bluuebunny/crossref_metadata_2025 huggingface dataset:
Variations of Equatorial Shear, Stratification, and Turbulence Within a Tropical Instability Wave Cycle
Authors: Inoue Ryuichiro , Lien Ren‐Chieh , Moum James N. , Perez Renellys C. , Gregg Michael C.
Published: February 2019

Equatorial Internal Wave Experiment observations at 0°, 140°W from October 2008 to February 2009 captured modulations of shear, stratification, and turbulence above the Equatorial Undercurrent by a series of tropical instability waves (TIWs). Analyzing these observations in terms of a four‐phase TIW cycle, we found that shear and stratification within the deep‐cycle layer being weakest in the middle of the N‐S phase (transition from northward to southward flow) and strongest in the late S phase (southward flow) and the early S‐N phase (transition from southward to northward flow). Turbulence was modulated but showed less dependence on the TIW cycle. The vertical diffusivity (KT) was largest during the N (northward flow) and N‐S phases, when stratification was weak, despite weak shear, and was smallest from the late S phase to the S‐N phase, when stratification was strong, despite strong shear. This tendency was less clear in turbulent heat flux because vertical temperature gradients were small at times when KT was large, and large when KT was small. We investigated the dynamics of shear and stratification variations within the TIW cycle by using an ocean general circulation model forced with observed winds. The model successfully reproduced the observed strong shear and stratification in the S phase, except for a small phase difference. The strong shear is explained by vortex stretching by TIWs. The strong stratification is explained by meridional and vertical advection.
Effects of Space Weathering and Porosity on the Far‐UV Reflectance of Amundsen Crater
Authors: Byron B. D. , Retherford K. D. , Greathouse T. K. , Mandt K. E. , Hendrix A. R. , Poston M. J. , Liu Y. , Cahill J. T. , Mazarico E.
Published: February 2019

The lunar South Pole crater Amundsen is a prime location to study the effects of space weathering in the far ultraviolet. Amundsen's equator‐facing terrace walls are highly illuminated while the northern side of the crater has permanently shaded regions (PSRs). Using data from the Lunar Reconnaissance Orbiter Lyman Alpha Mapping Project, we investigate signatures of space weathering in different regions of Amundsen. We find that regions of the surface that receive large amounts of solar illumination and solar wind flux (e.g., the southern terrace walls) display high Lyman‐α albedos and blue spectral slopes in the 175–190‐nm region, indicative of increased regolith maturity due to solar wind weathering and thermal cycling. Amundsen's PSRs, however, receive no direct solar illumination and very little solar wind flux and have a lower albedo across Lyman Alpha Mapping Project's entire band pass (57–197 nm) than illuminated regions of the crater. We conclude that the low PSR albedos correspond to high regolith porosity in the PSRs. These PSRs are extremely cold regions with very minor thermal cycling. Thermal cycling might be a process that reduces porosity in regions of the crater exposed to a wide range of temperatures, thus increasing their albedos across the entire wavelength range. However, our analysis of the present data set was unable to uniquely identify its role. The low albedos in the PSRs may also result from extreme charging effects inside the PSRs, causing lofting and redeposition of dust, as well as dielectric breakdown, which would act to increase regolith porosity.
Beyond Classical Observations in Hydrogeology: The Advantages of Including Exchange Flux, Temperature, Tracer Concentration, Residence Time, and Soil Moisture Observations in Groundwater Model Calibration
Authors: Schilling Oliver S. , Cook Peter G. , Brunner Philip
Published: February 2019

Traditionally, groundwater and surface water flow models have been calibrated against two observation types: hydraulic heads and surface water discharge. It has repeatedly been demonstrated, however, that these classical observations do not contain sufficient information to calibrate flow models. To reduce the predictive uncertainty of flow models, the consideration of other observation types constitutes a promising way forward. Despite the ever‐increasing availability of other observation types, however, they are still unconventional when it comes to flow model calibration. By reviewing studies that included nonclassical observations in flow model calibration, benefits and challenges associated with their integration in flow model calibration were identified, and their information content was analyzed. While explicit simulation of mass transport processes in flow models poses challenges, even simplified approaches to integrate tracer concentrations yield significantly better calibration results than using only classical observations. For a majority of calibrated flow models, observations of tracer concentrations and of exchange fluxes were beneficial. Temperature observations improved the simulation of heat transport but often worsened all other model outcomes. Only when temperature observations were made within 2 m of the surface water‐groundwater interface did they have the potential to also improve flow and mass transport simulations. Surprisingly, many models were calibrated manually rather than with the widely available, mathematically robust and automated tools. There is a clear need for more systematic implementation of unconventional observations and automated flow model calibration as well as for more systematic quantification of the information content of unconventional observations.
Striking Variation in the Provenance of the Lower and Upper Cretaceous Turbidites in the Central Pontides (Northern Turkey) Related to the Opening of the Black Sea
Authors: Akdoğan R. , Okay A. I. , Dunkl I.
Published: February 2019

