bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective Utilization of STEM Imaging Capability in FIB for Physical Failure Analysis on 20nm & 14nm Transistor Nodes in Semiconductor Wafer Foundries
Authors: Zhao W. , Nedeau D. , Kodali S. , Huang J. , Oh C.-K. , Lim S.-K. , Rai R. , Mai Z.-H. , Lam J.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Atomic Scale Composition Profiling of Ferroelectrics via Laser-Pulsed Atom Probe Tomography and Cross-Correlative Transmission Electron Microscopy
Authors: Kirchhofer R. , Diercks D.R. , Gorman B.P. , Brennecka G.L.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Using Spatial Distribution Maps to Estimate APT Efficiency
Authors: Geiser B.P. , Larson D.J. , Prosa T.J. , Kelly T.F. , Ulfig R.M.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Atom Probe Tomography Characterization of a White Etching Area in a Bearing Steel
Authors: Kang J. , Williams C. , Hosseinkhani B. , Rivera Diaz del Castillo P.E. , Bagot P.A. , Moody M.P.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Low kV Imaging using Charge Balancing
Authors: Png K.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Quantitative X-ray Photoelectron Spectroscopy Imaging for Small Feature Compositional Screening
Authors: Surman D.J. , Page S.C. , Roberts A.J. , Coultas S.J.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
High-Performance DyBa2Cu3O7-x Superconducting Coated Conductors Grown by Inclined Substrate Deposition with Ic Exceeding 1000 A cm-1
Authors: Aabdin Z. , Dürrschnabel M. , Eibl O.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
High Energy Resolution Monochromated EELS-STEM System
Authors: Krivanek O.L. , Lovejoy T.C. , Bacon N.J. , Corbin G.J. , Dellby N. , Hrncirik P. , Murfitt M.F. , Skone G. , Szilagyi Z.S. , Batson P.E. , Carpenter R.W.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
3D ChemiSTEM™ Tomography of Secondary and Tertiary γ' Precipitates in Ni-based Superalloys
Authors: Chowdhury R. , Sosa J.M. , Williams R.E. , Fraser H.L. , McComb D.W.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Chemical State Mapping via Soft X-rays using a Wavelength Dispersive Soft X-ray Emission Spectrometer with High Energy Resolution
Authors: Takahashi H. , Handa N. , Murano T. , Terauchi M. , Koike M. , Imazono T. , Hasegawa N. , Koeda M. , Nagano T. , Sasai H. , Oue Y. , Yonezawa Z. , Kuramoto S.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Recent Advancements in Laboratory X-ray Microscopes enabling 3D and 4D Science
Authors: Merkle A. , Gelb J.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Applications of 40-120kV Analytical TEM for Nanoscience
Authors: Kubo T. , Kobayashi H. , Hashimoto T. , Okada M. , Kondo M. , Nakano K. , Wayama M. , Kamino T.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
An Assessment of the Origin of Contrast in Off-Axis Electron Holographic Imaging of BaTiO3 Ferroelectric Domains
Authors: Tileli V. , Cooper D. , Dunin-Borkowski R.E.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Chemistry Underneath the Painting Surface: Palmierite Formation in/on a Painting by Johannes Vermeer and by Jacob Jordaens using Laboratory- and Synchrotron-aided Spectroscopic Methods
Authors: Boon J.J.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
The Degradation Process of Lead Chromate Yellows in Paintings by Vincent van Gogh
Authors: Monico L. , Janssens K. , Miliani C. , Vanmeert F. , Brunetti B.G. , Cotte M. , Hendriks E. , Geldof M.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Quantitative EDX Analysis of Smalt Pigment in Sixteenth and Eighteenth Century Paintings
Authors: Kugler V. , Bean S. , Spring M.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Structural Analysis of Flame Synthesized C-Doped TiO2 Nanocomposite Polymorphs for Energy Related Applications
Authors: Al-Sharab J. , Halim H. , Abeykoon M. , Billinge S.J. , Kear B. , Tse S.D.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
In-situ Study of Pt/Cu/Pt(111) Near-Surface Alloy Model Catalyst in CO
Authors: Nguyen L.T. , Tao F. , Cheng F. , Liu L.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Correlative Microscopy and Spectroscopy of Buried Interfaces in Tooth Enamel
Authors: Gordon L. , Cohen M.J. , Joester D.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Atomic Structure and Properties of Charged Domain Walls in BiFeO3 Films
Authors: Li L. , Gao P. , Nelson C. , Zhang Y. , Kim S.-J. , Melville A. , Adamo C. , Schlom D. , Pan X.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
Facets on Fatigue Fractures
Authors: Cherolis N.E.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
State-of-the-art Microanalysis at the nm-scale and Smaller: Going from Pretty Pictures to Quantitative Analysis of Hyperspectral Data
Authors: Kotula P.G.
Published: October 2016

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.
CME: Anämie im Alter
Authors: Rosegger Paula , Schleiffenbaum Boris Eugen
Published: October 2016

