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https://www.readbyqxmd.com/read/28328396/improved-medication-adherence-and-frequency-of-blood-glucose-self-testing-using-an-m-health-platform-versus-usual-care-in-a-multisite-randomized-clinical-trial-among-people-with-type-2-diabetes-in-india
#1
Nora J Kleinman, Avani Shah, Sanjiv Shah, Sanjeev Phatak, Vijay Viswanathan
BACKGROUND: In 2015, India had an estimated 69.2 million people with diabetes and a national prevalence of 8.7%. Evidence is mounting for the benefits of telemedicine in diabetes care, but remains limited on mobile-health (m-Health) interventions. INTRODUCTION: This study assessed the impact of an m-Health diabetes platform on clinical outcomes, patient-reported outcomes, patient and provider satisfaction, and app usage. MATERIALS AND METHODS: This open-label, two-arm parallel study enrolled 91 people at 3 sites in India, aged 18-65, with type 2 diabetes, and an A1c between 7...
March 6, 2017: Telemedicine Journal and E-health: the Official Journal of the American Telemedicine Association
https://www.readbyqxmd.com/read/28314820/amyloid-precursor-protein-in-drosophila-glia-regulates-sleep-and-genes-involved-in-glutamate-recycling
#2
Abud Jose Farca Luna, Magali Perier, Laurent Seugnet
The Amyloid Precursor Protein (App) plays a crucial role in Alzheimer disease (AD) via the production and deposition of toxic β-amyloid peptides. App is heavily expressed in neurons where the vast majority of studies investigating its function have been carried out, while almost nothing is known about its function in glia, where it is also expressed, and can potentially participate in the regulation of neuronal physiology. In this report, we investigated whether Appl, the Drosophila homolog of App, could influence sleep-wake regulation when its function is manipulated in glial cells...
March 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28299779/the-related-neuronal-endosomal-proteins-neep21-nsg1-and-p19-nsg2-have-divergent-expression-profiles-in-vivo
#3
Kelly Barford, Chan Choo Yap, Noelle D Dwyer, Bettina Winckler
Endosomal maturation and transport constitutes a complex trafficking system present in all cell types. Neurons have adapted their endosomal system to meet their unique and complex needs. These adaptations include repurposing existing proteins to diversify endocytosis and trafficking, as well as preferential expression of certain regulators more highly in neurons than other cell types. These neuronal regulators include the family of Neuron-Specific Gene family members (Nsg), NEEP21 (Nsg1), and P19 (Nsg2). NEEP21/Nsg1 plays a role in the trafficking of multiple receptors, including the cell adhesion molecule L1/NgCAM, the neurotransmitter receptor GluA2, and β-APP...
March 15, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28298292/cellular-cholesterol-homeostasis-in-alzheimer-s-disease
#4
Ta Yuan Chang, Yoshio Yamauchi, Mazahir Hasan, Catherine Cy Chang
Alzheimer's disease [AD] is the most common form of dementia in older adults. Currently, there is no cure for AD. The hallmark of AD is the accumulation of extracellular amyloid plaques composed of amyloid beta peptides [Abeta; especially Abeta1-42], and neurofibrillary tangles, composed of hyper-phosphorylated tau, accompanied with chronic neuroinflammation. Abeta are derived from the amyloid precursor protein APP. The oligomeric form of Abeta is probably the most neurotoxic species; its accumulation eventually forms the insoluble and aggregated amyloid plaques...
March 15, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28282865/utilizing-crowdsourced-data-for-studies-of-cycling-and-air-pollution-exposure-a-case-study-using-strava-data
#5
Yeran Sun, Amin Mobasheri
With the development of information and communications technology, user-generated content and crowdsourced data are playing a large role in studies of transport and public health. Recently, Strava, a popular website and mobile app dedicated to tracking athletic activity (cycling and running), began offering a data service called Strava Metro, designed to help transportation researchers and urban planners to improve infrastructure for cyclists and pedestrians. Strava Metro data has the potential to promote studies of cycling and health by indicating where commuting and non-commuting cycling activities are at a large spatial scale (street level and intersection level)...
