bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating genomics and multi-platform metabolomics enables metabolite QTL detection in breeding-relevant apple germplasm
Authors: Bilbrey Emma A. , Williamson Kathryn , Hatzakis Emmanuel , Miller Diane Doud , Fresnedo-Ramírez Jonathan , Cooperstone Jessica L. 
Published: February 2021

SummaryResearch ConductedApple (Malus × domestica) has commercial and nutritional value, but breeding constraints of tree crops limit varietal improvement. Marker-assisted selection minimizes these drawbacks, but breeders lack applications for targeting fruit phytochemicals. To understand genotype-phytochemical associations in apples, we have developed a high-throughput integration strategy for genomic and multi-platform metabolomics data.Methods124 apple genotypes, including members of three pedigree-connected breeding families alongside diverse cultivars and wild selections, were genotyped and phenotyped. Metabolite genome-wide association studies (mGWAS) were conducted with 10,000 single nucleotide polymorphisms and phenotypic data acquired via LC-MS and 1H NMR untargeted metabolomics. Putative metabolite quantitative trait loci (mQTL) were then validated via pedigree-based analyses (PBA).Key ResultsUsing our developed method, 519, 726, and 177 putative mQTL were detected in LC-MS positive and negative ionization modes and NMR, respectively. mQTL were indicated on each chromosome, with hotspots on linkage groups 16 and 17. A chlorogenic acid mQTL was discovered on chromosome 17 via mGWAS and validated with a two-step PBA, enabling discovery of novel candidate gene-metabolite relationships.Main ConclusionComplementary data from three metabolomics approaches and dual genomics analyses increased confidence in validity of compound annotation and mQTL detection. Our platform demonstrates the utility of multi-omics integration to advance data-driven, phytochemicalbased plant breeding.
Glycine receptor α3K governs mobility and conductance of L/K splice variant heteropentamers
Authors: Lemmens Veerle , Thevelein Bart , Kankowski Svenja , Mizuno Hideaki , Meier Jochen C. , Rocha Susana , Brône Bert , Hendrix Jelle 
Published: February 2021

AbstractGlycine receptors (GlyRs) are ligand-gated pentameric chloride channels in the central nervous system. GlyR-α3 is a possible target for chronic pain treatment and temporal lobe epilepsy. Alternative splicing into K or L variants determines the subcellular fate and function of GlyR-α3, yet it remains to be shown whether its different splice variants can functionally co-assemble, and what the properties of such heteropentamers would be. Here, we subjected GlyR-α3 to a combined fluorescence microscopy and electrophysiology analysis. We employ masked Pearson’s and dual-color spatiotemporal correlation analysis to prove that GlyR-α3 splice variants heteropentamerize, adopting the mobility of the K variant. Fluorescence-based single-subunit counting experiments revealed a variable and concentration ratio dependent hetero-stoichiometry. Via single-channel on-cell patch clamp we show heteropentameric conductances resemble those of the α3K splice variant. Our data are compatible with a model where α3 heteropentamerization fine-tunes mobility and activity of GlyR α3 channels, which is important to understand and tackle α3 related diseases.SummaryThe glycine receptor α3 is key to the central nervous system’s physiology and involved in chronic pain and epilepsy. In this paper, Lemmens et al. reveal and functionally characterize α3 splice variant heteropentamerization via advanced single-molecule fluorescence image analysis.DeclarationsFundingWe acknowledge the UHasselt Advanced Optical Microscopy Centre (AOMC). Prof. Em. Marcel Ameloot, the Research Foundation Flanders (FWO, project G0H3716N) and the province of Limburg (Belgium) (tUL Impuls II) are acknowledged for funding the microscopy hardware. V. Lemmens is grateful for a doctoral scholarship from the UHasselt (17DOC11BOF) and KU Leuven (C14/16/053) Special Research Funds (BOF).Conflicts of interest / competing interestsNo conflicts of interest apply.Ethics approvalNot applicableAvailability of data and materialAll data and material are available upon request.Code availabilityFluctuation imaging and co-localization analyses were performed in the software package PAM [71]. The software is available as source code, requiring MATLAB to run, or as pre-compiled standalone distributions for Windows or MacOS athttp://www.cup.uni-muenchen.de/pc/lamb/software/pam.htmlor hosted in Git repositories underhttp://www.gitlab.com/PAM-PIE/PAMandhttp://www.gitlab.com/PAM-PIE/PAMcompiled. A detailed user manual is available athttp://pam.readthedocs.io.Author contributionsConceptualization Meier J.C., Brône B. and Hendrix J.; Investigation and formal analysis Lemmens V. and Thevelein B.; Software development Hendrix J.; Writing the original draft Lemmens V., Thevelein B and Hendrix, J.; Review and editing by all authors.
A covalently crosslinked bioink for multi-materials drop-on-demand 3D bioprinting of three-dimensional cell cultures
Authors: Utama Robert H. , Tan Vincent T. G. , Tjandra Kristel C. , Sexton Andrew , Nguyen Duyen H. T. , O’Mahony Aidan P. , Ribeiro Julio C. C. , Kavallaris Maria , Gooding J. Justin 
Published: February 2021

