bluuebunny/crossref_metadata_2025 huggingface dataset:
Geological and geophysical interpretation of induced-polarization data on gold depoits in the Yana–Kolyma orogenic belt
Authors: Tkachev A.V. , Khasanov I.M. , Mikhalitsyna T.I.
Published: December 2017

This paper presents induced-polarization (IP) data on a number of gold deposits and occurrences in the Magadan Region. Geophysical works are effective for the study of gold-quartz deposits of different morphological types (vein, veinlet-vein, and veinlet-disseminated). It is shown that multifrequency IP sounding reliably identifies zones of carbon metasomatism, a reliable indicator of promising gold mineralization areas and zones in northeastern Russia. Evidence of carbon metasomatism is the typical shape of phase frequency response curves for graphite and graphitized rocks.
‘I'm not envious, I'm just jealous!’: On the Difference Between Envy and Jealousy
Authors: PROTASI SARA
Published: December 2017

I argue for the view that envy and jealousy are distinct emotions, and the crucial difference between them is that envy involves a perception of lack while jealousy involves a perception of loss. I start by noting the common practice of using ‘envy’ and ‘jealousy’ almost interchangeably, and I contrast it with the empirical evidence that shows that envy and jealousy are distinct, albeit similar and often co-occurring, emotions. I then argue in favor of a specific way of understanding their distinction: the view that envy is a response to a perceived lack of a valuable object, while jealousy is a response to a perceived loss of a valuable object. I compare such a view with the most compelling alternative theories and show that it accounts better for paradigmatic cases. I conclude by showing how the lack versus loss model can handle complications: ambiguous cases, that is, when it is epistemically unclear whether one experiences lack or loss; hybrid cases, that is, when one seems to experience both lack and loss; and borderline cases, that is, when it is metaphysically unclear whether one experiences lack or loss.
50 Tips for Clinical Trialists
Authors: Harvey Lisa A. , Glinsky Joanne V. , Herbert Robert D.
Published: December 2017

This paper presents ‘Tips’ for researchers of brain impairment who are interested in conducting randomised controlled trials. The paper is intended for researchers who are planning to undertake their first trial, but may also be of interest to more experienced trialists or clinicians who want to further their understandings of clinical trials. The Tips include suggestions for how to design, conduct, analyse and report clinical trials.
Rhythm and rate control of atrial fibrillation in the emergency department – A large community-based observational study
Authors: Gilbert Cameron J. , Angaran Paul , Mariano Zana , Aves Theresa , Dorian Paul
Published: December 2017

Objective

Atrial fibrillation (AF) is the most common arrhythmia presentation to the emergency department (ED) and frequently results in admission to the hospital. Although rarely life-threatening and not usually an emergent condition, AF places a large burden on our health-care system. The objective of this study was to describe the practices of ED physicians in the management of AF in a large urban Canadian city.

Methods

From January 1, 2010 to December 31, 2010, patients with a primary diagnosis of AF were identified across 10 EDs in Toronto, Canada (N=2,609). Fifty patients were selected at random from each hospital for a detailed chart review (n=500).

Results

Two hundred thirty-two patients (46%) received rate control, and 129 (26%) received rhythm control with the remainder (28%) receiving neither therapy. Sixty-seven percent of patients were discharged home. Most patients (79%) were symptomatic on arrival; however, only a minority of these (31%) received rhythm control. Factors that were associated with rhythm control included younger age, duration of palpitations ≤ 48 hours, a lower CHADS2 score, and the absence of left ventricular dysfunction.

Conclusion

Our data suggest a wide range of practice amongst ED physicians treating patients presenting to the ED with a primary diagnosis of AF. A randomized trial is needed to better understand the optimal management strategy in this patient population and setting.
Do Experts Understand Performance Measures? A Mixed-Methods Study of Infection Preventionists
Authors: Govindan Sushant , Wallace Beth , Iwashyna Theodore J. , Chopra Vineet
Published: December 2017

OBJECTIVE

Central line-associated bloodstream infection (CLABSI) is associated with significant morbidity and mortality. Despite a nationwide decline in CLABSI rates, individual hospital success in preventing CLABSI is variable. Difficulty in interpreting and applying complex CLABSI metrics may explain this problem. Therefore, we assessed expert interpretation of CLABSI quality data. DESIGN. Cross-sectional survey PARTICIPANTS. Members of the Society for Healthcare Epidemiology of America (SHEA) Research Network (SRN) METHODS. We administered a 10-item test of CLABSI data comprehension. The primary outcome was percent correct of attempted questions pertaining to the CLABSI data. We also assessed expert perceptions of CLABSI reporting.

RESULTS

The response rate was 51% (n=67).Among experts, the average proportion of correct responses was 73% (95% confidence interval [CI], 69%–77%). Expert performance on unadjusted data was significantly better than risk-adjusted data (86% [95% CI, 81%–90%] vs 65% [95% CI, 60%–70%];P<.001). Using a scale of 1 to 100 (0, never reliable; 100, always reliable), experts rated the reliability of CLABSI data as 61. Perceived reliability showed a significant inverse relationship with performance (r=–0.28;P=.03), and as interpretation of data improved, perceptions regarding reliability of those data decreased. Experts identified concerns regarding understanding and applying CLABSI definitions as barriers to care.

