bluuebunny/crossref_metadata_2025 huggingface dataset:
Beard's SPQR. A History of Ancient Rome as Background Reading in Classical Latin Courses. A Teaching Proposal
Authors: Beneyto Tamara Lobato
Published: December 2019

Contextual or background knowledge performs an important function in second language learning and reading comprehension, as a number of theoretical and empirical studies have shown (see, for instance, P. L. Carrell, 1983, 1982). To the extent that Ancient Greek and Latin are verbal codes too, they constitute no exception to the aforementioned principle. Indeed, contextual knowledge is particularly relevant to reading comprehension in Classical Languages, given the time, material, and cultural gap between their original context of use during antiquity, on the one hand, and the context of the contemporary learners of these languages, on the other. Addressing and integrating this type of knowledge into Classical Latin courses is, therefore, expected to aid student comprehension of both original and adapted classical texts.
Actors of Dionysus
Authors: Rogers Megan
Published: December 2019

Actors of Dionysus (aod) is a charity and theatre company with 26 years of experience of creating radical adaptations of Ancient Greek drama and new writing productions inspired by myth. Since 1993 we have toured over 50 productions nationally and internationally, performed to over 750,000 people and become the UK's leading interpreters in this field.
Forecasting Volcanic Eruptions with Artificial Intelligence
Authors: Underwood Emily
Published: December 2019

A machine learning algorithm automatically detects telltale signs of volcanic unrest.
Evaluating the Performance of Past Climate Model Projections
Authors: Hausfather Zeke , Drake Henri F. , Abbott Tristan , Schmidt Gavin A.
Published: December 2019

Retrospectively comparing future model projections to observations provides a robust and independent test of model skill. Here we analyze the performance of climate models published between 1970 and 2007 in projecting future global mean surface temperature (GMST) changes. Models are compared to observations based on both the change in GMST over time and the change in GMST over the change in external forcing. The latter approach accounts for mismatches in model forcings, a potential source of error in model projections independent of the accuracy of model physics. We find that climate models published over the past five decades were skillful in predicting subsequent GMST changes, with most models examined showing warming consistent with observations, particularly when mismatches between model‐projected and observationally estimated forcings were taken into account.
The 2013 and 2017 Ms 5 Seismic Swarms in Jilin, NEChina: Fluid‐Triggered Earthquakes?
Authors: Zhang Guangwei , Lei Jianshe , Sun Daoyuan
Published: December 2019

Understanding the mechanism of moderate earthquake swarm is important for the time‐dependent hazard assessment. Five Ms ≥ 5.0 earthquakes occurred between October and November 2013 in Qianguo, Jilin, a region with low seismicity in northeast China. After 4 years, two more Ms > 5.0 earthquakes struck Ningjiang, Jilin. To investigate the swarm mechanism and the relationship between these two swarm activities, we determine the full moment tensor solutions for 12 Ms > 3.5 earthquakes, including the seven Ms ≥ 5.0 events. The focal mechanisms show that the 2013 Ms ≥ 5.0 events mostly exhibit thrust compression with significant volume closure components, whereas the 2017 Ms ≥ 5.0 earthquakes illustrate a dominated strike‐slip type. In order to explain such differences, we conduct double‐difference tomography in the study region. Our tomographic results reveal that both swarms are located in the low‐velocity zones and the fault materials exhibit structural variations along the strike, possibly indicating that the structural contrast could be critical for the variations in the focal mechanism and hypocenter migration. The faults provide pathways for the upward intrusion of fluids that control the distribution and migration of the swarm sequences. A long‐term fluid‐rock interaction could lead to the fault materials intensely fractured in the 2013 swarm area but relatively less damaged in the 2017 swarm area. We can conclude that fluids play an important role in triggering the two seismic swarms.
Interpreting the Difference in Magnitudes of PETM Carbon Isotope Excursions in Paleosol Carbonate and Organic Matter: Oxidation of Methane in Soils Versus Elevated Soil Respiration Rates
Authors: Gallagher Timothy M. , Cacciatore Christopher G. , Breecker Daniel O.
Published: December 2019

Key Points

Possible mechanisms that could explain larger‐magnitude carbon isotope excursions in paleosol carbonate than organic matter are evaluated

Oxidation of methane in soil pore spaces is an unlikely explanation for the main excursion but may help explain the preonset excursion

At least a 4 times increase in soil respiration rates is required to explain the larger carbon isotope excursion in paleosol carbonate
A Re‐evaluation of the Plenus Cold Event, and the Links Between CO2, Temperature, and Seawater Chemistry During OAE 2
Authors: O'Connor Lauren K. , Jenkyns Hugh C. , Robinson Stuart A. , Remmelzwaal Serginio R. C. , Batenburg Sietske J. , Parkinson Ian J. , Gale Andy S.
Published: December 2019

