bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic and genetic analysis of cognitive performance in Major Depressive Disorder in the Generation Scotland: Scottish Family Health Study
Authors: Meijsen Joeri J. , Campbell Archie , Hayward Caroline , Porteous David J. , Deary Ian J. , Marioni Riccardo E. , Nicodemus Kristin K.
Published: March 2018

Lower performances in cognitive ability in individuals with Major Depressive Disorder (MDD) have been observed on multiple occasions. Understanding cognitive performance in MDD could provide a wider insight in the aetiology of MDD as a whole. Using a large, well characterised cohort (N = 7012), we tested for: differences in cognitive performance by MDD status and a gene (single SNP or polygenic score) by MDD interaction effect on cognitive performance. Linear regression was used to assess the association between cognitive performance and MDD status in a case-control, single-episode–recurrent MDD and control-recurrent MDD study design. Test scores on verbal declarative memory, executive functioning, vocabulary, and processing speed were examined. Cognitive performance measures showing a significant difference between groups were subsequently analysed for genetic associations. Those with recurrent MDD have lower processing speed versus controls and single-episode MDD (β = −2.44, p = 3.6 × 10−04; β = -2.86, p = 1.8 × 10−03, respectively). There were significantly higher vocabulary scores in MDD cases versus controls (β = 0.79, p = 2.0 × 10−06), and for recurrent MDD versus controls (β = 0.95, p = 5.8 × 10−05). Observed differences could not be linked to significant single-locus associations. Polygenic scores created from a processing speed meta-analysis GWAS explained 1% of variation in processing speed performance in the single-episode versus recurrent MDD study (p = 1.7 × 10−03) and 0.5% of variation in the control versus recurrent MDD study (p = 1.6 × 10−10). Individuals with recurrent MDD showed lower processing speed and executive function while showing higher vocabulary performance. Within MDD, persons with recurrent episodes show lower processing speed and executive function scores relative to individuals experiencing a single episode.
miR-27a inhibits cervical adenocarcinoma progression by downregulating the TGF-βRI signaling pathway
Authors: Fang Fang , Huang Bangxing , Sun Si , Xiao Man , Guo Jing , Yi Xiaoqing , Cai Jing , Wang Zehua
Published: March 2018

High-risk human papillomavirus infection is essential for the malignant transformation of cervical cancer and can inhibit host miR-27a expression. We investigated the role and mechanism of miR-27a in cervical cancer progression. miR-27a is decreased in cervical cancer cell lines and miR-27a-agomir inhibited the cell proliferation, migration, and invasion properties of HeLa (adenocarcinoma) cells, but not in SiHa cells (squamous cell carcinoma). Luciferase assays revealed that miR-27a directly targets the 3′-UTR of transforming growth factor beta receptor I (TGF-βRI) and downregulates TGF-β signaling. The co-transfection of a TGF-βRI expression vector largely restored the inhibition of TGF-β signaling, cell proliferation, migration, and invasion mediated by miR-27a-agomir. Also, miR-27a-agomir slows down the growth of subcutaneous HeLa xenografts and downregulates the TGF-βRI expression and TGF-β signaling in tumor in vivo. Tissue microarray analysis revealed a low miR-27a level in adenocarcinoma cells, but not in squamous cell carcinoma cells, which was negatively associated with TGF-βRI expression. High TGF-βRI correlated with deep stromal invasion and lymph node metastasis. These results suggest that miR-27a acts as a tumor suppressor in cervical cancer, especially in adenocarcinoma, by inhibiting TGF-βRI signaling pathway. Thus, enhancing miR-27a expression and function may be a novel treatment strategy for cervical adenocarcinoma.
Archimedes’ law explains penetration of solids into granular media
Authors: Kang Wenting , Feng Yajie , Liu Caishan , Blumenfeld Raphael
Published: March 2018

Understanding the response of granular matter to intrusion of solid objects is key to modelling many aspects of behaviour of granular matter, including plastic flow. Here we report a general model for such a quasistatic process. Using a range of experiments, we first show that the relation between the penetration depth and the force resisting it, transiently nonlinear and then linear, is scalable to a universal form. We show that the gradient of the steady-state part, K
ϕ
, depends only on the medium’s internal friction angle, ϕ, and that it is nonlinear in μ = tan ϕ, in contrast to an existing conjecture. We further show that the intrusion of any convex solid shape satisfies a modified Archimedes’ law and use this to: relate the zero-depth intercept of the linear part to K
ϕ
and the intruder’s cross-section; explain the curve’s nonlinear part in terms of the stagnant zone’s development.
Publisher Correction: Beyond a phenomenological description of magnetostriction
Authors: Reid A. H. , Shen X. , Maldonado P. , Chase T. , Jal E. , Granitzka P. W. , Carva K. , Li R. K. , Li J. , Wu L. , Vecchione T. , Liu T. , Chen Z. , Higley D. J. , Hartmann N. , Coffee R. , Wu J. , Dakowski G. L. , Schlotter W. F. , Ohldag H. , Takahashi Y. K. , Mehta V. , Hellwig O. , Fry A. , Zhu Y. , Cao J. , Fullerton E. E. , Stöhr J. , Oppeneer P. M. , Wang X. J. , Dürr H. A.
Published: March 2018

“The technical support from SLAC Accelerator Directorate, Technology Innovation Directorate, LCLS laser division and Test Facility Division is gratefully acknowledged. We thank S.P. Weathersby, R.K. Jobe, D. McCormick, A. Mitra, S. Carron and J. Corbett for their invaluable help and technical assistance. Research at SLAC was supported through the SIMES Institute which like the LCLS and SSRL user facilities is funded by the Office of Basic Energy Sciences of the U.S. Department of Energy under Contract No. DE-AC02-76SF00515. The UED work was performed at SLAC MeV-UED, which is supported in part by the DOE BES SUF Division Accelerator & Detector R&D program, the LCLS Facility, and SLAC under contract Nos. DE-AC02-05-CH11231 and DE-AC02-76SF00515. Use of the Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515.”

and

“Work at BNL was supported by DOE BES Materials Science and Engineering Division under Contract No: DE-AC02-98CH10886. J.C. would like to acknowledge the support from National Science Foundation Grant No. 1207252. E.E.F. would like to acknowledge support from the U.S. Department of Energy (DOE), Office of Basic Energy Sciences (BES) under Award No. DE-SC0003678.”

