bluuebunny/crossref_metadata_2025 huggingface dataset:
Saturn's Dusty Ionosphere
Authors: Morooka M. W. , Wahlund J.‐E. , Hadid L. Z. , Eriksson A. I. , Edberg N. J. T. , Vigren E. , Andrews D. J. , Persoon A. M. , Kurth W. S. , Gurnett D. A. , Farrell W. M. , Waite J. H. , Perryman R. S. , Perry M.
Published: March 2019

Measurements of electrons and ions in Saturn's ionosphere down to 1,500‐km altitudes as well as the ring crossing region above the ionosphere obtained by the Langmuir probe onboard the Cassini spacecraft are presented. Five nearly identical deep ionosphere flybys during the Grand Finale orbits and the Final plunge orbit revealed a rapid increase in the plasma densities and discrepancies between the electrons and ions densities (Ne and Ni) near the closest approach. The small Ne/Ni ratio indicates the presence of a dusty plasma, a plasma which charge carrier is dominated by negatively charged heavy particles. Comparison of the Langmuir probe obtained density with the light ion density obtained by the Ion and Neutral Mass Spectrometer confirmed the presence of heavy ions. An unexpected positive floating potential of the probe was also observed when Ne/Ni ≪ 1. This suggests that Saturn's ionosphere near the density peak is in a dusty plasma state consisting of negatively and positively charged heavy cluster ions. The electron temperature (Te) characteristics in the ionosphere are also investigated and unexpectedly high electron temperature value, up to 5000 K, has been observed below 2,500‐km altitude in a region where electron‐neutral collisions should be prominent. A well‐defined relationship between Te and Ne/Ni ratio was found, implying that the electron heating at low altitudes is related to the dusty plasma state of the ionosphere.
Anisotropic Electron Distributions and Whistler Waves in a Series of the Flux Transfer Events at the Magnetopause
Authors: Wang Shimou , Wang Rongsheng , Yao S. T. , Lu Quanming , Russell C. T. , Wang Shui
Published: March 2019

With the measurements of the Magnetospheric Multiscale mission at the magnetopause, we investigated the electron distribution and the whistler waves associated with a series of six ion‐scale flux transfer events (FTEs). Based on the magnetic field signature, each FTE can be divided into the core region and the draping region. In the draping regions of the most FTEs, the low‐energy electrons displayed a bidirectional field‐aligned distribution. The medium‐energy electrons showed a field‐aligned or beam distribution in the leading part, while a pancake distribution was presented for the electrons in the trailing part of the draping region, which has never been reported previously. The close correlation between the pancake distribution and the compression of the localized magnetic field suggests that the pancake distribution may be due to the betatron acceleration. The whistler waves associated with the FTEs were observed and categorized into the lower and upper bands according to the frequency range. The lower band whistler waves propagated in variable directions and therefore could be generated locally. The trailing part of the draping region with the electron pancake distribution was considered to be one possible source region. On the contrary, the upper band whistler waves were all found in the core region and propagated antiparallel to the magnetic field and therefore originated from the same source region. The observations confirmed that the FTEs are important channels for the mass and wave transport between the magnetosheath and the inner magnetosphere, and the electron dynamics can be modified during the FTE evolution.
Multi‐instrument Observations of Mesoscale Enhancement of Subauroral Polarization Stream Associated With an Injection
Authors: Wang Zihan , Zou Shasha , Shepherd Simon G. , Liang Jun , Gjerloev Jesper W. , Ruohoniemi J. Michael , Kunduri Bharat , Wygant John R.
Published: March 2019

Subauroral polarization streams (SAPS) prefer geomagnetically disturbed conditions and strongly correlate with geomagnetic indexes. However, the temporal evolution of SAPS and its relationship with dynamic and structured ring current and particle injection are still not well understood. In this study, we performed detailed analysis of temporal evolution of SAPS during a moderate storm on 18 May 2013 using conjugate observations of SAPS from the Van Allen Probes (VAP) and the Super Dual Auroral Radar Network (SuperDARN). The large‐scale SAPS (LS‐SAPS) formed during the main phase of this storm and decayed due to the northward turning of the interplanetary magnetic field. A mesoscale (approximately several hundreds of kilometers zonally) enhancement of SAPS was observed by SuperDARN at 0456 UT. In the conjugate magnetosphere, a large SAPS electric field (∼8 mV/m) pointing radially outward, a local magnetic field dip, and a dispersionless ion injection were observed simultaneously by VAP‐A at L shell = 3.5 and MLT = 20. The particle injection observed by VAP‐A is likely associated with the particle injection observed by the Geostationary Operational Environmental Satellite 15 near 20 MLT. Magnetic perturbations observed by the ground magnetometers and flow reversals observed by SuperDARN reveal that this mesoscale enhancement of SAPS developed near the Harang reversal and before the substorm onset. The observed complex signatures in both space and ground can be explained by a two‐loop current wedge generated by the perturbed plasma pressure gradient and the diamagnetic effect of the structured ring current following particle injection.
Targeting c-MET by Tivantinib through synergistic activation of JNK/c-jun pathway in cholangiocarcinoma
Authors: Wei Kai , Li Mao , Zöller Margot , Wang Meng , Mehrabi Arianeb , Hoffmann Katrin
Published: March 2019