The Lower and Upper Cretaceous turbidites cover large areas in the central Pontides (north‐central Turkey). The Lower Cretaceous turbidites are over 2 km thick and are exposed in an area of 400 × 90 km. The Upper Cretaceous (Campanian‐Maastrichtian) forearc turbidites are up to 1,200 m thick and crop out in NW‐SE trending elongate basins about 40 km wide, extending along the central and eastern Pontides. We present new detrital zircon U–Pb ages, petrography, and paleocurrent measurements from the Campanian‐Maastrichtian turbidites and compare them to those from the Lower Cretaceous turbidites. The Campanian‐Maastrichtian sandstones are dominated by carbonate and magmatic lithic grains. The paleocurrents indicate paleoflow directions parallel to the axis of the basin. The sandstones are dominated by Late Cretaceous zircons indicating derivation mainly from the coeval magmatic arc. In contrast, the Lower Cretaceous sandstones are dominated by quartz and feldspar, and paleocurrents indicate southward transport. The detrital zircons in the Lower Cretaceous sandstones are mainly Archean and Paleoproterozoic, indicating that in the Early Cretaceous, the source of turbidites was from the Archean‐Paleoproterozoic Ukrainian Shield to the north. After the opening of the Black Sea in the Late Cretaceous, the connection between the Pontides and the East European Platform was severed and the Campanian‐Maastrichtian turbidites were sourced principally from the magmatic arc in the Pontides. Our results indicate that the Campanian‐Maastrichtian turbidites represent the first turbiditic sequence deposited after the opening of the Black Sea.
Bridging the Weather-to-Climate Prediction Gap
Authors: Mariotti Annarita , Barnes Elizabeth , Chang Edmund , Lang Andrea , Dirmeyer Paul , Pegion Kathy , Barrie Daniel , Baggett Cory
Published: February 2019

A task force of researchers set out to bridge the gap between the 2-week weather forecast and long-term climate predictions; their findings could help in forecasting the likelihood of extreme events.
White House Science Adviser Outlines Vision
Authors: Showstack Randy
Published: February 2019

In his first major address, the director of the White House Office of Science and Technology Policy emphasized the roles of the private sector and the federal government.
Activation of mTORC1 in subchondral bone preosteoblasts promotes osteoarthritis by stimulating bone sclerosis and secretion of CXCL12
Authors: Lin Chuangxin , Liu Liangliang , Zeng Chun , Cui Zhong-Kai , Chen Yuhui , Lai Pinling , Wang Hong , Shao Yan , Zhang Haiyan , Zhang Rongkai , Zhao Chang , Fang Hang , Cai Daozhang , Bai Xiaochun
Published: February 2019

Increasing evidences show that aberrant subchondral bone remodeling plays an important role in the development of osteoarthritis (OA). However, how subchondral bone formation is activated and the mechanism by which increased subchondral bone turnover promotes cartilage degeneration during OA remains unclear. Here, we show that the mechanistic target of rapamycin complex 1 (mTORC1) pathway is activated in subchondral bone preosteoblasts (Osterix+) from OA patients and mice. Constitutive activation of mTORC1 in preosteoblasts by deletion of the mTORC1 upstream inhibitor, tuberous sclerosis 1, induced aberrant subchondral bone formation, and sclerosis with little-to-no effects on articular cartilage integrity, but accelerated post-traumatic OA development in mice. In contrast, inhibition of mTORC1 in preosteoblasts by disruption of Raptor (mTORC1-specific component) reduced subchondral bone formation and cartilage degeneration, and attenuated post-traumatic OA in mice. Mechanistically, mTORC1 activation promoted preosteoblast expansion and Cxcl12 secretion, which induced subchondral bone remodeling and cartilage degeneration during OA. A Cxcl12-neutralizing antibody reduced cartilage degeneration and alleviated OA in mice. Altogether, these findings demonstrate that mTORC1 activation in subchondral preosteoblasts is not sufficient to induce OA, but can induce aberrant subchondral bone formation and secrete of Cxcl12 to accelerate disease progression following surgical destabilization of the joint. Pharmaceutical inhibition of the pathway presents a promising therapeutic approach for OA treatment.
Succinylation-dependent mitochondrial translocation of PKM2 promotes cell survival in response to nutritional stress
Authors: Qi Hailong , Ning Xianling , Yu Chang , Ji Xin , Jin Yan , McNutt Michael A. , Yin Yuxin
Published: February 2019

Tumor growth and progression is characteristically associated with the synergistic effects of uncontrolled cellular proliferation and cell survival under stress. Pyruvate kinase M2 (PKM2) contributes to both of these effects. However, the specific mechanism by which PKM2 promotes uncontrolled proliferation or cell survival under stress in different nutritional environments is unclear. We show that succinylation mediated mitochondrial translocation of PKM2 under glucose starvation plays a role in switching the cellular machinery from proliferation to cell survival mode and vice versa. Mitochondrial PKM2 inhibits ubiquitination-mediated degradation of voltage-dependent anion channel 3 (VDAC3) and increases mitochondrial permeability to generate more ATP for cell survival under nutritional depletion. We found there is a positive correlation of upregulation of mitochondrial PKM2 and upregulation of VDAC3 in human colon cancer. This shows the mechanisms identified in this study in fact play a role in neoplastic biology. We therefore developed a small molecule designated compound 8 that blocks mitochondrial translocation of PKM2 and inhibits tumor development. Our data suggest that blocking PKM2 mitochondrial function with a small molecule inhibitor has potential for cancer treatment.
ZFP57 suppress proliferation of breast cancer cells through down-regulation of MEST-mediated Wnt/β-catenin signalling pathway
Authors: Chen Lie , Wu Xiaowei , Xie Hui , Yao Na , Xia Yiqin , Ma Ge , Qian Mengjia , Ge Han , Cui Yangyang , Huang Yue , Wang Shui , Zheng Mingjie
Published: February 2019