The greenhouse world of the mid‐Cretaceous (~94 Ma) was punctuated by an episode of abrupt climatic upheaval: Oceanic Anoxic Event 2. High‐resolution climate records reveal considerable changes in temperature, carbon cycling, and ocean chemistry during this climatic perturbation. In particular, an interval of cooling has been detected in the English Chalk on the basis of an invasive boreal fauna and bulk oxygen‐isotope excursions registered during the early stages of Oceanic Anoxic Event 2—a phenomenon known as the Plenus Cold Event, which has tentatively been correlated with climatic shifts worldwide. Here we present new high‐resolution neodymium‐, carbon‐, and oxygen‐isotope data, as well as elemental chromium concentrations and cerium anomalies, from the English Chalk exposed at Dover, UK, which we evaluate in the context of >400 records from across the globe. A negative carbon‐isotope excursion that correlates with the original “Plenus Cold Event” is consistently expressed worldwide, and CO2 proxy records, where available, indicate a rise and subsequent fall in CO2 over the Plenus interval. However, variability in the timing and expression of cooling at different sites suggests that, although sea‐surface paleotemperatures may reflect a response to global CO2 change, local processes likely played a dominant role at many sites. Variability in the timing and expression of changes in water mass character, and problems in determining the driver of observed proxy changes, suggest that no single simple mechanism can link the carbon cycle to oceanography during the Plenus interval and other factors including upwelling and circulation patterns were locally important. As such, it is proposed that the Plenus carbon‐isotope event is a more reliable stratigraphic marker to identify the Plenus interval, rather than any climatic shifts that may have been overprinted by local effects.
Effects of intranasal oxytocin administration on empathy and approach motivation in women with borderline personality disorder: a randomized controlled trial
Authors: Domes Gregor , Ower Nicole , von Dawans Bernadette , Spengler Franny B. , Dziobek Isabel , Bohus Martin , Matthies Swantje , Philipsen Alexandra , Heinrichs Markus
Published: December 2019

Borderline personality disorder (BPD) is characterized by severe interpersonal dysfunction with problems in social cognition, empathy and social approach. Although the neuropeptide oxytocin is known to regulate complex social cognition and behavior in healthy individuals and clinical populations, there is still a lack of evidence for a potential beneficial effect of oxytocin administration on social cognition and social approach in BPD. Fifty-one women with BPD and 51 matched healthy controls were randomized to a double-blind, placebo-controlled, between-subject experimental trial. We administered a single dose of 24 IU oxytocin or placebo intranasally prior to a standardized task measuring affective and cognitive empathy and approach motivation. All participants were free of hormonal contraception and tested in the mid-luteal phase of their menstrual cycle. In the placebo condition, patients with BPD showed reduced cognitive and affective empathy, and less approach behavior motivation than healthy controls. Intranasal oxytocin significantly increased affective empathy and approach motivation in both BPD patients and healthy controls compared to placebo. More importantly, oxytocin administration led to similar scores between BPD and healthy controls. These findings provide the first evidence for a beneficial effect of oxytocin on deficits in affective empathy and approach motivation of BPD. Our results indicate a beneficial effect of a single dose of oxytocin on affective empathy and approach motivation in women with BPD adapting their level of social functioning to healthy controls. Future clinical trials will need to investigate the long-term effects and effectiveness of oxytocin as an add-on treatment for social impairments in BPD.
Gastric cancer-derived mesenchymal stromal cells trigger M2 macrophage polarization that promotes metastasis and EMT in gastric cancer
Authors: Li Wei , Zhang Xu , Wu Fenglei , Zhou Ying , Bao Zengtao , Li Haining , Zheng Ping , Zhao Shaolin
Published: December 2019

Resident macrophages in the tumor microenvironment exert a dual role in tumor progression. So far, the mechanism of intratumoral macrophage generation is still largely unknown. In the present study, the importance of macrophages in the pro-tumor role of gastric cancer-derived mesenchymal stromal cells (GC-MSCs) was observed in a mouse xenograft model with macrophage depletion. In gastric cancer tissues, high expression levels of Ym-1, Fizz-1, arginase-1, and CCR-2, as well as a low expression level of iNOS, were verified, and co-localization of GC-MSCs and tumor-associated macrophages (TAMs) was observed by dual immunofluorescence histochemistry. TAMs isolated from gastric cancer tissues predominantly displayed an M2 phenotype. In a co-culture system, the contribution of GC-MSCs to M2 polarization of macrophages was confirmed by the M2-related protein expression, M2-like immunophenotype and cytokine profile of GC-MSC-primed macrophages in vitro. Blockade of IL-6/IL-8 by neutralizing antibodies significantly attenuated the promoting effect of GC-MSCs on M2-like macrophage polarization via the JAK2/STAT3 signaling pathway. In addition, GC-MSC-primed macrophages promoted the migration and invasion of gastric cancer cells, and the process of EMT in gastric cancer cells was significantly enhanced by GC-MSC-primed macrophage treatment. Our study showed that tumor-promoting GC-MSCs contribute to M2 macrophage polarization within the gastric cancer niche through considerable secretion of IL-6 and IL-8. These GC-MSC-primed macrophages can subsequently prompt gastric cancer metastasis via EMT promotion in gastric cancer cells.
Casein kinase-1γ1 and 3 stimulate tumor necrosis factor-induced necroptosis through RIPK3
Authors: Lee Song-Yi , Kim Hyunjoo , Li Cathena Meiling , Kang Jaemin , Najafov Ayaz , Jung Muhah , Kang Soosung , Wang Shaomeng , Yuan Junying , Jung Yong-Keun
Published: December 2019

