Interactions between Amyloid-β and Hemoglobin: Implications for Amyloid Plaque Formation in Alzheimer's Disease

Accumulation of amyloid-β (Aβ) peptides in the brain is one of the central pathogenic events in Alzheimer's disease (AD). However, why and how Aβ aggregates within the brain of AD patients remains elusive. Previously, we demonstrated hemoglobin (Hb) binds to Aβ and co-localizes with the plaque and vascular amyloid deposits in post-mortem AD brains. In this study, we further characterize the interactions between Hb and Aβ in vitro and in vivo and report the following observations: 1) the binding of Hb to Aβ required iron-containing heme; 2) other heme-containing proteins, such as myoglobin and cytochrome C, also bound to Aβ; 3) hemin-induced cytotoxicity was reduced in neuroblastoma cells by low levels of Aβ; 4) Hb was detected in neurons and glial cells of post-mortem AD brains and was up-regulated in aging and APP/PS1 transgenic mice; 5) microinjection of human Hb into the dorsal hippocampi of the APP/PS1 transgenic mice induced the formation of an envelope-like structure composed of Aβ surrounding the Hb droplets. Our results reveal an enhanced endogenous expression of Hb in aging brain cells, probably serving as a compensatory mechanism against hypoxia. In addition, Aβ binds to Hb and other hemoproteins via the iron-containing heme moiety, thereby reducing Hb/heme/iron-induced cytotoxicity. As some of the brain Hb could be derived from the peripheral circulation due to a compromised blood-brain barrier frequently observed in aged and AD brains, our work also suggests the genesis of some plaques may be a consequence of sustained amyloid accretion at sites of vascular injury

Inhibition of Serine Protease Activity Protects Against High Fat Diet-Induced Inflammation and Insulin Resistance.

Recent evidence suggests that enhanced protease-mediated inflammation may promote insulin resistance and result in diabetes. This study tested the hypothesis that serine protease plays a pivotal role in type 2 diabetes, and inhibition of serine protease activity prevents hyperglycemia in diabetic animals by modulating insulin signaling pathway. We conducted a single-center, cross-sectional study with 30 healthy controls and 57 patients with type 2 diabetes to compare plasma protease activities and inflammation marker between groups. Correlations of plasma total and serine protease activities with variables were calculated. In an in-vivo study, LDLR-/- mice were divided into normal chow diet, high-fat diet (HFD), and HFD with selective serine protease inhibition groups to examine the differences of obesity, blood glucose level, insulin resistance and serine protease activity among groups. Compared with controls, diabetic patients had significantly increased plasma total protease, serine protease activities, and also elevated inflammatory cytokines. Plasma serine protease activity was positively correlated with body mass index, hemoglobin A1c, homeostasis model assessment-insulin resistance index (HOMA-IR), tumor necrosis factor-α, and negatively with adiponectin concentration. In the animal study, administration of HFD progressively increased body weight, fasting glucose level, HOMA-IR, and upregulated serine protease activity. Furthermore, in-vivo serine protease inhibition significantly suppressed systemic inflammation, reduced fasting glucose level, and improved insulin resistance, and these effects probably mediated by modulating insulin receptor and cytokine expression in visceral adipose tissue. Our findings support the serine protease may play an important role in type 2 diabetes and suggest a rationale for a therapeutic strategy targeting serine protease for clinical prevention of type 2 diabetes

Hyperbaric oxygen therapy as an adjunctive treatment for sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery

