bluuebunny/crossref_metadata_2025 huggingface dataset:
Remote Sensing of Sargassum Biomass, Nutrients, and Pigments
Authors: Wang Mengqiu , Hu Chuanmin , Cannizzaro Jennifer , English David , Han Xingxing , Naar David , Lapointe Brian , Brewton Rachel , Hernandez Frank
Published: July 2018

Field and laboratory experiments are designed to measure Sargassum biomass per area (density), surface reflectance, nutrient contents, and pigment concentrations. An alternative floating algae index‐biomass density model is established to link the spectral reflectance to Sargassum biomass density, with a relative uncertainty of ~12%. Monthly mean integrated Sargassum biomass in the Caribbean Sea and central West Atlantic reached at least 4.4 million tons in July 2015. The average %C, %N, and %P per dry weight are 27.16, 1.06, and 0.10, respectively. The mean chlorophyll‐a (Chl‐a) concentration is ~0.05% of the dry weight. With these parameters, the amounts of nutrients and pigments can be estimated directly from remotely sensed Sargassum biomass. During bloom seasons, Sargassum carbon can account for ~18% of the total particulate organic carbon in the upper water column. This study provides the first quantitative assessment of the overall Sargassum biomass, nutrients, and pigment abundance from remote sensing observations, thus helping to quantify their ecological roles and facilitate management decisions.
Role of Greenland Sea Gyre Circulation on Atlantic Water Temperature Variability in the Fram Strait
Authors: Chatterjee Sourav , Raj Roshin P. , Bertino L. , Skagseth Ø. , Ravichandran M. , Johannessen Ola M.
Published: July 2018

Atlantic Water (AW) transported from the Nordic Seas is the major source of oceanic heat to the Arctic Ocean. Based on results from the TOPAZ reanalysis, a regional coupled ice‐ocean data assimilation system, we show that interannual variability of AW temperature in the Fram Strait (FS) is associated with the strength of the Greenland Sea gyre (GSG) circulation. The response of the GSG to the anomalous wind stress curl over the Nordic Seas modifies the AW inflow and thus influences the variability of AW temperature in the FS. A stronger (weaker) GSG circulation increases (decreases) the AW flow speed toward FS, leading to increased (decreased) oceanic heat content and higher (lower) AW temperature therein. This implies that the Nordic Seas circulation is not only a passive conduit of AW, but its response to overlying atmospheric variability can also largely influence the AW temperature in the FS by modifying the transport of AW.
On the Solstice Maxima and Azimuth‐Dependent Characteristics of the 150‐km Echoes Observed Using the Equatorial Atmosphere Radar
Authors: Pavan Chaitanya P. , Patra A. K. , Otsuka Y. , Yokoyama T. , Yamamoto M.
Published: July 2018

We present long overdue statistical analysis of the 150‐km echoes based on 10 years of observations made using the Equatorial Atmosphere Radar located at Kototabang, Indonesia. Analysis shows that while the basic features of the echoes are very similar to those observed from other equatorial/low‐latitude stations, occurrence and power/signal‐to‐noise ratio of the echoes are much higher in the solstices than in the equinoxes. Furthermore, both occurrence rate and power/signal‐to‐noise ratio of the echoes in the December solstice are marginally lower than those of the June solstice. The observed solstice‐equinox asymmetry has important implications with regard to the generation mechanism of the 150‐km echoes since this seasonal behavior cannot be accounted for by the recently proposed photoelectron‐induced enhanced plasma wave process alone. Equatorial Atmosphere Radar observations also display remarkable azimuthal variations of the echo characteristics, which indicate magnetic aspect angle dependence of the echoes. The implications of these results are discussed in terms of the origin of the 150‐km echoes.
Electron Energy Spectrum and Auroral Power Estimation From Incoherent Scatter Radar Measurements
Authors: Virtanen Ilkka I. , Gustavsson Björn , Aikio Anita , Kero Antti , Asamura Kazushi , Ogawa Yasunobu
Published: July 2018

Differential energy flux of electrons precipitating into the high‐latitude ionosphere can be estimated from incoherent scatter radar observations of the ionospheric electron density profile. We present a method called ELSPEC for electron spectrum estimation from incoherent scatter radar measurements, which is based on integration of the electron continuity equation and spectrum model selection by means of the Akaike information criterion. This approach allows us to use data with almost arbitrary time resolutions, enables spectrum estimation with dense energy grids, avoids noise amplifications in numerical derivatives, and yields statistical error estimates for all the output parameters, including the number and energy fluxes and upward field‐aligned currents carried by the precipitating electrons. The technique is targeted for auroral energies, 1–100 keV, which ionize the atmosphere mainly between 80 and 150 km altitudes. We validate the technique by means of a simulation study, which shows that Maxwellian, kappa, and mono‐energetic spectra, as well as combinations of those, can be reproduced. Comparison study for two conjugate satellite measurements to the EISCAT UHF radar are shown, for Reimei and Swarm, showing an agreement with the results. Finally, an example of a 2‐hr measurement by the EISCAT radar is shown, during which we observe a variety of precipitation characteristics, from soft background precipitation to mono‐energetic spectra with peak energies up to 60 keV. The upward field‐aligned current varies from 0 to 10 μAm−2 and the total energy flux from 0 to 250 mWm−2.
Timescales of Dayside and Nightside Field‐Aligned Current Response to Changes in Solar Wind‐Magnetosphere Coupling
Authors: Milan Stephen E. , Carter Jennifer Alyson , Sangha Harneet , Laundal Karl M. , Østgaard Nikolai , Tenfjord Paul , Reistad Jone Peter , Snekvik Kristian , Coxon John C , Korth Haje , Anderson Brian J.
Published: July 2018

