bluuebunny/crossref_metadata_2025 huggingface dataset:
Impacts of resonant magnetic perturbations on edge carbon transport and emission on EAST with EMC3-EIRENE modelling
Authors: Dai S. Y. , Zhang H. M. , Lyu B. , Wang L. , Feng Y. , Wang Z. X. , Wang D. Z.
Published: May 2020

The modelling of edge carbon transport and emission on EAST tokamak under resonant magnetic perturbation (RMP) fields has been conducted with the three-dimensional edge transport code EMC3-EIRENE. The measured vertical distribution of CVI emission by the extreme ultraviolet spectrometer system for the perturbed case shows a reduction in the CVI emission by 20 % compared to the equilibrium case. The chord-integrated CVI emission can be reconstructed by EMC3-EIRENE modelling, which presents an increase in the CVI emission with RMP fields. The discrepancy between experiments and simulations has been investigated by parameter study to examine the sensitivity of the simulation results on the edge plasma conditions and the impurity perpendicular transport. It is found that the variation of edge plasma conditions for the equilibrium case cannot resolve the discrepancy in the CVI emission between simulations and measurements. The simulations with enhanced impurity perpendicular transport coefficient allows a reasonable agreement with the measured reduction of CVI emission.
Partial inhibition of nitric oxide synthase activity stimulates the nuclear maturation progression of bovine cumulus–oocyte complex in vitro in the presence of hemisections of the follicular walls
Authors: Dubeibe Diego Fernando , Caldas-Bussiere Maria Clara , Maciel Valter Luiz , Sampaio Wlaisa , Gonçalves Paulo B.D. , De Cesaro Matheus P. , Quirino Celia Raquel , Faes Márcia R. , Paes de Carvalho Carla S.
Published: May 2020

This study aimed to assess the effects of the inhibition of nitric oxide synthase (NOS) on events that modulate bovine in vitro oocyte maturation. Cumulus–oocyte complexes (COCs) were cultured with hemisections (HSs) of the follicular walls in a maturation medium supplemented with different concentrations (0.1–10.0 mM) of Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME). Controls consisted of COCs cultured in the presence (+HSs) or absence of HSs (–HSs) with no additional l-NAME supplementation. The following parameters were assessed: oocyte nuclear maturation stage; cumulus cell (CC) membrane integrity; nitrate/nitrite, progesterone, and estradiol concentrations in the culture medium at 22 h of cultivation; and the concentrations of cGMP and cAMP in COCs during the first hour of maturation. The addition of 1.0 mM l-NAME increased the percentage of oocytes that reached metaphase II (MII) and the percentage of intact CCs (P < 0.05). All l-NAME concentrations reduced the nitrate/nitrite concentrations (P < 0.05), but none affected steroid concentrations compared with control +HSs (P > 0.05). The addition of 1.0 mM l-NAME reduced cGMP concentrations at 3 h and increased cAMP concentrations in the first hour of culture (P < 0.05). Our findings suggest that the NOS/NO/cGMP pathway participates in meiosis progression (MI to MII) of the bovine oocytes matured in vitro in the presence of hemisections of the follicular walls. Lastly, the mechanisms that lead to the progression of meiosis after NOS inhibition do not involve changes in steroid production.
Improving Educational Outcomes through Getting It Right for Every Child in Glasgow
Authors: McKenna Maureen
Published: May 2020

This article sketches the context of education in Glasgow, which is Scotland’s largest local authority, serving some of the most deprived communities in Scotland and the UK. It considers the ways in which we work with our schools to raise aspirations and extend young people’s horizons, and explores some of the successes and some of the challenges we have faced and continue to face in bridging the gap between school and higher education. In Scotland, higher education can be delivered through colleges as well as universities. This is an important dimension for our young people, as colleges offer a different learning experience for them and, for some, this can be a more successful learning pathway. There are also other pathways to higher education, for example through work-based learning, such as apprenticeships. Our partnerships with universities and colleges is very strong. Through this partnership there is a range of programmes which support young people across the city to learn about life in university. This is especially important for young people from deprived communities as, often, their families do not have prior experience of higher education. The means of funding and planning these programmes can be viewed as both an enabler and a barrier in certain contexts.
Beyond Quietism: Party Institutionalisation, Salafism, and the Economy
Authors: Cavatorta Francesco , Resta Valeria
Published: May 2020

Breaking with a long tradition of political quietism, many Salafis in Tunisia and Egypt decided to found political parties and participate in competitive elections after the collapse of the regime. In doing so, they had to present a political program to voters, including policy proposals on economic issues. The article examines how Salafi parties dealt with economic policy-making and finds that they reluctantly engaged with it, offering contradictory and naïve policies meant to pander to the electorate. Policy-making preferences and positions on economic issues are employed to look at the degree of party institutionalization Salafi parties have.
Separately-designable diplexer with multiple transmission zeroes using common stub-loaded SIR
Authors: Zhang Yu-Jing , Cai Jing , Chen Jian-Xin
Published: May 2020

