bluuebunny/crossref_metadata_2025 huggingface dataset:
On Correlated Change in Personality
Authors: Allemand Mathias , Martin Mike
Published: January 2017

Abstract. Correlated change in personality is essential to understanding change and development. It refers to the question of whether and to what degree changes in personality are interrelated over time within and between individuals. Compared to the longstanding literature on personality development, relatively less research has focused on correlated change in personality. The main goal of this paper is thus to discuss the potential of this concept for the field of personality development. First, we define correlated change and propose a categorization framework with multiple dimensions. Second, we discuss several theoretical concepts of correlated change that help understand the patterns, causes, and mechanisms underlying correlated change in personality. Third, we briefly describe several statistical approaches to modeling correlated change. Fourth, we summarize previous research on correlated change in personality. We focus our research on (a) correlated change within the Big Five personality traits, and (b) between the Big Five personality traits and three domains of life. Finally, we conclude by discussing challenges and future directions of the concept for the field of personality development.
Modular architecture for fully non-blocking silicon photonic switch fabric
Authors: Nikolova Dessislava , Calhoun David M. , Liu Yang , Rumley Sébastien , Novack Ari , Baehr-Jones Tom , Hochberg Michael , Bergman Keren
Published: January 2017

Integrated photonics offers the possibility of compact, low energy, bandwidth-dense interconnects for large port count spatial optical switches, facilitating flexible and energy efficient data movement in future data communications systems. To achieve widespread adoption, intimate integration with electronics has to be possible, requiring switch design using standard microelectronic foundry processes and available devices. We report on the feasibility of a switch fabric comprised of ubiquitous silicon photonic building blocks, opening the possibility to combine technologies, and materials towards a new path for switch fabric design. Rather than focus on integrating all devices on a single silicon chip die to achieve large port count optical switching, this work shifts the focus towards innovative packaging and integration schemes. In this work, we demonstrate 1×8 and 8×1 microring-based silicon photonic switch building blocks with software control, providing the feasibility of a full 8×8 architecture composed of silicon photonic building blocks. The proposed switch is fully non-blocking, has path-independent insertion loss, low crosstalk, and is straightforward to control. We further analyze this architecture and compare it with other common switching architectures for varying underlying technologies and radices, showing that the proposed architecture favorably scales to very large port counts when considering both crosstalk and architectural footprint. Separating a switch fabric into functional building blocks via multiple photonic integrated circuits offers the advantage of piece-wise manufacturing, packaging, and assembly, potentially reducing the number of optical I/O and electrical contacts on a single die.
Sox17 drives functional engraftment of endothelium converted from non-vascular cells
Authors: Schachterle William , Badwe Chaitanya R. , Palikuqi Brisa , Kunar Balvir , Ginsberg Michael , Lis Raphael , Yokoyama Masataka , Elemento Olivier , Scandura Joseph M. , Rafii Shahin
Published: January 2017

Transplanting vascular endothelial cells (ECs) to support metabolism and express regenerative paracrine factors is a strategy to treat vasculopathies and to promote tissue regeneration. However, transplantation strategies have been challenging to develop, because ECs are difficult to culture and little is known about how to direct them to stably integrate into vasculature. Here we show that only amniotic cells could convert to cells that maintain EC gene expression. Even so, these converted cells perform sub-optimally in transplantation studies. Constitutive Akt signalling increases expression of EC morphogenesis genes, including Sox17, shifts the genomic targeting of Fli1 to favour nearby Sox consensus sites and enhances the vascular function of converted cells. Enforced expression of Sox17 increases expression of morphogenesis genes and promotes integration of transplanted converted cells into injured vessels. Thus, Ets transcription factors specify non-vascular, amniotic cells to EC-like cells, whereas Sox17 expression is required to confer EC function.
The β-TrCP-FBXW2-SKP2 axis regulates lung cancer cell growth with FBXW2 acting as a tumour suppressor
Authors: Xu Jie , Zhou Weihua , Yang Fei , Chen Guoan , Li Haomin , Zhao Yongchao , Liu Pengyuan , Li Hua , Tan Mingjia , Xiong Xiufang , Sun Yi
Published: January 2017

β-TrCP and SKP2 are two well-studied F-box proteins, which often act as oncogenes. Whether and how they communicate with each other is unknown. Here we report that FBXW2, a poorly characterized F-box, is a substrate of β-TrCP1 and an E3 ligase for SKP2. While β-TrCP1 promotes FBXW2 ubiquitylation and shortens its half-life, FBXW2 does the same to SKP2. FBXW2 has tumour suppressor activity against lung cancer cells and blocks oncogenic function of both β-TrCP1 and SKP2. The levels of β-TrCP1-FBXW2-SKP2 are inversely correlated during cell cycle with FBXW2 and β-TrCP/SKP2 being high or low, respectively, in arrested cells, whereas the opposite is true in proliferating cells. Consistently, FBXW2 predicts a better patient survival, whereas β-TrCP1 and SKP2 predict a worse survival. Finally, the gain- and loss-of-function mutations of FBXW2 are found in various human cancers. Collectively, our data show that the β-TrCP-FBXW2-SKP2 axis forms an oncogene-tumour suppressor-oncogene cascade to control cancer cell growth with FBXW2 acting as a tumour suppressor by promoting SKP2 degradation.
A mast cell-ILC2-Th9 pathway promotes lung inflammation in cystic fibrosis
Authors: Moretti Silvia , Renga Giorgia , Oikonomou Vasilis , Galosi Claudia , Pariano Marilena , Iannitti Rossana G. , Borghi Monica , Puccetti Matteo , De Zuani Marco , Pucillo Carlo E. , Paolicelli Giuseppe , Zelante Teresa , Renauld Jean-Christophe , Bereshchenko Oxana , Sportoletti Paolo , Lucidi Vincenzina , Russo Maria Chiara , Colombo Carla , Fiscarelli Ersilia , Lass-Flörl Cornelia , Majo Fabio , Ricciotti Gabriella , Ellemunter Helmut , Ratclif Luigi , Talesa Vincenzo Nicola , Napolioni Valerio , Romani Luigina
Published: January 2017