Principal component analysis is performed on Birkeland or field‐aligned current (FAC) measurements from the Active Magnetosphere and Planetary Electrodynamics Response Experiment, to determine the response of dayside and nightside FACs to reversals in the orientation of the interplanetary magnetic field (IMF) and the occurrence of substorms. Dayside FACs respond promptly to changes in IMF BY, but the nightside response is delayed by up to an hour and can take up to 4 hr to develop fully, especially during northward IMF. Nightside FAC asymmetries grow during substorm growth phase when the IMF has a significant BY component, and also promptly at substorm onset. Our findings suggest that magnetotail twisting and/or BY penetration into the magnetotail, due to subsolar reconnection with east‐west orientated IMF, are the main cause of these nightside FAC asymmetries and that asymmetries also arise due to magnetotail reconnection of these twisted field lines.
Attenuation and Directional Spreading of Ocean Waves During a Storm Event in the Autumn Beaufort Sea Marginal Ice Zone
Authors: Montiel F. , Squire V. A. , Doble M. , Thomson J. , Wadhams P.
Published: July 2018

This paper investigates the attenuation and directional spreading of large amplitude waves traveling through pancake ice. Directional spectral density is analyzed from in situ wave buoy data collected during a 3‐day storm event in October 2015 in the Beaufort Sea. Two proxy metrics for wave amplitude obtained from energy density spectra, namely, spectral amplitude and significant wave height, are used to track the waves as they propagate along transects through the array of buoys in the predominantly pancake ice field. Two types of wave buoys are used in the analysis and compared, exhibiting significant differences in the wave energy density and directionality estimates. Although exponential decay is observed predominantly, one of the two buoy types indicates a potential positive correlation between wave energy density and the occurrence of linear wave decay, as opposed to exponential decay, in accord with recent observations in the Antarctic marginal ice zone. Factors affecting the validity of this observation are discussed. An empirical power law with exponent 2.2 is also found to hold between the exponential attenuation coefficient and wave frequency. The directional content of the wave spectrum appears to decrease consistently along the wave transects, confirming that wave energy is being dissipated by the pancake ice as opposed to being scattered by ice cakes.
On the Recent Ambiguity of the North Atlantic Subpolar Gyre Index
Authors: Hátún H. , Chafik L.
Published: July 2018

The so‐called gyre index appears to be related to core aspects of the North Atlantic subpolar gyre, meridional overturning circulation, hydrographic properties in the Atlantic inflows toward the Arctic, and in marine ecosystems in the northeast Atlantic Ocean. Recent publications, however, present a more linear version of this index with less of the key interannual‐to‐decadal variability. This has introduced uncertainty about the meaning and usefulness of the gyre index. We claim that these concerns are primarily caused by the fact that the recently produced “gyre index” is not the same as the original gyre index and discuss possible reasons.
Counterbalance: modulation of VEGF/VEGFR activities by TNFSF15
Authors: Yang Gui-Li , Li Lu-Yuan
Published: July 2018

Vascular hyperpermeability occurs in angiogenesis and several pathobiological conditions, producing elevated interstitial fluid pressure and lymphangiogenesis. How these closely related events are modulated is a fundamentally important question regarding the maintenance of vascular homeostasis and treatment of disease conditions such as cancer, stroke, and myocardial infarction. Signals mediated by vascular endothelial growth factor receptors, noticeably VEGFR-1, −2, and −3, are centrally involved in the promotion of both blood vessel and lymphatic vessel growth. These signaling pathways are counterbalanced or, in the case of VEGFR3, augmented by signals induced by tumor necrosis factor superfamily-15 (TNFSF15). TNFSF15 can simultaneously downregulate membrane-bound VEGFR1 and upregulate soluble VEGFR1, thus changing VEGF/VEGFR1 signals from pro-angiogenic to anti-angiogenic. In addition, TNFSF15 inhibits VEGF-induced VEGFR2 phosphorylation, thereby curbing VEGFR2-mediated enhancement of vascular permeability. Third, and perhaps more interestingly, TNFSF15 is capable of stimulatingVEGFR3gene expression in lymphatic endothelial cells, thus augmenting VEGF-C/D-VEGFR3-facilitated lymphangiogenesis. We discuss the intertwining relationship between the actions of TNFSF15 and VEGF in this review.
Overexpression of PEAK1 contributes to epithelial–mesenchymal transition and tumor metastasis in lung cancer through modulating ERK1/2 and JAK2 signaling
Authors: Ding Chenbo , Tang Wendong , Fan Xiaobo , Wang Xiyong , Wu Hairu , Xu Hongbo , Xu Wei , Gao Wei , Wu Guoqiu
Published: July 2018