Clinical treatment options for human cholangiocarcinoma (CC) are limited. c-MET, a high-affinity receptor for hepatocyte growth factor (HGF), is deregulated in many cancers. Its role in cholangiocarcinogenesis remains unclear. In current study, 23 corresponding tumor- and non-tumor tissues, taken from patients with intrahepatic (iCC) and perihilar cholangiocarcinoma (pCC), who underwent liver resection, were analyzed. The relationship of clinicopathological features and c-MET, as well as c-jun N-terminal kinase (JNK) was evaluated. The anti-tumor effects of Tivantinib, a small-molecule inhibitor with potent activity against the c-MET kinase, was investigated in three human CC cell lines, namely HUCC-T1, TFK-1, and EGI-1. In comparison with the results obtained in non-tumor tissue samples, c-MET was overexpressed in 91.3 % of tumor tissues (p < 0.01). The JNK expression was higher in tumor tissue compared with the corresponding non-tumor tissue sample in 17.4% patients (p < 0.01). The inhibition of aberrant c-MET expression in human CC cell lines was achieved by blocking the phosphorylation of c-MET with Tivantinib. Notable losses in cell viability and colony-forming capability were detected (p < 0.01). Synergistic activation of the JNK/c-jun pathway was demonstrated after Tivantinib treatment. Knockdown of the JNK by siRNA or competitive binding of c-MET receptor by stimulation with HGF-antagonized anti-tumor effects of Tivantinib was observed. Our data suggest that inhibition of c-MET could be a possible alternative approach for the treatment of human CC, for which Tivantinib may an effective inhibitor. The synergistic activation of the JNK/c-jun pathway contributed to the elevated apoptosis in CC cells via treatment with Tivantinib.
Inhibition of PINK1/Parkin-dependent mitophagy sensitizes multidrug-resistant cancer cells to B5G1, a new betulinic acid analog
Authors: Yao Nan , Wang Chenran , Hu Nan , Li Yingjie , Liu Mingqun , Lei Yuhe , Chen Minfeng , Chen Liping , Chen Chen , Lan Ping , Chen Weimin , Chen Zhesheng , Fu Dengrui , Ye Wencai , Zhang Dongmei
Published: March 2019

Betulinic acid (BA) and its derivatives are a class of high-profile drug candidates, but their anticancer effects on resistant cancer have rarely been reported. Although a few studies indicated mitophagy is related with drug resistance, its role in different cancer types and anticancer agents treatment remains largely unclear. Here, we find that B5G1, a new derivative of BA, induces cell death in multidrug resistant cancer cells HepG2/ADM and MCF-7/ADR through mitochondrial-apoptosis pathway. B5G1 also triggers mitophagy independent on Atg5/Beclin 1. Further mechanistic study indicates that B5G1 upregulates PTEN-induced putative kinase 1 (PINK1) to recruit Parkin to mitochondria followed by ubiquitination of Mfn2 to initiate mitophagy. Inhibition of mitophagy by PINK1 siRNA, mdivi-1, or bafilomycin A1 (Baf A1) promotes B5G1-induced cell death. In addition, ROS production and mitochondrial damage in B5G1-treated HepG2/ADM cells cause mitochondrial apoptosis and mitophagy. In vivo study shown that B5G1 dramatically inhibits HepG2/ADM xenograft growth accompanied by apoptosis and mitophagy induction. Together, our results provide the first demonstration that B5G1, as a novel mitophagy inducer, has the potential to be developed into a drug candidate for treating multidrug resistant cancer.
RETRACTED ARTICLE: Involvement of autophagy in hypoxia-BNIP3 signaling to promote epidermal keratinocyte migration
Authors: Zhang Junhui , Zhang Can , Jiang Xupin , Li Lingfei , Zhang Dongxia , Tang Di , Yan Tiantian , Zhang Qiong , Yuan Hongping , Jia Jiezhi , Hu Jiongyu , Zhang Jiaping , Huang Yuesheng
Published: March 2019

BNIP3 is an atypical BH3-only member of the Bcl-2 family with pro-death, pro-autophagic, and cytoprotective functions, depending on the type of stress and cellular context. Recently, we demonstrated that BNIP3 stimulates the migration of epidermal keratinocytes under hypoxia. In the present study found that autophagy and BNIP3 expression were concomitantly elevated in the migrating epidermis during wound healing in a hypoxia-dependent manner. Inhibition of autophagy through lysosome-specific chemicals (CQ and BafA1) or Atg5-targeted small-interfering RNAs greatly attenuated the hypoxia-induced cell migration, and knockdown of BNIP3 in keratinocytes significantly suppressed hypoxia-induced autophagy activation and cell migration, suggesting a positive role of BNIP3-induced autophagy in keratinocyte migration. Furthermore, these results indicated that the accumulation of reactive oxygen species (ROS) by hypoxia triggered the activation of p38 and JNK mitogen-activated protein kinase (MAPK) in human immortalized keratinocyte HaCaT cells. In turn, activated p38 and JNK MAPK mediated the activation of BNIP3-induced autophagy and the enhancement of keratinocyte migration. These data revealed a previously unknown mechanism that BNIP3-induced autophagy occurs through hypoxia-induced ROS-mediated p38 and JNK MAPK activation and supports the migration of epidermal keratinocytes during wound healing.
Diversifying the structure of zinc finger nucleases for high-precision genome editing
Authors: Paschon David E. , Lussier Stephanie , Wangzor Tenzin , Xia Danny F. , Li Patrick W. , Hinkley Sarah J. , Scarlott Nicholas A. , Lam Stephen C. , Waite Adam J. , Truong Lynn N. , Gandhi Nimisha , Kadam Bhakti N. , Patil Deepak P. , Shivak David A. , Lee Gary K. , Holmes Michael C. , Zhang Lei , Miller Jeffrey C. , Rebar Edward J.
Published: March 2019

