bluuebunny/crossref_metadata_2025 huggingface dataset:
Atomic-Level Structural Dynamics of Polyoxoniobates during DMMP Decomposition
Authors: Wang Qi , Chapleski Robert C. , Plonka Anna M. , Gordon Wesley O. , Guo Weiwei , Nguyen-Phan Thuy-Duong , Sharp Conor H. , Marinkovic Nebojsa S. , Senanayake Sanjaya D. , Morris John R. , Hill Craig L. , Troya Diego , Frenkel Anatoly I.
Published: April 2017

Ambient pressure in situ synchrotron-based spectroscopic techniques have been correlated to illuminate atomic-level details of bond breaking and formation during the hydrolysis of a chemical warfare nerve agent simulant over a polyoxometalate catalyst. Specifically, a Cs8[Nb6O19] polyoxoniobate catalyst has been shown to react readily with dimethyl methylphosphonate (DMMP). The atomic-level transformations of all reactant moieties, the [Nb6O19]8− polyanion, its Cs+ counterions, and the DMMP substrate, were tracked under ambient conditions by a combination of X-ray absorption fine structure spectroscopy, Raman spectroscopy, and X-ray diffraction. Results reveal that the reaction mechanism follows general base (in contrast to specific base) hydrolysis. Together with computational results, the work demonstrates that the ultimate fate of DMMP hydrolysis at the Cs8[Nb6O19] catalyst is strong binding of the (methyl) methylphosphonic acid ((M)MPA) product to the polyanions, which ultimately inhibits catalytic turnover.
Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells
Authors: Wahlin Karl J. , Maruotti Julien A. , Sripathi Srinivasa R. , Ball John , Angueyra Juan M. , Kim Catherine , Grebe Rhonda , Li Wei , Jones Bryan W. , Zack Donald J.
Published: April 2017

The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function. The advanced outer segment-like structures reported here support the notion that 3D retina cups could serve as a model for studying mature photoreceptor development and allow for more robust modeling of retinal degenerative disease in vitro.
Endothelial colony forming cells and mesenchymal progenitor cells form blood vessels and increase blood flow in ischemic muscle
Authors: Kang Kyu-Tae , Lin Ruei-Zeng , Kuppermann David , Melero-Martin Juan M. , Bischoff Joyce
Published: April 2017

Here we investigated whether endothelial colony forming cells (ECFC) and mesenchymal progenitor cells (MPC) form vascular networks and restore blood flow in ischemic skeletal muscle, and whether host myeloid cells play a role. ECFC + MPC, ECFC alone, MPC alone, or vehicle alone were injected into the hind limb ischemic muscle one day after ligation of femoral artery and vein. At day 5, hind limbs injected with ECFC + MPC showed greater blood flow recovery compared with ECFC, MPC, or vehicle. Tail vein injection of human endothelial specific Ulex europaeus agglutinin-I demonstrated an increased number of perfused human vessels in ECFC + MPC compared with ECFC. In vivo bioluminescence imaging showed ECFC persisted for 14 days in ECFC + MPC-injected hind limbs. Flow cytometric analysis of ischemic muscles at day 2 revealed increased myeloid lineage cells in ECFC + MPC-injected muscles compared to vehicle-injected muscles. Neutrophils declined by day 7, while the number of myeloid cells, macrophages, and monocytes did not. Systemic myeloid cell depletion with anti-Gr-1 antibody blocked the improved blood flow observed with ECFC + MPC and reduced ECFC and MPC retention. Our data suggest that ECFC + MPC delivery could be used to reestablish blood flow in ischemic tissues, and this may be enhanced by coordinated recruitment of host myeloid cells.
P2Y6-deficiency increases micturition frequency and attenuates sustained contractility of the urinary bladder in mice
Authors: Kira Satoru , Yoshiyama Mitsuharu , Tsuchiya Sachiko , Shigetomi Eiji , Miyamoto Tatsuya , Nakagomi Hiroshi , Shibata Keisuke , Mochizuki Tsutomu , Takeda Masayuki , Koizumi Schuichi
Published: April 2017

The role of the P2Y6 receptor in bladder function has recently attracted a great deal of attention in lower urinary tract research. We conducted this study to determine contributions of the P2Y6 receptor in lower urinary tract function of normal phenotypes by comparing P2Y6-deficient mice and wild-type mice. In in vivo experiments, P2Y6-deficient mice had more frequent micturition with smaller bladder capacity compared to wild-type mice; however, there was no difference between these groups in bladder-filling pressure/volume relationships during cystometry under decerebrate, unanaesthetized conditions. Analysis of in vivo bladder contraction revealed significant difference between the 2 groups, with P2Y6-deficient mice presenting markedly shorter bladder contraction duration but no difference in peak contraction pressure. However, analysis of in vitro experiments showed no P2Y6 involvements in contraction and relaxation of bladder muscle strips and in ATP release by mechanical stimulation of primary-cultured urothelial cells. These results suggest that the P2Y6 receptor in the central nervous system, dorsal root ganglion, or both is involved in inhibition of bladder afferent signalling or sensitivity in the pontine micturition centre and that the receptor in the detrusor may be implicated in facilitation to sustain bladder contraction force.
Magnetic nanoparticles coated with polyarabic acid demonstrate enhanced drug delivery and imaging properties for cancer theranostic applications
Authors: Patitsa Maria , Karathanou Konstantina , Kanaki Zoi , Tzioga Lamprini , Pippa Natassa , Demetzos Constantinos , Verganelakis Dimitris A. , Cournia Zoe , Klinakis Apostolos
Published: April 2017

