Dynamic changes in the brain protein interaction network correlates with progression of Aβ42 pathology in Drosophila

Alzheimer’s disease (AD), the most prevalent form of dementia, is a progressive and devastating neurodegenerative condition for which there are no effective treatments. Understanding the molecular pathology of AD during disease progression may identify new ways to reduce neuronal damage. Here, we present a longitudinal study tracking dynamic proteomic alterations in the brains of an inducible Drosophila melanogaster model of AD expressing the Arctic mutant Aβ42 gene. We identified 3093 proteins from flies that were induced to express Aβ42 and age-matched healthy controls using label-free quantitative ion-mobility data independent analysis mass spectrometry. Of these, 228 proteins were significantly altered by Aβ42 accumulation and were enriched for AD-associated processes. Network analyses further revealed that these proteins have distinct hub and bottleneck properties in the brain protein interaction network, suggesting that several may have significant effects on brain function. Our unbiased analysis provides useful insights into the key processes governing the progression of amyloid toxicity and forms a basis for further functional analyses in model organisms and translation to mammalian systems

Changes in late adolescents’ voting intentions during the election campaign: Disentangling the effects of political communication with parents, peers and media

This article investigates the effects of political discussions with parents, political discussions with peers and exposure to political news during an election campaign on the voting intentions and behaviour of first-time voters. Longitudinal data collected in the Czech Republic are employed in the main analysis (N=223). Results show that young people who frequently discuss politics with their peers are characterized by higher voting intentions and subsequent electoral participation. On the other hand, political discussions with parents and exposure to political news have no such effects. Furthermore, although it does not have an impact on voting intentions, more frequent political discussions with parents predict increased frequency of political discussions with peers. Overall, our results underscore the importance of peers in late adolescents' political socialization

Evaluating the effects of bilingual traffic signs on driver performance and safety

Variable Message Signs (VMS) can provide immediate and relevant information to road users and bilingual VMS can provide great flexibility in countries where a significant proportion of the population speak an alternative language to the majority. The study reported here evaluates the effect of various bilingual VMS configurations on driver behaviour and safety. The aim of the study was to determine whether or not the visual distraction associated with bilingual VMS signs of different configurations (length, complexity) impacted on driving performance. A driving simulator was used to allow full control over the scenarios, road environment and sign configuration and both longitudinal and lateral driver performance was assessed. Drivers were able to read one and two-line monolingual signs and two-line bilingual signs without disruption to their driving behaviour. However, drivers significantly reduced their speed in order to read four-line monolingual and four-line bilingual signs, accompanied by an increase in headway to the vehicle in front. This implies that drivers are possibly reading the irrelevant text on the bilingual sign and various methods for reducing this effect are discussed

Early adolescent disclosure and parental knowledge regarding online activities: Social anxiety and parental rule-setting as moderators

Early adolescents spend a lot of time online, yet little is currently known about the links between parental rule-setting, adolescent disclosure about online activities, and whether social anxiety may interfere with these processes. Using a longitudinal sample of 526 adolescents (269 girls; Mage = 14.00) and their parents (79% mothers, Mage = 43.66), the results from the current study showed low correspondence between parental knowledge, adolescent disclosure, as well as parents’ and adolescents’ ratings of parental legitimacy to set boundaries about online activities. High social anxiety interacted with high adolescent-rated parental rule-setting in predicting the least disclosure about chatting with strangers and posting online content over time. Also, high social anxiety interacted with low parent-rated control to predict more adolescent disclosure about chatting with strangers and money spent online over time. Thus, social anxiety and parental rule-setting moderated the links between disclosure and knowledge for some early adolescent online activities. Our results conflict with the value typically placed on parental rule-setting in online contexts, at least for socially anxious adolescents

Forty years studying British politics : the decline of Anglo-America

The still present belief some 40 years ago that British politics was both exceptional and superior has been replaced by more theoretically sophisticated analyses based on a wider and more rigorously deployed range of research techniques, although historical analysis appropriately remains important. The American influence on the study of British politics has declined, but the European Union dimension has not been fully integrated. The study of interest groups has been in some respects a fading paradigm, but important questions related to democratic health have still to be addressed. Public administration has been supplanted by public policy, but economic policy remains under-studied. A key challenge for the future is the study of the management of expectations

Painful rib hump: a new clinical sign for detecting intraspinal rib displacement in scoliosis due to neurofibromatosis

