bluuebunny/crossref_metadata_2025 huggingface dataset:
Viscous placebo and carbohydrate breakfasts similarly decrease appetite and increase resistance exercise performance compared with a control breakfast in trained males
Authors: Naharudin M. N. , Adams J. , Richardson H. , Thomson T. , Oxinou C. , Marshall C. , Clayton D. J. , Mears S. A. , Yusof A. , Hulston C. J. , James L. J.
Published: March 2020

Given the common view that pre-exercise nutrition/breakfast is important for performance, the present study investigated whether breakfast influences resistance exercise performance via a physiological or psychological effect. Twenty-two resistance-trained, breakfast-consuming men completed three experimental trials, consuming water-only (WAT), or semi-solid breakfasts containing 0 g/kg (PLA) or 1·5 g/kg (CHO) maltodextrin. PLA and CHO meals contained xanthan gum and low-energy flavouring (approximately 122 kJ), and subjects were told both ‘contained energy’. At 2 h post-meal, subjects completed four sets of back squat and bench press to failure at 90 % ten repetition maximum. Blood samples were taken pre-meal, 45 min and 105 min post-meal to measure serum/plasma glucose, insulin, ghrelin, glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations. Subjective hunger/fullness was also measured. Total back squat repetitions were greater in CHO (44 (sd 10) repetitions) and PLA (43 (sd 10) repetitions) than WAT (38 (sd 10) repetitions; P < 0·001). Total bench press repetitions were similar between trials (WAT 37 (sd 7) repetitions; CHO 39 (sd 7) repetitions; PLA 38 (sd 7) repetitions; P = 0·130). Performance was similar between CHO and PLA trials. Hunger was suppressed and fullness increased similarly in PLA and CHO, relative to WAT (P < 0·001). During CHO, plasma glucose was elevated at 45 min (P < 0·05), whilst serum insulin was elevated (P < 0·05) and plasma ghrelin suppressed at 45 and 105 min (P < 0·05). These results suggest that breakfast/pre-exercise nutrition enhances resistance exercise performance via a psychological effect, although a potential mediating role of hunger cannot be discounted.
A lower Silurian (Llandovery) diplobathrid crinoid (Camerata) from mid-Wales
Authors: Fearnhead Fiona E. , Donovan Stephen K. , Botting Joseph P. , Muir Lucy A.
Published: March 2020

Early Palaeozoic crinoids are known only patchily from the British Isles except for accumulations at starfish beds. A single, exquisitely preserved crinoid is reported from the Telychian (Llandovery, Silurian) of the Pysgotwr Grits Formation of the Llangurig area, Powys, mid-Wales. This sedimentary succession is turbiditic in origin and poorly fossiliferous. The crinoid is a diplobathrid camerate,Euptychocrinus longipinnulussp. nov., preserved as an external mould without counterpart. It has a high, shuttlecock-like crown; a conical, unsculptured cup; low infrabasals; a pair of long, slender, feather-like arms on each ray, each bearing numerous long pinnules; and a heteromorphic column. Most previous reports of this genus have been from the Upper Ordovician – lower Silurian series of Laurentia; uncertainly, it is described from the Upper Ordovician deposits of Morocco (Gondwana).Euptychocrinus longipinnulusis the first Avalonian occurrence. The beautiful preservation of the arms, including cover plates of pinnules, contrasts with the proxistele, which is a series of ‘broken sticks’. This crinoid responded to an adverse environmental fluctuation, probably a turbidity current, by autotomizing the stem, but it was carried downslope and buried alive.
Over-expression of cyclo-oxygenase-2 predicts poor survival of patients with nasopharyngeal carcinoma: a meta-analysis
Authors: Sim C-C , Sim E U-H
Published: March 2020

Objectives

The conclusive prognostic significance of cyclo-oxygenase-2 has been determined in various cancers but not in nasopharyngeal carcinoma. Therefore, this study aimed to evaluate the relationship of cyclo-oxygenase-2 expression with the survival outcome and treatment response of nasopharyngeal carcinoma patients via a systematic meta-analysis approach.

Methods

A meta-analysis was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (‘PRISMA’) checklist. The primary clinical characteristics of patients, and hazard ratios with 95 per cent confidence intervals of overall survival data, were tabulated from eligible studies. The relationship of cyclo-oxygenase-2 expression with survival outcome (expressed as hazard ratio) and treatment response (expressed as odds ratio) in nasopharyngeal carcinoma patients was analysed, and explained with the aid of forest plot charts.

Results and conclusion

The pooled hazard ratio for overall survival was 2.02 (95 per cent confidence interval = 1.65–2.47). This indicates that the over-expression of cyclo-oxygenase-2 is significantly associated with the poor survival of nasopharyngeal carcinoma patients. The pooled odds ratio of 0.98 (95 per cent confidence interval = 0.27–3.49) reveals that over-expression of cyclo-oxygenase-2 was not significantly related to the treatment outcome.
A gyrokinetic model for the plasma periphery of tokamak devices
Authors: Frei B. J. , Jorge R. , Ricci P.
Published: March 2020