AbstractIn vitro three-dimensional (3D) cell models have been accepted to better recapitulate aspects of in vivo organ environment than 2D cell culture. Currently, the production of these complex in vitro 3D cell models with multiple cell types and microenvironments remains challenging and prone to human error. Here we report a versatile bioink comprised of a 4-arm PEG based polymer with distal maleimide derivatives as the main ink component and a bis-thiol species as the activator that crosslinks the polymer to form the hydrogel in less than a second. The rapid gelation makes the polymer system compatible with 3D bioprinting. The ink is combined with a drop-on-demand 3D bioprinting platform consisting of eight independently addressable nozzles and high-throughput printing logic for creating complex 3D cell culture models. The combination of multiple nozzles and fast printing logic enables the rapid preparation of many complex 3D structures comprising multiple hydrogel environments in the one structure in a standard 96-well plate format. The platform compatibility for biological applications was validated using pancreatic ductal adenocarcinoma cancer (PDAC) cells with their phenotypic responses controlled by tuning the hydrogel microenvironment.
TKTDsimulation.jl and tktdjl2r: innovative packages for High Performance Computing of survival predictions in support of environmental risk assessment under time-variable scenarios
Authors: Baudrot Virgile , Charles Sandrine 
Published: February 2021

AbstractPredictive environmental risk scenarios are today of major interest for environmental risk assessment as they provide plausible and consistent descriptions of possible effects of chemicalin natura. In particular, they can be used for predictions of the future as consistent descriptions of pathways towards desired targets to protect. One single scenario would therefore be meaningless, as it could not capture all the variability and uncertainty involved in natural phenomenon combined with socio-economical events. A set of environmental risk scenarios is then a key asset to address sustainable and collaborative decision making associated with appropriate actions.Toxicokinetics-Toxicodynamics (TKTD) models are increasingly used for the assessment and the prediction of environmental risk assessment due to chemical products. This mechanistic modelling approach offers many advantages as the possibility to perform simulations under non-observed realistic situations with time-variable exposure profiles embedded in environmental risk scenarios. TKTD simulations can also be linked with other types of models (e.g., Individual Based Model) within a pipeline of computing inference as for example Bayesian inference or Machine Learning. To handle such challenges within the particular framework of TKTD models for survival, we present an innovative simulation tool written in the new programming language Julia, calledTKTDsimulations.jl. Given that TKTD models for survival usually require high performance computing due to the numerical integration of differential equations, our tool strongly benefits from Julia’s facilities, in particular a code that is fast to compile and easy to maintain. In addition, to ease the link with the already developed R-packagemorsededicated to the statistical handling of ecotoxicity data, we also developed a new R-package, calledtktdjl2r, interfacingmorsewith our new simulation toolTKTDsimulations.jlthat considerably faster predictions with the corresponding ready-to-usemorsefunctions.
Sharing happy stories increases interpersonal closeness mediated by enhancing interpersonal brain synchronization
Authors: Xie Enhui , Yin Qing , Li Keshuang , Nastase Samuel A. , Zhang Ruqian , Wang Ning , Li Xianchun 
Published: February 2021

