bluuebunny/crossref_metadata_2025 huggingface dataset:
Motivating Public Employees
Authors: Esteve Marc , Schuster Christian
Published: June 2019

What motivates public employees to work hard? This Element systematically reviews answers from public administration research. The authors locate this research in a novel two-dimensional typology, which shows that public employees can be motivated for other- and self-interested reasons and extrinsic (motivated by outcomes) and intrinsic (motivated by work itself) reasons. Public administration research sheds significant light on extrinsic motivators: working hard to help society (public service motivation), one's organization (organizational commitment) and oneself (financial incentives). Future research should focus on hitherto understudied motivators: symbolic rewards and intrinsic motivators, such as enjoyable work tasks, warm glow, and relatedness with colleagues. Supplementary material for this Element is available online.
Promoting voter registration: the effects of low-cost interventions on behaviour and norms
Authors: KÖLLE FELIX , LANE TOM , NOSENZO DANIELE , STARMER CHRIS
Published: June 2019

We report two studies investigating whether, and if so how, different low-cost interventions affect voter registration rates. Low-cost message-based interventions are increasingly used to promote target behaviours. While growing evidence shows that such ‘nudges’ often significantly impact behaviour, understanding of why interventions work or fail in particular contexts remains underdeveloped. In a natural field experiment conducted before the 2015 UK general election, we varied messages on a postcard sent by Oxford City Council to unregistered students encouraging them to join the electoral register. Our primary finding from the field study is that just one of our interventions – a reminder that people failing to register may be fined – has a significant positive impact. Offering small monetary rewards to register instead has a negative but insignificant effect. In a second study, using an online experiment we identify a particular mechanism explaining the influence of this intervention. Specifically, we show that our interventions have divergent effects on perceptions of the normative appropriateness of registering: emphasising that failing to register is punishable by law strengthened the perception that one ought to register, while offering monetary inducements for registering weakened the perception that doing so is an action already expected within society.
Nominal speech act structure: Evidence from the structural deficiency of impersonal pronouns
Authors: Ritter Elizabeth , Wiltschko Martina
Published: June 2019

In this paper, we propose that there is a speech-act structure in the nominal spine, just as there is in the clausal spine. Its function is to encode what we do when we utter a nominal: that is, we name, describe, or track individuals. Thus, speech-act structure establishes a link between the discourse referent and the speech-act situation. The evidence we discuss comes from nominals that lack this speech-act structure, namely impersonal pronouns. We argue that impersonal pronouns have in common that they lack nominal speech-act structure but are not otherwise a natural class: they vary in syntactic structure. Thus, we propose a novel formal typology of impersonal pronouns.
Addressing Disease-Related Stigma During Infectious Disease Outbreaks
Authors: Fischer Leah S. , Mansergh Gordon , Lynch Jonathan , Santibanez Scott
Published: June 2019

Outbreaks of emerging infectious disease are a constant threat. In the last 10 years, there have been outbreaks of 2009 influenza A (H1N1), Ebola virus disease, and Zika virus. Stigma associated with infectious disease can be a barrier to adopting healthy behaviors, leading to more severe health problems, ongoing disease transmission, and difficulty controlling infectious disease outbreaks. Much has been learned about infectious disease and stigma in the context of nearly 4 decades of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome pandemic. In this paper, we define stigma, discuss its relevance to infectious disease outbreaks, including how individuals and communities can be affected. Adapting lessons learned from the rich literature on HIV-related stigma, we propose a strategy for reducing stigma during infectious disease outbreaks such as Ebola virus disease and Zika virus. The implementation of brief, practical strategies such as the ones proposed here might help reduce stigma and facilitate more effective control of emerging infectious diseases.
Adapting culturally appropriate mental health screening tools for use among conflict-affected and other vulnerable adolescents in Nigeria
Authors: Kaiser B. N. , Ticao C. , Anoje C. , Minto J. , Boglosa J. , Kohrt B. A.
Published: June 2019

Background

The Boko Haram insurgency has brought turmoil and instability to Nigeria, generating a large number of internally displaced people and adding to the country's 17.5 million orphans and vulnerable children. Recently, steps have been taken to improve the mental healthcare infrastructure in Nigeria, including revamping national policies and initiating training of primary care providers in mental healthcare. In order for these efforts to succeed, they require means for community-based detection and linkage to care. A major gap preventing such efforts is the shortage of culturally appropriate, valid screening tools for identifying emotional and behavioral disorders among adolescents. In particular, studies have not conducted simultaneous validation of screening tools in multiple languages, to support screening and detection efforts in linguistically diverse populations. We aim to culturally adapt screening tools for emotional and behavioral disorders for use among adolescents in Nigeria, in order to facilitate future validation studies.

Methods

We used a rigorous mixed-method process to culturally adapt the Depression Self Rating Scale, Child PTSD Symptom Scale, and Disruptive Behavior Disorders Rating Scale. We employed expert translations, focus group discussions (N= 24), and piloting with cognitive interviewing (N= 24) to achieve semantic, content, technical, and criterion equivalence of screening tool items.