A gyrokinetic model is presented that can properly describe large and small amplitude electromagnetic fluctuations occurring on scale lengths ranging from the electron Larmor radius to the equilibrium perpendicular pressure gradient scale length, and the arbitrarily large deviations from thermal equilibrium that are present in the plasma periphery of tokamak devices. The formulation of the gyrokinetic model is based on a second-order accurate description of the single charged particle dynamics, derived from Lie perturbation theory, where the fast particle gyromotion is decoupled from the slow drifts assuming that the ratio of the ion sound Larmor radius to the perpendicular equilibrium pressure scale length is small. The collective behaviour of the plasma is obtained by a gyrokinetic Boltzmann equation that describes the evolution of the gyroaveraged distribution function. The collisional effects are included by a nonlinear gyrokinetic Dougherty collision operator. The gyrokinetic model is then developed into a set of coupled fluid equations referred to as the gyrokinetic moment hierarchy. To obtain this hierarchy, the gyroaveraged distribution function is expanded onto a Hermite–Laguerre velocity-space polynomial basis. Then, the gyrokinetic equation is projected onto the same basis yielding the spatial and temporal evolution of the Hermite–Laguerre expansion coefficients. A closed set of fluid equations for the lowest-order coefficients is presented. The Hermite–Laguerre projection is performed accurately at arbitrary perpendicular wavenumber values. Finally, the self-consistent evolution of the electromagnetic fields is described by a set of gyrokinetic Maxwell equations derived from a variational principle where the velocity integrals are explicitly evaluated.
Vagrant Servants as Disease Vectors: Regulation of Migrant Maidservants in Fin-de-Siècle Vienna
Authors: Natarajan Ambika
Published: March 2020

This article centers on the persistent notion that female domestics are vulnerable to prostitution. Focusing on Vienna in the last decades of the nineteenth century, the article highlights the underlying fallacies of this notion. The 1810 Vienna Servant Code created a system of policing that made it easier for officials to collect data on maidservants. Compounded by problems in classification, maidservants seemed to form a major contingent in police prostitution data. The data enabled physicians to justify extending their authority over the private lives of a swelling population of occupationally diverse working-class migrant women in fin-de-siècle Vienna.
The portrayal of elderly men and women in Hungarian television news programmes
Authors: Kovács Gábor , Aczél Petra , Bokor Tamás
Published: March 2020

Mass media research on the portrayal of older people has primarily focused on television series and advertisements. News programmes on television have received little attention. We argue that viewers perceive characters on the news as more direct and more accurate representations of social reality than fictional characters, and therefore portrayals on the news are more likely to be integrated in viewers’ stereotypes about elderly people or used as standards of comparison. In order to explore potential differences in the representation of senior men and women, we conducted a quantitative content analysis on a sample of 754 elderly people who appeared on the evening news programmes of four major Hungarian television channels with high viewership. Each character was coded in terms of 115 qualitative variables. Our results indicate that older men are portrayed significantly more often than women as affluent, elegant, knowledgeable, powerful and actively working. By contrast, women are more commonly shown as kind, family-oriented, in ordinary roles (e.g. as the ‘woman in the street’) and engaged in less-productive activities such as shopping. Based on previous research on the role of mass media in the socialisation process as well as social comparison theory, we discuss how these imbalances in the representation of older men and women may affect viewers of different age groups, genders and social status.
Problematizing EMI language policy in a transnational world
Authors: De Costa Peter I. , Green-Eneix Curtis A. , Li Wendy
Published: March 2020

Language policies generally seek to establish, regulate, and conform linguistic practices – whether explicit or implicit – that occur within an ‘authorized’ domain. While there are multiple levels (societal, institutional, and interpersonal) at which such policies are enacted (Hornberger & Johnson, 2007), academic institutions are often significant policy arbiters as they serve as crucial switchboards (Blommaert, 2010; De Costa, 2010) that connect policies at the societal and interpersonal levels. In particular, English medium of instruction (EMI) policies that mandate English as the primary means of academic content delivery have played a pivotal role in enabling universities in countries such as Bangladesh (Rahman & Mehar Singh, 2019), China (e.g., Hu, 2009; Song, 2019; Zhang, 2018), Saudi Arabia (Barnawi, 2018; Phan & Barnawi, 2015), and Vietnam (Phan, 2018) to establish themselves on the world stage and engage with the global community. Even though several scholars (e.g., Coleman, 2006; Jenkins, 2019a; Knight, 2013, 2016; Macaro et al., 2018) have investigated EMI policies across different contexts, the following central question concerning these policies still persists: in what ways has the implementation of EMI policies transformed the higher education sector, and subsequently affected primary social actors, such as students, teachers, and administrators embedded within these shifting contexts? These concerns, we posit, are amplified by the transnational movements of people and institutions (Duff, 2015) and the ever-increasing speed and agility with which TESOL as a field has to respond to the shifting tides of globalization (Barnawi, 2020). Given this conspicuous gap in an ever-evolving English language policy landscape, we set out to critically review previous works that have examined the implementation of EMI policies within atransnational higher education(TNHE) context. TNHE is characterized by the transformation of higher education across the globe (Knight, 2013; Kosmützky & Putty, 2016) as Western-based universities export models – driven by a neoliberal agenda to maximize financial profit – through the establishment of overseas branch campuses. In reviewing works that examine TNHE, we aim to stimulate dialogue on this contemporary phenomenon.
Guns and Butter in China: How Chinese Citizens Respond to Military Spending
Authors: Han Xiao , Sadler Michael , Quek Kai
Published: March 2020