CONCLUSIONS

Significant variability in the interpretation of CLABSI data exists among experts. This finding is likely related to data complexity, particularly with respect to risk-adjusted data. Improvements appear necessary in data sharing and public policy efforts to account for this complexity.

Infect Control Hosp Epidemiol2018;39:71–76
Prevalence of MRSA ST398 Carriage in Nursing Home Residents in an Area of Spain With a High Density of Pig Farming
Authors: Reynaga Esteban , Torres Carmen , Garcia-Nuñez Marian , Navarro Marian , Vilamala Anna , Puigoriol Emma , Enrico Lucchetti Gianni , Nunes Daniella , Silva Adriana , Sabrià Miquel
Published: December 2017

MRSA nasal carriage was detected in 15.7% of 204 residents from 6 nursing homes (NHs) in the Osona region (Barcelona, Spain), and the MRSA-ST398 lineage was identified in 15.6% of MRSA-positive residents and in 2.5% of all NH residents evaluated. Most MRSA-ST398 carriers (4 of 5) had direct or indirect contact with pig farms.

Infect Control Hosp Epidemiol 2018;39:90–93
Bilateral ischaemic lesions of the medial prefrontal cortex are anxiogenic in the rat
Authors: Déziel Robert A. , Tasker R. Andrew
Published: December 2017

Objective

Stroke patients often suffer from delayed disturbances of mood and cognition. In rodents, the prefrontal cortex (PFC) is involved in both higher order cognition and emotion. Our objective was to determine if bilateral focal ischaemic lesions restricted to the medial prefrontal cortex (mPFC) could be used to model post-stroke anxiety and/or cognitive deficits.

Methods

Groups of adult male Sprague-Dawley rats (n=9) received bilateral injections of either endothelin-1 (ET-1) (400 pmol) or vehicle (artificial cerebrospinal fluid) into the mPFC and were tested at various times using both a test of temporal order memory and in an elevated plus maze. Lesions were verified histologically.

Results

ET-1 lesioned rats had reduced mobility on post-surgery day 8 that had resolved by day 29 at which time they spent significantly more time in the closed arm of the plus maze

Conclusion

We conclude that ischaemic lesions localised to the mPFC can be used to model post-stroke anxiety in rats.
INCISED DESIGN FOR GOTHIC WINDOW TRACERY, WYMONDHAM ABBEY, NORFOLK
Authors: Harris Roland B
Published: December 2017

The building of new facilities at the east end of Wymondham Abbey, Norfolk, in 2014–15 involved re-opening a Romanesque arch. This had previously connected the nave’s north aisle with the north transept, and appears to have been blocked at the Dissolution when the transepts and eastern arm of the abbey church were demolished. As works progressed in 2014–15, a remarkable Gothic window tracery design was gradually revealed, incised on the early twelfth-century ashlar of the southern respond. The discovery is one of the most substantial and complete incised designs identified to date and, beyond being an important addition to the emerging corpus of incised designs on walls, it is significant for revealing use of black pigment to make the drawing more visible, for providing an insight into the lost monastic parts of the abbey and, most tantalisingly, for raising the possibility that Wymondham – like its nearby sister priory at Binham – was at the forefront of the development of bar tracery in England in the thirteenth century.
‘No, we don't mix languages’: Ideological power and the chronotopic organization of ethnolinguistic identities
Authors: Karimzad Farzad , Catedral Lydia
Published: December 2017

In this study we address ethnolinguistic identity using Bakhtin's (1981) notion of chronotope. Taking an ethnographic approach to linguistic data from Azerbaijani and Uzbek communities, we trace the impact of various chronotopes on our participants’ acts of ethnolinguistic identification. Building on Blommaert & De Fina (2017), we illustrate how ethnolinguistic identification is an outcome of the interaction between multiple levels of large- and small-scale chronotopes. Furthermore, we argue that chronotopes differ in terms of their power, depending on the ideological force behind them. We demonstrate how power differentials between chronotopes can account for certain interactional and linguistic patterns in conversation. The power inherent in chronotopes that link nationhood with specific languages makes the notions ofdiscrete languagesandstatic identities‘real’ for our participants. Therefore, discussions of language and identity as flexible and socially constructed, we argue, must not obscure the power of these notions in shaping the perceptions of sociolinguistic subjects. (Chronotope, ethnolinguistic identity, power, Uzbek, Azeri/Azerbaijani, nationalism, language mixing, language ideology)*
Harmony or Discord? Understanding children's valuations of a Sistema-inspired initiative
Authors: Rimmer Mark
Published: December 2017

This article explores children's reflections on the value of their participation in In Harmony, a social and music education programme whose approach and philosophy derives from the Venezuelan ‘El Sistema’ (‘The System’) model. More specifically, through an analysis of participating children's accounts (n=111) and an exploration of the key patterns evident within children's attribution of value to their In Harmony participation, the article highlights a series of ways in which the initiative's approach to music and musical learning threaten to undermine its core aims.
From Mars to the Multiverse
Authors: Rees Martin
Published: December 2017

