Expression of the alternative oxidase mitigates beta-amyloid production and toxicity in model systems

Mitochondrial dysfunction has been widely associated with the pathology of Alzheimer's disease, but there is no consensus on whether it is a cause or consequence of disease, nor on the precise mechanism(s). We addressed these issues by testing the effects of expressing the alternative oxidase AOX from Ciona intestinalis, in different models of AD pathology. AOX can restore respiratory electron flow when the cytochrome segment of the mitochondrial respiratory chain is inhibited, supporting ATP synthesis, maintaining cellular redox homeostasis and mitigating excess superoxide production at respiratory complexes I and III. In human HEK293-derived cells, AOX expression decreased the production of beta-amyloid peptide resulting from antimycin inhibition of respiratory complex III. Because hydrogen peroxide was neither a direct product nor substrate of AOX, the ability of AOX to mimic antioxidants in this assay must be indirect. In addition, AOX expression was able to partially alleviate the short lifespan of Drosophila models neuronally expressing human beta-amyloid peptides, whilst abrogating the induction of markers of oxidative stress. Our findings support the idea of respiratory chain dysfunction and excess ROS production as both an early step and as a pathologically meaningful target in Alzheimer's disease pathogenesis, supporting the concept of a mitochondrial vicious cycle underlying the disease. (C) 2016 The Authors. Published by Elsevier Inc.Peer reviewe

Stability and Evolution of Supernova Fallback Disks

We show that thin accretion disks made of Carbon or Oxygen are subject to the same thermal ionization instability as Hydrogen and Helium disks. We argue that the instability applies to disks of any metal content. The relevance of the instability to supernova fallback disks probably means that their power-law evolution breaks down when they first become neutral. We construct simple analytical models for the viscous evolution of fallback disks to show that it is possible for these disks to become neutral when they are still young (ages of a few 10^3 to 10^4 years), compact in size (a few 10^9 cm to 10^11 cm) and generally accreting at sub-Eddington rates (Mdot ~ a few 10^14 - 10^18 g/s). Based on recent results on the nature of viscosity in the disks of close binaries, we argue that this time may also correspond to the end of the disk activity period. Indeed, in the absence of a significant source of viscosity in the neutral phase, the entire disk will likely turn to dust and become passive. We discuss various applications of the evolutionary model, including anomalous X-ray pulsars and young radio pulsars. Our analysis indicates that metal-rich fallback disks around newly-born neutron stars and black holes become neutral generally inside the tidal truncation radius (Roche limit) for planets, at \~10^11 cm. Consequently, the efficiency of the planetary formation process in this context will mostly depend on the ability of the resulting disk of rocks to spread via collisions beyond the Roche limit. It appears easier for the merger product of a doubly degenerate binary, whether it is a massive white dwarf or a neutron star, to harbor planets because it can spread beyond the Roche limit before becoming neutral.[Abridged]Comment: 34 pages, 2 figures, accepted for publication in Ap

Identification of a 5-Protein Biomarker Molecular Signature for Predicting Alzheimer's Disease

Background: Alzheimer’s disease (AD) is a progressive brain disease with a huge cost to human lives. The impact of the disease is also a growing concern for the governments of developing countries, in particular due to the increasingly high number of elderly citizens at risk. Alzheimer’s is the most common form of dementia, a common term for memory loss and other cognitive impairments. There is no current cure for AD, but there are drug and non-drug based approaches for its treatment. In general the drug-treatments are directed at slowing the progression of symptoms. They have proved to be effective in a large group of patients but success is directly correlated with identifying the disease carriers at its early stages. This justifies the need for timely and accurate forms of diagnosis via molecular means. We report here a 5-protein biomarker molecular signature that achieves, on average, a 96% total accuracy in predicting clinical AD. The signature is composed of the abundances of IL-1α, IL-3, EGF, TNF-α and G-CSF. Methodology/Principal Findings: Our results are based on a recent molecular dataset that has attracted worldwide attention. Our paper illustrates that improved results can be obtained with the abundance of only five proteins. Our methodology consisted of the application of an integrative data analysis method. This four step process included: a) abundance quantization, b) feature selection, c) literature analysis, d) selection of a classifier algorithm which is independent of the feature selection process. These steps were performed without using any sample of the test datasets. For the first two steps, we used the application of Fayyad and Irani’s discretization algorithm for selection and quantization, which in turn creates an instance of the (alpha-beta)-k-Feature Set problem; a numerical solution of this problem led to the selection of only 10 proteins. Conclusions/Significance: the previous study has provided an extremely useful dataset for the identification of A biomarkers. However, our subsequent analysis also revealed several important facts worth reporting: 1. A 5-protein signature (which is a subset of the 18-protein signature of Ray et al.) has the same overall performance (when using the same classifier). 2. Using more than 20 different classifiers available in the widely-used Weka software package, our 5- protein signature has, on average, a smaller prediction error indicating the independence of the classifier and the robustness of this set of biomarkers (i.e. 96% accuracy when predicting AD against non-demented control). 3. Using very simple classifiers, like Simple Logistic or Logistic Model Trees, we have achieved the following results on 92 samples: 100 percent success to predict Alzheimer’s Disease and 92 percent to predict Non Demented Control on the AD dataset

