bluuebunny/crossref_metadata_2025 huggingface dataset:
Neonatal DNA methylation and early-onset conduct problems: A genome-wide, prospective study
Authors: Cecil Charlotte A. M. , Walton Esther , Jaffee Sara R. , O'Connor Tom , Maughan Barbara , Relton Caroline L. , Smith Rebecca G. , McArdle Wendy , Gaunt Tom R. , Ouellet-Morin Isabelle , Barker Edward D.
Published: June 2017

Early-onset conduct problems (CP) are a key predictor of adult criminality and poor mental health. While previous studies suggest that both genetic and environmental risks play an important role in the development of early-onset CP, little is known about potential biological processes underlying these associations. In this study, we examined prospective associations between DNA methylation (cord blood at birth) and trajectories of CP (4–13 years), using data drawn from the Avon Longitudinal Study of Parents and Children. Methylomic variation at seven loci across the genome (false discovery rate < 0.05) differentiated children who go on to develop early-onset (n = 174) versus low (n = 86) CP, including sites in the vicinity of the monoglyceride lipase (MGLL) gene (involved in endocannabinoid signaling and pain perception). Subthreshold associations in the vicinity of three candidate genes for CP (monoamine oxidase A [MAOA], brain-derived neurotrophic factor [BDNF], and FK506 binding protein 5 [FKBP5]) were also identified. Within the early-onset CP group, methylation levels of the identified sites did not distinguish children who will go on to persist versus desist in CP behavior over time. Overall, we found that several of the identified sites correlated with prenatal exposures, and none were linked to known genetic methylation quantitative trait loci. Findings contribute to a better understanding of epigenetic patterns associated with early-onset CP.
Broadband sub-THz spectroscopy modules integrated in 65-nm CMOS technology
Authors: Matters-Kammerer Marion K. , Van Goor Dave , Tripodi Lorenzo
Published: June 2017

The design and characterization of a broadband 20–480 GHz continuously tuneable on-chip spectrometer based on non-linear transmission lines in 65-nm CMOS technology is presented. The design procedure of the sampler that detects the ultra-broadband signal from the transmitter in time and frequency domain is described in detail. It consists of a non-linear transmission line, a passive pulse differentiator and a high-speed sample and hold-circuit. The relevance of the layout of the Schottky diodes in the sampler with a maximum RC-cutoff frequency of 430 GHz is described. Time domain and frequency domain measurements are presented to characterize the 480 GHz sampler bandwidth as well as the 3.1 ps sampler rise time. A signal to noise ratio of 90 dB at 100 GHz, 70 dB at 200 GHz and more than 30 dB at 480 GHz is reached. Two implementation of the spectrometer with antennas are presented, one with an on-chip antenna and one in a hybrid package. The antenna-less on-chip implementation of the transmitter and sampler requires no external lenses and is miniaturized to an area of 3 mm2. Future applications include analysis of fluids in microfluidic packages or droplet analysis in bio-medical or pharmaceutical applications.
Spanish-Language Adaptation of Morgeson and Humphrey’s Work Design Questionnaire (WDQ)
Authors: Fernández Ríos Manuel , Ramírez Vielma Raúl G. , Sánchez García José Carlos , Bargsted Aravena Mariana , Polo Vargas Jean David , Ruiz Díaz Miguel Ángel
Published: June 2017

Since work organizations became the subject of scientific research, how to operationalize and measure dimensions of work design has been an issue, mainly due to concerns about internal consistency and factor structure. In response, Morgeson and Humphrey (2006) built the Work Design Questionnaire –WDQ–, an instrument that identifies and measures these dimensions in different work and organizational contexts. This paper presents the instruent’s adaptation into Spanish using reliability and validity analysis and drawing on a sample of 1035 Spanish workers who hold various jobs in an array of occupational categories. The total instrument’s internal consistency was Cronbach’s alpha of .92 and the various scales’ reliability ranged from .70 to .96, except for three dimensions. There was initially a difference in the comparative fit of the two versions’ factor structures, but the model with 21 work characteristics (motivational -task and knowledge-, social, and work context) showed the highest goodness of fit of the various models tested, confirming previous results from the U.S. version as well as adaptations into other languages and contexts. CFA results indicated goodness of fit of factor configurations corresponding to each of the four major categories of work characteristics, with CFI and TLI around .90, as well as SRMR and RMSEA below .08. Thus it brings to the table a reliable, valid measure of work design with clear potential applications in research as well as professional practice, applications that could improve working conditions, boost productivity, and generate more personal and professional development opportunities for workers.
Instrument Development Enables Planetary Exploration
Authors: Feldman Sabrina , Beaty David , Ashley James
Published: June 2017

Third International Workshop on Instrumentation for Planetary Missions; Pasadena, California, 24–27 October 2016
Assessment of noise intensity in a dental teaching clinic
Authors: da Cunha Kelly Ferreira , dos Santos Rubem Beraldo , Klien Celso Afonso
Published: June 2017

Objectives/Aims:

The aim of this study is to evaluate if the duration of the consultation has influence on the intensity of noise in the dental clinic environment.

Materials and Methods:

The measurement was performed using the decibelmetre IDETEC 300. It was turned on among 10 dental equipment at basal time (BT) and in the first, second and third hours of activity by 10 times with 1-week interval.

Results:

The average noise was 67.39±1.11 dB for BT and 82.38±3.85, 80.99±4.78, and 70.06±6.95 dB for hours 1 to 3, respectively, representing a significant difference (ANOVA, F(3.36)=29.28, P<0.0001).