Activation of oncogenes by promoter hypomethylation plays an important role in tumorigenesis. Zinc finger protein 57 (ZFP57), a member of KRAB-ZFPs, could maintain DNA methylation in embryonic stem cells (ESCs), although its role and underlying mechanisms in breast cancer are not well understood. In this study, we found that ZFP57 had low expression in breast cancer, and overexpression of ZFP57 could inhibit the proliferation of breast cancer cells by inhibiting the Wnt/β-catenin pathway. MEST was validated as the direct target gene of ZFP57 and MEST may be down-regulated by ZFP57 through conserving DNA methylation. Furthermore, overexpression of MEST could restore the tumour-suppressed and the Wnt/β-catenin pathway inactivated effects of ZFP57. ZFP57-MEST and the Wnt/β-catenin pathway axis are involved in breast tumorigenesis, which may represent a potential diagnostic biomarker, and provide a new insight into a novel therapeutic strategy for breast cancer patients.
circTADA2As suppress breast cancer progression and metastasis via targeting miR-203a-3p/SOCS3 axis
Authors: Xu Jian-Zhen , Shao Chang-Chun , Wang Xiao-Jia , Zhao Xing , Chen Jun-Qing , Ouyang Yan-Xiu , Feng Jun , Zhang Fan , Huang Wen-He , Ying Qian , Chen Chun-Fa , Wei Xiao-Long , Dong Hong-Yan , Zhang Guo-Jun , Chen Min
Published: February 2019

More and more evidence indicates that circular RNAs (circRNAs) have important roles in several diseases, especially in cancers. However, their involvement remains to be investigated in breast cancer. Through screening circRNA profile, we identified 235 differentially expressed circRNAs in breast cancer. Subsequently, we explored the clinical significance of two circTADA2As in a large cohort of triple-negative breast cancer (TNBC), and performed functional analysis of circTADA2A-E6 in vitro and in vivo to support clinical findings. Finally, we evaluated the effect of circTADA2A-E6 on miR-203a-3p and its target gene SOCS3. We detected two circRNAs, circTADA2A-E6 and circTADA2A-E5/E6, which were among the top five differentially expressed circRNAs in breast cancer. They were consistently and significantly decreased in a large cohort of breast cancer patients, and their downregulation was associated with poor patient survival for TNBC. Especially, circTADA2A-E6 suppressed in vitro cell proliferation, migration, invasion, and clonogenicity and possessed tumor-suppressor capability. circTADA2A-E6 preferentially acted as a miR-203a-3p sponge to restore the expression of miRNA target gene SOCS3, resulting in a less aggressive oncogenic phenotype. circTADA2As as promising prognostic biomarkers in TNBC patients, and therapeutic targeting of circTADA2As/miRNA/mRNA network may be a potential strategy for the treatment of breast cancer.
Microglia as modulators of exosomal alpha-synuclein transmission
Authors: Xia Yun , Zhang Guoxin , Han Chao , Ma Kai , Guo Xingfang , Wan Fang , Kou Liang , Yin Sijia , Liu Ling , Huang Jinsha , Xiong Nian , Wang Tao
Published: February 2019

Recent researches regarding to exosomal involvement in alpha-synuclein (α-syn) transmission relating to the pathological process of Parkinson’s disease (PD) have attracted considerable attention. It is highly desirable to make clear the diffusion process and cellular uptake of α-syn-associated exosomes and the underlying mechanism of exosomes-involved communication in the synucleinopathy pathogenesis. To determine the contribution of α-syn-associated exosomes to the initiation and progression of PD, plasma exosomes derived from PD patients were stereotaxically injected into the striatum of mice brains. Exosomes extracted from plasma diagnosed with PD contained monomeric and oligomeric α-syn. Here, we found that microglia display a high potency for uptake of plasma exosomes derived from PD patients, and therefore could be activated by exogenous exosomes in vitro and in vivo. In addition, immunofluorescent double staining verified the transfer of exogenous human exosomal α-syn to neurons. The release of human exosomal α-syn from microglia may facilitate this propagation. Finally, we described a mechanism underlying this potential role of microglia in the transmission of exosomal α-syn. Specifically, exogenous exosomes were found to dysregulate autophagy of the BV2 mouse microglia cell line with presentation of increased accumulation of intracellular α-syn and accelerated secretion of α-syn into extracellular space. These results suggest that microglia play a crucial role in the transmission of α-syn via exosomal pathways, in additional to idea that the progression of PD may be altered by the modulation of exosome secretion and/or microglial states.
m6A methylation controls pluripotency of porcine induced pluripotent stem cells by targeting SOCS3/JAK2/STAT3 pathway in a YTHDF1/YTHDF2-orchestrated manner
Authors: Wu Ruifan , Liu Youhua , Zhao Yuanling , Bi Zhen , Yao Yongxi , Liu Qing , Wang Fengqin , Wang Yizhen , Wang Xinxia
Published: February 2019