Upon necroptosis activation, receptor interacting serine/threonine kinase (RIPK)1 and RIPK3 form a necrosome complex with pseudokinase mixed lineage kinase-like (MLKL). Although protein phosphorylation is a key event for RIPK1 and RIPK3 activation in response to a necroptosis signal, relatively little is known about other factors that might regulate the activity of these kinases or necrosome formation. Through a gain-of-function screen with 546 kinases and 127 phosphatases, we identified casein kinase 1 gamma (CK1γ) as a candidate necroptosis-promoting factor. Here, we show that the decreased activity or amounts of CK1γ1 and CK1γ3, either by treatment with a chemical inhibitor or knockdown in cells, reduced TNFα-induced necroptosis. Conversely, ectopic expression of CK1γ1 or CK1γ3 exacerbated necroptosis, but not apoptosis. Similar to RIPK1 and RIPK3, CK1γ1 was also cleaved at Asp343 by caspase-8 during apoptosis. CK1γ1 and CK1γ3 formed a protein complex and were recruited to the necrosome harboring RIPK1, RIPK3 and MLKL. In particular, an autophosphorylated form of CK1γ3 at Ser344/345 was detected in the necrosome and was required to mediate the necroptosis. In addition, in vitro assays with purified proteins showed that CK1γ phosphorylated RIPK3, affecting its activity, and in vivo assays showed that the CK1γ-specific inhibitor Gi prevented abrupt death in mice with hypothermia in a model of TNFα-induced systemic inflammatory response syndrome. Collectively, these data suggest that CK1γ1 and CK1γ3 are required for TNFα-induced necroptosis likely by regulating RIPK3.
Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses
Authors: Adams Ryan A. , Fernandes-Cerqueira Cátia , Notarnicola Antonella , Mertsching Elisabeth , Xu Zhiwen , Lo Wing-Sze , Ogilvie Kathleen , Chiang Kyle P. , Ampudia Jeanette , Rosengren Sanna , Cubitt Andrea , King David J. , Mendlein John D. , Yang Xiang-Lei , Nangle Leslie A. , Lundberg Ingrid E. , Jakobsson Per-Johan , Schimmel Paul
Published: December 2019

His-tRNA synthetase (HARS) is targeted by autoantibodies in chronic and acute inflammatory anti-Jo-1-positive antisynthetase syndrome. The extensive activation and migration of immune cells into lung and muscle are associated with interstitial lung disease, myositis, and morbidity. It is unknown whether the sequestration of HARS is an epiphenomenon or plays a causal role in the disease. Here, we show that HARS circulates in healthy individuals, but it is largely undetectable in the serum of anti-Jo-1-positive antisynthetase syndrome patients. In cultured primary human skeletal muscle myoblasts (HSkMC), HARS is released in increasing amounts during their differentiation into myotubes. We further show that HARS regulates immune cell engagement and inhibits CD4+and CD8+T-cell activation. In mouse and rodent models of acute inflammatory diseases, HARS administration downregulates immune activation. In contrast, neutralization of extracellular HARS by high-titer antibody responses during tissue injury increases susceptibility to immune attack, similar to what is seen in humans with anti-Jo-1-positive disease. Collectively, these data suggest that extracellular HARS is homeostatic in normal subjects, and its sequestration contributes to the morbidity of the anti-Jo-1-positive antisynthetase syndrome.
Resettable skin interfaced microfluidic sweat collection devices with chemesthetic hydration feedback
Authors: Reeder Jonathan T. , Xue Yeguang , Franklin Daniel , Deng Yujun , Choi Jungil , Prado Olivia , Kim Robin , Liu Claire , Hanson Justin , Ciraldo John , Bandodkar Amay J. , Krishnan Siddharth , Johnson Alexandra , Patnaude Emily , Avila Raudel , Huang Yonggang , Rogers John A.
Published: December 2019

Recently introduced classes of thin, soft, skin-mounted microfluidic systems offer powerful capabilities for continuous, real-time monitoring of total sweat loss, sweat rate and sweat biomarkers. Although these technologies operate without the cost, complexity, size, and weight associated with active components or power sources, rehydration events can render previous measurements irrelevant and detection of anomalous physiological events, such as high sweat loss, requires user engagement to observe colorimetric responses. Here we address these limitations through monolithic systems of pinch valves and suction pumps for purging of sweat as a reset mechanism to coincide with hydration events, microstructural optics for reversible readout of sweat loss, and effervescent pumps and chemesthetic agents for automated delivery of sensory warnings of excessive sweat loss. Human subject trials demonstrate the ability of these systems to alert users to the potential for dehydration via skin sensations initiated by sweat-triggered ejection of menthol and capsaicin.
Self-regenerating giant hyaluronan polymer brushes
Authors: Wei Wenbin , Faubel Jessica L. , Selvakumar Hemaa , Kovari Daniel T. , Tsao Joanna , Rivas Felipe , Mohabir Amar T. , Krecker Michelle , Rahbar Elaheh , Hall Adam R. , Filler Michael A. , Washburn Jennifer L. , Weigel Paul H. , Curtis Jennifer E.
Published: December 2019

Tailoring interfaces with polymer brushes is a commonly used strategy to create functional materials for numerous applications. Existing methods are limited in brush thickness, the ability to generate high-density brushes of biopolymers, and the potential for regeneration. Here we introduce a scheme to synthesize ultra-thick regenerating hyaluronan polymer brushes using hyaluronan synthase. The platform provides a dynamic interface with tunable brush heights that extend up to 20 microns – two orders of magnitude thicker than standard brushes. The brushes are easily sculpted into micropatterned landscapes by photo-deactivation of the enzyme. Further, they provide a continuous source of megadalton hyaluronan or they can be covalently-stabilized to the surface. Stabilized brushes exhibit superb resistance to biofilms, yet are locally digested by fibroblasts. This brush technology provides opportunities in a range of arenas including regenerating tailorable biointerfaces for implants, wound healing or lubrication as well as fundamental studies of the glycocalyx and polymer physics.
Dynamic and tunable metabolite control for robust minimal-equipment assessment of serum zinc
Authors: McNerney Monica P. , Michel Cirstyn L. , Kishore Krishi , Standeven Janet , Styczynski Mark P.
Published: December 2019

