1. |
- Chen, Qian Qian, et al.
(author)
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Age-dependent alpha-synuclein accumulation and aggregation in the colon of a transgenic mouse model of Parkinson's disease
- 2018
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In: Translational Neurodegeneration. - : Springer Science and Business Media LLC. - 2047-9158. ; 7:1
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Journal article (peer-reviewed)abstract
- Background: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, neuropathologically characterized by misfolded protein aggregation, called Lewy bodies and Lewy neurites. PD is a slow-progressive disease with colonic dysfunction appearing in the prodromal stage and lasting throughout the course of the disease. Methods: In order to study PD pathology in the colon, we examined the age-dependent morphological and pathological changes in the colon of a PD mouse model expressing human wildtype α-synuclein (α-syn) fused with the green fluorescent protein (GFP), under the endogenous mouse α-syn promoter. Results: We observed an age-dependent progressive expression and accumulation of α-syn-GFP in the enteric neurons of Meissner's (submucosal) and Auerbach's (myenteric) plexuses of the colon. Additionally, the phosphorylation of α-syn at serine 129 also increased with age and the aggregation of α-syn-GFP coincided with the appearance of motor deficits at 9 months of age. Furthermore, α-syn (-GFP) distinctly co-localized with different subtypes of neurons, as identified by immunohistochemical labeling of vasoactive intestinal peptide (VIP), neuronal nitric oxide synthase (nNOS), and calretinin. Conclusions: Our results show the development of α-syn pathology in the enteric neurons of the colon in a PD mouse model, which coincide with the appearance of motor deficits. Our mouse model possesses the potential and uniqueness for studying PD gastrointestinal dysfunction.
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2. |
- Zhang, Qi, et al.
(author)
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Muscle-like Artificial Molecular Actuators for Nanoparticles
- 2018
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In: Chem. - : Cell Press. - 2451-9308 .- 2451-9294. ; 4:11, s. 2670-2684
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Journal article (peer-reviewed)abstract
- Muscle tissue performs crucial contraction/extension motions that generate mechanical force and work by consuming chemical energy. Inspired by this naturally created biomolecular machine, artificial molecular muscles are designed and synthesized to undertake linear actuation functions. However, most of these muscle-like actuators are performed at large ensembles, while to realize the nanoscale actuation at the single-to few-molecule level remains challenging. Herein, we developed an artificial muscle-like molecular actuator that can reversibly control the proximity of the attached nano-objects, gold nanoparticles, within the single-molecule length level by its stimuli-responsive muscle-like linear contraction/extension motion. The molecular actuation motion is accompanied by an optical signal output resulting from the plasmonic resonance properties of gold nanoparticles. Meanwhile, the thermal noise of the muscle-like molecular actuator can be overcome by integrating the optical signal over a sufficiently long period.
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3. |
- Abolfathi, Bela, et al.
(author)
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The Fourteenth Data Release of the Sloan Digital Sky Survey : First Spectroscopic Data from the Extended Baryon Oscillation Spectroscopic Survey and from the Second Phase of the Apache Point Observatory Galactic Evolution Experiment
- 2018
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In: Astrophysical Journal Supplement Series. - : IOP Publishing Ltd. - 0067-0049 .- 1538-4365. ; 235:2
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Journal article (peer-reviewed)abstract
- The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since 2014 July. This paper describes the second data release from this phase, and the 14th from SDSS overall (making this Data Release Fourteen or DR14). This release makes the data taken by SDSS-IV in its first two years of operation (2014-2016 July) public. Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey; the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data-driven machine-learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from the SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS web site (www.sdss.org) has been updated for this release and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020 and will be followed by SDSS-V.
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4. |
- Li, Guoqiang, et al.