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, disease treatment, and organ transplantation. As the ethical issue of human ESCs and similarity of pig in human genome and physiological characteristics, the porcine iPSCs (piPSCs) have become an ideal alternative study model. N6-methyladenosine (m6A) methylation is the most prevalent modification in eukaryotic mRNAs, regulating the self-renewal and differentiation of pluripotency stem cells. However, the explicit m6A-regulating machinery remains controversial. Here, we demonstrate that m6A modification and its modulators play a crucial role in mediating piPSCs pluripotency. In brief, loss of METTL3 significantly impairs self-renewal and triggers differentiation of piPSCs by interfering JAK2 and SOCS3 expression, further inactivating JAK2–STAT3 pathway, which then blocks the transcription of KLF4 and SOX2. We identify that both of JAK2 and SOSC3 have m6A modification at 3′UTR by m6A-seq analysis. Dual-luciferase assay shows that METTL3 regulates JAK2 and SOCS3 expression in an m6A-dependent way. RIP-qPCR validates JAK2 and SOCS3 are the targets of YTHDF1 and YTHDF2, respectively. SiMETTL3 induced lower m6A levels of JAK2 and SOCS3 lead to the inhibition of YTHDF1-mediated JAK2 translation and the block of YTHDF2-dependent SOCS3 mRNA decay. Subsequently, the altered protein expressions of JAK2 and SOCS3 inhibit JAK2–STAT3 pathway and then the pluripotency of piPSCs. Collectively, our work uncovers the critical role of m6A modification and its modulators in regulating piPSCs pluripotency and provides insight into an orchestrated network linking the m6A methylation and SOCS3/JAK2/STAT3 pathway in pluripotency regulation.
Single gyroid-structured metallic nanoporous spheres fabricated from double gyroid-forming block copolymers via templated electroless plating
Authors: Yang Kai-Chieh , Yao Cheng-Thai , Huang Liang-Yu , Tsai Jing-Cherng , Hung Wei-Song , Hsueh Han-Yu , Ho Rong-Ming
Published: February 2019

Herein, we suggest a methodology for the fabrication of well-defined metallic nanoporous spheres with single gyroid (SG) structure by simply using self-assembled diblock copolymer with double gyroid (DG) structure as a template for electroless plating. Note that owing to the consideration of thermodynamic stability, the self-assembly of diblock copolymers gives rise to a DG phase instead of an SG phase. By controlling the nucleus density for the reduction of Pd ions within the diblock copolymer template, SG-structured Ni can be easily fabricated through the nucleation and growth processes. Consequently, nanoporous Ni spheres with uniform pore sizes and high specific surface areas can be fabricated. Moreover, nanoporous Ni spheres with controlled microscale particle sizes can thus be obtained by controlling the reduction time for the growth of Ni, which enables the feasibility of recyclability via magnetic fields. The combination of structural and morphological characteristics of the fabricated nanoporous Ni spheres make them appealing for use in a wide variety of applications, such as high-efficiency and well selectivity hydrogenation catalysts with recyclability due to their narrow pore size distributions, high specific surface areas, 3D curved surfaces, and controlled microscale particle sizes.
High capacity silicon anodes enabled by MXene viscous aqueous ink
Authors: Zhang Chuanfang , Park Sang-Hoon , Seral‐Ascaso Andrés , Barwich Sebastian , McEvoy Niall , Boland Conor S. , Coleman Jonathan N. , Gogotsi Yury , Nicolosi Valeria
Published: February 2019

The ever-increasing demands for advanced lithium-ion batteries have greatly stimulated the quest for robust electrodes with a high areal capacity. Producing thick electrodes from a high-performance active material would maximize this parameter. However, above a critical thickness, solution-processed films typically encounter electrical/mechanical problems, limiting the achievable areal capacity and rate performance as a result. Herein, we show that two-dimensional titanium carbide or carbonitride nanosheets, known as MXenes, can be used as a conductive binder for silicon electrodes produced by a simple and scalable slurry-casting technique without the need of any other additives. The nanosheets form a continuous metallic network, enable fast charge transport and provide good mechanical reinforcement for the thick electrode (up to 450 µm). Consequently, very high areal capacity anodes (up to 23.3 mAh cm−2) have been demonstrated.
Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming
Authors: Muraoka Naoto , Nara Kaori , Tamura Fumiya , Kojima Hidenori , Yamakawa Hiroyuki , Sadahiro Taketaro , Miyamoto Kazutaka , Isomi Mari , Haginiwa Sho , Tani Hidenori , Kurotsu Shota , Osakabe Rina , Torii Satoru , Shimizu Shigeomi , Okano Hideyuki , Sugimoto Yukihiko , Fukuda Keiichi , Ieda Masaki
Published: February 2019

Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging.
Targeting MC1R depalmitoylation to prevent melanomagenesis in redheads
Authors: Chen Shuyang , Han Changpeng , Miao Xiao , Li Xin , Yin Chengqian , Zou Junrong , Liu Min , Li Shanshan , Stawski Lukasz , Zhu Bo , Shi Qiong , Xu Zhi-Xiang , Li Chunying , Goding Colin R. , Zhou Jun , Cui Rutao
Published: February 2019

Some genetic melanocortin-1 receptor (MC1R) variants responsible for human red hair color (RHC-variants) are consequently associated with increased melanoma risk. Although MC1R signaling is critically dependent on its palmitoylation primarily mediated by the ZDHHC13 protein-acyl transferase, whether increasing MC1R palmitoylation represents a viable therapeutic target to limit melanomagenesis in redheads is unknown. Here we identify a specific and efficient in vivo strategy to induce MC1R palmitoylation for therapeutic benefit. We validate the importance of ZDHHC13 to MC1R signaling in vivo by targeted expression of ZDHHC13 in C57BL/6J-MC1RRHCmice and subsequently inhibit melanomagenesis. By identifying APT2 as the MC1R depalmitoylation enzyme, we are able to demonstrate that administration of the selective APT2 inhibitor ML349 treatment efficiently increases MC1R signaling and represses UVB-induced melanomagenesis in vitro and in vivo. Targeting APT2, therefore, represents a preventive/therapeutic strategy to reduce melanoma risk, especially in individuals with red hair.
Negative dielectric constant of water confined in nanosheets
Authors: Sugahara Akira , Ando Yasunobu , Kajiyama Satoshi , Yazawa Koji , Gotoh Kazuma , Otani Minoru , Okubo Masashi , Yamada Atsuo
Published: February 2019