This has been corrected in both the PDF and HTML versions of the Article.
Continuous-wave highly-efficient low-divergence terahertz wire lasers
Authors: Biasco Simone , Garrasi Katia , Castellano Fabrizio , Li Lianhe , Beere Harvey E. , Ritchie David A. , Linfield Edmund H. , Davies A. Giles , Vitiello Miriam S.
Published: March 2018

Terahertz (THz) quantum cascade lasers (QCLs) have undergone rapid development since their demonstration, showing high power, broad-tunability, quantum-limited linewidth, and ultra-broadband gain. Typically, to address applications needs, continuous-wave (CW) operation, low-divergent beam profiles and fine spectral control of the emitted radiation, are required. This, however, is very difficult to achieve in practice. Lithographic patterning has been extensively used to this purpose (via distributed feedback (DFB), photonic crystals or microcavities), to optimize either the beam divergence or the emission frequency, or, both of them simultaneously, in third-order DFBs, via a demanding fabrication procedure that precisely constrains the mode index to 3. Here, we demonstrate wire DFB THz QCLs, in which feedback is provided by a sinusoidal corrugation of the cavity, defining the frequency, while light extraction is ensured by an array of surface holes. This new architecture, extendable to a broad range of far-infrared frequencies, has led to the achievement of low-divergent beams (10°), single-mode emission, high slope efficiencies (250 mW/A), and stable CW operation.
A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
Authors: Ladds Marcus J. G. W. , van Leeuwen Ingeborg M. M. , Drummond Catherine J. , Chu Su , Healy Alan R. , Popova Gergana , Pastor Fernández Andrés , Mollick Tanzina , Darekar Suhas , Sedimbi Saikiran K. , Nekulova Marta , Sachweh Marijke C. C. , Campbell Johanna , Higgins Maureen , Tuck Chloe , Popa Mihaela , Safont Mireia Mayoral , Gelebart Pascal , Fandalyuk Zinayida , Thompson Alastair M. , Svensson Richard , Gustavsson Anna-Lena , Johansson Lars , Färnegårdh Katarina , Yngve Ulrika , Saleh Aljona , Haraldsson Martin , D’Hollander Agathe C. A. , Franco Marcela , Zhao Yan , Håkansson Maria , Walse Björn , Larsson Karin , Peat Emma M. , Pelechano Vicent , Lunec John , Vojtesek Borivoj , Carmena Mar , Earnshaw William C. , McCarthy Anna R. , Westwood Nicholas J. , Arsenian-Henriksson Marie , Lane David P. , Bhatia Ravi , McCormack Emmet , Laín Sonia
Published: March 2018

The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.
Asymmetric adhesion of rod-shaped bacteria controls microcolony morphogenesis
Authors: Duvernoy Marie-Cécilia , Mora Thierry , Ardré Maxime , Croquette Vincent , Bensimon David , Quilliet Catherine , Ghigo Jean-Marc , Balland Martial , Beloin Christophe , Lecuyer Sigolène , Desprat Nicolas
Published: March 2018

Surface colonization underpins microbial ecology on terrestrial environments. Although factors that mediate bacteria–substrate adhesion have been extensively studied, their spatiotemporal dynamics during the establishment of microcolonies remains largely unexplored. Here, we use laser ablation and force microscopy to monitor single-cell adhesion during the course of microcolony formation. We find that adhesion forces of the rod-shaped bacteria Escherichia coli and Pseudomonas aeruginosa are polar. This asymmetry induces mechanical tension, and drives daughter cell rearrangements, which eventually determine the shape of the microcolonies. Informed by experimental data, we develop a quantitative model of microcolony morphogenesis that enables the prediction of bacterial adhesion strength from simple time-lapse measurements. Our results demonstrate how patterns of surface colonization derive from the spatial distribution of adhesive factors on the cell envelope.
Author Correction: Nuclear lamin A/C harnesses the perinuclear apical actin cables to protect nuclear morphology
Authors: Kim Jeong-Ki , Louhghalam Arghavan , Lee Geonhui , Schafer Benjamin W. , Wirtz Denis , Kim Dong-Hwee
Published: March 2018

In the original version of this Article, the affiliation details for Arghavan Louhghalam were incorrectly given as ‘Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, MD, 21218, USA’, and it should have been given as ‘Department of Civil and Environmental Engineering, University of Massachusetts Dartmouth, Dartmouth, MA 02747, USA’. Furthermore, an incorrect grant number, R1610512, was acknowledged. The correct grant number is NRF-2016R1C1B2015018. These errors have now been corrected in both the PDF and HTML versions of the Article.
SUMO targets the APC/C to regulate transition from metaphase to anaphase
Authors: Eifler Karolin , Cuijpers Sabine A. G. , Willemstein Edwin , Raaijmakers Jonne A. , El Atmioui Dris , Ovaa Huib , Medema René H. , Vertegaal Alfred C. O.
Published: March 2018