Modelling vehicles acceleration during overtaking manoeuvres

[EN] Abstract: Overtaking manoeuvre is a key issue for two-lane rural roads. These roads should provide sufficient overtaking sight distance (OSD) at certain locations to allow faster vehicles to pass slower ones. However, overtaking requires occupying the opposing lane, which represents a serious safety concern. Severity of overtaking related crashes is very high, compared with other manoeuvres. The development of advanced driver assistance systems (ADAS) for overtaking is being a complex task. Only few systems have been developed, but are not still in use. This research incorporated accurate data of real manoeuvres to improve the knowledge of the phenomenon. The trajectory of the overtaking vehicles on the left lane was observed. An instrumented vehicle measured the overtaking time and distance, the abreast position, and the initial and final speed of 180 drivers that passed it during a field experiment. Six different kinematic models (such as uniform acceleration or linear variation of acceleration) were calibrated. Generally, drivers started to accelerate before changing to the opposing lane. These models may be applied to ADAS, to estimate OSD and to improve microsimulation models.Part of this research was included in the project 'Desarrollo de modelos de distancias de visibilidad de adelantamiento', with reference code TRA2010-21736 and subsidised by the Spanish Ministery of Economy and Competitivity. The authors also thank Prof Dr Sayed, from University of British Columbia, for his valuable review.Llorca Garcia, C.; Moreno, AT.; García García, A. (2016). Modelling vehicles acceleration during overtaking manoeuvres. IET Intelligent Transport Systems. 10(3):206-215. https://doi.org/10.1049/iet-its.2015.0035S206215103Gray, R., & Regan, D. M. (2005). Perceptual Processes Used by Drivers During Overtaking in a Driving Simulator. Human Factors: The Journal of the Human Factors and Ergonomics Society, 47(2), 394-417. doi:10.1518/0018720054679443Basilio, N., Morice, A. H. P., Marti, G., & Montagne, G. (2015). High- and Low-Order Overtaking-Ability Affordances. Human Factors: The Journal of the Human Factors and Ergonomics Society, 57(5), 879-894. doi:10.1177/0018720815583581Morice, A. H. P., Diaz, G. J., Fajen, B. R., Basilio, N., & Montagne, G. (2015). An Affordance-Based Approach to Visually Guided Overtaking. Ecological Psychology, 27(1), 1-25. doi:10.1080/10407413.2015.991641Farah, H., Bekhor, S., & Polus, A. (2009). Risk evaluation by modeling of passing behavior on two-lane rural highways. Accident Analysis & Prevention, 41(4), 887-894. doi:10.1016/j.aap.2009.05.006Hassan, Y., Easa, S. M., & El Halim, A. O. A. (1996). Passing sight distance on two-lane highways: Review and revision. Transportation Research Part A: Policy and Practice, 30(6), 453-467. doi:10.1016/0965-8564(95)00032-1Wang, Y., & Cartmell, M. P. (1998). New Model for Passing Sight Distance on Two-Lane Highways. Journal of Transportation Engineering, 124(6), 536-545. doi:10.1061/(asce)0733-947x(1998)124:6(536)Sparks, G. A., Neudorf, R. D., Robinson, J. B. L., & Good, D. (1993). Effect of Vehicle Length on Passing Operations. Journal of Transportation Engineering, 119(2), 272-283. doi:10.1061/(asce)0733-947x(1993)119:2(272)Hanley, P. F., & Forkenbrock, D. J. (2005). Safety of passing longer combination vehicles on two-lane highways. Transportation Research Part A: Policy and Practice, 39(1), 1-15. doi:10.1016/j.tra.2004.09.001Khoury, J. E., & Hobeika, A. G. (2012). Integrated Stochastic Approach for Risk and Service Estimation: Passing Sight Distance Application. Journal of Transportation Engineering, 138(5), 571-579. doi:10.1061/(asce)te.1943-5436.0000366Jenkins, J. M., & Rilett, L. R. (2004). Application of Distributed Traffic Simulation for Passing Behavior Study. Transportation Research Record: Journal of the Transportation Research Board, 1899(1), 11-18. doi:10.3141/1899-02Rakha, H., Ahn, K., & Trani, A. (2004). Development of VT-Micro model for estimating hot stabilized light duty vehicle and truck emissions. Transportation Research Part D: Transport and Environment, 9(1), 49-74. doi:10.1016/s1361-9209(03)00054-3Polus, A., Livneh, M., & Frischer, B. (2000). Evaluation of the Passing Process on Two-Lane Rural Highways. Transportation Research Record: Journal of the Transportation Research Board, 1701(1), 53-60. doi:10.3141/1701-07Harwood, D. W., Gilmore, D. K., & Richard, K. R. (2010). Criteria for Passing Sight Distance for Roadway Design and Marking. Transportation Research Record: Journal of the Transportation Research Board, 2195(1), 36-46. doi:10.3141/2195-05Hegeman, G., Tapani, A., & Hoogendoorn, S. (2009). Overtaking assistant assessment using traffic simulation. Transportation Research Part C: Emerging Technologies, 17(6), 617-630. doi:10.1016/j.trc.2009.04.010Milanés, V., Llorca, D. F., Villagrá, J., Pérez, J., Fernández, C., Parra, I., … Sotelo, M. A. (2012). Intelligent automatic overtaking system using vision for vehicle detection. Expert Systems with Applications, 39(3), 3362-3373. doi:10.1016/j.eswa.2011.09.024Isermann, R., Mannale, R., & Schmitt, K. (2012). Collision-avoidance systems PRORETA: Situation analysis and intervention control. Control Engineering Practice, 20(11), 1236-1246. doi:10.1016/j.conengprac.2012.06.003Petrov, P., & Nashashibi, F. (2014). Modeling and Nonlinear Adaptive Control for Autonomous Vehicle Overtaking. IEEE Transactions on Intelligent Transportation Systems, 15(4), 1643-1656. doi:10.1109/tits.2014.2303995Llorca, C., & García, A. (2011). Evaluation of Passing Process on Two-Lane Rural Highways in Spain with New Methodology Based on Video Data. Transportation Research Record: Journal of the Transportation Research Board, 2262(1), 42-51. doi:10.3141/2262-05Llorca, C., Moreno, A. T., García, A., & Pérez-Zuriaga, A. M. (2013). Daytime and Nighttime Passing Maneuvers on a Two-Lane Rural Road in Spain. Transportation Research Record: Journal of the Transportation Research Board, 2358(1), 3-11. doi:10.3141/2358-01Llorca, C., Moreno, A. T., Pérez-Zuriaga, A. M., & García, A. (2013). Influence of age, gender and delay on overtaking dynamics. IET Intelligent Transport Systems, 7(2), 174-181. doi:10.1049/iet-its.2012.0147Khoury, J. E., & Hobeika, A. (2007). Incorporating Uncertainty into the Estimation of the Passing Sight Distance Requirements. Computer-Aided Civil and Infrastructure Engineering, 22(5), 347-357. doi:10.1111/j.1467-8667.2007.00491.xRakha, H., Snare, M., & Dion, F. (2004). Vehicle Dynamics Model for Estimating Maximum Light-Duty Vehicle Acceleration Levels. Transportation Research Record: Journal of the Transportation Research Board, 1883(1), 40-49. doi:10.3141/1883-05Fitzpatrick, K., Chrysler, S. T., & Brewer, M. (2012). Deceleration Lengths for Exit Terminals. Journal of Transportation Engineering, 138(6), 768-775. doi:10.1061/(asce)te.1943-5436.000038