Unmanned spacecraft have visited the other planets of our Solar System (and some of their moons), beaming back pictures of varied and distinctive worlds – but none propitious for life. However, prospects are far more interesting when we extend our gaze to other stars. Most stars are orbited by retinues of planets. Our home Galaxy contains a billion planets like the Earth. Do some of these have biospheres? Moreover, our Galaxy is one of billions visible with a large telescope – all the aftermath of a cosmic ‘big bang’ 13.8 billion years ago. More astonishing still, ‘our’ big bang may not have been the only one. The remarkable advances in recent decades are primarily owed to new engineering and technology. Armchair theory alone doesn’t get us far.
Synthesis of non-uniform circular antenna arrays with multiple constraints
Authors: Guo Hua , Cui Lin , Zhang Xiaodan , Jiao Yameng
Published: December 2017

Synthesis of non-uniform circular antenna arrays using a hybrid invasive weed optimization is introduced in this paper. The excitation weights and positions of array elements are optimized to reduce the peak side lobe level (PSLL) of the radiation pattern. The method proposed in this paper can effectively constrain the number of the array elements, size of the array, and the angular spacing of the adjacent element simultaneously. The radiation pattern has the constraint of a fixed major lobe beamwidth. Synthesis results of three different circular antenna arrays are given. The results show the effectiveness and feasibility of the proposed synthesis method in non-uniform circular antenna arrays.
International humanitarian law's old questions and new perspectives: On what law has got to do with armed conflict
Authors: Forster Thomas
Published: December 2017

The question of whether international humanitarian law (IHL) has an impact on how armed conflicts are conducted is a controversial one. Sceptics claim that the law is virtually irrelevant in determining State behaviour in armed conflict. Proponents point to its importance in mitigating the suffering caused by war. This paper looks at recent scholarship from historians, political scientists, economists and lawyers that challenges traditional narratives held dear by the law's sceptics and proponents alike. It then discusses implications of these approaches for a current understanding of the role of IHL in today's armed conflicts. The new perspectives allow for a broader understanding of IHL's central issues and permit us to ask more pertinent questions when looking at the law with the aim of putting it to use for the protection of civilians.
Hands-on Learning for Classics: Building an Effective, Long-term Project
Authors: Jazwa Kyle Alexander
Published: December 2017

In this paper, I explore the use of long-term, hands-on learning activities for Classics courses. I will show that a carefully designed project can complement classroom lectures on Greek and Roman culture and contribute towards the development of students’ critical thinking and group work skills. As an example, I describe a successful hands-on learning project that I designed for my Ancient Greek Cities course at Monmouth College (USA). The students were tasked with researching and building an historically faithful, ancient Greek mudbrick building for the college's annual Classics Day event. With the success of this project in my class, I will show that Classics instructors can pursue similar long-term, hands-on learning activities for engaging students in ancient Greek and Roman culture and teaching essential skills.
Latin and Greek in London E17
Authors: Hogg David
Published: December 2017

Some years back, the English department for which I was Head of Key Stage 3 found that, due to a timetabling issue, Year 7s had an extra hour of English per fortnight. It seemed like a waste of an opportunity to pad this extra hour out with ‘more of the same’, so I made a decision to utilise that hour to teach something different - grammar.
Advice to a student of Classics
Authors: Lawrence William
Published: December 2017

Look at the secondary school timetable and you will see that almost all the subjects are ancient Greek words; so the Greeks studied these ideas first and are worth studying for their ideas in their own language (just like the Romans in Latin!). Greek: Biology, Physics, Zoology, Philosophy, Mathematics, Economics, Politics, Music, Drama, Geography, History, Technology, Theatre Studies. Latin: Greek, Latin, Art, Science, Information (Latin) Technology (Greek), Computer Science, Media Studies.
Is That A Fact? Language And Fact In Greek And Latin Constructions
Authors: Moran Jerome
Published: December 2017

It is true that Greek and Latin writers use the indicative to assert a fact. This is not to say that what Greek and Latin writers assert by means of the indicative is a fact. This distinction is central to this article. There is widespread (in many grammar and course books) misunderstanding (or at least misleading explanation) of the information conveyed by the forms of certain Greek and Latin constructions. The misunderstanding seems to be the result of a failure to distinguish between a fact and the writer's attitude to a fact; between what is the case and what the writer says or implies is the case; between what can and cannot be deduced about what the writer knows and does not know about the facts in question from the way in which the writer expresses himself. The misunderstanding affects more constructions in Latin than in Greek. I shall begin with the Greek constructions.
Advocating Classics Education – a new national project
Authors: Hall Edith , Holmes-Henderson Arlene
Published: December 2017

The ‘Advocating Classics Education’ (ACE) project is an initiative led by Professor Edith Hall and Dr Arlene Holmes-Henderson, based at King's College London. The project seeks to extend the availability of Classical Civilisation and Ancient History (CC/AH) qualifications to learners in non-fee-paying schools across the United Kingdom. To do so, Professor Hall has been awarded a Leadership Fellowship of £250,000 from the Arts and Humanities Research Council (AHRC). The project's full title is ‘Studying Classical Civilisation in Britain: recording the past and fostering the future’ and it runs from 1stMay 2017 to 31stAugust 2018.
Exploring the Restless Floor of Yellowstone Lake
Authors: Sohn Robert , Harris Robert , Linder Chris , Luttrell Karen , Lovalvo David , Morgan Lisa , Seyfried William , Shanks Pat
Published: December 2017