Signal transduction by small ubiquitin-like modifier (SUMO) regulates a myriad of nuclear processes. Here we report on the role of SUMO in mitosis in human cell lines. Knocking down the SUMO conjugation machinery results in a delay in mitosis and defects in mitotic chromosome separation. Searching for relevant SUMOylated proteins in mitosis, we identify the anaphase-promoting complex/cyclosome (APC/C), a master regulator of metaphase to anaphase transition. The APC4 subunit is the major SUMO target in the complex, containing SUMO acceptor lysines at positions 772 and 798. SUMOylation is crucial for accurate progression of cells through mitosis and increases APC/C ubiquitylation activity toward a subset of its targets, including the newly identified target KIF18B. Combined, our findings demonstrate the importance of SUMO signal transduction for genome integrity during mitotic progression and reveal how SUMO and ubiquitin cooperate to drive mitosis.
Publisher Correction: Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells
Authors: Caires-Júnior Luiz Carlos , Goulart Ernesto , Melo Uirá Souto , Araujo Bruno Henrique Silva , Alvizi Lucas , Soares-Schanoski Alessandra , de Oliveira Danyllo Felipe , Kobayashi Gerson Shigeru , Griesi-Oliveira Karina , Musso Camila Manso , Amaral Murilo Sena , daSilva Lucas Ferreira , Astray Renato Mancini , Suárez-Patiño Sandra Fernanda , Ventini Daniella Cristina , da Silva Sérgio Gomes , Yamamoto Guilherme Lopes , Ezquina Suzana , Naslavsky Michel Satya , Telles-Silva Kayque Alves , Weinmann Karina , van der Linden Vanessa , van der Linden Helio , de Oliveira João Ricardo Mendes , Arrais Nivia Maria Rodrigues , Melo Adriana , Figueiredo Thalita , Santos Silvana , Meira Joanna Goes Castro , Passos Saulo Duarte , de Almeida Roque Pacheco , Bispo Ana Jovina Barreto , Cavalheiro Esper Abrão , Kalil Jorge , Cunha-Neto Edécio , Nakaya Helder , Andreata-Santos Robert , de Souza Ferreira Luis Carlos , Verjovski-Almeida Sergio , Ho Paulo Lee , Passos-Bueno Maria Rita , Zatz Mayana
Published: March 2018

The original PDF version of this Article contained errors in the spelling of Luiz Carlos Caires-Júnior, Uirá Souto Melo, Bruno Henrique Silva Araujo, Alessandra Soares-Schanoski, Murilo Sena Amaral, Kayque Alves Telles-Silva, Vanessa van der Linden, Helio van der Linden, João Ricardo Mendes de Oliveira, Nivia Maria Rodrigues Arrais, Joanna Goes Castro Meira, Ana Jovina Barreto Bispo, Esper Abrão Cavalheiro, and Robert Andreata-Santos, which were incorrectly given as Luiz Carlos de Caires Jr., UiráSouto Melo, Bruno Silva Henrique Araujo, Alessandra Soares Schanoski, MuriloSena Amaral, Kayque Telles Alves Silva, Vanessa Van der Linden, Helio Van der Linden, João Mendes Ricardo de Oliveira, Nivia Rodrigues Maria Arrais, Joanna Castro Goes Meira, Ana JovinaBarreto Bispo, EsperAbrão Cavalheiro, and Robert Andreata Santos. Furthermore, in both the PDF and HTML versions of the Article, the top panel of Fig. 3e was incorrectly labeled ‘10608-1’ and should have been ‘10608-4’, and financial support from CAPES and DECIT-MS was inadvertently omitted from the Acknowledgements section. These errors have now been corrected in both the PDF and HTML versions of the Article.
A b map implying the first eastern rupture of the Nankai Trough earthquakes
Authors: Nanjo K. Z. , Yoshida A.
Published: March 2018

The Nankai Trough megathrust earthquakes inflicted catastrophic damage on Japanese society and more widely. Most research is aimed at identifying strongly coupled regions that are considered as a major source of future disastrous earthquakes. Here we present a b-value map for the entire Nankai Trough zone. The b value, which represents the rate of occurrence of small earthquakes relative to larger ones, is inversely dependent on differential stresses, and has been used to detect highly stressed areas on fault planes in various tectonic situations. A remarkable finding is that the b value is inversely correlated with the slip-deficit rate (SDR). Moreover, the b value for the areas of high SDR in the eastern part is lower than that in the western part, indicating that differential stress on asperities in the eastern part is higher than that in the western part. This may explain the history of the Nankai Trough earthquakes, in which the eastern part tends to rupture first.
Clathrin-adaptor ratio and membrane tension regulate the flat-to-curved transition of the clathrin coat during endocytosis
Authors: Bucher Delia , Frey Felix , Sochacki Kem A. , Kummer Susann , Bergeest Jan-Philip , Godinez William J. , Kräusslich Hans-Georg , Rohr Karl , Taraska Justin W. , Schwarz Ulrich S. , Boulant Steeve
Published: March 2018

Although essential for many cellular processes, the sequence of structural and molecular events during clathrin-mediated endocytosis remains elusive. While it was long believed that clathrin-coated pits grow with a constant curvature, it was recently suggested that clathrin first assembles to form flat structures that then bend while maintaining a constant surface area. Here, we combine correlative electron and light microscopy and mathematical growth laws to study the ultrastructural rearrangements of the clathrin coat during endocytosis in BSC-1 mammalian cells. We confirm that clathrin coats initially grow flat and demonstrate that curvature begins when around 70% of the final clathrin content is acquired. We find that this transition is marked by a change in the clathrin to clathrin-adaptor protein AP2 ratio and that membrane tension suppresses this transition. Our results support the notion that BSC-1 mammalian cells dynamically regulate the flat-to-curved transition in clathrin-mediated endocytosis by both biochemical and mechanical factors.
Publisher Correction: Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid
Authors: Song Youngzee , Zhou Huihao , Vo My-Nuong , Shi Yi , Nawaz Mir Hussain , Vargas-Rodriguez Oscar , Diedrich Jolene K. , Yates John R. , Kishi Shuji , Musier-Forsyth Karin , Schimmel Paul
Published: March 2018