A separately-designable diplexer with multiple transmission zeroes (TZs) using common stub-loaded stepped impedance resonator (SIR) is proposed. The common stub-loaded SIR operating in third harmonic (f3) and fifth harmonic (f5) is used for designing the two diplexer channels. The stub is loaded at the voltage-null point of f3 of the SIR. It can separately control f5 but has no effect on f3 so that the two channels can be separately designed. Meanwhile, the input port is tap-connected to the common stub-loaded SIR, which necessarily produces a TZ between f3 and f5, existing in both channel filtering responses. By properly choosing coupling schemes of the two channels, more TZs are realized at the desired locations. Thanks to the generation of the multiple TZs, both passband selectivity and isolation between the two channels are improved significantly. For demonstration, a diplexer operating at 2.22 and 2.95 GHz is designed, fabricated, and measured. The simulated and measured results are presented, showing good agreement.
Toleration and Repression: German States, the Law and the ‘Sects’ in the Long Nineteenth Century
Authors: Henke Manfred
Published: May 2020

At the beginning of the period, the Prussian General Law Code did not provide for equal rights for members of ‘churches’ and those of ‘sects’. However, the French Revolution decreed the separation of church and state and the principle of equal rights for all citizens. Between the Congress of Vienna (1815) and the revolution of 1848, Prussian monarchs pressed for the church union of Lutheran and Reformed and advocated the piety of the Evangelical Revival. The Old Lutherans felt obliged to leave the united church, thus eventually forming a ‘sect’ favoured by the king. Rationalists, who objected to biblicism and orthodoxy, were encouraged to leave, too. As Baptists, Catholic Apostolics and Methodists arrived from Britain and America, the number of ‘sects’ increased. New ways of curtailing their influence were devised, especially in Prussia and Saxony.
History, Sacred History and law at the Intersection of Law, Religion and History
Authors: Edge Peter W.
Published: May 2020

Lawyers, both practitioners and academics, engage with legal history in a variety of ways. Increasing attention is being paid to legal regulation of history and memory. This article argues that the interaction of law and history is particularly problematic within the context of a dispute with a religious element. It will use three case studies to illustrate these challenges: (1) The repeal of the Fradulent Mediums Act 1951 by the Consumer Protection from Unfair Trading Regulations 2008; (2) The Babri Masjid / Ram Temple dispute in Ayodhya, India; and (3) The Hindmarsh Island bridge controversy in South Australia. These case studies show the difficulties legal actors face when confronted with incompatible secular and sacred histories and diverse ways of ‘knowing history’, but also the importance, nonetheless, of understanding history in order to understand the relationship between law and religion.
The Political Background to the Establishment of the Slavic Nomocanon in the Thirteenth Century
Authors: Koprivica Marija
Published: May 2020

The first collection of canon law translated from the Greek into the Slavic language in the ninth century supported the consolidation of Christianity among the Slav peoples. This article focuses on the nomocanon of St Sava of Serbia (Kormchaia), a collection which was original and specific in its content; its relationship to other contemporary legal historical documents will be considered. The article also explores the political background to the emergence of Orthodox Slav collections of ecclesiastical and civil law. The political context in which these collections originated exercised a determinative influence on their contents, the selection of texts and the interpretation of the canons contained within them. The emergence of the Slavic nomocanon is interpreted within a context in which Balkan Slav states sought to foster their independence and aspired to form autocephalous national churches.
General Excommunications of Unknown Malefactors: Conscience, Community and Investigations in England, c.1150–1350
Authors: Hill Felicity
Published: May 2020

In high and late medieval England, general sentences of excommunication pronounced against unnamed wrongdoers were common. Responding to crimes whose perpetrators were unknown, general excommunications were a valuable tool that sought to discover and punish offenders in a number of ways. Solemn denunciations might convince the guilty to confess in order to avoid damnation, or persuade informants to volunteer information. General sentences were also, however, merely a precursor to investigations launched into those responsible. Public denunciations aided investigations conducted by clergy in the local community by publicizing and forcibly condemning the crime committed. Once discovered, suspects were summoned to the bishop's court and were either forced to make amends and do penance or excommunicated by name. This article therefore argues that general sentences were far more complex, effective and legally significant than they are often perceived to be.
The Bishops and the Deposition of Edward II
Authors: Lane Samuel
Published: May 2020

The deposition of Edward II was a watershed in the legal history of later medieval England. However, the significance of the church in its accomplishment has remained controversial. This article offers a reassessment by providing a brief narrative of the episcopate's involvement in events; analysing the importance of their contribution, with particular reference to the quasi-legal aspect of proceedings; considering whether this participation reflected their own initiative or was something about which they had no choice; and questioning why so many bishops turned to oppose Edward II. It becomes evident that prelates played a key part in Edward II's downfall, and that they became involved as a consequence of the oppressive treatment which he had meted out to them, to their families and to political society more broadly.
Kings’ Courts and Bishops’ Administrations in Fourteenth-Century England: A Study in Cooperation
Authors: McHardy Alison K.
Published: May 2020

Behind the rhetoric and theory of crown-church conflict there was much cooperation in the everyday world, where practice and pragmatism often overrode legal and theoretical rules. This article examines the ways in which fourteenth-century English bishops and their clerks responded to the demands made of them by the royal courts. Bishops were bombarded with commands from the crown, with a resulting impact on diocesan records. The crown sought historic information about finance and rights, and commanded bishops to collect clerics’ debts and to enforce their attendance before the lay courts in both civil and criminal cases. Enquiries about the current status of individuals, whether professed in religious orders or legitimate, made considerable work for bishops. How enthusiastically and efficiently these orders were carried out is also evaluated and discussed.
Intimate Partner Violence Perpetration and	Psychopathy: A Comprehensive Review
Authors: Robertson Emily L. , Walker Toni M. , Frick Paul J.
Published: May 2020