<p>Abstract</p> <p>Purpose</p> <p>A retrospective study to evaluate the effect of hyperbaric oxygen (HBO2) therapy on sternal infection and osteomyelitis following median sternotomy.</p> <p>Materials and methods</p> <p>A retrospective analysis of patients who received sternotomy and cardiothoracic surgery which developed sternal infection and osteomyelitis between 2002 and 2009. Twelve patients who received debridement and antibiotic treatment were selected, and six of them received additional HBO2 therapy. Demographic, clinical characteristics and outcome were compared between patients with and without HBO2 therapy.</p> <p>Results</p> <p>HBO2 therapy did not cause any treatment-related complication in patients receiving this additional treatment. Comparisons of the data between two study groups revealed that the length of stay in ICU (8.7 ± 2.7 days vs. 48.8 ± 10.5 days, p < 0.05), duration of invasive (4 ± 1.5 days vs. 34.8 ± 8.3 days, p < 0.05) and non-invasive (4 ± 1.9 days vs. 22.3 ± 6.2 days, p < 0.05) positive pressure ventilation were all significantly lower in patients with additional HBO2 therapy, as compared to patients without HBO2 therapy. Hospital mortality was also significantly lower in patients who received HBO2 therapy (0 case vs. 3 cases, p < 0.05), as compared to patients without the HBO2 therapy.</p> <p>Conclusions</p> <p>In addition to primary treatment with debridement and antibiotic use, HBO2 therapy may be used as an adjunctive and safe treatment to improve clinical outcomes in patients with sternal infection and osteomyelitis after sternotomy and cardiothoracic surgery.</p

Mineralization of Progenitor Cells with Different Implant Topographies

AbstractThe major challenge for dental implants is achieving an optimal osteoregeneration. Different levels of roughness processed through sand-blasting/ acid-etching (SLA) then further treated with silane and peptide were measured. Peptide bonded with silane on the SLA and machine ground titanium (Ti) surface were used as a culture substitute. The sample properties on the osteogenic abilities were compared by testing the interaction with mesenchymal stem cells (MSCs, D1). When comparing to the SLA only group, the silane treated Ti surface with peptide bonded had smaller wetting angle and the cell proliferative ability did differ with statistical significance (p<0.05). A rougher surface binding with peptide provided higher hydrophilic ability and had the potential ability to enhance the proliferation and mineralization of the progenitor cell D1. Accordingly, a novel implant surface treatment method having tissues integrated was obtained through the supplement of peptide on the surfaces through SLA treatment of titanium

Feasibility of GNSS-R Altimetry Using CyGNSS 8-Satellite Constellation Mission Data

Ponencia expuesta en Scientific Assembly of the International Association of Geodesy (2021) celebrado en Beijing del 28 de junio al 2 de juli

CYGNSS Ocean Altimetry: A Status Report

Comunicación expuesta online en el CYGNSS Science Team Summer Meeting celebrado del 27 al 29 de julio de 202

Mean structure and variability of the cold dome northeast of Taiwan

Author Posting. © The Oceanography Society, 2011. This article is posted here by permission of The Oceanography Society for personal use, not for redistribution. The definitive version was published in Oceanography 24 no. 4 (2011): 100–109, doi:10.5670/oceanog.2011.98.The "cold dome" off northeastern Taiwan is one of the distinctive oceanic features in the seas surrounding Taiwan. The cold dome is important because persistent upwelling makes the region highly biologically productive. This article uses historical data, recent observations, and satellite-observed sea surface temperatures (SST) to describe the mean structure and variability of the cold dome. The long-term mean position of the cold dome, using the temperature at 50 m depth as a reference, is centered at 25.625°N, 122.125°E. The cold dome has a diameter of approximately 100 km, and is maintained by cold ( 34.5) waters upwelled along the continental slope. The ocean currents around the cold dome, although weak, flow counterclockwise. The monsoon-driven winter intrusion of the Kuroshio current onto the East China Sea shelf intensifies the upwelling and carries more subsurface water up to the cold dome than during the summer monsoon season. On a shorter timescale, the cold dome's properties can be significantly modified by the passage of typhoons, which creates favorable physical conditions for short-term Kuroshio intrusions in summer. The surface expression of the cold dome viewed from satellite SST images is often not domelike but instead is an irregular shape with numerous filaments, and thus may contribute substantially to shelf/slope exchange. As a result of persistent upwelling, typhoon passage, and monsoon forcing, higher chlorophyll a concentrations, and thus higher primary productivity, are frequently observed in the vicinity of the cold dome.The National Science Council (NSC) of Taiwan sponsored this study under grant NSC98-2611-M-002-019-MY3. NSC supported C.-C. Chen under grant NSC98-2611-M-003-001-MY3

