Myricetin: A Naturally Occurring Regulator of Metal-Induced Amyloid-β Aggregation and Neurotoxicity

No AbstractPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84385/1/1198_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/84385/2/cbic_201000790_sm_miscellaneous_information.pd

Recent Development of Bifunctional Small Molecules to Study Metal-Amyloid-β Species in Alzheimer's Disease

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease related to the deposition of aggregated amyloid-β (Aβ) peptides in the brain. It has been proposed that metal ion dyshomeostasis and miscompartmentalization contribute to AD progression, especially as metal ions (e.g., Cu(II) and Zn(II)) found in Aβ plaques of the diseased brain can bind to Aβ and be linked to aggregation and neurotoxicity. The role of metal ions in AD pathogenesis, however, is uncertain. To accelerate understanding in this area and contribute to therapeutic development, recent efforts to devise suitable chemical reagents that can target metal ions associated with Aβ have been made using rational structure-based design that combines two functions (metal chelation and Aβ interaction) in the same molecule. This paper presents bifunctional compounds developed by two different design strategies (linkage or incorporation) and discusses progress in their applications as chemical tools and/or potential therapeutics

Monitoring daily evapotranspiration in Northeast Asia using MODIS and a regional Land Data Assimilation System

We applied an approach for daily estimation and monitoring of evapotranspiration (ET) over the Northeast Asia monsoon region using satellite remote sensing observations from the Moderate Resolution Imaging Spectroradiometer (MODIS). Frequent cloud cover results in a substantial loss of remote sensing information, limiting the capability of continuous ET monitoring for the monsoon region. Accordingly, we applied and evaluated a stand-alone MODIS ET algorithm for representative regional ecosystem types and an alternative algorithm to facilitate continuous regional ET estimates using surface meteorological inputs from the Korea Land Data Assimilation System (KLDAS) in addition to MODIS land products. The resulting ET calculations showed generally favorable agreement (root-mean-square error  \u3c 1.3 mm d−1) with respect to in situ measurements from eight regional flux tower sites. The estimated mean annual ET for 3 years (2006 to 2008) was approximately 362.0 ± 161.5 mm yr−1 over the Northeast Asia domain. In general, the MODIS and KLDAS-based ET (MODIS-KLDAS ET) results showed favorable performance when compared to tower observations, though the results were overestimated for a forest site by approximately 39.5% and underestimated for a cropland site in South Korea by 0.8%. The MODIS-KLDAS ET data were generally underestimated relative to the MODIS (MOD16) operational global terrestrial ET product for various biome types, excluding cropland; however, MODIS-KLDAS ET showed better agreement than MOD16 ET for forest and cropland sites in South Korea. Our results indicate that MODIS ET estimates are feasible but are limited by satellite optical-infrared remote sensing constraints over cloudy regions, whereas alternative ET estimates using continuous meteorological inputs from operational regional climate systems (e.g., KLDAS) provide accurate ET results and continuous monitoring capability under all-sky conditions

Fouling and performance of outer selective hollow fiber membrane in osmotic membrane bioreactor: Cross flow and air scouring effects

© 2019 Elsevier Ltd This study assessed impacts of cross-flow velocity (CFV) and air scouring on the performance and membrane fouling mitigation of a side-stream module containing outer-selective hollow fiber thin film composite forward osmosis membrane in osmosis membrane bioreactor (OMBR) system for urban wastewater treatment. CFV of draw solution was optimized, followed by the impact assessment of three CFVs on feed solution (FS) stream and periodic injection of air scouring into the side-stream module. Overall, the OMBR system exhibited high and stable performance with initial water flux of approximately 15 LMH, high removal efficiencies of bulk organic matter and nutrients. While FS's CFVs insignificantly affected the performance and membrane fouling, regular air scouring showed substantial impact with better performance and high efficiency in mitigating membrane fouling. These results indicated that periodic air scouring can be applied into the side-stream membrane module for efficient fouling mitigation without interruption the operation of the OMBR system