Yellowstone Lake, far from any ocean, hosts underwater hot springs similar to those on mid-ocean ridges. A research team is investigating the processes that drive the lake’s hydrothermal systems.
Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration
Authors: Nordenfelt Pontus , Moore Travis I. , Mehta Shalin B. , Kalappurakkal Joseph Mathew , Swaminathan Vinay , Koga Nobuyasu , Lambert Talley J. , Baker David , Waters Jennifer C. , Oldenbourg Rudolf , Tani Tomomi , Mayor Satyajit , Waterman Clare M. , Springer Timothy A.
Published: December 2017

Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here, we test whether the integrin, when engaged to an extracellular ligand and the cytoskeleton, adopts a specific orientation dictated by the direction of actin flow on the surface of migrating cells. We insert GFP into the rigid, ligand-binding head of the integrin, model with Rosetta the orientation of GFP and its transition dipole relative to the integrin head, and measure orientation with fluorescence polarization microscopy. Cytoskeleton and ligand-bound integrins orient in the same direction as retrograde actin flow with their cytoskeleton-binding β-subunits tilted by applied force. The measurements demonstrate that intracellular forces can orient cell surface integrins and support a molecular model of integrin activation by cytoskeletal force. Our results place atomic, Å-scale structures of cell surface receptors in the context of functional and cellular, μm-scale measurements.
Phenotypic plasticity promotes recombination and gene clustering in periodic environments
Authors: Gulisija Davorka , Plotkin Joshua B.
Published: December 2017

While theory offers clear predictions for when recombination will evolve in changing environments, it is unclear what natural scenarios can generate the necessary conditions. The Red Queen hypothesis provides one such scenario, but it requires antagonistic host–parasite interactions. Here we present a novel scenario for the evolution of recombination in finite populations: the genomic storage effect due to phenotypic plasticity. Using analytic approximations and Monte-Carlo simulations, we demonstrate that balanced polymorphism and recombination evolve between a target locus that codes for a seasonally selected trait and a plasticity modifier locus that modulates the effects of target-locus alleles. Furthermore, we show that selection suppresses recombination among multiple co-modulated target loci, in the absence of epistasis among them, which produces a cluster of linked selected loci. These results provide a novel biological scenario for the evolution of recombination and supergenes.
Magnetostriction-polarization coupling in multiferroic Mn2MnWO6
Authors: Li Man-Rong , McCabe Emma E. , Stephens Peter W. , Croft Mark , Collins Liam , Kalinin Sergei V. , Deng Zheng , Retuerto Maria , Sen Gupta Arnab , Padmanabhan Haricharan , Gopalan Venkatraman , Grams Christoph P. , Hemberger Joachim , Orlandi Fabio , Manuel Pascal , Li Wen-Min , Jin Chang-Qing , Walker David , Greenblatt Martha
Published: December 2017

Double corundum-related polar magnets are promising materials for multiferroic and magnetoelectric applications in spintronics. However, their design and synthesis is a challenge, and magnetoelectric coupling has only been observed in Ni3TeO6 among the known double corundum compounds to date. Here we address the high-pressure synthesis of a new polar and antiferromagnetic corundum derivative Mn2MnWO6, which adopts the Ni3TeO6-type structure with low temperature first-order field-induced metamagnetic phase transitions (TN = 58 K) and high spontaneous polarization (~ 63.3 μC·cm−2). The magnetostriction-polarization coupling in Mn2MnWO6 is evidenced by second harmonic generation effect, and corroborated by magnetic-field-dependent pyroresponse behavior, which together with the magnetic-field-dependent polarization and dielectric measurements, qualitatively indicate magnetoelectric coupling. Piezoresponse force microscopy imaging and spectroscopy studies on Mn2MnWO6 show switchable polarization, which motivates further exploration on magnetoelectric effect in single crystal/thin film specimens.
Post-transcriptional 3´-UTR cleavage of mRNA transcripts generates thousands of stable uncapped autonomous RNA fragments
Authors: Malka Yuval , Steiman-Shimony Avital , Rosenthal Eran , Argaman Liron , Cohen-Daniel Leonor , Arbib Eliran , Margalit Hanah , Kaplan Tommy , Berger Michael
Published: December 2017

The majority of mammalian genes contain one or more alternative polyadenylation sites. Choice of polyadenylation sites was suggested as one of the underlying mechanisms for generating longer/shorter transcript isoforms. Here, we demonstrate that mature mRNA transcripts can undergo additional cleavage and polyadenylation at a proximal internal site in the 3′-UTR, resulting in two stable, autonomous, RNA fragments: a coding sequence with a shorter 3′-UTR (body) and an uncapped 3′-UTR sequence downstream of the cleavage point (tail). Analyses of the human transcriptome has revealed thousands of such cleavage positions, suggesting a widespread post-transcriptional phenomenon producing thousands of stable 3′-UTR RNA tails that exist alongside their transcripts of origin. By analyzing the impact of microRNAs, we observed a significantly stronger effect for microRNA regulation at the body compared to the tail fragments. Our findings open a variety of future research prospects and call for a new perspective on 3′-UTR-dependent gene regulation.
Identification of regulatory targets for the bacterial Nus factor complex
Authors: Baniulyte Gabriele , Singh Navjot , Benoit Courtney , Johnson Richard , Ferguson Robert , Paramo Mauricio , Stringer Anne M. , Scott Ashley , Lapierre Pascal , Wade Joseph T.
Published: December 2017