Results

We identified and adapted items that were conceptually difficult for adolescents to understand, conceptually non-equivalent across languages, considered unacceptable to discuss, or stigmatizing. Findings regarding problematic items largely align with existing literature regarding cross-cultural adaptation.

Conclusions

Culturally adapting screening tools represents a vital first step toward improving community case detection.
Fertilizer Requirements of Rice on the Murrumbidgee Irrigation Area of New South Wales: The Importance of the Rice-Pasture Rotation
Authors: Boerema E. B. , D. J. McDonald
Published: June 2019

Nitrogen is the most important, and usually the only, nutrient necessary for high yields of rice in the South Western Riverina of N.S.W. Inclusion of a legume pasture phase in the rotation is a very effective method of improving the nitrogen status of the soil, but small additions of artificial fertilizer at sowing may still be necessary for maximum yields. The addition of phosphatic fertilizers is rarely necessary, except on a few isolated virgin soils, and where pastures are included in the rotation ample phosphate for the rice crop is usually present as a residue from topdressing. Potash and trace-elements do not improve rice yields in this area.
The United Nations in West Irian: A Critique
Authors: van der Veur Paul W.
Published: June 2019

UNTEA served the important function of buffer between contending forces and in general accomplished a remarkably smooth transfer. In this regard the United Nations operation was a major success. The smooth transfer was achieved, however, at the cost of rights specifically guaranteed in the agreement—the rights of free speech and assembly. Furthermore, the United Nations preparatory task and responsibility in the future “act of self-determination” was minimized.

It may be argued that UNTEA policy in West Irian merely reflects the weakness of the United Nations in a nation-state world. Lack of UNTEA power certainly was an important aspect. The explanation, however, is more complex. It is significant to recall that the United Nations assumed its task under severe handicaps: It was given no time for adequate recruitment and preparation; from the start it was confronted with the legitimized presence of Indonesian troops; the status of the “Papuan flag” was never mentioned in the agreement; and general Papuan primitivity along with political naïveté and schisms among the small and newly created Papuan élite influenced UNTEA's approach.

UNTEA also met continuous Indonesian pressure aimed at shortening the period of its administration and weakening its authority in general. Statements by Indonesian officials cast doubt on Indonesia's willingness to adhere to the wording of the agreement. In trying to interpret Indonesian feelings it might be conceded that most Dutch-Indonesian agreements have imposed conditions which could be considered obnoxious to Indonesia. The rights of self-determination for the Papuan inhabitants—stipulated in the August 15 agreement—fall into this category.
Bioactive peptides from milk: animal determinants and their implications in human health
Authors: Vargas-Bello-Pérez Einar , Márquez-Hernández Roberto I. , Hernández-Castellano Lorenzo E.
Published: June 2019

Milk is an important protein source in human diets, providing around 32 g protein/l (for bovine milk, which constitutes some 85% of global consumption). The most abundant milk proteins are α-lactalbumin, β-lactoglobulin, αs-casein, β-casein, and κ-casein. Besides their nutritional value, milk proteins play a crucial role in the processing properties of milk, such as solubility, water bonding, heat stability, renneting and foaming, among others. In addition, and most importantly for this review, these proteins are the main source of bioactive components in milk. Due to the wide range of proposed beneficial effects on human health, milk proteins are considered as potential ingredients for the production of health-promoting functional foods. However, most of the evidence for bioactive effects comes from in vitro studies, and there is a need for further research to fully evaluate the true potential of milk-derived bioactive factors. Animal genetics and animal nutrition play an important role in the relative proportions of milk proteins and could be used to manipulate the concentration of specific bioactive peptides in milk from ruminants. Unfortunately, only a few studies in the literature have focused on changes in milk bioactive peptides associated to animal genetics and animal nutrition. The knowledge described in the present review may set the basis for further research and for the development of new dairy products with healthy and beneficial properties for humans.
Is association of preterm birth with cognitive-neurophysiological impairments and ADHD symptoms consistent with a causal inference or due to familial confounds?
Authors: James Sarah-Naomi , Rommel Anna-Sophie , Rijsdijk Fruhling , Michelini Giorgia , McLoughlin Gráinne , Brandeis Daniel , Banaschewski Tobias , Asherson Philip , Kuntsi Jonna
Published: June 2019

Background

Preterm birth is associated with an increased risk for cognitive-neurophysiological impairments and attention-deficit/hyperactivity disorder (ADHD). Whether the associations are due to the preterm birth insult per se, or due to other risk factors that characterise families with preterm-born children, is largely unknown.

Methods

We employed a within-sibling comparison design, using cognitive-performance and event-related potential (ERP) measures from 104 preterm-born adolescents and 104 of their term-born siblings. Analyses focused on ADHD symptoms and cognitive and ERP measures from a cued continuous performance test, an arrow flanker task and a reaction time task.