T helper 9 (Th9) cells contribute to lung inflammation and allergy as sources of interleukin-9 (IL-9). However, the mechanisms by which IL-9/Th9 mediate immunopathology in the lung are unknown. Here we report an IL-9-driven positive feedback loop that reinforces allergic inflammation. We show that IL-9 increases IL-2 production by mast cells, which leads to expansion of CD25+type 2 innate lymphoid cells (ILC2) and subsequent activation of Th9 cells. Blocking IL-9 or inhibiting CD117 (c-Kit) signalling counteracts the pathogenic effect of the described IL-9-mast cell-IL-2 signalling axis. Overproduction of IL-9 is observed in expectorates from cystic fibrosis (CF) patients, and a sex-specific variant of IL-9 is predictive of allergic reactions in female patients. Our results suggest that blocking IL-9 may be a therapeutic strategy to ameliorate inflammation associated with microbial colonization in the lung, and offers a plausible explanation for gender differences in clinical outcomes of patients with CF.
Repo-Man/PP1 regulates heterochromatin formation in interphase
Authors: de Castro Inês J. , Budzak James , Di Giacinto Maria L. , Ligammari Lorena , Gokhan Ezgi , Spanos Christos , Moralli Daniela , Richardson Christine , de las Heras Jose I. , Salatino Silvia , Schirmer Eric C. , Ullman Katharine S. , Bickmore Wendy A. , Green Catherine , Rappsilber Juri , Lamble Sarah , Goldberg Martin W. , Vinciotti Veronica , Vagnarelli Paola
Published: January 2017

Repo-Man is a protein phosphatase 1 (PP1) targeting subunit that regulates mitotic progression and chromatin remodelling. After mitosis, Repo-Man/PP1 remains associated with chromatin but its function in interphase is not known. Here we show that Repo-Man, via Nup153, is enriched on condensed chromatin at the nuclear periphery and at the edge of the nucleopore basket. Repo-Man/PP1 regulates the formation of heterochromatin, dephosphorylates H3S28 and it is necessary and sufficient for heterochromatin protein 1 binding and H3K27me3 recruitment. Using a novel proteogenomic approach, we show that Repo-Man is enriched at subtelomeric regions together with H2AZ and H3.3 and that depletion of Repo-Man alters the peripheral localization of a subset of these regions and alleviates repression of some polycomb telomeric genes. This study shows a role for a mitotic phosphatase in the regulation of the epigenetic landscape and gene expression in interphase.
Massively parallel digital transcriptional profiling of single cells
Authors: Zheng Grace X. Y. , Terry Jessica M. , Belgrader Phillip , Ryvkin Paul , Bent Zachary W. , Wilson Ryan , Ziraldo Solongo B. , Wheeler Tobias D. , McDermott Geoff P. , Zhu Junjie , Gregory Mark T. , Shuga Joe , Montesclaros Luz , Underwood Jason G. , Masquelier Donald A. , Nishimura Stefanie Y. , Schnall-Levin Michael , Wyatt Paul W. , Hindson Christopher M. , Bharadwaj Rajiv , Wong Alexander , Ness Kevin D. , Beppu Lan W. , Deeg H. Joachim , McFarland Christopher , Loeb Keith R. , Valente William J. , Ericson Nolan G. , Stevens Emily A. , Radich Jerald P. , Mikkelsen Tarjei S. , Hindson Benjamin J. , Bielas Jason H.
Published: January 2017

Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3′ mRNA counting of tens of thousands of single cells per sample. Cell encapsulation, of up to 8 samples at a time, takes place in ∼6 min, with ∼50% cell capture efficiency. To demonstrate the system’s technical performance, we collected transcriptome data from ∼250k single cells across 29 samples. We validated the sensitivity of the system and its ability to detect rare populations using cell lines and synthetic RNAs. We profiled 68k peripheral blood mononuclear cells to demonstrate the system’s ability to characterize large immune populations. Finally, we used sequence variation in the transcriptome data to determine host and donor chimerism at single-cell resolution from bone marrow mononuclear cells isolated from transplant patients.
Cubosomes from hierarchical self-assembly of poly(ionic liquid) block copolymers
Authors: He Hongkun , Rahimi Khosrow , Zhong Mingjiang , Mourran Ahmed , Luebke David R. , Nulwala Hunaid B. , Möller Martin , Matyjaszewski Krzysztof
Published: January 2017