Genome editing for therapeutic applications often requires cleavage within a narrow sequence window. Here, to enable such high-precision targeting with zinc-finger nucleases (ZFNs), we have developed an expanded set of architectures that collectively increase the configurational options available for design by a factor of 64. These new architectures feature the functional attachment of the FokI cleavage domain to the amino terminus of one or both zinc-finger proteins (ZFPs) in the ZFN dimer, as well as the option to skip bases between the target triplets of otherwise adjacent fingers in each zinc-finger array. Using our new architectures, we demonstrate targeting of an arbitrarily chosen 28 bp genomic locus at a density that approaches 1.0 (i.e., efficient ZFNs available for targeting almost every base step). We show that these new architectures may be used for targeting three loci of therapeutic significance with a high degree of precision, efficiency, and specificity.
The Aryl hydrocarbon receptor mediates tobacco-induced PD-L1 expression and is associated with response to immunotherapy
Authors: Wang Gui-Zhen , Zhang Li , Zhao Xin-Chun , Gao San-Hui , Qu Li-Wei , Yu Hong , Fang Wen-Feng , Zhou Yong-Chun , Liang Fan , Zhang Chen , Huang Yun-Chao , Liu Zhihua , Fu Yang-Xin , Zhou Guang-Biao
Published: March 2019

Whether tobacco carcinogens enable exposed cells immune escape resulting in carcinogenesis, and why patients who smoke respond better to immunotherapies than non-smokers, remains poorly understood. Here we report that cigarette smoke and the carcinogen benzo(a)pyrene (BaP) induce PD-L1 expression on lung epithelial cells in vitro and in vivo, which is mediated by aryl hydrocarbon receptor (AhR). Anti-PD-L1 antibody or deficiency in AhR significantly suppresses BaP-induced lung cancer. In 37 patients treated with anti-PD-1 antibody pembrolizumab, 13/16 (81.3%) patients who achieve partial response or stable disease express high levels of AhR, whereas 12/16 (75%) patients with progression disease exhibit low levels of AhR in tumor tissues. AhR inhibitors exert significant antitumor activity and synergize with anti-PD-L1 antibody in lung cancer mouse models. These results demonstrate that tobacco smoke enables lung epithelial cells to escape from adaptive immunity to promote tumorigenesis, and AhR predicts the response to immunotherapy and represents an attractive therapeutic target.
Neurotrophin receptor tyrosine kinases regulated with near-infrared light
Authors: Leopold Anna V. , Chernov Konstantin G. , Shemetov Anton A. , Verkhusha Vladislav V.
Published: March 2019

Optical control over the activity of receptor tyrosine kinases (RTKs) provides an efficient way to reversibly and non-invasively map their functions. We combined catalytic domains of Trk (tropomyosin receptor kinase) family of RTKs, naturally activated by neurotrophins, with photosensory core module of DrBphP bacterial phytochrome to develop opto-kinases, termed Dr-TrkA and Dr-TrkB, reversibly switchable on and off with near-infrared and far-red light. We validated Dr-Trk ability to reversibly light-control several RTK pathways, calcium level, and demonstrated that their activation triggers canonical Trk signaling. Dr-TrkA induced apoptosis in neuroblastoma and glioblastoma, but not in other cell types. Absence of spectral crosstalk between Dr-Trks and blue-light-activatable LOV-domain-based translocation system enabled intracellular targeting of Dr-TrkA independently of its activation, additionally modulating Trk signaling. Dr-Trks have several superior characteristics that make them the opto-kinases of choice for regulation of RTK signaling: high activation range, fast and reversible photoswitching, and multiplexing with visible-light-controllable optogenetic tools.
Unraveling the mysterious failure of Cu/SAPO-34 selective catalytic reduction catalysts
Authors: Wang Aiyong , Chen Ying , Walter Eric D. , Washton Nancy M. , Mei Donghai , Varga Tamas , Wang Yilin , Szanyi János , Wang Yong , Peden Charles H. F. , Gao Feng
Published: March 2019

Commercial Cu/SAPO-34 selective catalytic reduction (SCR) catalysts have experienced unexpected and quite perplexing failure. Understanding the causes at an atomic level is vital for the synthesis of more robust Cu/SAPO-34 catalysts. Here we show, via application of model catalysts with homogeneously dispersed isolated Cu ions, that Cu transformations resulting from low-temperature hydrothermal aging and ambient temperature storage can be semi-quantitatively probed with 2-dimensional pulsed electron paramagnetic resonance. Coupled with kinetics, additional material characterizations and DFT simulations, we propose the following catalyst deactivation steps: (1) detachment of Cu(II) ions from cationic positions in the form of Cu(OH)2; (2) irreversible hydrolysis of the SAPO-34 framework forming terminal Al species; and (3) interaction between Cu(OH)2and terminal Al species forming SCR inactive, Cu-aluminate like species. Especially significant is that these reactions are greatly facilitated by condensed water molecules under wet ambient conditions, causing low temperature failure of the commercial Cu/SAPO-34 catalysts.
Framework nucleic acids as programmable carrier for transdermal drug delivery
Authors: Wiraja Christian , Zhu Ying , Lio Daniel Chin Shiuan , Yeo David C. , Xie Mo , Fang Weina , Li Qian , Zheng Mengjia , Van Steensel Maurice , Wang Lihua , Fan Chunhai , Xu Chenjie
Published: March 2019