Pseudopodium-enriched atypical kinase 1 (PEAK1), a novel non-receptor tyrosine kinase, has been demonstrated to act as an oncogenic regulator in breast and pancreatic cancers. However, the role of PEAK1 in the progression and metastasis of lung cancer is still unknown. Here, we observed that ectopic PEAK1 expression promoted lung cancer cell migration and invasion, while PEAK1 knockout resulted in suppressed cell migration and invasion. Interestingly, cell proliferation did not significantly increase or decrease in either the PEAK1 overexpression or knockout groups compared with the corresponding control cells. In addition, PEAK1 overexpression could induce epithelial-to-mesenchymal transition (EMT) and the expression of matrix metalloproteinase-2 (MMP2) and MMP9 both in vitro and in vivo, whereas PEAK1 knockout had the opposite effects. Then, we had confirmed that PEAK1 was significantly upregulated in lung cancer tissues, and correlated with a higher tumor node metastasis stage. Moreover, PEAK1 upregulation markedly enhanced the activation of extracellular signal-regulated kinase-1/2 (ERK1/2) and Janus kinase-2 (JAK2) signaling in lung cancer cells. Further work demonstrated that the combination of PD98059 with AZD1480 could reverse the effects of PEAK1-induced EMT, cell migration and invasion. Our findings highlight a newer mechanism for PEAK1 in regulating EMT and metastasis in lung cancer, which might serve as a therapeutic target for lung cancer patients.
A lincRNA-p21/miR-181 family feedback loop regulates microglial activation during systemic LPS- and MPTP- induced neuroinflammation
Authors: Ye Yongyi , He Xiaozheng , Lu Fengfei , Mao Hengxu , Zhu Zhiyuan , Yao Longping , Luo Wanxian , Sun Xiang , Wang Baoyan , Qian Chen , Zhang Yizhou , Lu Guohui , Zhang Shizhong
Published: July 2018

The role of microglial-mediated sustained neuroinflammation in the onset and progression of Parkinson’s disease (PD) is well established, but the mechanisms contributing to microglial activation remain unclear. LincRNA-p21, a well studied long intergenic noncoding RNA (lincRNA), plays pivotal roles in diverse biological processes and diseases. Its role in microglial activation and inflammation-induced neurotoxicity, however, has not yet been fully elucidated. Here, we report that lincRNA-p21 promotes microglial activation through a p53-dependent transcriptional pathway. We further demonstrate that lincRNA-p21 competitively binds to the miR-181 family and induces microglial activation through the miR-181/PKC-δ pathway. Moreover, PKC-δ induction further increases the expression of p53/lincRNA-p21 and thus forms a circuit. Taken together, our results suggest that p53/lincRNA-p21, together with miR-181/PKC-δ, form a double-negative feedback loop that facilitates sustained microglial activation and the deterioration of neurodegeneration.
ZDHHC8 critically regulates seizure susceptibility in epilepsy
Authors: Yang Qin , Zheng Fangshuo , Hu Yida , Yang Yi , Li Yun , Chen Guojun , Wang Wei , He Miaoqing , Zhou Ruijiao , Ma Yuanlin , Xu Demei , Tian Xin , Gao Xiaoya , Wang Qing , Wang Xuefeng
Published: July 2018

Epilepsy is one of the most prevalent and drug-refractory neurological disorders. Zinc finger DHHC-type containing 8 (ZDHHC8) is a putative palmitoyltransferase that is highly expressed in the brain. However, the impact of ZDHHC8 on seizures remains unclear. We aimed to explore the association of ZDHHC8 with epilepsy and investigate its in epileptogenesis in in vivo and in vitro models through behavioral, electrophysiological, and pathological studies. We used kainic acid- and pilocarpine-induced C57BL/6 mice and magnesium-free-induced pyramidal neurons as experimental epileptic models in this study. We first found increased ZDHHC8 expression in the brains of temporal lobe epilepsy (TLE) patients, similar to that observed in chronic epileptic mice, strongly suggesting that ZDHHC8 is correlated with human epilepsy. In the in vitro seizure models, knocking down ZDHHC8 using recombinant adeno-associated virus (rAAV) delayed seizure precipitation and decreased chronic spontaneous recurrent seizures (SRSs) and epileptiform-like discharges, while ZDHHC8 overexpression had the opposite effect. ZDHHC8 levels were consistent with seizure susceptibility in induced mice with SRSs. In an in vitro magnesium-free model, neuronal hyperexcitability and hypersynchrony were reduced in ZDHHC8-knockdown neurons but were increased in ZDHHC8-overexpressing neurons. To further explore the potential mechanisms, we observed that ZDHHC8 had a significant modulatory effect on 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid (AMPA) receptor-related excitatory, but not inhibitory, glutamatergic synaptic neurotransmission, further affecting the inward rectification of AMPA currents in acute hippocampal slices in whole-cell recordings. ZDHHC8 facilitated GluA1 trafficking to the neuronal surface in the hippocampus, as shown by immunoprecipitation and Western blotting. These results suggest that ZDHHC8 may promote the generation and propagation of seizures in humans and that knocking down ZDHHC8 might produce anti-epileptogenic effects in drug-resistant epilepsy. Our study provides evidence that may facilitate the development of an alternative approach for the treatment of epilepsy by modulating AMPA/GluA1-mediated neurotransmission.
Programmable DNA repair with CRISPRa/i enhanced homology-directed repair efficiency with a single Cas9
Authors: Ye Lupeng , Wang Chengkun , Hong Lingjuan , Sun Ninghe , Chen Danyang , Chen Sidi , Han Feng
Published: July 2018