Mono-anionic phosphopeptides produced by unexpected histidine alkylation exhibit high plk1 polo-box domain-binding affinities and enhanced antiproliferative effects in hela cells

Binding of polo-like kinase 1 (Plk1) polo-box domains (PBDs) to phosphothreonine (pThr)/phosphoserine (pSer)-containing sequences is critical for the proper function of Plk1. Although high-affinity synthetic pThr-containing peptides provide starting points for developing PBD-directed inhibitors, to date the efficacy of such peptides in whole cell assays has been poor. This potentially reflects limited cell membrane permeability arising, in part, from the di-anionic nature of the phosphoryl group or its mimetics. In our current article we report the unanticipated on-resin N(τ)-alkylation of histidine residues already bearing a N(π)- alkyl group. This resulted in cationic imidazolium-containing pThr peptides, several of which exhibit single-digit nanomolar PBD-binding affinities in extracellular assays and improved antimitotic efficacies in intact cells. We enhanced the cellular efficacies of these peptides further by applying bio-reversible pivaloyloxymethyl (POM) phosphoryl protection. New structural insights presented in our current study, including the potential utility of intramolecular charge masking, may be useful for the further development of PBD-binding peptides and peptide mimetics.National Institutes of Health (U.S.) (Grants ES015339 and GM104047

On the Nature of Propagating Intensity Disturbances in Polar Plumes during the 2017 Total Solar Eclipse

The propagating intensity disturbances (PIDs) in plumes are still poorly understood and their identity (magnetoacoustic waves or flows) remains an open question. We investigate PIDs in five plumes located in the northern polar coronal hole observed during the 2017 total solar eclipse. Three plumes are associated with coronal bright points, jets and macrospicules at their base (active plumes) and the other two plumes are not (quiet plumes). The electron temperature at the base of the plumes is obtained from the filter ratio of images taken with the X-ray Telescope on board Hinode and the passband ratio around 400 nm from an eclipse instrument, the Diagnostic Coronagraph Experiment (DICE). The phase speed (v_r), frequency (omega), and wavenumber (k) of the PIDs in the plumes are obtained by applying a Fourier transformation to the space-time (r-t plane) plots in images taken with the Atmospheric Imaging Assembly (AIA) in three different wavelength channels (171 A, 193 A, and 211 A). We found that the PIDs in the higher temperature AIA channels, 193 and 211 A, are faster than that of the cooler AIA 171 A channel. This tendency is more significant for the active plumes than the quiet ones. The observed speed ratio (~1.3) between the AIA 171 and 193 A channels is similar to the theoretical value (1.25) of a slow magnetoacoustic wave. Our results support the idea that PIDs in plumes represent a superposition of slow magnetoacoustic waves and plasma outflows that consist of dense cool flows and hot coronal jets.Comment: 18 pages, 8 figures, accepted for publication in Ap

Effects of warming and eutrophication on coastal phytoplankton production

Phytoplankton production in coastal waters influences seafood production and human health and can lead to harmful algal blooms. Water temperature and eutrophication are critical factors affecting phytoplankton production, although the combined effects of warming and nutrient changes on phytoplankton production in coastal waters are not well understood. To address this, phytoplankton production changes in natural waters were investigated using samples collected over eight months, and under 64 different initial conditions, established by combining four different water temperatures (i.e., ambient T, + 2, + 4, and + 6 degrees C), and two different nutrient conditions (i.e., non-enriched and enriched). Under the non-enriched conditions, the effect of warming on phytoplankton production was significantly positive in some months, significantly negative in others, or had no effect. However, under enriched conditions, warming affected phytoplankton production positively in all months except one, when the salinity was as low as 6.5. These results suggest that nutrient conditions can alter the effects of warming on phytoplankton production. Of several parameters, the ratio of initial nitrate concentration to chlorophyll a concentration [NCCA, mu M (pg L-1)(-1))] was one of the most critical factors determining the directionality of the warming effects. In laboratory experiments, when NCCA in the ambient or nutrient-enriched waters was >= 1.2, warming increased or did not change phytoplankton production with one exception; however, when NCCA was < 1.2, warming did not change or decreased production. In the time series data obtained from the coastal waters of four target countries, when NCCA was 1.5 or more, warming increased phytoplankton production, whereas when NCCA was lower than 1.5, warming lowered phytoplankton production, Thus, it is suggested that NCCA could be used as an index for predicting future phytoplankton production changes in coastal waters.11Ysciescopu