Therapeutic targeting of tumor cells with drug nanocarriers relies upon successful interaction with membranes and efficient cell internalization. A further consideration is that engineered nanomaterials should not damage healthy tissues upon contact. A critical factor in this process is the external coating of drug delivery nanodevices. Using in silico, in vitro and in vivo studies, we show for the first time that magnetic nanoparticles coated with polyarabic acid have superior imaging, therapeutic, and biocompatibility properties. We demonstrate that polyarabic acid coating allows for efficient penetration of cell membranes and internalization into breast cancer cells. Polyarabic acid also allows reversible loading of the chemotherapeutic drug Doxorubicin, which upon release suppresses tumor growth in vivo in a mouse model of breast cancer. Furthermore, these nanomaterials provide in vivo contrasting properties, which directly compare with commercial gadolinium-based contrasting agents. Finally, we report excellent biocompatibility, as these nanomaterial cause minimal, if any cytotoxicity in vitro and in vivo. We thus propose that magnetic nanodevices coated with polyarabic acid offer a new avenue for theranostics efforts as efficient drug carriers, while providing excellent contrasting properties due to their ferrous magnetic core, which can help the future design of nanomaterials for cancer imaging and therapy.
Polybenzoxazole Nanofiber-Reinforced Moisture-Responsive Soft Actuators
Authors: Chen Meiling , Frueh Johannes , Wang Daolin , Lin Xiankun , Xie Hui , He Qiang
Published: April 2017

Hydromorphic biological systems, such as morning glory flowers, pinecones, and awns, have inspired researchers to design moisture-sensitive soft actuators capable of directly converting the change of moisture into motion or mechanical work. Here, we report a moisture-sensitive poly(p-phenylene benzobisoxazole) nanofiber (PBONF)-reinforced carbon nanotube/poly(vinyl alcohol) (CNT/PVA) bilayer soft actuator with fine performance on conductivity and mechanical properties. The embedded PBONFs not only assist CNTs to form a continuous, conductive film, but also enhance the mechanical performance of the actuators. The PBONF-reinforced CNT/PVA bilayer actuators can unsymmetrically adsorb and desorb water, resulting in a reversible deformation. More importantly, the actuators show a pronounced increase of conductivity due to the deformation induced by the moisture change, which allows the integration of a moisture-sensitive actuator and a humidity sensor. Upon changing the environmental humidity, the actuators can respond by the deformation for shielding and report the humidity change in a visual manner, which has been demonstrated by a tweezer and a curtain. Such nanofiber-reinforced bilayer actuators with the sensing capability should hold considerable promise for the applications such as soft robots, sensors, intelligent switches, integrated devices, and material storage.
Cytological and molecular characterization of carotenoid accumulation in normal and high-lycopene mutant oranges
Authors: Lu Peng-jun , Wang Chun-yan , Yin Ting-ting , Zhong Si-lin , Grierson Don , Chen Kun-song , Xu Chang-jie
Published: April 2017

Ripe Cara Cara sweet orange contains 25 times as much carotenoids in flesh as Newhall sweet orange, due to high accumulation of carotenes, mainly phytoene, lycopene and phytofluene. Only yellow globular chromoplasts were observed in Newhall flesh. Distinct yellow globular and red elongated crystalline chromoplasts were found in Cara Cara but only one type of chromoplast was present in each cell. The red crystalline chromoplasts contained lycopene as a dominant carotenoid and were associated with characteristic carotenoid sequestering structures. The increased accumulation of linear carotenes in Cara Cara is not explained by differences in expression of all 18 carotenogenic genes or gene family members examined, or sequence or abundance of mRNAs from phytoene synthase (PSY) and chromoplast-specific lycopene β-cyclase (CYCB) alleles. 2-(4-Chlorophenylthio)-triethylamine hydrochloride (CPTA) enhanced lycopene accumulation and induced occurrence of red crystalline chromoplasts in cultured Newhall juice vesicles, indicating that carotenoid synthesis and accumulation can directly affect chromoplast differentiation and structure. Norflurazon (NFZ) treatment resulted in high accumulation of phytoene and phytofluene in both oranges, and the biosynthetic activity upstream of phytoene desaturase was similar in Newhall and Cara Cara. Possible mechanisms for high carotene accumulation and unique development of red crystalline chromoplasts in Cara Cara are discussed.
Down-regulation of miR-214 reverses erlotinib resistance in non-small-cell lung cancer through up-regulating LHX6 expression
Authors: Liao Jinrong , Lin Jinghui , Lin Dong , Zou Changyan , Kurata Jessica , Lin Renjang , He Zhiyong , Su Ying
Published: April 2017

