Phenylalanine-544 plays a key role in substrate and inhibitor binding by providing a hydrophobic packing point at the active site of insulin-regulated aminopeptidase

Inhibitors of insulin-regulated aminopeptidase (IRAP) improve memory and are being developed as a novel treatment for memory loss. In this study, the binding of a class of these inhibitors to human IRAP was investigated using molecular docking and site-directed mutagenesis. Four benzopyran-based IRAP inhibitors with different affinities were docked into a homology model of the catalytic site of IRAP. Two 4-pyridinyl derivatives orient with the benzopyran oxygen interacting with the Zn2+ ion and a direct parallel ring-stack interaction between the benzopyran rings and Phe544. In contrast, the two 4-quinolinyl derivatives orient in a different manner, interacting with the Zn2+ ion via the quinoline nitrogen, and Phe544 contributes an edge-face hydrophobic stacking point with the benzopyran moiety. Mutagenic replacement of Phe544 with alanine, isoleucine, or valine resulted in either complete loss of catalytic activity or altered hydrolysis velocity that was substrate-dependent. Phe544 is also important for inhibitor binding, because these mutations altered the Ki in some cases, and docking of the inhibitors into the corresponding Phe544 mutant models revealed how the interaction might be disturbed. These findings demonstrate a key role of Phe544 in the binding of the benzopyran IRAP inhibitors and for optimal positioning of enzyme substrates during catalysis.

Elves processing Christmas orders in an office SFX

A sound design that animates elves working in an office processing Christmas orders.

Away in a manger (Christmas pop carol)

Away in a manger, the famous Carol, is given the pop treatment.

Using camera motion to identify different types of American football plays

This paper presents a method that uses camera motion parameters to recognise 7 types of American football plays. The approach is based on the motion information extracted from the video and it can identify short and long pass plays, short and long running plays, quarterback sacks, punt plays and kickoff plays. This method has the advantage that it is fast and it does not require player or ball tracking. The system was trained and tested using 782 plays and the results show that the system has an overall classification accuracy of 68%.

Designing online role plays with a focus on story development to support engagement and critical learning for higher education students

Online role plays, as they are designed for use in higher education in Australia and internationally, are active and authentic learning activities (Wills, Leigh & Ip, 2011). In online role plays, students take a character role in developing a story that serves as a metaphor for real-life experience in order to develop a potentially wide range of subject-related and generic learning outcomes. The characteristics of these stories are rarely considered as factors in the design―and success―of these activities. The unspoken cultural assumptions, norms and rules in the stories that impact on the meanings students make from their experiences are also rarely scrutinised in the online role play literature. This paper presents findings from a case study of an asynchronous text-based online role play involving politics and journalism students from three Australian universities. The findings highlight the centrality of students’ collaborative story-building activity to their engagement and learning, including their development of critical perspectives. The study underlines the importance of certain aspects of the role play's design to support students' story-building activity.

Were the National Socialists a Völkisch Party? Paganism, Christianity, and the Nazi christmas

A trend in studies about National Socialism and religion in recent years argues for a deliberate distinction between the Nazi Party (NSDAP) and the antisemitic völkisch movement of nineteenth-century Germany. This article challenges that contention. Several researchers have published comprehensive studies on the heterogeneous nature of Christian responses to the Nazis, but a comparable approach looking at how the Nazis viewed religion has not yet been undertaken. A study of the latter type is certainly necessary, given that one of the consistent features of the völkisch movement was its diversity. As Roger Griffin has argued, a “striking feature of the sub-culture . . . was just how prolific and variegated it was . . . [T]he only denominator common to all was the myth of national rebirth.” In short, the völkisch movement contained a colorful, varied, and often bewildering range of religious beliefs.

The passion plays of celebrity culture

If there is a cultural arena today where passion plays a central and heightened role, then it is in the affecting and textural operations of celebrity. Celebrity representations are crafted out of passionate aesthetic signifiers and impassioned pleas to the senses, to the emotions and to the exaggerations of feeling that the consumer or fan is asked to register and then fully embody. Celebrity culture attempts to turn one into a passionate creature, ruled by the heart, lost in a sea of desires and desiring wants and needs, as the adoring figure that moves us, moves intimately before us. Such passions can and do go unrequited, of course; some are resisted and rejected, and some celebrity passions register as fully carnal and liberating encounters. That is to say, the plays of celebrity passion serve (hetero) normative and policed accounts of feeling and belonging in the world, fuel a desire for commodity objects and material possessions, and yet also open up the possibility for engagements that are violent, liberal and unregulated. In this article, I will explore the ways in which celebrity culture engages with passion and through the idea of it involving a modern form of the passion play. Following Lauren Berlant, I will argue that the passion ignited by the celebrity works to contain and regulate desire, and yet also offers up the opportunity for sensorial engagements that violate and resist the normative terms of desiring. I will suggest celebrity figures are themselves caught up in this passion play, suffering and feeling deeply at the same time, while channelling this violent crisis to their fans as they do so. Finally, I will write the article passionately, from an impassioned perspective, measuring and weighting my own desires in the contradictions and tensions of passion as they emerge in the body of the writer before you. This article is part of a themed issue entitled ‘Passion’.

The Christmas effect-special dividend announcements

This paper examines the Halloween effect in special dividend announcements. We find that firms are more likely to announce special dividends at the end of a year, especially in the months of November and December. There is a Halloween effect in the announcements, but more importantly, there is a Christmas effect in the propensity and abnormal returns of special dividends. This paper provides initial evidence on the Christmas effect of special dividend payments. It links monthly effects in stock returns and corporate events to explain the likelihood of the occurrence of special dividend announcements. The results of this paper shed light on why corporate events are more likely to occur in some periods, but less likely to occur in others.