Design Criteria for Minimum Passing Zone Lengths: Operational Efficiency and Safety Considerations

Passing zones are provided to improve operational efficiency of two-lane highways where passes can be performed safely. Minimum passing zone lengths of 120 m were established in MUTCD and Green Book, although some studies indicate a potential need to increase them. However, no changes have been recommended pending further research on the safety of short passing zones. The objective of this study is to develop design and marking criteria for minimum passing zone lengths that consider traffic operational efficiency and safety. In the first part of this study, a traffic microsimulation was carried out with Aimsun software. The calibration and validation included the observation of 1,750 passing maneuvers in Spain. The results indicate that passing zones shorter than 250 m add very little to operational efficiency. In the second part of the study, a reliability analysis was applied. It quantified the probability that a passing maneuver was completed beyond the end of the passing zone (noncompliant passing maneuvers). Afterwards, the number of non-compliant passing maneuvers was calculated. Traffic flow as well as passing zone length were contributing factors.. Findings from the analysis indicate that the minimum passing zone length should be increased to a minimum of 275 m, for high traffic volumes, 300 m for medium traffic volumes and 350 m for low traffic volumes. From this length, the number of non-compliant passing maneuvers decreases. The marginal increase in the minimum length of passing zones can potentially improve safety without significantly reducing the operational efficiency. The results can be directly used by practitioners to establish the minimum passing zone length based on the range of hourly volumes and the level of risk willing to assume.The authors thank the Spanish Ministry of Science and Innovation, which subsidizes the research project Estudio Experimental de la Funcionalidad y Seguridad de las Carreteras Convencionales (experimental study on road safety and traffic operation on two-lane rural roads).Moreno Chou, AT.; Llorca Garcia, C.; Lenorzer, A.; Casas, J.; García García, A. (2015). Design Criteria for Minimum Passing Zone Lengths: Operational Efficiency and Safety Considerations. Transportation Research Record. 2486:19-27. doi:10.3141/2486-03S1927248

