bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations among child abuse, mental health, and epigenetic modifications in the proopiomelanocortin gene (POMC): A study with children in Tanzania
Authors: Hecker Tobias , Radtke Karl M. , Hermenau Katharin , Papassotiropoulos Andreas , Elbert Thomas
Published: January 2016

Child abuse is associated with a number of emotional and behavioral problems. Nevertheless, it has been argued that these adverse consequences may not hold for societies in which many of the specific acts of abuse are culturally normed. Epigenetic modifications in the genes of the hypothalamus–pituitary–adrenal axis may provide a potential mechanism translating abuse into altered gene expression, which subsequently results in behavioral changes. Our investigation took place in Tanzania, a society in which many forms of abuse are commonly employed as disciplinary methods. We included 35 children with high exposure and compared them to 25 children with low exposure. Extreme group comparisons revealed that children with high exposure reported more mental health problems. Child abuse was associated with differential methylation in the proopiomelanocortin gene (POMC), measured both in saliva and in blood. Hierarchical clustering based on the methylation of thePOMCgene found two distinct clusters. These corresponded with children's self-reported abuse, with two-thirds of the children allocated into their respective group. Our results emphasize the consequences of child abuse based on both molecular and behavioral grounds, providing further evidence that acts of abuse affect children, even when culturally acceptable. Furthermore, on a molecular level, our findings strengthen the credibility of children's self-reports.
Data-driven learning for beginners: The case of German verb-preposition collocations
Authors: Vyatkina Nina
Published: January 2016

Research on data-driven learning (DDL), or teaching and learning languages with the help of electronic corpora, has shown that it is both effective and efficient. Nevertheless, DDL is still far from common pedagogical practice, not least because the empirical research on it is still limited and narrowly focused. This study addresses some gaps in that research by exploring the effectiveness of DDL for teaching low-proficiency learners lexico-grammatical constructions (verb-preposition collocations) in German, a morphologically rich language. The study employed a pretest-posttest design with intact third- and fourth-semester classes for German as a foreign language at a US university. The same collocations were taught to each group during one class period, with one group at each course level taking a paper-based DDL lesson with concordance lines from a native-speaker corpus and the other one taking a traditional rule-based lesson with textbook exercises. These constructions were new to third-semester students, whereas fourth-semester students had been exposed to them in the previous semester. The results show that, whereas the DDL method and the traditional method were both effective and resulted in lexical and grammatical gains, DDL was more effective for teaching new collocations. The study thus argues in favor of using paper-based DDL in the classroom at lower proficiency levels and for languages other than English.
Automatic Detection of Pearlite Spheroidization Grade of Steel Using Optical Metallography
Authors: Chen Naichao , Chen Yingchao , Ai Jun , Ren Jianxin , Zhu Rui , Ma Xingchi , Han Jun , Ma Qingqian
Published: January 2016

To eliminate the effect of subjective factors during manually determining the pearlite spheroidization grade of steel by analysis of optical metallography images, a novel method combining image mining and artificial neural networks (ANN) is proposed. The four co-occurrence matrices of angular second moment, contrast, correlation, and entropy are adopted to objectively characterize the images. ANN is employed to establish a mathematical model between the four co-occurrence matrices and the corresponding spheroidization grade. Three materials used in coal-fired power plants (ASTM A315-B steel, ASTM A335-P12 steel, and ASTM A355-P11 steel) were selected as the samples to test the validity of our proposed method. The results indicate that the accuracies of the calculated spheroidization grades reach 99.05, 95.46, and 93.63%, respectively. Hence, our newly proposed method is adequate for automatically detecting the pearlite spheroidization grade of steel using optical metallography.
Early claiming of higher-earning husbands, the survivor benefit, and the incidence of poverty among recent widows
Authors: DIEBOLD JEFFREY , MOULTON JEREMY , SCOTT JOHN
Published: January 2016

Social Security provides survivor benefits to lower-earning spouses of deceased workers entitled to a retirement benefit. The value of the survivor benefit depends on a number of factors including the deceased worker's claim age. We use the Health and Retirement Study and a discrete time hazard model to analyze how the claim age of married men influences the likelihood that their spouse will enter poverty in widowhood. We find that delayed claiming is associated with reduction in a widow's poverty risk. The magnitude of this relationship varies significantly with the claim age, Social Security dependence, and survivor benefit dependence.
Men, Muslims, and Attitudes toward Gender Inequality
Authors: Lussier Danielle N. , Fish M. Steven
Published: January 2016

Gender-based inequality is often regarded as a salient characteristic of Muslim societies, yet few works have systematically compared the status of women in Muslim and non-Muslim communities. Fish (2011) finds a gender gap in structural indicators of inequality in Muslim-majority countries that cannot be explained by levels of economic development, raising questions about whether attitudes favoring inequality are more prominent among Muslims. We investigate the impact of structural-situational factors and religious identification on attitudes toward gender-based inequality using hierarchical-level models. We find that: (1) Muslim self-identification and the size of a country's Muslim population predict attitudes supportive of inequality; (2) an individual's gender has a stronger effect on attitudes than does religious identification; and (3) measures of structural inequality also shape attitudes. The effects of these variables remain strong when we consider other contextual elements, such as gross domestic product per capita, education, age, location in the Middle East, and fuels dependence.
Association of detected depression and undetected depressive symptoms with long-term mortality in a cohort of institutionalised older people
Authors: Damián J. , Pastor-Barriuso R. , Valderrama-Gama E. , de Pedro-Cuesta J.
Published: January 2016

Background.

