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1.  Resolving the spin splitting in the conduction band of monolayer MoS2 
Nature Communications  2017;8:1938.
Time-reversal symmetry and broken spin degeneracy enable the exploration of spin and valley quantum degrees of freedom in monolayer transition-metal dichalcogenides. While the strength of the large spin splitting in the valance band of these materials is now well-known, probing the 10–100 times smaller splitting in the conduction band poses significant challenges. Since it is easier to achieve n-type conduction in most of them, resolving the energy levels in the conduction band is crucial for the prospect of developing new spintronic and valleytronic devices. Here, we study quantum transport in high mobility monolayer MoS2 devices where we observe well-developed quantized conductance in multiples of e 2/h in zero magnetic field. We extract a sub-band spacing energy of 0.8 meV. The application of a magnetic field gradually increases the interband spacing due to the valley-Zeeman effect. Here, we extract a g-factor of ~2.16 in the conduction band of monolayer MoS2.
In monolayer transition-metal dichalcogenides, lack of inversion symmetry results in spin-split valence and conduction bands, but the small conduction band splitting is hard to probe experimentally. Here, the authors extract a sub-band spacing energy of 0.8 meV in the conduction band of monolayer MoS2 via quantum transport measurements.
doi:10.1038/s41467-017-02047-5
PMCID: PMC5717150  PMID: 29209021
2.  Optospintronics in Graphene via Proximity Coupling 
ACS Nano  2017;11(11):11678-11686.
The observation of micrometer size spin relaxation makes graphene a promising material for applications in spintronics requiring long-distance spin communication. However, spin dependent scatterings at the contact/graphene interfaces affect the spin injection efficiencies and hence prevent the material from achieving its full potential. While this major issue could be eliminated by nondestructive direct optical spin injection schemes, graphene’s intrinsically low spin–orbit coupling strength and optical absorption place an obstacle in their realization. We overcome this challenge by creating sharp artificial interfaces between graphene and WSe2 monolayers. Application of circularly polarized light activates the spin-polarized charge carriers in the WSe2 layer due to its spin-coupled valley-selective absorption. These carriers diffuse into the superjacent graphene layer, transport over a 3.5 μm distance, and are finally detected electrically using Co/h-BN contacts in a nonlocal geometry. Polarization-dependent measurements confirm the spin origin of the nonlocal signal. We also demonstrate that such signal is absent if graphene is contacted to bilayer WSe2 where the inversion symmetry is restored.
doi:10.1021/acsnano.7b06800
PMCID: PMC5707628  PMID: 29068661
two-dimensional materials; spintronics; valleytronics; spin injection; graphene
3.  An On/Off Berry Phase Switch in Circular Graphene Resonators 
Science (New York, N.Y.)  2017;356(6340):845-849.
The phase of a quantum state may not return to its original value after the system's parameters cycle around a closed path; instead, the wavefunction may acquire a measurable phase difference called the Berry phase. Berry phases typically have been accessed through interference experiments. Here, we demonstrate an unusual Berry-phase-induced spectroscopic feature: a sudden and large increase in the energy of angular-momentum states in circular graphene p-n junction resonators when a small critical magnetic field is reached. This behavior results from turning on a π-Berry phase associated with the topological properties of Dirac fermions in graphene. The Berry phase can be switched on and off with small magnetic field changes on the order of 10 mT, potentially enabling a variety of optoelectronic graphene device applications.
doi:10.1126/science.aal0212
PMCID: PMC5576454  PMID: 28546211
4.  Widely tunable black phosphorus mid-infrared photodetector 
Nature Communications  2017;8:1672.
Lately rediscovered orthorhombic black phosphorus (BP) exhibits promising properties for near- and mid-infrared optoelectronics. Although recent electrical measurements indicate that a vertical electric field can effectively reduce its transport bandgap, the impact of the electric field on light-matter interaction remains unclear. Here we show that a vertical electric field can dynamically extend the photoresponse in a 5 nm-thick BP photodetector from 3.7 to beyond 7.7 μm, leveraging the Stark effect. We further demonstrate that such a widely tunable BP photodetector exhibits a peak extrinsic photo-responsivity of 518, 30, and 2.2 mA W−1 at 3.4, 5, and 7.7 μm, respectively, at 77 K. Furthermore, the extracted photo-carrier lifetime indicates a potential operational speed of 1.3 GHz. Our work not only demonstrates the potential of BP as an alternative mid-infrared material with broad optical tunability but also may enable the compact, integrated on-chip high-speed mid-infrared photodetectors, modulators, and spectrometers.
The bandgap of ultrathin black phosphorus can be tuned by a vertical electric field. Here, the authors leverage such electric field to extend the photoresponse of a black phosphorus photodetector to 7.7 μm, opening the doors to various mid-infrared applications.
doi:10.1038/s41467-017-01978-3
PMCID: PMC5698317  PMID: 29162821
5.  Quantum Light in Curved Low Dimensional Hexagonal Boron Nitride Systems 
Scientific Reports  2017;7:14758.
Low-dimensional wide bandgap semiconductors open a new playing field in quantum optics using sub-bandgap excitation. In this field, hexagonal boron nitride (h-BN) has been reported to host single quantum emitters (QEs), linking QE density to perimeters. Furthermore, curvature/perimeters in transition metal dichalcogenides (TMDCs) have demonstrated a key role in QE formation. We investigate a curvature-abundant BN system – quasi one-dimensional BN nanotubes (BNNTs) fabricated via a catalyst-free method. We find that non-treated BNNT is an abundant source of stable QEs and analyze their emission features down to single nanotubes, comparing dispersed/suspended material. Combining high spatial resolution of a scanning electron microscope, we categorize and pin-point emission origin to a scale of less than 20 nm, giving us a one-to-one validation of emission source with dimensions smaller than the laser excitation wavelength, elucidating nano-antenna effects. Two emission origins emerge: hybrid/entwined BNNT. By artificially curving h-BN flakes, similar QE spectral features are observed. The impact on emission of solvents used in commercial products and curved regions is also demonstrated. The ‘out of the box’ availability of QEs in BNNT, lacking processing contamination, is a milestone for unraveling their atomic features. These findings open possibilities for precision engineering of QEs, puts h-BN under a similar ‘umbrella’ of TMDC’s QEs and provides a model explaining QEs spatial localization/formation using electron/ion irradiation and chemical etching.
doi:10.1038/s41598-017-15398-2
PMCID: PMC5676806  PMID: 29116207
6.  Oxidative Cyclization in Natural Product Biosynthesis 
Chemical reviews  2016;117(8):5226-5333.