CRISPR systems have been proven as versatile tools for site-specific genome engineering in mammalian species. During the gene editing processes, these RNA-guide nucleases introduce DNA double strand breaks (DSBs), in which non-homologous DNA end joining (NHEJ) dominates the DNA repair pathway, limiting the efficiency of homology-directed repair (HDR), the alternative pathway essential for precise gene targeting. Multiple approaches have been developed to enhance HDR, including chemical compound or RNA interference-mediated inhibition of NHEJ factors, small molecule activation of HDR enzymes, or cell cycle timed delivery of CRISPR complex. However, these approaches face multiple challenges, yet have moderate or variable effects. Here we developed a new approach that programs both NHEJ and HDR pathways with CRISPR activation and interference (CRISPRa/i) to achieve significantly enhanced HDR efficiency of CRISPR-mediated gene editing. The manipulation of NHEJ and HDR pathway components, such as CtIP, CDK1, KU70, KU80, and LIG4, was mediated by catalytically dead guide RNAs (dgRNAs), thus relying on only a single catalytically active Cas9 to perform both CRISPRa/i and precise gene editing. While reprogramming of most DNA repair factors or their combinations tested enhanced HDR efficiency, simultaneously activating CDK1 and repressing KU80 has the strongest effect with increased HDR rate upto an order of magnitude. Doxycycline-induced dgRNA-based CRISPRa/i programming of DNA repair enzymes, as well as viral packaging enabled flexible and tunable HDR enhancement for broader applicability in mammalian cells. Our study provides an effective, flexible, and potentially safer strategy to enhance precise genome modifications, which might broadly impact human gene editing and therapy.
Operando and three-dimensional visualization of anion depletion and lithium growth by stimulated Raman scattering microscopy
Authors: Cheng Qian , Wei Lu , Liu Zhe , Ni Nan , Sang Zhe , Zhu Bin , Xu Weiheng , Chen Meijie , Miao Yupeng , Chen Long-Qing , Min Wei , Yang Yuan
Published: July 2018

Visualization of ion transport in electrolytes provides fundamental understandings of electrolyte dynamics and electrolyte-electrode interactions. However, this is challenging because existing techniques are hard to capture low ionic concentrations and fast electrolyte dynamics. Here we show that stimulated Raman scattering microscopy offers required resolutions to address a long-lasting question: how does the lithium-ion concentration correlate to uneven lithium deposition? In this study, anions are used to represent lithium ions since their concentrations should not deviate for more than 0.1 mM, even near nanoelectrodes. A three-stage lithium deposition process is uncovered, corresponding to no depletion, partial depletion, and full depletion of lithium ions. Further analysis reveals a feedback mechanism between the lithium dendrite growth and heterogeneity of local ionic concentration, which can be suppressed by artificial solid electrolyte interphase. This study shows that stimulated Raman scattering microscopy is a powerful tool for the materials and energy field.
Neutrophil extracellular trap formation requires OPA1-dependent glycolytic ATP production
Authors: Amini Poorya , Stojkov Darko , Felser Andrea , Jackson Christopher B. , Courage Carolina , Schaller André , Gelman Laurent , Soriano Maria Eugenia , Nuoffer Jean-Marc , Scorrano Luca , Benarafa Charaf , Yousefi Shida , Simon Hans-Uwe
Published: July 2018

Optic atrophy 1 (OPA1) is a mitochondrial inner membrane protein that has an important role in mitochondrial fusion and structural integrity. Dysfunctional OPA1 mutations cause atrophy of the optic nerve leading to blindness. Here, we show that OPA1 has an important role in the innate immune system. Using conditional knockout mice lacking Opa1 in neutrophils (Opa1N∆), we report that lack of OPA1 reduces the activity of mitochondrial electron transport complex I in neutrophils. This then causes a decline in adenosine-triphosphate (ATP) production through glycolysis due to lowered NAD+ availability. Additionally, we show that OPA1-dependent ATP production in these cells is required for microtubule network assembly and for the formation of neutrophil extracellular traps. Finally, we show that Opa1N∆ mice exhibit a reduced antibacterial defense capability against Pseudomonas aeruginosa.
Mechanical dissipation from charge and spin transitions in oxygen-deficient SrTiO3 surfaces
Authors: Kisiel Marcin , Brovko Oleg O. , Yildiz Dilek , Pawlak Rémy , Gysin Urs , Tosatti Erio , Meyer Ernst
Published: July 2018

Bodies in relative motion separated by a gap of a few nanometers can experience a tiny friction force. This non-contact dissipation can have various origins and can be successfully measured by a sensitive pendulum atomic force microscope tip oscillating laterally above the surface. Here, we report on the observation of dissipation peaks at selected voltage-dependent tip-surface distances for oxygen-deficient strontium titanate (SrTiO3) surface at low temperatures (T = 5 K). The observed dissipation peaks are attributed to tip-induced charge and spin state transitions in quantum-dot-like entities formed by single oxygen vacancies (and clusters thereof, possibly through a collective mechanism) at the SrTiO3 surface, which in view of technological and fundamental research relevance of the material opens important avenues for further studies and applications.
A user-friendly herbicide derived from photo-responsive supramolecular vesicles
Authors: Gao Cheng , Huang Qiaoxian , Lan Qingping , Feng Yu , Tang Fan , Hoi Maggie P. M. , Zhang Jianxiang , Lee Simon M. Y. , Wang Ruibing
Published: July 2018

Paraquat, as one of the most widely used herbicides globally, is highly toxic to humans, and chronic exposure and acute ingestion leads to high morbidity and mortality rates. Here, we report user-friendly, photo-responsive paraquat-loaded supramolecular vesicles, prepared via one-pot self-assembly of amphiphilic, ternary host-guest complexes between cucurbit[8]uril, paraquat, and an azobenzene derivative. In this vesicle formulation, paraquat is only released upon UV or sunlight irradiation that converts the azobenzene derivative from its trans- to its cis- form, which in turn dissociates the ternary host-guest complexations and the vesicles. The cytotoxicity evaluation of this vesicle formulation of paraquat on in vitro cell models, in vivo zebrafish models, and mouse models demonstrates an enhanced safety profile. Additionally, the PQ-loaded vesicles’ herbicidal activity against a model of invasive weed is nearly identical to that of free paraquat under natural sunlight. This study provides a safe yet effective herbicide formulation.
Nanometer-scale gradient atomic packing structure surrounding soft spots in metallic glasses
Authors: Wang Binbin , Luo Liangshun , Guo Enyu , Su Yanqing , Wang Mingyue , Ritchie Robert O. , Dong Fuyu , Wang Liang , Guo Jingjie , Fu Hengzhi
Published: July 2018

