bluuebunny/crossref_metadata_2025 huggingface dataset:
Gravity Wave Influences On Mesoscale Divergence: An Observational Case Study
Authors: Stephan C. C. , Lane T. P. , Jakob C.
Published: January 2020

Characteristics of tropospheric low‐frequency gravity waves are diagnosed in radiosonde soundings from the Tropical Warm Pool‐International Cloud Experiment near Darwin, Australia. The waves have typical vertical wavelengths of about 4 km, horizontal wavelengths of about 600 km, and intrinsic periods of about 12 hr. These scales match those of the vertical, horizontal, and temporal variability found in area‐averaged horizontal wind divergence over the same domain. Vertical profiles of divergence show wave‐like structures with variability of the order of 2 
 10
 s
in the free troposphere. The results for Darwin are similar to previously reported observed mesoscale patterns of divergence/convergence over the tropical Atlantic. The findings imply that tropical divergence on spatial scales of a few hundred kilometers, which is known to influence the organization of convection, may be forced by gravity waves.
Coordinated Observations of 8‐ and 6‐hr Tides in the Mesosphere and Lower Thermosphere by Three Meteor Radars Near 60°S Latitude
Authors: Liu Guiping , Janches Diego , Lieberman Ruth S. , Moffat‐Griffin Tracy , Fritts David C. , Mitchell Nicholas J.
Published: January 2020

Atmospheric 8‐ and 6‐hr tides are observed for the first time in the zonal and meridional winds at ~82–97 km altitudes simultaneously at Tierra del Fuego (TDF; 53.7°S, 67.7°W), King Edward Point (KEP; 54.3°S, 36.5°W), and Rothera (ROT; 67.5°S, 68.0°W) at Southern Hemisphere (SH) middle‐to‐high latitudes during long time spans, allowing to reveal climatology and migrating nature. The monthly averaged amplitudes vary between ~1 and 8 m/s for the 8‐hr tides while the amplitudes of 6‐hr tides are smaller ~0.5–4 m/s. Both tides exhibit an annual pattern having the amplitude maxima during SH winter and minima in SH summer. The tidal phases are smaller (earlier) in the zonal wind than in the meridional wind by about 90°. The phase differences observed between TDF and KEP, which are located at similar latitudes but different longitudes suggest the propagation of migrating tides. The study finds that 8‐ and 6‐hr tides are correlated.
Bias Correction of Paleoclimatic Reconstructions: A New Look at 1,200+ Years of Upper Colorado River Flow
Authors: Robeson Scott M. , Maxwell Justin T. , Ficklin Darren L.
Published: January 2020

Bias correction, while widely used with climate‐model output, is not typically applied to paleoclimatic reconstructions. While many reconstruction models have low average error, they still may contain bias, especially in the tails of distributions. Bias correction, used cautiously, can be a valuable procedure that alters interpretations of past events. Analyzing the iconic tree‐ring reconstruction of Upper Colorado River flow, we find that its probability distribution is markedly different from that of observed flow. Using quantile mapping to bias correct the reconstruction, we analyze the full reconstructed record and two events in particular: the 1100s megadrought and the early 1600s pluvial. Overall, bias correction made the 1100s megadrought, the largest in the 1,200+year record, even more extreme. After bias correction, the early 1600s pluvial marginally exceeds the early twentieth century pluvial in magnitude but not in duration. Overall, bias correction should be considered whenever paleoclimatic reconstructions are compared directly to observations.
Enhanced Carbon Uptake and Reduced Methane Emissions in a Newly Restored Wetland
Authors: Yang Hualei , Tang Jianwu , Zhang Chunsong , Dai Yuhang , Zhou Cheng , Xu Ping , Perry Danielle C. , Chen Xuechu
Published: January 2020

Wetlands play an important role in reducing global warming potential in response to global climate change. Unfortunately, due to the effects of human disturbance and natural erosion, wetlands are facing global extinction. It is essential to implement engineering measures to restore damaged wetlands. However, the carbon sink capacity of restored wetlands is unclear. We examined the seasonal change of greenhouse gas emissions in both restored wetland and natural wetland and then evaluated the carbon sequestration capacity of the restored wetland. We found that (1) the carbon sink capacity of the restored wetland showed clear daily and seasonal change, which was affected by light intensity, air temperature, and vegetation growth, and (2) the annual daytime (8–18 hr) sustained‐flux global warming potential was −11.23 ± 4.34 kg CO2 m−2 y−1, representing a much larger carbon sink than natural wetland (−5.04 ± 3.73 kg CO2 m−2 y−1) from April to December. In addition, the results showed that appropriate tidal flow management may help to reduce CH4 emission in wetland restoration. Thus, we proposed that the restored coastal wetland, via effective engineering measures, reliably acted as a large net carbon sink and has the potential to help mitigate climate change.
Imaging stressed organellesviasugar-conjugated color-switchable pH sensors
Authors: Zhang Enkang , Wang Siyu , Su Xinhui , Han Shoufa
Published: January 2020

Sugar-conjugated pH sensors discriminate stressed lysosomes in different cell starvation conditionsviared-to-green fluorescence switch.
Synthesis of planar chiral ferrocenes via a Pd(0)-catalyzed syn-carbopalladation/asymmetric C–H alkenylation process
Authors: Jia Lixiang , Liu Xiaobing , Zhang An-An , Wang Tao , Hua Yuanzhao , Li Heng , Liu Lantao
Published: January 2020

The Pd(0)-catalyzed tandem intermolecular syn-carbopalladation/asymmetric C–H alkenylation reaction of N-ferrocenyl propiolamides with aryl iodides has been realized, generating planar chiral ferrocene[1,2-d] pyrrolinones in good yields.
Regioselective synthesis of 4-fluoro-1,5-disubstituted-1,2,3-triazoles from synthetic surrogates of α-fluoroalkynes
Authors: Jana Sampad , Adhikari Sweta , Cox Michael R. , Roy Sudeshna
Published: January 2020