BACKGROUND: Spinal cord compression and associate neurological impairment is rare in patients with scoliosis and neurofibromatosis. Common reasons are vertebral subluxation, dislocation, angulation and tumorous lesions around the spinal canal. Only twelve cases of intraspinal rib dislocation have been reported in the literature. The aim of this report is to present a case of rib penetration through neural foramen at the apex of a scoliotic curve in neurofibromatosis and to introduce a new clinical sign for its detection. METHODS: A 13-year-old girl was evaluated for progressive left thoracic kyphoscoliotic curve due to a type I neurofibromatosis. Clinical examination revealed multiple large thoracic and abdominal "cafe-au-lait" spots, neurological impairment of the lower limbs and the presence of a thoracic gibbous that was painful to pressure at the level of the left eighth rib (Painful Rib Hump). CT-scan showed detachment and translocation of the cephalic end of the left eighth rib into the adjacent enlarged neural foramen. The M.R.I. examination of the spine showed neither cord abnormality nor neurogenic tumor. RESULTS: The patient underwent resection of the intraspinal mobile eighth rib head and posterior spinal instrumentation and was neurologically fully recovered six months postoperatively. CONCLUSION: Spine surgeons should be aware of intraspinal rib displacement in scoliotic curves in neurofibromatosis. Painful rib hump is a valuable diagnostic tool for this rare clinical entity

A comparison of baseline methodologies for 'Reducing Emissions from Deforestation and Degradation'

<p>Abstract</p> <p>Background</p> <p>A mechanism for emission reductions from deforestation and degradation (REDD) is very likely to be included in a future climate agreement. The choice of REDD baseline methodologies will crucially influence the environmental and economic effectiveness of the climate regime. We compare three different historical baseline methods and one innovative dynamic model baseline approach to appraise their applicability under a future REDD policy framework using a weighted multi-criteria analysis.</p> <p>Results</p> <p>The results show that each baseline method has its specific strengths and weaknesses. Although the dynamic model allows for the best environmental and for comparatively good economic performance, its high demand for data and technical capacity limit the current applicability in many developing countries.</p> <p>Conclusion</p> <p>The adoption of a multi-tier approach will allow countries to select the baseline method best suiting their specific capabilities and data availability while simultaneously ensuring scientific transparency, environmental effectiveness and broad political support.</p

A comprehensive evaluation of SAM, the SAM R-package and a simple modification to improve its performance

<p>Abstract</p> <p>Background</p> <p>The Significance Analysis of Microarrays (SAM) is a popular method for detecting significantly expressed genes and controlling the false discovery rate (FDR). Recently, it has been reported in the literature that the FDR is not well controlled by SAM. Due to the vast application of SAM in microarray data analysis, it is of great importance to have an extensive evaluation of SAM and its associated R-package (sam2.20).</p> <p>Results</p> <p>Our study has identified several discrepancies between SAM and sam2.20. One major difference is that SAM and sam2.20 use different methods for estimating FDR. Such discrepancies may cause confusion among the researchers who are using SAM or are developing the SAM-like methods. We have also shown that SAM provides no meaningful estimates of FDR and this problem has been corrected in sam2.20 by using a different formula for estimating FDR. However, we have found that, even with the improvement sam2.20 has made over SAM, sam2.20 may still produce erroneous and even conflicting results under certain situations. Using an example, we show that the problem of sam2.20 is caused by its use of asymmetric cutoffs which are due to the large variability of null scores at both ends of the order statistics. An obvious approach without the complication of the order statistics is the conventional symmetric cutoff method. For this reason, we have carried out extensive simulations to compare the performance of sam2.20 and the symmetric cutoff method. Finally, a simple modification is proposed to improve the FDR estimation of sam2.20 and the symmetric cutoff method.</p> <p>Conclusion</p> <p>Our study shows that the most serious drawback of SAM is its poor estimation of FDR. Although this drawback has been corrected in sam2.20, the control of FDR by sam2.20 is still not satisfactory. The comparison between sam2.20 and the symmetric cutoff method reveals that the relative performance of sam2.20 to the symmetric cutff method depends on the ratio of induced to repressed genes in a microarray data, and is also affected by the ratio of DE to EE genes and the distributions of induced and repressed genes. Numerical simulations show that the symmetric cutoff method has the biggest advantage over sam2.20 when there are equal number of induced and repressed genes (i.e., the ratio of induced to repressed genes is 1). As the ratio of induced to repressed genes moves away from 1, the advantage of the symmetric cutoff method to sam2.20 is gradually diminishing until eventually sam2.20 becomes significantly better than the symmetric cutoff method when the differentially expressed (DE) genes are either all induced or all repressed genes. Simulation results also show that our proposed simple modification provides improved control of FDR for both sam2.20 and the symmetric cutoff method.</p