| 1. |
- Cummings, Damian M, et al.
(författare)
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First effects of rising amyloid-β in transgenic mouse brain: synaptic transmission and gene expression.
- 2015
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 138:Pt 7, s. 1992-2004
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Tidskriftsartikel (refereegranskat)abstract
- Detecting and treating Alzheimer's disease, before cognitive deficits occur, has become the health challenge of our time. The earliest known event in Alzheimer's disease is rising amyloid-β. Previous studies have suggested that effects on synaptic transmission may precede plaque deposition. Here we report how relative levels of different soluble amyloid-β peptides in hippocampus, preceding plaque deposition, relate to synaptic and genomic changes. Immunoprecipitation-mass spectrometry was used to measure the early rise of different amyloid-β peptides in a mouse model of increasing amyloid-β ('TASTPM', transgenic for familial Alzheimer's disease genes APP/PSEN1). In the third postnatal week, several amyloid-β peptides were above the limit of detection, including amyloid-β40, amyloid-β38 and amyloid-β42 with an intensity ratio of 6:3:2, respectively. By 2 months amyloid-β levels had only increased by 50% and although the ratio of the different peptides remained constant, the first changes in synaptic currents, compared to wild-type mice could be detected with patch-clamp recordings. Between 2 and 4 months old, levels of amyloid-β40 rose by ∼7-fold, but amyloid-β42 rose by 25-fold, increasing the amyloid-β42:amyloid-β40 ratio to 1:1. Only at 4 months did plaque deposition become detectable and only in some mice; however, synaptic changes were evident in all hippocampal fields. These changes included increased glutamate release probability (P < 0.001, n = 7-9; consistent with the proposed physiological effect of amyloid-β) and loss of spontaneous action potential-mediated activity in the cornu ammonis 1 (CA1) and dentate gyrus regions of the hippocampus (P < 0.001, n = 7). Hence synaptic changes occur when the amyloid-β levels and amyloid-β42:amyloid-β40 ratio are still low compared to those necessary for plaque deposition. Genome-wide microarray analysis revealed changes in gene expression at 2-4 months including synaptic genes being strongly affected but often showing significant changes only by 4 months. We thus demonstrate that, in a mouse model of rising amyloid-β, the initial deposition of plaques does not occur until several months after the first amyloid-β becomes detectable but coincides with a rapid acceleration in the rise of amyloid-β levels and the amyloid-β42:amyloid-β40 ratio. Prior to acceleration, however, there is already a pronounced synaptic dysfunction, reflected as changes in synaptic transmission and altered gene expression, indicating that restoring synaptic function early in the disease progression may represent the earliest possible target for intervention in the onset of Alzheimer's disease.
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| 2. |
- Hadi, Sinan Jasim, et al.
(författare)
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Non-linear input variable selection approach integrated with non-tuned data intelligence model for streamflow pattern simulation
- 2019
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Ingår i: IEEE Access. - USA : IEEE. - 2169-3536. ; 7, s. 141533-141548
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Tidskriftsartikel (refereegranskat)abstract
- Streamflow modeling is considered as an essential component for water resources planning and management. There are numerous challenges related to streamflow prediction that are facing water resources engineers. These challenges due to the complex processes associated with several natural variables such as non-stationarity, non-linearity, and randomness. In this study, a new model is proposed to predict long-term streamflow. Several lags that cover several years are abstracted using the potential of Extreme Gradient Boosting (XGB) then after the selected inputs variables are imposed into the predictive model (i.e., Extreme Learning Machine (ELM)). The proposed model is compared with the stand-alone schema in which the optimum lags of the variables are supplied into the XGB and ELM models. Hydrological variables including rainfall, temperature and evapotranspiration are used to build the model and predict the streamflow at Goksu-Himmeti basin in Turkey. The results showed that XGB model performed an excellent result in which can be used for predicting the streamflow pattern. Also, it is clear from the attained results that the accuracy of the streamflow prediction using XGB technique could be improved when the high number of lags was used. However, the implementation of the XGB is tree-based technique in which several issues could be raised such as overfitting problem. The proposed schema XGBELM in which XGB approach is selected the correlated inputs and ranking them according to their importance; then after, the selected inputs are supplied into the ELM model for the prediction process. The XGBELM model outperformed the stand-alone schema of both XGB and ELM models and the high-lagged schema of the XGB. It is important to indicate that the XGBELM model found to improve the prediction ability with minimum variables number.
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| 3. |
- Hulsart-Billström, Gry, et al.
(författare)
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A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration : Results of a multicentre analysis
- 2016
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Ingår i: European Cells & Materials. - 1473-2262. ; 31, s. 312-322
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Tidskriftsartikel (refereegranskat)abstract
- New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines.
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| 4. |
- Muschitiello, Francesco, et al.
(författare)
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Fennoscandian freshwater control on Greenland hydroclimate shifts at the onset of the Younger Dryas
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Sources and timing of freshwater forcing relative to hydroclimate shifts recorded in Greenland ice cores at the onset of Younger Dryas, similar to 12,800 years ago, remain speculative. Here we show that progressive Fennoscandian Ice Sheet (FIS) melting 13,100-12,880 years ago generates a hydroclimate dipole with drier-colder conditions in Northern Europe and wetter-warmer conditions in Greenland. FIS melting culminates 12,880 years ago synchronously with the start of Greenland Stadial 1 and a large-scale hydroclimate transition lasting similar to 180 years. Transient climate model simulations forced with FIS freshwater reproduce the initial hydroclimate dipole through sea-ice feedbacks in the Nordic Seas. The transition is attributed to the export of excess sea ice to the subpolar North Atlantic and a subsequent southward shift of the westerly winds. We suggest that North Atlantic hydroclimate sensitivity to FIS freshwater can explain the pace and sign of shifts recorded in Greenland at the climate transition into the Younger Dryas.
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| 5. |
- Salih, Abubakr A. M., et al.
(författare)
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Sources of Sahelian-Sudan moisture : Insights from a moisture-tracing atmospheric model
- 2016
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Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 121:13, s. 7819-7832
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Tidskriftsartikel (refereegranskat)abstract
- The summer rainfall across Sahelian-Sudan is one of the main sources of water for agriculture, human, and animal needs. However, the rainfall is characterized by large interannual variability, which has attracted extensive scientific efforts to understand it. This study attempts to identify the source regions that contribute to the Sahelian-Sudan moisture budget during July through September. We have used an atmospheric general circulation model with an embedded moisture-tracing module (Community Atmosphere Model version 3), forced by observed (1979-2013) sea-surface temperatures. The result suggests that about 40% of the moisture comes with the moisture flow associated with the seasonal migration of the Intertropical Convergence Zone (ITCZ) and originates from Guinea Coast, central Africa, and the Western Sahel. The Mediterranean Sea, Arabian Peninsula, and South Indian Ocean regions account for 10.2%, 8.1%, and 6.4%, respectively. Local evaporation and the rest of the globe supply the region with 20.3% and 13.2%, respectively. We also compared the result from this study to a previous analysis that used the Lagrangian model FLEXPART forced by ERA-Interim. The two approaches differ when comparing individual regions, but are in better agreement when neighboring regions of similar atmospheric flow features are grouped together. Interannual variability with the rainfall over the region is highly correlated with contributions from regions that are associated with the ITCZ movement, which is in turn linked to the Atlantic Multidecadal Oscillation. Our result is expected to provide insights for the effort on seasonal forecasting of the rainy season over Sahelian Sudan.
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