DNA nanostructures are promising drug carriers with their intrinsic biocompatibility, uniformity and versatility. However, rapid serum disintegration leads to low bioavailability at targeted sites following systemic administration, hindering their biomedical applications. Here we demonstrate transdermal delivery of framework nucleic acids (FNAs) through topical applications. By designing FNAs with distinct shapes and sizes, we interrogate their penetration on mice and human skin explant. Skin histology reveals size-dependent penetration, with FNAs ≤75 nm effectively reaching dermis layer. 17 nm-tetrahedral FNAs show greatest penetration to 350 µm from skin periphery. Importantly, structural integrity is maintained during the skin penetration. Employing a mouse melanoma model, topical application of doxorubicin-loaded FNAs accommodates ≥2-fold improvement in drug accumulation and tumor inhibition relative to topically-applied free doxorubicin, or doxorubicin loaded in liposomes and polymeric nanoparticles. Programmable penetration with minimal systemic biodistribution underlines FNA potential as localized transdermal drug delivery carriers.
Subtyping of circulating exosome-bound amyloid β reflects brain plaque deposition
Authors: Lim Carine Z. J. , Zhang Yan , Chen Yu , Zhao Haitao , Stephenson Mary C. , Ho Nicholas R. Y. , Chen Yuan , Chung Jaehoon , Reilhac Anthonin , Loh Tze Ping , Chen Christopher L. H. , Shao Huilin
Published: March 2019

Despite intense interests in developing blood measurements of Alzheimer’s disease (AD), the progress has been confounded by limited sensitivity and poor correlation to brain pathology. Here, we present a dedicated analytical platform for measuring different populations of circulating amyloid β (Aβ) proteins – exosome-bound vs. unbound – directly from blood. The technology, termed amplified plasmonic exosome (APEX), leverages in situ enzymatic conversion of localized optical deposits and double-layered plasmonic nanostructures to enable sensitive, multiplexed population analysis. It demonstrates superior sensitivity (~200 exosomes), and enables diverse target co-localization in exosomes. Employing the platform, we find that prefibrillar Aβ aggregates preferentially bind with exosomes. We thus define a population of Aβ as exosome-bound (Aβ42+ CD63+) and measure its abundance directly from AD and control blood samples. As compared to the unbound or total circulating Aβ, the exosome-bound Aβ measurement could better reflect PET imaging of brain amyloid plaques and differentiate various clinical groups.
In-situ aerosol nanoparticle characterization by small angle X-ray scattering at ultra-low volume fraction
Authors: Bauer P. S. , Amenitsch H. , Baumgartner B. , Köberl G. , Rentenberger C. , Winkler P. M.
Published: March 2019

State-of-the-art aerosol nanoparticle techniques all have one feature in common: for analysis they remove the nanoparticles from their original environment. Therefore, physical and chemical properties of the particles might be changed or cannot be measured correctly. To overcome these shortcomings, we apply synchrotron based small angle X-ray scattering (SAXS) as an in-situ measurement technique. Contrasting other aerosol studies using SAXS, we focus on particle concentrations which allow direct comparison to common aerosol nanoparticle analyzers. To this end, we analyze aerosol nanoparticles at ambient pressure and concentrations of slightly above ~106 cm−3. A differential mobility particle sizer (DMPS) is operated in parallel. We find that SAXS enables measurement of the primary particles and the aggregates, whereas the DMPS detects only aggregates. We conclude that in-situ nanoparticle characterization with ultra-low volume fractions of ~10–10 is feasible with SAXS. Our technique opens up a doorway to the in-situ analysis of aerosol nanoparticles under atmospheric conditions.
Time-space-resolved origami hierarchical electronics for ultrasensitive detection of physical and chemical stimuli
Authors: Zhang Min , Sun Jiaxing Jeccy , Khatib Muhammad , Lin Zi-Yang , Chen Zi-Han , Saliba Walaa , Gharra A’laa , Horev Yehu David , Kloper Viki , Milyutin Yana , Huynh Tan-Phat , Brandon Simon , Shi Guoyue , Haick Hossam
Published: March 2019

Recent years have witnessed thriving progress of flexible and portable electronics, with very high demand for cost-effective and tailor-made multifunctional devices. Here, we report on an ingenious origami hierarchical sensor array (OHSA) written with a conductive ink. Thanks to origami as a controllable hierarchical framework for loading ink material, we have demonstrated that OHSA possesses unique time-space-resolved, high-discriminative pattern recognition (TSR-HDPR) features, qualifying it as a smart sensing device for simultaneous sensing and distinguishing of complex physical and chemical stimuli, including temperature, relative humidity, light and volatile organic compounds (VOCs). Of special importance, OSHA has shown very high sensitivity in differentiating between structural isomers and chiral enantiomers of VOCs – opening a door for wide variety of unique opportunities in several length scales.
Characterization of the hemodynamic response function in white matter tracts for event-related fMRI
Authors: Li Muwei , Newton Allen T. , Anderson Adam W. , Ding Zhaohua , Gore John C.
Published: March 2019

Accurate estimates of the BOLD hemodynamic response function (HRF) are crucial for the interpretation and analysis of event-related functional MRI data. To date, however, there have been no comprehensive measurements of the HRF in white matter (WM) despite increasing evidence that BOLD signals in WM change after a stimulus. We performed an event-related cognitive task (Stroop color-word interference) to measure the HRF in selected human WM pathways. The task was chosen in order to produce robust, distributed centers of activity throughout the cortex. To measure the HRF in WM, fiber tracts were reconstructed between each pair of activated cortical areas. We observed clear task-specific HRFs with reduced magnitudes, delayed onsets and prolonged initial dips in WM tracts compared with activated grey matter, thus calling for significant changes to current standard models for accurately characterizing the HRFs in WM and for modifications of standard methods of analysis of functional imaging data.
Systematic comparison of respiratory syncytial virus-induced memory B cell responses in two anatomical compartments
Authors: Shehata Laila , Wieland-Alter Wendy F. , Maurer Daniel P. , Chen Eunice , Connor Ruth I. , Wright Peter F. , Walker Laura M.
Published: March 2019