In the original version of this Article, extraneous text not belonging to the article was accidentally appended to end of the first paragraph of the discussion. This error has now been corrected in both the PDF and HTML versions of the Article.
Management of constipation in patients with Parkinson’s disease
Authors: Pedrosa Carrasco Anna J. , Timmermann Lars , Pedrosa David J.
Published: March 2018

A considerable body of research has recently emerged around nonmotor symptoms in Parkinson’s disease (PD) and their substantial impact on patients’ well-being. A prominent example is constipation which occurs in up to two thirds of all PD-patients thereby effecting psychological and social distress and consequently reducing quality of life. Despite the significant clinical relevance of constipation, unfortunately little knowledge exists on effective treatments. Therefore this systematic review aims at providing a synopsis on clinical effects and safety of available treatment options for constipation in PD. For this purpose, three electronic databases (MEDLINE, EMBASE, PsycINFO) were searched for experimental and quasi-experimental studies investigating the efficacy/effectiveness of interventions in the management of PD-associated constipation. Besides, adverse events were analyzed as secondary outcome. In total, 18 publications were identified involving 15 different interventions, of which none can be attributed sufficient evidence to derive strong recommendations. Nevertheless, some evidence indicates that dietetic interventions with probiotics and prebiotics may reduce symptom burden while providing a very favorable side-effects profile. Furthermore, the use of lubiprostone, macrogol and in the specific case of isolated or prominent outlet obstruction constipation injections of botulinum neurotoxin A into the puborectal muscles may as well be moderately supported. In summary, too little attention has been paid to treatment options for constipation in PD leaving abundant room for further research addressing this topic.
Population screening and transmission experiments indicate paramyxid-microsporidian co-infection in Echinogammarus marinus represents a non-hyperparasitic relationship between specific parasite strains
Authors: Guler Yasmin , Short Stephen , Green Etxabe Amaia , Kille Peter , Ford Alex T.
Published: March 2018

Phylogenetically distant parasites often infect the same host. Indeed, co-infections can occur at levels greater than expected by chance and are sometimes hyperparasitic. The amphipod Echinogammarus marinus presents high levels of co-infection by two intracellular and vertically transmitted parasites, a paramyxid (Paramarteilia sp. Em) and a microsporidian strain (Dictyocoela duebenum Em). This co-infection may be hyperparasitic and result from an exploitative ‘hitchhiking’ or a symbiotic relationship between the parasites. However, the best-studied amphipod species are often collected from contaminated environments and may be immune-compromised. Immune-challenged animals frequently present co-infections and contaminant-exposed amphipods present significantly higher levels of microsporidian infection. This suggests the co-infections in E. marinus may result from contaminant-associated compromised immunity. Inconsistent with hyperparasitism, we find that artificial infections transmit Paramarteilia without microsporidian. Our population surveys reveal the co-infection relationship is geographically widespread but find only chance co-infection between the Paramarteilia and another species of microsporidian, Dictyocoela berillonum. Furthermore, we identify a haplotype of the Paramarteilia that presents no co-infection, even in populations with otherwise high co-infection levels. Overall, our results do not support the compromised-immunity hypothesis but rather that the co-infection of E. marinus, although non-hyperparasitic, results from a relationship between specific Paramarteilia and Dictyocoela duebenum strains.
Adaptive Transcriptome Profiling of Subterranean Zokor, Myospalax baileyi, to High- Altitude Stresses in Tibet
Authors: Cai Zhenyuan , Wang Liuyang , Song Xiaoying , Tagore Somnath , Li Xiangfeng , Wang Huihua , Chen Jiarui , Li Kexin , Frenkel Zeev , Gao Dahai , Frenkel-Morgenstern Milana , Zhang Tongzuo , Nevo Eviatar
Published: March 2018