Abstract. Intimate partner violence (IPV) is the physical, sexual, and psychological abuse of an intimate partner and is a widespread, international public health crisis. An important proximate risk factor for IPV perpetration is the presence of psychopathic traits but there has not been a systematic review of the research linking psychopathic traits to IPV perpetration. We identified 43 studies using 13,476 participants (9,024 men and 4,452 women) across 10 countries that met our search criteria that led to the following conclusions. First, psychopathy was associated with IPV perpetration with medium effect sizes, even after accounting for various distal and proximate risk factors. Second, the different dimensions of psychopathy did not consistently differ in their prediction of IPV perpetration. Third, within individuals with a history of IPV perpetration, psychopathy did not relate to the frequency or severity of partner violence. Fourth, a few studies have tested the associations among child abuse, psychopathy, and IPV, with one study reporting that the combination of child abuse and psychopathic traits led to especially high risk for IPV perpetration. Lastly, we conclude by making recommendations for how future research and interventions should consider psychopathy to reduce the societal burden of IPV.
Analog and Numerical Experiments of Double Subduction Systems With Opposite Polarity in Adjacent Segments
Authors: Peral Mireia , Ruh Jonas , Zlotnik Sergio , Funiciello Francesca , Fernàndez Manel , Vergés Jaume , Gerya Taras
Published: May 2020

In this work we study the dynamics of double subduction systems with opposite polarity in adjacent segments. A combined approach of numerical and analog experiments allows us to compare results and exploit the strengths of both methodologies. High‐resolution numerical experiments complement laboratory results by providing quantities difficult to measure in the laboratory such as stress state, flow patterns, and energy dissipation. Results show strong asymmetries in the mantle flow that produce in turn asymmetries in the trench and in the downgoing slab deformation. The mantle flow pattern varies with time; the toroidal cells between the plates evolve until merging into one unique cell when the trenches align. In that moment the maximum upward flow is observed close to the trenches. The interaction between the mantle flow produced by each subducting plate makes the rollback processes slower than in a single subduction case. This is consistent with the observed energy dissipation rate that is smaller in the double subduction system than in two single subductions. Moreover, we provide a detailed analysis on the setup and boundary conditions required to numerically reproduce the analog experiments. Boundary conditions at the bottom of the domain are crucial to reproduce their analog counterparts. Numerical results are compared to natural examples of multi‐slab subduction systems in terms of upper mantle seismic anisotropy, relative trench retreat velocities, and composition of subduction‐related magmatism.
Strategies to approach high performance in Cr3+-doped phosphors for high-power NIR-LED light sources
Authors: Jia Zhenwei , Yuan Chenxu , Liu Yongfu , Wang Xiao-Jun , Sun Peng , Wang Lei , Jiang Haochuan , Jiang Jun
Published: May 2020

Broadband near-infrared (NIR)-emitting phosphors are key for next-generation smart NIR light sources based on blue LEDs. To achieve excellent NIR phosphors, we propose a strategy of enhancing the crystallinity, modifying the micromorphology, and maintaining the valence state of Cr3+ in Ca3Sc2Si3O12 garnet (CSSG). By adding fluxes and sintering in a reducing atmosphere, the internal quantum efficiency (IQE) is greatly enhanced to 92.3%. The optimized CSSG:6%Cr3+ exhibits excellent thermal stability. At 150 °C, 97.4% of the NIR emission at room temperature can be maintained. The fabricated NIR-LED device emits a high optical power of 109.9 mW at 520 mA. The performances of both the achieved phosphor and the NIR-LED are almost the best results until now. The mechanism for the optimization is investigated. An application of the NIR-LED light source is demonstrated.
Staufen 1 amplifies proapoptotic activation of the unfolded protein response
Authors: Gandelman Mandi , Dansithong Warunee , Figueroa Karla P. , Paul Sharan , Scoles Daniel R. , Pulst Stefan M.
Published: May 2020

Staufen-1 (STAU1) is an RNA-binding protein that becomes highly overabundant in numerous neurodegenerative disease models, including those carrying mutations in presenilin1 (PSEN1), microtubule-associated protein tau (MAPT), huntingtin (HTT), TAR DNA-binding protein-43 gene (TARDBP), or C9orf72. We previously reported that elevations in STAU1 determine autophagy defects and its knockdown is protective in models of several neurodegenerative diseases. Additional functional consequences of STAU1 overabundance, however, have not been investigated. We studied the role of STAU1 in the chronic activation of the unfolded protein response (UPR), a common feature among neurodegenerative diseases and often directly associated with neuronal death. Here we report that STAU1 is a novel modulator of the UPR, and is required for apoptosis induced by activation of the PERK–CHOP pathway. STAU1 levels increased in response to multiple endoplasmic reticulum (ER) stressors, and exogenous expression of STAU1 was sufficient to cause apoptosis through the PERK–CHOP pathway of the UPR. Cortical neurons and skin fibroblasts derived from Stau1−/− mice showed reduced UPR and apoptosis when challenged with thapsigargin. In fibroblasts from individuals with SCA2 or with ALS-causing TDP-43 and C9ORF72 mutations, we found highly increased STAU1 and CHOP levels in basal conditions, and STAU1 knockdown restored CHOP levels to normal. Taken together, these results show that STAU1 overabundance reduces cellular resistance to ER stress and precipitates apoptosis.
Dynamic reconfiguration of functional brain networks during working memory training
Authors: Finc Karolina , Bonna Kamil , He Xiaosong , Lydon-Staley David M. , Kühn Simone , Duch Włodzisław , Bassett Danielle S.
Published: May 2020