This TFA-catalyzed [3+2] cycloaddition of organic azides with α-fluoronitroalkenes, used as synthetic surrogates of α-fluoroalkynes, provides a new route to multi-substituted fluorotriazoles with broader substrate scopes and high regioselectivity.
Enantioselective (3+2) cycloaddition via N-heterocyclic carbene-catalyzed addition of homoenolates to cyclic N-sulfonyl trifluoromethylated ketimines: synthesis of fused N-heterocycle γ-lactams
Authors: Zhang Zhen-Zhen , Zhang Yongna , Duan Hui-Xin , Deng Zhuo-Fei , Wang You-Qing
Published: January 2020

An enantioselective (3+2) cycloaddition via N-heterocyclic carbene-catalyzed homoenolate addition to cyclic N-sulfonyl trifluoromethyl ketimines is realized, affording fused N-heterocycle γ-lactams with up to >20 : 1 dr and 94–99% ee.
Light-powered and transient peptide two-dimensional assembly driven by trans-to-cis isomerization of azobenzene side chains
Authors: Xie Xiaoming , Wang Liang , Liu Xiaohuan , Du Zhanglei , Li Yiwen , Li Bao , Wu Lixin , Li Wen
Published: January 2020

A 2D dissipative system is initiated by photo-powered trans-to-cis isomerization of azobenzene, which usually results in the collapse of ordered assemblies.
The regioselective annulation of alkylidenecyclopropanes by Rh(iii)-catalyzed C–H/C–C activation to access spirocyclic benzosultams
Authors: Li Qiuyun , Yuan Xin , Li Bin , Wang Baiquan
Published: January 2020

The synthesis of spirocyclic benzosultams fromN-sulfonyl ketimine and alkylidenecyclopropanes under Rh(iii) catalysis has been developed. This transformation enables the formation of two C–C bonds and a double bond with highE-selectivity.
Core-mediated synthesis, growth mechanism and near-infrared luminescence enhancement of α-NaGdF4@β-NaLuF4:Nd3+ core–shell nanocrystals
Authors: Shao Qinqin , Yang Chao , Chen Xiaoxu , Zhang Hong , Feng Guoying , Zhou Shouhuan
Published: January 2020

High-performance α-NaGdF4@β-NaLuF4:Nd3+ nanocrystals have been constructed based on a core-mediated method. Their near-infrared emission intensity was eventually enhanced by more than 2 times.
Facile template synthesis of dumbbell-like Mn2O3 with oxygen vacancies for efficient degradation of organic pollutants by activating peroxymonosulfate
Authors: Li Yang , Li Didi , Fan Shisuo , Yang Ting , Zhou Qi
Published: January 2020

A novel dumbbell-like Mn2O3 microstructure prepared under mild conditions was used as a catalyst to PMS activation for RhB degradation. In the Mn2O3/PMS system, the reactive oxygen species were revealed in the degradation process by PMS activation.
Improved electrochemical performance of 2D accordion-like MnV2O6 nanosheets as anode materials for Li-ion batteries
Authors: Zhang Xiaoyu , Li Xinjian , Jiang Fuyi , Du Wei , Hou Chuanxin , Xu Ziyang , Zhu Linwei , Wang Zhengkun , Liu Huan , Zhou Wenjiao , Yuan Hua
Published: January 2020

MnV2O6 is a promising anode material for lithium ion batteries with high theoretical specific capacity, abundant reserves and inexpensive constituent elements.
Towards the commercialization of colloidal quantum dot solar cells: perspectives on device structures and manufacturing
Authors: Lee Hyunho , Song Hyung-Jun , Shim Moonsub , Lee Changhee
Published: January 2020

A review towards the commercialization of colloidal quantum dot solar cells.
Screening of Lactobacillus salivarius strains from the feces of Chinese populations and the evaluation of their effects against intestinal inflammation in mice
Authors: Zhai Qixiao , Shen Xudan , Cen Shi , Zhang Chengcheng , Tian Fengwei , Zhao Jianxin , Zhang Hao , Xue Yuzheng , Chen Wei
Published: January 2020

Screening of Lactobacillus salivarius strains and the evaluation of their effects against intestinal inflammation in mice.
Recent advances in tuning the electronic structures of atomically dispersed M–N–C materials for efficient gas-involving electrocatalysis
Authors: Huang Dekang , Luo Yanzhu , Li Shu , Liao Li , Li Yunxiang , Chen Hao , Ye Jinhua
Published: January 2020

A focused review is presented to comprehensively summarize the reported electronic structure modulation strategies for achieving highly active M–N–C electrocatalysts.
Universally applicable RNA membrane-based microneedle system for transdermal drug delivery
Authors: Kim Dajeong , Kim Hyejin , Lee Peter C. W. , Lee Jong Bum
Published: January 2020

RNA membrane-based microneedle coating system for the facile fabrication of tailor-made microneedles for transdermal drug delivery.
Two-dimensional Bi2Se3 nanosheet based flexible infrared photodetector with pencil-drawn graphite electrodes on paper
Authors: Liu Shengqian , Huang Zongyu , Qiao Hui , Hu Rong , Ma Qian , Huang Kai , Li Hongxing , Qi Xiang
Published: January 2020

Flexible optoelectronic devices have been of great significance in recent years, owing to their extensive commercial and military applications.
Electrochemical sensor for sensitive detection of luteolin based on multi-walled carbon nanotubes/poly(3,4-ethylenedioxythiophene)–gold nanocomposites
Authors: Cheng Wenxue , Zeng Peiyi , Ma Cenhuai , Peng Haoming , Yang Jinsha , Huang Jianzhi , Zhang Min , Cheng Faliang
Published: January 2020

