APPLICATION FOR PROVIDING ACCURATE PHOTO TIMESTAMP

An application for providing a photo with an accurate timestamp in a computing device is disclosed. The application displays the correct time of the captured photo, and uses image processing and backend logic to fix the timestamp and location for the photo within a few hours of that time. Using the application, a user can geolocate each photo which can result in improved photo classification and searching

Cholesterol efflux in adipose tissue

Scope and Method of Study:The current studies are important to understand the reverse cholesterol transport (RCT) in vertebrates. Reverse cholesterol transport is the process by which excess unesterified cholesterol is transported from peripheral tissues to the liver for excretion from the body. Several lines of evidence suggest that defects in RCT contribute to the development of atherosclerosis. Adipose tissue constitutes a major site of cholesterol storage and it may play a role in the regulation of circulating cholesterol levels. The understanding of metabolic link between the lipolytic state (hydrolysis of triacyglycerol) of adipocytes and the mechanism of release of cellular cholesterol to external cholesterol acceptors like apolipoprotein A-I (apoA-I) and high density lipoprotein (HDL) is necessary to elucidate the role of adipose tissue in whole body cholesterol homeostasis.Findings and Conclusions:Our study shows that β-adrenergic activation of the lipolysis significantly increases the extent of cholesterol efflux to reconstituted discoidal HDL particles. The enhancement of cholesterol efflux is not due to the enrichment of plasma membrane cholesterol, or to the levels of the cholesterol transporters ABCA1 and SR-BI. The activation of lipolysis is accompanied by an increase in BFA-sensitive vesicular transport that in turn enhances cholesterol efflux to HDL. The study supports a metabolic link between the lipolytic activity of adipocytes and the rate of cellular cholesterol efflux to HDL. The activation of lipolysis does not induce a significant increase in the rate of cholesterol efflux to lipid free apoA-I. The known vesicular and non-vesicular cholesterol efflux inhibitors inhibit global cholesterol efflux significantly, but not specific cholesterol efflux to apoA-I. We have evidently presented that lipid free apoA-I undergo retroendocytosis in mouse adipose cells, human liver cells but not in human macrophage cells. The known cholesterol efflux inhibitory drugs had no effect on the uptake and recycling of apoA-I

Blood-brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism

Table S1. Demographic and clinical features of human subjects used in this study. Figure S1. Aβ deposition in microvessels in AD patients and APPSw/0 mice. Figure S2. Biochemical analysis of Aβ42 aggregates. Figure S3. Cy3-Aβ42 cellular uptake in wild type mouse brain slices within 30 min. Figure S4. Pericyte coverages in Lrp1lox/lox and Lrp1lox/lox; Cspg4-Cre mice. Figure S5.. LRP1 and apoE suppression with siRNA. (DOCX 1454 kb

Ventilator-associated Acinetobacter baumannii pneumonia

We report an outbreak of ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in 6 infants with acute lower respiratory tract infection. Non-bronchoscopic bronchoalveolar lavage isolated A. baumannii in all these infants. Environmental microbiological survey of the Pediatric intensive care unit and pediatric wards identified oxygen humidifying chambers as the source of Acinetobacter. Practices of cleaning and changing of the humidifiers were reviewed and the outbreak was controlled with new recommendations

Critical role of astroglial apolipoprotein E and liver X receptor-α expression for microglial Aβ phagocytosis

Liver X receptors (LXRs) regulate immune cell function and cholesterol metabolism, both factors that are critically involved in Alzheimer's disease (AD). To investigate the therapeutic potential of long-term LXR activation in amyloid-β (Aβ) peptide deposition in an AD model, 13-month-old, amyloid plaque-bearing APP23 mice were treated with the LXR agonist TO901317. Postmortem analysis demonstrated that TO901317 efficiently crossed the blood–brain barrier. Insoluble and soluble Aβ levels in the treated APP23 mice were reduced by 80% and 40%, respectively, compared with untreated animals. Amyloid precursor protein (APP) processing, however, was hardly changed by the compound, suggesting that the observed effects were instead mediated by Aβ disposal. Despite the profound effect on Aβ levels, spatial learning in the Morris water maze was only slightly improved by the treatment. ABCA1 (ATP-binding cassette transporter 1) and apolipoprotein E (ApoE) protein levels were increased and found to be primarily localized in astrocytes. Experiments using primary microglia demonstrated that medium derived from primary astrocytes exposed to TO901317 stimulated phagocytosis of fibrillar Aβ. Conditioned medium from TO901317-treated ApoE−/−or LXRα−/−astrocytes did not increase phagocytosis of Aβ. In APP23 mice, long-term treatment with TO901317 strongly increased the association of microglia and Aβ plaques. Short-term treatment of APP/PS1 mice with TO901317 also increased this association, which was dependent on the presence of LXRα and was accompanied by increased ApoE lipidation. Together, these data suggest that astrocytic LXRα activation and subsequent release of ApoE by astrocytes is critical for the ability of microglia to remove fibrillar Aβ in response to treatment with TO901317.</jats:p

Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation

Sleep deprivation reduces the dextran radial distribution and 125I-apoE inflow from CSF into brain. A-B) Representative images of cascade blue dextran (CB) in mice on normal sleep cycle (A) and in mice during sleep deprivation (SD) (B). Cascade blue dextran (10 kDa) was injected into cisterna magna and the mice perfusion fixed (PFA) at 15 min. The vasculature was outline by lectin (green). Scale bars 100 μm (A-B). C) 125I-ApoE2 (yellow column), 125I-apoE3 (red column) and 125I-apoE4 (orange column) inflow into brain from the CSF were reduced in SD mice. D) 14C-inulin inflow into brain from the CSF was reduced with SD and not affected by apoE isoforms. 125I-ApoE (10 nM) and 14C-inulin were intracisternally injected and the brain analyzed for radioactivity. Values are mean ± SEM. N = 6 mice per group. (EPS 15099 kb

In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis

BACKGROUND: The APOE4 allele variant is the strongest known genetic risk factor for developing late-onset Alzheimer’s disease. The link between apolipoprotein E (apoE) and Alzheimer’s disease is likely due in large part to the impact of apoE on the metabolism of amyloid β (Aβ) within the brain. Manipulation of apoE levels and lipidation within the brain has been proposed as a therapeutic target for the treatment of Alzheimer’s disease. However, we know little about the dynamic regulation of apoE levels and lipidation within the central nervous system. We have developed an assay to measure apoE levels in the brain interstitial fluid of awake and freely moving mice using large molecular weight cut-off microdialysis probes. RESULTS: We were able to recover apoE using microdialysis from human cerebrospinal fluid (CSF) in vitro and mouse brain parenchyma in vivo. Microdialysis probes were inserted into the hippocampus of wild-type mice and interstitial fluid was collected for 36 hours. Levels of apoE within the microdialysis samples were determined by ELISA. The levels of apoE were found to be relatively stable over 36 hours. No apoE was detected in microdialysis samples from apoE KO mice. Administration of the RXR agonist bexarotene increased ISF apoE levels while ISF Aβ levels were decreased. Extrapolation to zero-flow analysis allowed us to determine the absolute recoverable concentration of apoE3 in the brain ISF of apoE3 KI mice. Furthermore, analysis of microdialysis samples by non-denaturing gel electrophoresis determined lipidated apoE particles in microdialysis samples were consistent in size with apoE particles from CSF. Finally, we found that the concentration of apoE in the brain ISF was dependent upon apoE isoform in human apoE KI mice, following the pattern apoE2>apoE3>apoE4. CONCLUSIONS: We are able to collect lipidated apoE from the brain of awake and freely moving mice and monitor apoE levels over the course of several hours from a single mouse. Our technique enables assessment of brain apoE dynamics under physiological and pathophysiological conditions and in response to therapeutic interventions designed to affect apoE levels and lipidation within the brain

Comparison of plasma and CSF biomarkers in predicting cognitive decline

OBJECTIVES: Concentrations of amyloid-β peptides (Aβ42/Aβ40) and neurofilament light (NfL) can be measured in plasma or cerebrospinal fluid (CSF) and are associated with Alzheimer\u27s disease brain pathology and cognitive impairment. This study directly compared plasma and CSF measures of Aβ42/Aβ40 and NfL as predictors of cognitive decline. METHODS: Participants were 65 years or older and cognitively normal at baseline with at least one follow-up cognitive assessment. Analytes were measured with the following types of assays: plasma Aβ42/Aβ40, immunoprecipitation-mass spectrometry; plasma NfL, Simoa; CSF Aβ42/Aβ40, automated immunoassay; CSF NfL plate-based immunoassay. Mixed effects models evaluated the global cognitive composite score over a maximum of 6 years as predicted by the fluid biomarkers. RESULTS: Analyses included 371 cognitively normal participants, aged 72.7 ± 5.2 years (mean ± standard deviation) with an average length of follow-up of 3.9 ± 1.6 years. Standardized concentrations of biomarkers were associated with annualized cognitive change: plasma Aβ42/Aβ40, 0.014 standard deviations (95% confidence intervals 0.002 to 0.026); CSF Aβ42/Aβ40, 0.020 (0.008 to 0.032); plasma Nfl, -0.018 (-0.030 to -0.005); and CSF NfL, -0.024 (-0.036 to -0.012). Power analyses estimated that 266 individuals in each treatment arm would be needed to detect a 50% slowing of decline if identified by abnormal plasma measures versus 229 for CSF measures. INTERPRETATION: Both plasma and CSF measures of Aβ42/Aβ40 and NfL predicted cognitive decline. A clinical trial that enrolled individuals based on abnormal plasma Aβ42/Aβ40 and NfL levels would require only a marginally larger cohort than if CSF measures were used