The functional network of the brain continually adapts to changing environmental demands. The consequence of behavioral automation for task-related functional network architecture remains far from understood. We investigated the neural reflections of behavioral automation as participants mastered a dual n-back task. In four fMRI scans equally spanning a 6-week training period, we assessed brain network modularity, a substrate for adaptation in biological systems. We found that whole-brain modularity steadily increased during training for both conditions of the dual n-back task. In a dynamic analysis,we found that the autonomy of the default mode system and integration among task-positive systems were modulated by training. The automation of the n-back task through training resulted in non-linear changes in integration between the fronto-parietal and default mode systems, and integration with the subcortical system. Our findings suggest that the automation of a cognitively demanding task may result in more segregated network organization.
Oncogenic hijacking of a developmental transcription factor evokes vulnerability toward oxidative stress in Ewing sarcoma
Authors: Marchetto Aruna , Ohmura Shunya , Orth Martin F. , Knott Maximilian M. L. , Colombo Maria V. , Arrigoni Chiara , Bardinet Victor , Saucier David , Wehweck Fabienne S. , Li Jing , Stein Stefanie , Gerke Julia S. , Baldauf Michaela C. , Musa Julian , Dallmayer Marlene , Romero-Pérez Laura , Hölting Tilman L. B. , Amatruda James F. , Cossarizza Andrea , Henssen Anton G. , Kirchner Thomas , Moretti Matteo , Cidre-Aranaz Florencia , Sannino Giuseppina , Grünewald Thomas G. P.
Published: May 2020

Ewing sarcoma (EwS) is an aggressive childhood cancer likely originating from mesenchymal stem cells or osteo-chondrogenic progenitors. It is characterized by fusion oncoproteins involving EWSR1 and variable members of the ETS-family of transcription factors (in 85% FLI1). EWSR1-FLI1 can induce target genes by using GGAA-microsatellites as enhancers.

Here, we show that EWSR1-FLI1 hijacks the developmental transcription factor SOX6 – a physiological driver of proliferation of osteo-chondrogenic progenitors – by binding to an intronic GGAA-microsatellite, which promotes EwS growth in vitro and in vivo. Through integration of transcriptome-profiling, published drug-screening data, and functional in vitro and in vivo experiments including 3D and PDX models, we discover that constitutively high SOX6 expression promotes elevated levels of oxidative stress that create a therapeutic vulnerability toward the oxidative stress-inducing drug Elesclomol.

Collectively, our results exemplify how aberrant activation of a developmental transcription factor by a dominant oncogene can promote malignancy, but provide opportunities for targeted therapy.
Integrated nano-optomechanical displacement sensor with ultrawide optical bandwidth
Authors: Liu Tianran , Pagliano Francesco , van Veldhoven René , Pogoretskiy Vadim , Jiao Yuqing , Fiore Andrea
Published: May 2020

Optical read-out of motion is widely used in sensing applications. Recent developments in micro- and nano-optomechanical systems have given rise to on-chip mechanical sensing platforms, potentially leading to compact and integrated optical motion sensors. However, these systems typically exploit narrow spectral resonances and therefore require tuneable lasers with narrow linewidth and low spectral noise, which makes the integration of the read-out extremely challenging. Here, we report a step towards the practical application of nanomechanical sensors, by presenting a sensor with ultrawide (∼80 nm) optical bandwidth. It is based on a nanomechanical, three-dimensional directional coupler with integrated dual-channel waveguide photodiodes, and displays small displacement imprecision of only 45 fm/Hz1/2 as well as large dynamic range (>30 nm). The broad optical bandwidth releases the need for a tuneable laser and the on-chip photocurrent read-out replaces the external detector, opening the way to fully-integrated nanomechanical sensors.
Synergy between the anthocyanin and RDR6/SGS3/DCL4 siRNA pathways expose hidden features of Arabidopsis carbon metabolism
Authors: Jiang Nan , Gutierrez-Diaz Aimer , Mukundi Eric , Lee Yun Sun , Meyers Blake C. , Otegui Marisa S. , Grotewold Erich
Published: May 2020

Anthocyanin pigments furnish a powerful visual output of the stress and metabolic status of Arabidopsis thaliana plants. Essential for pigment accumulation is TRANSPARENT TESTA19 (TT19), a glutathione S-transferase proposed to bind and stabilize anthocyanins, participating in their vacuolar sequestration, a function conserved across the flowering plants. Here, we report the identification of genetic suppressors that result in anthocyanin accumulation in the absence of TT19. We show that mutations in RDR6, SGS3, or DCL4 suppress the anthocyanin defect of tt19 by pushing carbon towards flavonoid biosynthesis. This effect is not unique to tt19 and extends to at least one other anthocyanin pathway gene mutant. This synergy between mutations in components of the RDR6-SGS3-DCL4 siRNA system and the flavonoid pathway reveals genetic/epigenetic mechanisms regulating metabolic fluxes.
Electronic and magnetic structure of infinite-layer NdNiO2: trace of antiferromagnetic metal
Authors: Liu Zhao , Ren Zhi , Zhu Wei , Wang Zhengfei , Yang Jinlong
Published: May 2020