An electrochemical sensor based on MWCNTs/PEDT–Au nanocomposite modified GCE for electrochemical determination of luteolin was presented.
Synthesis and NMR study of trimethylphosphine gold(i)-appended calix[8]arenes as precursors of gold nanoparticles
Authors: Clément Marie , Abdellah Ibrahim , Ray Priyanka , Martini Cyril , Coppel Yannick , Remita Hynd , Lampre Isabelle , Huc Vincent
Published: January 2020

In this paper, the synthesis of gold(i)-calix[8]arene complexes from benzyloxycalix[8]arene is reported as well as their radiolytic reduction leading to gold nanoparticles.
Tuning the stability of organic radicals: from covalent approaches to non-covalent approaches
Authors: Tang Bohan , Zhao Jiantao , Xu Jiang-Fei , Zhang Xi
Published: January 2020

Covalent and non-covalent approaches to tune the stability of organic radicals through steric effects and the delocalization of spin density.
Discovery of low-temperature GeTe-based thermoelectric alloys with high performance competing with Bi2Te3
Authors: Wang Longquan , Li Junqin , Zhang Chunxiao , Ding Teng , Xie Yucheng , Li Yu , Liu Fusheng , Ao Weiqin , Zhang Chaohua
Published: January 2020

A kind of low-temperature thermoelectric material is discovered in quenched GeTe-based alloys with high performance superior to Bi2Te3-based alloys.
Anomalous lattice thermal conductivity in layered MNCl (M = Zr, Hf) materials driven by lanthanide contraction
Authors: Yu Xiaoxia , Shao Hezhu , Wang Xueyun , Zhu Yingcai , Fang Daining , Hong Jiawang
Published: January 2020

An abnormal high lattice thermal conductivity for the heavy material driven by lanthanide contraction.
Semiconductor-based photocatalysts for photocatalytic and photoelectrochemical water splitting: will we stop with photocorrosion?
Authors: Chen Sha , Huang Danlian , Xu Piao , Xue Wenjing , Lei Lei , Cheng Min , Wang Rongzhong , Liu Xigui , Deng Rui
Published: January 2020

This review outlines recent advances in strategies to improve the photoreaction stability of photocatalytic/photoelectrochemical water splitting systems, and discusses the tactics involved in improving the stability of such systems with different photocorrosion mechanisms.
Attenuating the defect activities with a rubidium additive for efficient and stable Sn-based halide perovskite solar cells
Authors: Khadka Dhruba B. , Shirai Yasuhiro , Yanagida Masatoshi , Miyano Kenjiro
Published: January 2020

Rb incorporation in FASnI3 improved the device performance and stability as a consequence of the suppression of the extent of Sn2+ oxidation and mitigating defect activities.
Metallic reflectors with notched RCS spectral signature using dielectric resonators
Authors: Alhaj Abbas A. , El‐Absi M. , Abuelhaija A. , Solbach K. , Kaiser T.
Published: January 2020

Dielectric resonators are placed in front of the metallic plane plate and corner reflectors. Excitation of the resonant mode produces strong scattering of an incident plane wave which shows up as narrow notch in the mono‐static radar cross section (RCS) spectral signature at the resonance frequency. Experimental proof at V‐band is given with a corner reflector of centimetre size with spherical dielectric resonators of 0.8 mm diameter showing a notch at 64 GHz.
Radio frequency reliability studies of CMOS RF integrated circuits for ultra‐thin flexible packages
Authors: Mitra D. , Hamidi S.B. , Roy P. , Biswas C. , Biswas A. , Dawn D.
Published: January 2020

This Letter presents for the first time radio frequency (RF) reliability studies of fully integrated CMOS RF integrated circuits (RFICs) for next generation wireless communication applications involving conformal bodies where wireless communication RFICs will be embedded on ultra‐thin flexible packages. As a test case, RF characteristics of a CMOS voltage‐controlled oscillator (VCO) chip with multiple die‐substrate thicknesses were measured and results are analysed. The CMOS VCO chip under study was designed and fabricated using 180 nm RF‐CMOS process. Reliability of performances of the VCO chips are characterised and results are compared before and after die thinning from 250 to 50, 35, and 25 μm, respectively. Critical RF performance parameters such as frequency of oscillation, output power, and phase noise are considered for analysis, respectively. All the dies are placed face‐up for probing on the top of a metal chuck with ground connection inside the micro‐chamber of a probe station. While the deviations of frequency and output power are within ±1% and ±1 dB, respectively, due to the die thinning affect, the phase noise deteriorations are observed significant. It confirms the well‐known fact of phase noise sensitiveness to the substrate thickness due to the leakage and SOI CMOS is discussed widely to minimise these parasitic effects.
Low‐profile broadband aperture coupled magneto‐electric dipole array antenna for millimetre‐wave applications
Authors: Yang Guopeng , Zhang Jinping , Zhou Zhipeng
Published: January 2020

This Letter presents a low‐profile broadband cavity‐backed magneto‐electric (ME) dipole antenna fed by a substrate integrated waveguide aperture. To reduce the antenna profile, a U‐shaped slot is etched on the electric dipole. Compared to the traditional ME dipole antenna whose profile is generally , the thickness of the proposed radiation structure is , where is the wavelength in the dielectric substrate. A array antenna with the proposed antenna as its element is then designed, simulated and fabricated. With the return loss is below −10 dB, a 19.1% (30.3–36.7 GHz) impedance bandwidth has been achieved. The radiation pattern of the proposed array antenna is quite stable, and the peak gain varies below 1 dB within the operating band.
Dual‐wideband dual‐polarised magnetoelectric dipole antenna for 4G/5G microcell base station
Authors: Zhu Congcong , Wang Bin , Luo Wei , Hao Honggang , Wang Ping
Published: January 2020