March 8, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28261150/intranasal-administration-of-the-antisecretory-peptide-af-16-reduces-edema-and-improves-cognitive-function-following-diffuse-traumatic-brain-injury-in-the-rat
#6
Fredrik Clausen, Hans-Arne Hansson, Johan Raud, Niklas Marklund
A synthetic peptide with antisecretory activity, antisecretory factor (AF)-16, improves injury-related deficits in water and ion transport and decreases intracranial pressure after experimental cold lesion injury and encephalitis although its role in traumatic brain injury (TBI) is unknown. AF-16 or an inactive reference peptide was administrated intranasally 30 min following midline fluid percussion injury (mFPI; n = 52), a model of diffuse mild-moderate TBI in rats. Sham-injured (n = 14) or naïve (n = 24) animals were used as controls...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28241068/liver-x-receptor-agonist-treatment-significantly-affects-phenotype-and-transcriptome-of-apoe3-and-apoe4-abca1-haplo-deficient-mice
#7
Alexis Y Carter, Florent Letronne, Nicholas F Fitz, Anais Mounier, Cody M Wolfe, Kyong Nyon Nam, Valerie L Reeves, Hafsa Kamboh, Iliya Lefterov, Radosveta Koldamova
ATP-binding cassette transporter A1 (ABCA1) controls cholesterol and phospholipid efflux to lipid-poor apolipoprotein E (APOE) and is transcriptionally controlled by Liver X receptors (LXRs) and Retinoic X Receptors (RXRs). In APP transgenic mice, lack of Abca1 increased Aβ deposition and cognitive deficits. Abca1 haplo-deficiency in mice expressing human APOE isoforms, increased level of Aβ oligomers and worsened memory deficits, preferentially in APOE4 mice. In contrast upregulation of Abca1 by LXR/RXR agonists significantly ameliorated pathological phenotype of those mice...
2017: PloS One
https://www.readbyqxmd.com/read/28197073/association-of-trka-and-app-is-promoted-by-ngf-and-reduced-by-cell-death-promoting-agents
#8
Nadia Canu, Ilaria Pagano, Luca Rosario La Rosa, Marsha Pellegrino, Maria Teresa Ciotti, Delio Mercanti, Fabiola Moretti, Valentina Sposato, Viviana Triaca, Carla Petrella, Ichiro N Maruyama, Andrea Levi, Pietro Calissano
The amyloid precursor protein (APP) interacts with the tropomyosin receptor kinase A (TrkA) in normal rat, mouse, and human brain tissue but not in Alzheimer's disease (AD) brain tissue. However, it has not been reported whether the two proteins interact directly, and if so, which domains are involved. Clarifying these points will increase our understanding of the role and regulation of the TrkA/APP interaction in normal brain functioning as well as in AD. Here we addressed these questions using bimolecular fluorescence complementation (BiFC) and the proximity ligation assay (PLA)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28159908/regulation-of-synaptic-amyloid-%C3%AE-generation-through-bace1-retrograde-transport-in-a-mouse-model-of-alzheimer-s-disease
#9
Xuan Ye, Tuancheng Feng, Prasad Tammineni, Qing Chang, Yu Young Jeong, David J Margolis, Huaibin Cai, Alexander Kusnecov, Qian Cai
Amyloid-β (Aβ) peptides play a key role in synaptic damage and memory deficits in the early pathogenesis of Alzheimer's disease (AD). Abnormal accumulation of Aβ at nerve terminals leads to synaptic pathology and ultimately to neurodegeneration. β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the major neuronal β-secretase for Aβ generation. However, the mechanisms regulating BACE1 distribution in axons and β cleavage of APP at synapses remain largely unknown. Here, we reveal that dynein-Snapin-mediated retrograde transport regulates BACE1 trafficking in axons and APP processing at presynaptic terminals...