The recent discovery of Sr-doped infinite-layer nickelate NdNiO2 offers a new platform for investigating unconventional superconductivity in nickelate-based compounds. Most intriguingly, the resistivity minimum and Hall coefficient drop were identified simultaneously in the experiment, reflecting a novel electronic structure and transport property of NdNiO2. Driven by this pioneering work, we present a first-principles calculation for the electronic and magnetic structure of undoped parent NdNiO2. By taking into account experimentally relevant interaction strength, we found that (π, π, π) antiferromagnetic NdNiO2 is a compensated bad metal with small Fermi pockets. However, due to the small exchange coupling between 3d-electrons of Ni and strong hybridization with 5d-electrons of Nd, the discovered antiferromagnetic ordering is very weak. Crucially, with the decreasing of temperature, there exists a phase transition between good paramagnetic metal and bad AFM metal. The estimated transition temperature is ~70–90 K, which is consistent with that for observing the resistivity minimum and Hall coefficient drop. In this regarding, our results provide a plausible physical interpretation for these significant experimental observations.
Inter-annual decrease in pulse rate and peak frequency of Southeast Pacific blue whale song types
Authors: Malige Franck , Patris Julie , Buchan Susannah J. , Stafford Kathleen M. , Shabangu Fannie , Findlay Ken , Hucke-Gaete Rodrigo , Neira Sergio , Clark Christopher W. , Glotin Hervé
Published: May 2020

A decrease in the frequency of two southeast Pacific blue whale song types was examined over decades, using acoustic data from several different sources in the eastern Pacific Ocean ranging between the Equator and Chilean Patagonia. The pulse rate of the song units as well as their peak frequency were measured using two different methods (summed auto-correlation and Fourier transform). The sources of error associated with each measurement were assessed. There was a linear decline in both parameters for the more common song type (southeast Pacific song type n.2) between 1997 to 2017. An abbreviated analysis, also showed a frequency decline in the scarcer southeast Pacific song type n.1 between 1970 to 2014, revealing that both song types are declining at similar rates. We discussed the use of measuring both pulse rate and peak frequency to examine the frequency decline. Finally, a comparison of the rates of frequency decline with other song types reported in the literature and a discussion on the reasons of the frequency shift are presented.
Molecular Profile of Locally Aggressive Well Differentiated Thyroid Cancers
Authors: Mady Leila J. , Grimes Michael C. , Khan Nayel I. , Rao R. Harsha , Chiosea Simion I. , Yip Linwah , Ferris Robert L. , Nikiforov Yuri E. , Carty Sally E. , Duvvuri Umamaheswar
Published: May 2020

Knowledge of the genetic landscape of aggressive well differentiated thyroid cancers (WDTC) is lacking. Retrospective review of institutional database was performed to identify locally-invasive thyroid carcinomas and a comparison cohort of low-risk WDTC. ThyroSeq v2 next-generation sequencing was performed on available tissue. Survival time was analyzed by Kaplan-Meier methods and compared between groups via the log-rank test. Time to recurrence, treating death as a competing risk, was analyzed by cumulative incidence and compared between groups. Of 80 T4 tumors, 29 (36%) were met inclusion criteria, of which, 25 had genetic and clinicopathologic data. Most (24/25, 96%) harbored at least one genetic alteration, most commonly BRAF V600E (19, 76%), followed by mutations in the promoter region of TERT (14, 56%). Co-occurrence of BRAF and TERT was identified in 12 (48%) and associated with significantly higher risk of recurrence (p < 0.05). Conversely, co-occurrence of BRAF and TERT was present in only 5 of 102 (5%) patients presenting with early-stage WDTC. Compared to early-stage WDTC, co-occurrence of BRAF and TERT mutations are common in locally advanced (T4) thyroid cancer and are associated with an increased risk of recurrence. This knowledge may help predict aggressive behavior pretreatment and inform perioperative decision-making.
Protopanaxadiol ginsenoside Rd protects against NMDA receptor-mediated excitotoxicity by attenuating calcineurin-regulated DAPK1 activity
Authors: Zhang Chen , Liu Xuedong , Xu Hui , Hu Gengyao , Zhang Xiao , Xie Zhen , Feng Dongyun , Wu Rui , Zhao Gang , Shi Ming
Published: May 2020