A novel dual‐wideband dual‐polarised magnetoelectric (ME) dipole antenna for the fourth generation (4G)/fifth generation (5G) microcell base station is proposed. Using a pair of orthogonal ME dipoles and Γ‐shaped tapered cross feeding lines, the initial antenna achieves dual‐band and dual‐polarised. Then, four U‐shaped gaps, added in electric dipoles, effectively extend the lower impedance bandwidth. Finally, a circular parasitic patch with capacitive properties is innovatively loaded above the ME antenna, which obviously reduces the high‐resonant frequency from 5.5 to 4.9 GHz. Meanwhile, a box‐shaped reflector is employed to achieve stable gain and radiation patterns. As a result, the measured results show the good dual‐wideband performance of 52.4% (2.14–3.66 GHz) and 7.4% (4.68–5.04 GHz) with voltage standing wave ratio (VSWR) < 2, high isolation (>25 dB) and high gain (9.5 and 5.5 dBi, respectively). In addition, a stable radiation pattern with a half‐power beam width of and good cross‐polarisation discrimination (>20 dB) on the E‐plane is realised over these two bands.
300‐GHz integrated heterodyne receiver with carrier lock‐in Costas loop
Authors: Yi C. , Choi S.‐H. , Kim M.
Published: January 2020

A carrier signal lock‐in experiment using a 300‐GHz integrated heterodyne circuit is presented. The circuit contains a single voltage‐controlled oscillator with a single set of quadrature mixers that are fabricated using 250‐nm InP double hetero‐junction bipolar transistor technology. An external feedback loop containing packaged baseband components such as amplifiers, a phase discriminator, and a filter is connected to the integrated circuit to form a complete receiver system. For a −25 dBm of input RF signal with 3.5‐GHz single‐tone carrier‐suppressed modulation, the receiver system responds with successful lock‐in range of 110 MHz centred around 311 GHz.
A parsec-scale wobbling jet in the high-synchrotron peaked blazar PG 1553+113
Authors: Lico R. , Liu J. , Giroletti M. , Orienti M. , Gómez J. L. , Piner B. G. , MacDonald N. R. , D’Ammando F. , Fuentes A.
Published: January 2020

Context. The detection of quasi-periodic variability in active galactic nuclei in general, and in blazars in particular, is key to our understanding of the origin and nature of these objects as well as their cosmological evolution. PG 1553+113 is the first blazar showing an approximately two-year quasi-periodic pattern in its γ-ray light curve, which is also revealed at optical frequencies.

Aims. Such quasi-periodicity might have a geometrical origin, possibly related to the precessing nature of the jet, or could be intrinsic to the source and related to pulsational accretion flow instabilities. In this work we investigate and characterise the high-resolution radio emission properties of PG 1553+113 on parsec scales in order to differentiate between these different physical scenarios.

Methods. We monitored the source with the very long baseline array (VLBA) at 15, 24, and 43 GHz during an entire cycle of γ-ray activity in the period 2015–2017, with a cadence of about 2 months, both in total and polarised intensity. We constrained the jet position angle across the different observing epochs by investigating the total intensity ridge lines.

Results. We find a core-dominated source with a limb-brightened jet structure extending for ∼1.5 mas in the northeast direction whose position angle varies in time in the range ∼40°−60°. No clear periodic pattern can be recognized in the VLBA light curves during 2015–2017 or in the 15 GHz Owens Valley Radio Observatory light curve during the period 2008–2018. The core region polarisation percentage varies in the range ∼1−4%, and the polarisation angle varies from being roughly parallel to roughly transverse to the jet axis. We estimate a rotation measure value in the core region of ∼−1.0 ± 0.4 × 104 rad m−2. The brightness temperature (TB) is found to decrease as the frequency increases with an intrinsic value of ∼1.5 × 1010 K and the estimated Doppler factor is ∼1.4.

Conclusions. Although the jet wobbling motion indicates that geometrical effects can produce an enhanced emission through the Doppler boosting modulation, additional mechanisms are required in order to account for the quasi-periodic variability patterns observed in γ rays. The intrinsic TB value indicates that the total energy in the core region is dominated by the magnetic field.
A Comprehensive Tyrosine Phosphoproteomic Analysis Reveals Novel Components of the Platelet CLEC-2 Signaling Cascade
Authors: Izquierdo Irene , Barrachina María N. , Hermida-Nogueira Lidia , Casas Vanessa , Morán Luis A. , Lacerenza Serena , Pinto-Llorente Roberto , Eble Johannes A. , de los Ríos Vivian , Domínguez Eduardo , Loza María I. , Casal José Ignacio , Carrascal Montserrat , Abián Joaquín , García Angel
Published: January 2020

C-type lectin-like receptor 2 (CLEC-2) plays a crucial role in different platelet-related physiological and pathological processes. It signals through a tyrosine kinase-mediated pathway that is highly dependent on the positive feedback exerted by the platelet-derived secondary mediators, adenosine diphosphate (ADP) and thromboxane A2 (TXA2). Here, we aimed to analyze the tyrosine phosphoproteome of platelets activated with the CLEC-2 agonist rhodocytin to identify relevant phosphorylated tyrosine residues (p-Tyr) and proteins involved in platelet activation downstream of this receptor. We identified 363 differentially p-Tyr residues, corresponding to the majority of proteins previously known to participate in CLEC-2 signaling and also novel ones, including adaptors (e.g., DAPP1, Dok1/3, CASS4, Nck1/2), kinases/phosphatases (e.g., FAK1, FES, FGR, JAK2, SHIP2), and membrane proteins (e.g., G6F, JAM-A, PECAM-1, TLT-1). To elucidate the contribution of ADP and TXA2 at different points of the CLEC-2 signaling cascade, we evaluated p-Tyr levels of residues identified in the analysis and known to be essential for the catalytic activity of kinases Syk(p-Tyr525+526) and Src(p-Tyr419), and for PLCγ2 activity (p-Tyr759). We demonstrated that Syk phosphorylation at Tyr525+526 also happens in the presence of ADP and TXA2 inhibitors, which is not the case for Src-pTyr419 and PLCγ2-pTyr759. Kinetics studies for the three phosphoproteins show some differences in the phosphorylation profile. Ca2+ mobilization assays confirmed the relevance of ADP and TXA2 for full CLEC-2-mediated platelet activation. The present study provides significant insights into the intracellular events that take place following CLEC-2 activation in platelets, contributing to elucidate in detail the CLEC-2 signalosome.
Reduced Plasma Magnesium Levels in Type-1 Diabetes Associate with Prothrombotic Changes in Fibrin Clotting and Fibrinolysis
Authors: Sobczak Amélie I. S. , Phoenix Fladia A. , Pitt Samantha J. , Ajjan Ramzi A. , Stewart Alan J.
Published: January 2020