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard treatments for advanced non-small-cell lung cancer (NSCLC) patients. However, acquired resistance to EGFR-TKIs is widely detected across the world, and the exact mechanisms have not been fully demonstrated until now. This study aimed to examine the role of miR-214 in the acquired resistance to erlotinib in NSCLC, and elucidate the underlying mechanisms. qRT-PCR assay detected higher miR-214 expression in the plasma of NSCLC patients with acquired EGFR-TKI resistance than prior to EGFR-TKI therapy, and in the generated erlotinib-resistant HCC827 (HCC827/ER) cells than in HCC827 cells. Bioinformatics analysis and dual-luciferase reporter assay indentified LHX6 as a direct target gene of miR-214, and LHX6 expression was detected to be down-regulated in erlotinib-resistant HCC827 cells. Transwell invasion assay revealed that overexpressing LHX6 reversed the increase in the invasive ability of HCC827 cells induced by miR-214 overexpression, and the CRISPR-Cas9 system-mediated LHX6 knockdown reversed the reduction in the invasion of erlotinib-resistant HCC827 cells caused by miR-214 down-regulation. The results of the present study demonstrate that down-regulation of miR-214 may reverse acquired resistance to erlotinib in NSCLC through mediating its direct target gene LHX6 expression.
In vitro biomimetic platforms featuring a perfusion system and 3D spheroid culture promote the construction of tissue-engineered corneal endothelial layers
Authors: Li Shanyi , Han Yuting , Lei Hao , Zeng Yingxin , Cui Zekai , Zeng Qiaolang , Zhu Deliang , Lian Ruiling , Zhang Jun , Chen Zhe , Chen Jiansu
Published: April 2017

Corneal endothelial cells (CECs) are very important for the maintenance of corneal transparency. However, in vitro, CECs display limited proliferation and loss of phenotype via endothelial to mesenchymal transformation (EMT) and cellular senescence. In this study, we demonstrate that continuous supplementary nutrition using a perfusion culture bioreactor and three-dimensional (3D) spheroid culture can be used to improve CEC expansion in culture and to construct a tissue-engineered CEC layer. Compared with static culture, perfusion-derived CECs exhibited an increased proliferative ability as well as formed close cell-cell contact junctions and numerous surface microvilli. We also demonstrated that the CEC spheroid culture significantly down-regulated gene expression of the proliferation marker Ki67 and EMT-related markers Vimentin and α-SMA, whereas the gene expression level of the CEC marker ATP1A1 was significantly up-regulated. Furthermore, use of the perfusion system in conjunction with a spheroid culture on decellularized corneal scaffolds and collagen sheets promoted the generation of CEC monolayers as well as neo-synthesized ECM formation. This study also confirmed that a CEC spheroid culture on a curved collagen sheet with controlled physiological intraocular pressure could generate a CEC monolayer. Thus, our results show that the use of a perfusion system and 3D spheroid culture can promote CEC expansion and the construction of tissue-engineered corneal endothelial layers in vitro.
Human PrimPol activity is enhanced by RPA
Authors: Martínez-Jiménez María I. , Lahera Antonio , Blanco Luis
Published: April 2017

Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.
Erratum: Molecular analysis of the factorless internal ribosome entry site in Cricket Paralysis virus infection
Authors: Kerr Craig H. , Ma Zi Wang , Jang Christopher J. , Thompson Sunnie R. , Jan Eric
Published: April 2017

Scientific Reports 6: Article number: 37319; published online: 17 November 2016; updated: 04 April 2017 This Article contains an error in Figure 2 in the column labelled ‘Nucleotide(s)’, row ‘mSLV-L2’. The subscript text ‘6144–45’ is missing between GC and CU. In addition, there is an error in the mutation column where mVLR is incorrectly given as VLRm.
Root biomass and exudates link plant diversity with soil bacterial and fungal biomass
Authors: Eisenhauer Nico , Lanoue Arnaud , Strecker Tanja , Scheu Stefan , Steinauer Katja , Thakur Madhav P. , Mommer Liesje
Published: April 2017

Plant diversity has been shown to determine the composition and functioning of soil biota. Although root-derived organic inputs are discussed as the main drivers of soil communities, experimental evidence is scarce. While there is some evidence that higher root biomass at high plant diversity increases substrate availability for soil biota, several studies have speculated that the quantity and diversity of root inputs into the soil, i.e. though root exudates, drive plant diversity effects on soil biota. Here we used a microcosm experiment to study the role of plant species richness on the biomass of soil bacteria and fungi as well as fungal-to-bacterial ratio via root biomass and root exudates. Plant diversity significantly increased shoot biomass, root biomass, the amount of root exudates, bacterial biomass, and fungal biomass. Fungal biomass increased most with increasing plant diversity resulting in a significant shift in the fungal-to-bacterial biomass ratio at high plant diversity. Fungal biomass increased significantly with plant diversity-induced increases in root biomass and the amount of root exudates. These results suggest that plant diversity enhances soil microbial biomass, particularly soil fungi, by increasing root-derived organic inputs.
Identification of Novel MAGE-G1-Interacting Partners in Retinoic Acid-Induced P19 Neuronal Differentiation Using SILAC-Based Proteomics
Authors: Liu Yong , Chen Yujian , Lin Shide , Yang Shuguang , Liu Shaojun
Published: April 2017