A retrospective analysis of second-line chemotherapy in patients with advanced gastric cancer

<p>Abstract</p> <p>Background</p> <p>Because treatment of advanced gastric cancer (AGC) patients after failure with first-line chemotherapy remains controversial, we performed this retrospective analysis based on the data obtained from 1455 patients registered in a first-line treatment cohort with respect to receiving or not receiving subsequent chemotherapy.</p> <p>Methods</p> <p>The decision for administering second-line chemotherapy was, in most cases, at the discretion of the physician. Seven-hundred twenty-five (50%) received second-line chemotherapy after first-line failure. Univariate and multivariate analyses were performed on the recognized baseline parameters for survival.</p> <p>Results</p> <p>At the time of initiating second-line chemotherapy, the patients' median age was 56 years (range, 22 to 86) and 139 (19%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or more. Seven (1%) complete and 108 (15%) partial responses to second-line chemotherapy were observed for an overall response rate of 16% (95% confidence interval [CI], 13 to 19%). The median progression-free and overall survivals, calculated from the start of second-line chemotherapy, were 2.9 months (95% CI, 2.6 to 3.3) and 6.7 months (95% CI, 5.8 to 7.5), respectively. Multivariate analysis revealed that low baseline hemoglobin level (hazard ratio [HR], 0.74; 95% CI 0.61–0.90) and a poor performance status (HR, 0.66; 95% CI, 0.52–0.83) were independent negative prognostic factors for overall survival.</p> <p>Conclusion</p> <p>Performance status, along with baseline hemoglobin level, could be used to identify the subgroup of patients most likely to benefit from second-line chemotherapy for AGC.</p

Metastatic lymph node in gastric cancer; Is it a real distant metastasis?

<p>Abstract</p> <p>Background</p> <p>Currently, the TNM staging system is a widely accepted method for assessing the prognosis of the disease and planning therapeutic strategies for cancer. Of the TNM system, the extent of lymph node involvement is the most important independent prognostic factor for gastric cancer. The aim of our study is to evaluate the survival and prognosis of gastric cancer patients with LN#12 or #13 involvement only and to assess the impact of anatomic regions of primary gastric tumor on survival in this particular subset of patients.</p> <p>Methods</p> <p>Among data of 1,008 stage IV gastric cancer patients who received curative R0 gastrectomy, a total of 79 patients with LN#12 (n = 68) and/or #13 (n = 11) were identified. All patients performed gastrectomy with D2 or D3 lymph node dissection.</p> <p>Results</p> <p>In 79 patients with LN#12/13 involvement, the estimated one-, three- and five-year survival rate was 77.2%, 41.8% and 26.6% respectively. When we compared the patients with LN#12/13 involvement to those without involvement, there was no significant difference in OS (21.0 months vs. 25.0 months, respectively; P = 0.140). However, OS was significantly longer in patients with LN#12/13 involvement only than in those with M1 lymph node involvement (14.3 months; P = 0.001). There was a significant difference in survival according to anatomic locations of the primary tumor (lower to mid-body vs. high body or whole stomach): 26.5 vs. 9.2 months (P = 0.009). In Cox proportional hazard analysis, only N stage (p = 0.002) had significance to predict poor survival.</p> <p>Conclusion</p> <p>In this study we found that curatively resected gastric cancer patients with pathologic involvement of LN #12 and/or LN #13 had favorable survival outcome, especially those with primary tumor location of mid-body to antrum. Prospective analysis of survival in gastric cancer patients with L N#12 or #13 metastasis is warranted especially with regards to primary tumor location.</p