Neuroprotective strategies in the treatment of stroke have been attracting a great deal of attentions. Our previous clinical and basic studies have demonstrated that protopanaxadiol ginsenoside-Rd (Rd), a monomer compound extracted fromPanax ginsengorPanax notoginseng, has neuroprotective effects against ischemic stroke, probably due to its ability to block Ca2+overload, an usual consequence of the overactivation of NMDA receptor (NMDAR). As an extending study, we explored here whether Rd exerted its neuroprotection as a novel NMDAR blocker. Our whole-cell patch-clamp results showed that Rd reduced NMDAR currents of cultured rat cortical neurons (EC50 = 7.7 μM) dose-dependently by acting on extrasynaptic NMDAR NR2b subunit. However, unexpectedly, cell transfection and radioligand binding assays revealed that Rd did not bind to the NMDAR channel directly. Alternatively, it inhibited the phosphorylation of NR2b at Ser-1303, a target of death associated protein kinase 1 (DAPK1). Moreover, cell-based and cell-free enzymatic assays showed that Rd did not inhibit the activity of DAPK1 directly, but blocked the activity of calcineurin, a key phosphatase for activating DAPK1. Importantly, other protopanaxadiol ginsenosides were also found to have potential inhibitory effects on calcineurin activity. Furthermore, as expected, calcineurin inhibition by cyclosporin A could mimic Rd’s effects and protect against NMDA-, oxygen glucose deprivation- or transient ischemic stroke-induced neuronal injury. Therefore, our present study provided the first evidence that Rd could exert an inhibitive effect on NMDAR-triggered currents and sequential excitotoxicity through mitigation of DAPK1-mediated NR2b phosphorylation by attenuating calcineurin activity.
Atypical chemokine receptor ACKR2-V41A has decreased CCL2 binding, scavenging, and activation, supporting sustained inflammation and increased Alzheimer’s disease risk
Authors: Murcia Josue D. Gonzalez , Weinert Allen , Freitas Claudia M. Tellez , Arens Daniel K. , Ferrel Meganne N. , Grose Julianne H. , Ridge Perry G. , Wilson Eric , Kauwe John S. K. , Weber K. Scott
Published: May 2020

A recent genome-wide association study (GWAS) of 59 cerebrospinal fluid (CSF) proteins with a connection to Alzheimer’s disease (AD) demonstrated an association between increased levels of chemokine ligand 2 (CCL2) with an atypical chemokine receptor chemokine-binding protein 2 variant V41A (ACKR2-V41A; rs2228467). High levels of CCL2 are associated with increased risk of AD development as well as other inflammatory diseases. In this study we characterized the biological function of the ACKR2-V41A receptor compared to the wild type allele by measuring its ligand binding affinity, CCL2 scavenging efficiency, and cell activation sensitivity. We transfected Chinese hamster ovary cells with plasmids carrying wild type ACKR2 (ACKR2-WT) or the mutant ACKR2-V41A receptor. Binding affinity assays showed that ACKR2-V41A has a lower binding affinity for CCL2 and CCL4 than ACKR2-WT. CCL2 scavenging results aligned with binding affinity assays, with ACKR2-V41A cells scavenging CCL2 with a lower efficiency than ACKR2-WT. Cell activation assays also showed that ACKR2-V41A cells had significantly lower receptor upregulation (β-Arrestin-dependent signaling pathway) upon stimulation compared to ACKR2-WT cells. These findings provide molecular and biological mechanistic insights into the GWAS association of ACKR2-V41A with increased levels of CCL2 in CSF and possibly other chemokine ligands. Increased CCL2 levels are associated with accelerated cognitive decline and increased risk of AD. Understanding how this atypical chemokine receptor allele increases serum markers of inflammation could lead to novel therapeutic solutions for AD.
Tuning Penta-Graphene Electronic Properties Through Engineered Line Defects
Authors: Santos Ramiro Marcelo dos , Sousa Leonardo Evaristo de , Galvão Douglas Soares , Ribeiro Luiz Antonio
Published: May 2020

Penta-graphene is a quasi-two-dimensional carbon allotrope consisting of a pentagonal lattice in which both sp2 and sp3-like carbons are present. Unlike graphene, penta-graphene exhibits a non-zero bandgap, which opens the possibility of its use in optoelectronic applications. However, as the observed bandgap is large, gap tuning strategies such as doping are required. In this work, density functional theory calculations are used to determine the effects of the different number of line defects of substitutional nitrogen or silicon atoms on the penta-graphene electronic behavior. Our results show that this doping can induce semiconductor, semimetallic, or metallic behavior depending on the doping atom and targeted hybridization (sp2 or sp3-like carbons). In particular, we observed that nitrogen doping of sp2-like carbons atoms can produce a bandgap modulation between semimetallic and semiconductor behavior. These results show that engineering line defects can be an effective way to tune penta-graphene electronic behavior.
Intraovarian injection of mesenchymal stem cells improves oocyte yield and in vitro embryo production in a bovine model of fertility loss
Authors: Malard Patricia F. , Peixer Mauricio A. S. , Grazia Joao G. , Brunel Hilana dos Santos Sena , Feres Luiz F. , Villarroel Carla L. , Siqueira Luiz G. B. , Dode Margot A. N. , Pogue Robert , Viana Joao Henrique M. , Carvalho Juliana L.
Published: May 2020

Valuable female cattle are continuously subject to follicular puncture (ovum pick-up - OPU). This technique is commonly used for in-vitro embryo production, but may result in ovarian lesion. Mesenchymal stem cells (MSC) ameliorate the function of injured tissues, but their use to treat ovarian lesions in cattle has not been established. We investigated whether a local injection of MSC would reduce the negative effects of repeated OPU under acute and chronic scenarios in bovines. First, we performed four OPU sessions and injected 2.5 × 106 MSCs immediately after the 4th OPU procedure (n = 5). The treated organs (right ovary) were compared to their saline-treated counterparts (left), and presented superior production of oocytes and embryos in the three following OPU sessions (P < 0.05). Then, cows with progressive fertility loss went through three OPU sessions. Animals received MSC, saline, or MSC + FSH in both ovaries after the first OPU. In the two following OPU sessions, the MSC and MSC + FSH - treated groups failed to present any significant alteration in the number of oocytes and embryos compared to saline-treated animals. Thus, MSC have beneficial effects on the fertility of OPU-lesioned cows, but not in cows with cystic ovarian disease and chronic ovarian lesions.
AxoNet: A deep learning-based tool to count retinal ganglion cell axons
Authors: Ritch Matthew D. , Hannon Bailey G. , Read A. Thomas , Feola Andrew J. , Cull Grant A. , Reynaud Juan , Morrison John C. , Burgoyne Claude F. , Pardue Machelle T. , Ethier C. Ross
Published: May 2020