MAGE-G1 is a protein plays role in the early process of neurogenesis. However, the fundamental roles MAGE-G1 played in neurogenesis have not yet been completely understood. Finding the partners MAGE-G1 interacting with will surely contribute to the function study of MAGE-G1. In this study, using Stable Isotope Labeling by Amino acids in Cell culture-immunoprecipitation quantitative proteomics, we screened the interacting proteins of MAGE-G1 during retinoic acid -induced neuronal differentiation of P19 cells and firstly found that FSCN1 and VIME were potential novel MAGE-G1-interacting proteins. Then, the interaction between overexpressed MAGE-G1 and FSCN1 or VIME was validated by GST-pull down assay in bacteria and by co-immunoprecipitation assay in COS7 cells. Endogenous co-immunoprecipitation assay further confirmed that MAGE-G1 interacted with FSCN1 or VIME in P19 cells after a 6-day retinoic acid-induced neuronal differentiation. Those results provide a functional linkage between MAGE-G1 and FSCN1 or VIME and may facilitate a better understanding of the fundamental aspects of MAGE-G1 during neurogenesis.
Visuomotor adaptation in head-mounted virtual reality versus conventional training
Authors: Anglin J. M. , Sugiyama T. , Liew S.-L.
Published: April 2017

Immersive, head-mounted virtual reality (HMD-VR) provides a unique opportunity to understand how changes in sensory environments affect motor learning. However, potential differences in mechanisms of motor learning and adaptation in HMD-VR versus a conventional training (CT) environment have not been extensively explored. Here, we investigated whether adaptation on a visuomotor rotation task in HMD-VR yields similar adaptation effects in CT and whether these effects are achieved through similar mechanisms. Specifically, recent work has shown that visuomotor adaptation may occur via both an implicit, error-based internal model and a more cognitive, explicit strategic component. We sought to measure both overall adaptation and balance between implicit and explicit mechanisms in HMD-VR versus CT. Twenty-four healthy individuals were placed in either HMD-VR or CT and trained on an identical visuomotor adaptation task that measured both implicit and explicit components. Our results showed that the overall timecourse of adaption was similar in both HMD-VR and CT. However, HMD-VR participants utilized a greater cognitive strategy than CT, while CT participants engaged in greater implicit learning. These results suggest that while both conditions produce similar results in overall adaptation, the mechanisms by which visuomotor adaption occurs in HMD-VR appear to be more reliant on cognitive strategies.
Inter-layer synchronization in non-identical multi-layer networks
Authors: Leyva I. , Sevilla-Escoboza R. , Sendiña-Nadal I. , Gutiérrez R. , Buldú J.M. , Boccaletti S.
Published: April 2017

Inter-layer synchronization is a dynamical process occurring in multi-layer networks composed of identical nodes. This process emerges when all layers are synchronized, while nodes in each layer do not necessarily evolve in unison. So far, the study of such inter-layer synchronization has been restricted to the case in which all layers have an identical connectivity structure. When layers are not identical, the inter-layer synchronous state is no longer a stable solution of the system. Nevertheless, when layers differ in just a few links, an approximate treatment is still feasible, and allows one to gather information on whether and how the system may wander around an inter-layer synchronous configuration. We report the details of an approximate analytical treatment for a two-layer multiplex, which results in the introduction of an extra inertial term accounting for structural differences. Numerical validation of the predictions highlights the usefulness of our approach, especially for small or moderate topological differences in the intra-layer coupling. Moreover, we identify a non-trivial relationship connecting the betweenness centrality of the missing links and the intra-layer coupling strength. Finally, by the use of multiplexed layers of electronic circuits, we study the inter-layer synchronization as a function of the removed links.
Magneto-Dendrite Effect: Copper Electrodeposition under High Magnetic Field
Authors: Miura Makoto , Oshikiri Yoshinobu , Sugiyama Atsushi , Morimoto Ryoichi , Mogi Iwao , Miura Miki , Takagi Satoshi , Yamauchi Yusuke , Aogaki Ryoichi
Published: April 2017

Ionic vacancy is a by-product in electrochemical reaction, composed of polarized free space of the order of 0.1 nm with a 1 s lifetime, and playing key roles in nano-electrochemical processes. However, its chemical nature has not yet been clarified. In copper electrodeposition under a high magnetic field of 15 T, using a new electrode system called cyclotron magnetohydrodynamic (MHD) electrode (CMHDE) composed of a pair of concentric cylindrical electrodes, we have found an extraordinary dendritic growth with a drastic positive potential shift from hydrogen-gas evolution potential. Dendritic deposition is characterized by the co-deposition of hydrogen molecule, but such a positive potential shift makes hydrogen-gas evolution impossible. However, in the high magnetic field, instead of flat deposit, remarkable dendritic growth emerged. By examining the chemical nature of ionic vacancy, it was concluded that ionic vacancy works on the dendrite formation with the extraordinary potential shift.
On-chip magnetic cooling of a nanoelectronic device
Authors: Bradley D. I. , Guénault A. M. , Gunnarsson D. , Haley R. P. , Holt S. , Jones A. T. , Pashkin Yu. A. , Penttilä J. , Prance J. R. , Prunnila M. , Roschier L.
Published: April 2017