Bacterial biosensors can enable programmable, selective chemical production, but difficulties incorporating metabolic pathways into complex sensor circuits have limited their development and applications. Here we overcome these challenges and present the development of fast-responding, tunable sensor cells that produce different pigmented metabolites based on extracellular concentrations of zinc (a critical micronutrient). We create a library of dual-input synthetic promoters that decouple cell growth from zinc-specific metabolite production, enabling visible cell coloration within 4 h. Using additional transcriptional and metabolic control methods, we shift the response thresholds by an order of magnitude to measure clinically relevant zinc concentrations. The resulting sensor cells report zinc concentrations in individual donor serum samples; we demonstrate that they can provide results in a minimal-equipment fashion, serving as the basis for a field-deployable assay for zinc deficiency. The presented advances are likely generalizable to the creation of other types of sensors and diagnostics.
Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts
Authors: Strohäker Timo , Jung Byung Chul , Liou Shu-Hao , Fernandez Claudio O. , Riedel Dietmar , Becker Stefan , Halliday Glenda M. , Bennati Marina , Kim Woojin S. , Lee Seung-Jae , Zweckstetter Markus
Published: December 2019

Parkinson’s disease (PD) and Multiple System Atrophy (MSA) are clinically distinctive diseases that feature a common neuropathological hallmark of aggregated α-synuclein. Little is known about how differences in α-synuclein aggregate structure affect disease phenotype. Here, we amplified α-synuclein aggregates from PD and MSA brain extracts and analyzed the conformational properties using fluorescent probes, NMR spectroscopy and electron paramagnetic resonance. We also generated and analyzed several in vitro α-synuclein polymorphs. We found that brain-derived α-synuclein fibrils were structurally different to all of the in vitro polymorphs analyzed. Importantly, there was a greater structural heterogeneity among α-synuclein fibrils from the PD brain compared to those from the MSA brain, possibly reflecting on the greater variability of disease phenotypes evident in PD. Our findings have significant ramifications for the use of non-brain-derived α-synuclein fibrils in PD and MSA studies, and raise important questions regarding the one disease-one strain hypothesis in the study of α-synucleinopathies.
Author Correction: Energetic costs regulated by cell mechanics and confinement are predictive of migration path during decision-making
Authors: Zanotelli Matthew R. , Rahman-Zaman Aniqua , VanderBurgh Jacob A. , Taufalele Paul V. , Jain Aadhar , Erickson David , Bordeleau Francois , Reinhart-King Cynthia A.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The role of the South Pacific in modulating Tropical Pacific variability
Authors: Chung Christine T. Y. , Power Scott B. , Sullivan Arnold , Delage François
Published: December 2019

Tropical Pacific variability (TPV) heavily influences global climate, but much is still unknown about its drivers. We examine the impact of South Pacific variability on the modes of TPV: the El Niño-Southern Oscillation (ENSO) and the Interdecadal Pacific Oscillation (IPO). We conduct idealised coupled experiments in which we suppress temperature and salinity variability at all oceanic levels in the South Pacific. This reduces decadal variability in the equatorial Pacific by ~30% and distorts the spatial pattern of the IPO. There is little change to overall interannual variability, however there is a decrease in the magnitude of the largest 5% of both El Niño and La Niña sea-surface temperature (SST) anomalies. Possible reasons for this include: (i) reduced decadal variability means that interannual SST variability is superposed onto a ‘flatter’ background signal, (ii) suppressing South Pacific variability leads to the alteration of coupled processes linking the South and equatorial Pacific. A small but significant mean state change arising from the imposed suppression may also contribute to the weakened extreme ENSO SST anomalies. The magnitude of both extreme El Niño and La Niña SST anomalies are reduced, and the associated spatial patterns of change of upper ocean heat content and wind stress anomalies are markedly different for both types of events.
High-resolution molecular identification of smalltooth sawfish prey
Authors: Hancock Taylor L. , Poulakis Gregg R. , Scharer Rachel M. , Tolley S. Gregory , Urakawa Hidetoshi
Published: December 2019

The foundation of food web analysis is a solid understanding of predator-prey associations. Traditional dietary studies of fishes have been by stomach content analysis. However, these methods are not applicable to Critically Endangered species such as the smalltooth sawfish (Pristis pectinata). Previous research using the combination of stable isotope signatures from fin clips and 18S rRNA gene sequencing of fecal samples identified the smalltooth sawfish as piscivorous at low taxonomic resolution. Here, we present a high taxonomic resolution molecular technique for identification of prey using opportunistically acquired fecal samples. To assess potential biases, primer sets of two mitochondrial genes, 12S and 16S rRNA, were used alongside 18S rRNA, which targets a wider spectrum of taxa. In total, 19 fish taxa from 7 orders and 11 families native to the Gulf of Mexico were successfully identified. The sawfish prey comprised diverse taxa, indicating that this species is a generalist piscivore. These findings and the molecular approach used will aid recovery planning for the smalltooth sawfish and have the potential to reveal previously unknown predator-prey associations from a wide range of taxa, especially rare and hard to sample species.
High efficiency photomodulators for millimeter wave and THz radiation
Authors: Hooper I. R. , Grant N. E. , Barr L. E. , Hornett S. M. , Murphy J. D. , Hendry E.
Published: December 2019