Respiratory syncytial virus (RSV) is a leading cause of hospitalization in infants and young children. Although it is widely agreed that an RSV vaccine should induce both mucosal and systemic antibody responses, little is known about the B cell response to RSV in mucosa-associated lymphoid tissues. Here, we analyze this response by isolating 806 RSV F-specific antibodies from paired adenoid and peripheral blood samples from 4 young children. Overall, the adenoid-derived antibodies show higher binding affinities and neutralization potencies compared to antibodies isolated from peripheral blood. Approximately 25% of the neutralizing antibodies isolated from adenoids originate from a unique population of IgM+and/or IgD+memory B cells that contain a high load of somatic mutations but lack expression of classical memory B cell markers. Altogether, the results provide insight into the local B cell response to RSV and have implications for the development of vaccines that stimulate potent mucosal responses.
Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins
Authors: Miliara Xeni , Tatsuta Takashi , Berry Jamie-Lee , Rouse Sarah L. , Solak Kübra , Chorev Dror S. , Wu Di , Robinson Carol V. , Matthews Stephen , Langer Thomas
Published: March 2019

Conserved lipid transfer proteins of the Ups/PRELI family regulate lipid accumulation in mitochondria by shuttling phospholipids in a lipid-specific manner across the intermembrane space. Here, we combine structural analysis, unbiased genetic approaches in yeast and molecular dynamics simulations to unravel determinants of lipid specificity within the conserved Ups/PRELI family. We present structures of human PRELID1–TRIAP1 and PRELID3b–TRIAP1 complexes, which exert lipid transfer activity for phosphatidic acid and phosphatidylserine, respectively. Reverse yeast genetic screens identify critical amino acid exchanges that broaden and swap their lipid specificities. We find that amino acids involved in head group recognition and the hydrophobicity of flexible loops regulate lipid entry into the binding cavity. Molecular dynamics simulations reveal different membrane orientations of PRELID1 and PRELID3b during the stepwise release of lipids. Our experiments thus define the structural determinants of lipid specificity and the dynamics of lipid interactions by Ups/PRELI proteins.
Band gap closure, incommensurability and molecular dissociation of dense chlorine
Authors: Dalladay-Simpson Philip , Binns Jack , Peña-Alvarez Miriam , Donnelly Mary-Ellen , Greenberg Eran , Prakapenka Vitali , Chen Xiao-Jia , Gregoryanz Eugene , Howie Ross T.
Published: March 2019

Diatomic elemental solids are highly compressible due to the weak interactions between molecules. However, as the density increases the intra- and intermolecular distances become comparable, leading to a range of phenomena, such as structural transformation, molecular dissociation, amorphization, and metallisation. Here we report, following the crystallization of chlorine at 1.15(30) GPa into an ordered orthorhombic structure (oC8), the existence of a mixed-molecular structure (mC8, 130(10)–241(10) GPa) and the concomitant observation of a continuous band gap closure, indicative of a transformation into a metallic molecular form around 200(10) GPa. The onset of dissociation of chlorine is identified by the observation of the incommensurate structure (i-oF4) above 200(10) GPa, before finally adopting a monatomic form (oI2) above 256(10) GPa.
Topological scoring of protein interaction networks
Authors: Sardiu Mihaela E. , Gilmore Joshua M. , Groppe Brad D. , Dutta Arnob , Florens Laurence , Washburn Michael P.
Published: March 2019

It remains a significant challenge to define individual protein associations within networks where an individual protein can directly interact with other proteins and/or be part of large complexes, which contain functional modules. Here we demonstrate the topological scoring (TopS) algorithm for the analysis of quantitative proteomic datasets from affinity purifications. Data is analyzed in a parallel fashion where a prey protein is scored in an individual affinity purification by aggregating information from the entire dataset. Topological scores span a broad range of values indicating the enrichment of an individual protein in every bait protein purification. TopS is applied to interaction networks derived from human DNA repair proteins and yeast chromatin remodeling complexes. TopS highlights potential direct protein interactions and modules within complexes. TopS is a rapid method for the efficient and informative computational analysis of datasets, is complementary to existing analysis pipelines, and provides important insights into protein interaction networks.
A novel range-verification method using ionoacoustic wave generated from spherical gold markers for particle-beam therapy: a simulation study
Authors: Takayanagi Taisuke , Uesaka Tomoki , Kitaoka Masanori , Unlu Mehmet Burcin , Umegaki Kikuo , Shirato Hiroki , Xing Lei , Matsuura Taeko
Published: March 2019

This study proposes a novel alternative range-verification method for proton beam with acoustic waves generated from spherical metal markers. When proton beam is incident on metal markers, most of the resulting pressure waves are confined in the markers because of the large difference in acoustic impedance between the metal and tissue. However, acoustic waves with frequency equal to marker’s resonant frequency escape this confinement; the marker briefly acts as an acoustic transmitter. Herein, this phenomenon is exploited to measure the range of the proton beam. We test the proposed strategy in 3-D simulations, combining the dose calculations with modelling of acoustic-wave propagation. A spherical gold marker of 2.0 mm diameter was placed in water with a 60 MeV proton beam incident on it. We investigated the dependence of pressure waves on the width of beam pulse and marker position. At short beam pulse, specific high-frequency acoustic waves of 1.62 MHz originating from the marker were observed in wave simulations, whose amplitude correlated with the distance between the marker and Bragg peak. Results indicate that the Bragg peak position can be estimated by measuring the acoustic wave amplitudes from the marker, using a single detector properly designed for the resonance frequency.
HIV infection and latency induce a unique metabolic signature in human macrophages
Authors: Castellano Paul , Prevedel Lisa , Valdebenito Silvana , Eugenin Eliseo A.
Published: March 2019