Zusammenfassung. Die Anämie im Alter stellt ein zunehmendes Problem dar, das keinesfalls als normaler Teil des Alterns gesehen werden darf. Zugrundeliegende Krankheiten können in ca. 70–80 % der Fälle gefunden werden, wobei die häufigsten Ursachen ein Eisenmangel, eine chronischen Erkrankung, eine Niereninsuffizienz oder ein Vitamin-B12-/Folat-Mangel sind. Bis zu einem Drittel der Fälle bleiben äthiologisch unklar. Unter diesen finden sich die Patienten mit einer klonalen hämatologischen Erkrankung, die letztlich in einem myelodysplastischen Syndrom (MDS) enden kann. Schon milde Formen der Anämie können, vor allem im Alter, Begleiterkrankungen und die Lebensqualität verschlechtern. Ihre Behandlung reduziert die Morbidität und Mortalität im Alter.
Scientists, Activists Call for Climate Topic in Wednesday’s Debate
Authors: Showstack Randy
Published: October 2016

As environmentalists petition for climate questions in the final presidential debate, some scientists are urging—and others taking polls about—climate as a topic for politicians to address.
Orphan GPR110 (ADGRF1) targeted by N-docosahexaenoylethanolamine in development of neurons and cognitive function
Authors: Lee Ji-Won , Huang Bill X. , Kwon HeungSun , Rashid Md Abdur , Kharebava Giorgi , Desai Abhishek , Patnaik Samarjit , Marugan Juan , Kim Hee-Yong
Published: October 2016

Docosahexaenoic acid (DHA, 22:6n-3) is an omega-3 fatty acid essential for proper brain development. N-docosahexaenoylethanolamine (synaptamide), an endogenous metabolite of DHA, potently promotes neurogenesis, neuritogenesis and synaptogenesis; however, the underlying molecular mechanism is not known. Here, we demonstrate orphan G-protein coupled receptor 110 (GPR110, ADGRF1) as the synaptamide receptor, mediating synaptamide-induced bioactivity in a cAMP-dependent manner. Mass spectrometry-based proteomic characterization and cellular fluorescence tracing with chemical analogues of synaptamide reveal specific binding of GPR110 to synaptamide, which triggers cAMP production with low nM potency. Disruption of this binding or GPR110 gene knockout abolishes while GPR110 overexpression enhances synaptamide-induced bioactivity. GPR110 is highly expressed in fetal brains but rapidly decreases after birth. GPR110 knockout mice show significant deficits in object recognition and spatial memory. GPR110 deorphanized as a functional synaptamide receptor provides a novel target for neurodevelopmental control and new insight into mechanisms by which DHA promotes brain development and function.
Precise localization of metal nanoparticles in dendrimer nanosnakes or inner periphery and consequences in catalysis
Authors: Liu Xiang , Gregurec Danijela , Irigoyen Joseba , Martinez Angel , Moya Sergio , Ciganda Roberto , Hermange Philippe , Ruiz Jaime , Astruc Didier
Published: October 2016

Understanding the relationship between the location of nanoparticles (NPs) in an organic matrix and their catalytic performances is essential for catalyst design. Here we show that catalytic activities of Au, Ag and CuNPs stabilized by dendrimers using coordination to intradendritic triazoles, galvanic replacement or stabilization outside dendrimers strongly depends on their location. AgNPs are found at the inner click dendrimer periphery, whereas CuNPs and AuNPs are encapsulated in click dendrimer nanosnakes. AuNPs and AgNPs formed by galvanic replacement are larger than precursors and only partly encapsulated. AuNPs are all the better 4-nitrophenol reduction catalysts as they are less sterically inhibited by the dendrimer interior, whereas on the contrary CuNPs are all the better alkyne azide cycloaddition catalysts as they are better protected from aerobic oxidation inside dendrimers. This work highlights the role of the location in macromolecules on the catalytic efficiency of metal nanoparticles and rationalizes optimization in catalyst engineering.
SIKs control osteocyte responses to parathyroid hormone
Authors: Wein Marc N. , Liang Yanke , Goransson Olga , Sundberg Thomas B. , Wang Jinhua , Williams Elizabeth A. , O’Meara Maureen J. , Govea Nicolas , Beqo Belinda , Nishimori Shigeki , Nagano Kenichi , Brooks Daniel J. , Martins Janaina S. , Corbin Braden , Anselmo Anthony , Sadreyev Ruslan , Wu Joy Y. , Sakamoto Kei , Foretz Marc , Xavier Ramnik J. , Baron Roland , Bouxsein Mary L. , Gardella Thomas J. , Divieti-Pajevic Paola , Gray Nathanael S. , Kronenberg Henry M.
Published: October 2016

Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2. SIK inhibition mimics many of the effects of PTH in osteocytes as assessed by RNA-seq in cultured osteocytes and following in vivo administration. Once daily treatment with the small molecule SIK inhibitor YKL-05-099 increases bone formation and bone mass. Therefore, a major arm of PTH signalling in osteocytes involves SIK inhibition, and small molecule SIK inhibitors may be applied therapeutically to mimic skeletal effects of PTH.
Ocean feedback to pulses of the Madden–Julian Oscillation in the equatorial Indian Ocean
Authors: Moum James N. , Pujiana Kandaga , Lien Ren-Chieh , Smyth William D.
Published: October 2016