The hidden order of atomic packing in amorphous structures and how this may provide the origin of plastic events have long been a goal in the understanding of plastic deformation in metallic glasses. To pursue this issue, we employ here molecular dynamic simulations to create three-dimensional models for a few metallic glasses where, based on the geometrical frustration of the coordination polyhedra, we classify the atoms in the amorphous structure into six distinct species, where “gradient atomic packing structure” exists. The local structure in the amorphous state can display a gradual transition from loose stacking to dense stacking of atoms, followed by a gradient evolution of atomic performance. As such, the amorphous alloy specifically comprises three discernible regions: solid-like, transition, and liquid-like regions, each one possessing different types of atoms. We also demonstrate that the liquid-like atoms correlate most strongly with fertile sites for shear transformation, the transition atoms take second place, whereas the solid-like atoms contribute the least because of their lowest correlation level with the liquid-like atoms. Unlike the “geometrically unfavored motifs” model which fails to consider the role of medium-range order, our model gives a definite structure for the so-called “soft spots”, that is, a combination of liquid-like atoms and their neighbors, in favor of quantifying and comparing their number between different metallic glasses, which can provide a rational explanation for the unique mechanical behavior of metallic glasses.
Nondestructive detector for exchange symmetry of photonic qubits
Authors: Stárek Robert , Mičuda Michal , Miková Martina , Straka Ivo , Dušek Miloslav , Marek Petr , Ježek Miroslav , Filip Radim , Fiurášek Jaromír
Published: July 2018

We experimentally realize a quantum Fredkin gate and use it for constructing a nondestructive detector of exchange symmetry for qubits. The detector, which discriminates between symmetric and anti-symmetric quantum states of two qubits, allows us to directly measure a purity and overlap of quantum states and implement a quantum state programmable measurement. Furthermore, the nondestructive nature of the detector can be used for analysis of the back-action of the measurements, as well as for realization of nonlinear quantum operations, such as quantum purification and quantum cloning. As a whole, the experiment demonstrates the utility of exchange symmetry measurements and their potential for multi-step characterization and processing of quantum states.
Matrine inhibits itching by lowering the activity of calcium channel
Authors: Geng Xiao , Shi Hao , Ye Fan , Du Han , Qian Linnan , Gu Leying , Wu Guanyi , Zhu Chan , Yang Yan , Wang Changming , Zhou Yuan , Yu Guang , Liu Qin , Dong Xinzhong , Yu Lei , Tang Zongxiang
Published: July 2018

Sophorae Flavescentis Radix(SFR) is a medicinal herb with many functions that are involved in anti-inflammation, antinociception, and anticancer.SFRis also used to treat a variety of itching diseases. Matrine (MT) is one of the main constituents in SFR and also has the effect of relieving itching, but the antipruritic mechanism is still unclear. Here, we investigated the effect of MT on anti-pruritus. In acute and chronic itch models, MT significantly inhibited the scratching behavior not only in acute itching induced by histamine (His), chloroquine (CQ) and compound 48/80 with a dose-depended manner, but also in the chronic pruritus models of atopic dermatitis (AD) and acetone-ether-water (AEW) in mice. Furthermore, MT could be detected in the blood after intraperitoneal injection (i.p.) and subcutaneous injection (s.c.). Finally, electrophysiological and calcium imaging results showed that MT inhibited the excitatory synaptic transmission from dorsal root ganglion (DRG) to the dorsal horn of the spinal cord by suppressing the presynaptic N-type calcium channel. Taken together, we believe that MT is a novel drug candidate in treating pruritus diseases, especially for histamine-independent and chronic pruritus, which might be attributed to inhibition of the presynaptic N-type calcium channel.
Author Correction: Prostaglandin E1 Attenuates Pulmonary Artery Remodeling by Activating Phosphorylation of CREB and the PTEN Signaling Pathway
Authors: Lai Ying-Ju , Hsu Hsao-Hsun , Chang Gwo-Jyh , Lin Shu-Hui , Chen Wei-Jan , Huang Chung-Chi , Pang Jong-Hwei S.
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Salvianolic acids from antithrombotic Traditional Chinese Medicine Danshen are antagonists of human P2Y1 and P2Y12 receptors
Authors: Liu Xuyang , Gao Zhan-Guo , Wu Yiran , Stevens Raymond C. , Jacobson Kenneth A. , Zhao Suwen
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Beyond autophagy: a novel role for autism-linked Wdfy3 in brain mitophagy
Authors: Napoli Eleonora , Song Gyu , Panoutsopoulos Alexios , Riyadh M. Asrafuzzaman , Kaushik Gaurav , Halmai Julian , Levenson Richard , Zarbalis Konstantinos S. , Giulivi Cecilia
Published: July 2018