Militaries are sustained by public money that is diverted away from other domestic ends. How the public react to the “guns-versus-butter” trade-off is thus an important question in understanding the microfoundations of Chinese military power. However, there are few studies on public attitudes towards military spending in China, whose rising power has been a grave concern to many policymakers around the world. We fielded a national online survey to investigate the nature of public support for military spending in China. We find that Chinese citizens support military spending in the abstract, but their support diminishes when considered alongside other domestic spending priorities. We also find that public support for military spending coexists surprisingly with anti-war sentiments and a significant strain of isolationism. In addition, while the conventional wisdom suggests that nationalism moves a state towards bellicosity and war, we find that Chinese citizens with a stronger sense of national pride report stronger anti-war sentiments than other citizens.
Evaluation of the Predictive Accuracy of the interRAI Falls Clinical Assessment Protocol, Scott Fall Risk Screen, and a Supplementary Falls Risk Assessment Tool Used in Residential Long-Term Care: A Retrospective Cohort Study
Authors: Norman Kathleen J. , Hirdes John P.
Published: March 2020

Falls in residential long-term care (LTC) facilities continue to be a leading cause of injury for residents and cost for the health care system. Interdisciplinary clinical teams are responsible for assessing risk levels for their residents and developing appropriate care plans and interventions in response. This study compares the predictive accuracy of three separate fall risk assessment tools: the interRAI Falls Clinical Assessment Protocol (CAP), derived from the LTC Facility (LTCF) or Minimum Data Set (MDS) 2.0 assessments; the Scott Fall Risk Screen; and a modified Fall Risk Tool that was implemented as part of a provincial Fall Reduction Strategy in Nova Scotia. To conduct this retrospective cohort study, secondary data were collected from 1,553 LTC residents with interRAI assessments completed between March 1, 2015 and September 29, 2016, across Nova Scotia and New Brunswick. For each resident, data were collected regarding the three fall risk assessments, along with fall incident data for use in sensitivity, specificity, and logistic regression analyses. This study found that although all three tools had limitations with sensitivity or specificity thresholds, the interRAI Falls CAP delivered the highest accuracy with a c-statistic of 0.673, compared with the Scott Fall Risk Screen at 0.529 and the modified Fall Risk Tool at 0.609. When diseases that have been established to be a risk factor for falls were added to the model, the overall accuracy of the interRAI Falls CAP combined with those covariates increased to 0.749. These results suggest that the best practice guidelines for fall risk assessment be revisited, and that the interRAI Falls CAP could potentially be updated to include certain diseases and controls for optimal predictive ability.
Demonstration, extension, and refinement of the re-proposed notion of design abduction
Authors: Koskela Lauri , Kroll Ehud
Published: March 2020

The original ideas on design abduction, inspired by treatments in philosophy of science, had a narrow conception on how novelty emerges in design, when looked at in terms of logic. The authors have previously presented a re-proposed notion of abduction in design, taking the differences between science and design into account. Now, in this article, the invention of the airplane by the Wright brothers is analyzed as a retrospective case study. Key parts of the re-proposed notion of design abduction are demonstrated, and two new types of design abduction are identified, namely strategic abduction and dynamic abduction. Perhaps even more importantly, a new hypothesis on the cognitive basis of design abduction is reached. While the importance of model-based abduction (and reasoning) is confirmed, the case also pinpoints the central role of verbalization and discussion in supporting design reasoning in general and especially abduction. All in all, it seems that an improved understanding of design abduction and its cognitive basis would be instrumental in promoting more effective and efficient designing.
Repair of isolated atrial septal defect in infants less than 12 months improves symptoms of chronic lung disease or shunt-related pulmonary hypertension
Authors: Charisopoulou Dafni , Bini Roberta Margarita , Riley Gillian , Janagarajan Kalai , Moledina Shahin , Marek Jan
Published: March 2020

Introduction:

Infants with isolated atrial septal defects are usually minimally symptomatic, and repair is typically performed after infancy. Early repair may be considered if there is high pulmonary blood flow and reduced respiratory reserve or early signs of pulmonary hypertension. Our aim was to review the characteristics and outcomes of a cohort of patients who underwent infant repair at our institute.

Methods:

The study included 56 infants (28 female, 19 trisomy 21) with isolated atrial septal defect (age: 8 months (1.5–12), weight: 6 kg (2.8–7.5), echo Qp/Qs: 1.9 ± 0.1) who underwent surgical closure (20 fenestrated). Three groups were identified: 1) chronic lung disease and pulmonary hypertension (group A: n = 28%); 2) acutely unwell infants with pulmonary hypertension but no chronic lung disease (group B: n = 20, 36%); and 3) infants with refractory congestive heart failure without either pulmonary hypertension or chronic lung disease (group C: n = 9, 16%).

Results:

Post-operatively, pulmonary hypertension infants (47/56) showed improvement in tricuspid annular plane systolic excursion z-score (p < 0.001) and right ventricular systolic/diastolic duration ratio (p < 0.05). All ventilator (14.3%) or oxygen-dependent (31.6%) infants could be weaned within 2 weeks after repair. One year later, weight z-score increased in all patients and by +1 in group A, +1.3 in group B and +2 in group C. Over a median follow-up of 1.4 years, three patients died, four patients continued to have pulmonary hypertension evidence and two remained on targeted pulmonary hypertension therapy.