In this work, we develop a robust, extensible tool to automatically and accurately count retinal ganglion cell axons in optic nerve (ON) tissue images from various animal models of glaucoma. We adapted deep learning to regress pixelwise axon count density estimates, which were then integrated over the image area to determine axon counts. The tool, termed AxoNet, was trained and evaluated using a dataset containing images of ON regions randomly selected from whole cross sections of both control and damaged rat ONs and manually annotated for axon count and location. This rat-trained network was then applied to a separate dataset of non-human primate (NHP) ON images. AxoNet was compared to two existing automated axon counting tools, AxonMaster and AxonJ, using both datasets. AxoNet outperformed the existing tools on both the rat and NHP ON datasets as judged by mean absolute error, R2 values when regressing automated vs. manual counts, and Bland-Altman analysis. AxoNet does not rely on hand-crafted image features for axon recognition and is robust to variations in the extent of ON tissue damage, image quality, and species of mammal. Therefore, AxoNet is not species-specific and can be extended to quantify additional ON characteristics in glaucoma and potentially other neurodegenerative diseases.
Mammalian CBX7 isoforms p36 and p22 exhibit differential responses to serum, varying functions for proliferation, and distinct subcellular localization
Authors: Cho Kyu-Won , Andrade Mark , Zhang Yu , Yoon Young-sup
Published: May 2020

CBX7 is a polycomb group protein, and despite being implicated in many diseases, its role in cell proliferation has been controversial: some groups described its pro-proliferative properties, but others illustrated its inhibitory effects on cell growth. To date, the reason for the divergent observations remains unknown. While several isoforms for CBX7 were reported, no studies investigated whether the divergent roles of CBX7 could be due to distinct functions of CBX7 isoforms. In this study, we newly identified mouse CBX7 transcript variant 1 (mCbx7v1), which is homologous to the human CBX7 gene (hCBX7v1) and is expressed in various mouse organs. We revealed that mCbx7v1 and hCBX7v1 encode a 36 kDa protein (p36CBX7) whereas mCbx7 and hCBX7v3 encode a 22 kDa protein (p22CBX7). This study further demonstrated that p36CBX7 was localized to the nucleus and endogenously expressed in proliferating cells whereas p22CBX7 was localized to the cytoplasm, induced by serum starvation in both human and mouse cells, and inhibited cell proliferation. Together, these data indicate that CBX7 isoforms are localized in different locations in a cell and play differing roles in cell proliferation. This varying function of CBX7 isoforms may help us understand the distinct function of CBX7 in various studies.
Oxidosqualene cyclases involved in the biosynthesis of triterpenoids in Quercus suber cork
Authors: Busta Lucas , Serra Olga , Kim Ok Tae , Molinas Marisa , Peré-Fossoul Irene , Figueras Mercè , Jetter Reinhard
Published: May 2020

Cork is a water-impermeable, suberin-based material harboring lignin, (hemi)cellulose, and extractable small molecules (primarily triterpenoids). Extractables strongly influence the properties of suberin-based materials. Though these previous findings suggest a key role for triterpenoids in cork material quality, directly testing this idea is hindered in part because it is not known which genes control cork triterpenoid biosynthesis. Here, we used gas chromatography and mass spectrometry to determine that the majority (>85%) of non-polar extractables from cork were pentacyclic triterpenoids, primarily betulinic acid, friedelin, and hydroxy-friedelin. In other plants, triterpenoids are generated by oxidosqualene cyclases (OSCs). Accordingly, we minedQuercus suberEST libraries for OSC fragments to use in a RACE PCR-based approach and cloned three full-length OSC transcripts from cork (QsOSC1-3). Heterologous expression inSaccharomyces cerevisiaerevealed thatQsOSC1-3respectively encoded enzymes with lupeol synthase, mixed α- and β-amyrin synthase, and mixed β-amyrin and friedelin synthase activities. These activities together account for the backbone structures of the major cork triterpenoids. Finally, we analyzed the sequences of QsOSC1-3 and other plant OSCs to identify residues associated with specific OSC activities, then combined this with analyses ofQ. subertranscriptomic and genomic data to evaluate potential redundancies in cork triterpenoid biosynthesis.
Interactions between brown planthopper (Nilaparvata lugens) and salinity stressed rice (Oryza sativa) plant are cultivar-specific
Authors: Quais Md Khairul , Munawar Asim , Ansari Naved Ahmad , Zhou Wen-Wu , Zhu Zeng-Rong
Published: May 2020