Electric double-layer capacitors are efficient energy storage devices that have the potential to account for uneven power demand in sustainable energy systems. Earlier attempts to improve an unsatisfactory capacitance of electric double-layer capacitors have focused on meso- or nanostructuring to increase the accessible surface area and minimize the distance between the adsorbed ions and the electrode. However, the dielectric constant of the electrolyte solvent embedded between adsorbed ions and the electrode surface, which also governs the capacitance, has not been previously exploited to manipulate the capacitance. Here we show that the capacitance of electric double-layer capacitor electrodes can be enlarged when the water molecules are strongly confined into the two-dimensional slits of titanium carbide MXene nanosheets. Using electrochemical methods and theoretical modeling, we find that dipolar polarization of strongly confined water resonantly overscreens an external electric field and enhances capacitance with a characteristically negative dielectric constant of a water molecule.
A sequestered fusion peptide in the structure of an HIV-1 transmitted founder envelope trimer
Authors: Ananthaswamy Neeti , Fang Qianglin , AlSalmi Wadad , Jain Swati , Chen Zhenguo , Klose Thomas , Sun Yingyuan , Liu Yue , Mahalingam Marthandan , Chand Subhash , Tovanabutra Sodsai , Robb Merlin L. , Rossmann Michael G. , Rao Venigalla B.
Published: February 2019

The envelope protein of human immunodeficiency virus-1 (HIV-1) and its fusion peptide are essential for cell entry and vaccine design. Here, we describe the 3.9-Å resolution structure of an envelope protein trimer from a very early transmitted founder virus (CRF01_AE T/F100) complexed with Fab from the broadly neutralizing antibody (bNAb) 8ANC195. The overall T/F100 trimer structure is similar to other reported “closed” state prefusion trimer structures. In contrast, the fusion peptide, which is exposed to solvent in reported closed structures, is sequestered (buried) in the hydrophobic core of the T/F100 trimer. A buried conformation has previously been observed in “open” state structures formed after CD4 receptor binding. The T/F100 trimer binds poorly to bNAbs including the fusion peptide-specific bNAbs PGT151 and VRC34.01. The T/F100 structure might represent a prefusion state, intermediate between the closed and open states. These observations are relevant to mechanisms of HIV-1 transmission and vaccine design.
Orthobunyavirus spike architecture and recognition by neutralizing antibodies
Authors: Hellert Jan , Aebischer Andrea , Wernike Kerstin , Haouz Ahmed , Brocchi Emiliana , Reiche Sven , Guardado-Calvo Pablo , Beer Martin , Rey Félix A.
Published: February 2019

Orthobunyaviruses (OBVs) form a distinct genus of arthropod-borne bunyaviruses that can cause severe disease upon zoonotic transmission to humans. Antigenic drift or genome segment re-assortment have in the past resulted in new pathogenic OBVs, making them potential candidates for causing emerging zoonoses in the future. Low-resolution electron cryo-tomography studies have shown that OBV particles feature prominent trimeric spikes, but their molecular organization remained unknown. Here we report X-ray crystallography studies of four different OBVs showing that the spikes are formed by an N-terminal extension of the fusion glycoprotein Gc. Using Schmallenberg virus, a recently emerged OBV, we also show that the projecting spike is the major target of the neutralizing antibody response, and provide X-ray structures in complex with two protecting antibodies. We further show that immunization of mice with the spike domains elicits virtually sterilizing immunity, providing fundamental knowledge essential in the preparation for potential newly emerging OBV zoonoses.
A silicon-on-insulator slab for topological valley transport
Authors: He Xin-Tao , Liang En-Tao , Yuan Jia-Jun , Qiu Hao-Yang , Chen Xiao-Dong , Zhao Fu-Li , Dong Jian-Wen
Published: February 2019

Backscattering suppression in silicon-on-insulator (SOI) is one of the central issues to reduce energy loss and signal distortion, enabling for capability improvement of modern information processing systems. Valley physics provides an intriguing way for robust information transfer and unidirectional coupling in topological nanophotonics. Here we realize topological transport in a SOI valley photonic crystal slab. Localized Berry curvature near zone corners guarantees the existence of valley-dependent edge states below light cone, maintaining in-plane robustness and light confinement simultaneously. Topologically robust transport at telecommunication is observed along two sharp-bend interfaces in subwavelength scale, showing flat-top high transmission of ~10% bandwidth. Topological photonic routing is achieved in a bearded-stack interface, due to unidirectional excitation of valley-chirality-locked edge state from the phase vortex of a nanoscale microdisk. These findings show the prototype of robustly integrated devices, and open a new door towards the observation of non-trivial states even in non-Hermitian systems.
Publisher Correction: Pharmacological reactivation of MYC-dependent apoptosis induces susceptibility to anti-PD-1 immunotherapy
Authors: Haikala Heidi M. , Anttila Johanna M. , Marques Elsa , Raatikainen Tiina , Ilander Mette , Hakanen Henna , Ala-Hongisto Hanna , Savelius Mariel , Balboa Diego , Von Eyss Bjoern , Eskelinen Vilja , Munne Pauliina , Nieminen Anni I. , Otonkoski Timo , Schüler Julia , Laajala Teemu D. , Aittokallio Tero , Sihto Harri , Mattson Johanna , Heikkilä Päivi , Leidenius Marjut , Joensuu Heikki , Mustjoki Satu , Kovanen Panu , Eilers Martin , Leverson Joel D. , Klefström Juha
Published: February 2019

