bluuebunny/crossref_metadata_2025 huggingface dataset:
Carboplatin, S-1 and concurrent thoracic radiotherapy for elderly patients with locally advanced non-small cell lung cancer: a multicenter Phase I/II study
Authors: Niho Seiji , Hosomi Yukio , Okamoto Hiroaki , Nihei Keiji , Tanaka Hiroshi , Hida Toyoaki , Umemura Shigeki , Goto Koichi , Akimoto Tetsuo , Ohe Yuichiro
Published: March 2019

Objectives

We conducted a Phase I/II study of carboplatin, S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients (71 years or older) with unresectable stage III non-small cell lung cancer (NSCLC).

Materials and methods

Patients received carboplatin (AUC 3-5) on Day 1 and S-1 (30–40 mg/m2 two times daily) on Days 1–14, every 2 weeks, for up to four cycles, plus concurrent TRT at a total dose of 60 Gy. The primary endpoint for the Phase II study was the 1-year progression-free survival (PFS) rate.

Results

Eighteen patients were enrolled in the Phase I study. Febrile neutropenia, a decreased platelet count and esophagitis were dose-limiting toxicities. The recommended doses for the Phase II study were determined to be an AUC of 3 for carboplatin, 40 mg/m2 twice daily for S-1. Twenty-eight patients were evaluated in the Phase II study. The 1-year PFS rate was 57.1% (90% CI 41.6–71.4%), and the median PFS was 16.8 months (95% CI 7.8–not assessable [NA]). The lower limit of the 90% CI for 1-year PFS exceeded the prespecified threshold value of 30%; therefore, the primary endpoint was met. Grades 3–4 toxicities included thrombocytopenia (21%) and hyponatremia (11%). Grade 3 radiation pneumonitis was observed in 18% of patients. No treatment-related deaths were observed.

Conclusion

Combination chemotherapy consisting of carboplatin plus S-1 and concurrent TRT had a promising efficacy in elderly patients with locally advanced NSCLC; however, radiation pneumonitis was frequently observed.
When to stop: an update on molecular mechanisms of floral meristem termination
Authors: Xu Yifeng , Yamaguchi Nobutoshi , Gan Eng-Seng , Ito Toshiro
Published: March 2019

Flowers have fascinated humans for millennia, not only because of their beauty, but also because they give rise to fruits, from which most agricultural products are derived. In most angiosperms, the number and position of floral organs are morphologically and genetically defined, and their development is tightly controlled by complex regulatory networks to ensure reproductive success. How flower development is temporally initiated and spatially maintained has been widely researched. As the flower develops, the balance between proliferation and differentiation dynamically shifts towards organogenesis and termination of floral stem cell maintenance. In this review, we focus on recent findings that further reveal the intricate molecular mechanisms for precise timing of floral meristem termination.
Shared expression of crassulacean acid metabolism (CAM) genes pre-dates the origin of CAM in the genus Yucca
Authors: Heyduk Karolina , Ray Jeremy N , Ayyampalayam Saaravanaraj , Moledina Nida , Borland Anne , Harding Scott A , Tsai Chung-Jui , Leebens-Mack Jim
Published: March 2019

Although large differences in metabolism exist between C3 and CAM species, we find that many CAM genes have similar expression patterns regardless of photosynthetic pathway, suggesting ancestral propensity for CAM.
Transnationalizing humour on social media: A linguistic analysis of ideology, identity and didactics in Robert Mugabe Quotes memes1
Authors: Onanuga Paul
Published: March 2019

Humour relies on dominant cultural values and outlooks in its environment in enacting its comic content. However, since humour sometimes encompasses global experiences, it often transcends artificial human barriers. Its transcendence has been facilitated through online digitized content, in the present case—Internet memes. In exploring transnationalization, fifty purposively selected memes are culled from the Facebook group Robert Mugabe Quotes and subjected to critical linguistic analysis. In the evaluation of the data which is achieved through the linguistic examination of cross-cultural themes in the formulation of identity, didactics, and ideology, sixteen memes, representative of the overarching tripartite concerns, are used as exemplifications. Reliant on the bipartite postulations of Critical Linguistic Stylistics—a linguistic theory that examines the style and peculiarities of linguistic data—and Relief Theory of Humour—which considers humour as a platform for the assuagement of tension and emotions, the memes are testamental of prevailing concerns— politics, technology, social/international relations, sex, male–female relations, etc.—in the human society at large. Linguistic markers such as oppositional expressions, capitalization, and other graphological features are annexed in meaning-formation. I conclude that although humour is generally regarded as a light-hearted routine geared towards the provision of momentary relief, a close scrutiny reveals that deep messages targeted at stimulating consciousness and social transformation find provenance in these artefacts.
Efficient selection of quasar candidates based on optical and infrared photometric data using machine learning
Authors: Jin Xin , Zhang Yanxia , Zhang Jingyi , Zhao Yongheng , Wu Xue-bing , Fan Dongwei
Published: March 2019