Conclusion:

In the first and second hours of clinical care there was more noise intensity in the work environment compared to BT and to the third time. Furthermore, the noise peaks became closer to the limit of 85 dB, which can threaten hearing loss with repeated exposure throughout a dentist’s career.

Discussion:

The findings presented here show how much the dental surgeon is exposed to the level of noise since his time of study.
Mesoscopic chaos mediated by Drude electron-hole plasma in silicon optomechanical oscillators
Authors: Wu Jiagui , Huang Shu-Wei , Huang Yongjun , Zhou Hao , Yang Jinghui , Liu Jia-Ming , Yu Mingbin , Lo Guoqiang , Kwong Dim-Lee , Duan Shukai , Wei Wong Chee
Published: June 2017

Chaos has revolutionized the field of nonlinear science and stimulated foundational studies from neural networks, extreme event statistics, to physics of electron transport. Recent studies in cavity optomechanics provide a new platform to uncover quintessential architectures of chaos generation and the underlying physics. Here, we report the generation of dynamical chaos in silicon-based monolithic optomechanical oscillators, enabled by the strong and coupled nonlinearities of two-photon absorption induced Drude electron–hole plasma. Deterministic chaotic oscillation is achieved, and statistical and entropic characterization quantifies the chaos complexity at 60 fJ intracavity energies. The correlation dimensionD2is determined at 1.67 for the chaotic attractor, along with a maximal Lyapunov exponent rate of about 2.94 times the fundamental optomechanical oscillation for fast adjacent trajectory divergence. Nonlinear dynamical maps demonstrate the subharmonics, bifurcations and stable regimes, along with distinct transitional routes into chaos. This provides a CMOS-compatible and scalable architecture for understanding complex dynamics on the mesoscopic scale.
Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences
Authors: Price D. , Tyler L. K. , Neto Henriques R. , Campbell K. L. , Williams N. , Treder M.S. , Taylor J. R. ,   Cam-CAN, Brayne Carol , Bullmore Edward T. , Calder Andrew C. , Cusack Rhodri , Dalgleish Tim , Duncan John , Matthews Fiona E. , Marslen-Wilson William D. , Rowe James B. , Shafto Meredith A. , Cheung Teresa , Davis Simon , Geerligs Linda , Kievit Rogier , McCarrey Anna , Mustafa Abdur , Samu David , Tsvetanov Kamen A. , van Belle Janna , Bates Lauren , Emery Tina , Erzinglioglu Sharon , Gadie Andrew , Gerbase Sofia , Georgieva Stanimira , Hanley Claire , Parkin Beth , Troy David , Auer Tibor , Correia Marta , Gao Lu , Green Emma , Allen Jodie , Amery Gillian , Amunts Liana , Barcroft Anne , Castle Amanda , Dias Cheryl , Dowrick Jonathan , Fair Melissa , Fisher Hayley , Goulding Anna , Grewal Adarsh , Hale Geoff , Hilton Andrew , Johnson Frances , Johnston Patricia , Kavanagh-Williamson Thea , Kwasniewska Magdalena , McMinn Alison , Norman Kim , Penrose Jessica , Roby Fiona , Rowland Diane , Sargeant John , Squire Maggie , Stevens Beth , Stoddart Aldabra , Stone Cheryl , Thompson Tracy , Yazlik Ozlem , Barnes Dan , Dixon Marie , Hillman Jaya , Mitchell Joanne , Villis Laura , Henson R. N. A.
Published: June 2017

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy.
Local probe of single phonon dynamics in warm ion crystals
Authors: Abdelrahman A. , Khosravani O. , Gessner M. , Buchleitner A. , Breuer H. -P. , Gorman D. , Masuda R. , Pruttivarasin T. , Ramm M. , Schindler P. , Häffner H.
Published: June 2017

The detailed characterization of non-trivial coherence properties of composite quantum systems of increasing size is an indispensable prerequisite for scalable quantum computation, as well as for understanding non-equilibrium many-body physics. Here, we show how autocorrelation functions in an interacting system of phonons as well as the quantum discord between distinct degrees of freedoms can be extracted from a small controllable part of the system. As a benchmark, we show this in chains of up to 42 trapped ions, by tracing a single phonon excitation through interferometric measurements of only a single ion in the chain. We observe the spreading and partial refocusing of the excitation in the chain, even on a background of thermal excitations. We further show how this local observable reflects the dynamical evolution of quantum discord between the electronic state and the vibrational degrees of freedom of the probe ion.
Constriction of the mitochondrial inner compartment is a priming event for mitochondrial division
Authors: Cho Bongki , Cho Hyo Min , Jo Youhwa , Kim Hee Dae , Song Myungjae , Moon Cheil , Kim Hyongbum , Kim Kyungjin , Sesaki Hiromi , Rhyu Im Joo , Kim Hyun , Sun Woong
Published: June 2017