Nus factors are broadly conserved across bacterial species, and are often essential for viability. A complex of five Nus factors (NusB, NusE, NusA, NusG and SuhB) is considered to be a dedicated regulator of ribosomal RNA folding, and has been shown to prevent Rho-dependent transcription termination. Here, we identify an additional cellular function for the Nus factor complex in Escherichia coli: repression of the Nus factor-encoding gene, suhB. This repression occurs primarily by translation inhibition, followed by Rho-dependent transcription termination. Thus, the Nus factor complex can prevent or promote Rho activity depending on the gene context. Conservation of putative NusB/E binding sites upstream of Nus factor genes suggests that Nus factor autoregulation occurs in many bacterial species. Additionally, many putative NusB/E binding sites are also found upstream of other genes in diverse species, and we demonstrate Nus factor regulation of one such gene in Citrobacter koseri. We conclude that Nus factors have an evolutionarily widespread regulatory function beyond ribosomal RNA, and that they are often autoregulatory.
EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer
Authors: Oldrini Barbara , Hsieh Wan-Ying , Erdjument-Bromage Hediye , Codega Paolo , Carro Maria Stella , Curiel-García Alvaro , Campos Carl , Pourmaleki Maryam , Grommes Christian , Vivanco Igor , Rohle Daniel , Bielski Craig M. , Taylor Barry S. , Hollmann Travis J. , Rosenblum Marc , Tempst Paul , Blenis John , Squatrito Massimo , Mellinghoff Ingo K.
Published: December 2017

Transport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains unclear. The epidermal growth factor receptor (EGFR) plays a critical role in normal development and in human cancer. Here we describe a mechanism of EGFR regulation through the importin β family member RAN-binding protein 6 (RanBP6), a protein of hitherto unknown functions. We show that RanBP6 silencing impairs nuclear translocation of signal transducer and activator of transcription 3 (STAT3), reduces STAT3 binding to the EGFR promoter, results in transcriptional derepression of EGFR, and increased EGFR pathway output. Focal deletions of the RanBP6 locus on chromosome 9p were found in a subset of glioblastoma (GBM) and silencing of RanBP6 promoted glioma growth in vivo. Our results provide an example of EGFR deregulation in cancer through silencing of components of the nuclear import pathway.
Two-dimensional topological superconductivity in Pb/Co/Si(111)
Authors: Ménard Gerbold C. , Guissart Sébastien , Brun Christophe , Leriche Raphaël T. , Trif Mircea , Debontridder François , Demaille Dominique , Roditchev Dimitri , Simon Pascal , Cren Tristan
Published: December 2017

Just like insulators can present topological phases characterized by Dirac edge states, superconductors can exhibit topological phases characterized by Majorana edge states. In particular, one-dimensional topological superconductors are predicted to host zero-energy Majorana fermions at their extremities. By contrast, two-dimensional superconductors have a one-dimensional boundary which would naturally lead to propagating Majorana edge states characterized by a Dirac-like dispersion. In this paper we present evidences of one-dimensional dispersive in-gap edge states surrounding a two-dimensional topological superconducting domain consisting of a monolayer of Pb covering magnetic Co–Si islands grown on Si(111). We interpret the measured dispersive in-gap states as a spatial topological transition with a gap closure. Our method could in principle be generalized to a large variety of heterostructures combining a Rashba superconductor with a magnetic layer in order to be used as a platform for engineering topological quantum phases.
Migratory dendritic cells acquire and present lymphatic endothelial cell-archived antigens during lymph node contraction
Authors: Kedl Ross M. , Lindsay Robin S. , Finlon Jeffrey M. , Lucas Erin D. , Friedman Rachel S. , Tamburini Beth A. Jirón
Published: December 2017

Antigens derived from viral infection or vaccination can persist within a host for many weeks after resolution of the infection or vaccine responses. We previously identified lymphatic endothelial cells (LEC) as the repository for this antigen archival, yet LECs are unable to present their archived antigens to CD8+T cells, and instead transfer their antigens to CD11c+antigen-presenting cells (APC). Here we show that the exchange of archived antigens between LECs and APCs is mediated by migratory dendritic cells (DC). After vaccination, both migratory basic leucine zipper ATF-like transcription factor 3 (BatF3)-dependent and BatF3-independent DCs are responsible for antigen exchange and cross-presentation. However, exchange of archived viral antigens is mediated only by BatF3-dependent migratory DCs potentially acquiring apoptotic LECs. In conclusion, LEC-archived antigens are exchanged with migratory DCs, both directly and through LEC apoptosis, to cross-present archived antigens to circulating T cells.
Estimation of immune cell content in tumour tissue using single-cell RNA-seq data
Authors: Schelker Max , Feau Sonia , Du Jinyan , Ranu Nav , Klipp Edda , MacBeath Gavin , Schoeberl Birgit , Raue Andreas
Published: December 2017