We demonstrate significant cooling of electrons in a nanostructure below 10 mK by demagnetisation of thin-film copper on a silicon chip. Our approach overcomes the typical bottleneck of weak electron-phonon scattering by coupling the electrons directly to a bath of refrigerated nuclei, rather than cooling via phonons in the host lattice. Consequently, weak electron-phonon scattering becomes an advant- age. It allows the electrons to be cooled for an experimentally useful period of time to temperatures colder than the dilution refrigerator platform, the incoming electrical connections, and the host lattice. There are efforts worldwide to reach sub-millikelvin electron temperatures in nanostructures to study coherent electronic phenomena and improve the operation of nanoelectronic devices. On-chip magnetic cooling is a promising approach to meet this challenge. The method can be used to reach low, local electron temperatures in other nanostructures, obviating the need to adapt traditional, large demagnetisation stages. We demonstrate the technique by applying it to a nanoelectronic primary thermometer that measures its internal electron temperature. Using an optimised demagnetisation process, we demonstrate cooling of the on-chip electrons from 9 mK to below 5 mK for over 1000 seconds.
Infections of virulent and avirulent viruses differentially influenced the expression of dicer-1, ago-1, and microRNAs in Bombus terrestris
Authors: Niu Jinzhi , Meeus Ivan , De Coninck Dieter IM , Deforce Dieter , Etebari Kayvan , Asgari Sassan , Smagghe Guy
Published: April 2017

The microRNA (miRNA) pathway is well established to be involved in host-pathogen interactions. As key insect pollinators, bees are suffering from widely spreading viruses, especially honeybees and bumblebees. In order to better understand bee-virus interaction, we comparatively analyzed the involvement of the bumblebee miRNA pathway upon infection by two different viruses. In our setup, an avirulent infection is induced by slow bee paralysis virus (SBPV) and a virulent infection is induced by Israeli acute paralysis virus (IAPV). Our results showed the increased expressions ofdicer-1andago-1upon SBPV infection. There were 17 and 12 bumblebee miRNAs differentially expressed upon SBPV and IAPV infections, respectively. These results may indicate the involvement of the host miRNA pathway in bumblebee-virus interaction. However, silencing ofdicer-1did not influence the genome copy number of SBPV. Target prediction for these differentially expressed miRNAs showed their possible involvement in targeting viral genomic RNA and in the regulation of networks in bumblebee. Our study opens a new insight into bee-virus interaction meditated by host miRNAs.
Genome-wide association analysis for chronic venous disease identifies EFEMP1 and KCNH8 as susceptibility loci
Authors: Ellinghaus Eva , Ellinghaus David , Krusche Petra , Greiner Aljoscha , Schreiber Claudia , Nikolaus Susanna , Gieger Christian , Strauch Konstantin , Lieb Wolfgang , Rosenstiel Philip , Frings Norbert , Fiebig Andreas , Schreiber Stefan , Franke Andre
Published: April 2017

Chronic venous disease (CVD) is a multifactorial condition representing one of the most common disorders among populations of Western countries. The heritability of about 17% suggests genetic risk factors in CVD etiology. However, so far the genetic causes are unknown. We undertook the hitherto first genome-wide association study (GWAS) for CVD, analyzing more than 1.93 M SNPs in 4,942 German individuals, followed by replication in two independent German data sets. The combined analysis of discovery and replication stages (2,269 cases and 7,765 controls) yielded robust associations within the two genes EFEMP1 and KCNH8 (rs17278665, rs727139 with P < 5 × 10−8), and suggestive association within gene SKAP2 (rs2030136 with P < 5 × 10−7). Association signals of rs17278665 and rs727139 reside in regions of low linkage disequilibrium containing no other genes. Data from the ENCODE and Roadmap Epigenomics projects show that tissue specific marks overlap with the variants. SNPs rs17278665 and rs2030136 are known eQTLs. Our study demonstrates that GWAS are a valuable tool to study the genetic component of CVD. With our approach, we identified two novel genome-wide significant susceptibility loci for this common disease. Particularly, the extracellular matrix glycoprotein EFEMP1 is promising for future functional studies due to its antagonistic role in vessel development and angiogenesis.
Transition between strong and weak topological insulator in ZrTe5 and HfTe5
Authors: Fan Zongjian , Liang Qi-Feng , Chen Y. B. , Yao Shu-Hua , Zhou Jian
Published: April 2017

ZrTe5 and HfTe5 have attracted increasingly attention recently since the theoretical prediction of being topological insulators (TIs). However, subsequent works show many contradictions about their topolog-ical nature. Three possible phases, i.e. strong TI, weak TI, and Dirac semi-metal, have been observed in different experiments until now. Essentially whether ZrTe5 or HfTe5 has a band gap or not is still a question. Here, we present detailed first-principles calculations on the electronic and topological prop-erties of ZrTe5 and HfTe5 on variant volumes and clearly demonstrate the topological phase transition from a strong TI, going through an intermediate Dirac semi-metal state, then to a weak TI when the crystal expands. Our work might give a unified explain about the divergent experimental results and propose the crucial clue to further experiments to elucidate the topological nature of these materials.
Enhancing current-induced torques by abutting additional spin polarizer layer to nonmagnetic metal layer
Authors: Go Gyungchoon , Lee Kyung-Jin , Kim Young Keun
Published: April 2017