Mitochondrial division is critical for the maintenance and regulation of mitochondrial function, quality and distribution. This process is controlled by cytosolic actin-based constriction machinery and dynamin-related protein 1 (Drp1) on mitochondrial outer membrane (OMM). Although mitochondrial physiology, including oxidative phosphorylation, is also important for efficient mitochondrial division, morphological alterations of the mitochondrial inner-membrane (IMM) have not been clearly elucidated. Here we report spontaneous and repetitive constriction of mitochondrial inner compartment (CoMIC) associated with subsequent division in neurons. Although CoMIC is potentiated by inhibition of Drp1 and occurs at the potential division spots contacting the endoplasmic reticulum, it appears on IMM independently of OMM. Intra-mitochondrial influx of Ca2+ induces and potentiates CoMIC, and leads to K+-mediated mitochondrial bulging and depolarization. Synergistically, optic atrophy 1 (Opa1) also regulates CoMIC via controlling Mic60-mediated OMM–IMM tethering. Therefore, we propose that CoMIC is a priming event for efficient mitochondrial division.
A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action
Authors: Campaner Elena , Rustighi Alessandra , Zannini Alessandro , Cristiani Alberto , Piazza Silvano , Ciani Yari , Kalid Ori , Golan Gali , Baloglu Erkan , Shacham Sharon , Valsasina Barbara , Cucchi Ulisse , Pippione Agnese Chiara , Lolli Marco Lucio , Giabbai Barbara , Storici Paola , Carloni Paolo , Rossetti Giulia , Benvenuti Federica , Bello Ezia , D’Incalci Maurizio , Cappuzzello Elisa , Rosato Antonio , Del Sal Giannino
Published: June 2017

The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority of cancers and its activity strongly contributes to tumour initiation and progression. Inactivation of PIN1 function conversely curbs tumour growth and cancer stem cell expansion, restores chemosensitivity and blocks metastatic spread, thus providing the rationale for a therapeutic strategy based on PIN1 inhibition. Notwithstanding, potent PIN1 inhibitors are still missing from the arsenal of anti-cancer drugs. By a mechanism-based screening, we have identified a novel covalent PIN1 inhibitor, KPT-6566, able to selectively inhibit PIN1 and target it for degradation. We demonstrate that KPT-6566 covalently binds to the catalytic site of PIN1. This interaction results in the release of a quinone-mimicking drug that generates reactive oxygen species and DNA damage, inducing cell death specifically in cancer cells. Accordingly, KPT-6566 treatment impairs PIN1-dependent cancer phenotypes in vitro and growth of lung metastasis in vivo.
Centromeres are maintained by fastening CENP-A to DNA and directing an arginine anchor-dependent nucleosome transition
Authors: Guo Lucie Y. , Allu Praveen Kumar , Zandarashvili Levani , McKinley Kara L. , Sekulic Nikolina , Dawicki-McKenna Jennine M. , Fachinetti Daniele , Logsdon Glennis A. , Jamiolkowski Ryan M. , Cleveland Don W. , Cheeseman Iain M. , Black Ben E.
Published: June 2017

Maintaining centromere identity relies upon the persistence of the epigenetic mark provided by the histone H3 variant, centromere protein A (CENP-A), but the molecular mechanisms that underlie its remarkable stability remain unclear. Here, we define the contributions of each of the three candidate CENP-A nucleosome-binding domains (two on CENP-C and one on CENP-N) to CENP-A stability using gene replacement and rapid protein degradation. Surprisingly, the most conserved domain, the CENP-C motif, is dispensable. Instead, the stability is conferred by the unfolded central domain of CENP-C and the folded N-terminal domain of CENP-N that becomes rigidified 1,000-fold upon crossbridging CENP-A and its adjacent nucleosomal DNA. Disrupting the ‘arginine anchor’ on CENP-C for the nucleosomal acidic patch disrupts the CENP-A nucleosome structural transition and removes CENP-A nucleosomes from centromeres. CENP-A nucleosome retention at centromeres requires a core centromeric nucleosome complex where CENP-C clamps down a stable nucleosome conformation and CENP-N fastens CENP-A to the DNA.
Temperature-regulated guest admission and release in microporous materials
Authors: Li Gang , Shang Jin , Gu Qinfen , Awati Rohan V. , Jensen Nathan , Grant Andrew , Zhang Xueying , Sholl David S. , Liu Jefferson Z. , Webley Paul A. , May Eric F.
Published: June 2017

While it has long been known that some highly adsorbing microporous materials suddenly become inaccessible to guest molecules below certain temperatures, previous attempts to explain this phenomenon have failed. Here we show that this anomalous sorption behaviour is a temperature-regulated guest admission process, where the pore-keeping group’s thermal fluctuations are influenced by interactions with guest molecules. A physical model is presented to explain the atomic-level chemistry and structure of these thermally regulated micropores, which is crucial to systematic engineering of new functional materials such as tunable molecular sieves, gated membranes and controlled-release nanocontainers. The model was validated experimentally with H2, N2, Ar and CH4 on three classes of microporous materials: trapdoor zeolites, supramolecular host calixarenes and metal-organic frameworks. We demonstrate how temperature can be exploited to achieve appreciable hydrogen and methane storage in such materials without sustained pressure. These findings also open new avenues for gas sensing and isotope separation.
A two-dimensional Dirac fermion microscope
Authors: Bøggild Peter , Caridad José M. , Stampfer Christoph , Calogero Gaetano , Papior Nick Rübner , Brandbyge Mads
Published: June 2017

The electron microscope has been a powerful, highly versatile workhorse in the fields of material and surface science, micro and nanotechnology, biology and geology, for nearly 80 years. The advent of two-dimensional materials opens new possibilities for realizing an analogy to electron microscopy in the solid state. Here we provide a perspective view on how a two-dimensional (2D) Dirac fermion-based microscope can be realistically implemented and operated, using graphene as a vacuum chamber for ballistic electrons. We use semiclassical simulations to propose concrete architectures and design rules of 2D electron guns, deflectors, tunable lenses and various detectors. The simulations show how simple objects can be imaged with well-controlled and collimated in-plane beams consisting of relativistic charge carriers. Finally, we discuss the potential of such microscopes for investigating edges, terminations and defects, as well as interfaces, including external nanoscale structures such as adsorbed molecules, nanoparticles or quantum dots.
Neural correlates of evidence accumulation during value-based decisions revealed via simultaneous EEG-fMRI
Authors: Pisauro M. Andrea , Fouragnan Elsa , Retzler Chris , Philiastides Marios G.
Published: June 2017