WD repeat and FYVE domain-containing 3 (WDFY3; also known as Autophagy-Linked FYVE or Alfy) is an identified intellectual disability, developmental delay and autism risk gene. This gene encodes for a scaffolding protein that is expressed in both the developing and adult central nervous system and required for autophagy and aggrephagy with yet unexplored roles in mitophagy. Given that mitochondrial trafficking, dynamics and remodeling have key roles in synaptic plasticity, we tested the role of Wdfy3 on brain bioenergetics by using Wdfy3+/lacZ mice, the only known Wdfy3 mutant animal model with overt neurodevelopmental anomalies that survive to adulthood. We found that Wdfy3 is required for sustaining brain bioenergetics and morphology via mitophagy. Decreased mitochondrial quality control by conventional mitophagy was partly compensated for by the increased formation of mitochondria-derived vesicles (MDV) targeted to lysosomal degradation (micromitophagy). These observations, extended through proteomic analysis of mitochondria-enriched cortical fractions, showed significant enrichment for pathways associated with mitophagy, mitochondrial transport and axon guidance via semaphorin, Robo, L1cam and Eph-ephrin signaling. Collectively, our findings support a critical role for Wdfy3 in mitochondrial homeostasis with implications for neuron differentiation, neurodevelopment and age-dependent neurodegeneration.
Streptozotocin-induced β-cell damage, high fat diet, and metformin administration regulate Hes3 expression in the adult mouse brain
Authors: Nikolakopoulou Polyxeni , Chatzigeorgiou Antonios , Kourtzelis Ioannis , Toutouna Louiza , Masjkur Jimmy , Arps-Forker Carina , Poser Steven W. , Rozman Jan , Rathkolb Birgit , Aguilar-Pimentel Juan Antonio ,   German Mouse Clinic Consortium, Becker Lore , Klopstock Thomas , Treise Irina , Busch Dirk H. , Beckers Johannes , Moreth Kristin , Bekeredjian Raffi , Garrett Lillian , Hölter Sabine M. , Zimprich Annemarie , Wurst Wolfgang , Brommage Robert , Amarie Oana , Graw Jochen , Calzada-Wack Julia , Neff Frauke , Zimmer Andreas , Östereicher Manuela , Steinkamp Ralph , Lengger Christoph , Maier Holger , Stoeger Claudia , Leuchtenberger Stefanie , Wolf Eckhard , Klingenspor Martin , Ollert Markus , Schmidt-Weber Carsten , Fuchs Helmut , Gailus-Durner Valerie , Hrabe de Angelis Martin , Tsata Vasiliki , Monasor Laura Sebastian , Troullinaki Maria , Witt Anke , Anastasiou Vivian , Chrousos George , Yi Chun-Xia , García-Cáceres Cristina , Tschöp Matthias H. , Bornstein Stefan R. , Androutsellis-Theotokis Andreas
Published: July 2018

Diabetes mellitus is a group of disorders characterized by prolonged high levels of circulating blood glucose. Type 1 diabetes is caused by decreased insulin production in the pancreas whereas type 2 diabetes may develop due to obesity and lack of exercise; it begins with insulin resistance whereby cells fail to respond properly to insulin and it may also progress to decreased insulin levels. The brain is an important target for insulin, and there is great interest in understanding how diabetes affects the brain. In addition to the direct effects of insulin on the brain, diabetes may also impact the brain through modulation of the inflammatory system. Here we investigate how perturbation of circulating insulin levels affects the expression of Hes3, a transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. Our data show that streptozotocin-induced β-cell damage, high fat diet, as well as metformin, a common type 2 diabetes medication, regulate Hes3 levels in the brain. This work suggests that Hes3 is a valuable biomarker helping to monitor the state of endogenous neural stem and progenitor cells in the context of diabetes mellitus.
Sputum Detection of Predisposing Genetic Mutations in Women with Pulmonary Nontuberculous Mycobacterial Disease
Authors: Philley Julie V. , Hertweck Kate L. , Kannan Anbarasu , Brown-Elliott Barbara A. , Wallace Richard J. , Kurdowska Anna , Ndetan Harrison , Singh Karan P. , Miller Edmund J. , Griffith David E. , Dasgupta Santanu
Published: July 2018

Nontuberculous mycobacterial lung disease (NTM), including Mycobacterium avium complex (MAC), is a growing health problem in North America and worldwide. Little is known about the molecular alterations occurring in the tissue microenvironment during NTM pathogenesis. Utilizing next generation sequencing, we sequenced sputum and matched lymphocyte DNA in 15 MAC patients for a panel of 19 genes known to harbor cancer susceptibility associated mutations. Thirteen of 15 NTM subjects had a diagnosis of breast cancer (BCa) before or after NTM infection. Thirty three percent (4/12) of these NTM-BCa cases exhibited at least 3 somatic mutations in sputa compared to matched lymphocytes. Twenty four somatic mutations were detected with at least one mutation in ATM, ERBB2, BARD1, BRCA1, BRCA2, AR, TP53, PALB2, CASP8, BRIP1, NBN and TGFB1 genes. All four NTM-BCa patients harboring somatic mutations also exhibited 15 germ line BRCA1 and BRCA2 mutations. The two NTM subjects without BCa exhibited twenty somatic mutations spanning BRCA1, BRCA1, BARD1, BRIP1, CHEK2, ERBB2, TP53, ATM, PALB2, TGFB1 and 3 germ line mutations in BRCA1 and BRCA2 genes. A single copy loss of STK11 and AR gene was noted in NTM-BCa subjects. Periodic screening of sputa may aid to develop risk assessment biomarkers for neoplastic diseases in NTM patients.
RNA-seq and flow-cytometry of conventional, scalp, and palmoplantar psoriasis reveal shared and distinct molecular pathways
Authors: Ahn Richard , Yan Di , Chang Hsin-Wen , Lee Kristina , Bhattarai Shrishti , Huang Zhi-Ming , Nakamura Mio , Singh Rasnik , Afifi Ladan , Taravati Keyon , Munoz-Sandoval Priscila , Pauli Mariela , Rosenblum Michael D. , Liao Wilson
Published: July 2018