Currently, a major barrier to curing HIV infection is the generation of tissue-associated, non-replicating, long-lasting viral reservoirs that are refractory to therapy and can be reactivated upon anti-retroviral therapy interruption. One of these reservoirs are latently HIV-infected macrophages. Here, we show that HIV infection of macrophages results in survival of a small population of infected cells that are metabolically altered and characterized by mitochondrial fusion, lipid accumulation, and reduced mitochondrial ATP production. No changes in glycolysis were detected. Metabolic analysis indicated an essential role of succinate and other TCA metabolites in the tricarboxylic acid (TCA) cycle in mediating lipid accumulation and oxidative phosphorylation (OXPHOS) in the mitochondria. Furthermore, we show that while uninfected and HIV infected macrophages use fatty acids and glucose as primary sources of energy, surviving HIV infected macrophages also use glutamine/glutamate as a major energy source, and blocking these new sources of energy resulted in the killing of latent HIV infected macrophages. Together, our data provide a new understanding of the formation, properties, and potential novel ways to eliminate macrophage viral reservoirs.
Application of Electrochemical Techniques for Determining and Extracting Natural Product (EgCg) by the Synthesized Conductive Polymer Electrode (Ppy/Pan/rGO) Impregnated with Nano-Particles of TiO2
Authors: Ferdosian Fatemeh , Ebadi Mehdi , Mehrabian Ramin Z. , Golsefidi Maziar A. , Moradi Ali V.
Published: March 2019

The polypyrrole/polyaniline-based electrode (Ppy/Pan/TiO2/rGO) was fabricated via the electrophoretic deposition technique on fluorine-doped tin oxide (FTO)-coated glass. Physico-electrochemical adsorption/desorption of epigallocatechin gallate (EgCg) as an electroactive species was enhanced by the fabricated electrode compared to the electroless technique extraction using the same electrode. EgCg was electrochemically extracted using chronoamperometry by electrophoretically deposited Ppy/Pan/TiO2/rGO film. Isolated EgCg was qualified and quantified by the voltammetry and high-performance liquid chromatography (HPLC) techniques. It was found that the extracted EgCg values were 3.38 and 0.72 ppm from a 10 ppm prepared solution using the electrochemically and physically based techniques, respectively. Morphology/elemental analysis and crystal structure of the prepared electrodes were characterized by field emission scanning electron microscopy/energy-dispersive X-ray (FESEM/EDX) and X-ray diffraction (XRD), respectively. The conductivity of the fabricated electrode was investigated by electrochemical impedance spectroscopy (EIS) and was calculated as 1.124 S/cm for the electrophoretically deposited electrodes (EPD).
Sediment delivery of partially-unfrozen loam soil rill by snow/glacier meltwater flow
Authors: Wan Dan , Li Fa-hu , Yu Wu , Chen Chao , Gao Yuan
Published: March 2019

Erosion of freeze-thaw soil by meltwater from snow/glacier is one of the main erosion types in high altitude or latitude regions. This study aims to experimentally measure soil erosion processes over partially-unfrozen soil slopes in laboratory. The experiments including three slope gradients of 10°, 15°, and 20°, three water flow rates of 1, 2, and 4 L/min (0.06, 0.12, and 0.24 m3/h), and three thawed-soil depths of 1, 2, and 5 cm were conducted to measure sediment concentration and calculate its delivery rate under seven slope lengths of 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, and 6.0 m. The sediment delivery rates from nonfrozen soil slopes under the corresponding slope gradients, flow rates, and slope lengths also were measured as control treatments. Results showed that the sediment delivery rate from both partially-unfrozen and nonfrozen soil slopes increased logarithmically with slope length. The sediment delivery rate from partially-unfrozen soil slope increased with the increased slope gradient and meltwater flow rate significantly, and the effect of water flow rate on it was greater than that of slope gradient. The thawed-soil depth did not significantly affect sediment delivery rate. The sediment delivery rate from a partially-unfrozen loamy soil slope averagely was 11.4% smaller than that from nonfrozen soil slope. This study is helpful to understand the erosion process of thawing-soil by meltwater from snow/glacier.
Local release of rapamycin by microparticles delays islet rejection within the anterior chamber of the eye
Authors: Fan Yanliang , Zheng Xiaofeng , Ali Yusuf , Berggren Per-Olof , Loo Say Chye Joachim
Published: March 2019

The anterior chamber of the eye (ACE) has emerged as a promising clinical islet transplantation site because of its multiple advantages over the conventional intra-hepatic portal site. This includes reduced surgical invasiveness and increased islet graft survival rate. It also allows for enhanced accessibility and monitoring of the islets. Although the ACE is initially an immuno-privileged site, this privilege is disrupted once the islet grafts are re-vascularized. Given that the ACE is a confined space, achieving graft immune tolerance through local immunosuppressive drug delivery is therefore feasible. Here, we show that islet rejection in the ACE of mice can be significantly suppressed through local delivery of rapamycin by carefully designed sustained-release microparticles. In this 30-day study, allogeneic islet grafts with blank microparticles were completely rejected 18 days post-transplantation into mice. Importantly, allogeneic islet grafts co-injected with rapamycin releasing microparticles into a different eye of the same recipient were preserved much longer, with some grafts surviving for more than 30 days. Hence, islet allograft survival was enhanced by a localized and prolonged delivery of an immunosuppressive drug. We envisage that this procedure will relieve diabetic transplant recipients from harsh systemic immune suppression, while achieving improved glycemic control and reduced insulin dependence.
ApoE-fragment/Aβ heteromers in the brain of patients with Alzheimer’s disease
Authors: Mouchard Amandine , Boutonnet Marie-Charlotte , Mazzocco Claire , Biendon Nathalie , Macrez Nathalie ,   Neuro-CEB Neuropathology Network
Published: March 2019