Current computational accounts posit that, in simple binary choices, humans accumulate evidence in favour of the different alternatives before committing to a decision. Neural correlates of this accumulating activity have been found during perceptual decisions in parietal and prefrontal cortex; however the source of such activity in value-based choices remains unknown. Here we use simultaneous EEG–fMRI and computational modelling to identify EEG signals reflecting an accumulation process and demonstrate that the within- and across-trial variability in these signals explains fMRI responses in posterior-medial frontal cortex. Consistent with its role in integrating the evidence prior to reaching a decision, this region also exhibits task-dependent coupling with the ventromedial prefrontal cortex and the striatum, brain areas known to encode the subjective value of the decision alternatives. These results further endorse the proposition of an evidence accumulation process during value-based decisions in humans and implicate the posterior-medial frontal cortex in this process.
Different populations of CD11b+ dendritic cells drive Th2 responses in the small intestine and colon
Authors: Mayer Johannes U. , Demiri Mimoza , Agace William W. , MacDonald Andrew S. , Svensson-Frej Marcus , Milling Simon W.
Published: June 2017

T-helper 2 (Th2) cell responses defend against parasites. Although dendritic cells (DCs) are vital for the induction of T-cell responses, the DC subpopulations that induce Th2 cells in the intestine are unidentified. Here we show that intestinal Th2 responses against Trichuris muris worms and Schistosoma mansoni eggs do not develop in mice with IRF-4-deficient DCs (IRF-4f/f CD11c-cre). Adoptive transfer of conventional DCs, in particular CD11b-expressing DCs from the intestine, is sufficient to prime S. mansoni-specific Th2 responses. Surprisingly, transferred IRF-4-deficient DCs also effectively prime S. mansoni-specific Th2 responses. Egg antigens do not induce the expression of IRF-4-related genes. Instead, IRF-4f/f CD11c-cre mice have fewer CD11b+ migrating DCs and fewer DCs carrying parasite antigens to the lymph nodes. Furthermore, CD11b+CD103+ DCs induce Th2 responses in the small intestine, whereas CD11b+CD103− DCs perform this role in the colon, revealing a specific functional heterogeneity among intestinal DCs in inducing Th2 responses.
Reactivation of associative structure specific outcome responses during prospective evaluation in reward-based choices
Authors: Wang Maya Zhe , Hayden Benjamin Y.
Published: June 2017

Before making a reward-based choice, we must evaluate each option. Some theories propose that prospective evaluation involves a reactivation of the neural response to the outcome. Others propose that it calls upon a response pattern that is specific to each underlying associative structure. We hypothesize that these views are reconcilable: during prospective evaluation, offers reactivate neural responses to outcomes that are unique to each associative structure; when the outcome occurs, this pattern is activated, simultaneously, with a general response to the reward. We recorded single-units from macaque orbitofrontal cortex (Area 13) in a riskless choice task with interleaved described and experienced offer trials. Here we report that neural activations to offers and their outcomes overlap, as do neural activations to the outcomes on the two trial types. Neural activations to experienced and described offers are unrelated even though they predict the same outcomes. Our reactivation theory parsimoniously explains these results.
Erratum: Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2
Authors: Zhang Haikuo , Brainson Christine Fillmore , Koyama Shohei , Redig Amanda J. , Chen Ting , Li Shuai , Gupta Manav , Garcia-de-Alba Carolina , Paschini Margherita , Herter-Sprie Grit S. , Lu Gang , Zhang Xin , Marsh Bryan P , Tuminello Stephanie J. , Xu Chunxiao , Chen Zhao , Wang Xiaoen , Akbay Esra A. , Zheng Mei , Palakurthi Sangeetha , Sholl Lynette M. , Rustgi Anil K. , Kwiatkowski David J. , Alan Diehl J. , Bass Adam J. , Sharpless Norman E. , Dranoff Glenn , Hammerman Peter S. , Ji Hongbin , Bardeesy Nabeel , Saur Dieter , Watanabe Hideo , Kim Carla F. , Wong Kwok-Kin
Published: June 2017

Nature Communications 8: Article number: 14922 (2017); Published 7 April 2017; Updated 9 June 2017 The affiliation details for Hideo Watanabe are incorrect in this Article. The correct affiliation details for this author are given below: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
TIP30 regulates lipid metabolism in hepatocellular carcinoma by regulating SREBP1 through the Akt/mTOR signaling pathway
Authors: Yin F , Sharen G , Yuan F , Peng Y , Chen R , Zhou X , Wei H , Li B , Jing W , Zhao J
Published: June 2017