Photomodulators for mm-wave and THz radiation are an essential component for many imaging and signal processing applications. While a myriad of schemes have been devised to enhance photomodulation by enhancing the light-matter interaction, there has been less focus on the photoconductive materials themselves, which are often the limiting factor. Here, we present an approach to increase the photomodulation efficiency of silicon by orders of magnitude, using post treatment of off-the-shelf silicon wafers. The increase in efficiency removes the need for bulky and costly amplified laser sources, and creates the potential for compact and cost-effective modulators for real-world applications. By passivating the surfaces of long bulk-lifetime silicon wafers with Al2O3, the recombination of the photoexcited carriers at the surfaces is mostly eliminated. This results in vastly longer excess carrier lifetimes (up to ~50 ms), with corresponding increases in photoconductivity. The resulting modulators are highly efficient, with the transmission through them being reduced from ~90% to <10% over a narrow frequency band with a continuous wave excitation intensity of just 10 Wm−2, whilst modulation factors of greater than 80% can be achieved over a broad band with similar intensities. We also discuss the limitations of such long-lifetime modulators for applications where the switching speed or spatial resolution of a modulator may be critical.
Machine learning: assessing neurovascular signals in the prefrontal cortex with non-invasive bimodal electro-optical neuroimaging in opiate addiction
Authors: Ieong Hada Fong-ha , Gao Fu , Yuan Zhen
Published: December 2019

Chronic and recurrent opiate use injuries brain tissue and cause serious pathophysiological changes in hemodynamic and subsequent inflammatory responses. Prefrontal cortex (PFC) has been implicated in drug addiction. However, the mechanism underlying systems-level neuroadaptations in PFC during abstinence has not been fully characterized. The objective of our study was to determine what neural oscillatory activity contributes to the chronic effect of opiate exposure and whether the activity could be coupled to neurovascular information in the PFC. We employed resting-state functional connectivity to explore alterations in 8 patients with heroin dependency who stayed abstinent (>3 months; HD) compared with 11 control subjects. A non-invasive neuroimaging strategy was applied to combine electrophysiological signals through electroencephalography (EEG) with hemodynamic signals through functional near-infrared spectroscopy (fNIRS). The electrophysiological signals indicate neural synchrony and the oscillatory activity, and the hemodynamic signals indicate blood oxygenation in small vessels in the PFC. A supervised machine learning method was used to obtain associations between EEG and fNIRS modalities to improve precision and localization. HD patients demonstrated desynchronized lower alpha rhythms and decreased connectivity in PFC networks. Asymmetric excitability and cerebrovascular injury were also observed. This pilot study suggests that cerebrovascular injury in PFC may result from chronic opiate intake.
Revisiting Goodenough-Kanamori rules in a new series of double perovskites LaSr1−xCaxNiReO6
Authors: Jana Somnath , Aich Payel , Kumar P. Anil , Forslund O. K. , Nocerino E. , Pomjakushin V. , Månsson M. , Sassa Y. , Svedlindh Peter , Karis Olof , Siruguri Vasudeva , Ray Sugata
Published: December 2019

The magnetic ground states in highly ordered double perovskites LaSr1−xCaxNiReO6 (x = 0.0, 0.5, 1.0) are studied in view of the Goodenough-Kanamori rules of superexchange interactions in this paper. In LaSrNiReO6, Ni and Re sublattices are found to exhibit curious magnetic states separately, but no long range magnetic ordering is achieved. The magnetic transition at ~255 K is identified with the independent Re sublattice magnetic ordering. Interestingly, the sublattice interactions are tuned by modifying the Ni-O-Re bond angles through Ca doping. Upon Ca doping, the Ni and Re sublattices start to display a ferrimagnetically ordered state at low temperature. The neutron powder diffraction data reveals long range ferrimagnetic ordering of the Ni and Re magnetic sublattices along the crystallographic b-axis. The transition temperature of the ferrimagnetic phase increases monotonically with increasing Ca concentration.
Investigation of potential pathogenicity of Willaertia magna by investigating the transfer of bacteria pathogenicity genes into its genome
Authors: Hasni Issam , Chelkha Nisrine , Baptiste Emeline , Mameri Mouh Rayane , Lachuer Joel , Plasson Fabrice , Colson Philippe , La Scola Bernard
Published: December 2019