Oxidative cyclizations are important transformations that occur widely during natural product biosynthesis. The transformations from acyclic precursors to cyclized products can afford morphed scaffolds, structural rigidity and biological activities. Some of the most dramatic structural alterations in natural product biosynthesis occur through oxidative cyclization. In this review, we examine the different strategies used by Nature to create new intra-(inter-)-molecular bonds via redox chemistry. The review will cover both oxidation- and reduction-enabled cyclization mechanisms, with an emphasis on the former. Radical cyclizations catalyzed by P450, nonheme iron, α-KG dependent oxygenases and radical SAM enzymes are discussed to illustrate the use of molecular oxygen and S-adenosylmethionine to forge new bonds at unactivated sites via one-electron manifolds. Nonradical cyclizations catalyzed by flavin-dependent monooxygenases and NAD(P)H-dependent reductases are covered to show the use of two-electron manifolds in initiating cyclization reactions. The oxidative installation of epoxides and halogens into acyclic scaffolds to drive subsequent cyclizations are separately discussed as examples of “disappearing” reactive handles. Lastly, oxidative rearrangement of rings systems, including contractions and expansions will be covered.
Graphical Abstract
doi:10.1021/acs.chemrev.6b00478
PMCID: PMC5406274  PMID: 27936626
7.  Significance of measurement of serum trough level and anti‐drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial 
Nakase, H. | Motoya, S. | Matsumoto, T. | Watanabe, K. | Hisamatsu, T. | Yoshimura, N. | Ishida, T. | Kato, S. | Nakagawa, T. | Esaki, M. | Nagahori, M. | Matsui, T. | Naito, Y. | Kanai, T. | Suzuki, Y. | Nojima, M. | Watanabe, M. | Hibi, T. | Andoh, Akira | Ashida, Toshifumi | Endo, Katsuya | Endo, Yutaka | Esaki, Motohiro | Fujita, Hiroshi | Fujiya, Mikihiro | Haruma, Ken | Hibi, Toshifumi | Hiraoka, Sakiko | Hirata, Ichiro | Hisamatsu, Tadakazu | Honda, Yutaka | Iijima, Hideki | Iizuka, Bunei | Ikeya, Kentaro | Inoue, Takuya | Inoue, Shuji | Ishida, Tetsuya | Ishiguro, Yo | Ishihara, Shunji | Ito, Hiroaki | Iwakiri, Ryuichi | Kagaya, Takashi | Kanai, Takanori | Kashida, Hiroshi | Kato, Shingo | Kato, Jun | Katsurada, Takehiko | Kinjyo, Fukunori | Kobayashi, Kiyonori | Kodama, Mayumi | Kunisaki, Reiko | Kurahara, Koichi | Kurokami, Takafumi | Kyouwon, Lee | Matsuda, Koichiro | Matsueda, Kazuhiro | Matsui, Toshiyuki | Matsumoto, Takayuki | Mitsuyama, Keiichi | Mizokami, Yuji | Motoya, Satoshi | Naito, Yuji | Nakagawa, Tomoo | Nakamura, Shiro | Nakase, Hiroshi | Nojima, Masanori | Nomura, Masafumi | Ogawa, Atsuhiro | Okazaki, Kazuichi | Otsuka, Kazuaki | Sakuraba, Hirotake | Saruta, Masayuki | Sasaki, Makoto | Shirai, Takayuki | Suga, Tomoaki | Sugimura, Kazuhito | Sugiyama, Toshiro | Suzuki, Yasuo | Takeshima, Fuminao | Tamaki, Hiroyuki | Tanaka, Shinji | Tanida, Satoshi | Tominaga, Keiichi | Tomizawa, Taku | Watanabe, Kenji | Watanabe, Mamoru | Yamamoto, Shojiro | Yamashita, Masaki | Yoshida, Atsushi | Yoshimura, Naoki
Summary
Background
Significance of monitoring adalimumab trough levels and anti‐adalimumab antibodies (AAA) for disease outcome in Crohn's disease (CD) patients remained unclear.
Aim
To evaluate the association of adalimumab trough levels and AAA at week 26 with clinical remission at week 52, the effect of azathiopurine on AAA and factors influencing trough levels in CD patients in the DIAMOND trial.
Methods
We performed this study using adalimumab trough levels, AAA at week 26 and 6‐thioguanine nucleotide (TGN) in red blood cells at week 12. A multiple regression model and receiver operating analysis was performed to identify factors influencing adalimumab trough levels and AAA, and adalimumab thresholds for predicting disease activity.
Results
There was a significant difference of adalimumab trough level at week 26 between patients with disease remission and without at week 52 (7.7 ± 3.3 μg/mL vs 5.4 ± 4.3 μg/mL: P <.001). Adalimumab trough level of 5.0 μg/mL yielded optimal sensitivity and specificity for remission prediction (80.2% and 55.6%, respectively). AAA development at week 26 significantly affected remission at week 52 (P = .021), which was strongly associated with adalimumab trough levels. Female gender and increasing body weight were independently associated with low adalimumab trough levels, and female gender was associated with AAA development. A cut‐off 6TGN level of >222.5 p mol/8 ×108 RBCs yielded sensitivity (100%) and specificity (60.6%) for AAA negativity.
Conclusion
Adalimumab trough levels and AAA occurrence were significantly associated with clinical remission. Higher 6TGN affected AAA negativity. The combination therapy is beneficial in some relevant aspects for CD patients. (UMIN Registration No. 000005146)
doi:10.1111/apt.14318
PMCID: PMC5656923  PMID: 28884856
8.  Electrotunable artificial molecules based on van der Waals heterostructures 
Science Advances  2017;3(10):e1701699.
Electrically controlled evolution from an artificial molecule to an artificial atom in atomically thin MoS2 is demonstrated.
Quantum confinement has made it possible to detect and manipulate single-electron charge and spin states. The recent focus on two-dimensional (2D) materials has attracted significant interests on possible applications to quantum devices, including detecting and manipulating either single-electron charging behavior or spin and valley degrees of freedom. However, the most popular model systems, consisting of tunable double-quantum-dot molecules, are still extremely difficult to realize in these materials. We show that an artificial molecule can be reversibly formed in atomically thin MoS2 sandwiched in hexagonal boron nitride, with each artificial atom controlled separately by electrostatic gating. The extracted values for coupling energies at different regimes indicate a single-electron transport behavior, with the coupling strength between the quantum dots tuned monotonically. Moreover, in the low-density regime, we observe a decrease of the conductance with magnetic field, suggesting the observation of Coulomb blockade weak anti-localization. Our experiments demonstrate for the first time the realization of an artificial quantum-dot molecule in a gated MoS2 van der Waals heterostructure, which could be used to investigate spin-valley physics. The compatibility with large-scale production, gate controllability, electron-hole bipolarity, and new quantum degrees of freedom in the family of 2D materials opens new possibilities for quantum electronics and its applications.
doi:10.1126/sciadv.1701699
PMCID: PMC5650488
9.  Direct exciton emission from atomically thin transition metal dichalcogenide heterostructures near the lifetime limit 
Scientific Reports  2017;7:12383.