Lipid reprogramming has been considered as a crucial characteristic in hepatocellular carcinoma (HCC) initiation and progression. However, detailed molecular mechanisms have yet to be clearly defined. Here, we examined the effects of tumor suppressor TIP30 on the regulation of HCC lipid metabolism. We found that decreased TIP30 expression leads to elevated fatty acid synthesis and enhanced levels of lipogenic enzymes SCD and FASN in HCC cells. Moreover, SREBP1 is one of the key transcription factors regulating liver lipid metabolism, and TIP30 deficiency significantly increased SREBP1 expression and nuclear accumulation. Small interfering RNAs targeting SREBP1 could reverse fatty acid synthesis induced by TIP30 deficiency. Furthermore, downregulating TIP30 activated the Akt/mTOR signaling pathway to upregulate SREBP1 expression, which promoted lipid metabolism by activating gene transcription of lipogenesis, including fasn and scd. We also showed that TIP30 deficiency-regulated lipid metabolism promoted proliferation of HCC cells. Clinically, our data revealed that TIP30 expression significantly correlated with SREBP1 in patients with HCC and that a combination of TIP30 and SREBP1 is a powerful predictor of HCC prognosis. Together, our data suggested a novel function of TIP30 in HCC progression and indicate that TIP30 regulation of SREBP1 may represent a novel target for HCC treatment.
Using variable importance measures to identify a small set of SNPs to predict heading date in perennial ryegrass
Authors: Byrne Stephen L. , Conaghan Patrick , Barth Susanne , Arojju Sai Krishna , Casler Michael , Michel Thibauld , Velmurugan Janaki , Milbourne Dan
Published: June 2017

Prior knowledge on heading date enables the selection of parents of synthetic cultivars that are well matched with respect to time of heading, which is essential to ensure plants put together will cross pollinate. Heading date of individual plants can be determined via direct phenotyping, which has a time and labour cost. It can also be inferred from family means, although the spread in days to heading within families demands roguing in first generation synthetics. Another option is to predict heading date from molecular markers. In this study we used a large training population consisting of individual plants to develop equations to predict heading date from marker genotypes. Using permutation-based variable selection measures we reduced the marker set from 217,563 to 50 without impacting the predictive ability. Opportunities exist to develop a cheap assay to sequence a small number of regions in linkage disequilibrium with heading date QTL in thousands of samples. Simultaneous use of these markers in non-linkage based marker-assisted selection approaches, such as paternity testing, should enhance the utility of such an approach.
High-Risk Human Papillomavirus E7 Alters Host DNA Methylome and Represses HLA-E Expression in Human Keratinocytes
Authors: Cicchini Louis , Blumhagen Rachel Z. , Westrich Joseph A. , Myers Mallory E. , Warren Cody J. , Siska Charlotte , Raben David , Kechris Katerina J. , Pyeon Dohun
Published: June 2017

Human papillomavirus (HPV) infection distinctly alters methylation patterns in HPV-associated cancer. We have recently reported that HPV E7-dependent promoter hypermethylation leads to downregulation of the chemokineCXCL14and suppression of antitumor immune responses. To investigate the extent of gene expression dysregulated by HPV E7-induced DNA methylation, we analyzed parallel global gene expression and DNA methylation using normal immortalized keratinocyte lines, NIKS, NIKS-16, NIKS-18, and NIKS-16∆E7. We show that expression of the MHC class I genes is downregulated in HPV-positive keratinocytes in an E7-dependent manner. Methylome analysis revealed hypermethylation at a distal CpG island (CGI) near theHLA-Egene in NIKS-16 cells compared to either NIKS cells or NIKS-16∆E7 cells, which lack E7 expression. TheHLA-ECGI functions as an active promoter element which is dramatically repressed by DNA methylation. HLA-E protein expression on cell surface is downregulated by high-risk HPV16 and HPV18 E7 expression, but not by low-risk HPV6 and HPV11 E7 expression. Conversely, demethylation at theHLA-ECGI restores HLA-E protein expression in HPV-positive keratinocytes. Because HLA-E plays an important role in antiviral immunity by regulating natural killer and CD8+T cells, epigenetic downregulation ofHLA-Eby high-risk HPV E7 may contribute to virus-induced immune evasion during HPV persistence.
Ferroelectric-assisted gold nanoparticles array for centimeter-scale highly reproducible SERS substrates
Authors: Liu Xiaoyan , Osada Minoru , Kitamura Kenji , Nagata Takahiro , Si Donghui
Published: June 2017

Assemble metal nanoparticles into various ordered structures with scale up to centimeter area is required to meet diverse needs of lab-on-a-chips and analytic components. Here, we present the uniform and high-yield fabrication of centimeter-scale gold nanoparticles (AuNPs) array for SERS substrates. Ferroelectric-assisted assembly of AuNPs line array is successfully fabricated by using a periodically poled LiNbO3 (PPLN) single crystal as a template. SNOM-Raman shows that the uniform assembly of AuNPs exhibits a high density of “hot spots” arising from strong electromagnetic (EM) field coupling induced by adjacent AuNPs. Quantitative analysis based on SERS detection describes an excellent reproducibility with an intensity variation less than 7% at 1649 cm−1 of Rhodamine 6G. SERS spectra combined with 3D-FDTD modelling indicate that the EM enhancement occurs at all three excitation wavelength of 515, 561 and 633 nm and the 561-nm-laser displays the strongest Raman enhancement with an enhancement factor in an order of 109. The corresponding experimental and theoretical results present a new strategy to fabricate large-area, highly reproducible and sensitive SERS substrates for practical applications.
Behavioural and physiological responses to prey-related cues reflect higher competitiveness of invasive vs. native ladybirds
Authors: Rondoni Gabriele , Ielo Fulvio , Ricci Carlo , Conti Eric
Published: June 2017