Results

Within-sibling analyses showed that preterm birth was significantly associated with increased ADHD symptoms (β = 0.32, p = 0.01, 95% CI 0.05 to 0.58) and specific cognitive-ERP impairments, such as IQ (β = −0.20, p = 0.02, 95% CI −0.40 to −0.01), preparation-vigilance measures and measures of error processing (ranging from β = 0.71, −0.35). There was a negligible within-sibling association between preterm birth with executive control measures of inhibition (NoGo-P3, β = −0.07, p = 0.45, 95% CI −0.33 to 0.15) or verbal working memory (digit span backward, β = −0.05, p = 0.63, 95% CI −0.30 to 0.18).

Conclusions

Our results suggest that the relationship between preterm birth with ADHD symptoms and specific cognitive-neurophysiological impairments (IQ, preparation-vigilance and error processing) is independent of family-level risk and consistent with a causal inference. In contrast, our results suggest that previously observed associations between preterm birth with executive control processes of inhibition and working memory are instead linked to background characteristics of families with a preterm-born child rather than preterm birth insult per se. These findings suggest that interventions need to target both preterm-birth specific and family-level risk factors.
Technology and the Spirit of Man
Authors: Berrigan Daniel
Published: June 2019

Men have invariably gone forward in history with the assumption that violent shifts in their relation to the world, or in their relations to other men, were subject to a limiting principle: to critique, to reason, to the review of memory. Barely during the event, more frequently after violence has spent itself, revolutions in the physical and moral order were understood to be subject to the judgment of the community that has brought them to pass, or of the civilized community as a whole. Revolutions brought new freedom in their wake, or they suppressed freedom; thev opened new geographical and spiritual horizons, or they cut them down. Sometimes the revolutions were predictable, often they were contained.
The intergenerational transmission of childhood maltreatment: Nonspecificity of maltreatment type and associations with borderline personality pathology
Authors: Paul Sarah E. , Boudreaux Michael J. , Bondy Erin , Tackett Jennifer L. , Oltmanns Thomas F. , Bogdan Ryan
Published: June 2019

One generation's experience of childhood maltreatment is associated with that of the next. However, whether this intergenerational transmission is specific to distinct forms of maltreatment and what factors may contribute to its continuity remains unclear. Borderline personality pathology is predicted by childhood maltreatment and characterized by features (e.g., dysregulated emotion, relationship instability, impulsivity, and inconsistent appraisals of others) that may contribute to its propagation. Among 364 older adults and 573 of their adult children (total n = 937), self-reported exposure to distinct forms of childhood maltreatment (i.e., emotional, physical, and sexual abuse, and emotional and physical neglect as assessed by the Childhood Trauma Questionnaire) showed homotypic and heterotypic associations across generations with little evidence that latent factors unique to specific forms of maltreatment show generational continuity. General nonspecific indices of childhood maltreatment showed evidence of intergenerational transmission after accounting for demographic factors and parent socioeconomic status (b = 0.126, p = 9.21 × 10−4). This continuity was partially mediated by parental borderline personality pathology (assessed longitudinally through a variety of measures and sources, indirect effect: b = 0.031, 95% confidence interval [0.003, 0.060]). The intergenerational continuity of childhood maltreatment may largely represent general risk for nonspecific maltreatment that may, in part, be propagated by borderline personality pathology and/or shared risk factors.
Exploring the Ingredients of Success: Studying Trajectories of the Vulnerable Unemployed Who Have Entered Work or Education in Denmark
Authors: Danneris Sophie , Caswell Dorte
Published: June 2019

When looking at clients with a long history of unemployment and substantial health and/or social problems, stories of success (in terms of moving from being on cash benefits to getting a job) are limited. Thus, when a client does manage to gain employment or enter education, it represents an unusual1story of success seen from a political, organisational and individual perspective. In this article, we investigate empirically what can be learnt about current active labour market policies from these client cases. Methodologically this is explored through interviews with former clients who have managed to find a job despite dealing with complex health or social issues, and interviews with their former caseworkers. Thus, the article aims to provide insights into the crucial elements in making the move from vulnerable unemployed to being ready for a job, as well as finding it and keeping it.
Education and Pleasure in the Early Church: Perspectives from East and West
Authors: Ludlow Morwenna , Lunn-Rockliffe Sophie
Published: June 2019

Early Christian teachers and preachers were often cautious about, if not suspicious of, pleasure, but they also had a lively awareness of the psychological aspects of pedagogy, and of the power of pleasure and delight to persuade, move, instruct and even convert. This article explores the treatment of pleasure as a pedagogical tool, tracing this subject through the lens of sermons, letters, treatises and poetry written in Latin and Greek and drawing out both classical and biblical themes. It notes that, while most of the authors considered acknowledge pleasure as a potential problem in pedagogy, it is a problem they attempt to navigate. The article sketches out various approaches to the problem, noting especially the pleasure involved in reading, performing and expounding Scripture; pleasure used as a conscious educational strategy; and discussions which weigh up the dangers and gains of pleasure in education.
Nature and Nurture in the Early Quaker Movement: Creating the Next Generation of Friends
Authors: Walsham Alexandra
Published: June 2019