We aim to select quasar candidates based on the two large survey databases, Pan-STARRS and AllWISE. Exploring the distribution of quasars and stars in the colour spaces, we find that the combination of infrared and optical photometry is more conducive to select quasar candidates. Two new colour criterions (yW1W2 and iW1zW2) are constructed to distinguish quasars from stars efficiently. With iW1zW2, 98.30 per cent of star contamination is eliminated, while 99.50 per cent of quasars are retained, at least to the magnitude limit of our training set of stars. Based on the optical and infrared colour features, we put forward an efficient schema to select quasar candidates and high-redshift quasar candidates, in which two machine learning algorithms (XGBoost and SVM) are implemented. The XGBoost and SVM classifiers have proven to be very effective with accuracy of $99.46{{\ \rm per\ cent}}$ when 8Color as input pattern and default model parameters. Applying the two optimal classifiers to the unknown Pan-STARRS and AllWISE cross-matched data set, a total of 2 006 632 intersected sources are predicted to be quasar candidates given quasar probability larger than 0.5 (i.e. PQSO > 0.5). Among them, 1 201 211 have high probability (PQSO > 0.95). For these newly predicted quasar candidates, a regressor is constructed to estimate their redshifts. Finally 7402 z > 3.5 quasars are obtained. Given the magnitude limitation and site of the LAMOST telescope, part of these candidates will be used as the input catalogue of the LAMOST telescope for follow-up observation, and the rest may be observed by other telescopes.
Fast radio bursts as synchrotron maser emission from decelerating relativistic blast waves
Authors: Metzger Brian D , Margalit Ben , Sironi Lorenzo
Published: March 2019

Fast radio bursts (FRBs) can arise from synchrotron maser emission at ultrarelativistic magnetized shocks, such as produced by flare ejecta from young magnetars. We combine particle-in-cell simulation results for the maser emission with the dynamics of self-similar shock deceleration, as commonly applied to gamma-ray bursts (GRBs), to explore the implications for FRBs. The upstream environment is a mildly relativistic baryon-loaded shell released following a previous flare, motivated by the high electron–ion injection rate $\dot{M} \sim 10^{19}\!-\!10^{21}$ g s−1 needed to power the persistent radio nebula coincident with the repeating burster FRB 121102 and its high rotation measure. The radio fluence peaks once the optical depth ahead of the shock to induced Compton scattering τc ≲ 3. Given intervals between major ion ejection events ΔT ∼ 105  s similar to the occurrence rate of the most powerful bursts from FRB 121102, we demonstrate the production of ∼0.1–10 GHz FRBs with isotropic radiated energies ∼1037–1040 erg and durations ∼0.1–10 ms for flare energies E ∼ 1043–1045 erg. Deceleration of the blast wave, and increasing transparency of the upstream medium, generates temporal decay of the peak frequency, similar to the observed downward frequency drift seen in FRB 121102 and FRB 180814.J0422+73. The delay ΔT ≳ 105 s between major ion-injection events needed to clear sufficiently low densities around the engine for FRB emission could explain prolonged ‘dark periods’ and clustered burst arrival times. Thermal electrons heated at the shock generate a short-lived ≲1 ms (1 s) synchrotron transient at gamma-ray (X-ray) energies, analogous to a scaled-down GRB afterglow.
E-cigarette Dependence Measures in Dual Users: Reliability and Relations With Dependence Criteria and E-cigarette Cessation
Authors: Piper Megan E , Baker Timothy B , Benowitz Neal L , Smith Stevens S , Jorenby Douglas E
Published: March 2019

Background

Electronic cigarettes (e-cigarettes) have drastically changed the nicotine and tobacco product landscape. However, their potential public health impact is still unclear. A reliable and valid measure of e-cigarette dependence would likely advance assessment and prognostication of the public health impact of e-cigarettes. The aim of this research was to examine the internal consistency, structure, and validity of three e-cigarette dependence scales.

Methods

Adult dual users (smokers who also vape, N = 256) enrolled in an observational cohort study (45.1% women, 70.7% white). At baseline, participants completed the e-cigarette Fagerström Test of Cigarette Dependence (e-FTCD), the e-cigarette Wisconsin Inventory of Smoking Dependence Motives (e-WISDM), and the Penn State Electronic Cigarette Dependence Index (PS-ECDI). All participants provided a urine sample for cotinine analysis and reported e-cigarette use at 1 year.

Results

The e-WISDM subscales had the highest internal consistency (α = .81–.96), then the PS-ECDI (α = .74) and e-FTCD (α = .51). A single-factor structure for the e-FTCD and an 11-factor structure for the e-WISDM were supported, but the PS-ECDI did not have a single-factor structure. All three e-cigarette dependence scales were highly correlated with validation criteria including continued e-cigarette use at 1 year, but not with e-liquid nicotine concentration or cotinine.

Conclusions

The e-WISDM and PS-ECDI had stronger internal consistency than did the e-FTCD, despite the e-FTCD’s single-factor structure, but all 3 measures appear to be valid measures of e-cigarette dependence as suggested by their significant relations with self-perceived addiction, heavy use, early use after overnight deprivation, and continued use over time.