Understanding the traits that might be linked with biological invasions represents a great challenge for preventing non-target effects on local biodiversity. In predatory insects, the ability to exploit habitats for oviposition and the physiological response to prey availability differs between species. Those species that respond more readily to environmental changes may confer to their offspring a competitive advantage over other species. Here, we tested the hypothesis that the invasive Harmonia axyridis (Coleoptera: Coccinellidae) makes better use of information from a plant-prey (Vicia faba - Aphis fabae) system compared to the native Oenopia conglobata. Y-tube olfactometer bioassays revealed that both species used olfactory cues from the system, but H. axyridis exhibited a more complete response. This species was also attracted by plants previously infested by aphids, indicating the capacity to exploit volatile synomones induced in plants by aphid attack. Oocyte resorption was investigated when different olfactory stimuli were provided under prey shortage and the readiness of new oogenesis was measured when prey was available again. H. axyridis exhibited higher plasticity in oogenesis related to the presence/absence of plant-aphid volatiles. Our results support the hypothesis that H. axyridis is more reactive than O. conglobata to olfactory cues from the plant-prey system.
A Sensory Material Approach for Reducing Variability in Additively Manufactured Metal Parts
Authors: Franco B. E. , Ma J. , Loveall B. , Tapia G. A. , Karayagiz K. , Liu J. , Elwany A. , Arroyave R. , Karaman I.
Published: June 2017

Despite the recent growth in interest for metal additive manufacturing (AM) in the biomedical and aerospace industries, variability in the performance, composition, and microstructure of AM parts remains a major impediment to its widespread adoption. The underlying physical mechanisms, which cause variability, as well as the scale and nature of variability are not well understood, and current methods are ineffective at capturing these details. Here, a Nickel-Titanium alloy is used as a sensory material in order to quantitatively, and rather rapidly, observe compositional and/or microstructural variability in selective laser melting manufactured parts; thereby providing a means to evaluate the role of process parameters on the variability. We perform detailed microstructural investigations using transmission electron microscopy at various locations to reveal the origins of microstructural variability in this sensory material. This approach helped reveal how reducing the distance between adjacent laser scans below a critical value greatly reduces both the in-sample and sample-to-sample variability. Microstructural investigations revealed that when the laser scan distance is wide, there is an inhomogeneity in subgrain size, precipitate distribution, and dislocation density in the microstructure, responsible for the observed variability. These results provide an important first step towards understanding the nature of variability in additively manufactured parts.
Highly conductive nano-sized Magnéli phases titanium oxide (TiOx)
Authors: Arif Aditya F. , Balgis Ratna , Ogi Takashi , Iskandar Ferry , Kinoshita Akihiro , Nakamura Keitaro , Okuyama Kikuo
Published: June 2017

Despite the strong recent revival of Magnéli phase TiOx as a promising conductive material, synthesis of Magnéli phase TiOx nanoparticles has been a challenge because of the heavy sintering nature of TiO2 at elevated temperatures. We have successfully synthesized chain-structured Magnéli phases TiOx with diameters under 30 nm using a thermal-induced plasma process. The synthesized nanoparticles consisted of a mixture of several Magnéli phases. A post-synthesis heat-treatment was performed to reduce the electrical resistivity without changing the particle morphology. The resistivity of the heat-treated particle was as low as 0.04 Ω.cm, with a specific surface area of 52.9 m2 g−1. The effects of heat-treatment on changes in the crystal structure and their correlation with the electron conductivity are discussed based on transmission electron microscopy images, X-ray diffraction spectra, and X-ray adsorption fine structure spectra. Electrochemical characterization using cyclic voltammetry and potentiodynamic scan shows a remarkable electrochemical stability in a strongly oxidizing environment.
The effect of Lasik surgery on myopic anisometropes’ sensory eye dominance
Authors: Feng Lixia , Lin Huimin , Chen Yao , Wang Jiafeng , Wang Yonghua , Liao Rongfeng , Zhou Jiawei , Hess Robert F.
Published: June 2017

Lasik is a common surgery for treating anisometropia. In this study, we asked a specific question: what’s the effect of Lasik surgery on anisometropes’ sensory eye dominance? Fifteen myopic anisometropes (mean age: 23 ± 6.9 years old; 6 females) participated in our experiment. We quantitatively measured participants’ sensory eye dominance before and after the Lasik surgery using a binocular phase combination paradigm. We found no significant change of sensory eye dominance within 16 weeks (measured between 8 to 96 days, for one or two repetitions) after the surgery (t(14) = −1.44, p = 0.17). A further following on eight patients showed that patients’ two eyes were much more balanced at 16 weeks or more (measured one or two times between 112 to 408 days) after the surgery (t(7) = −3.79, p = 0.007). Our results suggest that the benefit of Lasik surgery on anisometropes’ sensory eye dominance is not immediate, a long-term ‘adaptation’ period (16 weeks or more) is necessary to enable the surgery to be truly effective.
MicroRNA-29a Counteracts Synovitis in Knee Osteoarthritis Pathogenesis by Targeting VEGF
Authors: Ko Jih-Yang , Lee Mel S. , Lian Wei-Shiung , Weng Wen-Tsan , Sun Yi-Chih , Chen Yu-Shan , Wang Feng-Sheng
Published: June 2017