Conclusion:

Atrial septal defect repair within the first year may improve the clinical status and growth in infants with early signs of pulmonary hypertension or those requiring respiratory support and facilitate respiratory management.
Legalised Pedigrees: Sayyids and Shiʽi Islam in Pakistan
Authors: FUCHS SIMON WOLFGANG
Published: March 2020

This article draws on a wide range of Shiʽi periodicals and monographs from the 1950s until the present day to investigate debates on the status of Sayyids in Pakistan. I argue that the discussion by reformist and traditionalist Shiʽi scholars(ʽulama)and popular preachers has remained remarkably stable over this time period. Both ‘camps’ have avoided talking about any theological or miracle-working role of the Prophet's kin. This phenomenon is remarkable, given the fact that Sayyids share their pedigree with the Shiʽi Imams, who are credited with superhuman qualities. Instead, Shiʽi reformists and traditionalists have discussed Sayyids predominantly as a specific legal category. They are merely entitled to a distinct treatment as far as their claims to charity, patterns of marriage, and deference in daily life is concerned. I hold that this reductionist and largely legalising reading of Sayyids has to do with the intense competition over religious authority in post-Partition Pakistan. For both traditionalist and reformist Shiʽi authors,ʽulama,and preachers, there was no room to acknowledge Sayyids as potential further competitors in their efforts to convince the Shiʽi public about the proper ‘orthodoxy’ of their specific views.
Bidirectional cross-linguistic influence in object realization in Cantonese–English bilingual children
Authors: Zhou Jiangling , Mai Ziyin , Yip Virginia
Published: March 2020

This study reports a production experiment investigating the realization of objects with different verb types in controlled discourse contexts in 68 three- to seven-year-old sequential Cantonese–English bilingual children. The results show the bilingual children behaved similarly to the Cantonese monolingual peers in object omission, but exhibited protracted development and produced target-deviant forms following a Cantonese pattern in omitting objects specified in prior discourse in English. The bilingual children also showed non-target-like uses of the Cantonese post-verbal object pronounkeoi5,which were unattested in monolingual children. Our findings show evidence for bidirectional cross-linguistic influence: the direction of influence goes from the weaker to the stronger language and from the stronger to the weaker language. Vulnerability of object realization in bilingual acquisition can be better understood in terms of the interaction between cross-linguistic influence, input (e.g., quantity and structural frequencies) and other linguistic elements involved in the interface relation (e.g., verb type).
A new anthropometric index to predict percent body fat in young adults
Authors: Yang Hyuk In , Cho Wonhee , Ahn Ki Yong , Shin Seung-chul , Kim Ju-hwa , Yoo Seoungjae , Park Yong-in , Lee Eun-Young , Lee Dong Hoon , Spence John C , Jeon Justin Y
Published: March 2020

Objective:

To propose a new anthropometric index that can be employed to better predict percent body fat (PBF) among young adults and to compare with current anthropometric indices.

Design:

Cross-sectional.

Setting:

All measurements were taken in a controlled laboratory setting in Seoul (South Korea), between 1 December 2015 and 30 June 2016.

Participants:

Eighty-seven young adults (18–35 years) who underwent dual-energy x-ray absorptiometry (DXA) were used for analysis. Multiple regression analyses were conducted to develop a body fat index (BFI) using simple demographic and anthropometric information. Correlations of DXA measured PBF (DXA_PBF) with previously developed anthropometric indices and the BFI were analysed. Receiver operating characteristic curve analyses were conducted to compare the ability of anthropometric indices to identify obese individuals.

Results:

BFI showed a strong correlation with DXA_PBF (r = 0·84), which was higher than the correlations of DXA_PBF with the traditional (waist circumference, r = 0·49; waist to height ratio, r = 0·68; BMI, r = 0·36) and alternate anthropometric indices (a body shape index, r = 0·47; body roundness index, r = 0·68; body adiposity index, r = 0·70). Moreover, the BFI showed higher accuracy at identifying obese individuals (area under the curve (AUC) = 0·91), compared with the other anthropometric indices (AUC = 0·71–0·86).

Conclusions:

The BFI can accurately predict DXA_PBF in young adults, using simple demographic and anthropometric information that are commonly available in research and clinical settings. However, larger representative studies are required to build on our findings.
Exploring morpho-physiological profiles of a collection of tomato (Solanum lycopersicum) germplasm using multivariate statistics
Authors: Mellidou Ifigeneia , Krommydas Konstantinos , Nianiou-Obeidat Irini , Ouzounidou Georgia , Kalivas Apostolos , Ganopoulos Ioannis
Published: March 2020

A selection of tomato (Solanum lycopersicum L.) genotypes with diverse origin and breeding history including 33 landraces, eight modern varieties and two commercial hybrids has been characterized using a set of 25 qualitative descriptors and six quantitative traits. A wide range of variation was evident for the majority of traits, highlighting their utility for characterizing tomato germplasm collections. A plethora of qualitative traits including type of leaf blade, depression and ribbing at peduncle end, fruit shape at blossom end, number of locules and flowering time, as well as measured traits with economic importance such as fruit fresh weight, firmness and total yield per plant, were found to be highly variable within the collection, with a diversity index greater than 0.8. Strong correlations were detected among several traits related to fruit yield and quality. Two-dimensional principal component analysis as well as the unsupervised hierarchical clustering grouped genotypes according to their phenotypic resemblance and morphological characteristics to a great extent. Landraces from different origins were scattered across the whole variation spectrum of PC1 and PC2. A set of six qualitative traits could efficiently discriminate cultivars in PCA (explaining 75% of total variation), suggesting that it can serve as a valuable breeding tool for the germplasm characterization. The evaluation of the phenotypic diversity in the collection as well as the identification of traits that contribute most to heterogeneity have important implications for establishing core collections with high diversity, as well as designing breeding schemes across the Mediterranean basin.
Investigation of the Micromechanical Damage Process in a Granitic Rock Using an Inelastic Bonded Block Model (BBM)
Authors: Sinha S. , Shirole D. , Walton G.
Published: March 2020