Willaertia magna c2c maky is a thermophilic amoeba closely related to the genus Naegleria. This free-living amoeba has the ability to eliminate Legionella pneumophila, which is an amoeba-resisting bacterium living in an aquatic environment. To prevent the proliferation of L. pneumophila in cooling towers, the use of W. magna as natural biocide has been proposed. To provide a better understanding of the W. magna genome, whole-genome sequencing was performed through the study of virulence factors and lateral gene transfers. This amoeba harbors a genome of 36.5 megabases with 18,519 predicted genes. BLASTp analyses reported protein homology between 136 W. magna sequences and amoeba-resistant microorganisms. Horizontal gene transfers were observed based on the basis of the phylogenetic reconstruction hypothesis. We detected 15 homologs of N. fowleri genes related to virulence, although these latter were also found in the genome of N. gruberi, which is a non-pathogenic amoeba. Furthermore, the cytotoxicity test performed on human cells supports the hypothesis that the strain c2c maky is a non-pathogenic amoeba. This work explores the genomic repertory for the first draft genome of genus Willaertia and provides genomic data for further comparative studies on virulence of related pathogenic amoeba, N. fowleri.
A novel circRNA-miRNA-mRNA network identifies circ-YOD1 as a biomarker for coronary artery disease
Authors: Miao Liu , Yin Rui-Xing , Zhang Qing-Hui , Liao Pei-Juan , Wang Yong , Nie Rong-Jun , Li Hui
Published: December 2019

Circular RNAs (circRNAs) are involved in many physiological functions. Whether circulating circRNAs serve as markers for coronary artery disease (CAD) is unknown. Seven CAD-related microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed using clustering and functional enrichment to identify hub mRNAs and miRNAs. StarBase V3.0 and circinteractome databases were used to predict interactions between circRNAs and miRNAs whereas miRwalk and DIANA TOOLS were used to predict interactions between miRNAs and mRNAs. Altogether, this helped establish a circRNA-miRNA-mRNA triple network for diagnosis of CAD. Five non-coding RNAs (ncRNAs) were identified in our study population with the use of quantitative real-time PCR (RT-PCR). The prognostic values of circYOD1, hsa-miR-21-3p and hsa-miR-296-3p were evaluated using a receiver operating characteristic (ROC) curve. A CAD circRNA-miRNA-mRNA network was established from our analyses containing one circRNA, four miRNAs and thirteen mRNAs. After performing RT-PCR validation between CAD and non-CAD samples, only three ncRNAs of five ncRNAs showed significance for further analysis. The area under ROC curve (AUC) of circ-YOD1 was 0.824, the AUC of hsa-miR-21-3p was 0.731 and hsa-miR-296-3p was 0.776. The pairwise comparison results showed that circ-YOD1 had statistical significance (PYOD1-21 < 0.01 and PYOD1-296 < 0.05). The results of functional enrichment analysis of interacting genes and microRNAs showed that the shared circ-YOD1 may act as a new biomarker for CAD. Our investigation of the triple regulatory networks of circRNA-miRNA-mRNA in CAD revealed circ-YOD1 as a potential biomarker for CAD.
Male-Specific Protein Disulphide Isomerase Function is Essential for Plasmodium Transmission and a Vulnerable Target for Intervention
Authors: Angrisano Fiona , Sala Katarzyna A. , Tapanelli Sofia , Christophides George K. , Blagborough Andrew M.
Published: December 2019

Inhibiting transmission of Plasmodium is an essential strategy in malaria eradication, and the biological process of gamete fusion during fertilization is a proven target for this approach. Lack of knowledge of the mechanisms underlying fertilization have been a hindrance in the development of transmission-blocking interventions. Here we describe a protein disulphide isomerase essential for malarial transmission (PDI-Trans/PBANKA_0820300) to the mosquito. We show that PDI-Trans activity is male-specific, surface-expressed, essential for fertilization/transmission, and exhibits disulphide isomerase activity which is up-regulated post-gamete activation. We demonstrate that PDI-Trans is a viable anti-malarial drug and vaccine target blocking malarial transmission with the use of PDI inhibitor bacitracin (98.21%/92.48% reduction in intensity/prevalence), and anti-PDI-Trans antibodies (66.22%/33.16% reduction in intensity/prevalence). To our knowledge, these results provide the first evidence that PDI function is essential for malarial transmission, and emphasize the potential of anti-PDI agents to act as anti-malarials, facilitating the future development of novel transmission-blocking interventions.
Self-Assembly in ultrahigh molecular weight sphere-forming diblock copolymer thin films under strong confinement
Authors: Cao Wei , Xia Senlin , Appold Michael , Saxena Nitin , Bießmann Lorenz , Grott Sebastian , Li Nian , Gallei Markus , Bernstorff Sigrid , Müller-Buschbaum Peter
Published: December 2019

Ultrahigh molecular weight (UHMW) diblock copolymers (DBCs) have emerged as a promising template for fabricating large-sized nanostructures. Therefore, it is of high significance to systematically study the influence of film thickness and solvent vapor annealing (SVA) on the structure evolution of UHMW DBC thin films. In this work, spin coating of an asymmetric linear UHMW polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) DBC is used to fabricate thin films, which are spherically structured with an inter-domain distance larger than 150 nm. To enhance the polymer chain mobility and facilitate approaching equilibrium nanostructures, SVA is utilized as a post-treatment of the spin coated films. With increasing film thickness, a local hexagonal packing of PMMA half-spheres on the surface can be obtained, and the order is improved at larger thickness, as determined by grazing incidence small angle X-ray scattering (GISAXS). Additionally, the films with locally hexagonal packed half-spherical morphology show a poor order-order-poor order transition upon SVA, indicating the realization of ordered structure using suitable SVA parameters.
Highly specific Electrochemical Sensing of Pseudomonas aeruginosa in patients suffering from corneal ulcers: A comparative study
Authors: Khalifa Marwa M. , Elkhawaga Amal A. , Hassan Mona A. , Zahran Asmaa M. , Fathalla Ahmed M. , El-Said Waleed A. , El-Badawy Omnia
Published: December 2019