Dynamical understanding of the Madden–Julian Oscillation (MJO) has been elusive, and predictive capabilities therefore limited. New measurements of the ocean’s response to the intense surface winds and cooling by two successive MJO pulses, separated by several weeks, show persistent ocean currents and subsurface mixing after pulse passage, thereby reducing ocean heat energy available for later pulses by an amount significantly greater than via atmospheric surface cooling alone. This suggests that thermal mixing in the upper ocean from a particular pulse might affect the amplitude of the following pulse. Here we test this hypothesis by comparing 18 pulse pairs, each separated by <55 days, measured over a 33-year period. We find a significant tendency for weak (strong) pulses, associated with low (high) cooling rates, to be followed by stronger (weaker) pulses. We therefore propose that the ocean introduces a memory effect into the MJO, whereby each event is governed in part by the previous event.
Robust ultra-low-friction state of graphene via moiré superlattice confinement
Authors: Zheng Xiaohu , Gao Lei , Yao Quanzhou , Li Qunyang , Zhang Miao , Xie Xiaoming , Qiao Shan , Wang Gang , Ma Tianbao , Di Zengfeng , Luo Jianbin , Wang Xi
Published: October 2016

Two-dimensional (2D) materials possess outstanding lubrication property with their thicknesses down to a few atomic layers, but they are easily susceptible to sliding induced degradation or ubiquitous chemical modification. Maintaining the superior lubricating performance of 2D materials in a harsh working environment is highly desirable yet grandly challenging. Here we show that by proper alignment of graphene on a Ge(111) substrate, friction of graphene could be well preserved at an ultra-low level even after fluorination or oxidation. This behaviour is experimentally found to be closely related to the suppression of molecular-level deformation of graphene within the moiré superlattice structure. Atomistic simulations reveal that the formation of an interconnected meshwork with enhanced interfacial charge density imposes a strong anchoring effect on graphene even under chemical modification. Modulating molecular-level deformation by interfacial confinements may offer a unique strategy for tuning the mechanical or even chemical properties of 2D materials.
Stacking sequence and interlayer coupling in few-layer graphene revealed by in situ imaging
Authors: Wang Zhu-Jun , Dong Jichen , Cui Yi , Eres Gyula , Timpe Olaf , Fu Qiang , Ding Feng , Schloegl R. , Willinger Marc-Georg
Published: October 2016

In the transition from graphene to graphite, the addition of each individual graphene layer modifies the electronic structure and produces a different material with unique properties. Controlled growth of few-layer graphene is therefore of fundamental interest and will provide access to materials with engineered electronic structure. Here we combine isothermal growth and etching experiments with in situ scanning electron microscopy to reveal the stacking sequence and interlayer coupling strength in few-layer graphene. The observed layer-dependent etching rates reveal the relative strength of the graphene–graphene and graphene–substrate interaction and the resulting mode of adlayer growth. Scanning tunnelling microscopy and density functional theory calculations confirm a strong coupling between graphene edge atoms and platinum. Simulated etching confirms that etching can be viewed as reversed growth. This work demonstrates that real-time imaging under controlled atmosphere is a powerful method for designing synthesis protocols for sp2 carbon nanostructures in between graphene and graphite.
Nanopore sequencing in microgravity
Authors: McIntyre Alexa B R , Rizzardi Lindsay , Yu Angela M , Alexander Noah , Rosen Gail L , Botkin Douglas J , Stahl Sarah E , John Kristen K , Castro-Wallace Sarah L , McGrath Ken , Burton Aaron S , Feinberg Andrew P , Mason Christopher E
Published: October 2016

Rapid DNA sequencing and analysis has been a long-sought goal in remote research and point-of-care medicine. In microgravity, DNA sequencing can facilitate novel astrobiological research and close monitoring of crew health, but spaceflight places stringent restrictions on the mass and volume of instruments, crew operation time, and instrument functionality. The recent emergence of portable, nanopore-based tools with streamlined sample preparation protocols finally enables DNA sequencing on missions in microgravity. As a first step toward sequencing in space and aboard the International Space Station (ISS), we tested the Oxford Nanopore Technologies MinION during a parabolic flight to understand the effects of variable gravity on the instrument and data. In a successful proof-of-principle experiment, we found that the instrument generated DNA reads over the course of the flight, including the first ever sequenced in microgravity, and additional reads measured after the flight concluded its parabolas. Here we detail modifications to the sample-loading procedures to facilitate nanopore sequencing aboard the ISS and in other microgravity environments. We also evaluate existing analysis methods and outline two new approaches, the first based on a wave-fingerprint method and the second on entropy signal mapping. Computationally light analysis methods offer the potential for in situ species identification, but are limited by the error profiles (stays, skips, and mismatches) of older nanopore data. Higher accuracies attainable with modified sample processing methods and the latest version of flow cells will further enable the use of nanopore sequencers for diagnostics and research in space.
Correction: Corrigendum: Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ
Authors: Zarei Kasra , Scheetz Todd E. , Christopher Mark , Miller Kathy , Hedberg-Buenz Adam , Tandon Anamika , Anderson Michael G. , Fingert John H. , Abràmoff Michael David
Published: October 2016