Recently, the switching of a perpendicularly magnetized ferromagnet (FM) by injecting an in-plane current into an attached non-magnet (NM) has become of emerging technological interest. This magnetization switching is attributed to the spin-orbit torque (SOT) originating from the strong spin-orbit coupling of the NM layer. However, the switching efficiency of the NM/FM structure itself may be insufficient for practical use, as for example, in spin transfer torque (STT)-based magnetic random access memory (MRAM) devices. Here we investigate spin torque in an NM/FM structure with an additional spin polarizer (SP) layer abutted to the NM layer. In addition to the SOT contribution, a spin-polarized current from the SP layer creates an extra spin chemical potential difference at the NM/FM interface and gives rise to a STT on the FM layer. We show that, using typical parameters including device width, thickness, spin diffusion length, and the spin Hall angle, the spin torque from the SP layer can be much larger than that from the spin Hall effect (SHE) of the NM.
Genome-wide study of an elite rice pedigree reveals a complex history of genetic architecture for breeding improvement
Authors: Chen Shaoxia , Lin Zechuan , Zhou Degui , Wang Chongrong , Li Hong , Yu Renbo , Deng Hanchao , Tang Xiaoyan , Zhou Shaochuan , Wang Deng Xing , He Hang
Published: April 2017

Improving breeding has been widely utilized in crop breeding and contributed to yield and quality improvement, yet few researches have been done to analyze genetic architecture underlying breeding improvement comprehensively. Here, we collected genotype and phenotype data of 99 cultivars from the complete pedigree including Huanghuazhan, an elite, high-quality, conventional indica rice that has been grown over 4.5 million hectares in southern China and from which more than 20 excellent cultivars have been derived. We identified 1,313 selective sweeps (SSWs) revealing four stage-specific selection patterns corresponding to improvement preference during 65 years, and 1113 conserved Huanghuazhan traceable blocks (cHTBs) introduced from different donors and conserved in >3 breeding generations were the core genomic regions for superior performance of Huanghuazhan. Based on 151 quantitative trait loci (QTLs) identified for 13 improved traits in the pedigree, we reproduced their improvement process in silico, highlighting improving breeding works well for traits controlled by major/major + minor effect QTLs, but was inefficient for traits controlled by QTLs with complex interactions or explaining low levels of phenotypic variation. These results indicate long-term breeding improvement is efficient to construct superior genetic architecture for elite performance, yet molecular breeding with designed genotype of QTLs can facilitate complex traits improvement.
Inhibitory Effects of Dopamine Receptor D1 Agonist on Mammary Tumor and Bone Metastasis
Authors: Minami Kazumasa , Liu Shengzhi , Liu Yang , Chen Andy , Wan Qiaoqiao , Na Sungsoo , Li Bai-Yan , Matsuura Nariaki , Koizumi Masahiko , Yin Yukun , Gan Liangying , Xu Aihua , Li Jiliang , Nakshatri Harikrishna , Yokota Hiroki
Published: April 2017

Dopaminergic signaling plays a critical role in the nervous system, but little is known about its potential role in breast cancer and bone metabolism. A screening of ~1,000 biologically active compounds revealed that a selective agonist of dopamine receptor D1 (DRD1), A77636, inhibited proliferation of 4T1.2 mammary tumor cells as well as MDA-MB-231 breast cancer cells. Herein, we examined the effect of A77636 on bone quality using a mouse model of bone metastasis from mammary tumor. A77636 inhibited migration of cancer cells in a DRD1-dependent fashion and suppressed development of bone-resorbing osteoclasts by downregulating NFATc1 through the elevation of phosphorylation of eIF2α. In the mouse model of bone metastasis, A77636 reduced osteolytic lesions and prevented mechanical weakening of the femur and tibia. Collectively, we expect that dopaminergic signaling might provide a novel therapeutic target for breast cancer and bone metastasis.
Resveratrol protects podocytes against apoptosis via stimulation of autophagy in a mouse model of diabetic nephropathy
Authors: Huang Shan-Shan , Ding Da-Fa , Chen Sheng , Dong Cheng-Long , Ye Xiao-Long , Yuan Yang-Gang , Feng Ya-Min , You Na , Xu Jia-Rong , Miao Heng , You Qiang , Lu Xiang , Lu Yi-Bing
Published: April 2017

Podocyte apoptosis coincides with albuminuria onset and precedes podocytopenia in diabetic nephropathy. However, there is a lack of effective therapeutic drugs to protect podocytes from apoptosis. Here, we demonstrated that resveratrol relieved a series of indicators of diabetic nephropathy and attenuated apoptosis of podocytes in db/db diabetic model mice. In addition, resveratrol induced autophagy in both db/db mice and human podocytes. Furthermore, inhibition of autophagy by 3-methyladenine (3-MA) and autophagy gene 5 (Atg5) short hairpin RNA (shRNA) reversed the protective effects of resveratrol on podocytes. Finally, we found that resveratrol might regulate autophagy and apoptosis in db/db mice and podocytes through the suppression of microRNA-383-5p (miR-383-5p). Together, our results indicate that resveratrol effectively attenuates high glucose-induced apoptosis via the activation of autophagy in db/db mice and podocytes, which involves miR-383-5p. Thus, this study reveals a new possible strategy to treat diabetic nephropathy.
Vortices and antivortices in two-dimensional ultracold Fermi gases
Authors: Bighin G. , Salasnich L.
Published: April 2017