Studies on depression and mortality in nursing homes have shown inconclusive findings, and none has studied the role of detection. We sought to measure the association of depression with long-term all-cause mortality in institutionalised older people and evaluate a potential modification in the association by its detection status.

Methods.

We selected a stratified cluster sample of 591 residents aged 75 years or older (mean age 84.5 years) living in residential and nursing homes of Madrid, Spain, who were free of severe cognitive impairment at the 1998–1999 baseline interview. Mortality was ascertained until age 105 years or September 2013 (median/maximum follow-up 4.8/15.2 years) through linkage to the Spanish National Death Index. Detected depression was defined at baseline as a physician's diagnosis or antidepressant use, undetected depression as significant depressive symptoms (score of 4 or higher on the ten-item version of the Geriatric Depression Scale) without documented diagnosis or treatment, and no depression as the absence of diagnosis, treatment, and symptoms. Constant and age-dependent hazard ratios for mortality comparing detected and undetected depression with no depression were estimated using Cox models, and absolute years of life gained and lost using Weibull models.

Results.

The baseline prevalences of detected and undetected depression were 25.9 and 18.8%, respectively. A total of 499 participants died during 3575 person-years of follow-up. In models adjusted for age, sex, type of facility, number of chronic conditions, and functional dependency, overall depression was not associated with long-term all-cause mortality (hazard ratio 0.87, 95% confidence interval (CI): 0.70–1.08). However, compared with no depression, detected depression showed lower mortality (hazard ratio 0.63, 95% CI: 0.46–0.86), while undetected depression registered higher, not statistically significant, mortality (hazard ratio 1.35, 95% CI: 0.98–1.86). The median life expectancy increased by 1.8 years (95% CI: −3.1 to 6.7 years) in residents with detected depression and decreased by 6.3 years (95% CI: 2.6–10.1 years) in those undetected. Results were more marked in women than men and they were robust to the exclusion of antidepressants from the definition of depression and also to the use of a stricter cut-off for the presence of depressive symptoms.

Conclusions.

The long-term mortality risk associated with depression in nursing homes depends on its detection status, with better prognosis in residents with detected depression and worse in those undetected. The absolute impact of undetected depressive symptoms in terms of life expectancy can be prominent.
Standards for Experimental Research: Encouraging a Better Understanding of Experimental Methods
Authors: Mutz Diana C. , Pemantle Robin
Published: January 2016

In this essay, we closely examine three aspects of the Reporting Guidelines for this journal, as described by Gerber et al. (2014,Journal of Experimental Political Science1(1): 81–98) in the inaugural issue of the Journal of Experimental Political Science. These include manipulation checks and when the reporting of response rates is appropriate. The third, most critical, issue concerns the committee's recommendations for detecting errors in randomization. This is an area where there is evidence of widespread confusion about experimental methods throughout our major journals. Given that a goal of the Journal of Experimental Political Science is promoting best practices and a better understanding of experimental methods across the discipline, we recommend changes to the Standards that will allow the journal to play a leading role in correcting these misunderstandings.
Temporal activation of XRCC1-mediated DNA repair is essential for muscle differentiation
Authors: Al-Khalaf Mohammad H , Blake Leanne E , Larsen Brian D , Bell Ryan A , Brunette Steve , Parks Robin J , Rudnicki Michael A , McKinnon Peter J , Jeffrey Dilworth F , Megeney Lynn A
Published: January 2016

Transient DNA strand break formation has been identified as an effective means to enhance gene expression in living cells. In the muscle lineage, cell differentiation is contingent upon the induction of caspase-mediated DNA strand breaks, which act to establish the terminal gene expression program. This coordinated DNA nicking is rapidly resolved, suggesting that myoblasts may deploy DNA repair machinery to stabilize the genome and entrench the differentiated phenotype. Here, we identify the base excision repair pathway component XRCC1 as an indispensable mediator of muscle differentiation. Caspase-triggered XRCC1 repair foci form rapidly within differentiating myonuclei, and then dissipate as the maturation program proceeds. Skeletal myoblast deletion of Xrcc1 does not have an impact on cell growth, yet leads to perinatal lethality, with sustained DNA damage and impaired myofiber development. Together, these results demonstrate that XRCC1 manages a temporally responsive DNA repair process to advance the muscle differentiation program.
Antigen‐specific T cells fully conserve antitumour function following cryopreservation
Authors: Galeano Niño Jorge L , Kwan Rain YQ , Weninger Wolfgang , Biro Maté
Published: January 2016

