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

Cardiac arrest and catecholamine cardiomyopathy secondary to a misdiagnosed ectopic pheochromocytoma

Not required for Clinical Vignette

SOX2 Gene Regulates the Transcriptional Network of Oncogenes and Affects Tumorigenesis of Human Lung Cancer Cells

Recent studies demonstrated that cancer stem cells (CSCs) have higher tumorigenesis properties than those of differentiated cancer cells and that transcriptional factor-SOX2 plays a vital role in maintaining the unique properties of CSCs; however, the function and underlying mechanism of SOX2 in carcinogenesis of lung cancer are still elusive. This study applied immunohistochemistry to analyze the expression of SOX2 in human lung tissues of normal individuals as well as patients with adenocarcinoma, squamous cell carcinoma, and large cell and small cell carcinoma and demonstrated specific overexpression of SOX2 in all types of lung cancer tissues. This finding supports the notion that SOX2 contributes to the tumorigenesis of lung cancer cells and can be used as a diagnostic probe. In addition, obviously higher expression of oncogenes c-MYC, WNT1, WNT2, and NOTCH1 was detected in side population (SP) cells than in non-side population (NSP) cells of human lung adenocarcinoma cell line-A549, revealing a possible mechanism for the tenacious tumorigenic potential of CSCs. To further elucidate the function of SOX2 in tumorigenesis of cancer cells, A549 cells were established with expression of luciferase and doxycycline-inducible shRNA targeting SOX2. We found silencing of SOX2 gene reduces the tumorigenic property of A549 cells with attenuated expression of c-MYC, WNT1, WNT2, and NOTCH1 in xenografted NOD/SCID mice. By using the RNA-Seq method, an additional 246 target cancer genes of SOX2 were revealed. These results present evidence that SOX2 may regulate the expression of oncogenes in CSCs to promote the development of human lung cancer

Exploring Systematic Offsets Between Aerosol Products from the Two MODIS Sensors

Long-term measurements of global aerosol loading and optical properties are essential for assessing climate-related questions. Using observations of spectral reflectance and radiance, the dark-target (DT) aerosol retrieval algorithm is applied to Moderate Resolution Imaging Spectroradiometer sensors on both Terra (MODIS-T) and Aqua (MODIS-A) satellites, deriving products (known as MOD04 and MYD04, respectively) of global aerosol optical depth (AOD at 0.55microm) over both land and ocean, and an ngstrm exponent (AE derived from 0.55 and 0.86microm) over ocean. Here, we analyze the overlapping time series (since mid-2002) of the Collection 6 (C6) aerosol products. Global monthly mean AOD from MOD04 (Terra with morning overpass) is consistently higher than MYD04 (Aqua with afternoon overpass) by 13% (0.02 over land and 0.015 over ocean), and this offset (MOD04 - MYD04) has seasonal as well as long-term variability. Focusing on 2008 and deriving yearly gridded mean AOD and AE, we find that, over ocean, the MOD04 (morning) AOD is higher and the AE is lower. Over land, there is more variability, but only biomass-burning regions tend to have AOD lower for MOD04. Using simulated aerosol fields from the Goddard Earth Observing System (GEOS-5) Earth system model and sampling separately (in time and space) along each MODIS-observed swath during 2008, the magnitudes of morning versus afternoon offsets of AOD and AE are smaller than those in the C6 products. Since the differences are not easily attributed to either aerosol diurnal cycles or sampling issues, we test additional corrections to the input reflectance data. The first, known as C6+, corrects for long-term changes to each sensor's polarization sensitivity and the response versus the scan angle and to cross-calibration from MODIS-T to MODIS-A. A second convolves the detrending and cross-calibration into scaling factors. Each method was applied upstream of the aerosol retrieval using 2008 data. While both methods reduced the overall AOD offset over land from 0.02 to 0.01, neither significantly reduced the AOD offset over ocean. The overall negative AE offset was reduced. A collection (C6.1) of all MODIS Atmosphere products was released, but we expect that the C6.1 aerosol products will maintain similar overall AOD and AE offsets. We conclude that (a) users should not interpret global differences between Terra and Aqua aerosol products as representing a true diurnal signal in the aerosol. (b) Because the MODIS-A product appears to have an overall smaller bias compared to ground-truth data, it may be more suitable for some applications. However (c), since the AOD offset is only 0.02 and within the noise level for single retrievals, both MODIS products may be adequate for most applications

Magnetic metal organic frameworks (MOFs) composite for removal of lead and malachite green in wastewater

We designed and synthesized a magnetic metal organic frameworks (MOFs) composite, Cu-MOFs/FeO as the adsorbent for removal of lead (Pb(II)) and malachite green (MG) in wastewater. This Cu-MOFs/FeO can be easily prepared by in-situ growth of Cu-MOFs with doping FeO nanoparticles. The prepared Cu-MOFs/FeO composite was well characterized by SEM, XRD, and FTIR spectra. The adsorption experiments found that Cu-MOFs/FeO can serve as adsorbent for removal of Pb(II) and MG simultaneously. The adsorption capacities were found to be 113.67 mg/g for MG and 219.00 mg/g for Pb, respectively, which are significantly higher than reported materials. Adsorption isotherm, kinetics and recyclability of Cu-MOFs/FeO for removal of Pb(II) and MG were then studied. Adsorption of Pb(II) and MG exhibited Freundlich adsorption isotherm model, with the adsorption kinetics of available second-order kinetic. Physical adsorption for MG and chemical adsorption for Pb(II) were confirmed by Dubinin-Radushkevich (D-R) isothermal adsorption model. The adsorption of Pb(II) and MG in real water samples were then studied. The FeO/Cu-MOFs was found to be recyclable for removal of Pb(II) and MG, can be explored as the potential adsorbent for waste water treatment

Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep

Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant TR01-GM104948)National Institutes of Health (U.S.) (Grant T32-HL07901)Massachusetts General Hospital (Executive Committee on Research Fellowship)Massachusetts General Hospital. Dept. of Anesthesia, Critical Care, and Pain Medicin

TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Epigenetic silencing of tumor suppressor genes play important roles in NPC tumorgenesis. Tissue factor pathway inhibitor-2 (TFPI-2), is a protease inhibitor. Recently, <it>TFPI-2 </it>was suggested to be a tumor suppressor gene involved in tumorigenesis and metastasis in some cancers. In this study, we investigated whether <it>TFPI-2 </it>was inactivated epigenetically in nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Transcriptional expression levels of <it>TFPI-2 </it>was evaluated by RT-PCR. Methylation status were investigated by methylation specific PCR and bisulfate genomic sequencing. The role of <it>TFPI-2 </it>as a tumor suppressor gene in NPC was addressed by re-introducing <it>TFPI-2 </it>expression into the NPC cell line CNE2.</p> <p>Results</p> <p><it>TFPI-2 </it>mRNA transcription was inactivated in NPC cell lines. <it>TFPI-2 </it>was aberrantly methylated in 66.7% (4/6) NPC cell lines and 88.6% (62/70) of NPC primary tumors, but not in normal nasopharyngeal epithelia. <it>TFPI-2 </it>expression could be restored in NPC cells after demethylation treatment. Ectopic expression of TFPI-2 in NPC cells induced apoptosis and inhibited cell proliferation, colony formation and cell migration.</p> <p>Conclusions</p> <p>Epigenetic inactivation of <it>TFPI-2 </it>by promoter hypermethylation is a frequent and tumor specific event in NPC. <it>TFPI-2 </it>might be considering as a putative tumor suppressor gene in NPC.</p