We demonstrate the reduction of the inhomogeneous linewidth of the free excitons in atomically thin transition metal dichalcogenides (TMDCs) MoSe2, WSe2 and MoS2 by encapsulation within few nanometre thick hBN. Encapsulation is shown to result in a significant reduction of the 10 K excitonic linewidths down to ∼3.5 meV for n-MoSe2, ∼5.0  meV for p-WSe2 and ∼4.8 meV for n-MoS2. Evidence is obtained that the hBN environment effectively lowers the Fermi level since the relative spectral weight shifts towards the neutral exciton emission in n-doped TMDCs and towards charged exciton emission in p-doped TMDCs. Moreover, we find that fully encapsulated MoS2 shows resolvable exciton and trion emission even after high power density excitation in contrast to non-encapsulated materials. Our findings suggest that encapsulation of mechanically exfoliated few-monolayer TMDCs within nanometre thick hBN dramatically enhances optical quality, producing ultra-narrow linewidths that approach the homogeneous limit.
doi:10.1038/s41598-017-09739-4
PMCID: PMC5620059  PMID: 28959034
10.  Propagation of superconducting coherence via chiral quantum-Hall edge channels 
Scientific Reports  2017;7:10953.
Recently, there has been significant interest in superconducting coherence via chiral quantum-Hall (QH) edge channels at an interface between a two-dimensional normal conductor and a superconductor (N–S) in a strong transverse magnetic field. In the field range where the superconductivity and the QH state coexist, the coherent confinement of electron- and hole-like quasiparticles by the interplay of Andreev reflection and the QH effect leads to the formation of Andreev edge states (AES) along the N–S interface. Here, we report the electrical conductance characteristics via the AES formed in graphene–superconductor hybrid systems in a three-terminal configuration. This measurement configuration, involving the QH edge states outside a graphene–S interface, allows the detection of the longitudinal and QH conductance separately, excluding the bulk contribution. Convincing evidence for the superconducting coherence and its propagation via the chiral QH edge channels is provided by the conductance enhancement on both the upstream and the downstream sides of the superconducting electrode as well as in bias spectroscopy results below the superconducting critical temperature. Propagation of superconducting coherence via QH edge states was more evident as more edge channels participate in the Andreev process for high filling factors with reduced valley-mixing scattering.
doi:10.1038/s41598-017-11209-w
PMCID: PMC5591196  PMID: 28887486
11.  Identification of Circulating miRNAs Differentially Regulated by Opioid Treatment 
Emerging evidence demonstrates functional contributions of microRNAs (miRNAs) to μ-opioid receptor (MOR) signaling, but the information so far has been mostly limited to their intracellular regulatory mechanisms. The present study aimed to investigate changes in plasma miRNA profiles elicited by opioid treatment in blood samples collected from clinical studies. Healthy male subjects were orally administered with hydromorphone or oxycodone and blood samples were collected at a specified time after the drug treatment. A total of 179 plasma miRNAs were measured using multiplex qRT-PCR. Nine and seventeen miRNAs were commonly upregulated (let-7a-5p, miR-423-3p, miR-199a-3p, miR-146a-5p, miR-23b-3p, miR-24-3p, miR-221-3p, miR-223-3p, and miR-146b-5p) and downregulated (miR-144-3p, miR-215, miR-363-3p, etc.), respectively, following opioid treatment. The MOR signaling-associated miRNAs, namely let-7 family miRNAs (i.e., let-7d-5p, let-7f-5p, let-7c, let-7e-5p), miR-103a-3p, miR-339-3p, miR-146a-5p, miR-23b-3p, miR-23a-3p, and miR-181a-5p, were differentially expressed following drug treatment. These differentially expressed miRNAs are circulating biomarker candidates that can be used to evaluate MOR stimulation and serve as novel clinical diagnostic tools for improving clinical outcomes.
doi:10.3390/ijms18091991
PMCID: PMC5618640  PMID: 28926935
hydromorphone; oxycodone; μ-opioid receptor; microRNA; biomarker; qRT-PCR
12.  Mach-Zehnder interferometry using spin- and valley-polarized quantum Hall edge states in graphene 
Science Advances  2017;3(8):e1700600.
We realize an electronic Mach-Zehnder interferometer with quantum Hall edge channels along a pn junction in graphene.
Confined to a two-dimensional plane, electrons in a strong magnetic field travel along the edge in one-dimensional quantum Hall channels that are protected against backscattering. These channels can be used as solid-state analogs of monochromatic beams of light, providing a unique platform for studying electron interference. Electron interferometry is regarded as one of the most promising routes for studying fractional and non-Abelian statistics and quantum entanglement via two-particle interference. However, creating an edge-channel interferometer in which electron-electron interactions play an important role requires a clean system and long phase coherence lengths. We realize electronic Mach-Zehnder interferometers with record visibilities of up to 98% using spin- and valley-polarized edge channels that copropagate along a pn junction in graphene. We find that interchannel scattering between same-spin edge channels along the physical graphene edge can be used to form beamsplitters, whereas the absence of interchannel scattering along gate-defined interfaces can be used to form isolated interferometer arms. Surprisingly, our interferometer is robust to dephasing effects at energies an order of magnitude larger than those observed in pioneering experiments on GaAs/AlGaAs quantum wells. Our results shed light on the nature of edge-channel equilibration and open up new possibilities for studying exotic electron statistics and quantum phenomena.
doi:10.1126/sciadv.1700600
PMCID: PMC5562424
13.  Observation of ultralong valley lifetime in WSe2/MoS2 heterostructures 
Science Advances  2017;3(7):e1700518.
We report near-perfect generation of ultralong-lived valley polarization in TMD heterostructures for valleytronics applications.
The valley degree of freedom in two-dimensional (2D) crystals recently emerged as a novel information carrier in addition to spin and charge. The intrinsic valley lifetime in 2D transition metal dichalcogenides (TMD) is expected to be markedly long due to the unique spin-valley locking behavior, where the intervalley scattering of the electron simultaneously requires a large momentum transfer to the opposite valley and a flip of the electron spin. However, the experimentally observed valley lifetime in 2D TMDs has been limited to tens of nanoseconds thus far. We report efficient generation of microsecond-long-lived valley polarization in WSe2/MoS2 heterostructures by exploiting the ultrafast charge transfer processes in the heterostructure that efficiently creates resident holes in the WSe2 layer. These valley-polarized holes exhibit near-unity valley polarization and ultralong valley lifetime: We observe a valley-polarized hole population lifetime of more than 1 μs and a valley depolarization lifetime (that is, intervalley scattering lifetime) of more than 40 μs at 10 K. The near-perfect generation of valley-polarized holes in TMD heterostructures, combined with ultralong valley lifetime, which is orders of magnitude longer than previous results, opens up new opportunities for novel valleytronics and spintronics applications.
doi:10.1126/sciadv.1700518
PMCID: PMC5529060
14.  Realisation of topological zero-energy mode in bilayer graphene in zero magnetic field 
Scientific Reports  2017;7:6466.