Cubosomes are micro- and nanoparticles with a bicontinuous cubic two-phase structure, reported for the self-assembly of low molecular weight surfactants, for example, lipids, but rarely formed by polymers. These objects are characterized by a maximum continuous interface and high interface to volume ratio, which makes them promising candidates for efficient adsorbents and host-guest applications. Here we demonstrate self-assembly to nanoscale cuboidal particles with a bicontinuous cubic structure by amphiphilic poly(ionic liquid) diblock copolymers, poly(acrylic acid)-block-poly(4-vinylbenzyl)-3-butyl imidazolium bis(trifluoromethylsulfonyl)imide, in a mixture of tetrahydrofuran and water under optimized conditions. Structure determining parameters include polymer composition and concentration, temperature, and the variation of the solvent mixture. The formation of the cubosomes can be explained by the hierarchical interactions of the constituent components. The lattice structure of the block copolymers can be transferred to the shape of the particle as it is common for atomic and molecular faceted crystals.
Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease
Authors: Keliher Edmund J. , Ye Yu-Xiang , Wojtkiewicz Gregory R. , Aguirre Aaron D. , Tricot Benoit , Senders Max L. , Groenen Hannah , Fay Francois , Perez-Medina Carlos , Calcagno Claudia , Carlucci Giuseppe , Reiner Thomas , Sun Yuan , Courties Gabriel , Iwamoto Yoshiko , Kim Hye-Yeong , Wang Cuihua , Chen John W. , Swirski Filip K. , Wey Hsiao-Ying , Hooker Jacob , Fayad Zahi A. , Mulder Willem J. M. , Weissleder Ralph , Nahrendorf Matthias
Published: January 2017

Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients. Here we describe positron emission tomography (PET) imaging with 18F-Macroflor, a modified polyglucose nanoparticle with high avidity for macrophages. Due to its small size, Macroflor is excreted renally, a prerequisite for imaging with the isotope flourine-18. The particle’s short blood half-life, measured in three species, including a primate, enables macrophage imaging in inflamed cardiovascular tissues. Macroflor enriches in cardiac and plaque macrophages, thereby increasing PET signal in murine infarcts and both mouse and rabbit atherosclerotic plaques. In PET/magnetic resonance imaging (MRI) experiments, Macroflor PET imaging detects changes in macrophage population size while molecular MRI reports on increasing or resolving inflammation. These data suggest that Macroflor PET/MRI could be a clinical tool to non-invasively monitor macrophage biology.
Long-term efficient organic photovoltaics based on quaternary bulk heterojunctions
Authors: Nam Minwoo , Cha Minjeong , Lee Hyun Hwi , Hur Kahyun , Lee Kyu-Tae , Yoo Jaehong , Han Il Ki , Kwon S. Joon , Ko Doo-Hyun
Published: January 2017

A major impediment to the commercialization of organic photovoltaics (OPVs) is attaining long-term morphological stability of the bulk heterojunction (BHJ) layer. To secure the stability while pursuing optimized performance, multi-component BHJ-based OPVs have been strategically explored. Here we demonstrate the use of quaternary BHJs (q-BHJs) composed of two conjugated polymer donors and two fullerene acceptors as a novel platform to produce high-efficiency and long-term durable OPVs. A q-BHJ OPV (q-OPV) with an experimentally optimized composition exhibits an enhanced efficiency and extended operational lifetime than does the binary reference OPV. The q-OPV would retain more than 72% of its initial efficiency (for example, 8.42–6.06%) after a 1-year operation at an elevated temperature of 65 °C. This is superior to those of the state-of-the-art BHJ-based OPVs. We attribute the enhanced stability to the significant suppression of domain growth and phase separation between the components via kinetic trapping effect.
Intragranular cracking as a critical barrier for high-voltage usage of layer-structured cathode for lithium-ion batteries
Authors: Yan Pengfei , Zheng Jianming , Gu Meng , Xiao Jie , Zhang Ji-Guang , Wang Chong-Min
Published: January 2017

LiNi1/3Mn1/3Co1/3O2-layered cathode is often fabricated in the form of secondary particles, consisting of densely packed primary particles. This offers advantages for high energy density and alleviation of cathode side reactions/corrosions, but introduces drawbacks such as intergranular cracking. Here, we report unexpected observations on the nucleation and growth of intragranular cracks in a commercial LiNi1/3Mn1/3Co1/3O2 cathode by using advanced scanning transmission electron microscopy. We find the formation of the intragranular cracks is directly associated with high-voltage cycling, an electrochemically driven and diffusion-controlled process. The intragranular cracks are noticed to be characteristically initiated from the grain interior, a consequence of a dislocation-based crack incubation mechanism. This observation is in sharp contrast with general theoretical models, predicting the initiation of intragranular cracks from grain boundaries or particle surfaces. Our study emphasizes that maintaining structural stability is the key step towards high-voltage operation of layered-cathode materials.
Prediction and real-time compensation of qubit decoherence via machine learning
Authors: Mavadia Sandeep , Frey Virginia , Sastrawan Jarrah , Dona Stephen , Biercuk Michael J.
Published: January 2017

The wide-ranging adoption of quantum technologies requires practical, high-performance advances in our ability to maintain quantum coherence while facing the challenge of state collapse under measurement. Here we use techniques from control theory and machine learning to predict the future evolution of a qubit’s state; we deploy this information to suppress stochastic, semiclassical decoherence, even when access to measurements is limited. First, we implement a time-division multiplexed approach, interleaving measurement periods with periods of unsupervised but stabilised operation during which qubits are available, for example, in quantum information experiments. Second, we employ predictive feedback during sequential but time delayed measurements to reduce the Dick effect as encountered in passive frequency standards. Both experiments demonstrate significant improvements in qubit-phase stability over ‘traditional’ measurement-based feedback approaches by exploiting time domain correlations in the noise processes. This technique requires no additional hardware and is applicable to all two-level quantum systems where projective measurements are possible.
API5 confers cancer stem cell-like properties through the FGF2-NANOG axis
Authors: Song K-H , Cho H , Kim S , Lee H-J , Oh S J , Woo S R , Hong S-O , Jang H S , Noh K H , Choi C H , Chung J-Y , Hewitt S M , Kim J-H , Son M , Kim S-H , Lee B I , Park H-C , Bae Y-K , Kim T W
Published: January 2017

Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity. Critically, these CSC-like properties mediated by API5 are dependent on FGFR1 signaling, which is triggered by E2F1-dependent FGF2 expression. Furthermore, we uncovered the FGF2-NANOG molecular axis as a downstream component of API5 signaling that is conserved in cervical cancer patients. Finally, we found that the blockade of FGFR signaling is an effective strategy to control API5high human cancer. Thus, our findings reveal a crucial role of API5 in linking immune resistance and CSC-like properties, and provide the rationale for its therapeutic application for the treatment of API5+ refractory tumors.
Evaluation and comparison of classical interatomic potentials through a user-friendly interactive web-interface
Authors: Choudhary Kamal , Congo Faical Yannick P. , Liang Tao , Becker Chandler , Hennig Richard G. , Tavazza Francesca
Published: January 2017

Classical empirical potentials/force-fields (FF) provide atomistic insights into material phenomena through molecular dynamics and Monte Carlo simulations. Despite their wide applicability, a systematic evaluation of materials properties using such potentials and, especially, an easy-to-use user-interface for their comparison is still lacking. To address this deficiency, we computed energetics and elastic properties of variety of materials such as metals and ceramics using a wide range of empirical potentials and compared them to density functional theory (DFT) as well as to experimental data, where available. The database currently consists of 3248 entries including energetics and elastic property calculations, and it is still increasing. We also include computational tools for convex-hull plots for DFT and FF calculations. The data covers 1471 materials and 116 force-fields. In addition, both the complete database and the software coding used in the process have been released for public use online (presently at http://www.ctcms.nist.gov/∼knc6/periodic.html) in a user-friendly way designed to enable further material design and discovery.
Whole genome sequencing data and de novo draft assemblies for 66 teleost species
Authors: Malmstrøm Martin , Matschiner Michael , Tørresen Ole K. , Jakobsen Kjetill S. , Jentoft Sissel
Published: January 2017

Teleost fishes comprise more than half of all vertebrate species, yet genomic data are only available for 0.2% of their diversity. Here, we present whole genome sequencing data for 66 new species of teleosts, vastly expanding the availability of genomic data for this important vertebrate group. We report on de novo assemblies based on low-coverage (9–39×) sequencing and present detailed methodology for all analyses. To facilitate further utilization of this data set, we present statistical analyses of the gene space completeness and verify the expected phylogenetic position of the sequenced genomes in a large mitogenomic context. We further present a nuclear marker set used for phylogenetic inference and evaluate each gene tree in relation to the species tree to test for homogeneity in the phylogenetic signal. Collectively, these analyses illustrate the robustness of this highly diverse data set and enable extensive reuse of the selected phylogenetic markers and the genomic data in general. This data set covers all major teleost lineages and provides unprecedented opportunities for comparative studies of teleosts.
Unraveling the enhanced Oxygen Vacancy Formation in Complex Oxides during Annealing and Growth
Authors: Hensling Felix V. E. , Xu Chencheng , Gunkel Felix , Dittmann Regina
Published: January 2017

The reduction of oxides during annealing and growth in low pressure processes is a widely known problem. We hence investigate the influence of mere annealing and of growth in vacuum systems to shed light on the reasons behind the reduction of perovskites. When comparing the existing literature regarding the reduction of the perovskite model material SrTiO3 it is conspicuous that one finds different oxygen pressures required to achieve reduction for vacuum annealing and for chemically controlled reducing atmospheres. The unraveling of this discrepancy is of high interest for low pressure physical vapor depositions of thin films heterostructures to gain further understanding of the reduction of the SrTiO3. For thermal annealing, our results prove the attached measurement devices (mass spectrometer/ cold cathode gauge) to be primarily responsible for the reduction of SrTiO3 in the deposition chamber by shifting the thermodynamic equilibrium to a more reducing atmosphere. We investigated the impact of our findings on the pulsed laser deposition growth at low pressure for LaAlO3/SrTiO3. During deposition the reduction triggered by the presence of the laser plume dominates and the impact of the measurement devices plays a minor role. During post annealing a complete reoxidization of samples is inhibited by an insufficient supply of oxygen.
Apelin receptor homodimer-oligomers revealed by single-molecule imaging and novel G protein-dependent signaling
Authors: Cai Xin , Bai Bo , Zhang Rumin , Wang Chunmei , Chen Jing
Published: January 2017