Implications

This research provides empirical support for three e-cigarette dependence measures: the e-FTCD, the PS-ECDI, and the e-WISDM among dual users of e-cigarettes and combustible cigarettes. The PS-ECDI and e-WISDM are more reliable, but all three measures were strongly correlated with key dependence constructs such as heavy use and continued use over time.
The Confidence and Supply Agreement between the Conservative Party and the Democratic Unionist Party: Implications for the Barnett Formula and Intergovernmental Relations in the UK
Authors: Birrell Derek , Heenan Deirdre
Published: March 2019

This article assesses the implications of the 2017 Confidence and Supply Agreement between the Conservative Party and the Democratic Unionist Party (DUP) in the context of the Barnett Formula and intergovernmental relations post the devolution settlement and the Good Friday Agreement. In light of the parties’ shared objectives to strengthen and enhance the UK, the Confidence and Supply Agreement, sets out how the DUP would support the minority Conservative government in specific areas, including finance Bills and matters pertaining to the exit from the European Union. This article examines the nature and operation of this Agreement and assesses the extent to which it may be seen to have breached established conventions, rules and principles around devolved funding and the principle of political impartiality enshrined in the Good Friday Agreement. It is argued that the Confidence and Supply Agreement has contributed to the perceived shortcomings of the Barnett Formula as a robust, fair, financial methodology. The distribution of money to the devolved administrations should be modernised and based on need, accountability and transparency. It is also concluded that being locked into a parliamentary deal undermines the UK Government’s ability to be impartial between the competing interests in Northern Ireland.
Moral identity relates to the neural processing of third-party moral behavior
Authors: Pletti Carolina , Decety Jean , Paulus Markus
Published: March 2019

Moral identity, or moral self, is the degree to which being moral is important to a person’s self-concept. It is hypothesized to be the `missing link’ between moral judgment and moral action. However, its cognitive and psychophysiological mechanisms are still subject to debate. In this study, we used event-related potentials to examine whether the moral self-concept is related to how people process prosocial and antisocial actions. To this end, participants’ implicit and explicit moral self-concept were assessed. We examined whether individual differences in moral identity relate to differences in early, automatic processes [i.e. Early Posterior Negativity (EPN), N2] or late, cognitively controlled processes (i.e. late positive potential) while observing prosocial and antisocial situations. Results show that a higher implicit moral self was related to a lower EPN amplitude for prosocial scenarios. In addition, an enhanced explicit moral self was related to a lower N2 amplitude for prosocial scenarios. The findings demonstrate that the moral self affects the neural processing of morally relevant stimuli during third-party evaluations. They support theoretical considerations that the moral self already affects (early) processing of moral information.
A rapid and simple method for assessing and representing genome sequence relatedness
Authors: Briand M , Bouzid M , Hunault G , Legeay M , Fischer-Le Saux M , Barret M
Published: March 2019

Abstract

Coherent genomic groups are frequently used as a proxy for bacterial species delineation through computation of overall genome relatedness indices (OGRI). Average nucleotide identity (ANI) is a widely employed method for estimating relatedness between genomic sequences. However, pairwise comparisons of genome sequences based on ANI is relatively computationally intensive and therefore precludes analyses of large datasets composed of thousands of genome sequences.

In this work we proposed a workflow to compute and visualize relationships between genomic sequences. A dataset containing more than 3,500 Pseudomonas genome sequences was successfully classified with an alternative OGRI based on k-mer counts in few hours with the same precision as ANI. A new visualization method based on zoomable circle packing was employed for assessing relationships among the 350 groups generated. Amendment of databases with these Pseudomonas groups greatly improved the classification of metagenomic read sets with k-mer-based classifier.

The developed workflow was integrated in the user-friendly KI-S tool that is available at the following address:https://iris.angers.inra.fr/galaxypub-cfbp.
Diffusion Tensor Tractography of Brainstem Fibers and Its Application in Pain
Authors: Zhang Yu , Vakhtin Andrei A. , Jennings Jennifer S. , Massaband Payam , Wintermark Max , Craig Patricia L. , Ashford J. Wesson , Clark David J. , Furst Ansgar J.
Published: March 2019

Evaluation of brainstem pathways with diffusion tensor imaging (DTI) and tractography may provide insights into pathophysiologies associated with dysfunction of key brainstem circuits. However, identification of these tracts has been elusive, with relatively few in vivo human studies to date. In this paper we proposed an automated approach for reconstructing nine brainstem fiber trajectories of pathways that might be involved in pain modulation. We first performed native-space manual tractography of these fibers in a small normative cohort of participants and confirmed the anatomical precision of the results using existing anatomical literature. Second, region-of-interest pairs were manually defined at each extracted fiber’s termini and nonlinearly warped to a standard anatomical brain template to create an atlas of the region-of-interest pairs. The resulting atlas was then transformed non-linearly into the native space of 17 veteran patients’ brains for automated brainstem tractography. Lastly, we assessed the relationships between the integrity levels of the obtained fiber bundles and pain severity levels. Fractional anisotropy (FA) measures derived using automated tractography reflected the respective tracts’ FA levels obtained via manual tractography. A significant inverse relationship between FA and pain levels was detected within the automatically derived dorsal and medial longitudinal fasciculi of the brainstem. This study demonstrates the utility of DTI in exploring brainstem circuitries involved in pain processing. In this context, the described automated approach is a viable alternative to the time-consuming manual tractography. The physiological and functional relevance of the measures derived from automated tractography is evidenced by their relationships with individual pain severities.
Acute regulation of habituation learning via posttranslational palmitoylation
Authors: Nelson Jessica C. , Witze Eric , Ma Zhongming , Ciocco Francesca , Frerotte Abigaile , Foskett J. Kevin , Granato Michael
Published: March 2019