Immunotherapies based on the autologous adoptive transfer of ex vivo‐manipulated T cells are rapidly evolving for the treatment of both metastatic and primary malignancies. However, extended ex vivo culturing reduces the functionality of isolated T cells. Cryopreservation of rapidly expanded T cells for subsequent use throughout an immunotherapeutic regimen is a highly desirable recourse, thus far encumbered by a lack of studies investigating its effects on effector T‐cell functionality. Here we directly compare murine tumour‐reactive CD8+ T cells cryopreserved during ex vivo expansion to freshly isolated populations. We show that cryopreservation fully conserves the differentiation potential of effector T cells, secretion of pro‐inflammatory cytokines, cytotoxic function and does not impair the three‐dimensional scanning motility of T cells or their capacity to infiltrate and reject tumours.
Novel role for anti-Müllerian hormone in the regulation of GnRH neuron excitability and hormone secretion
Authors: Cimino Irene , Casoni Filippo , Liu Xinhuai , Messina Andrea , Parkash Jyoti , Jamin Soazik P. , Catteau-Jonard Sophie , Collier Francis , Baroncini Marc , Dewailly Didier , Pigny Pascal , Prescott Mel , Campbell Rebecca , Herbison Allan E. , Prevot Vincent , Giacobini Paolo
Published: January 2016

Anti-Müllerian hormone (AMH) plays crucial roles in sexual differentiation and gonadal functions. However, the possible extragonadal effects of AMH on the hypothalamic–pituitary–gonadal axis remain unexplored. Here we demonstrate that a significant subset of GnRH neurons both in mice and humans express the AMH receptor, and that AMH potently activates the GnRH neuron firing in mice. Combiningin vivoandin vitroexperiments, we show that AMH increases GnRH-dependent LH pulsatility and secretion, supporting a central action of AMH on GnRH neurons. Increased LH pulsatility is an important pathophysiological feature in many cases of polycystic ovary syndrome (PCOS), the most common cause of female infertility, in which circulating AMH levels are also often elevated. However, the origin of this dysregulation remains unknown. Our findings raise the intriguing hypothesis that AMH-dependent regulation of GnRH release could be involved in the pathophysiology of fertility and could hold therapeutic potential for treating PCOS.
Spatio-temporal propagation of cascading overload failures in spatially embedded networks
Authors: Zhao Jichang , Li Daqing , Sanhedrai Hillel , Cohen Reuven , Havlin Shlomo
Published: January 2016

Different from the direct contact in epidemics spread, overload failures propagate through hidden functional dependencies. Many studies focused on the critical conditions and catastrophic consequences of cascading failures. However, to understand the network vulnerability and mitigate the cascading overload failures, the knowledge of how the failures propagate in time and space is essential but still missing. Here we study the spatio-temporal propagation behaviour of cascading overload failures analytically and numerically on spatially embedded networks. The cascading overload failures are found to spread radially from the centre of the initial failure with an approximately constant velocity. The propagation velocity decreases with increasing tolerance, and can be well predicted by our theoretical framework with one single correction for all the tolerance values. This propagation velocity is found similar in various model networks and real network structures. Our findings may help to predict the dynamics of cascading overload failures in realistic systems.
Clouds enhance Greenland ice sheet meltwater runoff
Authors: Van Tricht K. , Lhermitte S. , Lenaerts J. T. M. , Gorodetskaya I. V. , L’Ecuyer T. S. , Noël B. , van den Broeke M. R. , Turner D. D. , van Lipzig N. P. M.
Published: January 2016

The Greenland ice sheet has become one of the main contributors to global sea level rise, predominantly through increased meltwater runoff. The main drivers of Greenland ice sheet runoff, however, remain poorly understood. Here we show that clouds enhance meltwater runoff by about one-third relative to clear skies, using a unique combination of active satellite observations, climate model data and snow model simulations. This impact results from a cloud radiative effect of 29.5 (±5.2) W m−2. Contrary to conventional wisdom, however, the Greenland ice sheet responds to this energy through a new pathway by which clouds reduce meltwater refreezing as opposed to increasing surface melt directly, thereby accelerating bare-ice exposure and enhancing meltwater runoff. The high sensitivity of the Greenland ice sheet to both ice-only and liquid-bearing clouds highlights the need for accurate cloud representations in climate models, to better predict future contributions of the Greenland ice sheet to global sea level rise.
Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2–JNK signalling in breast cancer
Authors: Puvirajesinghe Tania M. , Bertucci François , Jain Ashish , Scerbo Pierluigi , Belotti Edwige , Audebert Stéphane , Sebbagh Michael , Lopez Marc , Brech Andreas , Finetti Pascal , Charafe-Jauffret Emmanuelle , Chaffanet Max , Castellano Rémy , Restouin Audrey , Marchetto Sylvie , Collette Yves , Gonçalvès Anthony , Macara Ian , Birnbaum Daniel , Kodjabachian Laurent , Johansen Terje , Borg Jean-Paul
Published: January 2016

The non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway plays a crucial role in embryonic development. Recent work has linked defects of this pathway to breast cancer aggressiveness and proposed Wnt/PCP signalling as a therapeutic target. Here we show that the archetypal Wnt/PCP protein VANGL2 is overexpressed in basal breast cancers, associated with poor prognosis and implicated in tumour growth. We identify the scaffold p62/SQSTM1 protein as a novel VANGL2-binding partner and show its key role in an evolutionarily conserved VANGL2–p62/SQSTM1–JNK pathway. This proliferative signalling cascade is upregulated in breast cancer patients with shorter survival and can be inactivated in patient-derived xenograft cells by inhibition of the JNK pathway or by disruption of the VANGL2–p62/SQSTM1 interaction. VANGL2–JNK signalling is thus a potential target for breast cancer therapy.
Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus
Authors: Park Raehee , Moon Uk Yeol , Park Jun Young , Hughes Lucinda J. , Johnson Randy L. , Cho Seo-Hee , Kim Seonhee
Published: January 2016