The original version of this Article contained an error in Fig. 7. In panel b, the survival curves were shifted relative to the y axis. This error has been corrected in both the PDF and HTML versions of the Article.
Charged grain boundary transitions in ionic ceramics for energy applications
Authors: Vikrant K. S. N. , García R. Edwin
Published: February 2019

Surfaces and interfaces in ionic ceramics play a pivotal role in defining the transport limitations in many of the existing and emerging applications in energy-related systems such as fuel cells, rechargeable batteries, as well as advanced electronics such as those found in semiconducting, ferroelectric, and piezotronic applications. Here, a variational framework has been developed to understand the effects of the intrinsic and extrinsic ionic species and point defects on the structural and electrochemical stability of grain boundaries in polycrystalline ceramics. The theory predicts the conditions for the interfacial electrochemical and structural stability and phase transitions of charged interfaces and quantifies the properties induced by the broad region of electrochemical influence in front of a grain boundary capable of spanning anywhere from a few angtroms to entire grains. We demonstrate the validity of this theory for YxZr1−xO2−x/2, cubic yttria stabilized zirconia. For small crystallographic misorientations, sharp Debye-type interfaces, D(1):$${\mathrm{C}}^{VY}{\mathrm{S}}^{\underline {VY} }$$

C

V
Y

S

V
Y

̲

, are favored and promote high ionic conductivity in materials in polycrystalline form. For large grain boundary misorientations and large amounts of [Y2O3] substitutions, three Mott–Schottky interfaces, MS(2):$${\mathrm{C}}^{VY\,\underline h e}{\mathrm{S}}^{\underline {VYh} e}$$

C

V
Y

h

̲

e

S

V
Y
h

̲

e

, MS(2):$${\mathrm{C}}^{VY\underline h e}{\mathrm{S}}^{e\underline {hVY} }$$

C

V
Y

h

̲

e

S

e

h
V
Y

̲

, and MS(2):$${\mathrm{C}}^{VY}{\mathrm{S}}^{\underline h e}$$

C

V
Y

S

h

̲

e

are responsible for controlling grain boundary segregation and the observed poor macroscopic ionic transport, in great agreement with the scientific literature.
Electron engineering of metallic multiferroic polarons in epitaxial BaTiO3
Authors: Xu Tao , Shimada Takahiro , Araki Yasumitsu , Mori Masataka , Fujimoto Gen , Wang Jie , Zhang Tong-Yi , Kitamura Takayuki
Published: February 2019

The coexistence of ferroelectricity, conductivity, and magnetism in a single-phase material has attracted considerable attention due to fundamental interest and tremendous technological potential. However, their mutually exclusive mechanisms hinder the discovery of multifunctional conducting multiferroics. Here, we propose a new material design approach for electron engineering to enable these conflicting properties to coexist. We use first principles calculations to demonstrate that appropriate mechanical strain can turn the excess electrons in doped BaTiO3 from a free-carrier configuration to a localized polaronic state by modulating the electron–phonon coupling. The resulting localized spin-polarized electron survives the host ferroelectricity and consequently manifests as a multiferroic polaron. The multiferroic properties coexist with the electronic conductivity arising from the high-hopping mobility of the polaron, which enables the doped epitaxial BaTiO3 to act as a multiferroic conducting material. This mechanical control over the electron configuration is a potential path toward unusual coexisting properties.
Spin-polarized magneto-electronic properties in buckled monolayer GaAs
Authors: Chung Hsien-Ching , Chiu Chih-Wei , Lin Ming-Fa
Published: February 2019

We develop the generalized tight-binding model to fully explore the magneto-electronic properties of monolayer GaAs, where the buckled structure, multi-orbital chemical bondings, spin-orbit coupling, electric field, and magnetic field are considered simultaneously. The diverse magnetic quantization covers three groups of spin-polarized Landau levels (LLs) near the Fermi level, with the unique initial energies, LL degeneracy, energy spacings, magnetic-field-dependence, and spin splitting. Furthermore, the Landau state probabilities exhibit specific oscillation patterns, being composed of the localization centers, node regularities, and energy-dependent variations of the dominating orbitals. The density of states directly reflects the main features of the LL energy spectra in the form, height, number, and frequency of the spin-split delta-function-like prominent peaks. The electric field leads to the monotonous/nonmonotonous LL energy dispersions, LL crossing behavior, gap modulation, phase transition and enhancement of spin splitting. The complex gap modulations and even semiconductor-semimetal transitions are attributed to the strong competition among the intrinsic interactions, magnetic field, and electric field. Such predicted magneto-electronic properties could be verified by scanning tunneling spectroscopy and are helpful in designing the top-gated and phase-change electronic devices.
Nash Equilibria in the Response Strategy of Correlated Games
Authors: Correia A. D. , Stoof H. T. C.
Published: February 2019