(author)
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Orbital scale lake evolution in the Ejina Basin, central Gobi Desert, China revealed by K-feldspar luminescence dating of paleolake shoreline features
- 2018
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In: Quaternary International. - : Elsevier BV. - 1040-6182 .- 1873-4553. ; 482, s. 109-121
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Journal article (peer-reviewed)abstract
- The Ejina Basin in the central Gobi Desert contains the terminal lakes of the Heihe River. Paleoenvironmental changes in the basin are important since its deposits are a significant source of Northern Hemisphere dust. In this study we employed a K-feldspar pIRIR dating technique to date shoreline features <= 940 m at multiple locations in the Ejina Basin similar to 45-50 m above the modern basin floor. Internal checks of luminescence characteristics were employed to test the reliability of the pIRIR dating. In combination with our previously reported stratigraphy and chronology of shorelines at <= 927 m in the Ejina Basin, these results imply that a paleolake was present in the basin prior to similar to 350 ka. Other high stands in the basin occurred at similar to 320-310 ka, 240-180 ka, 120-80 ka, and similar to 5 ka, corresponding to MIS 9, MIS 7, MIS 5 and the mid Holocene (MIS 1), respectively, indicating a strong link with glacial-interglacial cycles. Extensions of the East Asian Summer Monsoon (EASM) during interglacial periods, possibly interacting with the Westerlies, apparently caused higher precipitation and lake formation. The impact of orbital eccentricity on the EASM/Westerlies appears to be responsible for the formation of major lake/desert cycles on the northeastern margin of the Tibetan Plateau.
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5. |
- Li, Zhixuan, et al.
(author)
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Revealing two radio-active galactic nuclei extremely near PSR J0437−4715
- 2018
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 476:1, s. 399-406
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Journal article (peer-reviewed)abstract
- Newton's gravitational constant G may vary with time at an extremely low level. The time variability of G will affect the orbital motion of a millisecond pulsar in a binary system and cause a tiny difference between the orbital period-dependent measurement of the kinematic distance and the direct measurement of the annual parallax distance. PSR J0437-4715 is the nearest millisecond pulsar and the brightest at radio wavelengths. To explore the feasibility of achieving a parallax distance accuracy of one light-year, comparable to the recent timing result, with the technique of differential astrometry, we searched for compact radio sources quite close to PSR J0437-4715. Using existing data from the Very Large Array and the Australia Telescope Compact Array, we detected two sources with flat spectra, relatively stable flux densities of 0.9 and 1.0 mJy at 8.4 GHz and separations of 13 and 45 arcsec. With a network consisting of the Long Baseline Array and the Kunming 40-m radio telescope, we found that both sources have a point-like structure and a brightness temperature of >= 10(7) K. According to these radio inputs and the absence of counterparts in other bands, we argue that they are most likely the compact radio cores of extragalactic active galactic nuclei, rather than Galactic radio stars. The finding of these two radio active galactic nuclei will enable us to achieve a sub-pc distance accuracy with in-beam phase-referencing very-long-baseline interferometric observations and provide one of the most stringent constraints on the time variability of G in the near future.
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6. |
- McKeown, Nicola M., et al.
(author)
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Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway : a meta-analysis
- 2018
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:2, s. 317-330
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits. Methods: Data from 11 cohorts (six discovery and five replication) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided association and interaction results from 34,748 adults of European descent. SSB intake (soft drinks, fruit punches, lemonades or other fruit drinks) was derived from food-frequency questionnaires and food diaries. In fixed-effects meta-analyses, we quantified: (1) the associations between SSBs and glycaemic traits (fasting glucose and fasting insulin); and (2) the interactions between SSBs and 18 independent SNPs related to the ChREBP-FGF21 pathway. Results: In our combined meta-analyses of discovery and replication cohorts, after adjustment for age, sex, energy intake, BMI and other dietary covariates, each additional serving of SSB intake was associated with higher fasting glucose (β ± SE 0.014 ± 0.004 [mmol/l], p = 1.5 × 10−3) and higher fasting insulin (0.030 ± 0.005 [loge pmol/l], p = 2.0 × 10−10). No significant interactions on glycaemic traits were observed between SSB intake and selected SNPs. While a suggestive interaction was observed in the discovery cohorts with a SNP (rs1542423) in the β-Klotho (KLB) locus on fasting insulin (0.030 ± 0.011 loge pmol/l, uncorrected p = 0.006), results in the replication cohorts and combined meta-analyses were non-significant. Conclusions/interpretation: In this large meta-analysis, we observed that SSB intake was associated with higher fasting glucose and insulin. Although a suggestive interaction with a genetic variant in the ChREBP-FGF21 pathway was observed in the discovery cohorts, this observation was not confirmed in the replication analysis. Trial registration: Trials related to this study were registered at clinicaltrials.govas NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT00005487 (Multi-Ethnic Study of Atherosclerosis) and NCT00005152 (Nurses’ Health Study).