Habituation is an adaptive learning process that enables animals to adjust innate behaviors to changes in the environment. Despite its well documented implications for a wide diversity of behaviors, the molecular and cellular basis of habituation learning is not well understood. Using whole genome sequencing of zebrafish mutants isolated in an unbiased genetic screen, we identified the palmitoyltransferase Hip14 as a critical regulator of habituation learning. We demonstrate that Hip14 regulates depression of sensory inputs onto an identified neuron and provide compelling evidence that Hip14 palmitoylates the Shaker-like channel subunit Kv1.1, thereby regulating Kv1.1 subcellular localization. Furthermore, we show that loss of either Kv1.1 or Hip14 leads to habituation deficits, and that Hip14 is dispensable in development and instead acts acutely to promote habituation. Combined, our results uncover a previously unappreciated role for acute post-translational palmitoylation at defined circuit components to regulate learning.
A non-canonical role and regulations of polo-like kinase-4 in fibroblast cell-type transition
Authors: Li Jing , Urabe Go , Zhang Mengxue , Huang Yitao , Wang Bowen , Marcho Lynn , Shen Hongtao , Kent K. Craig , Guo Lian-Wang
Published: March 2019

A divergent member of the polo-like kinase family, PLK4 is known for its canonical role in centriole duplication. Its non-canonical function and regulators are poorly defined. Here we investigated PLK4’s activation and expression and regulations thereof in rat adventitial fibroblast cell-type transition induced by platelet-derived growth factor (PDGF-AA).

Experiments using siRNA and selective inhibitor (centrinone-B) revealed a role for PLK4 not only in AA-induced proliferation/migration, but also in serum response factor (SRF) activation and smooth muscle α-actin expression. PDGFR (receptor) inhibition abrogated AA-stimulated PLK4 activation (phosphorylation) and expression; P38 inhibition (siRNA, inhibitor) downstream of PDGFR also mitigated PLK4 activation. Furthermore, transcription of PLK4 (and PDGFRα) was repressed by pan-inhibition of the bromodomain/extraterminal family of chromatin-bookmark readers (BRD2, BRD3, BRD4), an effect determined herein as mainly mediated by BRD4. In vivo, periadventitial administration of centrinone-B reduced collagen content and thickness of the adventitia in a rat model of carotid artery injury.

In summary, we have identified a non-canonical role for PLK4 in SRF activation and its regulations by BRD4/PDGFRα-dominated pathways. Results in this study suggest PLK4 inhibition as a potential anti-fibrotic intervention.
Sparse Infomax Based on Hoyer Projection and its Application to Simulated Structural MRI and SNP Data
Authors: Duan Kuaikuai , Silva Rogers F. , Chen Jiayu , Lin Dongdong , Calhoun Vince D. , Liu Jingyu
Published: March 2019

Independent component analysis has been widely applied to brain imaging and genetic data analyses for its ability to identify interpretable latent sources. Nevertheless, leveraging source sparsity in a more granular way may further improve its ability to optimize the solution for certain data types. For this purpose, we propose a sparse infomax algorithm based on nonlinear Hoyer projection, leveraging both sparsity and statistical independence of latent sources. The proposed algorithm iteratively updates the unmixing matrix by infomax (for independence) and the sources by Hoyer projection (for sparsity), feeding the sparse sources back as input data for the next iteration. Consequently, sparseness propagates effectively through infomax iterations, producing sources with more desirable properties. Simulation results on both brain imaging and genetic data demonstrate that the proposed algorithm yields improved pattern recovery, particularly under low signal-to-noise ratio conditions, as well as improved sparseness compared to traditional infomax.
A gravity-based three-dimensional compass in the mouse brain
Authors: Angelaki Dora E , Ng J , Abrego AM , Cham HX , Dickman JD , Laurens J
Published: March 2019

Head direction cells in the mammalian limbic system are thought to function as an allocentric neuronal compass. Although traditional views hold that the compass of ground-dwelling species is planar, we show that head-direction cells in the rodent thalamus, retrosplenial cortex and cingulum fiber bundle are tuned to conjunctive combinations of azimuth, pitch or roll, similarly to presubicular cells in flying bats. Pitch and roll orientation tuning is ubiquitous, anchored to gravity, and independent of visual landmarks. When head tilts, azimuth tuning is affixed to the head-horizontal plane, but also uses gravity to remain anchored to the terrestrial allocentric world. These findings suggest that gravity defines all three degrees of freedom of the allocentric orientation compass, and only the azimuth component can flexibly remap to local cues in different environments. Collectively, these results demonstrate that a three-dimensional, gravity-based, neural compass is likely a ubiquitous property of mammalian species, including ground-dwelling animals.
PESCA: A scalable platform for the development of cell-type-specific viral drivers
Authors: Hrvatin Sinisa , Tzeng Christopher P. , Nagy M. Aurel , Stroud Hume , Koutsioumpa Charalampia , Wilcox Oren F. , Assad Elena G. , Green Jonathan , Harvey Christopher D. , Griffith Eric C. , Greenberg Michael E.
Published: March 2019