Change in household fuels dominates the decrease in PM_(2.5) exposure and premature mortality in China in 2005–2015

To tackle the severe fine particle (PM_(2.5)) pollution in China, the government has implemented stringent control policies mainly on power plants, industry, and transportation since 2005, but estimates of the effectiveness of the policy and the temporal trends in health impacts are subject to large uncertainties. By adopting an integrated approach that combines chemical transport simulation, ambient/household exposure evaluation, and health-impact assessment, we find that the integrated population-weighted exposure to PM_(2.5) (IPWE) decreased by 47% (95% confidence interval, 37–55%) from 2005 [180 (146–219) μg/m^3] to 2015 [96 (83–111) μg/m^3]. Unexpectedly, 90% (86–93%) of such reduction is attributed to reduced household solid-fuel use, primarily resulting from rapid urbanization and improved incomes rather than specific control policies. The IPWE due to household fuels for both cooking and heating decreased, but the impact of cooking is significantly larger. The reduced household-related IPWE is estimated to avoid 0.40 (0.25–0.57) million premature deaths annually, accounting for 33% of the PM_(2.5)-induced mortality in 2015. The IPWE would be further reduced by 63% (57–68%) if the remaining household solid fuels were replaced by clean fuels, which would avoid an additional 0.51 (0.40–0.64) million premature deaths. Such a transition to clean fuels, especially for heating, requires technology innovation and policy support to overcome the barriers of high cost of distribution systems, as is recently being attempted in the Beijing–Tianjin–Hebei area. We suggest that household-fuel use be more highly prioritized in national control policies, considering its effects on PM_(2.5) exposures

A modeling study of the nonlinear response of fine particles to air pollutant emissions in the Beijing-Tianjin-Hebei region

The Beijing–Tianjin–Hebei (BTH) region has been suffering from the most severe fine-particle (PM2:5) pollution in China, which causes serious health damage and economic loss. Quantifying the source contributions to PM2:5 concentrations has been a challenging task because of the complicated nonlinear relationships between PM2:5 concentrations and emissions of multiple pollutants from multiple spatial regions and economic sectors. In this study, we use the extended response surface modeling (ERSM) technique to investigate the nonlinear response of PM2:5 concentrations to emissions of multiple pollutants from different regions and sectors over the BTH region, based on over 1000 simulations by a chemical transport model (CTM). The ERSM-predicted PM2:5 concentrations agree well with independent CTM simulations, with correlation coefficients larger than 0.99 and mean normalized errors less than 1 %. Using the ERSM technique, we find that, among all air pollutants, primary inorganic PM2:5 makes the largest contribution (24–36 %) to PM2:5 concentrations. The contribution of primary inorganic PM2:5 emissions is especially high in heavily polluted winter and is dominated by the industry as well as residential and commercial sectors, which should be prioritized in PM2:5 control strategies. The total contributions of all precursors (nitrogen oxides, NOx ; sulfur dioxides, SO2; ammonia, NH3; non-methane volatile organic compounds, NMVOCs; intermediate-volatility organic compounds, IVOCs; primary organic aerosol, POA) to PM2:5 concentrations range between 31 and 48 %. Among these precursors, PM2:5 concentrations are primarily sensitive to the emissions of NH3, NMVOCCIVOC, and POA. The sensitivities increase substantially for NH3 and NOx and decrease slightly for POA and NMVOCCIVOC with the increase in the emission reduction ratio, which illustrates the nonlinear relationships between precursor emissions and PM2:5 concentrations. The contributions of primary inorganic PM2:5 emissions to PM2:5 concentrations are dominated by local emission sources, which account for over 75% of the total primary inorganic PM2:5 contributions. For precursors, however, emissions from other regions could play similar roles to local emission sources in the summer and over the northern part of BTH. The source contribution features for various types of heavy-pollution episodes are distinctly different from each other and from the monthly mean results, illustrating that control strategies should be differentiated based on the major contributing sources during different types of episodes.publishedVersio