Scientific Reports 6: Article number: 26559; published online: 26 May 2016; updated: 19 October 2016 In the Supplementary Information file originally published with this Article, Supplemental Figure 1 was omitted. In addition, “Supplemental Software” was incorrectly given as “Software Legend” These errors have now been corrected in the Supplementary Information that now accompanies the Article.
Correction: Corrigendum: Real-Time Control of a Neuroprosthetic Hand by Magnetoencephalographic Signals from Paralysed Patients
Authors: Fukuma Ryohei , Yanagisawa Takufumi , Saitoh Youichi , Hosomi Koichi , Kishima Haruhiko , Shimizu Takeshi , Sugata Hisato , Yokoi Hiroshi , Hirata Masayuki , Kamitani Yukiyasu , Yoshimine Toshiki
Published: October 2016

Scientific Reports 6: Article number: 21781; published online: 24 February 2016; updated: 19 October 2016
Chronic stress prior to pregnancy potentiated long-lasting postpartum depressive-like behavior, regulated by Akt-mTOR signaling in the hippocampus
Authors: Xia Baomei , Chen Chang , Zhang Hailou , Xue Wenda , Tang Juanjuan , Tao Weiwei , Wu Ruyan , Ren Li , Wang Wei , Chen Gang
Published: October 2016

Postpartum depression (PPD) affects over 10% of new mothers and adversely impacts the health of offspring. One of the greatest risk factors for PPD is prepregnancy stress but the underlying biological mechanism is unknown. Here we constructed an animal model which recapitulated prepregnancy stress induced PPD and tested the role of Akt-mTOR signaling in the hippocampus. Female virgin Balb/c mice received chronic restraint stress, followed by co-housing with a normal male mouse. We found that the chronic stress led to a transient depressive-like condition that disappeared within two weeks. However, prepregnantly stressed females developed long-term postpartum depressive-like (PPD-like) symptoms as indicated by deficient performance in tests of sucrose preference, forced swim, and novelty-suppressed feeding. Chronic stress induced transient decrease in Akt-mTOR signaling and altered expressions of glutamate receptor subunits NR1 and GluR1, in contrast to long-term deficits in Akt-mTOR signaling, GluR1/NR1 ratio, and hippocampal neurogenesis in PPD-like mice. Acute ketamine improved the molecular signaling abnormality, and reversed the behavioral deficits in PPD-like mice in a rapid and persistent manner, in contrast to ineffectiveness by chronic fluoxetine treatment. Taken together, we find that chronic prepregnancy stress potentiates a long-term PPD, in which Akt-mTOR signaling may play a crucial role.
Correction: Corrigendum: Exactly solvable spin chain models corresponding to BDI class of topological superconductors
Authors: Jafari S. A. , Shahbazi Farhad
Published: October 2016

Scientific Reports 6: Article number: 32720; published online: 06 September 2016; updated: 19 October 2016
MPP2 is a postsynaptic MAGUK scaffold protein that links SynCAM1 cell adhesion molecules to core components of the postsynaptic density
Authors: Rademacher Nils , Schmerl Bettina , Lardong Jennifer A. , Wahl Markus C. , Shoichet Sarah A.
Published: October 2016

At neuronal synapses, multiprotein complexes of trans-synaptic adhesion molecules, scaffold proteins and neurotransmitter receptors assemble to essential building blocks required for synapse formation and maintenance. Here we describe a novel role for the membrane-associated guanylate kinase (MAGUK) protein MPP2 (MAGUK p55 subfamily member 2) at synapses of rat central neurons. Through interactions mediated by its C-terminal SH3-GK domain module, MPP2 binds to the abundant postsynaptic scaffold proteins PSD-95 and GKAP and localises to postsynaptic sites in hippocampal neurons. MPP2 also colocalises with the synaptic adhesion molecule SynCAM1. We demonstrate that the SynCAM1 C-terminus interacts directly with the MPP2 PDZ domain and that MPP2 does not interact in this manner with other highly abundant postsynaptic transmembrane proteins. Our results highlight a previously unexplored role for MPP2 at postsynaptic sites as a scaffold that links SynCAM1 cell adhesion molecules to core proteins of the postsynaptic density.
Correction: Corrigendum: An extended patch-dynamic framework for food chains in fragmented landscapes
Authors: Liao Jinbao , Chen Jiehong , Ying Zhixia , Hiebeler David E. , Nijs Ivan
Published: October 2016

Scientific Reports 6: Article number: 33100; published online: 09 September 2016; updated: 19 October 2016
Octopamine controls starvation resistance, life span and metabolic traits in Drosophila
Authors: Li Yong , Hoffmann Julia , Li Yang , Stephano Flora , Bruchhaus Iris , Fink Christine , Roeder Thomas
Published: October 2016

The monoamines octopamine (OA) and tyramine (TA) modulate numerous behaviours and physiological processes in invertebrates. Nevertheless, it is not clear whether these invertebrate counterparts of norepinephrine are important regulators of metabolic and life history traits. We show that flies (Drosophila melanogaster) lacking OA are more resistant to starvation, while their overall life span is substantially reduced compared with control flies. In addition, these animals have increased body fat deposits, reduced physical activity and a reduced metabolic resting rate. Increasing the release of OA from internal stores induced the opposite effects. Flies devoid of both OA and TA had normal body fat and metabolic rates, suggesting that OA and TA act antagonistically. Moreover, OA-deficient flies show increased insulin release rates. We inferred that the OA-mediated control of insulin release accounts for a substantial proportion of the alterations observed in these flies. Apparently, OA levels control the balance between thrifty and expenditure metabolic modes. Thus, changes in OA levels in response to external and internal signals orchestrate behaviour and metabolic processes to meet physiological needs. Moreover, chronic deregulation of the corresponding signalling systems in humans may be associated with metabolic disorders, such as obesity or diabetes.
CDK4 regulates cancer stemness and is a novel therapeutic target for triple-negative breast cancer
Authors: Dai Meiou , Zhang Chenjing , Ali Ayad , Hong Xinyuan , Tian Jun , Lo Chieh , Fils-Aimé Nadège , Burgos Sergio A. , Ali Suhad , Lebrun Jean-Jacques
Published: October 2016

