Protein-nucleic acids interactions: new ways of connecting structure, dynamics and function

No abstract available

Drug resistance outcomes of long-term ART with tenofovir disoproxil fumarate in the absence of virological monitoring

Objectives: The resistance profiles of patients receiving long-term ART in sub-Saharan Africa have been poorly described. This study obtained a sensitive assessment of the resistance patterns associated with long-term tenofovir-based ART in a programmatic setting where virological monitoring is yet to become part of routine care. Methods: We studied subjects who, after a median of 4.2 years of ART, replaced zidovudine or stavudine with tenofovir disoproxil fumarate while continuing lamivudine and an NNRTI. Using deep sequencing, resistance-associated mutations (RAMs) were detected in stored samples collected at tenofovir introduction (T0) and after a median of 4.0 years (T1). Results: At T0, 19/87 (21.8%) subjects showed a detectable viral load and 8/87 (9.2%) had one or more major NNRTI RAMs, whereas 82/87 (94.3%) retained full tenofovir susceptibility. At T1, 79/87 (90.8%) subjects remained on NNRTI-based ART, 5/87 (5.7%) had introduced lopinavir/ritonavir due to immunological failure, and 3/87 (3.4%) had interrupted ART. Whilst 68/87 (78.2%) subjects maintained or achieved virological suppression between T0 and T1, a detectable viral load with NNRTI RAMs at T0 predicted lack of virological suppression at T1. Each treatment interruption, usually reflecting unavailability of the dispensary, doubled the risk of T1 viraemia. Tenofovir, lamivudine and efavirenz selected for K65R, K70E/T, L74I/V and Y115F, alongside M184V and multiple NNRTI RAMs; this resistance profile was accompanied by high viral loads and low CD4 cell counts. Conclusions: Viraemia on tenofovir, lamivudine and efavirenz led to complex resistance patterns with implications for continued drug activity and risk of onward transmission

A preference for visual speed during smooth pursuit eye movement

Does the preference for visual speed extend to motion perception when the eye moves? Current evidence from psychophysics and neuroscience is limited to small patches of image motion and stationary fixation. Active observers, however, are more likely to use large patches of retinal flow and extra-retinal signals accompanying eye movement to judge motion. We therefore investigated whether speed remains a primary dimension during smooth pursuit using a ‘discrimination-contour’ technique. Our results showed that observers struggled most when trying to discriminate pursued stimuli that travelled at the same speed but moved over different distances and durations. This remained the case when retinal flow was added, and when we isolated trials in which extra-retinal signals were the only salient cue to motion. Our results suggest that preferential sensitivity for visual speed is quite general, supported by the many different types of motion mechanism used by active observers

The personal experience of parenting a child with Juvenile Huntington’s Disease: perceptions across Europe

The study reported here presents a detailed description of what it is like to parent a child with juvenile Huntington’s disease in families across four European countries. Its primary aim was to develop and extend findings from a previous UK study. The study recruited parents from four European countries: Holland, Italy, Poland and Sweden,. A secondary aim was to see the extent to which the findings from the UK study were repeated across Europe and the degree of commonality or divergence across the different countries. Fourteen parents who were the primary caregiver took part in a semistructured interview. These were analyzed using an established qualitative methodology, interpretative phenomenological analysis. Five analytic themes were derived from the analysis: the early signs of something wrong; parental understanding of juvenile Huntington’s disease; living with the disease; other people’s knowledge and understanding; and need for support. These are discussed in light of the considerable convergence between the experiences of families in the United Kingdom and elsewhere in Europe