As interactions between the immune system and tumour cells are governed by a complex network of cell–cell interactions, knowing the specific immune cell composition of a solid tumour may be essential to predict a patient’s response to immunotherapy. Here, we analyse in depth how to derive the cellular composition of a solid tumour from bulk gene expression data by mathematical deconvolution, using indication-specific and cell type-specific reference gene expression profiles (RGEPs) from tumour-derived single-cell RNA sequencing data. We demonstrate that tumour-derived RGEPs are essential for the successful deconvolution and that RGEPs from peripheral blood are insufficient. We distinguish nine major cell types, as well as three T cell subtypes. Using the tumour-derived RGEPs, we can estimate the content of many tumours associated immune and stromal cell types, their therapeutically relevant ratios, as well as an improved gene expression profile of the malignant cells.
Single-cell RNA-sequencing uncovers transcriptional states and fate decisions in haematopoiesis
Authors: Athanasiadis Emmanouil I. , Botthof Jan G. , Andres Helena , Ferreira Lauren , Lio Pietro , Cvejic Ana
Published: December 2017

The success of marker-based approaches for dissecting haematopoiesis in mouse and human is reliant on the presence of well-defined cell surface markers specific for diverse progenitor populations. An inherent problem with this approach is that the presence of specific cell surface markers does not directly reflect the transcriptional state of a cell. Here, we used a marker-free approach to computationally reconstruct the blood lineage tree in zebrafish and order cells along their differentiation trajectory, based on their global transcriptional differences. Within the population of transcriptionally similar stem and progenitor cells, our analysis reveals considerable cell-to-cell differences in their probability to transition to another committed state. Once fate decision is executed, the suppression of transcription of ribosomal genes and upregulation of lineage-specific factors coordinately controls lineage differentiation. Evolutionary analysis further demonstrates that this haematopoietic programme is highly conserved between zebrafish and higher vertebrates.
Eml1 loss impairs apical progenitor spindle length and soma shape in the developing cerebral cortex
Authors: Bizzotto Sara , Uzquiano Ana , Dingli Florent , Ershov Dmitry , Houllier Anne , Arras Guillaume , Richards Mark , Loew Damarys , Minc Nicolas , Croquelois Alexandre , Houdusse Anne , Francis Fiona
Published: December 2017

The ventricular zone (VZ) of the developing cerebral cortex is a pseudostratified epithelium that contains progenitors undergoing precisely regulated divisions at its most apical side, the ventricular lining (VL). Mitotic perturbations can contribute to pathological mechanisms leading to cortical malformations. The HeCo mutant mouse exhibits subcortical band heterotopia (SBH), likely to be initiated by progenitor delamination from the VZ early during corticogenesis. The causes for this are however, currently unknown. Eml1, a microtubule (MT)-associated protein of the EMAP family, is impaired in these mice. We first show that MT dynamics are perturbed in mutant progenitor cells in vitro. These may influence interphase and mitotic MT mechanisms and indeed, centrosome and primary cilia were altered and spindles were found to be abnormally long in HeCo progenitors. Consistently, MT and spindle length regulators were identified in EML1 pulldowns from embryonic brain extracts. Finally, we found that mitotic cell shape is also abnormal in the mutant VZ. These previously unidentified VZ characteristics suggest altered cell constraints which may contribute to cell delamination.
Molecular cloning of novel transcripts of human kallikrein-related peptidases 5, 6, 7, 8 and 9 (KLK5 – KLK9), using Next-generation sequencing
Authors: Adamopoulos Panagiotis G. , Kontos Christos K. , Scorilas Andreas
Published: December 2017

Alternative splicing of cancer-related genes is a common cellular mechanism accounting for cancer cell transcriptome complexity and affecting cell cycle control, proliferation, apoptosis, angiogenesis, invasion, and metastasis. In this study, we describe the discovery and molecular cloning of thirty novel transcripts of the human KLK5, KLK6, KLK7, KLK8 and KLK9 genes, using 3′ rapid amplification of cDNA ends (3′ RACE) and NGS technology, as well as their expression analysis in many established cell lines, originating from several distinct cancerous and normal tissues. Extensive bioinformatic analysis revealed novel splice variants of these five members of the KLK family, comprising entirely new exons, previously unknown boundaries of the already annotated exons (extensions and truncations) as well as alternative splicing events between these exons. Nested RT-PCR in a panel of human cell lines originating from seventeen cancerous and two normal tissues with the use of variant-specific pairs of primers was carried out for expression analysis of these novel splice variants, and Sanger sequencing of the respective amplicons confirmed our NGS results. Given that some splice variants of KLK family members possess clinical value, novel alternatively spliced transcripts appear as new candidate biomarkers for diagnostic and/or prognostic purposes and as targets for therapeutic strategies.
Comparative genome analysis of the vineyard weed endophyte Pseudomonas viridiflava CDRTc14 showing selective herbicidal activity
Authors: Samad Abdul , Antonielli Livio , Sessitsch Angela , Compant Stéphane , Trognitz Friederike
Published: December 2017