Animals living at high altitudes have evolved distinct phenotypic and genotypic adaptations against stressful environments. We studied the adaptive patterns of altitudinal stresses on transcriptome turnover in subterranean plateau zokors (Myospalax baileyi) in the high-altitude Qinghai-Tibetan Plateau. Transcriptomes of zokors from three populations with distinct altitudes and ecologies (Low: 2846 m,Middle: 3282 m,High: 3,714 m) were sequenced and compared. Phylogenetic and principal component analyses classified them into three divergent altitudinal population clusters. Genetic polymorphisms showed that the population atH, approaching the uppermost species boundary, harbors the highest genetic polymorphism. Moreover, 1056 highly up-regulated UniGenes were identified fromMtoH. Gene ontologies reveal genes likeEPAS1andCOX1were overexpressed under hypoxia conditions.EPAS1,EGLN1, andCOX1were convergent in high-altitude adaptation against stresses in other species. The fixation indices (FSTandGST)-based outlier analysis identified 191 and 211 genes, highly differentiated amongL,M, andH. We observed adaptive transcriptome changes inMyospalax baileyi, across a few hundred meters, near the uppermost species boundary, regardless of their relatively stable underground burrows’ microclimate. The highly variant genes identified inMyospalaxwere involved in hypoxia tolerance, hypercapnia tolerance, ATP-pathway energetics, and temperature changes.
An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis
Authors: Ogura Yoji , Takeda Kazuki , Kou Ikuyo , Khanshour Anas , Grauers Anna , Zhou Hang , Liu Gang , Fan Yan-Hui , Zhou Taifeng , Wu Zhihong , Takahashi Yohei , Matsumoto Morio ,   Japan Scoliosis Clinical Research Group (JSCRG), Kawakami Noriaki , Tsuji Taichi , Uno Koki , Suzuki Teppei , Ito Manabu , Minami Shohei , Kotani Toshiaki , Sakuma Tsuyoshi , Yanagida Haruhisa , Taneichi Hiroshi , Yonezawa Ikuho , Sudo Hideki , Chiba Kazuhiro , Hosogane Naobumi , Nishida Kotaro , Kakutani Kenichiro , Akazawa Tsutomu , Kaito Takashi , Watanabe Kei , Harimaya Katsumi , Taniguchi Yuki , Shigematsu Hideki , Demura Satoru , Iida Takahiro , Kono Katsuki , Okada Eijiro , Fujita Nobuyuki , Yagi Mitsuru , Nakamura Masaya ,   Texas Scottish Rite Hospital for Children Clinical Group (TSRHCCG), Karol Lori A. , Rathjen Karl E. , Sucato Daniel J. , Birch John G. , Johnston Charles E. , Richards Benjamin S. , Ramo Brandon , McIntosh Amy L. , Herring John A. , Milbrandt Todd A. , Talwakar Vishwas R. , Iwinski Henry J. , Muchow Ryan D. , Tassone J. Channing , Liu X. -C. , Shindell Richard , Schrader William , Eberson Craig , Lapinsky Anthony , Loder Randall , Davey Joseph , Einarsdottir Elisabet , Kere Juha , Huang Dongsheng , Qiu Guixing , Xu Leilei , Qiu Yong , Wise Carol A. , Song You-Qiang , Wu Nan , Su Peiqiang , Gerdhem Paul , Watanabe Kota , Ikegawa Shiro
Published: March 2018

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10−18 (odds ratio = 1.19, 95% confidence interval = 1.14–1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.
Author Correction: Electroporation of mice zygotes with dual guide RNA/Cas9 complexes for simple and efficient cloning-free genome editing
Authors: Teixeira Marie , Py Bénédicte F. , Bosc Christophe , Laubreton Daphné , Moutin Marie-Jo , Marvel Jacqueline , Flamant Frédéric , Markossian Suzy
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Coupling of SK channels, L-type Ca2+ channels, and ryanodine receptors in cardiomyocytes
Authors: Zhang Xiao-Dong , Coulibaly Zana A. , Chen Wei Chun , Ledford Hannah A. , Lee Jeong Han , Sirish Padmini , Dai Gu , Jian Zhong , Chuang Frank , Brust-Mascher Ingrid , Yamoah Ebenezer N. , Chen-Izu Ye , Izu Leighton T. , Chiamvimonvat Nipavan
Published: March 2018

Small-conductance Ca2+-activated K+ (SK) channels regulate the excitability of cardiomyocytes by integrating intracellular Ca2+ and membrane potentials on a beat-to-beat basis. The inextricable interplay between activation of SK channels and Ca2+ dynamics suggests the pathology of one begets another. Yet, the exact mechanistic underpinning for the activation of cardiac SK channels remains unaddressed. Here, we investigated the intracellular Ca2+ microdomains necessary for SK channel activation. SK currents coupled with Ca2+ influx via L-type Ca2+ channels (LTCCs) continued to be elicited after application of caffeine, ryanodine or thapsigargin to deplete SR Ca2+ store, suggesting that LTCCs provide the immediate Ca2+ microdomain for the activation of SK channels in cardiomyocytes. Super-resolution imaging of SK2, Cav1.2 Ca2+ channel, and ryanodine receptor 2 (RyR2) was performed to quantify the nearest neighbor distances (NND) and localized the three molecules within hundreds of nanometers. The distribution of NND between SK2 and RyR2 as well as SK2 and Cav1.2 was bimodal, suggesting a spatial relationship between the channels. The activation mechanism revealed by our study paved the way for the understanding of the roles of SK channels on the feedback mechanism to regulate the activities of LTCCs and RyR2 to influence local and global Ca2+ signaling.
Estimation of interaction energy and contact stiffness in atomic-scale sliding on a model sodium chloride surface in ethanol
Authors: Agmon Liron , Shahar Itai , Yosufov Danny , Pimentel Carlos , Pina Carlos M. , Gnecco Enrico , Berkovich Ronen
Published: March 2018

Friction force microscopy (FFM) in aqueous environments has recently proven to be a very effective method for lattice-resolution imaging of crystal surfaces. Here we demonstrate the use of ethanol for similar measurements on water-soluble materials. Lattice resolved frictional stick-slip traces of a cleaved NaCl(100) surface submerged in ethanol are compared with previous obtained FFM results in ultrahigh vacuum (UHV). We use the Prandtl-Tomlinson framework to estimate the amplitude of the corrugation potential and the contact stiffness. The surface potential amplitude scales with the applied normal loads are in good agreement with data obtained for NaCl measured under UHV conditions, but demonstrates deviations from the ideal periodic potential given by the Prandtl-Tomlinson model. An additional finding is that the use of ethanol allows us to explore higher load ranges without detectable evidence of surface wear. The contact stiffness does not vary significantly with the normal load up to 38 nN, while above it a sudden increase by almost one order of magnitude was observed. Comparing this to previous results suggests that considerable atom rearrangements may occur in the contact region, although the (100) surface structure is preserved by ethanol-assisted diffusion of Na and Cl ions.
Cannabinoid-induced increase of quantal size and enhanced neuromuscular transmission
Authors: Morsch Marco , Protti Dario A. , Cheng Delfine , Braet Filip , Chung Roger S. , Reddel Stephen W. , Phillips William D.
Published: March 2018