Triple negative breast cancers exhibit very aggressive features and poor patient outcomes. These tumors are enriched in cancer stem cells and exhibit resistance to most treatments and chemotherapy. In this study, we found the cyclin-dependent kinase (CDK4) to act as a cancer stem cell regulator and novel prognostic marker in triple negative breast cancers. We found CDK4 to be highly expressed in these tumors and its expression to correlate with poor overall and relapse free survival outcomes, high tumor grade and poor prognostic features of triple negative breast cancer patients. Moreover, we found that blocking CDK4 expression or kinase activity, using a pharmacological inhibitor prevented breast cancer stem cell self-renewal. Interestingly, suppression of CDK4 expression or kinase activity reversed the basal-B TNBC mesenchymal phenotype to an epithelial- and luminal-like phenotype which correlates with better clinical prognosis. Finally, blocking CDK4 activity efficiently eliminated both normal and chemotherapy-resistant cancer cells in triple negative breast cancers, highlighting CDK4 as a promising novel therapeutic target for these aggressive breast tumors.
Realizing the measure-device-independent quantum-key-distribution with passive heralded-single photon sources
Authors: Wang Qin , Zhou Xing-Yu , Guo Guang-Can
Published: October 2016

In this paper, we put forward a new approach towards realizing measurement-device-independent quantum key distribution with passive heralded single-photon sources. In this approach, both Alice and Bob prepare the parametric down-conversion source, where the heralding photons are labeled according to different types of clicks from the local detectors, and the heralded ones can correspondingly be marked with different tags at the receiver’s side. Then one can obtain four sets of data through using only one-intensity of pump light by observing different kinds of clicks of local detectors. By employing the newest formulae to do parameter estimation, we could achieve very precise prediction for the two-single-photon pulse contribution. Furthermore, by carrying out corresponding numerical simulations, we compare the new method with other practical schemes of measurement-device-independent quantum key distribution. We demonstrate that our new proposed passive scheme can exhibit remarkable improvement over the conventional three-intensity decoy-state measurement-device-independent quantum key distribution with either heralded single-photon sources or weak coherent sources. Besides, it does not need intensity modulation and can thus diminish source-error defects existing in several other active decoy-state methods. Therefore, if taking intensity modulating errors into account, our new method will show even more brilliant performance.
Single and Transient Ca2+ Peaks in Podocytes do not induce Changes in Glomerular Filtration and Perfusion
Authors: Koehler Sybille , Brähler Sebastian , Kuczkowski Alexander , Binz Julia , Hackl Matthias J. , Hagmann Henning , Höhne Martin , Vogt Merly C. , Wunderlich Claudia M. , Wunderlich F. Thomas , Schweda Frank , Schermer Bernhard , Benzing Thomas , Brinkkoetter Paul T.
Published: October 2016

Chronic alterations in calcium (Ca2+) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca2+ peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusively Activated by a Designer Drug) knock-in mouse line to manipulate intracellular Ca2+ levels. By mating to a podocyte-specific Cre driver we are able to investigate the impact of Ca2+ peaks on podocyte biology in living animals. Activation of the engineered G-protein coupled receptor with the synthetic compound clozapine-N-oxide (CNO) evoked a short and transient Ca2+ peak in podocytes immediately after CNO administration in vivo. Interestingly, this Ca2+ peak did neither affect glomerular perfusion nor filtration in the animals. Moreover, no obvious alterations in the glomerular morphology could be observed. Taken together, these in vivo findings suggest that chronic alterations and calcium overload rather than an induction of transient Ca2+ peaks contribute to podocyte disease.
Hepatic 3D spheroid models for the detection and study of compounds with cholestatic liability
Authors: Hendriks Delilah F. G. , Fredriksson Puigvert Lisa , Messner Simon , Mortiz Wolfgang , Ingelman-Sundberg Magnus
Published: October 2016

Drug-induced cholestasis (DIC) is poorly understood and its preclinical prediction is mainly limited to assessing the compound’s potential to inhibit the bile salt export pump (BSEP). Here, we evaluated two 3D spheroid models, one from primary human hepatocytes (PHH) and one from HepaRG cells, for the detection of compounds with cholestatic liability. By repeatedly co-exposing both models to a set of compounds with different mechanisms of hepatotoxicity and a non-toxic concentrated bile acid (BA) mixture for 8 days we observed a selective synergistic toxicity of compounds known to cause cholestatic or mixed cholestatic/hepatocellular toxicity and the BA mixture compared to exposure to the compounds alone, a phenomenon that was more pronounced after extending the exposure time to 14 days. In contrast, no such synergism was observed after both 8 and 14 days of exposure to the BA mixture for compounds that cause non-cholestatic hepatotoxicity. Mechanisms behind the toxicity of the cholestatic compound chlorpromazine were accurately detected in both spheroid models, including intracellular BA accumulation, inhibition of ABCB11 expression and disruption of the F-actin cytoskeleton. Furthermore, the observed synergistic toxicity of chlorpromazine and BA was associated with increased oxidative stress and modulation of death receptor signalling. Combined, our results demonstrate that the hepatic spheroid models presented here can be used to detect and study compounds with cholestatic liability.
Effects of patch contrast and arrangement on benefits of clonal integration in a rhizomatous clonal plant
Authors: Wang Yong-Jian , Shi Xue-Ping , Wu Xiao-Jing , Meng Xue-Feng , Wang Peng-Cheng , Zhou Zhi-Xiang , Luo Fang-Li , Yu Fei-Hai
Published: October 2016