Vortices are commonly observed in the context of classical hydrodynamics: from whirlpools after stirring the coffee in a cup to a violent atmospheric phenomenon such as a tornado, all classical vortices are characterized by an arbitrary circulation value of the local velocity field. On the other hand the appearance of vortices with quantized circulation represents one of the fundamental signatures of macroscopic quantum phenomena. In two-dimensional superfluids quantized vortices play a key role in determining finite-temperature properties, as the superfluid phase and the normal state are separated by a vortex unbinding transition, the Berezinskii-Kosterlitz-Thouless transition. Very recent experiments with two-dimensional superfluid fermions motivate the present work: we present theoretical results based on the renormalization group showing that the universal jump of the superfluid density and the critical temperature crucially depend on the interaction strength, providing a strong benchmark for forthcoming investigations.
Solar eclipse demonstrating the importance of photochemistry in new particle formation
Authors: Jokinen Tuija , Kontkanen Jenni , Lehtipalo Katrianne , Manninen Hanna E. , Aalto Juho , Porcar-Castell Albert , Garmash Olga , Nieminen Tuomo , Ehn Mikael , Kangasluoma Juha , Junninen Heikki , Levula Janne , Duplissy Jonathan , Ahonen Lauri R. , Rantala Pekka , Heikkinen Liine , Yan Chao , Sipilä Mikko , Worsnop Douglas R. , Bäck Jaana , Petäjä Tuukka , Kerminen Veli-Matti , Kulmala Markku
Published: April 2017

Solar eclipses provide unique possibilities to investigate atmospheric processes, such as new particle formation (NPF), important to the global aerosol load and radiative balance. The temporary absence of solar radiation gives particular insight into different oxidation and clustering processes leading to NPF. This is crucial because our mechanistic understanding on how NPF is related to photochemistry is still rather limited. During a partial solar eclipse over Finland in 2015, we found that this phenomenon had prominent effects on atmospheric on-going NPF. During the eclipse, the sources of aerosol precursor gases, such as sulphuric acid and nitrogen- containing highly oxidised organic compounds, decreased considerably, which was followed by a reduced formation of small clusters and nanoparticles and thus termination of NPF. After the eclipse, aerosol precursor molecule concentrations recovered and re-initiated NPF. Our results provide direct evidence on the key role of the photochemical production of sulphuric acid and highly oxidized organic compounds in maintaining atmospheric NPF. Our results also explain the rare occurrence of this phenomenon under dark conditions, as well as its seemingly weak connection with atmospheric ions.
Epidemiology Investigation of stroke among Mongolian and Han population aged over 45 in Inner Mongolia
Authors: Zhang Chunyu , Lan Tian , Zhe Yan , Hu Baolige , Zhang Guohua , He Juan , Wang Zhiguang , Jiang Mingfang , Hu Riletemuer
Published: April 2017

To discuss the status of epidemiology of stroke in the Mongolian and Han population aged over 45 years and to understand the treatment and prevention of stroke. Data collected on stroke populations aged over 45 years in the six areas in Inner Mongolia were analyzed by using stratified multi-stage cluster sampling. The prevalence rate of stroke in patients aged over 45 years in Inner Mongolia was 4.62%. The stroke prevalence rate increased with age in both males and females, the Han and Mongolian populations, and was higher in males than in females in Inner Mongolia. The prevalence rate of stroke in the Mongolian population was higher than in the Han population. The incidence rate of stroke in patients aged over 45 years in Inner Mongolia was 0.28%, of which the rate of relapsed ischemic stroke was 23.29%. The proportion of ischemic stroke in the stroke patients was higher than hemorrhagic stroke. The prevalence and incidence rates of stroke in patients aged over 45 years in Inner Mongolia were high. The prevalence rate of stroke in both the Han population and the Mongolian population increased with age. Ischemic stroke was the major form of stroke.
Genome-wide identification of membrane-bound fatty acid desaturase genes in Gossypium hirsutum and their expressions during abiotic stress
Authors: Feng Jiyu , Dong Yating , Liu Wei , He Qiuling , Daud M. K. , Chen Jinhong , Zhu Shuijin
Published: April 2017

Membrane-bound fatty acid desaturases (FADs) are of great importance and play multiple roles in plant growth and development. In the present study, 39 full-length FAD genes, based on database searches, were identified in tetraploid upland cotton (Gossypium hirsutumL.) and were phylogenetically clustered into four subfamilies. Genomic localization revealed that 34 genes were mapped on 22 chromosomes, and five genes were positioned on the scaffold sequences. The FAD genes ofG. hirsutumin the same subfamily had similar gene structures. The structures of paralogous genes were considerably conserved in exons number and introns length. It was suggested that the FAD gene families inG. hirsutummight be duplicated mainly by segmental duplication. Moreover, the FAD genes were differentially expressed in differentG. hirsutumtissues in response to different levels of salt and cold stresses, as determined by qRT-PCR analysis. The identification and functional analysis of FAD genes inG. hirsutummay provide more candidate genes for genetic modification.
Indium gallium nitride-based ultraviolet, blue, and green light-emitting diodes functionalized with shallow periodic hole patterns
Authors: Jeong Hyun , Salas-Montiel Rafael , Lerondel Gilles , Jeong Mun Seok
Published: April 2017