Cannabinoids exert dynamic control over many physiological processes including memory formation, cognition and pain perception. In the central nervous system endocannabinoids mediate negative feedback of quantal transmitter release following postsynaptic depolarization. The influence of cannabinoids in the peripheral nervous system is less clear and might have broad implications for the therapeutic application of cannabinoids. We report a novel cannabinoid effect upon the mouse neuromuscular synapse: acutely increasing synaptic vesicle volume and raising the quantal amplitudes. In a mouse model of myasthenia gravis the cannabinoid receptor agonist WIN 55,212 reversed fatiguing failure of neuromuscular transmission, suggesting future therapeutic potential. Our data suggest an endogenous pathway by which cannabinoids might help to regulate transmitter release at the neuromuscular junction.
Imaging of conditional gene silencing in vivo using a bioluminescence-based method with thermo-inducible microRNAs
Authors: Pinel Karine , Genevois Coralie , Debeissat Christelle , Couillaud Franck
Published: March 2018

RNA interference (RNAi)-based gene therapy has great potential in cancer and infectious disease treatment to correct abnormal up-regulation of gene expression. We show a new original method uses synthetic microRNAs combined with a thermo-inducible promoter to reduce specific gene expression. The targeted gene is the luciferase firefly reporter gene overexpressed in a subcutaneous tumor which allows the RNAi monitoring by bioluminescence imaging (BLI). The inducible inhibition was first demonstrated in vitro using genetically modified cells lines and then in vivo using the corresponding xenograft model in mice. Achieving spatio-temporal control, we demonstrate the feasibility to induce, in vivo, a specific gene inhibition on demand. Future applications of this RNAi-based gene therapy, which can be restricted to pathological tissue, would offer wide-ranging potential for disease treatment.
Production of antibody against elephant endotheliotropic herpesvirus (EEHV) unveils tissue tropisms and routes of viral transmission in EEHV-infected Asian elephants
Authors: Kochagul Varankpicha , Srivorakul Saralee , Boonsri Kittikorn , Somgird Chalermchart , Sthitmatee Nattawooti , Thitaram Chatchote , Pringproa Kidsadagon
Published: March 2018

Elephant endotheliotropic herpesvirus (EEHV) is one of the most devastating viral infectious diseases in elephants worldwide. To date, it remains unclear how elephants get infected by the virus, where the virus persists, and what mechanisms drive the pathogenesis of the disease. The present study was aimed to develop an antibody against glycoprotein B (gB) of EEHV, investigate the EEHV tissue tropisms, and provide the possible routes of EEHV transmission in Asian elephants. Samples from elephant organs that had died from EEHV1A and EEHV4 infections, peripheral blood mononuclear cells (PBMC) from EEHV4- and non-EEHV-infected calves were used in this study. The results of western immunoblotting indicated that the antibody can be used for detection of gB antigens in both EEHV1A- and EEHV4-infected samples. Immunohistochemical detection indicated that the EEHV gB antigens were distributed mainly in the epithelial cells of the salivary glands, stomach and intestines. Immunofluorescence test of PBMC for EEHV gB in the EEHV4-infected calf indicated that the virus was observed predominantly in the mononuclear phagocytic cells. The findings in the present study unveil tissue tropisms in the EEHV1A- and EEHV4-infected calves and point out that saliva and intestinal content are likely sources for virus transmission in EEHV-infected Asian elephants.
Perinatal stress and human hippocampal volume: Findings from typically developing young adults
Authors: Marečková Klára , Mareček Radek , Bencurova Petra , Klánová Jana , Dušek Ladislav , Brázdil Milan
Published: March 2018

The main objective of this study was to investigate the impact of prenatal and early postnatal stress on hippocampal volume in young adulthood. In sharp contrast to numerous results in animal models, our data from a neuroimaging follow-up (n = 131) of a community-based birth cohort from the Czech Republic (European Longitudinal Study of Pregnancy and Childhood) showed that in typically developing young adults, hippocampal volume was not associated with birth weight, stressful life events during the prenatal or early postnatal period, or dysregulated mood and wellbeing in the mother during the early postnatal period. Interestingly, mother’s anxiety/co-dependence during the first weeks after birth did show long-lasting effects on the hippocampal volume in young adult offspring irrespective of sex. Further analyses revealed that these effects were subfield-specific; present in CA1, CA2/3, CA4, GC-DG, subiculum, molecular layer, and HATA, hippocampal subfields identified by translational research as most stress- and glucocorticoid-sensitive, but not in the remaining subfields. Our findings provide evidence that the type of early stress is critical when studying its effects on the human brain.
A proteomic insight into vitellogenesis during tick ovary maturation
Authors: Xavier Marina Amaral , Tirloni Lucas , Pinto Antônio F. M. , Diedrich Jolene K. , Yates John R. , Mulenga Albert , Logullo Carlos , da Silva Vaz Itabajara , Seixas Adriana , Termignoni Carlos
Published: March 2018

Ticks are arthropod ectoparasites of importance for public and veterinary health. The understanding of tick oogenesis and embryogenesis could contribute to the development of novel control methods. However, to date, studies on the temporal dynamics of proteins during ovary development were not reported. In the present study we followed protein profile during ovary maturation. Proteomic analysis of ovary extracts was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using shotgun strategy, in addition to dimethyl labelling-based protein quantification. A total of 3,756 proteins were identified, which were functionally annotated into 30 categories. Circa 80% of the annotated proteins belong to categories related to basal metabolism, such as protein synthesis and modification machineries, nuclear regulation, cytoskeleton, proteasome machinery, transcriptional machinery, energetic metabolism, extracellular matrix/cell adhesion, immunity, oxidation/detoxification metabolism, signal transduction, and storage. The abundance of selected proteins involved in yolk uptake and degradation, as well as vitellin accumulation during ovary maturation, was assessed using dimethyl-labelling quantification. In conclusion, proteins identified in this study provide a framework for future studies to elucidate tick development and validate candidate targets for novel control methods.
Hydrophobin gene deletion and environmental growth conditions impact mechanical properties of mycelium by affecting the density of the material
Authors: Appels Freek V. W. , Dijksterhuis Jan , Lukasiewicz Catherine E. , Jansen Kaspar M. B. , Wösten Han A. B. , Krijgsheld Pauline
Published: March 2018