This study numerically investigates the damage process in a granite using an inelastic multiminerallic block model in two‐dimensional Universal Distinct Element Code. In addition to the commonly considered calibration targets like uniaxial and triaxial strengths, tensile strength, and Young's modulus, attention was paid to reproduce additional attributes such as postpeak response, residual strengths, and confinement‐dependent dilatancy to minimize the nonuniqueness potential of the models. The fracture pattern transitioned from axial cracking to shear banding as the specimen confinement was increased from 0 to 60 MPa. Most notably, the model could exhibit the cohesion‐weakening‐frictional‐strengthening behavior that is typically associated with brittle rocks. The progressive damage mechanism in the unconfined bonded block model (BBM) was subsequently studied using the 2‐D digital image correlation (2‐D‐DIC) approach. To date, the application of the 2‐D‐DIC approach has been restricted only to real material testing; this study, therefore, is an attempt to extend its applicability to numerical models. It was found that 2‐D‐DIC is capable of imaging the simulated microcracking process very well and the results were similar to those observed from real testing on a different granitic rock. Lastly, the numerical‐based DIC results were analyzed to clarify that even if the point of axial stress‐axial strain nonlinearity does not coincide with the point of volumetric strain reversal in unconfined BBMs, the axial stress‐axial strain nonlinearity approach should always be used for determining the crack damage threshold in BBMs.
Mesoscale Eddy Effects on the Subduction of North Pacific Eastern Subtropical Mode Water
Authors: Wang Ran , Cheng Xuhua , Xu Lixiao , Chen Jiajia
Published: March 2020

The effects of mesoscale eddies on the subduction of the North Pacific eastern subtropical mode water (ESTMW) are studied by comparing observations with results from the Ocean Model for the Earth Simulator (OFES). Both observations and the OFES show that mesoscale eddies exist in the ESTMW subduction region. Compared to the observations, the OFES reproduces the characteristics of the ESTMW and subduction quite well. Subduction of the ESTMW mainly occurs within a low‐density advection region, which leads to the formation of low potential vorticity water. The eddy subduction rate accounts for nearly 56% of the total subduction rate, creating high peaks in the ESTMW subduction volume histogram. Case study results show that the propagation of eddies is responsible for the shallowing of the mixed‐layer depth, which allows low potential vorticity water to subduct under the mixed‐layer bottom and prevents it from being entrained back into the mixed layer. The eddy subduction process investigated here has important implications for the further study of ESTMW subduction and transport, which is helpful for better understanding the interior transportation between the tropics and subtropics.
Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism
Authors: Chao Owen Y. , Marron Fernandez de Velasco Ezequiel , Pathak Salil Saurav , Maitra Swati , Zhang Hao , Duvick Lisa , Wickman Kevin , Orr Harry T. , Hirai Hirokazu , Yang Yi-Mei
Published: March 2020

Autism spectrum disorder (ASD) encompasses wide-ranging neuropsychiatric symptoms with unclear etiology. Although the cerebellum is a key region implicated in ASD, it remains elusive how the cerebellar circuitry is altered and whether the cerebellum can serve as a therapeutic target to rectify the phenotype of idiopathic ASD with polygenic abnormalities. Using a syndromic ASD model, e.g., Black and Tan BRachyury T+Itpr3tf/J (BTBR) mice, we revealed that increased excitability of presynaptic interneurons (INs) and decreased intrinsic excitability of postsynaptic Purkinje neurons (PNs) resulted in low PN firing rates in the cerebellum. Knowing that downregulation of Kv1.2 potassium channel in the IN nerve terminals likely augmented their excitability and GABA release, we applied a positive Kv1.2 modulator to mitigate the presynaptic over-inhibition and social impairment of BTBR mice. Selective restoration of the PN activity by a new chemogenetic approach alleviated core ASD-like behaviors of the BTBR strain. These findings highlight complex mechanisms converging onto the cerebellar dysfunction in the phenotypic model and provide effective strategies for potential therapies of ASD.
It does not always take two to tango: “Syntrophy” via hydrogen cycling in one bacterial cell
Authors: Wiechmann Anja , Ciurus Sarah , Oswald Florian , Seiler Vinca N , Müller Volker
Published: March 2020

Interspecies hydrogen transfer in anoxic ecosystems is essential for the complete microbial breakdown of organic matter to methane. Acetogenic bacteria are key players in anaerobic food webs and have been considered as prime candidates for hydrogen cycling. We have tested this hypothesis by mutational analysis of the hydrogenase in the model acetogen Acetobacterium woodii. Hydrogenase-deletion mutants no longer grew on H2 + CO2 or organic substrates such as fructose, lactate, or ethanol. Heterotrophic growth could be restored by addition of molecular hydrogen to the culture, indicating that hydrogen is an intermediate in heterotrophic growth. Indeed, hydrogen production from fructose was detected in a stirred-tank reactor. The mutant grew well on organic substrates plus caffeate, an alternative electron acceptor that does not require molecular hydrogen but NADH as reductant. These data are consistent with the notion that molecular hydrogen is produced from organic substrates and then used as reductant for CO2 reduction. Surprisingly, hydrogen cycling in A. woodii is different from the known modes of interspecies or intraspecies hydrogen cycling. Our data are consistent with a novel type of hydrogen cycling that connects an oxidative and reductive metabolic module in one bacterial cell, “intracellular syntrophy.”
Circulating microRNA 134 sheds light on the diagnosis of major depressive disorder
Authors: Zhang Han-ping , Liu Xiao-lei , Chen Jian-jun , Cheng Ke , Bai Shun-Jie , Zheng Peng , Zhou Chan-juan , Wang Wei , Wang Hai-yang , Zhong Lian-mei , Xie Peng
Published: March 2020