The availabilities of light and soil water resources usually spatially co-vary in natural habitats, and the spatial pattern of such co-variation may affect the benefits of physiological integration between connected ramets of clonal plants. In a greenhouse experiment, we grew connected or disconnected ramet pairs [consisting of a proximal (relatively old) and a distal (relative young) ramet] of a rhizomatous herb Iris japonica in four heterogeneous environments differing in patch arrangement (reciprocal vs. parallel patchiness of light and soil water) and patch contrast (high vs. low contrast of light and water). Biomass of the proximal part, distal part and clonal fragment of I. japonica were all significantly greater in the intact than in the severed treatment, in the parallel than in the reciprocal patchiness treatment and in the high than in the low contrast treatment, but the effect of severing the connection between ramet pairs did not depend on patch arrangement or contrast. Severing the connection decreased number of ramets of the distal part and the clonal fragment in the parallel patchiness arrangement, but not in the reciprocal patchiness arrangement. Therefore, the spatial arrangement of resource patches can alter the effects of clonal integration on asexual reproduction in I. japonica.
mdRNA-Seq analysis of marine microbial communities from the northern Red Sea
Authors: Hou Shengwei , Pfreundt Ulrike , Miller Dan , Berman-Frank Ilana , Hess Wolfgang R.
Published: October 2016

Metatranscriptomic differential RNA-Seq (mdRNA-Seq) identifies the suite of active transcriptional start sites at single-nucleotide resolution through enrichment of primary transcript 5′ ends. Here we analyzed the microbial community at 45 m depth at Station A in the northern Gulf of Aqaba, Red Sea, during 500 m deep mixing in February 2012 using mdRNA-Seq and a parallel classical RNA-Seq approach. We identified promoters active in situ for five different pico-planktonic genera (the SAR11 clade of Alphaproteobacteria, Synechococcus of Cyanobacteria, Euryarchaeota, Thaumarchaeota, and Micromonas as an example for picoeukaryotic algae), showing the applicability of this approach to highly diverse microbial communities. 16S rDNA quantification revealed that 24% of the analyzed community were group II marine Euryarchaeota in which we identified a highly abundant non-coding RNA, Tan1, and detected very high expression of genes encoding intrinsically disordered proteins, as well as enzymes for the synthesis of specific B vitamins, extracellular peptidases, carbohydrate-active enzymes, and transport systems. These results highlight previously unknown functions of Euryarchaeota with community-wide relevance. The complementation of metatranscriptomic studies with mdRNA-Seq provides substantial additional information regarding transcriptional start sites, promoter activities, and the identification of non-coding RNAs.
TGF-β induces p53/Smads complex formation in the PAI-1 promoter to activate transcription
Authors: Kawarada Yuki , Inoue Yasumichi , Kawasaki Fumihiro , Fukuura Keishi , Sato Koichi , Tanaka Takahito , Itoh Yuka , Hayashi Hidetoshi
Published: October 2016

Transforming growth factor β (TGF-β) signaling facilitates tumor development during the advanced stages of tumorigenesis, but induces cell-cycle arrest for tumor suppression during the early stages. However, the mechanism of functional switching of TGF-β is still unknown, and it is unclear whether inhibition of TGF-β signaling results amelioration or exacerbation of cancers. Here we show that the tumor suppressor p53 cooperates with Smad proteins, which are TGF-β signal transducers, to selectively activate plasminogen activator inhibitor type-1 (PAI-1) transcription. p53 forms a complex with Smad2/3 in the PAI-1 promoter to recruit histone acetyltransferase CREB-binding protein (CBP) and enhance histone H3 acetylation, resulting in transcriptional activation of the PAI-1 gene. Importantly, p53 is required for TGF-β-induced cytostasis and PAI-1 is involved in the cytostatic activity of TGF-β in several cell lines. Our results suggest that p53 enhances TGF-β-induced cytostatic effects by activating PAI-1 transcription, and the functional switching of TGF-β is partially caused by p53 mutation or p53 inactivation during cancer progression. It is expected that these findings will contribute to optimization of TGF-β-targeting therapies for cancer.
LncRNA SRA promotes hepatic steatosis through repressing the expression of adipose triglyceride lipase (ATGL)
Authors: Chen Gang , Yu Dongsheng , Nian Xue , Liu Junyi , Koenig Ronald J. , Xu Bin , Sheng Liang
Published: October 2016

Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, manifests as an over-accumulation of hepatic fat. We have recently shown that mice with genetic knockout of a long non-coding RNA (lncRNA) steroid receptor RNA activator (SRA) (SRAKO) are resistant to high fat diet-induced obesity with a phenotype that includes improved glucose tolerance and attenuated hepatic steatosis. The underlying mechanism was investigated in the present study. We found that hepatic levels of SRA and adipose triglyceride lipase (ATGL), a major hepatic triacylglycerol (TAG) hydrolase, were inversely regulated by fasting in mice, and the expression of liver ATGL was induced by SRAKO under normal and high fat diet (HFD) feeding. Loss of SRA in primary hepatocytes or a hepatocyte cell line upregulates, but forced expression of SRA inhibits ATGL expression and free fatty acids (FFA) β-oxidation. SRA inhibits ATGL promoter activity, primarily by inhibiting the otherwise-inductive effects of the transcription factor, forkhead box protein O1 (FoxO1). Our data reveal a novel function of SRA in promoting hepatic steatosis through repression of ATGL expression.
Gas Protection of Two-Dimensional Nanomaterials from High-Energy Impacts
Authors: Xing Tan , Mateti Srikanth , Li Lu Hua , Ma Fengxian , Du Aijun , Gogotsi Yury , Chen Ying
Published: October 2016

Two-dimensional (2D) materials can be produced using ball milling with the help of liquid surfactants or solid exfoliation agents, as ball milling of bulk precursor materials usually produces nanosized particles because of high-energy impacts. Post-milling treatment is thus needed to purify the nanosheets. We show here that nanosheets of graphene, BN, and MoS2 can be produced by ball milling of their bulk crystals in the presence of ammonia or a hydrocarbon ethylene gas and the obtained nanosheets remain flat and maintain their single-crystalline structure with low defects density even after a long period of time; post-milling treatment is not needed. This study does not just demonstrate production of nanosheets using ball milling, but reveals surprising indestructible behaviour of 2D nanomaterials in ammonia or hydrocarbon gas under the high-energy impacts; in other milling atmospheres such as air, nitrogen or argon the same milling treatment produces nanosized particles. A systematic study reveals chemisorption of ammonia and hydrocarbon gases and chemical reactions occurring at defect sites, which heal the defects by saturating the dangling bonds. Density functional theory was used to understand the mechanism of mechanochemical reactions. Ball milling in ammonia or hydrocarbon is promising for mass-production of pure nanosheets.
Independent Long Fingers are not Essential for a Grasping Hand
Authors: Montagnani Federico , Controzzi Marco , Cipriani Christian
Published: October 2016

The human hand is a complex integrated system with motor and sensory components that provides individuals with high functionality and elegant behaviour. In direct connection with the brain, the hand is capable of performing countless actions ranging from fine digit manipulation to the handling of heavy objects. However the question of which movements mostly contribute to the manipulation skills of the hand, and thus should be included in prosthetic hands, is yet to be answered. Building from our previous work, and assuming that a hand with independent long fingers allowed performance comparable to a hand with coupled fingers, here we explored the actual contribution of independent fingers while performing activities of daily living using custom built orthoses. Our findings show that, when an opposable thumb is present, independent long fingers provide a measureable advantage in performing activities of daily living only when precision grasps are involved. In addition, the results suggest that the remarkable grasping skills of the human hand rely more on the independent abduction/adduction of the fingers than on their independent flexion/extension. These findings are of interest to the designers of artificial hands, including biomimetic prostheses and exoskeletons.
Choline and betaine consumption lowers cancer risk: a meta-analysis of epidemiologic studies
Authors: Sun Shanwen , Li Xiao , Ren Anjing , Du Mulong , Du Haina , Shu Yongqian , Zhu Lingjun , Wang Wei
Published: October 2016

A number of human and animal in vitro or in vivo studies have investigated the relationship between dietary choline and betaine and cancer risk, suggesting that choline and betaine consumption may be protective for cancer. There are also a few epidemiologic studies exploring this relationship, however, with inconsistent conclusions. The PubMed and Embase were searched, from their inception to March 2016, to identify relevant studies and we brought 11 articles into this meta-analysis eventually. The pooled relative risks (RRs) of cancer for the highest versus the lowest range were 0.82 (95% CI, 0.70 to 0.97) for choline consumption only, 0.86 (95%CI, 0.76 to 0.97) for betaine consumption only and 0.60 (95%CI, 0.40 to 0.90) for choline plus betaine consumption, respectively. Significant protective effect of dietary choline and betaine for cancer was observed when stratified by study design, location, cancer type, publication year, sex and quality score of study. An increment of 100 mg/day of choline plus betaine intake helped reduce cancer incidence by 11% (0.89, 95% CI, 0.87 to 0.92) through a dose-response analysis. To conclude, choline and betaine consumption lowers cancer incidence in this meta-analysis, but further studies are warranted to verify the results.
Cytoplasmic proliferating cell nuclear antigen connects glycolysis and cell survival in acute myeloid leukemia
Authors: Ohayon Delphine , De Chiara Alessia , Chapuis Nicolas , Candalh Céline , Mocek Julie , Ribeil Jean-Antoine , Haddaoui Lamya , Ifrah Norbert , Hermine Olivier , Bouillaud Frédéric , Frachet Philippe , Bouscary Didier , Witko-Sarsat Véronique
Published: October 2016

Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNA replication, has been described as a key element in survival of mature neutrophil granulocytes, which are non-proliferating cells. Herein, we demonstrated an active export of PCNA involved in cell survival and chemotherapy resistance. Notably, daunorubicin-resistant HL-60 cells (HL-60R) have a prominent cytosolic PCNA localization due to increased nuclear export compared to daunorubicin-sensitive HL-60 cells (HL-60S). By interacting with nicotinamide phosphoribosyltransferase (NAMPT), a protein involved in NAD biosynthesis, PCNA coordinates glycolysis and survival, especially in HL-60R cells. These cells showed a dramatic increase in intracellular NAD+ concentration as well as glycolysis including increased expression and activity of hexokinase 1 and increased lactate production. Furthermore, this functional activity of cytoplasmic PCNA was also demonstrated in patients with acute myeloid leukemia (AML). Our data uncover a novel pathway of nuclear export of PCNA that drives cell survival by increasing metabolism flux.
Regional-specific effect of fluoxetine on rapidly dividing progenitors along the dorsoventral axis of the hippocampus
Authors: Zhou Qi-Gang , Lee Daehoon , Ro Eun Jeoung , Suh Hoonkyo
Published: October 2016

Hippocampus-dependent cognitive and emotional function appears to be regionally dissociated along the dorsoventral (DV) axis of the hippocampus. Recent observations that adult hippocampal neurogenesis plays a critical role in both cognition and emotion raised an interesting question whether adult neurogenesis within specific subregions of the hippocampus contributes to these distinct functions. We examined the regional-specific and cell type-specific effects of fluoxetine, which requires adult hippocampal neurogenesis to function as an antidepressant, on the proliferation of hippocampal neural stem cells (NSCs). Fluoxetine specifically increased proliferation of NSCs located in the ventral region of the hippocampus while the mitotic index of NSCs in the dorsal portion of the hippocampus remained unaltered. Moreover, within the ventral hippocampus, type II NSC and neuroblast populations specifically responded to fluoxetine, showing increased proliferation; however, proliferation of type I NSCs was unchanged in response to fluoxetine. Activation or inhibition of serotonin receptor 1A (5-HTR1A) recapitulated or abolished the effect of fluoxetine on proliferation of type II NSCs and neuroblast populations in the ventral hippocampus. Our study showed that the effect of fluoxetine on proliferation is dependent upon the type and the position of the NSCs along the DV axis of the hippocampus.
Factor XIII-A transglutaminase deficient mice show signs of metabolically healthy obesity on high fat diet
Authors: Myneni Vamsee D. , Mousa Aisha , Kaartinen Mari T.
Published: October 2016

F13A1 gene, which encodes for Factor XIII-A blood clotting factor and a transglutaminase enzyme, was recently identified as a potential causative gene for obesity in humans. In our previous in vitro work, we showed that FXIII-A regulates preadipocyte differentiation and modulates insulin signaling via promoting plasma fibronectin assembly into the extracellular matrix. To understand the role of FXIII-A in whole body energy metabolism, here we have characterized the metabolic phenotype of F13a1−/− mice. F13a1−/− and F13a1+/+ type mice were fed chow or obesogenic, high fat diet for 20 weeks. Weight gain, total fat mass and fat pad mass, glucose handling, insulin sensitivity, energy expenditure and, morphological and biochemical analysis of adipose tissue was performed. We show that mice lacking FXIII-A gain weight on obesogenic diet, similarly as wild type mice, but exhibit a number of features of metabolically healthy obesity such as protection from developing diet-induced insulin resistance and hyperinsulinemia. Mice also show normal fasting glucose levels, larger adipocytes, decreased extracellular matrix accumulation and inflammation of adipose tissue, as well as decreased circulating triglycerides. This study reveals that FXIII-A transglutaminase can regulate whole body insulin sensitivity and may have a role in the development of diet-induced metabolic disturbances.
Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA) binds human erythrocytes independent of Duffy antigen status
Authors: Cheng Yang , Lu Feng , Wang Bo , Li Jian , Han Jin-Hee , Ito Daisuke , Kong Deok-Hoon , Jiang Lubin , Wu Jian , Ha Kwon-Soo , Takashima Eizo , Sattabongkot Jetsumon , Cao Jun , Nyunt Myat Htut , Kyaw Myat Phone , Desai Sanjay A. , Miller Louis H. , Tsuboi Takafumi , Han Eun-Taek
Published: October 2016

Plasmodium vivax, a major agent of malaria in both temperate and tropical climates, has been thought to be unable to infect humans lacking the Duffy (Fy) blood group antigen because this receptor is critical for erythrocyte invasion. Recent surveys in various endemic regions, however, have reported P. vivax infections in Duffy-negative individuals, suggesting that the parasite may utilize alternative receptor-ligand pairs to complete the erythrocyte invasion. Here, we identified and characterized a novel parasite ligand, Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA), that bound human erythrocytes regardless of Duffy antigen status. PvGAMA was localized at the microneme in the mature schizont-stage parasites. The antibodies against PvGAMA fragments inhibited PvGAMA binding to erythrocytes in a dose-dependent manner. The erythrocyte-specific binding activities of PvGAMA were significantly reduced by chymotrypsin treatment. Thus, PvGAMA may be an adhesion molecule for the invasion of Duffy-positive and -negative human erythrocytes.