This article explores the place of education within the early Quaker movement in England. It examines how Quaker attitudes towards human nature shaped their views on the role of nurture in the creation of a community of believers, and probes the theological assumptions that underpinned this, notably their repudiation of conventional Protestant ideas about original sin and predestination. It also traces the evolution of Quaker views on spiritual direction in domestic and institutional settings against the backdrop of the transformation of the Society of Friends from a radical evangelical sect to a more sober and disciplined movement in the later seventeenth century. Particular attention is paid to the part that education played in ensuring that Quakerism was passed down to the next generation, once the heady excitement of its initial conversionary phase had waned.
Does Perceiving Discrimination Influence Partisanship among U.S. Immigrant Minorities? Evidence from Five Experiments
Authors: Hopkins Daniel J. , Kaiser Cheryl R. , Pérez Efrén O. , Hagá Sara , Ramos Corin , Zárate Michael
Published: June 2019

Perceived discrimination (PD) is reliably and strongly associated with partisan identity (PID) among US immigrant minorities such as Latinos and Asian Americans. Yet whether PD causes PID remains unclear, since it is possible that partisanship influences perceptions of discrimination or that other factors drive the observed association. Here, we assess the causal influence of group-level PD on PID using five experiments with Latino and Asian American adults. These experiments varied in important ways: they took place inside and outside the lab, occurred prior to and during Donald Trump’s presidential campaign, and tested different manifestations of PD and partisan attitudes (total n = 2,528). These efforts point to a simple but unexpected conclusion: our experiments and operationalizations do not support the claim that group-targeted PD directly causes PID. These results have important implications for understanding partisanship among immigrants and their co-ethnics and the political incorporation of Latinos and Asian Americans.
Evaluation of the Stationarity Assumption for Meteorological Drought Risk Estimation at the Multidecadal Scale in Contiguous United States
Authors: Apurv Tushar , Cai Ximing
Published: June 2019

In this study, we analyze the nonstationarity in meteorological droughts at the multidecadal scale in different parts of the contiguous United States during 1901–2017. We develop metrics to compare the drought risk calculated under the assumptions of stationarity and nonstationarity and identify their spatial and temporal patterns. By analyzing the variability of drought risk in the past and exploring its ongoing patterns, we evaluate in which regions of the contiguous United States the assumption of stationarity can be safely used for drought risk planning and management. We find statistically significant interdecadal changes in the probability distribution functions of drought severity in parts of the Northwest, upper Midwest, the Northeast, eastern parts of Great Plains and in parts of Arizona, New Mexico, Utah, and Nevada in the Southwest. In these regions, the nonstationary risk has been significantly higher than the stationary estimate of risk in the past, which shows that the assumption of stationarity can lead to the underestimation of drought risk in these regions. The multidecadal drought risk shows low variability in California, parts of northern and western Great Plains, Ohio Valley, and in the Southeast, since the statistical properties of droughts have not changed significantly in these regions during 1901–2017. However, the meteorological drought risk has increased in California and the Southeast in the recent decades due to the influence of global warming and hence the assumption of stationarity for risk estimation may lead to underestimation of drought risk in future in these regions if this effect of global warming persists.
Targeting EZH2 histone methyltransferase activity alleviates experimental intestinal inflammation
Authors: Zhou Jie , Huang Shuo , Wang Zhongyu , Huang Jiani , Xu Liang , Tang Xuefeng , Wan Yisong Y. , Li Qi-jing , Symonds Alistair L. J. , Long Haixia , Zhu Bo
Published: June 2019

Enhancer of zeste homolog 2 (EZH2)-mediated trimethylation of histone 3 lysine 27 (H3K27Me3) is critical for immune regulation. However, evidence is lacking to address the effect of EZH2 enzyme’s activity on intestinal immune responses during inflammatory bowel disease (IBD). Here we report that suppressing EZH2 activity ameliorates experimental intestinal inflammation and delayed the onset of colitis-associated cancer. In addition, we identified an increased number of functional MDSCs in the colons, which are essential for EZH2 inhibitor activity. Moreover, inhibition of EZH2 activity promotes the generation of MDSCs from hematopoietic progenitor cells in vitro, demonstrating a previously unappreciated role for EZH2 in the development of MDSCs. Together, these findings suggest the feasibility of EZH2 inhibitor clinical trials for the control of IBD. In addition, this study identifies MDSC-promoting effects of EZH2 inhibitors that may be undesirable in other therapeutic contexts and should be addressed in a clinical trial setting.
Ampk regulates IgD expression but not energy stress with B cell activation
Authors: Waters Lynnea R. , Ahsan Fasih M. , ten Hoeve Johanna , Hong Jason S. , Kim Diane N. H. , Minasyan Aspram , Braas Daniel , Graeber Thomas G. , Zangle Thomas A. , Teitell Michael A.
Published: June 2019