Individuals with type-1 diabetes mellitus (T1DM) have a higher risk of thrombosis and low plasma magnesium concentrations. As magnesium is a known regulator of fibrin network formation, we investigated potential associations between fibrin clot properties and plasma magnesium concentrations in 45 individuals with T1DM and 47 age- and sex-matched controls without diabetes. Fibrin clot characteristics were assessed using a validated turbidimetric assay and associations with plasma magnesium concentration were examined. Plasma concentrations of fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and lipids were measured and fibrin fiber diameters assessed using scanning electron microscopy. Fibrin clot maximum absorbance was unchanged in subjects with T1DM compared with controls, while lysis time was prolonged (p = 0.0273). No differences in fibrin fiber diameters or in lipid profile were observed between T1DM and controls. PAI-1 concentration was lower in the T1DM group compared with the controls (p = 0.0232) and positively correlated with lysis time (p = 0.0023). Plasma magnesium concentration was lower in the T1DM group compared with controls (p < 0.0001). Magnesium concentration negatively correlated with clot maximum absorbance (p = 0.0215) and lysis time (p = 0.0464). A turbidimetric fibrin clot lysis assay performed in a purified system that included PAI-1 and 0 to 3.2 mM Mg2+ showed a shortening of lysis time with increasing Mg2+ concentrations (p = 0.0004). Our findings reveal that plasma magnesium concentration is associated with changes in fibrin clot and lysis parameters.
Translation of the intrinsically disordered protein α-synuclein is inhibited by a small molecule targeting its structured mRNA
Authors: Zhang Peiyuan , Park Hye-Jin , Zhang Jie , Junn Eunsung , Andrews Ryan J. , Velagapudi Sai Pradeep , Abegg Daniel , Vishnu Kamalakannan , Costales Matthew G. , Childs-Disney Jessica L. , Adibekian Alexander , Moss Walter N. , Mouradian M. Maral , Disney Matthew D.
Published: January 2020

Many proteins are refractory to targeting because they lack small-molecule binding pockets. An alternative to drugging these proteins directly is to target the messenger (m)RNA that encodes them, thereby reducing protein levels. We describe such an approach for the difficult-to-target protein α-synuclein encoded by the
SNCA
gene. Multiplication of the
SNCA
gene locus causes dominantly inherited Parkinson’s disease (PD), and α-synuclein protein aggregates in Lewy bodies and Lewy neurites in sporadic PD. Thus, reducing the expression of α-synuclein protein is expected to have therapeutic value. Fortuitously, the
SNCA
mRNA has a structured iron-responsive element (IRE) in its 5′ untranslated region (5′ UTR) that controls its translation. Using sequence-based design, we discovered small molecules that target the IRE structure and inhibit
SNCA
translation in cells, the most potent of which is named Synucleozid. Both in vitro and cellular profiling studies showed Synucleozid directly targets the α-synuclein mRNA 5′ UTR at the designed site. Mechanistic studies revealed that Synucleozid reduces α-synuclein protein levels by decreasing the amount of
SNCA
mRNA loaded into polysomes, mechanistically providing a cytoprotective effect in cells. Proteome- and transcriptome-wide studies showed that the compound’s selectivity makes Synucleozid suitable for further development. Importantly, transcriptome-wide analysis of mRNAs that encode intrinsically disordered proteins revealed that each has structured regions that could be targeted with small molecules. These findings demonstrate the potential for targeting undruggable proteins at the level of their coding mRNAs. This approach, as applied to
SNCA
, is a promising disease-modifying therapeutic strategy for PD and other α-synucleinopathies.
Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans
Authors: Yang Tzu-Jing , Chang Yen-Chen , Ko Tzu-Ping , Draczkowski Piotr , Chien Yu-Chun , Chang Yuan-Chih , Wu Kuen-Phon , Khoo Kay-Hooi , Chang Hui-Wen , Hsu Shang-Te Danny
Published: January 2020

Feline infectious peritonitis virus (FIPV) is an alphacoronavirus that causes a nearly 100% mortality rate without effective treatment. Here we report a 3.3-Å cryoelectron microscopy (cryo-EM) structure of the serotype I FIPV spike (S) protein, which is responsible for host recognition and viral entry. Mass spectrometry provided site-specific compositions of densely distributed high-mannose and complex-type N-glycans that account for 1/4 of the total molecular mass; most of the N-glycans could be visualized by cryo-EM. Specifically, the N-glycans that wedge between 2 galectin-like domains within the S1 subunit of FIPV S protein result in a unique propeller-like conformation, underscoring the importance of glycosylation in maintaining protein structures. The cleavage site within the S2 subunit responsible for activation also showed distinct structural features and glycosylation. These structural insights provide a blueprint for a better molecular understanding of the pathogenesis of FIP.
NK cells clear α-synuclein and the depletion of NK cells exacerbates synuclein pathology in a mouse model of α-synucleinopathy
Authors: Earls Rachael H. , Menees Kelly B. , Chung Jaegwon , Gutekunst Claire-Anne , Lee Hyun Joon , Hazim Manuel G. , Rada Balázs , Wood Levi B. , Lee Jae-Kyung
Published: January 2020

