Does control of rheumatic disease raise the standard of living in developing countries?

[No abstract available

Crystal Structure of T7 Gene 4 Ring Helicase Indicates a Mechanism for Sequential Hydrolysis of Nucleotides

AbstractWe have determined the crystal structure of an active, hexameric fragment of the gene 4 helicase from bacteriophage T7. The structure reveals how subunit contacts stabilize the hexamer. Deviation from expected six-fold symmetry of the hexamer indicates that the structure is of an intermediate on the catalytic pathway. The structural consequences of the asymmetry suggest a “binding change” mechanism to explain how cooperative binding and hydrolysis of nucleotides are coupled to conformational changes in the ring that most likely accompany duplex unwinding. The structure of a complex with a nonhydrolyzable ATP analog provides additional evidence for this hypothesis, with only four of the six possible nucleotide binding sites being occupied in this conformation of the hexamer. This model suggests a mechanism for DNA translocation

Hsp90 inhibition: A promising therapeutic approach for arsacs

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenera-tive disease caused by mutations in the SACS gene, encoding the 520 kDa modular protein sacsin, which comprises multiple functional sequence domains that suggest a role either as a scaffold in protein folding or in proteostasis. Cells from patients with ARSACS display a distinct phenotype including altered organisation of the intermediate filament cytoskeleton and a hyperfused mitochon-drial network where mitochondrial respiration is compromised. Here, we used vimentin bundling as a biomarker of sacsin function to test the therapeutic potential of Hsp90 inhibition with the C-terminal-domain-targeted compound KU-32, which has demonstrated mitochondrial activity. This study shows that ARSACS patient cells have significantly increased vimentin bundling compared to control, and this was also present in ARSACS carriers despite them being asymptomatic. We found that KU-32 treatment significantly reduced vimentin bundling in carrier and patient cells. We also found that cells from patients with ARSACS were unable to maintain mitochondrial membrane potential upon challenge with mitotoxins, and that the electron transport chain function was restored upon KU-32 treatment. Our preliminary findings presented here suggest that targeting the heat-shock response by Hsp90 inhibition alleviates vimentin bundling and may represent a promising area for the development of therapeutics for ARSACS

Quantum tunneling dynamics of an interacting Bose-Einstein condensate through a Gaussian barrier

The transmission of an interacting Bose-Einstein condensate incident on a repulsive Gaussian barrier is investigated through numerical simulation. The dynamics associated with interatomic interactions are studied across a broad parameter range not previously explored. Effective 1D Gross-Pitaevskii equation (GPE) simulations are compared to classical Boltzmann-Vlasov equation (BVE) simulations in order to isolate purely coherent matterwave effects. Quantum tunneling is then defined as the portion of the GPE transmission not described by the classical BVE. An exponential dependence of transmission on barrier height is observed in the purely classical simulation, suggesting that observing such exponential dependence is not a sufficient condition for quantum tunneling. Furthermore, the transmission is found to be predominately described by classical effects, although interatomic interactions are shown to modify the magnitude of the quantum tunneling. Interactions are also seen to affect the amount of classical transmission, producing transmission in regions where the non-interacting equivalent has none. This theoretical investigation clarifies the contribution quantum tunneling makes to overall transmission in many-particle interacting systems, potentially informing future tunneling experiments with ultracold atoms.Comment: Close to the published versio

Kate Loves Topshop: Celebrity Endorsements and the Lovemarks Concept in a Fashion Retail Context

Fashion designers and retailers often employ celebrities as endorsers due to celebrities’ power to influence consumer attitudes, drive sales and command loyalty. This power may be predicated on the transfer of a celebrity’s perceived personality to the promoted brand, thus enhancing consumer attitudes toward it. Celebrity endorsement is regarded as one component of contemporary brand management, the practice of which has two consequences: first, consumers increasingly expect ‘good’ brand performance from ALL brands; second, brands correspondingly find it difficult to continually distinguish themselves. One response has been the Lovemarks concept (Roberts 2005). A Lovemark is distinguished from conventional brands by inspiring deep, long-lasting relationships based on emotional responses invoked by the characteristics and personality it represents. While the Lovemark model is considered useful to practitioners (Bain 2004; Cooper & Pawle 2006), its academic study is limited, especially in its application to established marketing concepts. Here, a qualitative case-study explores the Lovemark concept in context of celebrity endorsement by examining the congruency between emotions felt for UK fashion retailer Topshop, and its associated celebrity, Kate Moss. Findings suggest that emotional responses to a celebrity have resonance on attitudes toward a brand; these and implications for practice and theory will be presented

Non-destructive shadowgraph imaging of ultracold atoms

An imaging system is presented that is capable of far-detuned non-destructive imaging of a Bose-Einstein condensate with the signal proportional to the second spatial derivative of the density. Whilst demonstrated with application to $^{85}\text{Rb}$, the technique generalizes to other atomic species and is shown to be capable of a signal to noise of ${\sim}25$ at $1$GHz detuning with $100$ in-trap images showing no observable heating or atom loss. The technique is also applied to the observation of individual trajectories of stochastic dynamics inaccessible to single shot imaging. Coupled with a fast optical phase lock loop, the system is capable of dynamically switching to resonant absorption imaging during the experiment.Comment: 4 pages, 5 figure