Ampk is an energy gatekeeper that responds to decreases in ATP by inhibiting energy-consuming anabolic processes and promoting energy-generating catabolic processes. Recently, we showed that Lkb1, an understudied kinase in B lymphocytes and a major upstream kinase for Ampk, had critical and unexpected roles in activating naïve B cells and in germinal center formation. Therefore, we examined whether Lkb1 activities during B cell activation depend on Ampk and report surprising Ampk activation with in vitro B cell stimulation in the absence of energy stress, coupled to rapid biomass accumulation. Despite Ampk activation and a controlling role for Lkb1 in B cell activation, Ampk knockout did not significantly affect B cell activation, differentiation, nutrient dynamics, gene expression, or humoral immune responses. Instead, Ampk loss specifically repressed the transcriptional expression of IgD and its regulator, Zfp318. Results also reveal that early activation of Ampk by phenformin treatment impairs germinal center formation but does not significantly alter antibody responses. Combined, the data show an unexpectedly specific role for Ampk in the regulation of IgD expression during B cell activation.
Classification and Temporal Variability in Urinary 8-oxodG and 8-oxoGuo: Analysis by UHPLC-MS/MS
Authors: Li Ziqi , Yao Yuan , Zhang Yanfei , Zhang Yining , Shao Yijun , Tang Chuanxi , Qu Weidong , Zhou Ying
Published: June 2019

Oxidative stress damage has been found to be associated with exposure of children to environmental pollutants, but there are few data on the variability of urinary oxidative stress biomarkers and the accuracy of biomarker concentration classification. We performed a longitudinal study in Chinese school-aged children to investigate the variability of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) concentrations and the ability of a single first morning urine sample to assess accuracy and sensitivity of biomarkers concentration classification. After adjusting for both creatinine and specific gravity, we characterized the distribution and reproducibility of repeated measurement of 8-oxodG and 8-oxoGuo by using intraclass correlation coefficients (ICCs) derived from linear mixed model and performed surrogate category analyses to determine whether a single spot sample could accurately classify 8-oxodG and 8-oxoGuo levels. Results indicated that the geometric mean (GM) concentrations of 8-oxodG and 8-oxoGuo were 3.865 ng/mL and 5.725 ng/mL, respectively. High variability of 8-oxodG and 8-oxoGuo was observed in the single spot first morning urine sample (ICC = 0.25 and 0.18, respectively). Three repeated urinary specimens achieved sensitivity of 0.87 for 8-oxodG and 0.83 for 8-oxoGuo in low tertile and sensitivity of 0.78 in high tertile. But classification in medium tertile was less accurate for both 8-oxodG and 8-oxoGuo. In conclusion, high variability of urinary 8-oxodG and 8-oxoGuo levels results in repeated samplings needed for accurate classification.
Measurement of collateral perfusion in acute stroke: a vessel-encoded arterial spin labeling study
Authors: Okell Thomas W. , Harston George W. J. , Chappell Michael A. , Sheerin Fintan , Kennedy James , Jezzard Peter
Published: June 2019

Collateral perfusion is important for sustaining tissue viability in acute ischemic stroke. Conventional techniques for its visualization are invasive, require contrast agents and demonstrate collateral vessels, rather than measuring perfusion directly. In this study we utilize a non-invasive, non-contrast magnetic resonance imaging (MRI)-based method to directly quantify collateral perfusion in acute stroke patients. Vessel-encoded multi-postlabeling delay arterial spin labeling (ASL) was used to separately quantify the blood flow and blood arrival time from four arteries supplying the brain in patients presenting within 18 hours of stroke onset. Twenty-nine acute ischemic stroke patients were scanned with a median time of onset to first MRI of 3 hours. Collateral perfusion at presentation was associated with tissue fate at 1-week. It sustained tissue prior to reperfusion, but was less effective than direct blood flow at maintaining tissue viability in patients who did not reperfuse. Delay in the blood arrival around the ischemic region was found at presentation and reduced over time but was not consistently associated with collateral perfusion. Vessel-encoded multi-postlabeling delay ASL provides a non-invasive tool for direct measurement of collateral perfusion and delayed blood arrival in acute stroke patients.
Comparative genomic analysis of monosporidial and monoteliosporic cultures for unraveling the complexity of molecular pathogenesis of Tilletia indica pathogen of wheat
Authors: Mishra Pallavi , Maurya Ranjeet , Gupta Vijai K. , Ramteke Pramod W. , Marla Soma S. , Kumar Anil
Published: June 2019

Tilletia indica (Ti) - a quarantined fungal pathogen of wheat and its pathogenesis is chiefly governed by pathogen effectors secreted inside the host plant. The de novo genome sequencing of several field isolates and stages available could be used for understanding the molecular pathogenesis. The presence of gaps and low coverage of assembled genomes poses a problem in accurate functional annotation of such functions. In the present study attempts were made to improve the Ti draft genome through reconciliation of globally available datasets of three highly virulent monoteliospore cultures of Ti field isolates. It has sequence depth of 107x and N50 scaffold size of 80,772 (more than 26 times as large as achieved in the draft assembly) with highest sequence contiguity, more accurate and nearly complete. Functional annotation revealed that Ti genome contains 9209 genes evolved with many expanded gene families and arranged mostly in a cluster. About 79% of Ti genes were orthologous to other basidiomycetes fungi, Around 7.93% proteins were having secretary signals and 6.66% were identified as highly virulent pathogenicity genes. Using improved Ti genome as a reference, the genomic variation was assessed with respect to repeats, SNPs/InDel, gene families and correct set of virulence associated genes during its life cycle. The comparative intra-species, inter-stage and inter-species genomic variation will have broader implications to understand the gene regulatory networks involved in growth, mating and virulence behaviour of Tilletia f. spp. and also for better appreciation of fungal biology and disease management.
Opposing effects of acute versus chronic inhibition of p53 on decitabine’s efficacy in myeloid neoplasms
Authors: Tamura Moe , Yonezawa Taishi , Liu Xiaoxiao , Asada Shuhei , Hayashi Yasutaka , Fukuyama Tomofusa , Tanaka Yosuke , Kitamura Toshio , Goyama Susumu
Published: June 2019