Pseudomonas aeruginosa is the most common pathogenic gram-negative bacteria causing corneal ulcers globally. In severe cases, often after trauma and eye injury, corneal destruction progresses rapidly and may be completed within 24–48 h causing blindness. In our preliminary work, we have established an ultrasensitive polyaniline (PANI)/gold nanoparticles (Au NPs)/indium tin oxide (ITO) modified sensor for rapid detection of pyocyanin (PYO) in P. aeruginosa infections with a linear range from 238 μM to 1.9 μM and a detection limit of 500 nM. In the present study, we evaluated the efficiency of the established modified electrochemical sensor in the diagnosis of P. aeruginosa in 50 samples collected from patients suffering from corneal ulcers. The obtained results were compared with the results gained by the screen-printed electrode, conventional techniques, automated identification method, and the amplification of the 16 s rRNA gene by PCR as a gold standard test for P. aeruginosa identification. We have found that the electrochemical detection of PYO by square wave voltammetry technique using PANI/Au NPs modified ITO electrode was the only technique showing 100% agreement with the molecular method in sensitivity, specificity, positive and negative predictive values when compared with the SPE, conventional and automated methods.
Effects of Long-term Cotton Continuous Cropping on Soil Microbiome
Authors: Xi Hui , Shen Jili , Qu Zheng , Yang Dingyi , Liu Shiming , Nie Xinhui , Zhu Longfu
Published: December 2019

Verticillium wilt is a severe disease of cotton crops in Xinjiang and affecting yields and quality, due to the continuous cotton cropping in the past decades. The relationship between continuous cropping and the changes induced on soil microbiome remains unclear to date. In this study, the culture types of 15 isolates from Bole (5F), Kuitun (7F), and Shihezi (8F) of north Xinjiang were sclerotium type. Only isolates from field 5F belonged to nondefoliating pathotype, the others belonged to defoliating pathotype. The isolates showed pathogenicity differentiation in cotton. Fungal and bacterial communities in soils had some difference in alpha-diversity, relative abundance, structure and taxonomic composition, but microbial groups showed similarity in the same habitat, despite different sampling sites. The fungal phyla Ascomycota, and the bacterial phyla Proteobacteria, Actinobacteria, Chloroflexi, Acidobacteria and Gemmatimonadetes were strongly enriched. Verticillium abundance was significantly and positively correlated with AN, but negatively correlated with soil OM, AK and pH. Moreover, Verticillium was correlated in abundances with 5 fungal and 6 bacterial genera. Overall, we demonstrate that soil microbiome communities have similar responses to long-term continuous cotton cropping, providing new insights into the effects of continuous cotton cropping on soil microbial communities.
Angiopoietin-2 predicts morbidity in adults with Fontan physiology
Authors: Shirali Aditya S. , Lluri Gentian , Guihard Pierre J. , Conrad Miles B. , Kim Helen , Pawlikowska Ludmila , Boström Kristina I. , Iruela-Arispe M. Luisa , Aboulhosn Jamil A.
Published: December 2019

Morbidity in patients with single-ventricle Fontan circulation is common and includes arrhythmias, edema, and pulmonary arteriovenous malformations (PAVM) among others. We sought to identify biomarkers that may predict such complications. Twenty-five patients with Fontan physiology and 12 control patients with atrial septal defects (ASD) that underwent cardiac catheterization were included. Plasma was collected from the hepatic vein and superior vena cava and underwent protein profiling for a panel of 20 analytes involved in angiogenesis and endothelial dysfunction. Ten (40%) of Fontan patients had evidence of PAVM, eighteen (72%) had a history of arrhythmia, and five (20%) were actively in arrhythmia or had a recent arrhythmia. Angiopoietin-2 (Ang-2) was higher in Fontan patients (8,875.4 ± 3,336.9 pg/mL) versus the ASD group (1,663.6 ± 587.3 pg/mL, p < 0.0001). Ang-2 was higher in Fontan patients with active or recent arrhythmia (11,396.0 ± 3,457.7 vs 8,118.2 ± 2,795.1 pg/mL, p < 0.05). A threshold of 8,500 pg/mL gives Ang-2 a negative predictive value of 100% and positive predictive value of 42% in diagnosing recent arrhythmia. Ang-2 is elevated among adults with Fontan physiology. Ang-2 level is associated with active or recent arrhythmia, but was not found to be associated with PAVM.
Identification of QTL for Target Leaf Spot resistance in Sorghum bicolor and investigation of relationships between disease resistance and variation in the MAMP response
Authors: Kimball Jennifer , Cui Yaya , Chen Dongqin , Brown Pat , Rooney William L. , Stacey Gary , Balint-Kurti Peter J.
Published: December 2019

Target leaf spot (TLS) of sorghum, a foliar disease caused by the necrotrophic fungus Bipolaris cookei (also known as Bipolaris sorghicola), can affect grain yield in sorghum by causing premature drying of leaves and defoliation. Two sorghum recombinant inbred line (RIL) populations, BTx623/BTx642 and BTx623/SC155-14E, were assessed for TLS resistance in replicated trials. Using least square mean trait data, four TLS resistance QTL were identified, two in each population. Of these, three were previously unidentified while a major QTL on chromosome 5 in the BTx623/BTx642 RIL population corresponded to the previously identified TLS resistance gene ds1. A set of sorghum lines were assessed for production of reactive oxygen species induced by treatment with the microbe-associated molecular pattern (MAMP) flg22 (a derivative of flagellin). Flg22-induced ROS production varied between lines in a consistent fashion. One QTL associated with variation in the flg22 response was detected in the RIL populations. No evidence was found to link variation in the MAMP response to variation in TLS resistance
Tailoring parameter distributions to specific germplasm: impact on crop model-based ideotyping
Authors: Paleari Livia , Movedi Ermes , Vesely Fosco Mattia , Confalonieri Roberto
Published: December 2019