Major depressive disorder (MDD) is a prevalent and debilitating psychiatric mood disorder that lacks objective laboratory-based tests to support its diagnosis. A class of microRNAs (miRNAs) has been found to be centrally involved in regulating many molecular processes fundamental to central nervous system function. Among these miRNAs, miRNA-134 (miR-134) has been reported to be related to neurogenesis and synaptic plasticity. In this study, the hypothesis that plasma miR-134 can be used to diagnose MDD was tested. Perturbation of peripheral and central miR-134 in a depressive-like rat model was also examined. By reverse-transcription quantitative PCR, miR-134 was comparatively measured in a small set of plasma samples from MDD and healthy control (HC) subjects. To determine its diagnostic efficacy, plasma miR-134 levels were assessed in 100 MDD, 50 bipolar disorder (BD), 50 schizophrenic (SCZ), and 100 HC subjects. A chronic unpredictable mild stress (CUMS) rat model was also developed to evaluate miR-134 expression in plasma, hippocampus (HIP), prefrontal cortex (PFC), and olfactory bulb. We found that plasma miR-134 was significantly downregulated in MDD subjects. Diagnostically, plasma miR-134 levels could effectively distinguish MDD from HC with 79% sensitivity and 84% specificity, while distinguishing MDD from HC, BD, and SCZ subjects with 79% sensitivity and 76.5% specificity. Congruent with these clinical findings, CUMS significantly reduced miR-134 levels in the rat plasma, HIP, and PFC. Although limited by the relatively small sample size, these results demonstrated that plasma miR-134 displays potential ability as a biomarker for MDD.
Long-term cardiac outcomes of patients with HER2-positive breast cancer treated in the adjuvant lapatinib and/or trastuzumab Treatment Optimization Trial
Authors: Eiger Daniel , Pondé Noam F. , Agbor-Tarh Dominique , Moreno-Aspitia Alvaro , Piccart Martine , Hilbers Florentine S. , Werner Olena , Chumsri Saranya , Dueck Amylou , Kroep Judith R. , Gomez Henry , Láng István , Rodeheffer Richard J. , Ewer Michael S. , Suter Thomas , de Azambuja Evandro
Published: March 2020

Background

Cardiotoxicity is the most significant adverse event associated with trastuzumab (T), the main component of HER2-positive breast cancer (BC) treatment. Less is known about the cardiotoxicity of dual HER2 blockade with T plus lapatinib (L), although this regimen is used in the metastatic setting.

Methods

This is a sub-analysis of the ALTTO trial comparing adjuvant treatment options for patients with early HER2-positive BC. Patients randomised to either T or concomitant T + L were eligible. Cardiac events (CEs) rates were compared according to treatment arm.

Results

With 6.9 years of median follow-up (FU) and 4190 patients, CE were observed in 363 (8.6%): 166 (7.9%) of patient in T + L arm vs. 197 (9.3%) in T arm (OR = 0.85 [95% CI, 0.68–1.05]). During anti-HER2 treatment 270 CE (6.4%) occurred while 93 (2.2%) were during FU (median time to onset = 6.6 months [IQR = 3.4–11.7]). While 265 CEs were asymptomatic (73%), 94 were symptomatic (26%) and four were cardiac deaths (1%). Recovery was observed in 301 cases (83.8%). Identified cardiac risk factors were: baseline LVEF < 55% (vs > 64%, OR 3.1 [95% CI 1.54–6.25]), diabetes mellitus (OR 1.85 [95% CI 1.25–2.75]), BMI > 30 kg/m2 (vs < 25 mg/kg2, OR 2.21 [95% CI 1.40–3.49]), cumulative dose of doxorubicin ≥240 mg/m2 (OR 1.36 [95% CI 1.01–1.82]) and of epirubicin≥ 480 mg/m2 (OR 2.33 [95% CI 1.55–3.51]).

Conclusions

Dual HER2 blockade with T + L is a safe regimen from a cardiac perspective, but cardiac-focused history for proper patient selection is crucial.