The pathological hallmark of synucleinopathies, including Lewy body dementia and Parkinson’s disease (PD), is the presence of Lewy bodies, which are primarily composed of intracellular inclusions of misfolded α-synuclein (α-syn) among other proteins. α-Syn is found in extracellular biological fluids in PD patients and has been implicated in modulating immune responses in the central nervous system (CNS) and the periphery. Natural killer (NK) cells are innate effector lymphocytes that are present in the CNS in homeostatic and pathological conditions. NK cell numbers are increased in the blood of PD patients and their activity is associated with disease severity; however, the role of NK cells in the context of α-synucleinopathies has never been explored. Here, we show that human NK cells can efficiently internalize and degrade α-syn aggregates via the endosomal/lysosomal pathway. We demonstrate that α-syn aggregates attenuate NK cell cytotoxicity in a dose-dependent manner and decrease the release of the proinflammatory cytokine, IFN-γ. To address the role of NK cells in PD pathogenesis, NK cell function was investigated in a preformed fibril α-syn–induced mouse PD model. Our studies demonstrate that in vivo depletion of NK cells in a preclinical mouse PD model resulted in exacerbated motor deficits and increased phosphorylated α-syn deposits. Collectively, our data provide a role of NK cells in modulating synuclein pathology and motor symptoms in a preclinical mouse model of PD, which could be developed into a therapeutic for PD and other synucleinopathies.
Highly efficient binary copper−iron catalyst for photoelectrochemical carbon dioxide reduction toward methane
Authors: Zhou Baowen , Ou Pengfei , Pant Nick , Cheng Shaobo , Vanka Srinivas , Chu Sheng , Rashid Roksana Tonny , Botton Gianluigi , Song Jun , Mi Zetian
Published: January 2020

Significance

The production of solar fuels from CO
2
using sunlight and electricity provides one promising route for reducing atmospheric carbon emissions and storing intermittent solar energy. The rational design of an efficient and inexpensive electrocatalyst is the key. We developed a binary copper−iron catalyst for photoelectrochemical CO
2
reduction toward methane. The theoretical calculations suggest that Cu and Fe in the binary system can work in synergy to spontaneously favor CO
2
activation and conversion for methane synthesis. The earth-abundant CuFe catalyst exhibits a high current density with an impressive methane Faradaic efficiency using industry-ready planar silicon photoelectrodes under one-sun illumination. This work presents a unique, highly efficient, and inexpensive route for solar fuels synthesis.
The rhizobial autotransporter determines the symbiotic nitrogen fixation activity ofLotus japonicusin a host-specific manner
Authors: Shimoda Yoshikazu , Nishigaya Yuki , Yamaya-Ito Hiroko , Inagaki Noritoshi , Umehara Yosuke , Hirakawa Hideki , Sato Shusei , Yamazaki Toshimasa , Hayashi Makoto
Published: January 2020

Leguminous plants establish endosymbiotic associations with rhizobia and form root nodules in which the rhizobia fix atmospheric nitrogen. The host plant and intracellular rhizobia strictly control this symbiotic nitrogen fixation. We recently reported aLotus japonicusFix−mutant,apn1(aspartic peptidase nodule-induced 1), that impairs symbiotic nitrogen fixation. APN1 encodes a nodule-specific aspartic peptidase involved in the Fix−phenotype in a rhizobial strain-specific manner. This host-strain specificity implies that some molecular interactions between host plant APN1 and rhizobial factors are required, although the biological function of APN1 in nodules and the mechanisms governing the interactions are unknown. To clarify how rhizobial factors are involved in strain-specific nitrogen fixation, we explored transposon mutants ofMesorhizobium lotistrain TONO, which normally form Fix−nodules onapn1roots, and identified TONO mutants that formed Fix+nodules onapn1. The identified causal gene encodes an autotransporter, part of a protein secretion system of Gram-negative bacteria. Expression of the autotransporter gene inM. lotistrain MAFF3030399, which normally forms Fix+nodules onapn1roots, resulted in Fix−nodules. The autotransporter of TONO functions to secrete a part of its own protein (a passenger domain) into extracellular spaces, and the recombinant APN1 protein cleaved the passenger protein in vitro. TheM. lotiautotransporter showed the activity to induce the genes involved in nodule senescence in a dose-dependent manner. Therefore, we conclude that the nodule-specific aspartic peptidase, APN1, suppresses negative effects of the rhizobial autotransporter in order to maintain effective symbiotic nitrogen fixation in root nodules.
Identification and characterization of extrachromosomal circular DNA in maternal plasma
Authors: Sin Sarah T. K. , Jiang Peiyong , Deng Jiaen , Ji Lu , Cheng Suk Hang , Dutta Anindya , Leung Tak Y. , Chan K. C. Allen , Chiu Rossa W. K. , Lo Y. M. Dennis
Published: January 2020

We explored the presence of extrachromosomal circular DNA (eccDNA) in the plasma of pregnant women. Through sequencing following either restriction enzyme or Tn5 transposase treatment, we identified eccDNA molecules in the plasma of pregnant women. These eccDNA molecules showed bimodal size distributions peaking at ∼202 and ∼338 bp with distinct 10-bp periodicity observed throughout the size ranges within both peaks, suggestive of their nucleosomal origin. Also, the predominance of the 338-bp peak of eccDNA indicated that eccDNA had a larger size distribution than linear DNA in human plasma. Moreover, eccDNA of fetal origin were shorter than the maternal eccDNA. Genomic annotation of the overall population of eccDNA molecules revealed a preference of these molecules to be generated from 5′-untranslated regions (5′-UTRs), exonic regions, and CpG island regions. Two sets of trinucleotide repeat motifs flanking the junctional sites of eccDNA supported multiple possible models for eccDNA generation. This work highlights the topologic analysis of plasma DNA, which is an emerging direction for circulating nucleic acid research and applications.
The clock gene
Bmal1
inhibits macrophage motility, phagocytosis, and impairs defense against pneumonia
Authors: Kitchen Gareth B. , Cunningham Peter S. , Poolman Toryn M. , Iqbal Mudassar , Maidstone Robert , Baxter Matthew , Bagnall James , Begley Nicola , Saer Ben , Hussell Tracy , Matthews Laura C. , Dockrell David H. , Durrington Hannah J. , Gibbs Julie E. , Blaikley John F. , Loudon Andrew S. , Ray David W.
Published: January 2020