Filamentous fungi colonize substrates by forming a mycelium. This network of hyphae can be used as a bio-based material. Here, we assessed the impact of environmental growth conditions and deletion of the hydrophobin gene sc3 on material properties of the mycelium of the mushroom forming fungus Schizophyllum commune. Thermogravimetric analysis showed that Δsc3 mycelium retained more water with increasing temperature when compared to the wild type. The Young’s modulus (E) of the mycelium ranged between 438 and 913 MPa when the wild type strain was grown in the dark or in the light at low or high CO2 levels. This was accompanied by a maximum tensile strength (σ) of 5.1–9.6 MPa. In contrast, E and σ of the Δsc3 strain were 3–4- fold higher with values of 1237–2727 MPa and 15.6–40.4 MPa, respectively. These values correlated with mycelium density, while no differences in chemical composition of the mycelia were observed as shown by ATR-FTIR. Together, genetic modification and environmental growth conditions impact mechanical properties of the mycelium by affecting the density of the mycelium. As a result, mechanical properties of wild type mycelium were similar to those of natural materials, while those of Δsc3 were more similar to thermoplastics.
Controlling the size of Pt nanoparticles with a cationic surfactant, CnTABr
Authors: Seo Jongsu , Lee Siwon , Koo Bonjae , Jung WooChul
Published: March 2018

We report how the size of Pt nanoparticles varies by using a wide range of chain lengths and concentrations of CnTABr, a cationic surfactant, in aqueous-based colloidal synthesis and confirm that the chemical affinity between the organic complex formed in the solution and the aggregate of the surfactant is an important factor for Pt particle growth.
Drying-induced atomic structural rearrangements in sodium-based calcium-alumino-silicate-hydrate gel and the mitigating effects of ZrO2 nanoparticles
Authors: Yang Kengran , Özçelik V. Ongun , Garg Nishant , Gong Kai , White Claire E.
Published: March 2018

Drying-induced nanoscopic alterations to the local atomic structure of silicate-activated slag and the mitigated effects of nano-ZrO2 are elucidated using in situ X-ray pair distribution function analysis.
On the prediction of core level binding energies in molecules, surfaces and solids
Authors: Viñes Francesc , Sousa Carmen , Illas Francesc
Published: March 2018

Core level binding energies, measured by X-ray photoelectron spectroscopy providing unique information regarding the chemical environment of atoms in a system, can be estimated by a diversity of state-of-the-art accurate methods here detailed.
Organic molecule-based photothermal agents: an expanding photothermal therapy universe
Authors: Jung Hyo Sung , Verwilst Peter , Sharma Amit , Shin Jinwoo , Sessler Jonathan L. , Kim Jong Seung
Published: March 2018

Over the last decade, organic photothermal therapy (PTT) agents have attracted increasing attention as a potential complement for, or alternative to, classical drugs and sensitizers involving inorganic nanomaterials.
Steel-based electrocatalysts for efficient and durable oxygen evolution in acidic media
Authors: Schäfer Helmut , Küpper Karsten , Schmidt Mercedes , Müller-Buschbaum Klaus , Stangl Johannes , Daum Diemo , Steinhart Martin , Schulz-Kölbel Christine , Han Weijia , Wollschläger Joachim , Krupp Ulrich , Hou Peilong , Liu Xiaogang
Published: March 2018

Upon electro-oxidation in LiOH, Ni42 alloy was rendered in an OER electrocatalyst that efficiently and durably works in the acidic regime.
Captivation with encapsulation: a dozen years of exploring uranyl peroxide capsules
Authors: Burns Peter C. , Nyman May
Published: March 2018

Uranyl peroxide cages are an extensive family of topologically varied self-assembling nanoscale clusters with fascinating properties and applications.
Carbon capture and storage (CCS): the way forward
Authors: Bui Mai , Adjiman Claire S. , Bardow André , Anthony Edward J. , Boston Andy , Brown Solomon , Fennell Paul S. , Fuss Sabine , Galindo Amparo , Hackett Leigh A. , Hallett Jason P. , Herzog Howard J. , Jackson George , Kemper Jasmin , Krevor Samuel , Maitland Geoffrey C. , Matuszewski Michael , Metcalfe Ian S. , Petit Camille , Puxty Graeme , Reimer Jeffrey , Reiner David M. , Rubin Edward S. , Scott Stuart A. , Shah Nilay , Smit Berend , Trusler J. P. Martin , Webley Paul , Wilcox Jennifer , Mac Dowell Niall
Published: March 2018

Carbon capture and storage (CCS) is vital to climate change mitigation, and has application across the economy, in addition to facilitating atmospheric carbon dioxide removal resulting in emissions offsets and net negative emissions. This contribution reviews the state-of-the-art and identifies key challenges which must be overcome in order to pave the way for its large-scale deployment.
Self-generation of two-dimensional droplet array using oil–water immiscibility and replacement
Authors: Yasuga Hiroki , Kamiya Koki , Takeuchi Shoji , Miki Norihisa
Published: March 2018

We developed a method to generate 2D droplet array without precise liquid injection by using a connected circular well array.
A very facile strategy for the synthesis of ultrathin CuO nanorods towards non-enzymatic glucose sensing
Authors: Gou Xufeng , Sun Shaodong , Yang Qing , Li Pengju , Liang Shuhua , Zhang Xiaojing , Yang Zhimao
Published: March 2018