AbstractOur lives revolve around sharing stories with others. Expressing emotion (i.e., happy and sad) is an essential characteristic of sharing stories and could enhance the similarity of story comprehension across speaker–listener pairs. The Emotions as Social Information Model (EASI) suggests that emotional communication may influence interpersonal closeness, but the effect of sharing emotional (happy/sad) stories on interpersonal closeness remains poorly understood. Here, one speaker watched emotional videos and communicated the content of the videos to thirty-two listeners (happy/sad/neutral group). Both speaker and listeners’ neural activities were recorded using EEG. After listening, we assessed the interpersonal closeness between the speaker and listeners. Compared to the sad group, sharing happy stories showed a better recall quality and a higher rating of interpersonal closeness.Meanwhile, the happy group showed higher interpersonal brain synchronization (IBS) in the prefrontal cortex (PFC) and temporal cortex (specifically TPJ) than the sad group. Moreover, such IBS mediated the relationship between the quality of sharing stories and interpersonal closeness, and happy emotion moderated this mediation model. The magnitude of IBS differentiated high interpersonal closeness from low interpersonal closeness. Exploratory analysis using support vector regression showed that the IBS could also predict the ratings of interpersonal closeness in left-out subjects. These results suggest that IBS could serve as an indicator of whether sharing emotional stories facilitate interpersonal closeness. These findings improve our understanding of sharing emotional information among individuals that guide behaviors during interpersonal interactions.
Evolving a new efficient mode of fructose utilization for improved bioproduction inCorynebacterium glutamicum
Authors: Krahn Irene , Bonder Daniel , Torregrosa Lucia , Stoppel Dominik , Krause Jens P. , Rosenfeldt Natalie , Meiswinkel Tobias M. , Seibold Gerd M. , Wendisch Volker F. , Lindner Steffen N. 
Published: February 2021

AbstractFructose utilization inCorynebacterium glutamicumstarts with its uptake and concomitant phosphorylation via the phosphotransferase system (PTS) to yield intracellular fructose 1-phosphate, which enters glycolysis upon ATP dependent phosphorylation to fructose 1,6-bisphosphate by 1-phosphofructokinase. This is known to result in a significantly reduced oxidative pentose phosphate pathway (oxPPP) flux on fructose (~10 %) compared to glucose (~60 %). Consequently, the biosynthesis of NADPH demanding products, e.g. L-lysine, byC. glutamicumis largely decreased, when fructose is the only carbon source. Previous works reported that fructose is partially utilized via the glucose specific PTS presumably generating fructose 6-phosphate. This closer proximity to the entry point of the oxPPP might increase oxPPP flux and consequently NADPH availability. Here, we generated deletion strains either lacking in the fructose-specific PTS or 1-phosphofructokinase activity. We used these strains in short-term evolution experiments on fructose minimal medium and isolated mutant strains, which regained the ability of fast growth on fructose as a sole carbon source. In these fructose mutants, the deletion of the glucose specific PTS, as well as the 6-phosphofructokinase gene, abolished growth, unequivocally showing fructose phosphorylation via glucose specific PTS to fructose 6-phosphate. Gene sequencing revealed three independent amino acid substitutions in PtsG (M260V, M260T, P318S). These three PtsG variants mediated faster fructose uptake and utilization compared to native PtsG. In-depth analysis of the effects of fructose utilization via these PtsG variants revealed significantly increased biomass formation, reduced side-product accumulation, and increased L-lysine production by 50 %.
Structural basis of drug recognition by the multidrug transporter ABCG2
Authors: Kowal Julia , Ni Dongchun , Jackson Scott M , Manolaridis Ioannis , Stahlberg Henning , Locher Kaspar P 
Published: February 2021