The apelin receptor (APJ) belongs to family A of the G protein-coupled receptors (GPCRs) and is a potential pharmacotherapeutic target for heart failure, hypertension, and other cardiovascular diseases. There is evidence APJ heterodimerizes with other GPCRs; however, the existence of APJ homodimers and oligomers remains to be investigated. Here, we measured APJ monomer-homodimer-oligomer interconversion by monitoring APJ dynamically on cells and compared their proportions, spatial arrangement, and mobility using total internal reflection fluorescence microscopy, resonance energy transfer, and proximity biotinylation. In cells with <0.3 receptor particles/μm2, approximately 60% of APJ molecules were present as dimers or oligomers. APJ dimers were present on the cell surface in a dynamic equilibrium with constant formation and dissociation of receptor complexes. Furthermore, we applied interference peptides and MALDI-TOF mass spectrometry to confirm APJ homo-dimer and explore the dimer-interfaces. Peptides corresponding to transmembrane domain (TMD)1, 2, 3, and 4, but not TMD5, 6, and 7, disrupted APJ dimerization. APJ mutants in TMD1 and TMD2 also decreased bioluminescence resonance energy transfer of APJ dimer. APJ dimerization resulted in novel functional characteristics, such as a distinct G-protein binding profile and cell responses after agonist stimulation. Thus, dimerization may serve as a unique mechanism for fine-tuning APJ-mediated functions.
Perceived Stress and Colorectal Cancer Incidence: The Japan Collaborative Cohort Study
Authors: Kikuchi Norimasa , Nishiyama Takeshi , Sawada Takayuki , Wang Chaochen , Lin Yingsong , Watanabe Yoshiyuki , Tamakoshi Akiko , Kikuchi Shogo
Published: January 2017

Colorectal cancer is the third most common cancer worldwide, and many risk factors for colorectal cancer have been established. However, it remains uncertain whether psychological stress contributes to the onset of colorectal cancer. Therefore, we conducted a large-scale prospective cohort study to confirm the association between perceived stress and colorectal cancer incidence. We identified 680 cases of colon cancer and 330 cases of rectal cancer during a maximum of 21-year follow-up of 61,563 Japanese men and women. Cox regression analysis adjusted for potential confounders revealed a significant association of perceived stress with rectal cancer incidence but not with colon cancer incidence. This finding is partly consistent with that from only one previous study that addressed an association between perceived stress and the risk of colorectal cancer. However, studies on this topic are sparse and warrant further exploration.
Binding of N-methylscopolamine to the extracellular domain of muscarinic acetylcholine receptors
Authors: Jakubík Jan , Randáková Alena , Zimčík Pavel , El-Fakahany Esam E. , Doležal Vladimír
Published: January 2017

Interaction of orthosteric ligands with extracellular domain was described at several aminergic G protein-coupled receptors, including muscarinic acetylcholine receptors. The orthosteric antagonists quinuclidinyl benzilate (QNB) and N-methylscopolamine (NMS) bind to the binding pocket of the muscarinic acetylcholine receptor formed by transmembrane α-helices. We show that high concentrations of either QNB or NMS slow down dissociation of their radiolabeled species from all five subtypes of muscarinic acetylcholine receptors, suggesting allosteric binding. The affinity of NMS at the allosteric site is in the micromolar range for all receptor subtypes. Using molecular modelling of the M2 receptor we found that E172 and E175 in the second extracellular loop and N419 in the third extracellular loop are involved in allosteric binding of NMS. Mutation of these amino acids to alanine decreased affinity of NMS for the allosteric binding site confirming results of molecular modelling. The allosteric binding site of NMS overlaps with the binding site of some allosteric, ectopic and bitopic ligands. Understanding of interactions of NMS at the allosteric binding site is essential for correct analysis of binding and action of these ligands.
Imbalance of Th17/Treg cells in pathogenesis of patients with human leukocyte antigen B27 associated acute anterior uveitis
Authors: Zhuang Zhenchao , Wang Yuqin , Zhu Gejing , Gu Yunfeng , Mao Liping , Hong Meng , Li Yali , Zheng Meiqin
Published: January 2017

Th17 and regulatory T cells, involved in the pathogenesis of several autoimmune diseases, are new lineages of CD4+ T helper cells. However, the role of their imbalance in human leukocyte antigen B27-associated acute anterior uveitis has not been elucidated. In our study, the percentages of Th17 and Treg cells, their molecular markers and related factors in peripheral blood of patients and healthy controls were measured by flow cytometry, real-time RT-PCR and ELISA. We observed a remarkable increase of CD4+ and CD4+IL-17+ T cells in peripheral blood of patients compared to controls. The molecular markers and related factors of Th17 cell were also showed a distinct elevation. Interestingly, we observed an obvious decrease of CD4+CD25+Foxp3+ T cells and Foxp3 mRNA level in patients. The ratio of Th17/Treg in patients was dramatically higher than controls. Moreover, the ratio of Th17/Treg cells had a more significantly positive correlation with the disease activity score than Th17 cells whereas Treg cells had a negative correlation. Our findings demonstrated a distinct increase of Th17 cells and a significant decrease of Treg cells in patients compared to controls. The imbalance of Th17 and Treg cells may play a vital role in the pathogenesis of the disease.
Simple, Efficient and Controllable Synthesis of Iodo/Di-iodoarenes via Ipsoiododecarboxylation/Consecutive Iodination Strategy
Authors: Yang Yun , Zhang Lijuan , Deng Guo-Jun , Gong Hang
Published: January 2017

A practical, efficient, and operationally simple strategy for the ipsoiododecarboxylation and di-iodination of aromatic carboxylic acids using the low-cost commercial reagent succinimide (NIS) as iodine source is reported. This iodination or di-iodination process can be easily controlled through reaction conditions, thereby providing corresponding iodination or di-iodination products with high yields. Furthermore, these two reactions can be easily scaled up to gram-scale by using palladium catalyst (0.66 mol%), which provides high isolated yield.
Reversible Martensitic Transformation under Low Magnetic Fields in Magnetic Shape Memory Alloys
Authors: Bruno N. M. , Wang S. , Karaman I. , Chumlyakov Y. I.
Published: January 2017