It has long been recognized that anatomic location is an important feature for defining distinct subtypes of plaque psoriasis. However, little is known about the molecular differences between scalp, palmoplantar, and conventional plaque psoriasis. To investigate the molecular heterogeneity of these psoriasis subtypes, we performed RNA-seq and flow cytometry on skin samples from individuals with scalp, palmoplantar, and conventional plaque psoriasis, along with samples from healthy control patients. We performed differential expression analysis and network analysis using weighted gene coexpression network analysis (WGCNA). Our analysis revealed a core set of 763 differentially expressed genes common to all sub-types of psoriasis. In contrast, we identified 605, 632, and 262 genes uniquely differentially expressed in conventional, scalp, and palmoplantar psoriasis, respectively. WGCNA and pathway analysis revealed biological processes for the core genes as well as subtype-specific genes. Flow cytometry analysis revealed a shared increase in the percentage of CD4+ T regulatory cells in all psoriasis subtypes relative to controls, whereas distinct psoriasis subtypes displayed differences in IL-17A, IFN-gamma, and IL-22 production. This work reveals the molecular heterogeneity of plaque psoriasis and identifies subtype-specific signaling pathways that will aid in the development of therapy that is appropriate for each subtype of plaque psoriasis.
Comprehensive organic profiling of biological particles derived from blood
Authors: Wu Cheng-Yeu , Martel Jan , Young John D.
Published: July 2018

Mineral nanoparticles form in physiological and pathological processes occurring in the human body. The calcium phosphate mineral phase of the particles has affinity for proteins and lipids, but the complete profiling of the organic molecules that bind to the particles has not been described in detail. We report here a comprehensive analysis of organic components found in mineralo-organic particles derived from body fluids. Based on biological staining, fluorescent tagging, proteomics and metabolomics, our results indicate that the mineral particles bind to proteins, amino acids, carbohydrates, polysaccharides, phospholipids, fatty acids, DNA and low molecular weight metabolites. These results can be used to study the formation and effects of mineralo-organic particles in biological fluids.
Ocean sprawl facilitates dispersal and connectivity of protected species
Authors: Henry Lea-Anne , Mayorga-Adame Claudia G. , Fox Alan D. , Polton Jeff A. , Ferris Joseph S. , McLellan Faron , McCabe Chris , Kutti Tina , Roberts J. Murray
Published: July 2018

Highly connected networks generally improve resilience in complex systems. We present a novel application of this paradigm and investigated the potential for anthropogenic structures in the ocean to enhance connectivity of a protected species threatened by human pressures and climate change. Biophysical dispersal models of a protected coral species simulated potential connectivity between oil and gas installations across the North Sea but also metapopulation outcomes for naturally occurring corals downstream. Network analyses illustrated how just a single generation of virtual larvae released from these installations could create a highly connected anthropogenic system, with larvae becoming competent to settle over a range of natural deep-sea, shelf and fjord coral ecosystems including a marine protected area. These results provide the first study showing that a system of anthropogenic structures can have international conservation significance by creating ecologically connected networks and by acting as stepping stones for cross-border interconnection to natural populations.
Utilization of 3D printing technology to facilitate and standardize soft tissue testing
Authors: Scholze Mario , Singh Aqeeda , Lozano Pamela F. , Ondruschka Benjamin , Ramezani Maziar , Werner Michael , Hammer Niels
Published: July 2018

Three-dimensional (3D) printing has become broadly available and can be utilized to customize clamping mechanisms in biomechanical experiments. This report will describe our experience using 3D printed clamps to mount soft tissues from different anatomical regions. The feasibility and potential limitations of the technology will be discussed. Tissues were sourced in a fresh condition, including human skin, ligaments and tendons. Standardized clamps and fixtures were 3D printed and used to mount specimens. Inquasi-statictensile tests combined with digital image correlation andfatiguetrials we characterized the applicability of the clamping technique. Scanning electron microscopy was utilized to evaluate the specimens to assess the integrity of the extracellular matrix following the mechanical tests. 3D printed clamps showed no signs of clamping-related failure during thequasi-statictests, and intact extracellular matrix was found in the clamping area, at the transition clamping area and the central area from where the strain data was obtained. In thefatiguetests, material slippage was low, allowing for cyclic tests beyond 105cycles. Comparison to other clamping techniques yields that 3D printed clamps ease and expedite specimen handling, are highly adaptable to specimen geometries and ideal for high-standardization and high-throughput experiments in soft tissue biomechanics.
Author Correction: Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
Authors: Coleman Verena , Sa-Nguanmoo Piangkwan , Koenig Jeannette , Schulz Tim J. , Grune Tilman , Klaus Susanne , Kipp Anna P. , Ost Mario
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Trees represent community composition of other plant life-forms, but not their diversity, abundance or responses to fragmentation
Authors: Pasion Bonifacio O. , Roeder Mareike , Liu Jiajia , Yasuda Mika , Corlett Richard T. , Slik J. W. Ferry , Tomlinson Kyle W.
Published: July 2018