Synovitis contributes to the development of osteoarthritis (OA) of the knee. MicroRNAs regulate joint microenvironment homeostasis and deterioration. This study was undertaken to characterize the actions of microRNA-29a (miR-29a) to synovial remodeling in OA joints. Synovial specimens isolated from patients with end-stage OA knees showed abundant fibrotic matrix and vessel histopathology concomitant with weak miR-29a expression. In vitro, miR-29a knockdown caused synovial fibroblasts to exhibit high expressions of collagen III, TGF-β1, MMP9, MMP13, and ADAMTS5, whereas miR-29a overexpression diminished these joint-deleterious factors. In collagenase-mediated OA pathogenesis, miR-29a-overexpressing transgenic mice showed minor responses to hyperplasia, macrophage infiltration, fibrosis, hyperangiogenesis, and VEGF expression in synovial lesions. These effects mitigated articular cartilage loss and gait aberrance of injured joints. Intra-articular administration of miR-29a precursor lessened the collagenase aggravation of excessive synovial remodeling reactions and thereby sustained joint tissue integrity. miR-29a lowered VEGF production and angiogenic activities in synovial fibroblasts through targeting the 3′-UTR of VEGF. Taken together, miR-29a deficiency exacerbated synovitis pathogenesis in the end-stage OA knees. miR-29a signaling fends off excessive synovial angiogenesis and fibrosis, which delays joint destruction. This study sheds new light on the protective effects against synovial deterioration and the therapeutic advantage of miR-29a in OA knees.
Bioinspired nanocoatings for biofouling prevention by photocatalytic redox reactions
Authors: Sathe Priyanka , Laxman Karthik , Myint Myo Tay Zar , Dobretsov Sergey , Richter Jutta , Dutta Joydeep
Published: June 2017

Aquaculture is a billion dollar industry and biofouling of aquaculture installations has heavy economic penalties. The natural antifouling (AF) defence mechanism of some seaweed that inhibits biofouling by production of reactive oxygen species (ROS) inspired us to mimic this process by fabricating ZnO photocatalytic nanocoating. AF activity of fishing nets modified with ZnO nanocoating was compared with uncoated nets (control) and nets painted with copper-based AF paint. One month experiment in tropical waters showed that nanocoatings reduce abundances of microfouling organisms by 3-fold compared to the control and had higher antifouling performance over AF paint. Metagenomic analysis of prokaryotic and eukaryotic fouling organisms using next generation sequencing platform proved that nanocoatings compared to AF paint were not selectively enriching communities with the resistant and pathogenic species. The proposed bio-inspired nanocoating is an important contribution towards environmentally friendly AF technologies for aquaculture.
Main and epistatic loci studies in soybean for Sclerotinia sclerotiorum resistance reveal multiple modes of resistance in multi-environments
Authors: Moellers Tara C. , Singh Arti , Zhang Jiaoping , Brungardt Jae , Kabbage Mehdi , Mueller Daren S. , Grau Craig R. , Ranjan Ashish , Smith Damon L. , Chowda-Reddy R. V. , Singh Asheesh K.
Published: June 2017

Genome-wide association (GWAS) and epistatic (GWES) studies along with expression studies in soybean [Glycine max (L.) Merr.] were leveraged to dissect the genetics of Sclerotinia stem rot (SSR) [caused by Sclerotinia sclerotiorum (Lib.) de Bary], a significant fungal disease causing yield and quality losses. A large association panel of 466 diverse plant introduction accessions were phenotyped in multiple field and controlled environments to: (1) discover sources of resistance, (2) identify SNPs associated with resistance, and (3) determine putative candidate genes to elucidate the mode of resistance. We report 58 significant main effect loci and 24 significant epistatic interactions associated with SSR resistance, with candidate genes involved in a wide range of processes including cell wall structure, hormone signaling, and sugar allocation related to plant immunity, revealing the complex nature of SSR resistance. Putative candidate genes [for example, PHYTOALEXIN DEFFICIENT 4 (PAD4), ETHYLENE-INSENSITIVE 3-LIKE 1 (EIL3), and ETHYLENE RESPONSE FACTOR 1 (ERF1)] clustered into salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) pathways suggest the involvement of a complex hormonal network typically activated by both necrotrophic (ET/JA) and biotrophic (SA) pathogens supporting that S. sclerotiorum is a hemibiotrophic plant pathogen.
Different signaling patterns contribute to loss of keratinocyte cohesion dependent on autoantibody profile in pemphigus
Authors: Walter Elias , Vielmuth Franziska , Rotkopf Lukas , Sárdy Miklós , Horváth Orsolya N. , Goebeler Matthias , Schmidt Enno , Eming Rüdiger , Hertl Michael , Spindler Volker , Waschke Jens
Published: June 2017

Pemphigus is an autoimmune blistering skin disease caused primarily by autoantibodies against desmoglein (Dsg)1 and 3. Here, we characterized the mechanisms engaged by pemphigus IgG from patients with different clinical phenotypes and autoantibody profiles. All pemphigus vulgaris (PV) and pemphigus foliaceus (PF) IgG and AK23, a monoclonal mouse antibody against Dsg3, caused loss of cell cohesion, cytokeratin retraction and p38MAPK activation. Strong alterations in Dsg3 distribution were caused by mucosal (aDsg3 antibodies), mucocutaneous (aDsg1 + aDsg3) as well as atypical (aDsg3) PV-IgG. All PV-IgG fractions and AK23 compromised Dsg3 but not Dsg1 binding and enhanced Src activity. In contrast, rapid Ca2+ influx and Erk activation were induced by mucocutaneous PV-IgG and pemphigus foliaceus (PF) IgG (aDsg1) whereas cAMP was increased by mucosal and mucocutaneous PV-IgG only. Selective inhibition of p38MAPK, Src or PKC blocked loss of keratinocyte cohesion in response to all autoantibody fractions whereas Erk inhibition was protective against mucocutaneous PV-IgG and PF-IgG only. These results demonstrate that signaling patterns parallel the clinical phenotype as some mechanisms involved in loss of cell cohesion are caused by antibodies targeting Dsg3 whereas others correlate with autoantibodies against Dsg1. The concept of key desmosome regulators may explain observations from several experimental models of pemphigus.
Attenuation of cGVHD by C5a/C5aR blockade is associated with increased frequency of Treg
Authors: Wang Yulian , Lai Peilong , Chen Xiaomei , He Chang , Huang Xin , Geng Suxia , Luo Chenwei , Wu Suijing , Ling Wei , Zhong Liye , Lu Zesheng , Li Peng , Weng Jianyu , Du Xin
Published: June 2017