March 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28154138/pka-of-glu325-in-lacy
#10
Natalia Grytsyk, Junichi Sugihara, H Ronald Kaback, Petra Hellwig
Lactose permease (LacY), a paradigm for the largest family of membrane transport proteins, catalyzes the coupled translocation of a galactoside and a H(+) across the cytoplasmic membrane of Escherichia coli (galactoside/H(+) symport). One of the most important aspects of the mechanism is the relationship between protonation and binding of the cargo galactopyranoside. In this regard, it has been shown that protonation is required for binding. Furthermore when galactoside affinity is measured as a function of pH, an apparent pK (pK(app)) of ∼10...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28106559/abca1-deficiency-affects-basal-cognitive-deficits-and-dendritic-density-in-mice
#11
Nicholas F Fitz, Alexis Y Carter, Victor Tapias, Emilie L Castranio, Ravindra Kodali, Iliya Lefterov, Radosveta Koldamova
ATP-binding cassette transporter A1 (ABCA1) mediates cholesterol efflux to lipid-free apolipoproteins and regulates the generation of high density lipoproteins. Previously, we have shown that lack of Abca1 significantly increases amyloid deposition and cognitive deficits in Alzheimer's disease model mice expressing human amyloid-β protein precursor (APP). The goal of this study was to determine if ABCA1 plays a role in memory deficits caused by amyloid-β (Aβ) oligomers and examine neurite architecture of pyramidal hippocampal neurons...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28053030/tau-isoforms-imbalance-impairs-the-axonal-transport-of-the-amyloid-precursor-protein-in-human-neurons
#12
Valentina Lacovich, Sonia L Espindola, Matías Alloatti, Victorio Pozo Devoto, Lucas E Cromberg, Mária E Čarná, Giancarlo Forte, Jean-Marc Gallo, Luciana Bruno, Gorazd B Stokin, M Elena Avale, Tomás L Falzone
Tau, as a microtubule (MT)-associated protein, participates in key neuronal functions such as the regulation of MT dynamics, axonal transport, and neurite outgrowth. Alternative splicing of exon 10 in the tau primary transcript gives rise to protein isoforms with three (3R) or four (4R) MT binding repeats. Although tau isoforms are balanced in the normal adult human brain, imbalances in 3R:4R ratio have been tightly associated with the pathogenesis of several neurodegenerative disorders, yet the underlying molecular mechanisms remain elusive...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28028177/autophagy-mediated-regulation-of-bace1-protein-trafficking-and-degradation
#13
Tuancheng Feng, Prasad Tammineni, Chanchal Agrawal, Yu Young Jeong, Qian Cai
β-Site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) is the major neuronal β-secretase for amyloid-β generation and is degraded in lysosomes. The autophagy-lysosomal system plays a key role in the maintenance of cellular homeostasis in neurons. Recent studies established that nascent autophagosomes in distal axons move predominantly in the retrograde direction toward the soma, where mature lysosomes are mainly located. However, it remains unknown whether autophagy plays a critical role in regulation of BACE1 trafficking and degradation...
February 3, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28005987/metabolic-characterization-of-intact-cells-reveals-intracellular-amyloid-beta-but-not-its-precursor-protein-to-reduce-mitochondrial-respiration
#14
Patrick M Schaefer, Bjoern von Einem, Paul Walther, Enrico Calzia, Christine A F von Arnim
One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological localization of APP and Aβ, it is pending what triggers the mitochondrial defect. Thus, the aim of this study was to dissect the impact of APP versus Aβ in inducing mitochondrial alterations with respect to their subcellular localization...
2016: PloS One
https://www.readbyqxmd.com/read/28000370/amyloid-precursor-protein-traffics-from-the-golgi-directly-to-early-endosomes-in-an-arl5b-and-ap4-dependent-pathway
#15
Wei Hong Toh, Jing Zhi A Tan, Khalisah L Zulkefli, Fiona J Houghton, Paul A Gleeson
The intracellular trafficking and proteolytic processing of the membrane-bound amyloid precursor protein (APP) are coordinated events leading to the generation of pathogenic amyloid-beta (Aβ) peptides. The membrane transport of newly synthesized APP from the Golgi to the endolysosomal system is not well defined, yet it is likely to be critical for regulating its processing by β-secretase (BACE1) and γ-secretase. Here, we show that the majority of newly synthesized APP is transported from the trans-Golgi network (TGN) directly to early endosomes and then subsequently to the late endosomes/lysosomes with very little transported to the cell surface...