Timely generation and normal maturation of ependymal cells along the aqueduct are critical for preventing physical blockage between the third and fourth ventricles and the development of fetal non-communicating hydrocephalus. Our study identifies Yap, the downstream effector of the evolutionarily conserved Hippo pathway, as a central regulator for generating developmentally controlled ependymal cells along the ventricular lining of the aqueduct. Yap function is necessary for proper proliferation of progenitors and apical attachment of ependymal precursor cells. Importantly, an injury signal initiated by lysophosphatidic acid (LPA), an upstream regulator of Yap that can cause fetal haemorrhagic hydrocephalus, deregulates Yap in the developing aqueduct. LPA exposure leads to the loss of N-cadherin concentrations at the apical endfeet, which can be partially restored by forced Yap expression and more efficiently by phosphomimetic Yap. These results reveal a novel function of Yap in retaining tissue junctions during normal development and after fetal brain injury.
A draft map of the mouse pluripotent stem cell spatial proteome
Authors: Christoforou Andy , Mulvey Claire M. , Breckels Lisa M. , Geladaki Aikaterini , Hurrell Tracey , Hayward Penelope C. , Naake Thomas , Gatto Laurent , Viner Rosa , Arias Alfonso Martinez , Lilley Kathryn S.
Published: January 2016

Knowledge of the subcellular distribution of proteins is vital for understanding cellular mechanisms. Capturing the subcellular proteome in a single experiment has proven challenging, with studies focusing on specific compartments or assigning proteins to subcellular niches with low resolution and/or accuracy. Here we introduce hyperLOPIT, a method that couples extensive fractionation, quantitative high-resolution accurate mass spectrometry with multivariate data analysis. We apply hyperLOPIT to a pluripotent stem cell population whose subcellular proteome has not been extensively studied. We provide localization data on over 5,000 proteins with unprecedented spatial resolution to reveal the organization of organelles, sub-organellar compartments, protein complexes, functional networks and steady-state dynamics of proteins and unexpected subcellular locations. The method paves the way for characterizing the impact of post-transcriptional and post-translational modification on protein location and studies involving proteome-level locational changes on cellular perturbation. An interactive open-source resource is presented that enables exploration of these data.
Erratum: Disordering of the vortex lattice through successive destruction of positional and orientational order in a weakly pinned Co0.0075NbSe2 single crystal
Authors: Ganguli Somesh Chandra , Singh Harkirat , Saraswat Garima , Ganguly Rini , Bagwe Vivas , Shirage Parasharam , Thamizhavel Arumugam , Raychaudhuri Pratap
Published: January 2016

The vortex lattice in a Type II superconductor provides a versatile model system to investigate the order-disorder transition in a periodic medium in the presence of random pinning. Here, using scanning tunnelling spectroscopy in a weakly pinned Co0.0075NbSe2 single crystal, we show that the vortex lattice in a 3-dimensional superconductor disorders through successive destruction of positional and orientational order, as the magnetic field is increased across the peak effect. At the onset of the peak effect, the equilibrium quasi-long range ordered state transforms into an orientational glass through the proliferation of dislocations. At a higher field, the dislocations dissociate into isolated disclination giving rise to an amorphous vortex glass. We also show the existence of a variety of additional non-equilibrium metastable states, which can be accessed through different thermomagnetic cycling.
The Type II Secreted Lipase/Esterase LesA is a Key Virulence Factor Required for Xylella fastidiosa Pathogenesis in Grapevines
Authors: Nascimento Rafael , Gouran Hossein , Chakraborty Sandeep , Gillespie Hyrum W. , Almeida-Souza Hebréia O. , Tu Aye , Rao Basuthkar J. , Feldstein Paul A. , Bruening George , Goulart Luiz R. , Dandekar Abhaya M.
Published: January 2016

Pierce’s disease (PD) of grapevines is caused by Xylella fastidiosa (Xf), a xylem-limited gamma-proteobacterium that is responsible for several economically important crop diseases. The occlusion of xylem elements and interference with water transport by Xf and its associated biofilm have been posited as the main cause of PD symptom development; however, Xf virulence mechanisms have not been described. Analysis of the Xf secretome revealed a putative lipase/esterase (LesA) that was abundantly secreted in bacterial culture supernatant and was characterized as a protein ortholog of the cell wall-degrading enzyme LipA of Xanthomonas strains. LesA was secreted by Xf and associated with a biofilm filamentous network. Additional proteomic analysis revealed its abundant presence in outer membrane vesicles (OMVs). Accumulation of LesA in leaf regions associated positively with PD symptoms and inversely with bacterial titer. The lipase/esterase also elicited a hypersensitive response in grapevine. Xf lesA mutants were significantly deficient for virulence when mechanically inoculated into grapevines. We propose that Xf pathogenesis is caused by LesA secretion mediated by OMV cargos and that its release and accumulation in leaf margins leads to early stages of observed PD symptoms.
Impact of the 2010 Deepwater Horizon oil spill on population size and genetic structure of horse flies in Louisiana marshes
Authors: Husseneder Claudia , Donaldson Jennifer R. , Foil Lane D.
Published: January 2016