Salinity stress triggers changes in plant morphology, physiology and molecular responses which can subsequently influence plant-insect interactions; however, these consequences remain poorly understood. We analyzed plant biomass, insect population growth rates, feeding behaviors and plant gene expression to characterize the mechanisms of the underlying interactions between the rice plant and brown planthopper (BPH) under salinity stress. Plant bioassays showed that plant growth and vigor losses were higher in control and low salinity conditions compared to high salinity stressed TN1 (salt-planthopper susceptible cultivar) in response to BPH feeding. In contrast, the losses were higher in the high salinity treated TPX (salt-planthopper resistant cultivar). BPH population growth was reduced on TN1, but increased on TPX under high salinity condition compared to the control. This cultivar-specific effect was reflected in BPH feeding behaviors on the corresponding plants. Quantification of abscisic acid (ABA) and salicylic acid (SA) signaling transcripts indicated that salinity-induced down-regulation of ABA signaling increased SA-dependent defense in TN1. While, up-regulation of ABA related genes in salinity stressed TPX resulted in the decrease in SA-signaling genes. Thus, ABA and SA antagonism might be a key element in the interaction between BPH and salinity stress. Taken together, we concluded that plant-planthopper interactions are markedly shaped by salinity and might be cultivar specific.
Reorganization of theta phase-locking in the orbitofrontal cortex drives cocaine choice under the influence
Authors: Guillem Karine , Ahmed Serge H.
Published: May 2020

Cortical theta oscillations of neuronal activity are a fundamental mechanism driving goal-directed behavior. We previously identified in the rat orbitofrontal cortex (OFC) a neuronal correlate of individual preferences between cocaine use and an alternative nondrug reward (i.e. saccharin). Whether theta oscillations are also associated with choice behavior between a drug and a nondrug reward remains unknown. Here we investigated the temporal structure between single unit activity and theta band oscillations (4–12 Hz) in the OFC of rats choosing between cocaine and saccharin. First, we found that the relative amplitude of theta oscillations is associated with subjective value and preference between two rewards. Second, OFC phase-locked neurons fired on opposite phase of the theta oscillation during saccharin and cocaine rewards, suggesting the existence of two separable neuronal assemblies. Finally, the pharmacological influence of cocaine at the moment of choice altered both theta band power and theta phase-locking in the OFC. That is, this drug influence shifted spike-phase relative to theta cycle and decreased the synchronization of OFC neurons relative to the theta oscillation. Overall, this study indicates that the reorganization of theta phase-locking under the influence of cocaine biases OFC neuronal assemblies in favor of cocaine choice and at the expense of a normally preferred alternative, a neuronal change that may contribute to drug preference in cocaine addiction.
Identification of candidate chromosome region of Sbwm1 for Soil-borne wheat mosaic virus resistance in wheat
Authors: Liu Shubing , Bai Guihua , Lin Meng , Luo Mingcheng , Zhang Dadong , Jin Feng , Tian Bin , Trick Harold N. , Yan Liuling
Published: May 2020

Soil-borne wheat mosaic virus (SBWMV) causes a serious viral disease that can significantly reduce grain yield in winter wheat worldwide. Using resistant cultivars is the only feasible strategy to reduce the losses caused by SBWMV. To fine map the resistance gene Sbwm1, 205 wheat accessions was genotyped using wheat Infinium iSelect Beadchips with 90 K SNPs. Association analysis identified 35 SNPs in 12 wheat genes and one intergenic SNP in the Sbwm1 region that showed a significant association with SBWMV resistance. Those SNPs were converted into Kompetitive Allele-Specific Polymerase assays (KASP) and analyzed in two F6-derived recombinant inbred line (RIL) populations derived from the crosses between two resistant cultivars ‘Wesley’ and ‘Deliver’ and a susceptible line ‘OK03825-5403-6’. Linkage analysis mapped this gene on chromosome 5D at intervals of 5.1 cM and 3.4 cM in the two populations, respectively. The two flanking markers in both populations delimited the gene to a 620 kb region where 19 genes were annotated. Comparative analysis identified a syntenic region of 660 kb in Ae. tauschii with 18 annotated genes and a syntenic region in chromosome 1 of B. distachyon. The candidate region includes several disease resistance related genes and we identified a PTI1-like tyrosine-protein kinase 1 gene as a putative candidate gene for Sbwm1. The two flanking SNPs for Sbwm1 can effectively separate the resistant and susceptible lines in a new diversity panel of 159 wheat germplasm. The results from this study lay a solid foundation for the cloning, functional characterization and marker-assisted selection of Sbwm1.
Development of novel detection system for sweet potato leaf curl virus using recombinant scFv
Authors: Cho Sang-Ho , Kil Eui-Joon , Cho Sungrae , Byun Hee-Seong , Kang Eun-Ha , Choi Hong-Soo , Lee Mi-Gi , Lee Jong Suk , Lee Young-Gyu , Lee Sukchan
Published: May 2020

Sweet potato leaf curl virus (SPLCV) causes yield losses in sweet potato cultivation. Diagnostic techniques such as serological detection have been developed because these plant viruses are difficult to treat. Serological assays have been used extensively with recombinant antibodies such as whole immunoglobulin or single-chain variable fragments (scFv). An scFv consists of variable heavy (VH) and variable light (VL) chains joined with a short, flexible peptide linker. An scFv can serve as a diagnostic application using various combinations of variable chains. Two SPLCV-specific scFv clones, F7 and G7, were screened by bio-panning process with a yeast cell which expressed coat protein (CP) of SPLCV. The scFv genes were subcloned and expressed in Escherichia coli. The binding affinity and characteristics of the expressed proteins were confirmed by enzyme-linked immunosorbent assay using SPLCV-infected plant leaves. Virus-specific scFv selection by a combination of yeast-surface display and scFv-phage display can be applied to detection of any virus.