ABSTRACTABCG2 is an ATP-binding cassette (ABC) transporter whose function affects the pharmacokinetics of drugs and contributes to multidrug resistance of cancer cells. While its interaction with the endogenous substrate estrone-3-sulfate (E1S) has been elucidated at a structural level, the recognition and recruitment of exogenous compounds is not understood at sufficiently high resolution. Here we present three cryo-EM structures of nanodisc-reconstituted, human ABCG2 bound to anticancer drugs tariquidar, topotecan and mitoxantrone. To enable structural insight at high resolution, we used Fab fragments of the ABCG2-specific monoclonal antibody 5D3, which binds to the external side of the transporter but does not interfere with drug-induced stimulation of ATPase activity. We observed that the binding pocket of ABCG2 can accommodate a single tariquidar molecule in a C-shaped conformation, similar to one of the two tariquidar molecules bound to ABCB1, where tariquidar acts as an inhibitor. We also found single copies of topotecan and mitoxantrone bound between key phenylalanine residues. Mutagenesis experiments confirmed the functional importance of two residues in the binding pocket, F439 and N436. Using 3D variability analyses, we found a correlation between substrate binding and reduced dynamics of the nucleotide binding domains (NBDs), suggesting a structural explanation for drug-induced ATPase stimulation. Our findings provide insight into how ABCG2 differentiates between inhibitors and substrates and may guide a rational design of new modulators and substrates.
Mosquito Larvae (Culex spp.) Startle Responses to Vibration Stimuli
Authors: Harrison Ellie R. , Budenberg William J. 
Published: February 2021

AbstractWe explored startle responses ofCulex spp.larvae to varying frequencies and durations of vibrations, before investigating habituation (a behavioural learning phenomenon). The startle response consists of a rapid movement to permit escape from a potentially dangerous stimulus. We used the automated Zantiks MWP_vb unit to analyse larval startle responses through the built-in live video tracking. Set within the unit’s controlled environmental chamber, we recorded distance travelled by the larvae. These results were used to optimise the vibration startle response for use in habituation studies. Repeated vibrations appeared to reduce larvae startle responses, although further analysis is required to confirm habituation. This study not only provides an insight into the learning ability of mosquito larvae, but demonstrates the ease, replicability and control conferred by the automated unit. Furthermore, this method is applicable to many other organisms and shows potential for more sophisticated environmental effect testing, such as behavioural toxicology.
Alzheimer’s-like remodeling of neuronal ryanodine receptor in COVID-19
Authors: Reiken Steve , Dridi Haikel , Sittenfeld Leah , Liu Xiaoping , Marks Andrew R 
Published: February 2021

SummaryCOVID-19, caused by SARS-CoV-2 involves multiple organs including cardiovascular, pulmonary and central nervous system. Understanding how SARS-CoV-2 infection afflicts diverse organ systems remains challenging1,2. Particularly vexing has been the problem posed by persistent organ dysfunction known as “long COVID,” which includes cognitive impairment3. Here we provide evidence linking SARS-CoV-2 infection to activation of TGF-ß signaling and oxidative overload. One consequence is oxidation of the ryanodine receptor/calcium (Ca2+) release channels (RyR) on the endo/sarcoplasmic (ER/SR) reticuli in heart, lung and brains of patients who succumbed to COVID-19. This depletes the channels of the stabilizing subunit calstabin2 causing them to leak Ca2+which can promote heart failure4,5, pulmonary insufficiency6and cognitive and behavioral defects7–9.Ex-vivotreatment of heart, lung, and brain tissues from COVID-19 patients using a Rycal drug (ARM210)10prevented calstabin2 loss and fixed the channel leak. Of particular interest is that neuropathological pathways activated downstream of leaky RyR2 channels in Alzheimer’s Disease (AD) patients were activated in COVID-19 patients. Thus, leaky RyR2 Ca2+channels may play a role in COVID-19 pathophysiology and could be a therapeutic target for amelioration of some comorbidities associated with SARS-CoV-2 infection.
Interacting rhythms enhance sensitivity of target detection in a fronto-parietal computational model of visual attention
Authors: Aussel Amélie , Fiebelkorn Ian C. , Kastner Sabine , Kopell Nancy J. , Pittman-Polletta Benjamin R. 
Published: February 2021

AbstractEven during sustained attention, enhanced processing of attended stimuli waxes and wanes rhythmically, with periods of enhanced and relatively diminished visual processing (and subsequent target detection) alternating at 4 or 8 Hz in a sustained visual attention task. These alternating attentional states occur alongside alternating dynamical states, in which lateral intraparietal cortex (LIP), the frontal eye field (FEF), and the mediodorsal pulvinar (mdPul) exhibit different activity and functional connectivity atα, β, andγfrequencies—rhythms associated with visual processing, working memory, and motor suppression. To assess whether and how these multiple interacting rhythms contribute to periodicity in attention, we propose a detailed computational model of FEF and LIP. When driven byθ-rhythmic inputs simulating experimentally-observed mdPul activity, this model reproduced the rhythmic dynamics and behavioral consequences of observed attentional states, revealing that the frequencies and mechanisms of the observed rhythms allow for peak sensitivity in visual target detection while maintaining functional flexibility.
A roadmap for sustainability assessment in the food supply chain
Authors: León Bravo Verónica , Moretto Antonella , Caniato Federico 
Published: February 2021