Bilayer graphene (BLG) gapped by a vertical electric field represents a valley-symmetry-protected topological insulating state. Emergence of a new topological zero-energy mode has been proposed in BLG at a boundary between regions of inverted band gaps induced by two oppositely polarized vertical electric fields. However, its realisation has been challenged by the enormous difficulty in arranging two pairs of accurately aligned split gates on the top and bottom surfaces of clean BLG. Here we report realisation of the topological zero-energy mode in ballistic BLG, with zero-bias differential conductance close to the ideal value of 4 e 2/h (e is the electron charge and h is Planck’s constant) along a boundary channel between a pair of gate-defined inverted band gaps. This constitutes the bona fide electrical-gate-tuned generation of a valley-symmetry-protected topological boundary conducting channel in BLG in zero magnetic field, which is essential to valleytronics applications of BLG.
doi:10.1038/s41598-017-06902-9
PMCID: PMC5527089  PMID: 28743948
15.  Enzyme-Catalyzed Cationic Epoxide Rearrangements in Quinolone Alkaloid Biosynthesis 
Nature chemical biology  2017;13(3):325-332.
Epoxides are highly useful synthons and biosynthons in the construction of complex natural products during total synthesis and biosynthesis, respectively. Among enzyme-catalyzed epoxide transformations, a notably missing reaction, compared to the synthetic toolbox, is cationic rearrangement that takes place under strong acids. This is a challenging transformation for enzyme catalysis, as stabilization of the carbocation intermediate upon epoxide cleavage is required. Here, we discovered two Brønsted acid enzymes that can catalyze two unprecedented epoxide transformations in biology. PenF from the penigequinolone pathway catalyzes a cationic epoxide rearrangement under physiological conditions to generate a quaternary carbon center, while AsqO from the aspoquinolone pathway catalyzes a 3-exo-tet cyclization to forge a cyclopropane-tetrahydrofuran ring system. The discovery of these new epoxide-modifying enzymes further highlights the versatility of epoxides in complexity generation during natural product biosynthesis.
doi:10.1038/nchembio.2283
PMCID: PMC5310975  PMID: 28114276
16.  Ballistic superconductivity in semiconductor nanowires 
Nature Communications  2017;8:16025.
Semiconductor nanowires have opened new research avenues in quantum transport owing to their confined geometry and electrostatic tunability. They have offered an exceptional testbed for superconductivity, leading to the realization of hybrid systems combining the macroscopic quantum properties of superconductors with the possibility to control charges down to a single electron. These advances brought semiconductor nanowires to the forefront of efforts to realize topological superconductivity and Majorana modes. A prime challenge to benefit from the topological properties of Majoranas is to reduce the disorder in hybrid nanowire devices. Here we show ballistic superconductivity in InSb semiconductor nanowires. Our structural and chemical analyses demonstrate a high-quality interface between the nanowire and a NbTiN superconductor that enables ballistic transport. This is manifested by a quantized conductance for normal carriers, a strongly enhanced conductance for Andreev-reflecting carriers, and an induced hard gap with a significantly reduced density of states. These results pave the way for disorder-free Majorana devices.
Disorder has been a prime challenge to study the topological properties in a hybrid system. Here, Zhang et al. report ballistic superconductivity in InSb nanowires interfacing with a NbTiN superconductor, paving the way for disorder-free Majorana devices.
doi:10.1038/ncomms16025
PMCID: PMC5504288  PMID: 28681843
17.  Topical Application of Trisodium Ascorbyl 6-Palmitate 2-Phosphate Actively Supplies Ascorbate to Skin Cells in an Ascorbate Transporter-Independent Manner 
Nutrients  2017;9(7):645.
Ascorbic acid (AA) possesses multiple beneficial functions, such as regulating collagen biosynthesis and redox balance in the skin. AA derivatives have been developed to overcome this compound’s high fragility and to assist with AA supplementation to the skin. However, how AA derivatives are transferred into cells and converted to AA in the skin remains unclear. In the present study, we showed that AA treatment failed to increase the cellular AA level in the presence of AA transporter inhibitors, indicating an AA transporter-dependent action. In contrast, torisodium ascorbyl 6-palmitate 2-phosphate (APPS) treatment significantly enhanced the cellular AA level in skin cells despite the presence of inhibitors. In ex vivo experiments, APPS treatment also increased the AA content in a human epidermis model. Interestingly, APPS was readily metabolized and converted to AA in keratinocyte lysates via an intrinsic mechanism. Furthermore, APPS markedly repressed the intracellular superoxide generation and promoted viability associated with an enhanced AA level in Sod1-deficient skin cells. These findings indicate that APPS effectively restores the AA level and normalizes the redox balance in skin cells in an AA transporter-independent manner. Topical treatment of APPS is a beneficial strategy for supplying AA and improving the physiology of damaged skin.
