the microbiology quiz may have helped their recall. The majority of students valued the testing as a useful learning exercise. References: Custers, E. J. F. M. (2010). Long-term retention of basic science knowledge: a review study. Advances in Health Science Education, 15, 109-128. Smales, K. (2010). Learning and applying biosciences to clinical practice in nursing. Nursing Standard, 24(33), 35-39. Logan, P.A., & Angel, L. (2011). Nursing as a scientific undertaking and the intersection with science in undergraduate studies: implications for nursing management. Journal of Nursing Management, 19(3), 407-417.

Can social resilience inform SA/SIA for adaptive planning for climate change in vulnerable regions?

Social resilience concepts are gaining momentum in environmental planning through an emerging understanding of the socio-ecological nature of biophysical systems. There is a disconnect, however, between these concepts and the sociological and psychological literature related to social resilience. Further still, both schools of thought are not well connected to the concepts of social assessment (SA) and social impact assessment (SIA) that are the more standard tools supporting planning and decision-making. This raises questions as to how emerging social resilience concepts can translate into improved SA/SIA practices to inform regional-scale adaptation. Through a review of the literature, this paper suggests that more cross-disciplinary integration is needed if social resilience concepts are to have a genuine impact in helping vulnerable regions tackle climate change.

Lessons from a Church Mural

A travel article about the Moselle Valley, Germany. There’s a school of thought that says you shouldn’t look back in life. This is not the received wisdom in Cochem, a village on the Moselle river known, like many others in the area, for its white wine and fairytale castle. Here, they say, it’s bad luck if you don’t turn around for one last look at a mural of St Christopher that graces the castle’s main tower...

An analysis of digital storytelling as a documentation tool for research in the creative and performing arts

This paper examines the capacity of digital storytelling to document research activity in the creative and performing arts. In particular, it seeks to identify the thought processes and methods that underpin this research and to capture them using the digital storytelling medium. Interest in this issue was prompted by the author’s work with the creative and performing artists from the Queensland Conservatorium and the Queensland College of Art as part of the Federal government’s Research Quality Framework (RQF) in 2007. The RQF compelled artists to address what it means to undertake research in their disciplines, to describe this, measure it and quantify it; for many practitioners this represents a significant challenge. These issues continue to be pertinent in the context of the Excellence in Research for Australia (ERA) initiative. This research is significant because it seeks to identify, in layman’s terms, the research methods and thought processes used by artists in their research practice. It seeks to do so free of the encumbrances of the professional doctorate policies, the higher education research quality frameworks, and the dense philosophical debates that have to-date dominated discussions of this issue. The research involves qualitative data collection methods including a detailed literature review, interviews with key practitioners and academics involved in the creative and performing arts, and three case studies. The literature review focuses on publications that explore issues of research practice and method in the creative and performing arts. The case studies involve three Queensland-based artists. Digital stories will be developed (and presented) with Marcus and Mafe using their visual materials and drawing on the issues identified in the literature review and interviews. Emmerson’s DVD provided a point of comparison with the digital stories. (Brief bios are attached)

Deletions and other pleasures : Episode 1: The pleasures of science fiction

"Christy Dena’s online-remix-narrative takes iconic images of popular culture and builds with them a strange world where the human fallibility is programmatically deleted. Both dystopic and playful, Dena’s work is an ironic reimagining of pleasure as a state of robotic flatlining, using tropes of science fiction to critique processes of social normalisation and increasing alienation from emotionality." This creative response began as a completely different story and form. What excited me in the end was the concept of deletion and how it could be an interesting mechanic: where the only thing you can do in the world is delete. I thought about deleting parts of robots to make them better. Healing comes from taking away, from removing things. Memories of Joseph Weizenbaum’s chatbot ELIZA came flooding back: where the (human) player is a patient talking to a Rogerian psychotherapist. But in this work I’m switching the roles and making the player the doctor, a doctor to robots…a doctor that can only prescribe deletions. I conceived of the work as a branching narrative, and started writing it in Twine. With every robot patient, the player chose one of many deletions. But when I realised I wouldn’t be able to arrange an artist and sound designer I looked for another option. I played with Zeega and felt that I could get the mood I was after with that platform. So the piece transformed into a work where the player/viewer is imprisoned in the decisions of the deleting protagonist…which has its own effect on the experience and meaning.