C5aR signaling plays an important role in the regulation of T cell activation and alloimmune responses in chronic graft-versus-host disease (cGVHD). However, direct evidence of this modulation and the efficacy of C5aR blockade in the treatment of cGVHD have not been demonstrated. We observed higher expression of C5aR on both monocytes and T cells of patients with cGVHD compared with healthy controls and non-GVHD patients after allogeneic hematopoietic stem cell transplantation. Our data also demonstrated a significant negative correlation between C5aR expression and regulatory T cells (Treg) frequency in cGVHD patients, indicating a potential role of C5aR in the generation and regulation of Treg. In addition, an in vitro experiment revealed C5aR deficiency promoted the development of Treg whereas C5a activation abolished the differentiation of Treg. Importantly, we found C5aR blockade by PMX53 attenuated the pathology of cGVHD and improved the survival of cGVHD mice. PMX53 had a direct regulatory effect on Treg commitment and increased TGF-β1 expression. Thus, C5aR signaling may induce and intensify cGVHD by down-regulating Treg induction. The modulation of C5aR activation by PMX53 may provide a potential therapy for cGVHD.
A bacterial acetyltransferase triggers immunity in Arabidopsis thaliana independent of hypersensitive response
Authors: Jayaraman Jay , Choi Sera , Prokchorchik Maxim , Choi Du Seok , Spiandore Amandine , Rikkerink Erik H. , Templeton Matthew D. , Segonzac Cécile , Sohn Kee Hoon
Published: June 2017

Type-III secreted effectors (T3Es) play critical roles during bacterial pathogenesis in plants. Plant recognition of certain T3Es can trigger defence, often accompanied by macroscopic cell death, termed the hypersensitive response (HR). Economically important species of kiwifruit are susceptible to Pseudomonas syringae pv. actinidiae (Psa), the causal agent of kiwifruit bacterial canker. Although Psa is non-pathogenic in Arabidopsis thaliana, we observed that a T3E, HopZ5 that is unique to a global outbreak clade of Psa, triggers HR and defence in Arabidopsis accession Ct-1. Ws-2 and Col-0 accessions are unable to produce an HR in response to Pseudomonas-delivered HopZ5. While Ws-2 is susceptible to virulent bacterial strain Pseudomonas syringae pv. tomato DC3000 carrying HopZ5, Col-0 is resistant despite the lack of an HR. We show that HopZ5, like other members of the YopJ superfamily of acetyltransferases that it belongs to, autoacetylates lysine residues. Through comparisons to other family members, we identified an acetyltransferase catalytic activity and demonstrate its requirement for triggering defence in Arabidopsis and Nicotiana species. Collectively, data herein indicate that HopZ5 is a plasma membrane-localized acetyltransferase with autoacetylation activity required for avirulence.
Molecular dynamics exploration of poration and leaking caused by Kalata B1 in HIV-infected cell membrane compared to host and HIV membranes
Authors: Nawae Wanapinun , Hannongbua Supa , Ruengjitchatchawalya Marasri
Published: June 2017

The membrane disruption activities of kalata B1 (kB1) were investigated using molecular dynamics simulations with membrane models. The models were constructed to mimic the lipid microdomain formation in membranes of HIV particle, HIV-infected cell, and host cell. The differences in the lipid ratios of these membranes caused the formation of liquid ordered (lo) domains of different sizes, which affected the binding and activity of kB1. Stronger kB1 disruptive activity was observed for the membrane with small sized lo domain. Our results show that kB1 causes membrane leaking without bilayer penetration. The membrane poration mechanism involved in the disorganization of the lo domain and in cholesterol inter-leaflet translocation is described. This study enhances our understanding of the membrane activity of kB1, which may be useful for designing novel and potentially therapeutic peptides based on the kB1 framework.
Measurement of the magnetic moment of single Magnetospirillum gryphiswaldense cells by magnetic tweezers
Authors: Zahn C. , Keller S. , Toro-Nahuelpan M. , Dorscht P. , Gross W. , Laumann M. , Gekle S. , Zimmermann W. , Schüler D. , Kress H.
Published: June 2017

Magnetospirillum gryphiswaldense is a helix-shaped magnetotactic bacterium that synthesizes iron-oxide nanocrystals, which allow navigation along the geomagnetic field. The bacterium has already been thoroughly investigated at the molecular and cellular levels. However, the fundamental physical property enabling it to perform magnetotaxis, its magnetic moment, remains to be elucidated at the single cell level. We present a method based on magnetic tweezers; in combination with Stokesian dynamics and Boundary Integral Method calculations, this method allows the simultaneous measurement of the magnetic moments of multiple single bacteria. The method is demonstrated by quantifying the distribution of the individual magnetic moments of several hundred cells of M. gryphiswaldense. In contrast to other techniques for measuring the average magnetic moment of bacterial populations, our method accounts for the size and the helical shape of each individual cell. In addition, we determined the distribution of the saturation magnetic moments of the bacteria from electron microscopy data. Our results are in agreement with the known relative magnetization behavior of the bacteria. Our method can be combined with single cell imaging techniques and thus can address novel questions about the functions of components of the molecular magnetosome biosynthesis machinery and their correlation with the resulting magnetic moment.