Enhancers are the primary DNA regulatory elements that confer cell type specificity of gene expression. Recent studies characterizing individual enhancers have revealed their potential to direct heterologous gene expression in a highly cell-type-specific manner. However, it has not yet been possible to systematically identify and test the function of enhancers for each of the many cell types in an organism. We have developed PESCA, a scalable and generalizable method that leverages ATAC- and single-cell RNA-sequencing protocols, to characterize cell-type-specific enhancers that should enable genetic access and perturbation of gene function across mammalian cell types. Focusing on the highly heterogeneous mammalian cerebral cortex, we apply PESCA to find enhancers and generate viral reagents capable of accessing and manipulating a subset of somatostatin-expressing cortical interneurons with high specificity. This study demonstrates the utility of this platform for developing new cell-type-specific viral reagents, with significant implications for both basic and translational research.

One sentence summary

Highly paralleled functional evaluation of enhancer activity in single cells generates new cell-type-specific tools with broad medical and scientific applications.
A simplified analytical model of sound propagation in the human ear
Authors: Gambin Wiktor L.
Published: March 2019

A simple mechanical model of sound propagation in the human ear from the entrance to the ear canal up to the round window membrane is outlined. The model shows the outer, middle and inner ear as two waveguides connected by a lever mechanism. The case when a sound wave from a sound source at a given frequency and intensity goes into the ear is considered. The sound as a plane elastic wave in the air of the ear canal is partially reflected from the eardrum and after relocation by a lever of the ossicles; it runs as a plane elastic wave in the cochlea fluid to be finally damped at the round window membrane. The basilar membrane excited by the running sound wave in the cochlea is taken as a chain of separate fibers. The power of the sound reaching the ear is compared with the power of the sound carriers in the ear. As a result, simple rules for the amplitude of the stapes footplate as well as for the amplitude and pressure of the forced acoustic wave in the cochlea are obtained. The formulas for the amplitudes of the membrane of the round window and the basilar membrane are also shown. The results of calculations based on these rules were compared with the measurements made on temporal bone specimens. The tests were done for the level of the sound source intensity of 90 dB and a set of frequencies from the range of 400-10,000 Hz. The amplitudes of the stapes-footplate and the round window membrane were measured. A mean difference, between the calculated and the measured values, for the stapes-footplate reached 31%, and for the round window membrane, it was 21%. A ratio of the basilar membrane velocity to the stapes footplate velocity as a function of the frequencies was shown. The obtained graph was close to that got by others as a result of the measurements.
N-glycosylation of the protein disulfide isomerase Pdi1 ensuresUstilago maydisvirulence
Authors: Marín-Menguiano Miriam , Moreno-Sánchez Ismael , Barrales Ramón R. , Fernández-Álvarez Alfonso , Ibeas José Ignacio
Published: March 2019

Fungal pathogenesis depends on accurate secretion and location of virulence factors which drive host colonization. Protein glycosylation is a common posttranslational modification of cell wall components and other secreted factors, typically required for correct protein localization, secretion and function. Thus, the absence of glycosylation is associated with animal and plant pathogen avirulence. While the relevance of protein glycosylation for pathogenesis has been well established, the main glycoproteins responsible for the loss of virulence observed in glycosylation-defective fungi have not been identified. Here, we devise a proteomics approach to identify such proteins and use it to demonstrate a role for the highly conserved protein disulfide isomerase Pdi1 in virulence. We show that efficient Pdi1 N-glycosylation, which promotes folding into the correct protein conformation, is required for full pathogenic development of the corn smut fungusUstilago maydis. Remarkably, the observed virulence defects are reminiscent of those seen in glycosylation-defective cells suggesting that the N-glycosylation of Pdi1 is necessary for the full secretion of virulence factors. All these observations, together with the fact that Pdi1 protein and RNA expression levels rise upon virulence program induction, suggest that Pdi1 glycosylation is a crucial event for pathogenic development inU. maydis. Our results provide new insights into the role of glycosylation in fungal pathogenesis.

Author summary

Fungal pathogens require virulence factors to be properly secreted and localized to guarantee complete infection. In common with many proteins, virulence factors must be post-translationally modified by glycosylation for normal localization, secretion and function. This is especially important for virulence factors, which are mainly comprised of cell wall and secreted proteins. Aberrant glycosylation leads to a loss of virulence in both animal and plant pathogenic fungi. We have previously demonstrated that glycosylation is important for virulence of the corn smut fungus,Ustilago maydis. However, the glycoproteins involved and their specific roles in the infection process have not yet been reported. Here, we describe a proteomic assay designed to identify glycoproteins involved in plant infection. Using this method, we define the role of Pdi1 protein disulfide isomerase in virulence. Interestingly, abolishing Pdi1 N-glycosylation mimics Δpdi1defects observed during infection, suggesting that Pdi1 N-glycosylation is required for the secretion of virulence factors. We hypothesize that Pdi1 N-glycosylation is crucial for maintaining proper effector protein folding during the infection process, especially in the harsh conditions found inside the maize plant.
Nanopore sequencing for fast determination of plasmids, phages, virulence markers, and antimicrobial resistance genes in Shiga toxin-producingEscherichia coli
Authors: Gonzalez-Escalona Narjol , Allard Marc A. , Brown Eric W. , Sharma Shashi , Hoffmann Maria
Published: March 2019