Identification of endogenous pathological amyloid β peptides (Aβ) forms in the brains of patients with Alzheimer’s disease (AD) is still unclear. In healthy brain, Aβ can associate with Apolipoprotein E (ApoE) which is involved in its metabolism and clearance. In the brain of patients with AD, ApoE is cleaved and produces ApoE fragments. We studied the forms of Aβ and their interaction with the ApoE fragments in post-mortem brains from control and AD patients by western blots and co-immunoprecipitation. Three Aβ-containing peptides and three ApoE fragments were specifically found in the brain of AD patients. Co-immunoprecipitations showed that ApoE fragments and Aβ1–42 peptides are co-partners in heteromers of 18 and 16 kDa while ApoE-fragments and Aβ peptides of 12 kDa did not interact with each other. Formation of the 18 kDa ApoE-fragment/Aβ heteromers is specifically increased in ApoE4 carriers and is a strong brain marker of AD while 16 kDa ApoE-fragment/Aβ and Aβ 12 kDa correlate to memory deficit. These data show that in patients with AD, ApoE fragmentation generates peptides that trap Aβ in the brain. Inhibiting the fragmentation or targeting ApoE fragments could be exploited to define strategies to detect or reverse AD.
Synthesis of Hydroxyapatite with Antibacterial Properties Using a Microwave-Assisted Combustion Method
Authors: Lamkhao Suphatchaya , Phaya Manlika , Jansakun Chutima , Chandet Nopakarn , Thongkorn Kriangkrai , Rujijanagul Gobwute , Bangrak Phuwadol , Randorn Chamnan
Published: March 2019

The prevention of implant-associated infections has been increasing clinically in orthopedic surgery. Hydroxyapatite with antibacterial properties was synthesized using a microwave-assisted combustion method. High crystallinity at low temperature can be achieved using this method. The synthesized hydroxyapatite exhibited a superior clear zone for both Gram-positive and Gram-negative bacteria. Electron spin resonance (ESR) and X-ray photoelectron spectroscopy (XPS) were used for the radical investigation. The application of intelligent ink testing and an antioxidant assay using DPPH reduction were also used to confirm the existence of radicals. These techniques provided data confirming that radicals are responsible for the antibacterial properties. The synthesized antibacterial hydroxyapatite would be a good candidate for the prevention any infection with medical implants and injection materials causing failure in bone repair.
Transcriptomics of cytokinin and auxin metabolism and signaling genes during seed maturation in dormant and non-dormant wheat genotypes
Authors: Tuan Pham Anh , Yamasaki Yuji , Kanno Yuri , Seo Mitsunori , Ayele Belay T.
Published: March 2019

To gain insights into the roles of cytokinin (CK) and auxin in regulating dormancy during seed maturation in wheat, we examined changes in the levels of CK and indole-3-acetic acid (IAA) and expression patterns of their metabolism and signaling genes in embryonic and endospermic tissues of dormant and non-dormant genotypes. Seed maturation was associated with a decrease in the levels of isopentenyladenine in both tissues mainly via repression of the CK biosynthetic TaLOG genes. Differential embryonic trans-zeatin content and expression patterns of the CK related genes including TacZOG, TaGLU and TaARR12 between maturing seeds of the two genotypes implicate CK in the control of seed dormancy induction and maintenance. Seed maturation induced a decrease of IAA level in both tissues irrespective of genotype, and this appeared to be mediated by repression of specific IAA biosynthesis, transport and IAA-conjugate hydrolysis genes. The differential embryonic IAA content and expression pattern of the IAA biosynthetic gene TaAO during the early stage of seed maturation between the two genotypes imply the role of IAA in dormancy induction. It appears from our data that the expression of specific auxin signaling genes including TaRUB, TaAXR and TaARF mediate the role of auxin signaling in dormancy induction and maintenance during seed maturation in wheat.
Fine particulate matter (PM2.5) inhibits ciliogenesis by increasing SPRR3 expression via c-Jun activation in RPE cells and skin keratinocytes
Authors: Bae Ji-Eun , Choi Hyunjung , Shin Dong Woon , Na Hye-Won , Park Na Yeon , Kim Joon Bum , Jo Doo Sin , Cho Min Ji , Lyu Jung Ho , Chang Jeong Ho , Lee Eunjoo H. , Lee Tae Ryong , Kim Hyoung-June , Cho Dong-Hyung
Published: March 2019