March 2017: Traffic
https://www.readbyqxmd.com/read/28000173/in-vitro-evaluation-of-absorption-characteristics-of-peramivir-for-oral-delivery
#16
Ying Li, Zhiyuan Wang, Xin Li, Wei Gong, Xiangyang Xie, Yang Yang, Wu Zhong, Aiping Zheng
BACKGROUND AND OBJECTIVE: Peramivir is a novel antiviral agent approved for the treatment of severe influenza. However, the development of oral formulation of peramivir has been severely hurdled by poor bioavailability (human, ≤3%). The present work aims to evaluate oral permeability characteristics of peramivir. METHODS: In vitro gastrointestinal stability, metabolic stability in human intestinal S9 fraction and Caco-2 permeability were performed. The liquid chromatography with tandem mass spectrometric (LC-MS/MS) was used to quantify peramivir in buffer and biological sample...
December 21, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27993762/smartphone-apps-for-measuring-human-health-and-climate-change-co-benefits-a-comparison-and-quality-rating-of-available-apps
#17
Rachel K Sullivan, Samantha Marsh, Jakob Halvarsson, Michelle Holdsworth, Wilma Waterlander, Maartje P Poelman, Jennifer Ann Salmond, Hayley Christian, Lenny Sc Koh, Janet E Cade, John C Spence, Alistair Woodward, Ralph Maddison
BACKGROUND: Climate change and the burden of noncommunicable diseases are major global challenges. Opportunities exist to investigate health and climate change co-benefits through a shift from motorized to active transport (walking and cycling) and a shift in dietary patterns away from a globalized diet to reduced consumption of meat and energy dense foods. Given the ubiquitous use and proliferation of smartphone apps, an opportunity exists to use this technology to capture individual travel and dietary behavior and the associated impact on the environment and health...
December 19, 2016: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/27932950/amyloid-precursor-proteins-are-dynamically-trafficked-and-processed-during-neuronal-development
#18
Jenna M Ramaker, Robert S Cargill, Tracy L Swanson, Hanil Quirindongo, Marlène Cassar, Doris Kretzschmar, Philip F Copenhaver
Proteolytic processing of the Amyloid Precursor Protein (APP) produces beta-amyloid (Aβ) peptide fragments that accumulate in Alzheimer's Disease (AD), but APP may also regulate multiple aspects of neuronal development, albeit via mechanisms that are not well understood. APP is a member of a family of transmembrane glycoproteins expressed by all higher organisms, including two mammalian orthologs (APLP1 and APLP2) that have complicated investigations into the specific activities of APP. By comparison, insects express only a single APP-related protein (APP-Like, or APPL) that contains the same protein interaction domains identified in APP...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27915995/lack-of-p-glycoprotein-results-in-impairment-of-removal-of-beta-amyloid-and-increased-intraparenchymal-cerebral-amyloid-angiopathy-after-active-immunization-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#19
Sascha Brückmann, Anja Brenn, Markus Grube, Katharina Niedrig, Silva Holtfreter, Oliver von Bohlen Und Halbach, Martin Groschup, Markus Keller, Silke Vogelgesang
Immunization against beta-amyloid (Aβ) reduces cerebral Aβ deposits and improves cognitive capacities in transgenic mouse models, and thus has been considered a promising disease-modifying therapeutic approach for Alzheimer's disease (AD). Although clinical trials in AD patients have yielded evidence for clearance of parenchymal Aβ plaques, Aβ increases in blood vessels of treated patients. We hypothesize that an age-related decline in the mechanisms that clear Aβ from the brain might be at least in part responsible for the failure to purge and re-distribute Aβ...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27911305/nitrosylation-of-vesicular-transporters-in-brain-of-amyloid-precursor-protein-presenilin-1-double-transgenic-mice
#20
Ying Wang, Zhu Zhou, Hua Tan, Shenghua Zhu, Yiran Wang, Yingxia Sun, Xin-Min Li, Jun-Feng Wang
Nitric oxide can attack thiol groups of cysteine residues in proteins and induce protein cysteine S-nitrosylation. Cholinergic and glutamatergic systems are dysregulated in Alzheimer's disease. Vesicular acetylcholine transporter (VAChT) and vesicular glutamate transporter 1 (VGLUT1) are important in packaging acetylcholine and glutamate into vesicles, which is an important step for neurotransmission. Previously we found that VAChT and VGLUT1 can be nitrosylated and that S-nitrosylation of these transporters inhibits vesicular uptake of acetylcholine and glutamate...
2017: Journal of Alzheimer's Disease: JAD
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