Whole genome sequencing can provide essential public health information. However, it is now known that widely used short-read methods have the potential to miss some randomly-distributed segments of genomes. This can prevent phages, plasmids, and virulence factors from being detected or properly identified. Here, we compared assemblies of three complete STEC O26:H11 genomes from two different sequence types (ST21 and 29), each acquired using the MiSeq-Nextera XT, MinION nanopore-based sequencing, and Pacific Biosciences (PacBio) sequencing. Each closed genome consisted of a single chromosome, approximately 5.7 Mb for CFSAN027343, 5.6 Mb for CFSAN027346, and 5.4 MB for CFSAN027350. However, short-read WGS using MiSeq-Nextera failed to identify some virulence genes in plasmids and on the chromosome, both of which were detected using the long-read platforms. Results from long-read MinION and PacBio allowed us to identify differences in plasmid content: a single 88 kb plasmid in CFSAN027343; a 157kb plasmid in CFSAN027350; and two plasmids in CFSAN027346 (one 95 Kb, one 72 Kb). These data enabled rapid characterization of the virulome, detection of antimicrobial genes, and composition/location of Stx phages. Taken together, positive correlations between the two long-read methods for determining plasmids, virulome, antimicrobial resistance genes, and phage composition support MinION sequencing as one accurate and economical option for closing STEC genomes and identifying specific virulence markers.
Effects of estrogen on Survival and Neuronal Differentiation of adult human olfactory bulb neural stem Cells Transplanted into Spinal Cord Injured Rats
Authors: Rezk S , Althani A , Abd-Elmaksoud A , Kassab M , Farag A , Lashen S , Cenciarelli C , Caceci T , Marei HE
Published: March 2019

In the present study we developed an excitotoxic spinal cord injury (SCI) model using kainic acid (KA) to evaluate of the therapeutic potential of human olfactory bulb neural stem cells (h-OBNSCs) for spinal cord injury (SCI). In a previous study, we assessed the therapeutic potential of these cells for SCI; all transplanted animals showed successful engraftment. These cells differentiated predominantly as astrocytes, not motor neurons, so no improvement in motor functions was detected. In the current study we used estrogen as neuroprotective therapy before transplantation of OBNSCs to preserve some of endogenous neurons and enhance the differentiation of these cells towards neurons. The present work demonstrated that the h-GFP-OBNSCs were able to survive for more than eight weeks after sub-acute transplantation into injured spinal cord. Stereological quantification of OBNSCs showed approximately a 2.38-fold increase in the initial cell population transplanted. 40.91% of OBNSCs showed differentiation along the neuronal lineages, which was the predominant fate of these cells. 36.36% of the cells differentiated into mature astrocytes; meanwhile 22.73% of the cells differentiated into oligodendrocytes. Improvement in motor functions was also detected after cell transplantation.
Brand as a cognitive mediator: investigating the effect of media brands as a structural feature of textual news messages
Authors: Laaksonen Salla-Maaria , Falco Alessio , Salminen Mikko , Aula Pekka , Ravaja Niklas
Published: March 2019

Purpose

This study investigates how media brand knowledge, defined as a structural feature of the message, influences emotional and attentional responses to, and memory of, news messages.

Design/methodology/approach

Self-reports, facial electromyography (EMG) and electroencephalography were used as indices of emotional valence, arousal and attention in response to 42 news messages, which varied along the valence and involvement dimensions and were framed with different media brands varying along the familiarity and credibility dimensions.

Findings

Compared to the no-brand condition, news framed with brands elicited more attention. The memory tests indicated that strong media brands override the effect of involvement in information encoding, whereas details of news presented with Facebook were not well encoded. However, the headlines of news framed with Facebook were well retrieved. In addition, negative and high-involvement news elicited higher arousal ratings and corrugator EMG activity. News framed with familiar and high-credibility brands elicited higher arousal ratings.

Research limitations/implications

Relevant for both brand managers and audiences, the findings show that building credibility and familiarity both work as brand attributes to differentiate media brands and influence information processing.

Originality/value

The results highlight the importance of media brands in news reading: as a structural feature, the brand is used as a proxy to process the message content. The study contributes by investigating how the type of source influences the reception and encoding of the mediated information; by investigating the emotional effects of brands; and by confirming previous findings in media psychology literature.
Multi-tier store brand strategies: a case study
Authors: Gorgitano Maria Teresa , Sodano Valeria
Published: March 2019

Purpose

This paper aims to describe and understand the offer of premium private labels (PPLs) in Italy, with a case study on the extra virgin olive oil (EVOO).

Design/methodology/approach

The empirical study on EVOO in Italy was aimed to investigate the drivers of the offer of PPLs and its effects on assortment policies. The study was carried out in three Italian provinces, using a cross-sectional design with data collected through direct observation. A two-step data analysis was performed. First, descriptive statistics were used to preliminary appraise hypotheses on the rationale underlying the offer of PPL, and then, the drivers of PPL policy were studied using a logistic regression model.