In nature and society, problems that arise when different interests are difficult to reconcile are modeled in game theory. While most applications assume that the players make decisions based only on the payoff matrix, a more detailed modeling is necessary if we also want to consider the influence of correlations on the decisions of the players. We therefore extend here the existing framework of correlated strategies by giving the players the freedom to respond to the instructions of the correlation device by probabilistically following or not following its suggestions. This creates a new type of games that we call “correlated games”. The associated response strategies that can solve these games turn out to have a rich structure of Nash equilibria that goes beyond the correlated equilibrium and pure or mixed-strategy solutions and also gives better payoffs in certain cases. We here determine these Nash equilibria for all possible correlated Snowdrift games and we find these solutions to be describable by Ising models in thermal equilibrium. We believe that our approach paves the way to a study of correlations in games that uncovers the existence of interesting underlying interaction mechanisms, without compromising the independence of the players.
Identification of a Xist silencing domain by Tiling CRISPR
Authors: Wang Yang , Zhong Yang , Zhou Yingyao , Tanaseichuk Olga , Li Zhizhong , Zhao Jing Crystal
Published: February 2019

Despite essential roles played by long noncoding RNAs (lncRNAs) in development and disease, methods to determine lncRNA cis-elements are lacking. Here, we developed a screening method named “Tiling CRISPR” to identify lncRNA functional domains. Using this approach, we identified Xist A-Repeats as the silencing domain, an observation in agreement with published work, suggesting Tiling CRISPR feasibility. Mechanistic analysis suggested a novel function for Xist A-repeats in promoting Xist transcription. Overall, our method allows mapping of lncRNA functional domains in an unbiased and potentially high-throughput manner to facilitate the understanding of lncRNA functions.
Recommendation of long-term and systemic management according to the risk factors in rectal NETs patients
Authors: Kojima Motohiro , Chen Yu , Ikeda Koji , Tsukada Yuichiro , Takahashi Daigoro , Kawano Shingo , Amemiya Kota , Ito Masaaki , Ohki Rieko , Ochiai Atsushi
Published: February 2019

Rectal neuroendocrine tumors (NETs) are often found as small lesions, which can be treated by endoscopic resection. However, high risk cases with lymph node (LN) metastasis are indication of radical surgery. Furthermore, rectal NETs are often associated with late recurrences and/or multiple cancer development. Therefore, proper surgical indication and patients’ management are required. We investigated the clinicopathological features of 79 rectal NET cases in order to elucidate risk factors for synchronous LN metastasis, recurrence, and multiple cancers. Recently, we reported that in pancreatic NET patients, a loss of heterozygosity (LOH) in PHLDA3 was associated with poorer prognosis, and that LOH of both PHLDA3 and MEN1 was frequently observed. Therefore, PHLDA3 and MEN1 LOH were also assessed in rectal NET patients for their association with clinicopathological features. Of the 79 patients, LN metastases were found in 12.7%, recurrences in 3.8%, and multiple cancers in 30.4% of the subjects. PHLDA3 and MEN1 LOH were found in 60.0% and 66.7% of the subjects, respectively. Lymphatic invasion and WHO classification 2010 were found to be independent risks for LN metastasis. There were three cases of recurrence, all of which occurred more than 3 years after resection and two of which exhibited LN metastasis. Older age and LOH in PHLDA3 were associated with the presence of multiple cancers. Long-term and systemic management of patients with rectal NETs is therefore recommended in accordance with these risk factors.
A vegetation configuration pattern with a high-efficiency purification ability for TN, TP, AN, AP, and COD based on comprehensive assessment results
Authors: Hou Guirong , Bi Huaxing , Yu Xinxiao , Jia Guodong , Wang Dandan , Zhang Zhenyao , Liu Ziqiang
Published: February 2019

To identify a vegetation configuration pattern with a high-efficiency purification ability for total nitrogen (TN), available nitrogen (AN), total phosphorous (TP), available phosphorous (AP), and chemical oxygen demand (COD) based on comprehensive assessment results, a water discharge experiment was performed in the Luan River in China with the following riparian forests: I, pure broad-leaved; II, mixed broad-leaved; III, mixed coniferous and broad-leaved; IV, mixed coniferous; and V, pure coniferous. From the riparian buffer zone to the river channel, the evaluation showed that pattern I had the highest purification ability at 1 m and 2 m; at a width of 4 m, pattern III had the highest purification ability; at a distance of 7 m, pattern V showed the highest purification ability; at 10 m, pattern IV showed the highest purification ability, pattern II the lowest. It is advisable to give priority to plant coniferous species from 0 m to 4 m from the river bank, while it is advisable to give priority to plant broad-leaved species from 4 m to 10 m from the river bank. We therefore recommend these vegetation configuration patterns in the development and management of runoff purification systems.
Identification and profiling of microRNAs during gonadal development in the giant freshwater prawn Macrobrachium rosenbergii
Authors: Liu Xue , Luo Bi-Yun , Feng Jian-Bin , Zhou Ling-Xia , Ma Ke-Yi , Qiu Gao-Feng
Published: February 2019