Gender perspectives on views and preferences of older people on exercise to prevent falls: a systematic mixed studies review

Background: To offer fall prevention exercise programs that attract older people of both sexes there is a need to understand both womens and mens views and preferences regarding these programs. This paper aims to systematically review the literature to explore any underlying gender perspectives or gender interpretations on older peoples views or preferences regarding uptake and adherence to exercise to prevent falls. Methods: A review of the literature was carried out using a convergent qualitative design based on systematic searches of seven electronic databases (PubMed, CINAHL, Amed, PsycINFO, Scopus, PEDro, and OTseeker). Two investigators identified eligible studies. Each included article was read by at least two authors independently to extract data into tables. Views and preferences reported were coded and summarized in themes of facilitators and barriers using a thematic analysis approach. Results: Nine hundred and nine unique studies were identified. Twenty five studies met the criteria for inclusion. Only five of these contained a gender analysis of mens and womens views on fall prevention exercises. The results suggests that both women and men see women as more receptive to and in more need of fall prevention messages. The synthesis from all 25 studies identified six themes illustrating facilitators and six themes describing barriers for older people either starting or adhering to fall prevention exercise. The facilitators were: support from professionals or family; social interaction; perceived benefits; a supportive exercise context; feelings of commitment; and having fun. Barriers were: practical issues; concerns about exercise; unawareness; reduced health status; lack of support; and lack of interest. Considerably more women than men were included in the studies. Conclusion: Although there is plenty of information on the facilitators and barriers to falls prevention exercise in older people, there is a distinct lack of studies investigating differences or similarities in older womens and mens views regarding fall prevention exercise. In order to ensure that fall prevention exercise is appealing to both sexes and that the inclusion of both men and women are encouraged, more research is needed to find out whether gender differences exists and whether practitioners need to offer a range of opportunities and support strategies to attract both women and men to falls prevention exercise.Funding Agencies|Swedish Research Council [2015-03481]; Strategic Research Programme in Care Sciences, Umea University; Karolinska Institute, Sweden; Umea University</p

Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats

This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy, and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets

Lay perceptions of predictive testing for diabetes based on DNA test results versus family history assessment: a focus group study

<p>Abstract</p> <p>Background</p> <p>This study assessed lay perceptions of issues related to predictive genetic testing for multifactorial diseases. These perceived issues may differ from the "classic" issues, e.g. autonomy, discrimination, and psychological harm that are considered important in predictive testing for monogenic disorders. In this study, type 2 diabetes was used as an example, and perceptions with regard to predictive testing based on DNA test results and family history assessment were compared.</p> <p>Methods</p> <p>Eight focus group interviews were held with 45 individuals aged 35-70 years with (n = 3) and without (n = 1) a family history of diabetes, mixed groups of these two (n = 2), and diabetes patients (n = 2). All interviews were transcribed and analysed using Atlas-ti.</p> <p>Results</p> <p>Most participants believed in the ability of a predictive test to identify people at risk for diabetes and to motivate preventive behaviour. Different reasons underlying motivation were considered when comparing DNA test results and a family history risk assessment. A perceived drawback of DNA testing was that diabetes was considered not severe enough for this type of risk assessment. In addition, diabetes family history assessment was not considered useful by some participants, since there are also other risk factors involved, not everyone has a diabetes family history or knows their family history, and it might have a negative influence on family relations. Respect for autonomy of individuals was emphasized more with regard to DNA testing than family history assessment. Other issues such as psychological harm, discrimination, and privacy were only briefly mentioned for both tests.</p> <p>Conclusion</p> <p>The results suggest that most participants believe a predictive genetic test could be used in the prevention of multifactorial disorders, such as diabetes, but indicate points to consider before both these tests are applied. These considerations differ with regard to the method of assessment (DNA test or obtaining family history) and also differ from monogenic disorders.</p