Findings

The estimated model indicates that in the case of EVOO the probability of offering a PPL is higher for stronger with a stronger competitive position (with respect to other stores), and increases with the size of the category assortment (Total Assortment Width) and with the share of the PL products offered by the store (PL Assortment Index). It also increases if the average price (Total Average Price) and the average price of the standard private label (SPL Average Price) improve; by contrast, it decreases if the national brand (NB) share in the assortment (NB Assortment Index) augments.

Research limitations/implications

Overall, the study confirms that the multi-tiered PL strategy is one of the current competitive strategies of top retailers, centred more on a differentiation than on a low cost/price policy. Such a differentiation policy may have various effects in terms of channel structure and social welfare depending on the underlying corporate and consumer goals and beliefs and on the existing institutional framework.

Originality/value

This is the first study to investigate the PPL market in Italy using original data and taking into account policies actually carried out at the individual store level. A further element of novelty is the attention given to the welfare effects of multi-tier strategies. This paper suggests that these latter may have various effects in terms of channel structure and social welfare depending on the underlying corporate and consumer goals and beliefs and on the existing institutional framework.
Research Note: Low‐frequency pneumatic seismic sources
Authors: Chelminski Steve , Watson Leighton M. , Ronen Shuki
Published: March 2019

Pneumatic seismic sources, commonly known as airguns, have been serving us well for decades, but there is an increasing need for sources with improved low‐frequency signal and reduced environmental impact. In this paper, we present a new pneumatic source that is designed to achieve these goals by operating with lower pressures and larger volumes. The new source will release more air creating larger bubbles with longer bubble periods than airguns. The release of the air will be tuned so that the rise time will be longer and the sound pressure level and its slope will be lower. Certain engineering features will eliminate cavitation. Larger bubbles increase low‐frequency content of the signal, longer rise times decrease mid‐frequency content and the elimination of cavitation reduces high‐frequency content. We have not yet built a full‐scale version of the new source. However, we have manufactured a small‐scale low‐pressure source incorporating most of the engineering features, and tested it in a lake. Here, we present the lake data that, as expected, show a significant reduction in the sound pressure level, increase in rise time, decrease in slope and decrease in high‐frequency content while maintaining the same low‐frequency content when the source prototype is operated at low pressure compared with high pressure. Synthetic data produced by numerical modelling of the full‐scale proposed pneumatic source suggest that the new source will improve the low‐frequency content and can produce geophysically useful signal down to 1 Hz.
Beyond health: medicines, food supplements, energetics and the commodification of self‐performance in Maputo
Authors: F. Rodrigues Carla , Lopes Noémia , Hardon Anita
Published: March 2019

With an increasing range of products in global and local markets, more options are available for individuals to enhance their image and their (cognitive, social and physical) performance. These ‘performance consumptions’ relate to ideals of well‐being and improvement, and are based on constructed desires, expectations and needs that go beyond the (often blurred) dichotomy of health and illness. Drawing from mixed‐methods research in Maputo, Mozambique, this paper discusses individuals’ use of medicines and other substances – pharmaceuticals, food supplements, traditional herbs, cosmetics and energy drinks – for managing different aspects of their everyday lives. Through an overview of the main consumption practices, we explore the underlying purposes and strategies of users, and the perceived legitimacy and risks involved when using a variety of products accessible through formal and informal exchange channels. From tiredness to sexual and aesthetic management, we show how the body becomes the locus of experimentation and investment to perform in accordance with socially expected roles, individual aspirations and everyday tasks. With insights from individuals’ accounts in Maputo, we aim to add to discussions on pharmaceuticalisation of body management by showing how the emergence of new performance consumptions is articulated with the reconfiguration of more ‘traditional’ consumption practices.
The influence of dietary chestnut and quebracho tannins mix on rabbit meat quality
Authors: Mancini Simone , Minieri Sara , Buccioni Arianna , Marzoni Fecia di Cossato Margherita , Russo Claudia , Paci Gisella
Published: March 2019

Tannins were recently evaluated as feed additives in order to increase antioxidant compounds in animal diet, mainly to enhance resistance to lipid oxidation in meat. Rabbit meat is one of the most susceptible animal products, thus the main aim of this study was to evaluate the capacity of tannins to elongate shelf life of rabbit meat. Ninety hybrid rabbits were fed with three different diets: basal diet (control, C) and basal diet supplemented with 0.3% or 0.6% of tannins mix. Meat samples were refrigerated as raw at 4°C up to 11 days and analysed both as raw and cooked for physical‐chemical characteristics, fatty acids profile, lipid oxidation and antioxidant capacity. Results showed that dietary tannins affected meat colour of raw samples (mostly yellowness). Lipid peroxidation (TBARS) of raw samples was lower in tannins group than C group; a further inhibition of peroxidation was showed also in cooked samples only by the highest dose of tannins mix. Moreover, antioxidant capacity (ABTS) of raw samples increased with the percentage of tannins. In conclusion, supplementation with 0.6% of tannins mix seems to positively affect the lipid peroxidation and antioxidant capacity of meat without modifying the intrinsic characteristics of rabbit meat.
Longitudinal brain functional changes between mania and euthymia in bipolar disorder
Authors: Alonso‐Lana Silvia , Moro Noemí , McKenna Peter J. , Sarró Salvador , Romaguera Anna , Monté Gemma C. , Maristany Teresa , Goikolea José M. , Vieta Eduard , Salvador Raymond , Pomarol‐Clotet Edith
Published: March 2019

Objectives

While widespread cortical and subcortical brain functional abnormalities have been found in bipolar disorder, the changes that take place between illness phases and recovery are less clearly documented. Only a small number of longitudinal studies of manic patients, in particular, have been carried out.