As post-transcriptional regulators, microRNAs (miRNAs) play an important role in growth and reproductive processes. So far, there is limited information regarding crustacean miRNAs. To explore the potential role of miRNAs in the gonadal development of the prawn Macrobrachium rosenbergii, we constructed seven small RNA libraries from ovarian and testicular tissues at various stages using somatic tissue as the control. A total of 1,954 known and 129 novel miRNAs were retrieved. By comparing differentially expressed miRNAs (DEMs) between testes and ovaries, forty-one miRNAs were identified with sex-biased expression patterns, including 17 ovary-biased and 24 testis-biased patterns. Furthermore, the putative target genes of the sex-biased miRNAs, such as cyclin L1, mitogen-activated protein kinase 7 (MAPK 7), heat shock protein (HSP), and zinc finger protein, were significantly enriched in many reproduction-related pathways including the Gonadotropin-releasing hormone (GnRH) pathway, glycolysis, gluconeogenesis pathway, ovarian steroidogenesis, estrogen signaling pathway, MAPK pathway, Wnt pathway, and insulin signaling pathway, implicating potential regulatory roles of miRNAs in reproduction. These data aid in the further investigation of the mechanism of gonadal development and reproductive regulation mediated by miRNA in M. rosenbergii.
Biochar reduces the efficiency of nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) mitigating N2O emissions
Authors: Fuertes-Mendizábal T. , Huérfano X. , Vega-Mas I. , Torralbo F. , Menéndez S. , Ippolito J. A. , Kammann C. , Wrage-Mönnig N. , Cayuela M. L. , Borchard N. , Spokas K. , Novak J. , González-Moro M. B. , González-Murua C. , Estavillo J. M.
Published: February 2019

Among strategies suggested to decrease agricultural soil N2O losses, the use of nitrification inhibitors such as DMPP (3,4-dimethylpyrazole phosphate) has been proposed. However, the efficiency of DMPP might be affected by soil amendments, such as biochar, which has been shown to reduce N2O emissions. This study evaluated the synergic effect of a woody biochar applied with DMPP on soil N2O emissions. A incubation study was conducted with a silt loam soil and a biochar obtained from Pinus taeda at 500 °C. Two biochar rates (0 and 2% (w/w)) and three different nitrogen treatments (unfertilized, fertilized and fertilized + DMPP) were assayed under two contrasting soil water content levels (40% and 80% of water filled pore space (WFPS)) over a 163 day incubation period. Results showed that DMPP reduced N2O emissions by reducing ammonia-oxidizing bacteria (AOB) populations and promoting the last step of denitrification (measured by the ratio nosZI + nosZII/nirS + nirK genes). Biochar mitigated N2O emissions only at 40% WFPS due to a reduction in AOB population. However, when DMPP was applied to the biochar amended soil, a counteracting effect was observed, since the N2O mitigation induced by DMPP was lower than in control soil, demonstrating that this biochar diminishes the efficiency of the DMPP both at low and high soil water contents.
Modular type I polyketide synthase acyl carrier protein domains share a common N-terminally extended fold
Authors: Moretto Luisa , Heylen Rachel , Holroyd Natalie , Vance Steven , Broadhurst R. William
Published: February 2019

Acyl carrier protein (ACP) domains act as interaction hubs within modular polyketide synthase (PKS) systems, employing specific protein-protein interactions to present acyl substrates to a series of enzyme active sites. Many domains from the multimodular PKS that generates the toxin mycolactone display an unusually high degree of sequence similarity, implying that the few sites which vary may do so for functional reasons. When domain boundaries based on prior studies were used to prepare two isolated ACP segments from this system for studies of their interaction properties, one fragment adopted the expected tertiary structure, but the other failed to fold, despite sharing a sequence identity of 49%. Secondary structure prediction uncovered a previously undetected helical region (H0) that precedes the canonical helix-bundle ACP topology in both cases. This article reports the NMR solution structures of two N-terminally extended mycolactone mACP constructs, mH0ACPa and mH0ACPb, both of which possess an additional α-helix that behaves like a rigid component of the domain. The interactions of these species with a phosphopantetheinyl transferase and a ketoreductase domain are unaffected by the presence of H0, but a shorter construct that lacks the H0 region is shown to be substantially less thermostable than mH0ACPb. Bioinformatics analysis suggests that the extended H0-ACP motif is present in 98% of type I cis-acyltransferase PKS chain-extension modules. The polypeptide linker that connects an H0-ACP motif to the preceding domain must therefore be ~12 residues shorter than previously thought, imposing strict limits on ACP-mediated substrate delivery within and between PKS modules.
Quantitative assessment of outer retinal folds on enface optical coherence tomography after vitrectomy for rhegmatogenous retinal detachment
Authors: Fukuyama H. , Yagiri H. , Araki T. , Iwami H. , Yoshida Y. , Ishikawa H. , Kimura N. , Kakusho K. , Okadome T. , Gomi F.
Published: February 2019

We aimed to investigate the possible causes of metamorphopsia for rhegmatogenous retinal detachment (RRD) based on findings of enface optical coherence tomography (OCT). The study was a retrospective, consecutive case series of 33 eyes with macula-off RRD. Metamorphopsia was measured by M-CHARTS and enface OCT images covering a macular area of 6 × 6 mm square obtained at 1, 3, and 6 months postoperatively. Within the outer retinal slabs of enface OCT, multiple lines that looked like folds were delineated in all eyes at month 1, and we succeeded in extracting images of folds by subtracting retinal vessels. We calculated their density by an image-processing technique. The mean M-CHARTS scores were 0.62 ± 0.47 at month 1 and 0.30 ± 0.29 at month 6 (P < 0.001). The fold density was 8.3 ± 4.2 at month 1 and 6.1 ± 3.1 at month 6 (P = 0.0044). The M-CHARTS scores at 6 months were significantly associated with the fold density at 1 month (r = 0.515, P = 0.002). In conclusion, enface OCT visualized the outer retinal folds in eyes that had undergone successful RRD surgery, and a larger number of folds was related to the remaining metamorphopsia.