The ZntA-like NpunR4017 plays a key role in maintaining homeostatic levels of zinc in Nostoc punctiforme

Analysis of cellular response to zinc exposure provides insights into how organisms maintain homeostatic levels of zinc that are essential, while avoiding potentially toxic cytosolic levels. Using the cyanobacterium Nostoc punctiforme as a model, qRT-PCR analyses established a profile of the changes in relative mRNA levels of the ZntA-like zinc efflux transporter NpunR4017 in response to extracellular zinc. In cells treated with 18 μM of zinc for 1 h, NpunR4017 mRNA levels increased by up to 1300 % above basal levels. The accumulation and retention of radiolabelled (65)Zn by NpunR4107-deficient and overexpressing strains were compared to wild-type levels. Disruption of NpunR4017 resulted in a significant increase in zinc accumulation up to 24 % greater than the wild type, while cells overexpressing NpunR4107 accumulated 22 % less than the wild type. Accumulation of (65)Zn in ZntA(-) Escherichia coli overexpressing NpunR4017 was reduced by up to 21 %, indicating the capacity for NpunR4017 to compensate for the loss of ZntA. These findings establish the newly identified NpunR4017 as a zinc efflux transporter and a key transporter for maintaining zinc homeostasis in N. punctiforme.

The passage of authority: imagining the political transformation of Australia’s Christmas Island, from sovereignty to governance

In 2012, Australia’s Christmas Island is best known as an island of immigration detention, a key component of Australia’s growing offshore border security apparatus, where interdicted boat arrivals seeking asylum are detained and processed. This article offers one account of how the Island came to be what it is, by providing two snapshots of the operable set of power relations on Christmas Island, then and now: ‘Island in the Sun’, and ‘Tropics of Governance’. Side by side, their stark contrast reveals the passage of authority through time and place, from the embodied, unified voice of the sovereignty of the British Empire to the palliative communication and bureaucratic sincerity that characterise governance. By disclosing shifting patterns of emergence and decay and showing border security’s intimate relation to governance, this article seeks to offer a deepened understanding of the current detention situation in its immanence. What can now be seen as Christmas Island’s past follies also reveals the restless work of successive political imaginations, the shifting ways and means by which an island can be translated into a solution to a political problem, and how successive solutions tend toward wreck and ruin.

Inhibition of HDAC3- and HDAC6-promoted survivin expression plays an important role in SAHA-induced autophagy and viability reduction in breast cancer cells

SAHA is a class I HDAC/HDAC6 co-inhibitor and an autophagy inducer currently undergoing clinical investigations in breast cancer patients. However, the molecular mechanism of action of SAHA in breast cancer cells remains unclear. In this study, we found that SAHA is equally effective in targeting cells of different breast cancer subtypes and tamoxifen sensitivity. Importantly, we found that down-regulation of survivin plays an important role in SAHA-induced autophagy and cell viability reduction in human breast cancer cells. SAHA decreased survivin and XIAP gene transcription, induced survivin protein acetylation and early nuclear translocation in MCF7 and MDA-MB-231 breast cancer cells. It also reduced survivin and XIAP protein stability in part through modulating the expression and activation of the 26S proteasome and heat-shock protein 90. Interestingly, targeting HDAC3 and HDAC6, but not other HDAC isoforms, by siRNA/pharmacological inhibitors mimicked the effects of SAHA in modulating the acetylation, expression, and nuclear translocation of survivin and induced autophagy in MCF7 and MDA-MB-231 cancer cells. Targeting HDAC3 also mimicked the effect of SAHA in up-regulating the expression and activity of proteasome, which might lead to the reduced protein stability of survivin in breast cancer cells. In conclusion, this study provides new insights into SAHA's molecular mechanism of actions in breast cancer cells. Our findings emphasize the complexity of the regulatory roles in different HDAC isoforms and potentially assist in predicting the mechanism of novel HDAC inhibitors in targeted or combinational therapies in the future.

A single panmictic population of endemic red crabs, Gecarcoidea natalis, on Christmas Island with high levels of genetic diversity

The red crab, Gecarcoidea natalis, is endemic to Christmas Island in the Indian Ocean and largely responsible for shaping the unique ecosystem found throughout the island's rainforests. However, the introduction and establishment of supercolonies of the highly invasive yellow crazy ant, Anoplolepis gracilipes, has decimated red crab numbers over the last several decades. This poses a significant risk to the future conservation of G. natalis and consequently threatens the integrity of the unique island ecosystem. Here we undertook a population genetic analysis of G. natalis using a combination of 11 microsatellite markers and sequencing of the mitochondrial cytochrome oxidase subunit I gene from samples collected on Christmas Island as well as a single location from North Keeling Island (located approximately 900 km west of Christmas Island). The genetic results indicate that G. natalis is a single panmictic population on Christmas Island, with no spatial genetic structure or restricted gene flow apparent between sampled locations. Further, G. natalis from North Keeling Island are not genetically distinct and are recent immigrants from Christmas Island. The effective population size of G. natalis has likely remained large and stable on Christmas Island throughout its evolutionary history with relatively moderate to high levels of genetic diversity in microsatellite loci and mitochondrial haplotypes assessed in this study. For management purposes G. natalis can be considered a single panmictic population, which should simplify conservation efforts for the genetic management of this iconic island species. © 2014 Springer Science+Business Media Dordrecht.