Ultrathin CuO nanorods for non-enzymatic glucose sensing have been readily synthesized by simply mixing Cu2+/OH−/ethanol with water at high temperature.
Single-step rapid synthesis of monolithic mesoporous carbon/graphene aerogels with improved double layer capacitance
Authors: Chandrasekaran Naveen , Premkumar Viji , Senthil Kumar Sakkarapalayam Murugesan , Ram Rahul
Published: March 2018

Graphene oxide is used as an acid catalyst for the gelation of a resorcinol–formaldehyde (R–F) network. Pyrolytic conversion of the GO/R–F network leads to the formation of graphene/mesoporous carbon network with enhanced specific capacitance.
Combining gold nanoparticle antennas with single-molecule fluorescence resonance energy transfer (smFRET) to study DNA hairpin dynamics
Authors: Hu Jinyong , Wu Meiyan , Jiang Li , Zhong Zhensheng , Zhou Zhangkai , Rujiralai Thitima , Ma Jie
Published: March 2018

Gold nanoparticle antennas as a promising platform not only for fluorescence enhancement but also for the studies of single-molecule kinetics.
Touching the theoretical capacity: synthesizing cubic LiTi2(PO4)3/C nanocomposites for high-performance lithium-ion battery
Authors: Deng Wenjun , Wang Xusheng , Liu Chunyi , Li Chang , Xue Mianqi , Li Rui , Pan Feng
Published: March 2018

Cubic LiTi2(PO4)3/C nanocomposites rich in C–O bonds deliver an unprecedented close to the theoretical capacity.
Highly photoluminescent and stable silicon nanocrystals functionalized via microwave-assisted hydrosilylation
Authors: Beri Deski , Busko Dmitry , Mazilkin Andrey , Howard Ian A. , Richards Bryce S. , Turshatov Andrey
Published: March 2018

Herein, we report a microwave-assisted hydrosilylation (MWH) reaction for the surface passivation of silicon nanocrystals (Si-NCs) with linear alkenes.
Impact of helical organization on the photovoltaic properties of oligothiophene supramolecular polymers
Authors: Ouchi Hayato , Kizaki Takahiro , Yamato Masaki , Lin Xu , Hoshi Nagahiro , Silly Fabien , Kajitani Takashi , Fukushima Takanori , Nakayama Ken-ichi , Yagai Shiki
Published: March 2018

Higher order structures of semiconducting supramolecular polymers have a huge impact on their BHJ-OPV device performance.
A sensitive UPLC-APCI-MS/MS method for the determination of dexamethasone and its application in an ocular tissue distribution study in rabbits following topical administration
Authors: Matta Murali K. , Narayanasamy Suresh , Thomas Christopher D. , Xu Lin , Stewart Sharron , Chockalingam Ashok , Patel Vikram , Rouse Rodney
Published: March 2018

A sensitive, specific and rapid ultra-performance liquid chromatography tandem mass spectrometry method has been developed and validated for the determination of dexamethasone (DEX) in ocular tissues of rabbits.
Dynamic charge acceptance and hydrogen evolution of a new MXene additive in advanced lead-acid batteriesviaa rapid screening three-electrode method
Authors: Kang Shuai , Shang Mingwei , Spence Matthew A. , Andrew Michael , Liu Shuangyi , Niu Junjie
Published: March 2018

A three-electrode system was developed to rapidly screen additives such as MXene through dynamic charge acceptance in lead-acid batteries.
Intracellular self-assembly of Ru(bpy)32+ nanoparticles enables persistent phosphorescence imaging of tumors
Authors: Li Jindan , Hai Zijuan , Xiao Huiqiong , Yi Xiaoyi , Liang Gaolin
Published: March 2018

The small molecular Ru(bpy)32+-derivative probe 1 was rationally designed for intracellular self-assembly of 1-NPs for tumor imaging with persistent phosphorescence.
Exploring the features on the OH + SO2potential energy surface using theory and testing its accuracy by comparison to experimental data
Authors: Medeiros D. J. , Blitz M. A. , Seakins P. W.
Published: March 2018

Ab initiotheory has been used to identify the pre-reaction complex in the atmospherically important reaction between OH + SO2, (R1), where the binding energy of the pre-reaction complex was determined to be 7.2 kJ mol−1.
2D carbon sheets with negative Gaussian curvature assembled from pentagonal carbon nanoflakes
Authors: Zhang Cunzhi , Wang Fancy Qian , Yu Jiabing , Gong Sheng , Li Xiaoyin , Sun Qiang
Published: March 2018

Based on the recent experimental synthesis of pentagonal graphene nanoflakes and the novel properties of penta-graphene, we report a series of 2D assembled carbon allotropes (CG568-80, CG568-180 and CG568-320) that have unusual properties.
Correlations between gaseous and liquid phase chemistries induced by cold atmospheric plasmas in a physiological buffer
Authors: Girard Fanny , Peret Mathieu , Dumont Natacha , Badets Vasilica , Blanc Sylvie , Gazeli Kristaq , Noël Cédric , Belmonte Thierry , Marlin Laurent , Cambus Jean-Pierre , Simon Guillaume , Sojic Neso , Held Bernard , Arbault Stéphane , Clément Franck
Published: March 2018

Understanding the role of gaseous environment in plasma–liquid interactions is crucial for multiple applications of CAPs.
One-pot production of porous assemblies by PISA of star architecture copolymers: a simulation study
Authors: Wang Junfeng , Li Jiawei , Yao Qiang , Sun Xiaoli , Yan Youguo , Zhang Jun
Published: March 2018

Porous vesicles can be produced in one-pot by the PISA of star architecture copolymers.