Our understanding of the patterns of plant diversity in tropical forests and their responses to fragmentation are mostly based on tree surveys. But are these patterns and responses representative of other plant life-forms? We sampled trees, lianas, herbs, and ferns in a fragmented tropical forest landscape in South-west China. We compared community types generated by clustering presence-absence data for the non-tree life-forms with those generated for trees. We tested how well measures of tree diversity, density and composition, predicted cognate indices in other life-forms. We compared fragmentation responses, with respect to the three measures, of all four life-forms. Presence-absence data from all life-forms generated three community clusters, with only small differences between classifications, suggesting that tree data identified community types representative of all vascular plant life-forms. Tree species diversity and density indices poorly predicted cognate indices of lianas and ferns, but represented herbs well. However, the slopes of these relationships differed substantially between community types. All life-forms responded to fragmentation variables but their responses did not consistently match with responses of trees. Plot-level tree data can identify vegetation community types, but is poorly representative of the richness and density of other life-forms, and poorly represents forest fragmentation responses for the entire plant community.
Composition, structure and tensile biomechanical properties of equine articular cartilage during growth and maturation
Authors: Oinas J. , Ronkainen A. P. , Rieppo L. , Finnilä M. A. J. , Iivarinen J. T. , van Weeren P. R. , Helminen H. J. , Brama P. A. J. , Korhonen R. K. , Saarakkala S.
Published: July 2018

Articular cartilage undergoes structural and biochemical changes during maturation, but the knowledge on how these changes relate to articular cartilage function at different stages of maturation is lacking. Equine articular cartilage samples of four different maturation levels (newborn, 5-month-old, 11-month-old and adult) were collected (N = 25). Biomechanical tensile testing, Fourier transform infrared microspectroscopy (FTIR-MS) and polarized light microscopy were used to study the tensile, biochemical and structural properties of articular cartilage, respectively. The tensile modulus was highest and the breaking energy lowest in the newborn group. The collagen and the proteoglycan contents increased with age. The collagen orientation developed with age into an arcade-like orientation. The collagen content, proteoglycan content, and collagen orientation were important predictors of the tensile modulus (p < 0.05 in multivariable regression) and correlated significantly also with the breaking energy (p < 0.05 in multivariable regression). Partial least squares regression analysis of FTIR-MS data provided accurate predictions for the tensile modulus (r = 0.79) and the breaking energy (r = 0.65). To conclude, the composition and structure of equine articular cartilage undergoes changes with depth that alter functional properties during maturation, with the typical properties of mature tissue reached at the age of 5–11 months.
Jug r 6 is the allergenic vicilin present in walnut responsible for IgE cross-reactivities to other tree nuts and seeds
Authors: Dubiela Pawel , Kabasser Stefan , Smargiasso Nicolas , Geiselhart Sabine , Bublin Merima , Hafner Christine , Mazzucchelli Gabriel , Hoffmann-Sommergruber Karin
Published: July 2018

Walnuts are ranked high in the list of the culprit foods inducing severe allergic reactions. Jug r 2 has been identified as a major allergen in common walnut by cDNA cloning from a somatic cell line. So far, studies were performed on the allergenic activity of recombinant Jug r 2, yet there is still no evidence about the physicochemical characteristics of the natural allergen. Therefore, we aimed to purify and deeply characterize natural Jug r 2 and to assess IgE cross-reactivity among vicilins from different tree nuts. Extensive mass spectrometry analysis of the obtained purified vicilin allowed identification of the protein sequence that displayed only 44% identity to Jug r 2. The newly identified vicilin (Jug r 6) was recognized by IgE of 26% in walnut allergic patients’ sera tested. In contrast to Jug r 2, Jug r 6 displayed a remarkable level of cross-reactivity when tested with homologues from hazelnut, sesame and pistachio. It is the first report showing the necessity of proteomic studies to improve allergy component resolved diagnosis.
Automatic microscopic detection of mycobacteria in sputum: a proof-of-concept
Authors: Zingue D. , Weber P. , Soltani F. , Raoult D. , Drancourt M.
Published: July 2018

The laboratory diagnosis of lung mycobacterioses including tuberculosis comprises the microscopic examination of sputum smear after appropriate staining such as Ziehl-Neelsen staining to observe acid-fast bacilli. This standard procedure is operator-dependant and its sensitivity depends on the duration of observation. We developed and evaluated an operator-independent microscopic examination of sputum smears for the automated detection and enumeration of acid-fast bacilli using a ZEISS Axio Scan.Z1 microscope. The sensitivity, specificity, positive predictive value, negative predictive values and accuracy were calculated using standard formulations by comparison with standard microscopic examination. After in-house parameterization of the automatic microscope and counting software, the limit of detection evaluated by seeding negative sputa with Mycobacterium bovis BCG or Mycobacterium tuberculosis H37Rv (100–105 bacilli/mL) was of 102 bacilli/mL of sputum with a 100% positivity rate. Then, the evaluation of 93 sputum specimens including 34 smear-positive and 59 smear-negative specimens yielded a sensitivity of 97.06% [84.67–99.93%], a specificity of 86.44% [73.01–92.78%]. Up to 100 smear slides could be stocked for reading in the microscope magazine and results are exportable into the laboratory information system. Based on these preliminary results, we are implanting this automatic protocol in the routine workflow so that only smears detected positive by automatic microscopy are confirmed by standard microscopic examination.
The Inverse Poisson Functional for forecasting response time to environmental events and global climate change
Authors: Zachary Daniel S.
Published: July 2018

A series of Poisson distributions are fit to sets of global cost-of-impact data representing large-scale accidents and anthropogenic catastrophes. The fits are used to build a function representing data means and are designated the Inverse Poisson Functional. Climate and environmental data have been used to develop a cost-frequency population distribution and to estimate the expected time between events. On a global scale, we show that expected wait- or reaction- times can be estimated using the Poisson density function. The functional is generated, representing the locus of means (peaks) from the individual Poisson distributions from different impact costs. Past (ex-post) forecasts relate to a range of natural and anthropogenic disasters; future (ex-ante) forecast presents global CO2emissions. This paper shows that a substantial reaction to global climate change (CO2emissions extremum) will occur in 55 to 120 years (95% CI) with a model prediction of 80 years.