The greenhead horse fly, Tabanus nigrovittatus Macquart, is frequently found in coastal marshes of the Eastern United States. The greenhead horse fly larvae are top predators in the marsh and thus vulnerable to changes in the environment and the adults potentially are attracted to polarized surfaces like oil. Therefore, horse fly populations could serve as bioindicators of marsh health and toxic effects of oil intrusion. In this study, we describe the impact of the April 2010 Deep Water Horizon oil spill in the Gulf of Mexico on tabanid population abundance and genetics as well as mating structure. Horse fly populations were sampled biweekly from oiled and unaffected locations immediately after the oil spill in June 2010 until October 2011. Horse fly abundance estimates showed severe crashes of tabanid populations in oiled areas. Microsatellite genotyping of six pristine and seven oiled populations at ten polymorphic loci detected genetic bottlenecks in six of the oiled populations in association with fewer breeding parents, reduced effective population size, lower number of family clusters and fewer migrants among populations. This is the first study assessing the impact of oil contamination at the level of a top arthropod predator of the invertebrate community in salt marshes.
Conformation-controlled binding kinetics of antibodies
Authors: Galanti Marta , Fanelli Duccio , Piazza Francesco
Published: January 2016

Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.
Material properties of evolutionary diverse spider silks described by variation in a single structural parameter
Authors: Madurga Rodrigo , Plaza Gustavo R. , Blackledge Todd A. , Guinea Gustavo.V. , Elices Manuel , Pérez-Rigueiro José
Published: January 2016

Spider major ampullate gland silks (MAS) vary greatly in material properties among species but, this variation is shown here to be confined to evolutionary shifts along a single universal performance trajectory. This reveals an underlying design principle that is maintained across large changes in both spider ecology and silk chemistry. Persistence of this design principle becomes apparent after the material properties are defined relative to the true alignment parameter, which describes the orientation and stretching of the protein chains in the silk fiber. Our results show that the mechanical behavior of all Entelegynae major ampullate silk fibers, under any conditions, are described by this single parameter that connects the sequential action of three deformation micromechanisms during stretching: stressing of protein-protein hydrogen bonds, rotation of the β-nanocrystals and growth of the ordered fraction. Conservation of these traits for over 230 million years is an indication of the optimal design of the material and gives valuable clues for the production of biomimetic counterparts based on major ampullate spider silk.
Geometrical Patterning of Super-Hydrophobic Biosensing Transistors Enables Space and Time Resolved Analysis of Biological Mixtures
Authors: Gentile Francesco , Ferrara Lorenzo , Villani Marco , Bettelli Manuele , Iannotta Salvatore , Zappettini Andrea , Cesarelli Mario , Di Fabrizio Enzo , Coppedè Nicola
Published: January 2016

PEDOT:PSS is a conductive polymer that can be integrated into last generation Organic Electrochemical Transistor (OECT) devices for biological inspection, identification and analysis. While a variety of reports in literature demonstrated the chemical and biological sensitivity of these devices, still their ability in resolving complex mixtures remains controversial. Similar OECT devices display good time dynamics behavior but lack spatial resolution. In this work, we integrated PEDOT:PSS with patterns of super-hydrophobic pillars in which a finite number of those pillars is independently controlled for site-selective measurement of a solution. We obtained a multifunctional, hierarchical OECT device that bridges the micro- to the nano-scales for specific, combined time and space resolved analysis of the sample. Due to super-hydrophobic surface properties, the biological species in the drop are driven by convection, diffusion and the externally applied electric field: the balance/unbalance between these forces will cause the molecules to be transported differently within its volume depending on particle size thus realizing a size-selective separation. Within this framework, the separation and identification of two different molecules, namely Cetyl Trimethyl Ammonium Bromid (CTAB) and adrenaline, in a biological mixture have been demonstrated, showing that geometrical control at the micro-nano scale impart unprecedented selectivity to the devices.
Direct observation of deterministic domain wall trajectory in magnetic network structures
Authors: Sethi P. , Murapaka C. , Goolaup S. , Chen Y. J. , Leong S. H. , Lew W. S.
Published: January 2016

Controlling the domain wall (DW) trajectory in magnetic network structures is crucial for spin-based device related applications. The understanding of DW dynamics in network structures is also important for study of fundamental properties like observation of magnetic monopoles at room temperature in artificial spin ice lattice. The trajectory of DW in magnetic network structures has been shown to be chirality dependent. However, the DW chirality periodically oscillates as it propagates a distance longer than its fidelity length due to Walker breakdown phenomenon. This leads to a stochastic behavior in the DW propagation through the network structure. In this study, we show that the DW trajectory can be deterministically controlled in the magnetic network structures irrespective of its chirality by introducing a potential barrier. The DW propagation in the network structure is governed by the geometrically induced potential barrier and pinning strength against the propagation. This technique can be extended for controlling the trajectory of magnetic charge carriers in an artificial spin ice lattice.
Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response
Authors: Li Tiejun , Cheng Hao , Yuan Hong , Xu Qiming , Shu Chang , Zhang Yuefan , Xu Pengbiao , Tan Jason , Rui Yaocheng , Li Pingwei , Tan Xiangshi
Published: January 2016