Crop models are increasingly used to identify promising ideotypes for given environmental and management conditions. However, uncertainty must be properly managed to maximize the in vivo realizability of ideotypes. We focused on the impact of adopting germplasm-specific distributions while exploring potential combinations of traits. A field experiment was conducted on 43 Italian rice varieties representative of the Italian rice germplasm, where the following traits were measured: light extinction coefficient, radiation use efficiency, specific leaf area at emergence and tillering. Data were used to derive germplasm-specific distributions, which were used to re-run a previous modelling experiment aimed at identifying optimal combinations of plant trait values. The analysis, performed using the rice model WARM and sensitivity analysis techniques, was conducted under current conditions and climate change scenarios. Results revealed that the adoption of germplasm-specific distributions may markedly affect ideotyping, especially for the identification of most promising traits. A re-ranking of some of the most relevant parameters was observed (radiation use efficiency shifted from 4th to 1st), without clear relationships between changes in rankings and differences in distributions for single traits. Ideotype profiles (i.e., values of the ideotype traits) were instead more consistent, although differences in trait values were found.
GWAS studies reveal a possible genetic link between cancer and suicide attempt
Authors: Voskarides Konstantinos , Chatzittofis Andreas
Published: December 2019

Inuit is the population with the highest incidence of suicide attempt and cancer in the world. Previous studies reported that people attempted suicide have a higher future risk for cancer. In view of these data, the largest available genome wide association studies (GWAS) for four major mental disorder groups were screened here for any common genes with all known cancer associated genes and oncogenes/tumor suppressor genes. A common genetic background came out only between suicide attempt and cancer (cancer associated genes analysis: RR = 1.64, p = 7.83 × 10−5; oncogenes/tumor suppressor genes analysis: RR = 2.55, p = 2.82 × 10−22), this supporting existing epidemiological data. Incidence/prevalence of both conditions was found to correlate with extreme cold geographical regions (adjusted R2 = 0.135, p = 3.00 × 10−4); this is not the case for other mental disorders. Our results show a possible genetic link between suicide attempt and cancer and a possible evolutionary connection of both diseases with extreme cold environments. These data are useful for future molecular studies or even for investigation of possible therapeutic protocols.
Heparin Forms Polymers with Cell-free DNA Which Elongate Under Shear in Flowing Blood
Authors: de Vries Joost C. , Barendrecht Arjan D. , Clark Chantal C. , Urbanus Rolf T. , Boross Peter , de Maat Steven , Maas Coen
Published: December 2019

Heparin is a widely used anticoagulant which inhibits factor Xa and thrombin through potentiation of antithrombin. We recently identified that the nucleic acid stain SYTOX reacts with platelet polyphosphate due to molecular similarities, some of which are shared by heparin. We attempted to study heparin in flowing blood by live-cell fluorescence microscopy, using SYTOX for heparin visualisation. Immunostaining was performed with monoclonal antibodies directed against various heparin-binding proteins. In addition, we studied modulation of heparin activity in coagulation assays, as well its effects on fibrin formation under flow in recalcified whole blood. We found that SYTOX-positive polymers appear in heparinised blood under flow. These polymers typically associate with platelet aggregates and their length (reversibly) increases with shear rate. Immunostaining revealed that of the heparin-binding proteins assessed, they only contain histones. In coagulation assays and flow studies on fibrin formation, we found that addition of exogenous histones reverses the anticoagulant effects of heparin. Furthermore, the polymers do not appear in the presence of DNase I, heparinase I/III, or the heparin antidote protamine. These findings suggest that heparin forms polymeric complexes with cell-free DNA in whole blood through a currently unidentified mechanism.
Structural consequences of BMPR2 kinase domain mutations causing pulmonary arterial hypertension
Authors: Chaikuad Apirat , Thangaratnarajah Chancievan , von Delft Frank , Bullock Alex N.
Published: December 2019

Bone morphogenetic proteins (BMPs) are secreted ligands of the transforming growth factor-β (TGF-β) family that control embryonic patterning, as well as tissue development and homeostasis. Loss of function mutations in the type II BMP receptor BMPR2 are the leading cause of pulmonary arterial hypertension (PAH), a rare disease of vascular occlusion that leads to high blood pressure in the pulmonary arteries. To understand the structural consequences of these mutations, we determined the crystal structure of the human wild-type BMPR2 kinase domain at 2.35 Å resolution. The structure revealed an active conformation of the catalytic domain that formed canonical interactions with the bound ligand Mg-ADP. Disease-associated missense mutations were mapped throughout the protein structure, but clustered predominantly in the larger kinase C-lobe. Modelling revealed that the mutations will destabilize the protein structure by varying extents consistent with their previously reported functional heterogeneity. The most severe mutations introduced steric clashes in the hydrophobic protein core, whereas those found on the protein surface were less destabilizing and potentially most favorable for therapeutic rescue strategies currently under clinical investigation.