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Amyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer Disease. In situ identification of early-stage amyloid aggregates in Alzheimer’s disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months. A significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with poly(propylene imine) dendrimers with histidine-maltose shell (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating their putative therapeutic properties of in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques.

With the rapid development of urbanization, the ecological environment is being degraded. Taking the Barcelona Metropolitan Region as an example, this paper developed an ecological environment quality-assessment system suitable for different times and regions, based on remote sensing, to evaluate the quality of the ecological environment from 2006 to 2018. We also built various ordinary least squares models to analyze multiple variables affecting the ecological environment. Finally, the characteristic triangular spatial structure was used to explain the interaction between the two key variables. The results showed that the ecological quality was unevenly distributed. The largest green space contributed the most benefits but was decreasing and becoming fragmented. NDVI (normalized difference vegetation index) was the most significant natural variable related to the distribution of green space. Precipitation was the most closely related climate factor to NDVI. There was a complex two-way interaction mechanism between the two, and its boundary value was getting higher and higher. In conclusion, the environmental quality of the BMR needs improvement. The characteristic triangle can effectively explain the interaction mechanism between precipitation and NDVI. This study deeply analyzes how various factors affect environmental quality from both the global and internal perspectives and provides a scientific basis for urban ecological management and sustainable development.

This paper seeks to extend the definition of a sub-centre beyond the usual definition as a place with significantly larger employment density that has an effect on the overall employment density of the nearby locations. Together with the previous conditions, it is suggested that it is necessary to include another which represents a structural element of an urban sub-system within the metropolitan configuration—that is, a place with intense spatial interaction with its hinterland. Therefore, a metropolitan area can be seen as one comprising urban sub-systems characterised by greater or lesser polycentrism. In this paper, a 'bottom-up' methodology based on commuter flows is proposed in order to detect metropolitan sub-centres. Using empirical data from the Metropolitan Region of Barcelona, the proposed methodology is tested, comparing its results with those of other commonly used methodologies (cut-offs, parametric and non-parametric models). The results suggest that the proposed methodology permits optimising the sub-centre delimitation process.

Amyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer's disease. In situ identification of early-stage amyloid aggregates in Alzheimer's disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice and Octodon degus for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months whereas very little formation of fibrils is found in aged Octodon degus. Finally, significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with G4-His-Mal dendrimers (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating putative therapeutic properties of G4-His-Mal dendrimers in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques.

Heterologous expression of human membrane proteins is a challenge in structural biology towards drug discovery. Here we report a complete expression and purification process of a functional human sodium/D-glucose co-transporter 1 (hSGLT1) in Pichia pastoris as representative example of a useful strategy for any human membrane protein. hSGLT1 gene was cloned in two different plasmids to develop parallel strategies: one which includes green fluorescent protein fusion for screening optimal conditions, and another for large scale protein production for structural biology and biophysics studies. Our strategy yields at least 1 mg of monodisperse purified recombinant hSGLT1 per liter of culture, which can be characterized by circular dichroism and infrared spectroscopy as an alpha-helical fold protein. This purified hSGLT1 transports co-substrates (Na + and glucose) and it is inhibited by phlorizin in electrophysiological experiments performed in planar lipid membranes.

Editor's Note: this Article has been retracted; the Retraction Note is available at https://www.nature.com/articles/s41598-020-76208-w.Editor's Note: this Article has been retracted; the Retraction Note is available at https://www.nature.com/articles/s41598-020-76208-w.

Amyloid plaques composed of Aβ amyloid peptides and neurofibrillary tangles are a pathological hallmark of Alzheimer’s disease. In situ identification of early-stage amyloid aggregates in Alzheimer’s disease is relevant for their importance as potential targets for effective drugs. Synchrotron-based infrared imaging is here used to identify early-stage oligomeric/granular aggregated amyloid species in situ in the brain of APP/PS1 transgenic mice and Octodon degus for the first time. Also, APP/PS1 mice show fibrillary aggregates at 6 and 12 months whereas very little formation of fibrils is found in aged Octodon degus . Finally, significant decreased burden of early-stage aggregates and fibrillary aggregates is obtained following treatment with G4-His-Mal dendrimers (a neurodegenerative protector) in 6-month-old APP/PS1 mice, thus demonstrating putative therapeutic properties of G4-His-Mal dendrimers in AD models. Identification, localization, and characterization using infrared imaging of these non-fibrillary species in the cerebral cortex at early stages of AD progression in transgenic mice point to their relevance as putative pharmacological targets. No less important, early detection of these structures may be useful in the search for markers for non-invasive diagnostic techniques.

Structural analysis of biological membranes is important for understanding cell and sub-cellular organelle function as well as their interaction with the surrounding environment. Imaging of whole cells in three dimension at high spatial resolution remains a significant challenge, particularly for thick cells. Cryo-transmission soft X-ray microscopy (cryo-TXM) has recently gained popularity to image, in 3D, intact thick cells (∼10μm) with details of sub-cellular architecture and organization in near-native state. This paper reports a new tool to segment and quantify structural changes of biological membranes in 3D from cryo-TXM images by tracking an initial 2D contour along the third axis of the microscope, through a multi-scale ridge detection followed by an active contours-based model, with a subsequent refinement along the other two axes. A quantitative metric that assesses the grayscale profiles perpendicular to the membrane surfaces is introduced and shown to be linearly related to the membrane thickness. Our methodology has been validated on synthetic phantoms using realistic microscope properties and structure dimensions, as well as on real cryo-TXM data. Results demonstrate the validity of our algorithms for cryo-TXM data analysis.

En el presente documento se reportan los resultados obtenidos en el análisis multicriterio CRITIC y espacial realizado a 1062 viviendas en Mazatlán, Sinaloa (México); asimismo, se especifican las variables que conforman el Valor Catastral para cada una de las categorías catastrales de vivienda que van de M2 hasta M7, establecidas en el Instructivo de Valuación del estado de Sinaloa; donde se obtuvieron las ponderaciones de cada criterio y la información con la que se analiza la situación actual de influencia de cada variable y cómo, a partir de estos datos, se puede demostrar la inequidad al obtener el valor catastral de vivienda.

Homeostasis is crucial for cell function, and disturbances in homeostasis can lead to health disorders. Under normal conditions, intracellular pH is maintained between 7.35 and 7.45. Altered endosomal and lysosomal pH together with a general drop in brain pH are associated with the aggregation of amyloid-β-peptide (Aβ) and the development of Alzheimer’s disease. Under acidic conditions, close to the Aβ isoelectric point, the absence of charges favors the formation of intermolecular contacts and promotes aggregation. Here, we analyzed how pH levels affect the aggregation of Aβ40 considering the variations in brain pH and the coexistence of different aggregated conformations. Our results suggest that different macromolecular conformations can interact with each other and influence the aggregation process. In addition, we showed that neutral pH and physiological salt concentrations favor a slow aggregation, resulting in ordered, stable fibrils, with low cytotoxic effects. Overall, we highlight the complexity of the aggregation processes occurring in different physiological and pathological environments.