Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome

The DNA context of nucleotides that a protein recognizes can influence the strength of the protein-DNA interaction. Moreover, in prokaryotes, understanding the quantitative differences in binding affinities that result in part from the DNA context is often important in describing regulatory mechanisms. Nevertheless, these issues have not been a major focus yet for the investigation of protein-DNA interactions in eukaryotes. In this study, we explored the binding specificity and the range of affinities that the BPV-1 E2 transcriptional activator has for DNA. Because E2 binding sites are positioned near several different BPV-1 promoters, such quantitative information may be important to understand transcriptional regulatory mechanisms in BPV-1. Gel retardation assays and DNA footprinting were used to quantitate the affinities of the E2 binding sites in the viral genome. In the process, five sites were discovered, which, on the basis of sequence, had not been predicted previously to interact with the E2 protein. Equilibrium and kinetic studies show that the range of E2 affinities of the 17 sites varied over 300-fold. The sequence elements responsible for E2 recognition of DNA were determined by missing contact analysis of several sites and a point mutation analysis of one site. The results presented show that the affinity of an E2 binding site is to a large extent determined by the availability of specific contacts, but the data also strongly suggest that DNA structure plays an important role

Longitudinal stability of genetic and environmental influences on the association between diurnal preference and sleep quality in young adult twins and siblings

Overlapping genetic influences have been implicated in diurnal preference and subjective sleep quality. Our overall aim was to examine overlapping concurrent and longitudinal genetic and environmental effects on diurnal preference and sleep quality over ~5 years. Behavioural genetic analyses were performed on data from the longitudinal British G1219 study of young adult twins and non-twin siblings. 1556 twins and siblings provided data on diurnal preference (Morningness-Eveningness Questionnaire) and sleep quality (Pittsburgh Sleep Quality Index) at time 1 (mean age=20.30 years, SD=1.76; 62% female); and 862 participated at time 2 (mean age=25.30 years, SD=1.81; 66% female). Preference for eveningness was associated with poorer sleep quality at both time-points (r=.25[95% confidence intervals, (CI)=.20-.30], and r=.21[CI=.15-.28]). There was substantial overlap in the genetic influences on diurnal preference and sleep quality individually, across time (genetic correlations [rA’s]: .64[95% CI = .59-.67] and .48[95% CI = .42-.53]). There were moderate genetic correlations between diurnal preference and sleep quality concurrently and longitudinally (rAs=.29-.60). Non-shared environmental overlap was substantially smaller for all cross-phenotype associations (non-shared environmental correlations [rE’s]=-.02-.08). All concurrent and longitudinal associations within and between phenotypes were largely accounted for by genetic factors (explaining between 60%-100% of the associations). All shared environmental effects were non-significant. Non-shared environmental influences played a smaller role on the associations between phenotypes (explaining between -.06%-40% of the associations). These results suggest that to some extent similar genes contribute to the stability of diurnal preference and sleep quality throughout young adulthood, but also that different genes play a part over this relatively short time-frame. While there was evidence of genetic overlap between phenotypes concurrently and longitudinally, the possible emergence of new genetic factors (or decline of previously associated factors) suggests that molecular genetic studies focussing on young adults should consider more tightly specified age-groups, given that genetic effects may be time-specific

Minimum Information about a Neuroscience Investigation (MINI) Electrophysiology

This module represents the formalized opinion of the authors and the CARMEN consortium, which identifies the minimum information required to report the use of electrophysiology in a neuroscience study, for submission to the CARMEN system (www.carmen.org.uk).
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Applying the Higher Education Academy framework for partnership in learning and teaching in higher education to online partnership learning communities: A case study and an extended model

As internet access and use increase exponentially, pedagogical practice becomes increasingly embedded in online platforms. We report on an online initiative of engaged student learning, the peer-led, staff-assisted e-helpdesk for research methods and statistics, which we evaluated and redeveloped using the lens and guiding principles of the framework for partnership in learning and teaching of the Higher Education Academy (HEA). The aim of the redevelopment was to steer the initiative towards a more integrative and sustainable implementation, as manifest in the applied construct of an online partnership learning community. Our evolving experience of the e-helpdesk highlighted the central role of the facilitator in engineering and maintaining social presence in the online community. We propose an extended model for building an online partnership learning community, whereby partnership encapsulates all the essential elements of student and staff partnership as outlined in the HEA framework, but is also critically defined by similar parameters of partnership between users and facilitators. In this model, the facilitator’s role becomes more involved in instructional teaching as disciplinary expertise increases, but descending levels of disciplinary expertise can foster ascending levels of independent learning and shared discovery for both users and facilitators.  &nbsp

A pilot study of eye movement during mammography interpretation: Eyetracker results and workstation design implications

Digital mammography can potentially improve mammography image and interpretation quality. On-line interpretation from a workstation may improve interpretation logistics and increase availability of comparison images. Interpretation of eight 4k- x 5k-pixel mammograms on two to four 2k- x 2.5k-pixel monitors is problematic because of the time spent in choosing which images display on which monitors, and zooming and roaming on individual images that are too large to display completely at full resolution. The authors used an eyetracker to measure radiologists viewing behavior during mammography interpretation with film on a viewbox. It was observed that a significant portion of the mammographers' time is spent viewing "comparison pairs" (typically two or more comparisons per case), such as the left mediolateral and craniocaudal images or old and new images. From the eyetracker measurements, we estimated that the number of image display, roam, and zoom operations decreases from an average of 64 for one monitor to 31 for four monitors, with the largest change going from one to two monitors. We also show that fewer monitors with a faster response time is superior to more monitors with a slower response time. Finally, the authors demonstrate the applicability of time-motion analysis to mammographic workstation design

Identification of the occurrence and pattern of masseter muscle activities during sleep using EMG and accelerometer systems

<p>Abstract</p> <p>Background</p> <p>Sleep bruxism has been described as a combination of different orofacial motor activities that include grinding, clenching and tapping, although accurate distribution of the activities still remains to be clarified.</p> <p>Methods</p> <p>We developed a new system for analyzing sleep bruxism to examine the muscle activities and mandibular movement patterns during sleep bruxism. The system consisted of a 2-axis accelerometer, electroencephalography and electromyography. Nineteen healthy volunteers were recruited and screened to evaluate sleep bruxism in the sleep laboratory.</p> <p>Results</p> <p>The new system could easily distinguish the different patterns of bruxism movement of the mandible and the body movement. Results showed that grinding (59.5%) was most common, followed by clenching (35.6%) based on relative activity to maximum voluntary contraction (%MVC), whereas tapping was only (4.9%).</p> <p>Conclusion</p> <p>It was concluded that the tapping, clenching, and grinding movement of the mandible could be effectively differentiated by the new system and sleep bruxism was predominantly perceived as clenching and grinding, which varied between individuals.</p