Microbes produce a variety of secondary metabolites to be explored for herbicidal activities. We investigated an endophyte Pseudomonas viridiflava CDRTc14, which impacted growth of its host Lepidium draba L., to better understand the possible genetic determinants for herbicidal and host-interaction traits. Inoculation tests with a variety of target plants revealed that CDRTc14 shows plant-specific effects ranging from beneficial to negative. Its herbicidal effect appeared to be dose-dependent and resembled phenotypically the germination arrest factor of Pseudomonas fluorescens WH6. CDRTc14 shares 183 genes with the herbicidal strain WH6 but the formylaminooxyvinylglycine (FVG) biosynthetic genes responsible for germination arrest of WH6 was not detected. CDRTc14 showed phosphate solubilizing ability, indole acetic acid and siderophores production in vitro and harbors genes for these functions. Moreover, genes for quorum sensing, hydrogen cyanide and ACC deaminase production were also found in this strain. Although, CDRTc14 is related to plant pathogens, we neither found a complete pathogenicity island in the genome, nor pathogenicity symptoms on susceptible plant species upon CDRTc14 inoculation. Comparison with other related genomes showed several unique genes involved in abiotic stress tolerance in CDRTc14 like genes responsible for heavy metal and herbicide resistance indicating recent adaptation to plant protection measures applied in vineyards.
Understanding population structure and historical demography of Litsea auriculata (Lauraceae), an endangered species in east China
Authors: Geng Qifang , Sun Lin , Zhang Peihua , Wang Zhongsheng , Qiu Yingxiong , Liu Hong , Lian Chunlan
Published: December 2017

Detecting how historical and contemporary factors contribute to genetic divergence and genetic structure is a central question in ecology and evolution. We examine this question by intergrating population genetics with ecological niche modelling ofLitsea auriculata(Lauraceae), which is endangered and native to east China. Geographical and environmental factors including climatic fluctuations since the last glacial maximum (LGM) have also contribute to population demography and patterns of genetic structure.L.auriculatapopulations underwent expansion after divergence and dramatically decreased to the current small size with relative population bottlenecks due to climate changes. Populations separated by physical geographical barrier including geographic distance and Yangtze River, as a result contemporary gene flow amongL.auriculatapopulations showed drastic declines in comparison with historical gene flow, resulting in a high level of population divergence. Thus, patterns of genetic structure ofL.auriculatacan result from both geographic and environmental factors including climate changes. This information is helpful in forming conservation strategies forL.auriculatain China.
Identification of a gene signature for discriminating metastatic from primary melanoma using a molecular interaction network approach
Authors: Metri Rahul , Mohan Abhilash , Nsengimana Jérémie , Pozniak Joanna , Molina-Paris Carmen , Newton-Bishop Julia , Bishop David , Chandra Nagasuma
Published: December 2017

Understanding the biological factors that are characteristic of metastasis in melanoma remains a key approach to improving treatment. In this study, we seek to identify a gene signature of metastatic melanoma. We configured a new network-based computational pipeline, combined with a machine learning method, to mine publicly available transcriptomic data from melanoma patient samples. Our method is unbiased and scans a genome-wide protein-protein interaction network using a novel formulation for network scoring. Using this, we identify the most influential, differentially expressed nodes in metastatic as compared to primary melanoma. We evaluated the shortlisted genes by a machine learning method to rank them by their discriminatory capacities. From this, we identified a panel of 6 genes, ALDH1A1, HSP90AB1, KIT, KRT16, SPRR3 and TMEM45B whose expression values discriminated metastatic from primary melanoma (87% classification accuracy). In an independent transcriptomic data set derived from 703 primary melanomas, we showed that all six genes were significant in predicting melanoma specific survival (MSS) in a univariate analysis, which was also consistent with AJCC staging. Further, 3 of these genes, HSP90AB1, SPRR3 and KRT16 remained significant predictors of MSS in a joint analysis (HR = 2.3, P = 0.03) although, HSP90AB1 (HR = 1.9, P = 2 × 10−4) alone remained predictive after adjusting for clinical predictors.
Ensemble Modeling Approach Targeting Heterogeneous RNA-Seq data: Application to Melanoma Pseudogenes
Authors: Capobianco Enrico , Valdes Camilo , Sarti Samanta , Jiang Zhijie , Poliseno Laura , Tsinoremas Nicolas F.
Published: December 2017

We studied the transcriptome landscape of skin cutaneous melanoma (SKCM) using 103 primary tumor samples from TCGA, and measured the expression levels of both protein coding genes and non-coding RNAs (ncRNAs). In particular, we emphasized pseudogenes potentially relevant to this cancer. While cataloguing the profiles based on the known biotypes, all the employed RNA-Seq methods generated just a small consensus of significant biotypes. We thus designed an approach to reconcile the profiles from all methods following a simple strategy: we selected genes that were confirmed as differentially expressed by the ensemble predictions obtained in a regression model. The main advantages of this approach are: 1) Selection of a high-confidence gene set identifying relevant pathways; 2) Use of a regression model whose covariates embed all method-driven outcomes to predict an averaged profile; 3) Method-specific assessment of prediction power and significance. Furthermore, the approach can be generalized to any biological system for which noisy RNA-Seq profiles are computed. As our analyses concerned bio-annotations of both high-quality protein coding genes and ncRNAs, we considered the associations between pseudogenes and parental genes (targets). Among the candidate targets that were validated, we identified PINK1, which is studied in patients with Parkinson and cancer (especially melanoma).
A neuronal signature of accurate imitative learning in wild-caught songbirds (swamp sparrows, Melospiza georgiana)
Authors: Moseley Dana L. , Joshi Narendra R. , Prather Jonathan F. , Podos Jeffrey , Remage-Healey Luke
Published: December 2017