Exposure to fine particulate matter (PM) with diameter <2.5 µm (PM2.5) causes epithelium injury and endothelial dysfunction. Primary cilia are sensory organelles that transmit extracellular signals into intracellular biochemical responses and have roles in physiology. To date, there have been no studies investigating whether PM2.5 affects primary cilia in skin. We addressed this in the present study using normal human epidermal keratinocytes (NHEKs) and retinal pigment epithelium (RPE) cells. We found that formation of primary cilium is increased in differentiated NHEKs. However, treatment with PM2.5 blocked increased ciliogenesis in NHEKs and RPE cells. Furthermore, PM2.5 transcriptionally upregulated small proline rich protein 3 (SPRR3) expression by activating c-Jun, and ectopic expression of SPRR3 inhibits suppressed the ciliogenesis. Accordingly, treatment with c-Jun activator (anisomycin) induced SPRR3 expression, whereas the inhibitor (SP600125) recovered the ciliated cells and cilium length in PM2.5-treated cells. Moreover, c-Jun inhibitor suppressed upregulation of SPRR3 in PM2.5-treated cells. Taken together, our finding suggested that PM2.5 inhibits ciliogenesis by increasing SPRR3 expression via c-Jun activation in RPE cells and keratinocytes.
Mesenchymal actomyosin contractility is required for androgen-driven urethral masculinization in mice
Authors: Acebedo Alvin R. , Suzuki Kentaro , Hino Shinjiro , Alcantara Mellissa C. , Sato Yuki , Haga Hisashi , Matsumoto Ken-ichi , Nakao Mitsuyoshi , Shimamura Kenji , Takeo Toru , Nakagata Naomi , Miyagawa Shinichi , Nishinakamura Ryuichi , Adelstein Robert S. , Yamada Gen
Published: March 2019

The morphogenesis of mammalian embryonic external genitalia (eExG) shows dynamic differences between males and females. In genotypic males, eExG are masculinized in response to androgen signaling. Disruption of this process can give rise to multiple male reproductive organ defects. Currently, mechanisms of androgen-driven sexually dimorphic organogenesis are still unclear. We show here that mesenchymal-derived actomyosin contractility, by MYH10, is essential for the masculinization of mouse eExG. MYH10 is expressed prominently in the bilateral mesenchyme of male eExG. Androgen induces MYH10 protein expression and actomyosin contractility in the bilateral mesenchyme. Inhibition of actomyosin contractility through blebbistatin treatment and mesenchymal genetic deletion induced defective urethral masculinization with reduced mesenchymal condensation. We also suggest that actomyosin contractility regulates androgen-dependent mesenchymal directional cell migration to form the condensation in the bilateral mesenchyme leading to changes in urethral plate shape to accomplish urethral masculinization. Thus, mesenchymal-derived actomyosin contractility is indispensable for androgen-driven urethral masculinization.
Identification of evolutionarily conserved virulence factor by selective pressure analysis of Streptococcus pneumoniae
Authors: Yamaguchi Masaya , Goto Kana , Hirose Yujiro , Yamaguchi Yuka , Sumitomo Tomoko , Nakata Masanobu , Nakano Kazuhiko , Kawabata Shigetada
Published: March 2019

Evolutionarily conserved virulence factors can be candidate therapeutic targets or vaccine antigens. Here, we investigated the evolutionary selective pressures on 16 pneumococcal choline-binding cell-surface proteins since Streptococcus pneumoniae is one of the pathogens posing the greatest threats to human health. Phylogenetic and molecular analyses revealed that cbpJ had the highest codon rates to total numbers of codons under considerable negative selection among those examined. Our in vitro and in vivo assays indicated that CbpJ functions as a virulence factor in pneumococcal pneumonia by contributing to evasion of neutrophil killing. Deficiency of cbpL under relaxed selective pressure also caused a similar tendency but showed no significant difference in mouse intranasal infection. Thus, molecular evolutionary analysis is a powerful tool that reveals the importance of virulence factors in real-world infection and transmission, since calculations are performed based on bacterial genome diversity following transmission of infection in an uncontrolled population.
Lignin oxidation by MnO2 under the irradiation of blue light
Authors: Dai Jinhuo , Patti Antonio F. , Styles Gavin N. , Nanayakkara Sepa , Spiccia Leone , Arena Francesco , Italiano Cristina , Saito Kei
Published: March 2019

We investigated a photocatalytic heterogeneous system using recyclable MnO2 under the irradiation of blue light for lignin oxidation.
Making the move towards modernized greener separations: introduction of the analytical method greenness score (AMGS) calculator
Authors: Hicks Michael B. , Farrell William , Aurigemma Christine , Lehmann Laurent , Weisel Lauren , Nadeau Kelly , Lee Heewon , Moraff Carol , Wong Mengling , Huang Yun , Ferguson Paul
Published: March 2019

A single easy-to-use tool to provide a built-in quantitative way to show how method choices impact greenness.
Imidazolium chloride-Co(iii) complex immobilized on Fe3O4@SiO2 as a highly active bifunctional nanocatalyst for the copper-, phosphine-, and base-free Heck and Sonogashira reactions
Authors: Kazemnejadi Milad , Alavi G. Seyyedeh Ameneh , Rezazadeh Zinat , Nasseri Mohammad Ali , Allahresani Ali , Esmaeilpour Mohsen
Published: March 2019

A green and efficient method has been developed for Heck and Sonogashira reactions by a magnetic Co(iii) bi-functional catalyst.
Non-contact monitoring of extra-cellular field potentials with a multi-electrode array
Authors: Sharf Tal , Hansma Paul K. , Hari Mukund A. , Kosik Kenneth S.
Published: March 2019

A single set of electrical sensors can probe the activity of electrogenic cells grown on disposable coverslips without degrading its performance.
Synthesis and biological evaluation of zinc chelating compounds as metallo-β-lactamase inhibitors
Authors: Kildahl-Andersen Geir , Schnaars Christian , Prandina Anthony , Radix Sylvie , Le Borgne Marc , Jordheim Lars Petter , Gjøen Tor , Andresen Adriana Magalhães Santos , Lauksund Silje , Fröhlich Christopher , Samuelsen Ørjan , Rongved Pål , Åstrand Ove Alexander Høgmoen
Published: March 2019

New MBL inhibitor renders resistant Gram negative bacteria susceptible to carbapenems.