In this study, we investigated the improvement in the light output power of indium gallium nitride (InGaN)-based ultraviolet (UV), blue, and green light-emitting diodes (LEDs) by fabricating shallow periodic hole patterns (PHPs) on the LED surface through laser interference lithography and inductively coupled plasma etching. Noticeably, different enhancements were observed in the light output powers of the UV, blue, and green LEDs with negligible changes in the electrical properties in the light output power versus current and current versus voltage curves. In addition, confocal scanning electroluminescence microscopy is employed to verify the correlation between the enhancement in the light output power of the LEDs with PHPs and carrier localization of InGaN/GaN multiple quantum wells. Light propagation through the PHPs on the UV, blue, and green LEDs is simulated using a three-dimensional finite-difference time-domain method to confirm the experimental results. Finally, we suggest optimal conditions of PHPs for improving the light output power of InGaN LEDs based on the experimental and theoretical results.
Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy
Authors: Liu Zhigang , Ren Bo , Wang Yihui , Zou Chen , Qiao Qinglian , Diao Zhijun , Mi Yashi , Zhu Di , Liu Xuebo
Published: April 2017

Sesamol, a nutritional phenolic antioxidant compound enriched in sesame seeds, has been shown to have potential anticancer activities. This study aims at characterizing the antitumor efficacy of sesamol and unveiling the importance of mitochondria in sesamol-induced effects using a human hepatocellular carcinoma cell line, HepG2 cells. Results of this study showed that sesamol treatment suppressed colony formation, elicited S phase arrest during cell cycle progression, and induced both intrinsic and extrinsic apoptotic pathway in vitro with a dose-dependent manner. Furthermore, sesamol treatment elicited mitochondrial dysfunction by inducing a loss of mitochondrial membrane potential. Impaired mitochondria and accumulated H2O2 production resulted in disturbance of redox-sensitive signaling including Akt and MAPKs pathways. Mitochondrial biogenesis was inhibited as suggested by the decline in expression of mitochondrial complex I subunit ND1, and the upstream AMPK/PGC1α signals. Importantly, sesamol inhibited mitophagy and autophagy through impeding the PI3K Class III/Belin-1 pathway. Autophagy stimulator rapamycin reversed sesamol-induced apoptosis and mitochondrial respiration disorders. Moreover, it was also shown that sesamol has potent anti-hepatoma activity in a xenograft nude mice model. These data suggest that mitochondria play an essential role in sesamol-induced HepG2 cells death, and further research targeting mitochondria will provide more chemotherapeutic opportunities.
Quantification of bioluminescence from the surface to the deep sea demonstrates its predominance as an ecological trait
Authors: Martini Séverine , Haddock Steven H. D.
Published: April 2017

The capability of animals to emit light, called bioluminescence, is considered to be a major factor in ecological interactions. Because it occurs across diverse taxa, measurements of bioluminescence can be powerful to detect and quantify organisms in the ocean. In this study, 17 years of video observations were recorded by remotely operated vehicles during surveys off the California Coast, from the surface down to 3,900 m depth. More than 350,000 observations are classified for their bioluminescence capability based on literature descriptions. The organisms represented 553 phylogenetic concepts (species, genera or families, at the most precise taxonomic level defined from the images), distributed within 13 broader taxonomic categories. The importance of bioluminescent marine taxa is highlighted in the water column, as we showed that 76% of the observed individuals have bioluminescence capability. More than 97% of Cnidarians were bioluminescent, and 9 of the 13 taxonomic categories were found to be bioluminescent dominant. The percentage of bioluminescent animals is remarkably uniform over depth. Moreover, the proportion of bioluminescent and non-bioluminescent animals within taxonomic groups changes with depth for Ctenophora, Scyphozoa, Chaetognatha, and Crustacea. Given these results, bioluminescence has to be considered an important ecological trait from the surface to the deep-sea.
Efficacy of alirocumab according to background statin type and dose: pooled analysis of 8 ODYSSEY Phase 3 clinical trials
Authors: Catapano Alberico L. , Lee L. Veronica , Louie Michael J. , Thompson Desmond , Bergeron Jean , Krempf Michel
Published: April 2017

Low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 monoclonal antibody alirocumab may be affected by background statin dose due to increased PCSK9 levels with higher statin doses. Data from 8 Phase 3 trials conducted with background statin (n = 4629) were pooled by alirocumab dose (75 or 150 mg every 2 weeks) and control (placebo/ezetimibe), and analyzed by background statin type/dose. Overall, 58.4% received high-dose statins (atorvastatin 40–80 mg, rosuvastatin 20–40 mg, simvastatin 80 mg), 28.6% moderate-dose statins (atorvastatin 20–<40 mg, rosuvastatin 10–<20 mg, simvastatin 40–<80 mg), and 12.9% low-dose statins (atorvastatin <20 mg, rosuvastatin <10 mg, simvastatin <40 mg). Mean baseline PCSK9 levels were higher with high versus moderate and low statin doses (318.5 vs 280.6 ng/mL). Baseline LDL-C levels were similar across pools, regardless of statin intensity. No associations were observed between statin type/dose and LDL-C % change from baseline or % of patients achieving LDL-C goals at Week 24 for alirocumab versus control (interaction P-values non-significant). Incidence of adverse events was similar for alirocumab versus control, except for a higher rate of injection-site reactions with alirocumab. In summary, alirocumab provided consistent LDL-C reductions and was generally well tolerated independent of background statin type/dose.