Magnetic field-induced, reversible martensitic transformations in NiCoMnIn meta-magnetic shape memory alloys were studied under constant and varying mechanical loads to understand the role of coupled magneto-mechanical loading on the transformation characteristics and the magnetic field levels required for reversible phase transformations. The samples with two distinct microstructures were tested along the [001] austenite crystallographic direction using a custom designed magneto-thermo-mechanical characterization device while carefully controlling their thermodynamic states through isothermal constant stress and stress-varying magnetic field ramping. Measurements revealed that these meta-magnetic shape memory alloys were capable of generating entropy changes of 14 J kg−1 K−1 or 22 J kg −1 K−1, and corresponding magnetocaloric cooling with reversible shape changes as high as 5.6% under only 1.3 T, or 3 T applied magnetic fields, respectively. Thus, we demonstrate that this alloy is suitable as an active component in near room temperature devices, such as magnetocaloric regenerators, and that the field levels generated by permanent magnets can be sufficient to completely transform the alloy between its martensitic and austenitic states if the loading sequence developed, herein, is employed.
Improvement of thermoelectric properties and their correlations with electron effective mass in Cu1.98SxSe1−x
Authors: Zhao Lanling , Fei Frank Yun , Wang Jun , Wang Funing , Wang Chunlei , Li Jichao , Wang Jiyang , Cheng Zhenxiang , Dou Shixue , Wang Xiaolin
Published: January 2017

Sulphur doping effects on the crystal structures, thermoelectric properties, density-of-states, and effective mass in Cu1.98SxSe1−x were studied based on the electrical and thermal transport property measurements, and first-principles calculations. The X-ray diffraction patterns and Rietveld refinements indicate that room temperature Cu1.98SxSe1−x (x = 0, 0.02, 0.08, 0.16) and Cu1.98SxSe1−x (x = 0.8, 0.9, 1.0) have the same crystal structure as monoclinic-Cu2Se and orthorhombic-Cu2S, respectively. Sulphur doping can greatly enhance zT values when x is in the range of 0.8≤ × ≤1.0. Furthermore, all doped samples show stable thermoelectric compatibility factors over a broad temperature range from 700 to 1000 K, which could greatly benefit their practical applications. First-principles calculations indicate that both the electron density-of-sates and the effective mass for all the compounds exhibit non-monotonic sulphur doping dependence. It is concluded that the overall thermoelectric performance of the Cu1.98SxSe1−x system is mainly correlated with the electron effective mass and the density-of-states.
Corydalis edulis Maxim. Promotes Insulin Secretion via the Activation of Protein Kinase Cs (PKCs) in Mice and Pancreatic β Cells
Authors: Zheng Jiao , Zhao Yunfang , Lun Qixing , Song Yuelin , Shi Shepo , Gu Xiaopan , Pan Bo , Qu Changhai , Li Jun , Tu Pengfei
Published: January 2017

Corydalis edulisMaxim., a widely grown plant in China, had been proposed for the treatment for type 2 diabetes mellitus. In this study, we found thatC. edulisextract (CE) is protective against diabetes in mice. The treatment of hyperglycemic and hyperlipidemic apolipoprotein E (ApoE)−/− mice with a high dose of CE reduced serum glucose by 28.84% and serum total cholesterol by 17.34% and increased insulin release. We also found that CE significantly enhanced insulin secretion in a glucose-independent manner in hamster pancreatic β cell (HIT-T15). Further investigation revealed that CE stimulated insulin exocytosis by a protein kinase C (PKC)-dependent signaling pathway and that CE selectively activated novel protein kinase Cs (nPKCs) and atypical PKCs (aPKCs) but not conventional PKCs (cPKCs) in HIT-T15 cells. To the best of our knowledge, our study is the first to identify the PKC pathway as a direct target and one of the major mechanisms underlying the antidiabetic effect of CE. Given the good insulinotropic effect of this herbal medicine, CE is a promising agent for the development of new drugs for treating diabetes.
MircoRNA-145 promotes activation of hepatic stellate cells via targeting krüppel-like factor 4
Authors: Men Ruoting , Wen Maoyao , Zhao Mingyue , Dan Xuelian , Yang Zongze , Wu Wenchao , Wang Maggie Haitian , Liu Xiaojing , Yang Li
Published: January 2017

Krüppel-like Factor 4 (KLF4), a target gene of miR-145, can negatively regulate lung fibrosis. However, the potential role of KLF4 and miR-145 in hepatic stellate cells (HSCs) activation or in hepatic fibrosis keeps unclear. This study aims to characterize miR-145 and KLF4 in activated HSCs and liver cirrhotic, and the underlying molecular basis. miR-145 was significantly up-regulated, while KLF4 was dramatically down-regulated during the activation of rat primary HSCs and TGF-βtreated HSCs. Furthermore, miR-145 mimics induced and inhibition of miR-145 reduced α-SMA and COL-I expression in primary HSCs. Additionally, the mRNA and protein levels of KLF4 in the liver of cirrhotic patients and rats were significantly down-regulated. α-SMA and COL-I were increased after inhibition of KLF4 by specific shRNA in primary HSCs. Forced KLF4 expression led to a reduction of α-SMA and COL-I expression in HSCs. miR-145 promotes HSC activation and liver fibrosis by targeting KLF4.
Population expansions dominate demographic histories of endemic and widespread Pacific reef fishes
Authors: Delrieu-Trottin Erwan , Mona Stefano , Maynard Jeffrey , Neglia Valentina , Veuille Michel , Planes Serge
Published: January 2017