Immunotherapy is one of the key strategies for cancer treatment. The cGAS-cGAMP-STING-IRF3 pathway of cytosolic DNA sensing plays a pivotal role in antiviral defense. We report that the STING activator cGAMP possesses significant antitumor activity in mice by triggering the STING-dependent pathway directly. cGAMP enhances innate immune responses by inducing production of cytokines such as interferon-β, interferon-γ and stimulating dendritic cells activation, which induces the cross-priming of CD8+ T cells. The antitumor mechanism of cGAMP was verified by STING and IRF3, which were up-regulated upon cGAMP treatment. STING-deficiency dramatically reduced the antitumor effect of cGAMP. Furthermore, cGAMP improved the antitumor activity of 5-FU and clearly reduced the toxicity of 5-FU. These results demonstrated that cGAMP is a novel antitumor agent and has potential applications in cancer immunotherapy.
iMiRNA-SSF: Improving the Identification of MicroRNA Precursors by Combining Negative Sets with Different Distributions
Authors: Chen Junjie , Wang Xiaolong , Liu Bin
Published: January 2016

The identification of microRNA precursors (pre-miRNAs) helps in understanding regulator in biological processes. The performance of computational predictors depends on their training sets, in which the negative sets play an important role. In this regard, we investigated the influence of benchmark datasets on the predictive performance of computational predictors in the field of miRNA identification and found that the negative samples have significant impact on the predictive results of various methods. We constructed a new benchmark set with different data distributions of negative samples. Trained with this high quality benchmark dataset, a new computational predictor called iMiRNA-SSF was proposed, which employed various features extracted from RNA sequences. Experimental results showed that iMiRNA-SSF outperforms three state-of-the-art computational methods. For practical applications, a web-server of iMiRNA-SSF was established at the website http://bioinformatics.hitsz.edu.cn/iMiRNA-SSF/.
Signaling through NOD-2 and TLR-4 Bolsters the T cell Priming Capability of Dendritic cells by Inducing Autophagy
Authors: Khan Nargis , Vidyarthi Aurobind , Pahari Susanta , Negi Shikha , Aqdas Mohammad , Nadeem Sajid , Agnihotri Tapan , Agrewala Javed N.
Published: January 2016

T cells play a cardinal role in mediating protection against intracellular pathogens like Mycobacterium tuberculosis (Mtb). It is important to understand the factors that govern the T cell response; thereby can modulate its activity. Dendritic cells (DCs) are the major player in initiation and augmentation of T cell response. Targeting DCs to induce their optimum maturation and activation can lead to a better T cell response. Interestingly, we observed that combinatorial signaling of DCs through NOD-2 and TLR-4 fortified better yield of IL-12p40/70, IL-6 and IFN-γ and upregulated the expression of CD40, CD80 and CD86 costimulatory molecules. Further, we noticed improved phagocytic capabilities of DCs. Furthermore, NOD-2 and TLR-4 induced autophagy in DCs, which enhanced the activation of T cells. This study signifies that NOD-2 and TLR-4 exhibit synergism in invigorating the activity of DCs. Consequently, this strategy may have significant immunotherapeutic potential in bolstering the function of DCs and thus improving the immunity against pathogens.
Molecular mechanism of peptide editing in the tapasin–MHC I complex
Authors: Fisette Olivier , Wingbermühle Sebastian , Tampé Robert , Schäfer Lars V.
Published: January 2016

Immune recognition of infected or malignantly transformed cells relies on antigenic peptides exposed at the cell surface by major histocompatibility complex class I (MHC I) molecules. Selection and loading of peptides onto MHC I is orchestrated by the peptide-loading complex (PLC), a multiprotein assembly whose structure has not yet been resolved. Tapasin, a central component of the PLC, stabilises MHC I and catalyses the exchange of low-affinity against high-affinity, immunodominant peptides. Up to now, the molecular basis of this peptide editing mechanism remained elusive. Here, using all-atom molecular dynamics (MD) simulations, we unravel the atomic details of how tapasin and antigen peptides act on the MHC I binding groove. Force distribution analysis reveals an intriguing molecular tug-of-war mechanism: only high-affinity peptides can exert sufficiently large forces to close the binding groove, thus overcoming the opposite forces exerted by tapasin to open it. Tapasin therefore accelerates the release of low-affinity peptides until a high-affinity antigen binds, promoting subsequent PLC break-down. Fluctuation and entropy analyses show how tapasin chaperones MHC I by stabilising it in a peptide-receptive conformation. Our results explain previous experiments and mark a key step towards a better understanding of adaptive immunity.
The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for extensive oligomerization at the plasma membrane and viral egress
Authors: Johnson Kristen A. , Taghon Geoffrey J. F. , Scott Jordan L. , Stahelin Robert V.
Published: January 2016