In humans and other animals, behavioural variation in learning has been associated with variation in neural features like morphology and myelination. By contrast, it is essentially unknown whether cognitive performance scales with electrophysiological properties of individual neurons. Birdsong learning offers a rich system to investigate this topic as song acquisition is similar to human language learning. Here, we address the interface between behavioural learning and neurophysiology in a cohort of wild-caught, hand-reared songbirds (swamp sparrows, Melospiza georgiana). We report the discovery in the forebrain HVC of sensorimotor ‘bridge’ neurons that simultaneously and selectively represent two critical learning-related schemas: the bird’s own song, and the specific tutor model from which that song was copied. Furthermore, the prevalence and response properties of bridge neurons correlate with learning ability – males that copied tutor songs more accurately had more bridge neurons. Our results are consistent with the hypothesis that accurate imitative learning depends on a successful bridge, within single cortical neurons, between the representation of learning models and their sensorimotor copies. Whether such bridge neurons are a necessary mechanism for accurate learning or an outcome of learning accuracy is unknown at this stage, but can now be addressed in future developmental studies.
Bis(monoacylglycero)phosphate lipids in the retinal pigment epithelium implicate lysosomal/endosomal dysfunction in a model of Stargardt disease and human retinas
Authors: Anderson David M. G. , Ablonczy Zsolt , Koutalos Yiannis , Hanneken Anne M. , Spraggins Jeffrey M. , Calcutt M. Wade , Crouch Rosalie K. , Caprioli Richard M. , Schey Kevin L.
Published: December 2017

Stargardt disease is a juvenile onset retinal degeneration, associated with elevated levels of lipofuscin and its bis-retinoid components, such as N-retinylidene-N-retinylethanolamine (A2E). However, the pathogenesis of Stargardt is still poorly understood and targeted treatments are not available. Utilizing high spatial and high mass resolution matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS), we determined alterations of lipid profiles specifically localized to the retinal pigment epithelium (RPE) in Abca4
−/−
Stargardt model mice compared to their relevant background strain. Extensive analysis by LC-MS/MS in both positive and negative ion mode was required to accurately confirm the identity of one highly expressed lipid class, bis(monoacylgylercoro)phosphate (BMP) lipids, and to distinguish them from isobaric species. The same BMP lipids were also detected in the RPE of healthy human retina. BMP lipids have been previously associated with the endosomal/lysosomal storage diseases Niemann-Pick and neuronal ceroid lipofuscinosis and have been reported to regulate cholesterol levels in endosomes. These results suggest that perturbations in lipid metabolism associated with late endosomal/lysosomal dysfunction may play a role in the pathogenesis of Stargardt disease and is evidenced in human retinas.
Whole-genome sequencing and SNV genotyping of ‘Nebbiolo’ (Vitis vinifera L.) clones
Authors: Gambino Giorgio , Dal Molin Alessandra , Boccacci Paolo , Minio Andrea , Chitarra Walter , Avanzato Carla Giuseppina , Tononi Paola , Perrone Irene , Raimondi Stefano , Schneider Anna , Pezzotti Mario , Mannini Franco , Gribaudo Ivana , Delledonne Massimo
Published: December 2017

‘Nebbiolo’ (Vitis vinifera) is among the most ancient and prestigious wine grape varieties characterised by a wide genetic variability exhibited by a high number of clones (vegetatively propagated lines of selected mother plants). However, limited information is available for this cultivar at the molecular and genomic levels. The whole-genomes of three ‘Nebbiolo’ clones (CVT 71, CVT 185 and CVT 423) were re-sequenced and a de novo transcriptome assembly was produced. Important remarks about the genetic peculiarities of ‘Nebbiolo’ and its intra-varietal variability useful for clonal identification were reported. In particular, several varietal transcripts identified for the first time in ‘Nebbiolo’ were disease resistance genes and single-nucleotide variants (SNVs) identified in ‘Nebbiolo’, but not in other cultivars, were associated with genes involved in the stress response. Ten newly discovered SNVs were successfully employed to identify some periclinal chimeras and to classify 98 ‘Nebbiolo’ clones in seven main genotypes, which resulted to be linked to the geographical origin of accessions. In addition, for the first time it was possible to discriminate some ‘Nebbiolo’ clones from the others.
Laser-induced blurring of molecular structure information in high harmonic spectroscopy
Authors: Risoud François , Lévêque Camille , Labeye Marie , Caillat Jérémie , Maquet Alfred , Salières Pascal , Taïeb Richard , Shaaran Tahir
Published: December 2017

High harmonic spectroscopy gives access to molecular structure with Angström resolution. Such information is encoded in the destructive interferences occurring between the harmonic emissions from the different parts of the molecule. By solving the time-dependent Schrödinger equation, either numerically or with the molecular strong-field approximation, we show that the electron dynamics in the emission process generally results in a strong spectral smoothing of the interferences, blurring the structural information. However we identify specific generation conditions where they are unaffected. These findings have important consequences for molecular imaging and orbital tomography using high harmonic spectroscopy.