doi:10.3390/nu9070645
PMCID: PMC5537765  PMID: 28640219
ascorbic acid; ascorbic acid transporter; ascorbic acid derivative; skin
18.  World Congress Integrative Medicine & Health 2017: Part one 
Brinkhaus, Benno | Falkenberg, Torkel | Haramati, Aviad | Willich, Stefan N. | Briggs, Josephine P. | Willcox, Merlin | Linde, Klaus | Theorell, Töres | Wong, Lisa M. | Dusek, Jeffrey | Wu, Darong | Eisenberg, David | Haramati, Aviad | Berger, Bettina | Kemper, Kathi | Stock-Schröer, Beate | Sützl-Klein, Hedda | Ferreri, Rosaria | Kaplan, Gary | Matthes, Harald | Rotter, Gabriele | Schiff, Elad | Arnon, Zahi | Hahn, Eckhard | Luberto, Christina M. | Martin, David | Schwarz, Silke | Tauschel, Diethard | Flower, Andrew | Gramminger, Harsha | Gupta, Hedwig H. | Gupta, S. N. | Kerckhoff, Annette | Kessler, Christian S. | Michalsen, Andreas | Kessler, Christian S. | Kim, Eun S. | Jang, Eun H. | Kim, Rana | Jan, Sae B. | Mittwede, Martin | Mohme, Wiebke | Ben-Arye, Eran | Bonucci, Massimo | Saad, Bashar | Breitkreuz, Thomas | Rossi, Elio | Kebudi, Rejin | Daher, Michel | Razaq, Samaher | Gafer, Nahla | Nimri, Omar | Hablas, Mohamed | Kienle, Gunver Sophia | Samuels, Noah | Silbermann, Michael | Bandelin, Lena | Lang, Anna-Lena | Wartner, Eva | Holtermann, Christoph | Binstock, Maxwell | Riebau, Robert | Mujkanovic, Edin | Cramer, Holger | Lauche, Romy | Michalsen, Andres | Ward, Lesley | Cramer, Holger | Irnich, Dominik | Stör, Wolfram | Burnstock, Geoffrey | Schaible, Hans-Georg | Ots, Thomas | Langhorst, Jost | Lauche, Romy | Sundberg, Tobias | Falkenberg, Torkel | Amarell, Catherina | Amarell, Catherina | Anheyer, Melanie | Eckert, Marion | Eckert, Marion | Ogal, Mercedes | Eckert, Marion | Amarell, Catherina | Schönauer, Annette | Reisenberger, Birgit | Brand, Bernhard | Anheyer, Dennis | Dobos, Gustav | Kroez, Matthias | Martin, David | Matthes, Harald | Ammendola, Aldo | Mao, Jun J. | Witt, Claudia | Yang, Yufei | Dobos, Gustav | Oritz, Miriam | Horneber, Markus | Voiß, Petra | Reisenberger, Birgit | von Rosenstiel, Alexandra | Eckert, Marion | Ogal, Mercedes | Amarell, Catharina | Anheyer, Melanie | Schad, Friedemann | Schläppi, Marc | Kröz, Matthias | Büssing, Arndt | Bar-Sela, Gil | Matthes, Harald | Schiff, Elad | Ben-Arye, Eran | Arnon, Zahi | Avshalomov, David | Attias, Samuel | Schönauer, Annette | Haramati, Aviad | Witt, Claudia | Brinkhaus, Benno | Cotton, Sian | Jong, Miek | Jong, Mats | Scheffer, Christian | Haramati, Aviad | Tauschel, Diethard | Edelhäuser, Friedrich | AlBedah, Abdullah | Lee, Myeong Soo | Khalil, Mohamed | Ogawa, Keiko | Motoo, Yoshiharu | Arimitsu, Junsuke | Ogawa, Masao | Shimizu, Genki | Stange, Rainer | Kraft, Karin | Kuchta, Kenny | Watanabe, Kenji | Bonin, D | Büssing, Arndt | Gruber, Harald | Koch, Sabine | Gruber, Harald | Pohlmann, Urs | Caldwell, Christine | Krantz, Barbara | Kortum, Ria | Martin, Lily | Wieland, Lisa S. | Kligler, Ben | Gould-Fogerite, Susan | Zhang, Yuqing | Wieland, Lisa S. | Riva, John J. | Lumpkin, Michael | Ratner, Emily | Ping, Liu | Jian, Pei | Hamme, Gesa-Meyer | Mao, Xiaosong | Chouping, Han | Schröder, Sven | Hummelsberger, Josef | Wullinger, Michael | Brodzky, Marc | Zalpour, Christoff | Langley, Julia | Weber, Wendy | Mudd, Lanay M. | Wayne, Peter | Witt, Clauda | Weidenhammer, Wolfgang | Fønnebø, Vinjar | Boon, Heather | Steel, Amie | Bugarcic, Andrea | Rangitakatu, Melisa | Steel, Amie | Adams, Jon | Sibbritt, David | Wardle, Jon | Leach, Matthew | Schloss, Janet | Dieze, Helene | Boon, Heather | Ijaz, Nadine | Willcox, Merlin | Heinrich, Michael | Lewith, George | Flower, Andrew | Graz, Bertrand | Adam, Daniela | Grabenhenrich, Linus | Ortiz, Miriam | Binting, Sylvia | Reinhold, Thomas | Brinkhaus, Benno | Andermo, Susanne | Sundberg, Tobias | Falkenberg, Torkel | Nordberg, Johanna Hök | Arman, Maria | Bhasin, Manoj | Fan, Xueyi | Libermann, Towia | Fricchione, Gregory | Denninger, John | Benson, Herbert | Berger, Bettina | Stange, Rainer | Michalsen, Andreas | Martin, David D. | Boers, Inge | Vlieger, Arine | Jong, Miek | Brinkhaus, Benno | Teut, Michael | Ullmann, Alexander | Ortiz, Miriam | Rotter, Gabriele | Binting, Sylvia | Lotz, Fabian | Roll, Stephanie | Canella, Claudia | Mikolasek, Michael | Rostock, Matthias | Beyer, Jörg | Guckenberger, Matthias | Jenewein, Josef | Linka, Esther | Six, Claudia | Stoll, Sarah | Stupp, Roger | Witt, Claudia M. | Chuang, Elisabeth | Kligler, Ben | McKee, Melissa D. | Cramer, Holger | Lauche, Romy | Klose, Petra | Lange, Silke | Langhorst, Jost | Dobos, Gustav | Chung, Vincent C. H. | Wong, Hoi L. C. | Wu, Xin Y. | Wen, Grace Y. G. | Ho, Robin S. T. | Ching, Jessica Y. L. | Wu, Justin C. Y. | Coakley, Amanda | Flanagan, Jane | Annese, Christine | Empoliti, Joanne | Gao, Zishan | Liu, Xugang | Yu, Shuguang | Yan, Xianzhong | Liang, Fanrong | Hohmann, Christoph D. | Steckhan, Nico | Ostermann, Thomas | Paetow, Arion | Hoff, Evelyn | Michalsen, Andreas | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Jeitler, Michael | Zillgen, Hannah | Högl, Manuel | Steckhan, Nico | Stöckigt, Barbara | Seifert, Georg | Michalsen, Andreas | Kessler, Christian | Khadivzadeh, Talat | Bashtian, Maryam Hassanzadeh | Aval, Shapour Badiee | Esmaily, Habibollah | Kim, Jihye | Kim, Keun H. | Klocke, Carina | Joos, Stefanie | Koshak, Abdulrahman | Wie, Li | Koshak, Emad | Wali, Siraj | Alamoudi, Omer | Demerdash, Abdulrahman | Qutub, Majdy | Pushparaj, Peter | Heinrich, Michael | Kruse, Sigrid | Fischer, Isabell | Tremel, Nadine | Rosenecker, Joseph | Leung, Brenda | Takeda, Wendy | Liang, Ning | Feng, Xue | Liu, Jian-ping | Cao, Hui-juan | Luberto, Christina M. | Shinday, Nina | Philpotts, Lisa | Park, Elyse | Fricchione, Gregory L. | Yeh, Gloria | Munk, Niki | Zakeresfahani, Arash | Foote, Trevor R. | Ralston, Rick | Boulanger, Karen | Özbe, Dominik | Gräßel, Elmar | Luttenberger, Katharina | Pendergrass, Anna | Pach, Daniel | Bellmann-Strobl, Judit | Chang, Yinhui | Pasura, Laura | Liu, Bin | Jäger, Sven F. | Loerch, Ronny | Jin, Li | Brinkhaus, Benno | Ortiz, Miriam | Reinhold, Thomas | Roll, Stephanie | Binting, Sylvia | Icke, Katja | Shi, Xuemin | Paul, Friedemann | Witt, Claudia M. | Rütz, Michaela | Lynen, Andreas | Schömitz, Meike | Vahle, Maik | Salomon, Nir | Lang, Alon | Lahat, Adi | Kopylov, Uri | Ben-Horin, Shomron | Har-Noi, Ofir | Avidan, Benjamin | Elyakim, Rami | Gamus, Dorit | NG, Siew | Chang, Jessica | Wu, Justin | Kaimiklotis, John | Schumann, Dania | Buttó, Ludovica | Langhorst, Jost | Dobos, Gustav | Haller, Dirk | Cramer, Holger | Smith, Caroline | de Lacey, Sheryl | Chapman, Michael | Ratcliffe, Julie | Johnson, Neil | Lyttleton, Jane | Boothroyd, Clare | Fahey, Paul | Tjaden, Bram | van Vliet, Marja | van Wietmarschen, Herman | Jong, Miek | Tröger, Wilfried | Vuolanto, Pia | Aarva, Paulina | Sorsa, Minna | Helin, Kaija | Wenzel, Claudia | Zoderer, Iris | Pammer, Patricia | Simon, Patrick | Tucek, Gerhard | Wode, Kathrin | Henriksson, Roger | Sharp, Lena | Stoltenberg, Anna | Nordberg, Johanna Hök | Xiao-ying, Yang | Wang, Li-qiong | Li, Jin-gen | Liang, Ning | Wang, Ying | Liu, Jian-ping | Balneaves, Lynda | Capler, Rielle | Bocci, Chiara | Guffi, Marta | Paolini, Marina | Meaglia, Ilaria | Porcu, Patrizia | Ivaldi, Giovanni B. | Dragan, Simona | Bucuras, Petru | Pah, Ana M. | Badalica-Petrescu, Marius | Buleu, Florina | Hogea-Stoichescu, Gheorghe | Christodorescu, Ruxandra | Kao, Lan | Cho, Yumin | Klafke, Nadja | Mahler, Cornelia | von Hagens, Cornelia | Uhlmann, Lorenz | Bentner, Martina | Schneeweiss, Andreas | Mueller, Andreas | Szecsenyi, Joachim | Joos, Stefanie | Neri, Isabella | Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Rossi, Elio | Baccetti, Sonia | Firenzuoli, Fabio | Monechi, Maria V. | Di Stefano, Mariella | Amunni, Gianni | Wong, Wendy | Chen, Bingzhong | Wu, Justin | Amri, Hakima | Haramati, Aviad | Kotlyanskaya, Lucy | Anderson, Belinda | Evans, Roni | Kligler, Ben | Marantz, Paul | Bradley, Ryan | Booth-LaForce, Cathryn | Zwickey, Heather | Kligler, Benjamin | Brooks, Audrey | Kreitzer, Mary J. | Lebensohn, Patricia | Goldblatt, Elisabeth | Esmel-Esmel, Neus | Jiménez-Herrera, Maria | Ijaz, Nadine | Boon, Heather | Jocham, Alexandra | Stock-Schröer, Beate | Berberat, Pascal O. | Schneider, Antonius | Linde, Klaus | Masetti, Morgana | Murakozy, Henriette | Van Vliet, Marja | Jong, Mats | Jong, Miek | Agdal, Rita | Atarzadeh, Fatemeh | Jaladat, Amir M. | Hoseini, Leila | Amini, Fatemeh | Bai, Chen | Liu, Tiegang | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Daneshfard, Babak | Nimrouzi, Majid | Tafazoli, Vahid | Alorizi, Seyed M. Emami | Saghebi, Seyed A. | Fattahi, Mohammad R. | Salehi, Alireza | Rezaeizadeh, Hossein | Zarshenas, Mohammad M. | Nimrouzi, Majid | Fox, Kealoha | Hughes, John | Kostanjsek, Nenad | Espinosa, Stéphane | Lewith, George | Fisher, Peter | Latif, Abdul | Lefeber, Donald | Paske, William | Öztürk, Ali Ö. | Öztürk, Gizemnur | Boers, Inge | Tissing, Wim | Naafs, Marianne | Busch, Martine | Jong, Miek | Daneshfard, Babak | Sanaye, Mohammad R. | Dräger, Kilian | Fisher, Peter | Kreitzer, Mary J. | Evans, Roni | Leininger, Brent | Shafto, Kate | Breen, Jenny | Sanaye, Mohammad R. | Daneshfard, Babak | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | White, Shelley | Wiesener, Solveig | Salamonsen, Anita | Stub, Trine | Fønnebø, Vinjar | Abanades, Sergio | Blanco, Mar | Masllorens, Laia | Sala, Roser | Al-Ahnoumy, Shafekah | Han, Dongwoon | He, Luzhu | Kim, Ha Yun | In Choi, Da | Alræk, Terje | Stub, Trine | Kristoffersen, Agnete | von Sceidt, Christel | Michalsen, Andreas | Bruset, Stig | Musial, Frauke | Anheyer, Dennis | Cramer, Holger | Lauche, Romy | Saha, Felix J. | Dobos, Gustav | Anheyer, Dennis | Haller, Heidemarie | Lauche, Romy | Dobos, Gustav | Cramer, Holger | Azizi, Hoda | Khadem, Nayereh | Hassanzadeh, Malihe | Estiri, Nazanin | Azizi, Hamideh | Tavassoli, Fatemeh | Lotfalizadeh, Marzieh | Zabihi, Reza | Esmaily, Habibollah | Azizi, Hoda | Shabestari, Mahmoud Mohammadzadeh | Paeizi, Reza | Azari, Masoumeh Alvandi | Bahrami-Taghanaki, Hamidreza | Zabihi, Reza | Azizi, Hamideh | Esmaily, Habibollah | Baars, Erik | De Bruin, Anja | Ponstein, Anne | Baccetti, Sonia | Di Stefano, Mariella | Rossi, Elio | Firenzuoli, Fabio | Segantini, Sergio | Monechi, Maria Valeria | Voller, Fabio | Barth, Jürgen | Kern, Alexandra | Lüthi, Sebastian | Witt, Claudia | Barth, Jürgen | Zieger, Anja | Otto, Fabius | Witt, Claudia | Beccia, Ariel | Dunlap, Corina | Courneene, Brendan | Bedregal, Paula | Passi, Alvaro | Rodríguez, Alfredo | Chang, Mayling | Gutiérrez, Soledad | Beissner, Florian | Beissner, Florian | Preibisch, Christine | Schweizer-Arau, Annemarie | Popovici, Roxana | Meissner, Karin | Beljanski, Sylvie | Belland, Laura | Rivera-Reyes, Laura | Hwang, Ula | Berger, Bettina | Sethe, Dominik | Hilgard, Dörte | Heusser, Peter | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Holmes, Michelle | Lewith, George | Yardley, Lucy | Little, Paul | Cooper, Cyrus | Bogani, Patrizia | Maggini, Valentina | Gallo, Eugenia | Miceli, Elisangela | Biffi, Sauro | Mengoni, Alessio | Fani, Renato | Firenzuoli, Fabio | Brands-Guendling, Nadine | Guendling, Peter W. | Bronfort, Gert | Evans, Roni | Haas, Mitch | Leininger, Brent | Schulz, Craig | Bu, Xiangwei | Wang, J. | Fang, T. | Shen, Z. | He, Y. | Zhang, X. | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Büssing, Arndt | Baumann, Klaus | Frick, Eckhard | Jacobs, Christoph | Büssing, Arndt | Grünther, Ralph-Achim | Lötzke, Désirée | Büssing, Arndt | Jung, Sonny | Lötzke, Désirée | Recchia, Daniela R. | Robens, Sibylle | Ostermann, Thomas | Berger, Bettina | Stankewitz, Josephin | Kröz, Matthias | Jeitler, Mika | Kessler, Christian | Michalsen, Andreas | Cheon, Chunhoo | Jang, Bo H. | Ko, Seong G. | Huang, Ching W. | Sasaki, Yui | Ko, Youme | Cheshire, Anna | Ridge, Damien | Hughes, John | Peters, David | Panagioti, Maria | Simon, Chantal | Lewith, George | Cho, Hyun J. | Han, Dongwoon | Choi, Soo J. | Jung, Young S. | Im, Hyea B | Cooley, Kieran | Tummon-Simmons, Laura | Cotton, Sian | Luberto, Christina M. | Wasson, Rachel | Kraemer, Kristen | Sears, Richard | Hueber, Carly | Derk, Gwendolyn | Lill, JR | An, Ruopeng | Steinberg, Lois | Rodriguez, Lourdes Diaz | la Fuente, Francisca García-de | De la Vega, Miguel | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Cantarero-Villanueva, Irene | Rodriguez, Lourdes Diaz | García-De la Fuente, Francisca | Jiménez-Guerrero, Fanny | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Galiano-Castillo, Noelia | Diaz-Saez, Gualberto | Torres-Jimenez, José I. | Garcia-Gomez, Olga | Hortal-Muñoz, Luis | Diaz-Diez, Camino | Dicen, Demijon | Diezel, Helene | Adams, Jon | Steel, Amie | Wardle, Jon | Diezel, Helene | Steel, Amie | Frawley, Jane | Wardle, Jon | Broom, Alex | Adams, Jon | Dong, Fei | Yu, He | Liu, Tiegang | Ma, Xueyan | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Gu, Xiaohong | Dong, Fei | Yu, He | Wu, Liqun | Liu, Tiegang | Ma, Xueyan | Ma, Jiaju | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Zhen, Jianhua | Gu, Xiaohong | Dubois, Julie | Rodondi, Pierre-Yves | Edelhäuser, Friedrich | Schwartze, Sophia | Trapp, Barbara | Cysarz, Dirk
doi:10.1186/s12906-017-1782-4
PMCID: PMC5498855
19.  Mechanical properties of atomically thin boron nitride and the role of interlayer interactions 
Nature Communications  2017;8:15815.
Atomically thin boron nitride (BN) nanosheets are important two-dimensional nanomaterials with many unique properties distinct from those of graphene, but investigation into their mechanical properties remains incomplete. Here we report that high-quality single-crystalline mono- and few-layer BN nanosheets are one of the strongest electrically insulating materials. More intriguingly, few-layer BN shows mechanical behaviours quite different from those of few-layer graphene under indentation. In striking contrast to graphene, whose strength decreases by more than 30% when the number of layers increases from 1 to 8, the mechanical strength of BN nanosheets is not sensitive to increasing thickness. We attribute this difference to the distinct interlayer interactions and hence sliding tendencies in these two materials under indentation. The significantly better interlayer integrity of BN nanosheets makes them a more attractive candidate than graphene for several applications, for example, as mechanical reinforcements.
Atomically thin boron nitride remains undercharacterized in terms of their mechanical properties. Here authors test high-quality mono- and few-layer BN and show it to be one of the strongest electrically insulating materials and dramatically better in interlayer integrity than graphene under indentation.
doi:10.1038/ncomms15815
PMCID: PMC5489686  PMID: 28639613
20.  Patency Capsule Tolerability in School-Aged Children 
Digestion  2017;96(1):46-51.
Background
A patency capsule (PC) can help predict capsule endoscope (CE) retention; however, PC tolerability is unknown in children. We retrospectively evaluated PC tolerability in school-aged children.
Methods
Sixty-one patients (median age, 12.9 years; range 7.4–17.3 years) who underwent PC examination were analyzed for occurrence and determinants of ingestion difficulty and relationships between ingestion of the 2 capsules. We defined ingestion difficulty as taking 30 min or more, or failure, to ingest the PC.
Results
Thirty-nine patients (64%) successfully ingested the PC without ingestion difficulty. The other 22 had ingestion difficulty and were significantly younger (11.7 ± 2.2 vs. 13.0 ± 1.8 years; p = 0.04) and shorter (143.3 ± 14.0 vs. 154.6 ± 12.5 cm; p = 0.003) than those without ingestion difficulty. Multivariate analysis showed that the most significant factor for predicting PC ingestion difficulty was height (cutoff value, 152 cm). Time to ingest the CE was significantly shorter than that for PC ingestion (8 ± 32 vs. 20 ± 58 min; p = 0.01). All patients indicated that ingestion of the CE was easier because of its smooth surface compared with the PC.
Conclusions
PC ingestion is not guaranteed in school-aged children. PC ingestion ability should be evaluated by considering the child's height and lack of experience ingesting capsules prior to PC examination.
doi:10.1159/000477579
PMCID: PMC5637285  PMID: 28637030
Patency capsule; Children; Capsule endoscopy; Ingestion
21.  Biochemical Characterization of a Eukaryotic Decalin-Forming Diels–Alderase 
Journal of the American Chemical Society  2016;138(49):15837-15840.