Decitabine is a DNA methyltransferase inhibitor and is considered a promising drug to treat myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) with p53 mutations. However, whether loss of p53 in fact increases the response of MDS/AML cells to decitabine remains unclear. In this study, we assessed the role of p53 in MDS and AML cells treated with decitabine using mouse models for MLL-AF9-driven AML and mutant ASXL1-driven MDS/AML. CRISPR/Cas9-mediated depletion of p53 in MDS/AML cells did not increase, but rather decreased their sensitivity to decitabine. Forced expression of a dominant-negative p53 fragment (p53DD) in these cells also decreased their responses to decitabine, confirming that acute inhibition of p53 conferred resistance to decitabine in AML and MDS/AML cells. In contrast, MLL-AF9-expressing AML cells generated from bone marrow progenitors of Trp53-deficient mice were more sensitive to decitabine in vivo than their wild-type counterparts, suggesting that long-term chronic p53 deficiency increases decitabine sensitivity in AML cells. Taken together, these data revealed a multifaceted role for p53 to regulate responses of myeloid neoplasms to decitabine treatment.
Injuries to the Stomatognathic System in Brazilian Jiu-Jitsu Athletes
Authors: Macêdo-Filho R. A. , Leal T. R. , Cardoso A. M. R. , Sarmento D. J. S. , Verli F. D. , Marinho S. A.
Published: June 2019

As a contact sport, Brazilian jiu-jitsu requires the fighter to expose his/her stomatognathic system to the adversary, making him/her more susceptible to oral and maxillofacial injuries and disorders. The aim of the present study was to determine the prevalence of injuries and disorders of the stomatognathic system and associated factors among practitioners of Brazilian jiu-jitsu. A total of 179 athletes were interviewed and submitted to a physical examination. The majority was male, in the beginner category and had participated in competitions. Athletes with more experience had a higher frequency of orofacial injuries (PR = 1.77; 95% CI: 1.01–1.38), such as oral mucous lacerations and skin abrasions in the facial region, which mainly occurred during training sessions. A mouthguard is not mandatory for the sport and many athletes (both beginners and more experienced athletes) do not use one due to difficulty breathing with the device. A prefabricated (type II) mouthguard was the most common among the athletes who used this equipment, although it does not offer adequate protection. Athletes on more advanced levels wore mouthguards significantly more often (PR = 1.96; 95% CI: 1.11–2.45). In conclusion, more experienced jiu-jitsu athletes had a higher frequency of orofacial injuries, such as lacerations and abrasions, and are more likely to wear a mouthguard. However, longitudinal studies are needed in order to assess the possible causes and risks.
An electrical characterisation methodology for identifying the switching mechanism in TiO2 memristive stacks
Authors: Michalas L. , Stathopoulos S. , Khiat A. , Prodromakis T.
Published: June 2019

Resistive random access memories (RRAMs) can be programmed to discrete resistive levels on demand via voltage pulses with appropriate amplitude and widths. This tuneability enables the design of various emerging concepts, to name a few: neuromorphic applications and reconfigurable circuits. Despite the wide interest in RRAM technologies there is still room for improvement and the key lies with understanding better the underpinning mechanism responsible for resistive switching. This work presents a methodology that aids such efforts, by revealing the nature of the resistive switching through assessing the transport properties in the non-switching operation regimes, before and after switching occurs. Variation in the transport properties obtained by analysing the current-voltage characteristics at distinct temperatures provides experimental evidence for understanding the nature of the responsible mechanism. This study is performed on prototyped device stacks that possess common Au bottom electrodes, identical TiO2 active layers while employing three different top electrodes, Au, Ni and Pt. Our results support in all cases an interface controlled transport due to Schottky emission and suggest that the acquired gradual switching originates by the bias induced modification of the interfacial barrier. Throughout this study, the top electrode material was found to play a role in determining the electroforming requirements and thus indirectly the devices’ memristive characteristics whilst both the top and bottom metal/oxide interfaces are found to be modified as result of this process.
Prior contact with permethrin decreases its irritancy at the following exposure among a pyrethroid-resistant malaria vector Anopheles gambiae
Authors: Mulatier Margaux , Pennetier Cédric , Porciani Angélique , Chandre Fabrice , Dormont Laurent , Cohuet Anna
Published: June 2019