VP40 is one of eight proteins encoded by the Ebola Virus (EBOV) and serves as the primary matrix protein, forming virus like particles (VLPs) from mammalian cells without the need for other EBOV proteins. While VP40 is required for viral assembly and budding from host cells during infection, the mechanisms that target VP40 to the plasma membrane are not well understood. Phosphatidylserine is required for VP40 plasma membrane binding, VP40 hexamer formation and VLP egress, However, PS also becomes exposed on the outer membrane leaflet at sites of VP40 budding, raising the question of how VP40 maintains an interaction with the plasma membrane inner leaflet when PS is flipped to the opposite side. To address this question, cellular and in vitro assays were employed to determine if phosphoinositides are important for efficient VP40 localization to the plasma membrane. Cellular studies demonstrated that PI(4,5)P2 was an important component of VP40 assembly at the plasma membrane and subsequent virus like particle formation. Additionally, PI(4,5)P2 was required for formation of extensive oligomers of VP40, suggesting PS and PI(4,5)P2 have different roles in VP40 assembly where PS regulates formation of hexamers from VP40 dimers and PI(4,5)P2 stabilizes and/or induces extensive VP40 oligomerization at the plasma membrane.
Nanoscale mapping of plasmon and exciton in ZnO tetrapods coupled with Au nanoparticles
Authors: Bertoni Giovanni , Fabbri Filippo , Villani Marco , Lazzarini Laura , Turner Stuart , Van Tendeloo Gustaaf , Calestani Davide , Gradečak Silvija , Zappettini Andrea , Salviati Giancarlo
Published: January 2016

Metallic nanoparticles can be used to enhance optical absorption or emission in semiconductors, thanks to a strong interaction of collective excitations of free charges (plasmons) with electromagnetic fields. Herein we present direct imaging at the nanoscale of plasmon-exciton coupling in Au/ZnO nanostructures by combining scanning transmission electron energy loss and cathodoluminescence spectroscopy and mapping. The Au nanoparticles (~30 nm in diameter) are grown in-situ on ZnO nanotetrapods by means of a photochemical process without the need of binding agents or capping molecules, resulting in clean interfaces. Interestingly, the Au plasmon resonance is localized at the Au/vacuum interface, rather than presenting an isotropic distribution around the nanoparticle. On the contrary, a localization of the ZnO signal has been observed inside the Au nanoparticle, as also confirmed by numerical simulations.
APN1 is a functional receptor of Cry1Ac but not Cry2Ab in Helicoverpa zea
Authors: Wei Jizhen , Zhang Min , Liang Gemei , Wu Kongming , Guo Yuyuan , Ni Xinzhi , Li Xianchun
Published: January 2016

Lepidopteran midgut aminopeptidases N (APNs) are phylogenetically divided into eight clusters, designated as APN1–8. Although APN1 has been implicated as one of the receptors for Cry1Ac in several species, its potential role in the mode of action of Cry2Ab has not been functionally determined so far. To test whether APN1 also acts as one of the receptors for Cry1Ac in Helicoverpa zea and even for Cry2Ab in this species, we conducted a gain of function analysis by heterologously expressing H. zea APN1 (HzAPN1) in the midgut and fat body cell lines of H. zea and the ovarian cell line of Spodoptera frugiperda (Sf9) and a loss of function analysis by RNAi (RNA interference) silencing of the endogenous APN1 in the three cell lines using the HzAPN1 double strand RNA (dsRNA). Heterologous expression of HzAPN1 significantly increased the susceptibility of the three cell lines to Cry1Ac, but had no effects on their susceptibility to Cry2Ab. Knocking down of the endogenous APN1 made the three cell lines resistant to Cry1Ac, but didn’t change cell lines susceptibility to Cry2Ab. The findings from this study demonstrate that HzAPN1 is a functional receptor of Cry1Ac, but not Cry2Ab.
Dioscorea bulbifera polysaccharide and cyclophosphamide combination enhances anti-cervical cancer effect and attenuates immunosuppression and oxidative stress in mice
Authors: Cui Hongxia , Li Ting , Wang Liping , Su Yan , Xian Cory J.
Published: January 2016

Cyclophosphamide (CTX) is commonly used in cancer chemotherapy, which causes immunosuppression and tissue oxidative stress at high doses. As potential protective agents, some polysaccharides were shown to have anti-tumor, anti-inflammatory and/or anti-oxidant properties. This study explored potential effects of oral treatment of Dioscorea bulbifera polysaccharides (DBLP at 100 or 150 mg/kg) in U14 cervical tumor-bearing mice treated with CTX (25 mg/kg). While CTX suppressed tumor growth (65.4% inhibition) and DBLP alone also inhibited tumor (25.6% at 100 mg/kg or 37.6% at 150 mg/kg), CTX+DBLP combination produced tumor inhibition rates of 5.6 (for 100 mg/kg DBLP) or 9% (for 150 mg/kg) higher than CTX alone. While tumor itself and CTX treatment reduced thymus and/or spleen/body weight indices, DBLP alone or CTX + DBLP combination attenuated this reduction. DBLP lowered peripheral blood T-cell subpopulation CD4+/CD8+ ratio and DBLP+CTX combination attenuated CTX effect in lifting CD4+/CD8+ ratio. Tumor itself and CTX treatment heightened oxidative stress (with decreased superoxide dismutase but increased lactate dehydrogenase and malondialdehyde levels in serum and tissues), which was attenuated by DBLP treatment and DBLP+CTX combination suppressed CTX-induced oxidative stress. Combination use of DBLP with CTX can potentially enhance CTX anti-tumor effect and can attenuate CTX-induced immunosuppression and oxidative stress in U14 cervical tumor-bearing mice.
Emergence of a super-synchronized mobbing state in a large population of coupled chemical oscillators
Authors: Ghoshal Gourab , Muñuzuri Alberto P. , Pérez-Mercader Juan
Published: January 2016