Methods

Twenty‐six bipolar patients underwent fMRI during performance of the n‐back working memory task when manic and again after recovery. Twenty‐six matched healthy controls were also scanned on two occasions. Task‐related activations and de‐activations were examined.

Results

When manic, the patients showed clusters of significantly reduced activation in the left dorsolateral prefrontal cortex (DLPFC)/precentral cortex and the parietal cortex/superior precuneus bilaterally. They also showed failure of de‐activation in the ventromedial frontal cortex (vmPFC). After recovery, activation in the left DLPFC/precentral cortex and in the bilateral parietal cortex/superior precuneus clusters increased significantly. However, failure of de‐activation remained present in the vmPFC.

Conclusions

Recovery from mania is associated with normalization of DLPFC and parietal hypoactivation, but not with vmPFC failure of de‐activation, which accordingly appears to represent a trait abnormality in the disorder.
Teacher educators as gatekeepers: Preparing the next generation of teachers for technology integration in education
Authors: Tondeur Jo , Scherer Ronny , Baran Evrim , Siddiq Fazilat , Valtonen Teemu , Sointu Erkko
Published: March 2019

This study aims at investigating the profiles of teacher educators in order to explore their ability to prepare preservice teachers for technology integration in education. Specifically, the current study examines whether teacher educators can be grouped on the basis of their attitudes toward ICT (in education), their ICT self‐efficacy to design ICT‐rich learning environments, their competencies to use ICT in their teaching practice and the strategies they use to prepare preservice teachers for technology integration. These strategies are included in the SQD (Synthesis of Qualitative Data) model and comprise: (1) teacher educators as role models, (2) reflecting on the role of technology in education, (3) learning how to use technology by design, (4) collaboration with peers, (5) scaffolding authentic technology experiences and (6) providing continuous feedback. Data were collected from a sample of 284 teacher educators in Flanders, the Dutch‐speaking part of Belgium, and submitted to latent profile analysis. The added value of the current study lies in the account of how SQD strategies and a typical set of determinants of ICT integration can be associated within teacher educators’ profile. Based on the profiles emerging from this study, teacher training institutions should consider their teacher educators to be gatekeepers when preparing future generations of teachers for the learning environments of the twenty‐first century. In the discussion section, the implications for practice and future research are discussed.
Protein inhibitor of activated STAT1 Ser503 phosphorylation‐mediated Elk‐1 SUMOylation promotes neuronal survival in APP/PS1 mice
Authors: Liu Shau‐Yu , Ma Yun‐Li , Hsu Wei‐Lun , Chiou Hsin‐Ying , Lee Eminy H.Y.
Published: March 2019

Background and Purpose

Protein inhibitor of activated STAT1 (PIAS1) is phosphorylated by IKKα at Ser90 in a PIAS1 E3 ligase activity‐dependent manner. Whether PIAS1 is also phosphorylated at other residues and the functional significance of these additional phosphorylation events are not known. The transcription factor Elk‐1 remains SUMOylated under basal conditions, but the role of Elk‐1 SUMOylation in brain is unknown. Here, we examined the functional significance of PIAS1‐mediated Elk‐1 SUMOylation in Alzheimer's disease (AD) using the APP/PS1 mouse model of AD and amyloid β (Aβ) microinjections in vivo.

Experimental Approach

Novel phosphorylation site(s) on PIAS1 were identified by LC–MS/MS, and MAPK/ERK‐mediated phosphorylation of Elk‐1 demonstrated using in vitro kinase assays. Elk‐1 SUMOylation by PIAS1 in brain was determined using in vitro SUMOylation assays. Apoptosis in hippocampus was assessed by measuring GADD45α expression by western blotting, and apoptosis of hippocampal neurons in APP/PS1 mice was assessed by TUNEL assay.

Key Results

Using LC–MS/MS, we identified a novel MAPK/ERK‐mediated phosphorylation site on PIAS1 at Ser503 and showed this phosphorylation determines PIAS1 E3 ligase activity. In rat brain, Elk‐1 was SUMOylated by PIAS1, which decreased Elk‐1 phosphorylation and down‐regulated GADD45α expression. Moreover, lentiviral‐mediated transduction of Elk‐1‐SUMO1 reduced the number of hippocampal apoptotic neurons in APP/PS1 mice.

Conclusions and Implications

MAPK/ERK‐mediated phosphorylation of PIAS1 at Ser503 determines PIAS1 E3 ligase activity. Moreover, PIAS1 mediates SUMOylation of Elk‐1, which functions as an endogenous defence mechanism against Aβ toxicity in vivo. Targeting Elk‐1 SUMOylation could be considered a novel therapeutic strategy against AD.