Mutations that abrogate human immunodeficiency virus type 1 reverse transcriptase dimerization affect maturation of the reverse transcriptase heterodimer

The specific impact of mutations that abrogate human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) dimerization on virus replication is not known, as mutations shown previously to inhibit RT dimerization also impact Gag-Pol stability, resulting in pleiotropic effects on HIV-1 replication. We have previously characterized mutations at codon 401 in the HIV-1 RT tryptophan repeat motif that abrogate RT dimerization in vitro, leading to a loss in polymerase activity. The introduction of the RT dimerization-inhibiting mutations W401L and W401A into HIV-1 resulted in the formation of noninfectious viruses with reduced levels of both virion-associated and intracellular RT activity compared to the wild-type virus and the W401F mutant, which does not inhibit RT dimerization in vitro. Steady-state levels of the p66 and p51 RT subunits in viral lysates of the W401L and W401A mutants were reduced, but no significant decrease in Gag-Pol was observed compared to the wild type. In contrast, there was a decrease in processing of p66 to p51 in cell lysates for the dimerization-defective mutants compared to the wild type. The treatment of transfected cells with indinavir suggested that the HIV-1 protease contributed to the degradation of virion-associated RT subunits. These data demonstrate that mutations near the RT dimer interface that abrogate RT dimerization in vitro result in the production of replication-impaired viruses without detectable effects on Gag-Pol stability or virion incorporation. The inhibition of RT activity is most likely due to a defect in RT maturation, suggesting that RT dimerization represents a valid drug target for chemotherapeutic intervention.

Functional (GT)n polymorphisms in promoter region of N-methyl-d-aspartate receptor 2A subunit (GRIN2A) gene affect hippocampal and amygdala volumes

The glutamate system including N-methyl-d-aspartate (NMDA) affects synaptic formation, plasticity and maintenance. Recent studies have shown a variable (GT)n polymorphism in the promoter region of the NMDA subunit gene (GRIN2A) and a length-dependent inhibition of transcriptional activity by the (GT)n repeat. In the present study, we examined whether the GRIN2A polymorphism is associated with regional brain volume especially in medial temporal lobe structures, in which the NMDA-dependent synaptic processes have been most extensively studied. Gray matter regions of interest (ROIs) for the bilateral amygdala and hippocampus were outlined manually on the magnetic resonance images of 144 healthy individuals. In addition, voxel-based morphometry (VBM) was conducted to explore the association of genotype with regional gray matter volume from everywhere in the brain in the same sample. The manually measured hippocampal and amygdala volumes were significantly larger in subjects with short allele carriers (n = 89) than in those with homozygous long alleles (n = 55) when individual differences in intracranial volume were accounted for. The VBM showed no significant association between the genotype and regional gray matter volume in any brain region. These findings suggest that the functional GRIN2A (GT)n polymorphism could weakly but significantly impact on human medial temporal lobe volume in a length-dependent manner, providing in vivo evidence of the role of the NMDA receptor in human brain development.

How does contingent reward affect enterprise resource planning continuance intention? The role of contingent reward transactional leadership

During the past decade, an increased focus on charismatic and transformational leadership has led to a diminished recognition of the importance of transactional leadership behaviours for successful information systems. We say that this is important because recent studies have shown that transactional leadership, in the form of contingent reward behaviour, can have substantial effects on employee attitudes, perceptions and behaviour. Therefore, in this study we discuss how contingent reward transactional leadership behaviour influences enterprise resource planning (ERP) users’ continuance intention by proposing a research model that explains how contingent reward has a positive effect on ERP users’ satisfaction and perceived usefulness which leads to ERP continuance intention. We further argue that distributive justice mediates this relationship. This study calls for managers to pay attention to the importance of contingent reward leadership behaviour in continuous intention of ERP.

Invigorating play : the role of affect in online multiplayer fps games

This chapter reexamines the relationship between the representative capacities of violent video games and the military industrial entertainment complex. It proposes a study of the affective capacities of violent militarised online multiplayer games to expand the limited accounts of the dominance of the military discourse and better understand what is going one while gamers play.

On memory, affect and atonement : the Long Tan memorial cross(es)

This article analyses the history of the Long Tan Memorial in Vietnam in order to open up a space for engaging with the memorialisation of war as something that can go beyond nationalistic sentimentality and create a space for more complex political and social engagements. In doing so I am concerned with exploring the value of an approach to heritage significance that prioritises relationships between places and peoples rather than authenticity and originality. I explore this question by making use of the fact that the Australian War Memorial has borrowed the original Long Tan Cross now in the custodianship of the Dong Nai Museum for a special exhibition to commemorate the Vietnam War. The Australian Vietnam Volunteers Reconstruction Group, who has official custodianship of the replica cross at the Long Tan Memorial site in Vietnam, has expressed disquiet over the loan. I use the Acting Director’s reply to the AVVRG’s Chairman to open up a discussion about the differences in meanings between these two crosses, what underlies these and how we might theorise them in order to open up an understanding of war heritage that recognises its potentials and its limitations.

The factors that affect the cost estimation activities in the tender preparation process in the Malaysian construction industry

The possibility of winning the tender is subject to the cost estimation proposed by the contractors compared to the cost estimation prepared by the client’s representative. Studies indicated that one of the construction company failures in the tendering process is due to the uncertain, incorrect, and unrealistic cost estimation. Failure to provide a competitive cost estimation on time is the main reason the contractor is not successful in winning the tender, and will not be considered for the tender evaluation stage. The aim of this paper is to validate the key factors that affect the cost estimation activities in the tender preparation process. This paper describes the results of a pilot study, from a questionnaire survey on the factors that affect the cost estimation activities in the tender preparation process. The study shows the importance of all the factors in the cost estimation activities in the tender preparation process in terms of human factors, working culture, and information technology.

Understanding the role of affect in producing a critical pedagogy for history museums

While the existence of uncritical exhibition practices that support nostalgic narratives about the past cannot be denied, this paper is focused on demonstrating both the existence of critical exhibitions and on explaining how they work. In particularly, this paper looks at the ways in which the production of affective, nonrational forms of experience aimed at inducing a heightened level of engagement on the part of visitors is being used to facilitate a more critical reflection on the relationship between past and present. My examples, drawn from curatorial practices in Australia dealing either with contact histories or histories of migration, will be used to explore how explicit forms of engagement with the senses in contemporary exhibition practices gesture toward not only a new understanding of the pedagogical role of museums but also to new forms of pedagogical practice.