Oscillatory phenomena are ubiquitous in Nature. The ability of a large population of coupled oscillators to synchronize constitutes an important mechanism to express information and establish communication among members. To understand such phenomena, models and experimental realizations of globally coupled oscillators have proven to be invaluable in settings as varied as chemical, biological and physical systems. A variety of rich dynamical behavior has been uncovered, although usually in the context of a single state of synchronization or lack thereof. Through the experimental and numerical study of a large population of discrete chemical oscillators, here we report on the unexpected discovery of a new phenomenon revealing the existence of dynamically distinct synchronized states reflecting different degrees of communication. Specifically, we discover a novel large-amplitude super-synchronized state separated from the conventionally reported synchronized and quiescent states through an unusual sharp jump transition when sampling the strong coupling limit. Our results assume significance for further elucidating globally coherent phenomena, such as in neuropathologies, bacterial cell colonies, social systems and semiconductor lasers.
The effect of annealing on a 3D SnO2/graphene foam as an advanced lithium-ion battery anode
Authors: Tian Ran , Zhang Yangyang , Chen Zhihang , Duan Huanan , Xu Biyi , Guo Yiping , Kang Hongmei , Li Hua , Liu Hezhou
Published: January 2016

3D annealed SnO2/graphene sheet foams (ASGFs) are synthesized by in situ self-assembly of graphene sheets prepared by mild chemical reduction. L-ascorbyl acid is used to effectively reduce the SnO2 nanoparticles/graphene oxide colloidal solution and form the 3D conductive graphene networks. The annealing treatment contributes to the formation of the Sn-O-C bonds between the SnO2 nanoparticles and the reduced graphene sheets, which improves the electrochemical performance of the foams. The ASGF has features of typical aerogels: low density (about 19 mg cm−3), smooth surface and porous structure. The ASGF anodes exhibit good specific capacity, excellent cycling stability and superior rate capability. The first reversible specific capacity is as high as 984.2 mAh g−1 at a specific current of 200 mA g−1. Even at the high specific current of 1000 mA g−1 after 150 cycles, the reversible specific capacity of ASGF is still as high as 533.7 mAh g−1, about twice as much as that of SGF (297.6 mAh g−1) after the same test. This synthesis method can be scaled up to prepare other metal oxides particles/ graphene sheet foams for high performance lithium-ion batteries, supercapacitors and catalysts, etc.
Locating single-point sources from arrival times containing large picking errors (LPEs): the virtual field optimization method (VFOM)
Authors: Li Xi-Bing , Wang Ze-Wei , Dong Long-Jun
Published: January 2016

Microseismic monitoring systems using local location techniques tend to be timely, automatic and stable. One basic requirement of these systems is the automatic picking of arrival times. However, arrival times generated by automated techniques always contain large picking errors (LPEs), which may make the location solution unreliable and cause the integrated system to be unstable. To overcome the LPE issue, we propose the virtual field optimization method (VFOM) for locating single-point sources. In contrast to existing approaches, the VFOM optimizes a continuous and virtually established objective function to search the space for the common intersection of the hyperboloids, which is determined by sensor pairs other than the least residual between the model-calculated and measured arrivals. The results of numerical examples and in-site blasts show that the VFOM can obtain more precise and stable solutions than traditional methods when the input data contain LPEs. Furthermore, we discuss the impact of LPEs on objective functions to determine the LPE-tolerant mechanism, velocity sensitivity and stopping criteria of the VFOM. The proposed method is also capable of locating acoustic sources using passive techniques such as passive sonar detection and acoustic emission.
A Viral mRNA Motif at the 3′-Untranslated Region that Confers Translatability in a Cell-Specific Manner. Implications for Virus Evolution
Authors: Garcia-Moreno Manuel , Sanz Miguel Angel , Carrasco Luis
Published: January 2016

Sindbis virus (SINV) mRNAs contain several motifs that participate in the regulation of their translation. We have discovered a motif at the 3′ untranslated region (UTR) of viral mRNAs, constituted by three repeated sequences, which is involved in the translation of both SINV genomic and subgenomic mRNAs in insect, but not in mammalian cells. These data illustrate for the first time that an element present at the 3′-UTR confers translatability to mRNAs from an animal virus in a cell-specific manner. Sequences located at the beginning of the 5′-UTR may also regulate SINV subgenomic mRNA translation in both cell lines in a context of infection. Moreover, a replicon derived from Sleeping disease virus, an alphavirus that have no known arthropod vector for transmission, is much more efficient in insect cells when the repeated sequences from SINV are inserted at its 3′-UTR, due to the enhanced translatability of its mRNAs. Thus, these findings provide a clue to understand, at the molecular level, the evolution of alphaviruses and their host range.