Trial registration number

ClinicalTrials.gov Identifier: NCT00490139 (registration date: 22/06/2007); EudraCT Number: 2006–000562–36 (registration date: 04/05/2007); Sponsor Protocol Number: BIG2–06 /EGF106708/N063D.
Chiral twisting in a bacterial cytoskeletal polymer affects filament size and orientation
Authors: Shi Handuo , Quint David A. , Grason Gregory M. , Gopinathan Ajay , Huang Kerwyn Casey
Published: March 2020

In many rod-shaped bacteria, the actin homolog MreB directs cell-wall insertion and maintains cell shape, but it remains unclear how structural changes to MreB affect its organization in vivo. Here, we perform molecular dynamics simulations for Caulobacter crescentus MreB to extract mechanical parameters for inputs into a coarse-grained biophysical polymer model that successfully predicts MreB filament properties in vivo. Our analyses indicate that MreB double protofilaments can exhibit left-handed twisting that is dependent on the bound nucleotide and membrane binding; the degree of twisting correlates with the length and orientation of MreB filaments observed in vitro and in vivo. Our molecular dynamics simulations also suggest that membrane binding of MreB double protofilaments induces a stable membrane curvature of similar magnitude to that observed in vivo. Thus, our multiscale modeling correlates cytoskeletal filament size with conformational changes inferred from molecular dynamics simulations, providing a paradigm for connecting protein filament structure and mechanics to cellular organization and function.
Synergistic electroreduction of carbon dioxide to carbon monoxide on bimetallic layered conjugated metal-organic frameworks
Authors: Zhong Haixia , Ghorbani-Asl Mahdi , Ly Khoa Hoang , Zhang Jichao , Ge Jin , Wang Mingchao , Liao Zhongquan , Makarov Denys , Zschech Ehrenfried , Brunner Eike , Weidinger Inez M. , Zhang Jian , Krasheninnikov Arkady V. , Kaskel Stefan , Dong Renhao , Feng Xinliang
Published: March 2020

Highly effective electrocatalysts promoting CO2 reduction reaction (CO2RR) is extremely desirable to produce value-added chemicals/fuels while addressing current environmental challenges. Herein, we develop a layer-stacked, bimetallic two-dimensional conjugated metal-organic framework (2D c-MOF) with copper-phthalocyanine as ligand (CuN4) and zinc-bis(dihydroxy) complex (ZnO4) as linkage (PcCu-O8-Zn). The PcCu-O8-Zn exhibits high CO selectivity of 88%, turnover frequency of 0.39 s−1 and long-term durability (>10 h), surpassing thus by far reported MOF-based electrocatalysts. The molar H2/CO ratio (1:7 to 4:1) can be tuned by varying metal centers and applied potential, making 2D c-MOFs highly relevant for syngas industry applications. The contrast experiments combined with operando spectroelectrochemistry and theoretical calculation unveil a synergistic catalytic mechanism; ZnO4 complexes act as CO2RR catalytic sites while CuN4 centers promote the protonation of adsorbed CO2 during CO2RR. This work offers a strategy on developing bimetallic MOF electrocatalysts for synergistically catalyzing CO2RR toward syngas synthesis.
Observation of an antiferromagnetic quantum critical point in high-purity LaNiO3
Authors: Liu Changjiang , Humbert Vincent F. C. , Bretz-Sullivan Terence M. , Wang Gensheng , Hong Deshun , Wrobel Friederike , Zhang Jianjie , Hoffman Jason D. , Pearson John E. , Jiang J. Samuel , Chang Clarence , Suslov Alexey , Mason Nadya , Norman M. R. , Bhattacharya Anand
Published: March 2020

Amongst the rare-earth perovskite nickelates, LaNiO3 (LNO) is an exception. While the former have insulating and antiferromagnetic ground states, LNO remains metallic and non-magnetic down to the lowest temperatures. It is believed that LNO is a strange metal, on the verge of an antiferromagnetic instability. Our work suggests that LNO is a quantum critical metal, close to an antiferromagnetic quantum critical point (QCP). The QCP behavior in LNO is manifested in epitaxial thin films with unprecedented high purities. We find that the temperature and magnetic field dependences of the resistivity of LNO at low temperatures are consistent with scatterings of charge carriers from weak disorder and quantum fluctuations of an antiferromagnetic nature. Furthermore, we find that the introduction of a small concentration of magnetic impurities qualitatively changes the magnetotransport properties of LNO, resembling that found in some heavy-fermion Kondo lattice systems in the vicinity of an antiferromagnetic QCP.
Impact of functional synapse clusters on neuronal response selectivity
Authors: Ujfalussy Balázs B. , Makara Judit K.
Published: March 2020

Clustering of functionally similar synapses in dendrites is thought to affect neuronal input-output transformation by triggering local nonlinearities. However, neither the in vivo impact of synaptic clusters on somatic membrane potential (sVm), nor the rules of cluster formation are elucidated. We develop a computational approach to measure the effect of functional synaptic clusters on sVm response of biophysical model CA1 and L2/3 pyramidal neurons to in vivo-like inputs. We demonstrate that small synaptic clusters appearing with random connectivity do not influence sVm. With structured connectivity,  ~10–20 synapses/cluster are optimal for clustering-based tuning via state-dependent mechanisms, but larger selectivity is achieved by 2-fold potentiation of the same synapses. We further show that without nonlinear amplification of the effect of random clusters, action potential-based, global plasticity rules cannot generate functional clustering. Our results suggest that clusters likely form via local synaptic interactions, and have to be moderately large to impact sVm responses.
Causal networks for climate model evaluation and constrained projections
Authors: Nowack Peer , Runge Jakob , Eyring Veronika , Haigh Joanna D.
Published: March 2020