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7. |
- Zhang, Ping, et al.
(author)
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Deficiency of alkaline SMase enhances dextran sulfate sodium-induced colitis in mice with upregulation of autotaxin
- 2018
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In: Journal of Lipid Research. - 1539-7262. ; 59:10, s. 1841-1850
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Journal article (peer-reviewed)abstract
- Intestinal alkaline SMase (Alk-SMase) cleaves phosphocholine from SM, platelet-activating factor (PAF), and lysophosphatidylcholine. We recently found that colitis-associated colon cancer was 4- to 5-fold enhanced in Alk-SMase KO mice. Here, we further studied the pathogenesis of colitis induced by dextran sulfate sodium (DSS) in WT and KO mice. Compared with WT mice, KO mice demonstrated greater body weight loss, more severe bloody diarrhea, broader inflammatory cell infiltration, and more serious epithelial injury. Higher levels of PAF and lower levels of interleukin (IL)10 were identified in KO mice 2 days after DSS treatment. A greater and progressive increase of lysophosphatidic acid (LPA) was identified. The change was associated with increased autotaxin expression in both small intestine and colon, which was identified by immunohistochemistry study, Western blot, and sandwich ELISA. The upregulation of autotaxin coincided with an early increase of PAF. IL6 and TNFα were increased in both WT and KO mice. At the later stage (day 8), significant decreases in IL6, IL10, and PAF were identified, and the decreases were greater in KO mice. In conclusion, deficiency of Alk-SMase enhances DSS-induced colitis by mechanisms related to increased autotaxin expression and LPA formation. The early increase of PAF might be a trigger for such reactions.
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8. |
- Chen, XÍ, et al.
(author)
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TDHQ Enabling Fine-granularity Adaptive Loading for SSB-DMT Systems
- 2018
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In: IEEE Photonics Technology Letters. - : Institute of Electrical and Electronics Engineers Inc.. - 1041-1135 .- 1941-0174. ; 30:19, s. 1687-1690
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Journal article (peer-reviewed)abstract
- In this letter, we introduce time domain hybrid quadrature amplitude modulation (TDHQ) for the single sideband (SSB) discrete multi-tone (DMT) systems. Experimental results reveal that with a single precoding set and the proposed adaptive loading algorithm, the TDHQ scheme can achieve finer granularity and therefore smoother continuous growth of data rate than that with the conventional quadrature amplitude modulation (QAM). Besides, thanks to the frame construction and the tailored mapping rule, the scheme with TDHQ has an obviously better peak to average power ratio (PAPR).
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9. |
- Collin-Dufresne, Pierre, et al.
(author)
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Activism, Strategic Trading, and Liquidity
- 2018
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In: Econometrica. - : Econometric Society: Econometrica. - 1468-0262 .- 0012-9682. ; 86:4, s. 1431-1463
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Journal article (peer-reviewed)abstract
- We analyze dynamic trading by an activist investor who can expend costly effort to affect firm value. We obtain the equilibrium in closed form for a general activism technology, including both binary and continuous outcomes. Variation in parameters can produce either positive or negative relations between market liquidity and economic efficiency, depending on the activism technology and model parameters. Two results that contrast with the previous literature are that (a) the relationship between market liquidity and economic efficiency is independent of the activist's initial stake for a broad set of activism technologies, and (b) an increase in noise trading can reduce market liquidity because it increases uncertainty about the activist's trades (the activist trades in the opposite direction of noise traders) and thereby increases information asymmetry about the activist's intentions.
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