Insecticide-treated nets (ITNs) remain major components for vector control despite the spread of resistance mechanisms among mosquito populations. Multiple exposures to pyrethroids may induce physiological and behavioral changes in mosquitoes, possibly reducing efficacy of control tools. Despite epidemiological relevance, the effects of multiple exposures to pyrethroids on their efficacy against pyrethroid-resistant mosquitoes has received little interest. In the present study, we assessed the effects of a blood-meal successfully obtained upon a permethrin-treated net on the success at taking a second blood-meal in presence of permethrin in Anopheles gambiae, carrying pyrethroid resistance alleles. We also measured the impact of exposure to permethrin on life-history traits to address the delayed efficacy of ITNs. Our results showed that females that successfully blood-fed upon a permethrin-treated net were no longer inhibited by permethrin at the following exposure. Blood-meal inhibition due to permethrin was not affected by female size nor by exposure of mothers when testing the offspring, allowing to discard the effect of genetic or physiological selection. Besides, in our assays, exposure to permethrin did not affect mosquito fecundity, fertility nor survival. These results give insights to understand the long-term efficacy of ITNs, and allow to reevaluate the criteria used when choosing compounds for fighting malaria mosquitoes.
Advanced FRET normalization allows quantitative analysis of protein interactions including stoichiometries and relative affinities in living cells
Authors: Hochreiter Bernhard , Kunze Markus , Moser Bernhard , Schmid Johannes A.
Published: June 2019

FRET (Fluorescence Resonance Energy Transfer) measurements are commonly applied to proof protein-protein interactions. However, standard methods of live cell FRET microscopy and signal normalization only allow a principle assessment of mutual binding and are unable to deduce quantitative information of the interaction. We present an evaluation and normalization procedure for 3-filter FRET measurements, which reflects the process of complex formation by plotting FRET-saturation curves. The advantage of this approach relative to traditional signal normalizations is demonstrated by mathematical simulations. Thereby, we also identify the contribution of critical parameters such as the total amount of donor and acceptor molecules and their molar ratio. When combined with a fitting procedure, this normalization facilitates the extraction of key properties of protein complexes such as the interaction stoichiometry or the apparent affinity of the binding partners. Finally, the feasibility of our method is verified by investigating three exemplary protein complexes. Altogether, our approach offers a novel method for a quantitative analysis of protein interactions by 3-filter FRET microscopy, as well as flow cytometry. To facilitate the application of this method, we created macros and routines for the programs ImageJ, R and MS-Excel, which we make publicly available.
Hes1 expression in mature neurons in the adult mouse brain is required for normal behaviors
Authors: Matsuzaki Tadanobu , Yoshihara Toru , Ohtsuka Toshiyuki , Kageyama Ryoichiro
Published: June 2019

Hes1 regulates the maintenance and proliferation of neural stem/progenitor cells as an essential effector of the Notch signaling pathway. Although Notch signaling is also involved in the functions of mature neurons in learning and memory and in the risk factors for mental disorders such as schizophrenia and bipolar disorder, the in-vivo role of Hes1 in mature neurons remains unknown. Here, we found that Hes1 is expressed by subsets of both excitatory and inhibitory neurons in the adult mouse brain, and that Hes1 expression is induced by neuronal stimulation. Furthermore, inactivation of Hes1 in excitatory neurons resulted in abnormal fear and anxiety behaviors concomitantly with higher neuronal excitability in the amygdala, while inactivation of Hes1 in inhibitory neurons resulted in increased sociability and perseverative tendencies. These results indicated that Hes1 is functionally important for normal behaviors not only in excitatory neurons but also in inhibitory neurons in the adult brain.
p38α MAPK inhibition translates to cell cycle re-entry of neonatal rat ventricular cardiomyocytes and de novo nestin expression in response to thrombin and after apex resection
Authors: Hertig Vanessa , Brezai Andra , Bergeron Alexandre , Villeneuve Louis , Gillis Marc-Antoine , Calderone Angelino
Published: June 2019

The present study tested the hypothesis that p38α MAPK inhibition leads to cell cycle re-entry of neonatal ventricular cardiomyocytes (NNVMs) and de novo nestin expression in response to thrombin and after apex resection of the neonatal rat heart. Thrombin (1 U/ml) treatment of 1-day old NNVMs did not induce cell cycle re-entry or nestin expression. Acute exposure of NNVMs to thrombin increased p38α MAPK and HSP27 phosphorylation and p38α/β MAPK inhibitor SB203580 abrogated HSP27 phosphorylation. Thrombin and SB203580 co-treatment of NNVMs led to bromodeoxyuridine incorporation and nestin expression. SB203580 (5 mg/kg) administration immediately after apex resection of 1-day old neonatal rat hearts and continued for two additional days shortened the fibrin clot length sealing the exposed left ventricular chamber. SB203580-treatment increased the density of troponin-T(+)-NNVMs that incorporated bromodeoxyuridine and expressed nuclear phosphohistone-3. Nestin(+)-NNVMs were selectively detected at the border of the fibrin clot and SB203580 potentiated the density that re-entered the cell cycle. These data suggest that the greater density of ventricular cardiomyocytes and nestin(+)-ventricular cardiomyocytes that re-entered the cell cycle after SB203580 treatment of the apex-resected neonatal rat heart during the acute phase of fibrin clot formation may be attributed in part to inhibition of thrombin-mediated p38α MAPK signalling.
Influence of the corticospinal tract wiring pattern on sensorimotor functional connectivity and clinical correlates of upper limb function in unilateral cerebral palsy
Authors: Simon-Martinez Cristina , Jaspers Ellen , Alaerts Kaat , Ortibus Els , Balsters Joshua , Mailleux Lisa , Blommaert Jeroen , Sleurs Charlotte , Klingels Katrijn , Amant Frédéric , Uyttebroeck Anne , Wenderoth Nicole , Feys Hilde
Published: June 2019