Global climate models are central tools for understanding past and future climate change. The assessment of model skill, in turn, can benefit from modern data science approaches. Here we apply causal discovery algorithms to sea level pressure data from a large set of climate model simulations and, as a proxy for observations, meteorological reanalyses. We demonstrate how the resulting causal networks (fingerprints) offer an objective pathway for process-oriented model evaluation. Models with fingerprints closer to observations better reproduce important precipitation patterns over highly populated areas such as the Indian subcontinent, Africa, East Asia, Europe and North America. We further identify expected model interdependencies due to shared development backgrounds. Finally, our network metrics provide stronger relationships for constraining precipitation projections under climate change as compared to traditional evaluation metrics for storm tracks or precipitation itself. Such emergent relationships highlight the potential of causal networks to constrain longstanding uncertainties in climate change projections.
Parallel evolution of dominant pistil-side self-incompatibility suppressors in Arabidopsis
Authors: Fujii Sota , Shimosato-Asano Hiroko , Kakita Mitsuru , Kitanishi Takashi , Iwano Megumi , Takayama Seiji
Published: March 2020

Selfing is a frequent evolutionary trend in angiosperms, and is a suitable model for studying the recurrent patterns underlying adaptive evolution. Many plants avoid self-fertilization by physiological processes referred to as self-incompatibility (SI). In the Brassicaceae, direct and specific interactions between the male ligand SP11/SCR and the female receptor kinase SRK are required for the SI response. Although Arabidopsis thaliana acquired autogamy through loss of these genes, molecular evolution contributed to the spread of self-compatibility alleles requires further investigation. We show here that in this species, dominant SRK silencing genes have evolved at least twice. Different inverted repeat sequences were found in the relic SRK region of the Col-0 and C24 strains. Both types of inverted repeats suppress the functional SRK sequence in a dominant fashion with different target specificities. It is possible that these dominant suppressors of SI contributed to the rapid fixation of self-compatibility in A. thaliana.
Dissecting the early steps of MLL induced leukaemogenic transformation using a mouse model of AML
Authors: Basilico Silvia , Wang Xiaonan , Kennedy Alison , Tzelepis Konstantinos , Giotopoulos George , Kinston Sarah J. , Quiros Pedro M. , Wong Kim , Adams David J. , Carnevalli Larissa S. , Huntly Brian J. P. , Vassiliou George S. , Calero-Nieto Fernando J. , Göttgens Berthold
Published: March 2020

Leukaemogenic mutations commonly disrupt cellular differentiation and/or enhance proliferation, thus perturbing the regulatory programs that control self-renewal and differentiation of stem and progenitor cells. Translocations involving theMll1(Kmt2a) gene generate powerful oncogenic fusion proteins, predominantly affecting infant and paediatric AML and ALL patients. The early stages of leukaemogenic transformation are typically inaccessible from human patients and conventional mouse models. Here, we take advantage of cells conditionally blocked at the multipotent haematopoietic progenitor stage to develop a MLL-r model capturing early cellular and molecular consequences of MLL-ENL expression based on a clear clonal relationship between parental and leukaemic cells. Through a combination of scRNA-seq, ATAC-seq and genome-scale CRISPR-Cas9 screening, we identify pathways and genes likely to drive the early phases of leukaemogenesis. Finally, we demonstrate the broad utility of using matched parental and transformed cells for small molecule inhibitor studies by validating both previously known and other potential therapeutic targets.
Chromatin accessibility promotes hematopoietic and leukemia stem cell activity
Authors: Cabal-Hierro Lucia , van Galen Peter , Prado Miguel A. , Higby Kelly J. , Togami Katsuhiro , Mowery Cody T. , Paulo Joao A. , Xie Yingtian , Cejas Paloma , Furusawa Takashi , Bustin Michael , Long Henry W. , Sykes David B. , Gygi Steven P. , Finley Daniel , Bernstein Bradley E. , Lane Andrew A.
Published: March 2020

Chromatin organization is a highly orchestrated process that influences gene expression, in part by modulating access of regulatory factors to DNA and nucleosomes. Here, we report that the chromatin accessibility regulator HMGN1, a target of recurrent DNA copy gains in leukemia, controls myeloid differentiation. HMGN1 amplification is associated with increased accessibility, expression, and histone H3K27 acetylation of loci important for hematopoietic stem cells (HSCs) and leukemia, such as HoxA cluster genes. In vivo, HMGN1 overexpression is linked to decreased quiescence and increased HSC activity in bone marrow transplantation. HMGN1 overexpression also cooperates with the AML-ETO9a fusion oncoprotein to impair myeloid differentiation and enhance leukemia stem cell (LSC) activity. Inhibition of histone acetyltransferases CBP/p300 relieves the HMGN1-associated differentiation block. These data nominate factors that modulate chromatin accessibility as regulators of HSCs and LSCs, and suggest that targeting HMGN1 or its downstream effects on histone acetylation could be therapeutically active in AML.
Self-regulated spacing in a massive open online course is related to better learning
Authors: Carvalho Paulo F. , Sana Faria , Yan Veronica X.
Published: March 2020

In this study, we examined students’ natural studying behaviors in massive, open, online course (MOOC) on introductory psychology. We found that, overall, distributing study across multiple sessions—increasing spacing—was related to increased performance on end-of-unit quizzes, even when comparing the same student across different time-points in the course. Moreover, we found important variation on who is more likely to engage in spaced study and benefit from it. Students with higher ability and students who were more likely to complete course activities were more likely to space their study. Spacing benefits, however, were largest for the lower-ability students and for those students who were less likely to complete activities. These results suggest that spaced study might work as a buffer, improving performance for low ability students and those who do not engage in active practices. This study highlights the positive impact of spacing in real-world learning situations, but more importantly, the role of self-regulated learning decisions in shaping the impact of spaced practice.