Despite the unique nature of endemic species, their origin and population history remain poorly studied. We investigated the population history of 28 coral reef fish species, close related, from the Gambier and Marquesas Islands, from five families, with range size varying from widespread to small-range endemic. We analyzed both mitochondrial and nuclear sequence data using neutrality test and Bayesian analysis (EBSP and ABC). We found evidence for demographic expansions for most species (24 of 28), irrespective of range size, reproduction strategy or archipelago. The timing of the expansions varied greatly among species, from 8,000 to 2,000,000 years ago. The typical hypothesis for reef fish that links population expansions to the Last Glacial Maximum fit for 14 of the 24 demographic expansions. We propose two evolutionary processes that could lead to expansions older than the LGM: (a) we are retrieving the signature of an old colonization process for widespread, large-range endemic and paleoendemic species or (b) speciation; the expansion reflects the birth of the species for neoendemic species. We show for the first time that the demographic histories of endemic and widespread reef fish are not distinctly different and suggest that a number of processes drive endemism.
Pirfenidone controls the feedback loop of the AT1R/p38 MAPK/renin-angiotensin system axis by regulating liver X receptor-α in myocardial infarction-induced cardiac fibrosis
Authors: Li Chunmei , Han Rui , Kang Le , Wang Jianping , Gao Yonglin , Li Yanshen , He Jie , Tian Jingwei
Published: January 2017

Pirfenidone (PFD), an anti-fibrotic small molecule drug, is used to treat fibrotic diseases, but its effects on myocardial infarction (MI)-induced cardiac fibrosis are unknown. The aim of this study was to determine the effects of PFD on MI-induced cardiac fibrosis and the possible underlying mechanisms in rats. After establishment of the model, animals were administered PFD by gavage for 4 weeks. During the development of MI-induced cardiac fibrosis, we found activation of a positive feedback loop between the angiotensin II type 1 receptor (AT1R)/phospho-p38 mitogen-activated protein kinase (p38 MAPK) pathway and renin-angiotensin system (RAS), which was accompanied by down-regulation of liver X receptor-α (LXR-α) expression. PFD attenuated body weight, heart weight, left ventricular weight, left ventricular systolic pressure, and ±dp/dtmax changes induced by MI, which were associated with a reduction in cardiac fibrosis, infarct size, and hydroxyproline concentration. Moreover, PFD inhibited the AT1R/p38 MAPK pathway, corrected the RAS imbalance [decreased angiotensin-converting enzyme (ACE), angiotensin II, and angiotensin II type 1 receptor expression, but increased ACE2 and angiotensin (1-7) activity and Mas expression] and strongly enhanced heart LXR-α expression. These results indicate that the cardioprotective effects of PFD may be due, in large part, to controlling the feedback loop of the AT1R/p38 MAPK/RAS axis by activation of LXR-α.
Transcriptomic basis for drought-resistance in Brassica napus L.
Authors: Wang Pei , Yang Cuiling , Chen Hao , Song Chunpeng , Zhang Xiao , Wang Daojie
Published: January 2017

Based on transcriptomic data from four experimental settings with drought-resistant and drought-sensitive cultivars under drought and well-watered conditions, statistical analysis revealed three categories encompassing 169 highly differentially expressed genes (DEGs) in response to drought in Brassica napus L., including 37 drought-resistant cultivar-related genes, 35 drought-sensitive cultivar-related genes and 97 cultivar non-specific ones. We provide evidence that the identified DEGs were fairly uniformly distributed on different chromosomes and their expression patterns are variety specific. Except commonly enriched in response to various stimuli or stresses, different categories of DEGs show specific enrichment in certain biological processes or pathways, which indicated the possibility of functional differences among the three categories. Network analysis revealed relationships among the 169 DEGs, annotated biological processes and pathways. The 169 DEGs can be classified into different functional categories via preferred pathways or biological processes. Some pathways might simultaneously involve a large number of shared DEGs, and these pathways are likely to cross-talk and have overlapping biological functions. Several members of the identified DEGs fit to drought stress signal transduction pathway in Arabidopsis thaliana. Finally, quantitative real-time PCR validations confirmed the reproducibility of the RNA-seq data. These investigations are profitable for the improvement of crop varieties through transgenic engineering.
Switch from sexual to parthenogenetic reproduction in a zebra shark
Authors: Dudgeon Christine L. , Coulton Laura , Bone Ren , Ovenden Jennifer R. , Thomas Severine
Published: January 2017

Parthenogenesis is a natural form of asexual reproduction in which embryos develop in the absence of fertilisation. Most commonly found in plants and invertebrate organisms, an increasing number of vertebrate species have recently been reported employing this reproductive strategy. Here we use DNA genotyping to report the first demonstration of an intra-individual switch from sexual to parthenogenetic reproduction in a shark species, the zebra shark Stegostoma fasciatum. A co-housed, sexually produced daughter zebra shark also commenced parthenogenetic reproduction at the onset of maturity without any prior mating. The demonstration of parthenogenesis in these two conspecific individuals with different sexual histories provides further support that elasmobranch fishes may flexibly adapt their reproductive strategy to environmental circumstances.
Efficient generation of hPSC-derived midbrain dopaminergic neurons in a fully defined, scalable, 3D biomaterial platform
Authors: Adil Maroof M. , Rodrigues Gonçalo M. C. , Kulkarni Rishikesh U. , Rao Antara T. , Chernavsky Nicole E. , Miller Evan W. , Schaffer David V.
Published: January 2017

Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson’s Disease (PD) therapy; however, production of these cells typically involves undefined components and difficult to scale 2D culture formats. Here, we used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing mDA neurons after 25 days of differentiation (~40% tyrosine hydroxylase (TH) positive, maturing into 25% cells exhibiting mDA neuron-like spiking behavior). Importantly, mDA neurons generated in 3D exhibited a 30-fold increase in viability upon implantation into rat striatum compared to neurons generated on 2D, consistent with the elevated expression of survival markers FOXA2 and EN1 in 3D. A defined, scalable, and resource-efficient cell culture platform can thus rapidly generate high quality differentiated cells, both neurons and potentially other cell types, with strong potential to accelerate both basic and translational research.
VEGF-B promotes recovery of corneal innervations and trophic functions in diabetic mice
Authors: Di Guohu , Zhao Xiaowen , Qi Xia , Zhang Songmei , Feng Lu , Shi Weiyun , Zhou Qingjun
Published: January 2017

Vascular endothelial growth factor (VEGF)-B possesses the capacity of promoting injured peripheral nerve regeneration and restore their sensory and trophic functions. However, the contribution and mechanism of VEGF-B in diabetic peripheral neuropathy remains unclear. In the present study, we investigated the expression and role of VEGF-B in diabetic corneal neuropathy by using type 1 diabetic mice and cultured trigeminal ganglion (TG) neurons. Hyperglycemia attenuated the endogenous expression of VEGF-B in regenerated diabetic corneal epithelium, but not that of VEGF receptors in diabetic TG neurons and axons. Exogenous VEGF-B promoted diabetic corneal nerve fiber regeneration through the reactivation of PI-3K/Akt-GSK3β-mTOR signaling and the attenuation of neuronal mitochondria dysfunction via the VEGF receptor-1 and neuropilin-1. Moreover, VEGF-B improved corneal sensation and epithelial regeneration in both normal and diabetic mice, accompanied with the elevated corneal content of pigment epithelial-derived factor (PEDF). PEDF blockade partially abolished trophic function of VEGF-B in diabetic corneal re-innervation. In conclusion, hyperglycemia suppressed endogenous VEGF-B expression in regenerated corneal epithelium of diabetic mice, while exogenous VEGF-B promoted recovery of corneal innervations and trophic functions through reactivating PI-3K/Akt-GSK-3β-mTOR signaling, attenuating neuronal oxidative stress and elevating PEDF expression.
Mitotic catastrophe is a putative mechanism underlying the weak correlation between sensitivity to carbon ions and cisplatin
Authors: Kobayashi Daijiro , Oike Takahiro , Shibata Atsushi , Niimi Atsuko , Kubota Yoshiki , Sakai Makoto , Amornwhichet Napapat , Yoshimoto Yuya , Hagiwara Yoshihiko , Kimura Yuka , Hirota Yuka , Sato Hiro , Isono Mayu , Yoshida Yukari , Kohno Takashi , Ohno Tatsuya , Nakano Takashi
Published: January 2017

In cancer therapy today, carbon ion radiotherapy is used mainly as monotherapy, whereas cisplatin is used concomitantly with X-ray radiotherapy. The effectiveness of concomitant carbon ions and cisplatin is unclear. To obtain the information on the mechanisms potentially shared between carbon ions or X-rays and cisplatin, we assessed the correlation of sensitivity to the single treatments. In 20 human cancer cell lines, sensitivity to X-rays strongly correlated with sensitivity to cisplatin, indicating the presence of potentially shared target mechanisms. Interestingly, the correlation of sensitivity to carbon ions and cisplatin was much weaker than that of sensitivity to X-rays and cisplatin, indicating the presence of potentially different target mechanisms between carbon ions and cisplatin. Assessment of clonogenic cell death by 4′,6-diamidino-2-phenylindole dihydrochloride staining showed that mitotic catastrophe was more efficiently induced by carbon ions than by the same physical dose of X-rays, while apoptosis and senescence were not. These data indicate that the correlation of sensitivity to carbon ions and cisplatin is weaker than that of sensitivity to X-rays and cisplatin, which are helpful as biological basis to understand the potentially shared mechanism among these treatments. Further investigation is mandatory to elucidate the clinical efficacy of carbon ions and cisplatin combination.
Brain Structural Differences between Normal and Obese Adults and their Links with Lack of Perseverance, Negative Urgency, and Sensation Seeking
Authors: Wang Haifeng , Wen Baohong , Cheng Jingliang , Li Hongpeng
Published: January 2017

In order to examine the difference in brain structure between obese and normal weight individuals, and to explore the relationship between the neuroanatomical changes and impulsivity traits, this study used a voxel-based morphometry method to examine gray matter (GM) volume alterations related to impulsive personality traits in obese individuals relative to normal weight. Eighty adults that completed the UPPS-P Impulsive Behavior Scale were analyzed. Possible GM volume alterations were first analyzed at the whole brain level, and then the relationship between regional GM volume differences and UPPS-P scores were examined in selected regions of interest. Reduced GM volumes were found in the frontal and limbic regions in the obese group compared to normal weight individuals. In the normal weight group, lack of perseverance was negatively correlated with GM volume in the anterior cingulate cortex, and negative urgency was negatively correlated with GM volume in the insula. In the obese group, sensation seeking was negatively correlated with GM volume in the left amygdala and right pallidum. These findings might improve our understanding of the relationship between lack of perseverance, negative urgency, and sensation seeking and body weight fluctuations.