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Anna Bauereiss Oliver Welzel Jasmin Jung Simon Grosse‐Holz Natalia Lelental Piotr Lewczuk Eva M. Wenzel Johannes Kornhuber Teja W. Groemer 《Traffic (Copenhagen, Denmark)》2015,16(6):655-675
Amyloid‐β (Aβ)‐peptide, the major constituent of the plaques that develop during Alzheimer's disease, is generated via the cleavage of Aβ precursor protein (APP) by β‐site APP‐cleaving enzyme (BACE). Using live‐cell imaging of APP and BACE labeled with pH‐sensitive proteins, we could detect the release events of APP and BACE and their distinct kinetics. We provide kinetic evidence for the cleavage of APP by α‐secretase on the cellular surface after exocytosis. Furthermore, simultaneous dual‐color evanescent field illumination revealed that the two proteins are trafficked to the surface in separate compartments. Perturbing the membrane lipid composition resulted in a reduced frequency of exocytosis and affected BACE more strongly than APP. We propose that surface fusion frequency is a key factor regulating the aggregation of APP and BACE in the same membrane compartment and that this process can be modulated via pharmacological intervention. 相似文献
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Oliver W. Howarth 《Molecular Engineering》1993,3(1-3):131-140
A range of 1D and 2D NMR methods has been developed for the investigation of polyoxometallate solutions, to complement and extend the insights obtained from crystallography and potentiometry. Static, dynamic and structural information can be obtained from1H,17O,51V and183W NMR. Applications are given in the elucidation of the structures and chemical interrelationships of isopolytungstates and vanadates, molybdotungstates, tungstovanadates and molybdovanadates. 相似文献
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Aysun Çapcı Karagöz Christoph Reiter Ean-Jeong Seo Lisa Gruber Friedrich Hahn Maria Leidenberger Volker Klein Frank Hampel Oliver Friedrich Manfred Marschall Barbara Kappes Thomas Efferth Svetlana B. Tsogoeva 《Bioorganic & medicinal chemistry》2018,26(12):3610-3618
Hybridization of natural products has high potential to further improve their activities and may produce synergistic effects between linked pharmacophores. Here we report synthesis of nine new hybrids of natural products egonol, homoegonol, thymoquinone and artemisinin and evaluation of their activities against P. falciparum 3D7 parasites, human cytomegalovirus, sensitive and multidrug-resistant human leukemia cells. Most of the new hybrids exceed their parent compounds in antimalarial, antiviral and antileukemia activities and in some cases show higher in vitro efficacy than clinically used reference drugs chloroquine, ganciclovir and doxorubicin. Combined, our findings stress the high potency of these hybrids and encourages further use of the hybridization concept in applied pharmacological research. 相似文献
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Selene Báez Agustina Malizia Julieta Carilla Cecilia Blundo Manuel Aguilar Nikolay Aguirre Zhofre Aquirre Esteban álvarez Francisco Cuesta álvaro Duque William Farfán-Ríos Karina García-Cabrera Ricardo Grau Jürgen Homeier Reynaldo Linares-Palomino Lucio R. Malizia Omar Melo Cruz Oriana Osinaga Oliver L. Phillips Carlos Reynel Miles R. Silman Kenneth J. Feeley 《PloS one》2015,10(5)
General patterns of forest dynamics and productivity in the Andes Mountains are poorly characterized. Here we present the first large-scale study of Andean forest dynamics using a set of 63 permanent forest plots assembled over the past two decades. In the North-Central Andes tree turnover (mortality and recruitment) and tree growth declined with increasing elevation and decreasing temperature. In addition, basal area increased in Lower Montane Moist Forests but did not change in Higher Montane Humid Forests. However, at higher elevations the lack of net basal area change and excess of mortality over recruitment suggests negative environmental impacts. In North-Western Argentina, forest dynamics appear to be influenced by land use history in addition to environmental variation. Taken together, our results indicate that combinations of abiotic and biotic factors that vary across elevation gradients are important determinants of tree turnover and productivity in the Andes. More extensive and longer-term monitoring and analyses of forest dynamics in permanent plots will be necessary to understand how demographic processes and woody biomass are responding to changing environmental conditions along elevation gradients through this century. 相似文献
8.
Gera A. de Haan Bart J. M. Melis-Dankers Wiebo H. Brouwer Oliver Tucha Joost Heutink 《PloS one》2015,10(8)
IntroductionHomonymous visual field defects (HVFD) are a common consequence of postchiasmatic acquired brain injury and often lead to mobility-related difficulties. Different types of compensatory scanning training have been developed, aimed at decreasing consequences of the HVFD by changing visual scanning.AimThe aim of the present study is to examine the effects of a compensatory scanning training program using horizontal scanning on mobility-related activities and participation in daily life.MethodThe main interest of this study is to assess the effectiveness of training on mobility-related activities and participation in daily life. Visual scanning tests, such as dot counting and visual search, and control measures for visual functions and reading have been included as well. First, it is examined how performance on scanning and mobility-related measures is affected in patients with HVFD by comparing scores with scores of a healthy control group (n = 25). Second, the effect of training is assessed using an RCT design, in which performance of 26 patients before and after training is compared to performance of 23 patients in a waiting list control group.ResultsSelf-reported improvements after training were found, accompanied by improvements in detecting peripheral stimuli and avoiding obstacles during walking, especially in dual task situations in which a second task limits the attentional capacity available for compensatory scanning. Training only improved mobility-related activities in which detection of peripheral stimuli is important, while no improvement was found on tests that require other visual skills, such as reading, visual counting and visual search.ConclusionThis is the first RCT to evaluate the effects of a compensatory scanning training that is based on a systematic horizontal scanning rhythm. This training improved mobility-related activities. The results suggest that different types of compensatory scanning strategies are appropriate for different types of activities.
Trial Registration
ISRCTN Registry ISRCTN16833414 相似文献9.
This study measured changes in switches of attention between 1 and 9 months of age in 67 typically developing infants. Remote eye-tracking (Tobii X120) was used to measure saccadic latencies, related to switches of fixation, as a measure of shifts of attention, from a central stimulus to a peripheral visual target, measured in the Fixation Shift Paradigm. Fixation shifts occur later if the central fixation stimulus stays visible when the peripheral target appears (competition condition), than if the central stimulus disappears as the peripheral target appears (non-competition condition). This difference decreases with age. Our results show significantly faster disengagement in infants over 4 months than in the younger group, and provide more precise measures of fixation shifts, than behavioural observation with the same paradigm. Reduced saccadic latencies in the course of a test session indicate a novel learning effect. The Fixation Shift Paradigm combined with remote eye-tracking measures showed improved temporal and spatial accuracy compared to direct observation by a trained observer, and allowed an increased number of trials in a short testing time. This makes it an infant-friendly non-invasive procedure, involving minimal observational training, suitable for use in future studies of clinical populations to detect early attentional abnormalities in the first few months of life. 相似文献
10.
Elie A. Akl Fadi El-Jardali Lama Bou Karroum Jamale El-Eid Hneine Brax Chaza Akik Mona Osman Ghayda Hassan Mira Itani Aida Farha Kevin Pottie Sandy Oliver 《PloS one》2015,10(9)