The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time of day, but the mechanisms involved remain undefined. Here we show that loss of the core clock protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. Infected mice show both reduced weight loss and lower bacterial burden in circulating blood. In vivo studies of macrophage phagocytosis reveal increased bacterial ingestion following
Bmal1
deletion, which was also seen in vitro. BMAL1
−/−
macrophages exhibited marked differences in actin cytoskeletal organization, a phosphoproteome enriched for cytoskeletal changes, with reduced phosphocofilin and increased active RhoA. Further analysis of the BMAL1
−/−
macrophages identified altered cell morphology and increased motility. Mechanistically, BMAL1 regulated a network of cell movement genes, 148 of which were within 100 kb of high-confidence BMAL1 binding sites. Links to RhoA function were identified, with 29 genes impacting RhoA expression or activation. RhoA inhibition restored the phagocytic phenotype to that seen in control macrophages. In summary, we identify a surprising gain of antibacterial function due to loss of BMAL1 in macrophages, associated with a RhoA-dependent cytoskeletal change, an increase in cell motility, and gain of phagocytic function.
Structures of cofilin-induced structural changes reveal local and asymmetric perturbations of actin filaments
Authors: Huehn Andrew R. , Bibeau Jeffrey P. , Schramm Anthony C. , Cao Wenxiang , De La Cruz Enrique M. , Sindelar Charles V.
Published: January 2020

Members of the cofilin/ADF family of proteins sever actin filaments, increasing the number of filament ends available for polymerization or depolymerization. Cofilin binds actin filaments with positive cooperativity, forming clusters of contiguously bound cofilin along the filament lattice. Filament severing occurs preferentially at boundaries between bare and cofilin-decorated (cofilactin) segments and is biased at 1 side of a cluster. A molecular understanding of cooperative binding and filament severing has been impeded by a lack of structural data describing boundaries. Here, we apply methods for analyzing filament cryo-electron microscopy (cryo-EM) data at the single subunit level to directly investigate the structure of boundaries within partially decorated cofilactin filaments. Subnanometer resolution maps of isolated, bound cofilin molecules and an actin-cofilactin boundary indicate that cofilin-induced actin conformational changes are local and limited to subunits directly contacting bound cofilin. An isolated, bound cofilin compromises longitudinal filament contacts of 1 protofilament, consistent with a single cofilin having filament-severing activity. An individual, bound phosphomimetic (S3D) cofilin with weak severing activity adopts a unique binding mode that does not perturb actin structure. Cofilin clusters disrupt both protofilaments, consistent with a higher severing activity at boundaries compared to single cofilin. Comparison of these structures indicates that this disruption is substantially greater at pointed end sides of cofilactin clusters than at the barbed end. These structures, with the distribution of bound cofilin clusters, suggest that maximum binding cooperativity is achieved when 2 cofilins occupy adjacent sites. These results reveal the structural origins of cooperative cofilin binding and actin filament severing.
Long-range interdomain communications in eIF5B regulate GTP hydrolysis and translation initiation
Authors: Huang Bridget Y. , Fernández Israel S.
Published: January 2020

Translation initiation controls protein synthesis by regulating the delivery of the first aminoacyl-tRNA to messenger RNAs (mRNAs). In eukaryotes, initiation is sophisticated, requiring dozens of protein factors and 2 GTP-regulated steps. The GTPase eIF5B gates progression to elongation during the second GTP-regulated step. Using electron cryomicroscopy (cryo-EM), we imaged an in vitro initiation reaction which is set up with purified yeast components and designed to stall with eIF5B and a nonhydrolyzable GTP analog. A high-resolution reconstruction of a “dead-end” intermediate at 3.6 Å allowed us to visualize eIF5B in its ribosome-bound conformation. We identified a stretch of residues in eIF5B, located close to the γ-phosphate of GTP and centered around the universally conserved tyrosine 837 (
Saccharomyces cerevisiae
numbering), that contacts the catalytic histidine of eIF5B (H480). Site-directed mutagenesis confirmed the essential role that these residues play in regulating ribosome binding, GTP hydrolysis, and translation initiation both in vitro and in vivo. Our results illustrate how eIF5B transmits the presence of a properly delivered initiator aminoacyl-tRNA at the P site to the distant GTPase center through interdomain communications and underscore the importance of the multidomain architecture in translation factors to sense and communicate ribosomal states.
Global shape of Toll activation is determined bywntDenhancer properties
Authors: Rahimi Neta , Carmon Shari , Averbukh Inna , Khajouei Farzaneh , Sinha Saurabh , Schejter Eyal D. , Barkai Naama , Shilo Ben-Zion
Published: January 2020

Significance

A central issue in robust patterning mediated by morphogens is how to buffer variability in morphogen distribution between embryos. We previously described a class of mechanisms that buffers variability through “distal pinning,” a global feedback mechanism that modulates the spread of the gradient and terminates only when morphogen values at a distal position reach some given, fixed level. We have previously shown inDrosophilaembryonic dorso-ventral patterning that the secreted WntD protein modulates Toll pathway activation. We have altered the wntD enhancer and demonstrate a global contraction of the Toll gradient. The demonstration of a direct link between the enhancer properties of the modulator gene and the morphogen activation profile establishes a molecular mechanism for buffering variability in morphogen distribution.
Microstructure and texture evolution during annealing of Ti–6Al–4V alloy
Authors: Debta M. K. , Bishoyi B. D. , Sabat R. K. , Muhammad W. , Sahoo S. K.
Published: January 2020