The trans-decalin structure formed as a result of intramolecular Diels–Alder cycloaddition is widely present among bioactive natural products isolated from fungi. In this work, we elucidated the concise, three-enzyme biosynthetic pathway of the cytotoxic myceliothermophin and biochemically characterized the Diels–Alderase (DAase) that catalyzes formation of trans-decalin from an acyclic substrate. Computational studies on the reaction mechanisms rationalizes both the substrate- and stereoselectivity of the enzyme.
Graphical Abstract
doi:10.1021/jacs.6b10452
PMCID: PMC5323083  PMID: 27960349
22.  Surface transport and quantum Hall effect in ambipolar black phosphorus double quantum wells 
Science Advances  2017;3(6):e1603179.
Few-layer black phosphorus acts as tunable ambipolar wide quantum wells.
Quantum wells (QWs) constitute one of the most important classes of devices in the study of two-dimensional (2D) systems. In a double-layer QW, the additional “which-layer” degree of freedom gives rise to celebrated phenomena, such as Coulomb drag, Hall drag, and exciton condensation. We demonstrate facile formation of wide QWs in few-layer black phosphorus devices that host double layers of charge carriers. In contrast to traditional QWs, each 2D layer is ambipolar and can be tuned into n-doped, p-doped, or intrinsic regimes. Fully spin-polarized quantum Hall states are observed on each layer, with an enhanced Landé g factor that is attributed to exchange interactions. Our work opens the door for using 2D semiconductors as ambipolar single, double, or wide QWs with unusual properties, such as high anisotropy.
doi:10.1126/sciadv.1603179
PMCID: PMC5457033
Black Phosphorus; Quantum Wells; Surface Transport; Quantum Hall Effect
23.  Deep sequencing of the transcriptome in the anterior pituitary of heifers before and after ovulation 
We aimed to determine gene expression patterns in the anterior pituitary (AP) of heifers before and after ovulation via deep sequencing of the transcriptome (RNA-seq) to identify new genes and clarify important pathways. Heifers were slaughtered on the estrus day (pre-ovulation; n=5) or 3 days after ovulation (post-ovulation; n=5) for AP collection. We randomly selected 4 pre-ovulation and 4 post-ovulation APs, and the ribosomal RNA-depleted poly (A)+RNA were prepared to assemble next-generation sequencing libraries. The bovine APs expressed 12,769 annotated genes at pre- or post-ovulation. The sum of the reads per kilobase of exon model per million mapped reads (RPKM) values of all transcriptomes were 599,676 ± 38,913 and 668,209 ± 23,690, and 32.2 ± 2.6% and 44.0 ± 4.4% of these corresponded to the AP hormones in the APs of pre- and post-ovulation heifers, respectively. The bovine AP showed differential expression of 396 genes (P<0.05) in the pre- and post-ovulation APs. The 396 genes included two G-protein-coupled receptor (GPCR) genes (GPR61 and GPR153) and those encoding 13 binding proteins. The AP also expressed 259 receptor and other 364 binding proteins. Moreover, ingenuity pathway analysis for the 396 genes revealed (P=2.4 × 10−3) a canonical pathway linking GPCR to cytoskeleton reorganization, actin polymerization, microtubule growth, and gene expression. Thus, the present study clarified the novel genes found to be differentially expressed before and after ovulation and clarified an important pathway in the AP.
doi:10.1292/jvms.16-0531
PMCID: PMC5487774  PMID: 28442638
G-protein-coupled receptor; Rho family GTPase; RNA-seq; ruminant
24.  Van der Waals engineering of ferromagnetic semiconductor heterostructures for spin and valleytronics 
Science Advances  2017;3(5):e1603113.
A van der Waals heterostructure of monolayer WSe2 and ferromagnetic CrI3 enables exceptional control of valley pseudospin.
The integration of magnetic material with semiconductors has been fertile ground for fundamental science as well as of great practical interest toward the seamless integration of information processing and storage. We create van der Waals heterostructures formed by an ultrathin ferromagnetic semiconductor CrI3 and a monolayer of WSe2. We observe unprecedented control of the spin and valley pseudospin in WSe2, where we detect a large magnetic exchange field of nearly 13 T and rapid switching of the WSe2 valley splitting and polarization via flipping of the CrI3 magnetization. The WSe2 photoluminescence intensity strongly depends on the relative alignment between photoexcited spins in WSe2 and the CrI3 magnetization, because of ultrafast spin-dependent charge hopping across the heterostructure interface. The photoluminescence detection of valley pseudospin provides a simple and sensitive method to probe the intriguing domain dynamics in the ultrathin magnet, as well as the rich spin interactions within the heterostructure.
doi:10.1126/sciadv.1603113
PMCID: PMC5451195
van der Waals heterostructure; ferromagnetic semiconductor; Valleytronics; Spintronics; 2D materials; monolayer semiconductor; magnetic proximity effect; Exchange interaction; ultrafast charge transfer
25.  Oxidative Trans-to-Cis Isomerization of Olefin in Polyketide Biosynthesis** 
Geometric isomerization can expand the scope of biological activities of natural products. The observed chemical diversity among the pseurotin-type fungal secondary metabolites is part generated by a trans-to-cis isomerization of an olefin. In vitro characterizations of pseurotin biosynthetic enzymes revealed that the glutathione S-transferase PsoE required a participation of the bifunctional C-methyltransferase–epoxidase PsoF to complete the trans-to-cis isomerization of a pathway intermediate, presynerazol. The PsoE–glutathione–presynerazol complex crystal structure indicated stereospecific glutathione–presynerazol conjugate formation is the principal function of PsoE. Moreover, PsoF was identified to have an additional, unexpected oxidative isomerase activity, making it a trifunctional enzyme that is key to the complexity generation in pseurotin biosynthesis. Through the study, we identified a novel mechanism of accomplishing a seemingly simple trans-to-cis isomerization reaction.
Graphical Abstract
In vitro study revealed that the glutathione S-transferase PsoE required the bifunctional PsoF to complete the isomerization of a pseurotin biosynthetic pathway intermediate. The PsoE crystal structure indicated that the intermediate–glutathione conjugation as the sole function of PsoE. PsoF was identified with an additional oxidative isomerase activity, making it a trifunctional enzyme key to complexity generation in pseurotin biosynthesis.
doi:10.1002/anie.201600940
PMCID: PMC5089960  PMID: 27072782
isomerization; glutathione S-transferase; multifunctional enzyme; biosynthesis; fungal natural product

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