In children with unilateral cerebral palsy (uCP), the corticospinal tract (CST)-wiring patterns may differ (contralateral, ipsilateral or bilateral), partially determining motor deficits. However, the impact of such CST-wiring on functional connectivity remains unknown. Here, we explored resting-state sensorimotor functional connectivity in 26 uCP with periventricular white matter lesions (mean age (standard deviation): 12.87 m (±4.5), CST wiring: 9 contralateral, 9 ipsilateral, 6 bilateral) compared to 60 healthy controls (mean age (standard deviation): 14.54 (±4.8)), and between CST-wiring patterns. Functional connectivity from each M1 to three bilateral sensorimotor regions of interest (primary sensory cortex, dorsal and ventral premotor cortex) and the supplementary motor area was compared between groups (controls vs. uCP; and controls vs. each CST-wiring group). Seed-to-voxel analyses from bilateral M1 were compared between groups. Additionally, relations with upper limb motor deficits were explored. Aberrant sensorimotor functional connectivity seemed to be CST-dependent rather than specific from all the uCP population: in the dominant hemisphere, the contralateral CST group showed increased connectivity between M1 and premotor cortices, whereas the bilateral CST group showed higher connectivity between M1 and somatosensory association areas. These results suggest that functional connectivity of the sensorimotor network is CST-wiring-dependent, although the impact on upper limb function remains unclear.
Comparative Proteomics of Phytase-transgenic Maize Seeds Indicates Environmental Influence is More Important than that of Gene Insertion
Authors: Tan Yanhua , Zhang Jiaming , Sun Yong , Tong Zheng , Peng Cunzhi , Chang Lili , Guo Anping , Wang Xuchu
Published: June 2019

Proteomic differences were compared between phytase-transgenic (PT) maize seeds and nontransgenic (NT) maize seeds through two-dimensional electrophoresis (2-DE) with mass spectrometry (MS). When maize was grown under field conditions, 30 differentially accumulated proteins (DAPs) were successfully identified in PT seeds (PT/NT). Clusters of Orthologous Groups (COG) functional classification of these proteins showed that the largest group was associated with posttranslational modifications. To investigate the effects of environmental factors, we further compared the seed protein profiles of the same maize planted in a greenhouse or under field conditions. There were 76 DAPs between the greenhouse- and field-grown NT maize seeds and 77 DAPs between the greenhouse- and field-grown PT maize seeds However, under the same planting conditions, there were only 43 DAPs (planted in the greenhouse) or 37 DAPs (planted in the field) between PT and NT maize seeds. The results revealed that DAPs caused by environmental factors were more common than those caused by the insertion of exogenous genes, indicating that the environment has much more important effects on the seed protein profiles. Our maize seed proteomics results also indicated that the occurrence of unintended effects is not specific to genetically modified crops (GMCs); instead, such effects often occur in traditionally bred plants. Our data may be beneficial for biosafety assessments of GMCs at the protein profile level in the future.
A Novel Small RNA-Cleaving Deoxyribozyme with a Short Binding Arm
Authors: Wang Yueyao , Yang Jintao , Yuan Xin , Cao Jin , Xu Jiacui , Chaput John C. , Li Zhe , Yu Hanyang
Published: June 2019

Deoxyribozymes capable of catalyzing sequence-specific RNA cleavage have found broad applications in biotechnology, DNA computing and environmental sensing. Among these, deoxyribozyme 8–17 is the most common small DNA motif capable of catalyzing RNA cleavage. However, the extent to which other DNA molecules with similar catalytic motifs exist remains elusive. Here we report a novel RNA-cleaving deoxyribozyme called 10–12opt that functions with an equally small catalytic motif and an unusually short binding arm. This deoxyribozyme contains a 14-nucleotide catalytic core that preferentially catalyzes RNA cleavage at UN dinucleotide junctions (kobs = 0.9 h−1 for UU cleavage). Surprisingly, the left binding arm contains only three nucleotides and forms two canonical base pairs with the RNA substrate. Mutational analysis reveals that a riboguanosine residue 3-nucleotide downstream of cleavage site must not form canonical base pairing for the optimal catalysis, and this nucleobase likely participates in catalysis with its carbonyl O6 atom. Furthermore, we demonstrate that deoxyribozyme 10–12opt can be utilized to cleave certain microRNA sequences which are not preferentially cleaved by 8–17. Together, these results suggest that this novel RNA-cleaving deoxyribozyme forms a distinct catalytic structure than 8–17 and that sequence space may contain additional examples of DNA molecules that can cleave RNA at site-specific locations.