Ti–6Al–4V plates were subjected to warm rolling at 600°C up to 85% reduction in thickness followed by annealing at 850°C for different soak periods. It was observed that the ‘β’ grains were prevalent along the grain boundaries and at the triple junctions of ‘α’ grains. The samples were found to be fully recrystallised after 30 min of annealing time. Further, globularizarion of ‘α’ grains was observed during the progress of annealing. The recrystallisation mechanism was identified to be through sub-grain formation and its growth. A dominant near basal texture, i.e. [Formula: see text][Formula: see text], was observed in the samples after annealing.
Microstructure and mechanical properties of TA1/3A21 composite plate fabricated via explosive welding
Authors: Cui Y. , Liu D. , Fan M. Y. , Deng G. P. , Sun L. X. , Zhang Y. , Chen D. , Zhang Z. W.
Published: January 2020

The microstructure and mechanical properties of explosively welded TA1/3A21 composite plate were studied. The results suggested that the bonding interface had a wavy appearance, and two types of Ti–Al solid solutions were found in the crest region. Most of the interfaces had a thin diffusion layer with a thickness of approximately 3 µm, and no brittle intermetallic compounds were formed. The interface of the explosively welded TA1 Ti/3A21 Al composite plate exhibited reliable shear and bending properties. The propagation of the facile cracks initiated at the Ti–Al solid solution/Al interface, and the Ti–Al solid solution region at the vortex could be terminated by the Ti matrix. In addition, the complex bonding interface structure inhibited the crack propagation along the interface.
Beneficial Opioid Management Strategies: A Review of the Evidence for the use of Opioid Treatment Agreements
Authors: McAuliffe Staehler Tuesday M. , Palombi Laura C.
Published: January 2020

Background: The Centers for Disease Control and Prevention (CDC) and American Society of Interventional Pain Physicians (ASIPP) guidelines recommend opioid treatment agreements to reduce the misuse and abuse of opioids, but evidence of their effectiveness has not been well-established. This controversy has led to their varied use in primary care settings. The purpose of this review is to collect studies that assess the value of opioid treatment agreements and associated opioid misuse outcomes in patients with chronic non-cancer pain.

Methods: This study used a modified preferred reporting items for systematic reviews and meta-analyses (PRISMA) approach which is organized by five distinct elements or steps: beginning with a clearly formulated question, using the question to develop clear inclusion criteria to identify relevant studies, using an approach to appraise the studies or a subset of the studies, summarizing the evidence using an explicit methodology, and interpreting the findings of the review.

Results: Of 283 articles identified, six eligible studies were evaluated and assessed for quality. The study design, setting, and participants varied across the studies evaluated, and the methods of measuring primary and secondary outcomes were also diverse across all studies. One study was a randomized clinical trial (RCT), four studies were retrospective cohort studies (RCS), and one study was a prospective cohort study (PCS). The design, methods, and indication for misuse of these studies contributed to quality scores of very low for one study, low for four studies, and moderate for one study.

Conclusion: This systematic review shows weak evidence to support the effectiveness of patient prescriber agreements in the reduction and mitigation of opioid misuse and abuse. Further research is needed to determine if these agreements are beneficial as an opioid management strategy.
Characteristics of physiology of and genomic mutations in aggregation-enhanced mutants of Methanothermobacter sp. CaT2
Authors: Sumikawa Kana , Kosaka Tomoyuki , Udo Koichi , Kanesaki Yu , Yoshikawa Hirofumi , Yamada Mamoru
Published: January 2020

The thermophilic hydrogenotrophic methanogen Methanothermobacter sp. CaT2 aggregates by itself. CaT2 is known to have a surface sugar layer and extracellular proteins that may be related to its aggregation. Aggregation-enhanced mutants, CHA001 and CHA002, were isolated after repeated cultivation for more than two years. When treated with proteinase K, CHA001 and CaT2 similarly exhibited a very low degree of aggregation and CHA002 exhibited less aggregation but still retained aggregation, suggesting protein-based aggregation via extracellular proteins in both CHA001 and CHA002, presumably via a putative membrane-bound and extracellularly protruding protein, MTCT_1020, identified previously. Genomic analysis revealed that CHA001 and CHA002 shared a missense mutation of MTCT_1348 and had distinct mutations. These results suggested that the MTCT_1348 mutation provides subsidiary support to the adhesive function of extracellular proteins and that there is an additional mutation(s) in CHA002 for the non-proteinous aggregation capability.
Imperatorin alleviates ROS-mediated airway remodeling by targeting the Nrf2/HO-1 signaling pathway
Authors: Xian Zhemin , Choi Yun Ho , Zheng Mingyu , Jiang Jingzhi , Zhao Yuzhe , Wang Chongyang , Li Junfeng , Li Yan , Li Liangchang , Piao Hongmei , Yan Guanghai
Published: January 2020

In this study, we investigated the role and mechanism of imperatorin (IMP) in chronic inflammation and airway remodeling. The levels of TNF-α, IL-1β, IL-6, IL-8, VEGF, α-SMA, and ROS were detected by ELISA, immunohistochemistry (IHC), immunofluorescence, and Western blot. In addition, we evaluated the effect of IMP on MAPK, PI3K/Akt, NF-κB, and Nrf2/HO-1 signaling pathways. IMP treatment obviously attenuated the production of inflammatory cytokines and inflammatory cells in bronchoalveolar lavage ﬂuid of OVA-induced airway remodeling model. Meanwhile, it significantly inhibited inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition, VEGF production, α-SMA, and ROS expression. Our study has shown that IMP could regulate the signaling pathways including MAPK, PI3K/Akt, NF-κB, and Nrf2/HO-1 to release the inflammatory responses. IMP might attenuate airway remodeling by the down-regulation of Nrf2/HO-1/ROS/PI3K/Akt, Nrf2/HO-1/ROS/MAPK, and Nrf2/HO-1/ROS/NF-κB signaling pathways.