PurposeTo develop a roadmap of sustainability practices and assessment mechanisms to advance in the sustainable supply chain (SSC) performance assessment in the food supply chain. The analysis is grounded on the contingency and stakeholder theories.Design/methodology/approachThe study follows a multiple case study approach analyzing the sustainability practices implementation and assessment across different supply chain stages in the food industry in Italy. The set of cases comprises 12 companies in the fresh fruit and vegetables (FFV), and seven companies in the “Balsamic Vinegar of Modena” (BVM) supply chains.FindingsThe sustainability practices and assessment in each company in both supply chains according to their objectives are identified. Different stakeholder pressures for sustainability implementation and assessment are analyzed. The contingency factors that foster sustainability assessment are outlined as well. Finally, the study develops a roadmap with five levels of progress considering the groups of practices implemented and the type of assessment applied.Practical implicationsThe roadmap is a decision-making tool for planning and monitoring progress on SSC performance along five possible levels of progress. While identifying the assessment mechanisms implemented for different kind of sustainability practices, companies can develop a strategy according to their aims and capabilities and stakeholder's expectations.Originality/valueThe novelties in this study are threefold. First, the roadmap with five levels of progress. Second, investigating two different food supply chains that allowed for a broader view regarding sustainability practices and assessment. Third, the adoption of stakeholder and contingency theories in SSC studies.
Certification label and fresh organic produce category in an emerging country: an experimental study on consumer trust and purchase intention
Authors: Watanabe Eluiza Alberto de Morais , Alfinito Solange , Barbirato Luisa Lourenço 
Published: February 2021

PurposeOrganic food consumption is growing, increasing the need for studies investigating the importance of organic certification labels in emerging countries. The research aims to identify the influence of certification labels and fresh organic produce categories (greenery, vegetable or fruit) on consumer trust and purchase intention.Design/methodology/approachAn online experimental survey 3 × 3 was administered among 349 Brazilian consumers. Certification label and fresh organic produce category were designated as independent variables and manipulated to explore consumer trust and purchase intention. The authors performed a multivariate covariance analysis (MANCOVA) to analyze the data.FindingsResults show that the certification label does not directly affect the dependent variables. It acts as a moderator and indirectly affects both consumer trust and purchase intention. Moreover, depending on the fresh organic produce category considered (greenery, vegetable or fruit), consumer trust changes. Sociodemographic characteristics, age and household income are also important. Finally, the greater the purchase frequency (the main predictor of the model), the greater the purchase intention and consumer trust.Originality/valueThe study contributes to deepen and expand studies involving organic food and to pave the way for future studies that aim to investigate the importance of certification labels of organic foods for consumers.
Emerging social and business trends associated with the Covid-19 pandemic
Authors: Yeganeh Hamid 
Published: February 2021

Purpose
This paper aims to identify, classify and study emerging social and business trends associated with the outbreak of the Covid-19 pandemic.

Design/methodology/approach
By adopting the meta-synthesis method, the study scrutinizes, synthesizes and interprets the findings from a pool of publications. This approach results in identifying 53 key ideas that are classified under nine dominant trends.

Findings
The study identifies and examines nine major trends caused and intensified by the Covid-19 pandemic, i.e. the rise of authoritarianism, the new era of corporate welfare, deep imbalances in public finances, exacerbated inequalities, higher risks of poverty and famine, the dominance of giant corporations, the increasing influence of big tech, the accelerated innovation and the fluidity of work and organizations. The paper suggests that these trends are the continuation of the past three decades’ transformations, are contributing to the rising concentration of power and wealth and are leading to a new type of globalization marked by high connectivity and low tangibility.

Originality/value
The originality of this paper resides in adopting a multidisciplinary approach to analyzing various social and business dimensions of a complex phenomenon. While the study should not be viewed as a comprehensive investigation, it offers a groundwork for further research on Covid-19.