bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of different moisture and temperature levels on Salmonella survival in poultry fat
Authors: Trinetta Valentina , McDaniel Austin , Magossi Gabriela , Yucel Umut , Jones Cassandra
Published: June 2019

Fat products have been historically thought to have too low water activity to harbor pathogens. However, it has been recently reported that high moisture levels in fats may lead to Salmonella presence and growth. Limited research on strategies to eliminate pathogens in these environments is available, and the mechanisms contributing to microbial presence and growth are not yet well understood. The purpose of this research was to evaluate the effects of moisture levels and storage temperatures on the growth and survival of Salmonella in poultry fat. Samples were stored for 7 d at 48°C or 76°C and remaining Salmonella was evaluated. When poultry fat was challenged with a wet high inoculum, more than a 4 log CFU/mL difference in Salmonella population was observed with 1% and 3% moisture levels at 48°C after 5 d (P < 0.05). No differences between moisture levels (P > 0.05) were observed when samples were tested with a wet low inoculum. Counts below detectable limits were observed after 24 h in samples challenged at 76°C, regardless of inoculum level. When poultry fat was stored at 48°C and inoculated with low levels of Salmonella spp., bacterial growth was influenced only by time (P < 0.05) and not affected (P > 0.05) by moisture level. However, when poultry fat was stored at 48°C and inoculated with high levels of Salmonella spp., bacterial decrease was easier (P < 0.05) in samples containing greater moisture. This research suggests that residual moisture in containers during transportation of poultry fat largely does not affect Salmonella spp. growth.
Vitamin D status in Sudanese pregnant women: a cross-sectional study
Authors: Gaffer Ahmed A , Rayis Duria A , Elhussein Osama G , Adam Ishag
Published: June 2019

Background

Maternal vitamin D deficiency is associated with maternal and perinatal adverse effects. This study was conducted to assess the vitamin D status among pregnant Sudanese women.

Methods

A total of 180 pregnant women were enrolled in a cross-sectional study in Saad Abualila Hospital, Khartoum, Sudan. The medical history of each woman was collected and 25-hydroxyvitamin D [25(OH)D] was measured using an electrochemiluminescence immunoassay.

Results

The median age, gravidity and gestational age was 27.7 y, 1.0 and 10.7 weeks, respectively. Of the 180 woman, 169 (93.9%) had vitamin D deficiency (≤20 ng/ml). There was no correlation between the 25(OH)D level and body mass index (r=−0.135, p=0.071) or haemoglobin level (r= 0.001, p=0.999).

Conclusions

The current study showed a high prevalence of vitamin D deficiency. Further studies investigating the risk factors for vitamin D deficiency and the outcome of pregnancy are needed.
Cranial morphology and phylogenetic relationships of the Middle Permian pareiasaur Embrithosaurus schwarzi from the Karoo Basin of South Africa
Authors: Van den Brandt Marc Johan , Abdala Fernando , Rubidge Bruce Sidney
Published: June 2019

Pareiasaurs were globally distributed, abundant, herbivorous parareptiles of the Middle to Late Permian, with the basal-most members found in the Middle Permian of South Africa. These basal taxa were particularly abundant and went extinct at the end of the Gaudalupian (Capitanian) at the top of the Tapinocephalus Assemblage Zone. Currently four taxa are recognized in this group: Bradysaurus seeleyi, B. baini, Nochelesaurus alexanderi and Embrithosaurus schwarzi, but they are all poorly understood. We here present the first detailed cranial description and updated diagnosis for Embrithosaurus schwarzi. No cranial autapomorphies were identified. However, Embrithosaurus schwarzi is a distinct taxon in this group, based on its unique dentition and using a combination of cranial features. It has nine marginal cusps on all maxillary and mandibular teeth, and wider maxillary teeth than in the co-occurring taxa, due to the marginal cusps being arranged more regularly around the crown, and the apex of the crown lacking the long, central, three-cusped trident. Our updated phylogenetic analysis recovers the four Middle Permian South African taxa as a monophyletic group for the first time, which we call Bradysauria, comprising a clade including Embrithosaurus, Bradysaurus baini and a polytomy including Nochelesaurus and Bradysaurus seeleyi.
Ants learn fast and do not forget: associative olfactory learning, memory and extinction inFormica fusca
Authors: Piqueret Baptiste , Sandoz Jean-Christophe , d'Ettorre Patrizia
Published: June 2019

Learning is a widespread phenomenon that allows behavioural flexibility when individuals face new situations. However, learned information may lose its value over time. If such a memory endures, it can be deleterious to individuals. The process of extinction allows memory updating when the initial information is not relevant anymore. Extinction is widespread among animals, including humans. We investigated associative appetitive learning in an ant species that is widely distributed in the Northern Hemisphere,Formica fusca. We studied acquisition and memory between 1 h and one week after conditioning, as well as the extinction process. Ants learn very rapidly, their memory lasts up to 3 days, decreases slowly over time and is highly resistant to extinction, even after a single conditioning trial. Using a pharmacological approach, we show that this single-trial memory critically depends on protein synthesis (long-term memory). These results indicate that individual ant workers ofF. fuscashow remarkable learning and memory performances. Intriguingly, they also show a strong resistance to updating learned associations. Resistance to extinction may be advantageous when the environment is stochastic and individuals need to switch often from one learned task to another.
Dissipation potentials from elastic collapse
Authors: Goddard Joe , Kamrin Ken
Published: June 2019

Generalizing Maxwell's (Maxwell 1867 IV.
Phil. Trans. R. Soc. Lond.
157
, 49–88 (
doi:10.1098/rstl.1867.0004
)) classical formula, this paper shows how the dissipation potentials for a dissipative system can be derived from the elastic potential of an elastic system undergoing continual failure and recovery. Hence, stored elastic energy gives way to dissipated elastic energy. This continuum-level response is attributed broadly to dissipative microscopic transitions over a multi-well potential energy landscape of a type studied in several previous works, dating from Prandtl's (Prandtl 1928 Ein Gedankenmodell zur kinetischen Theorie der festen Körper.
ZAMM
8
, 85–106) model of plasticity. Such transitions are assumed to take place on a characteristic time scale
T
, with a nonlinear viscous response that becomes a plastic response for

T
→
0

. We consider both discrete mechanical systems and their continuum mechanical analogues, showing how the Reiner–Rivlin fluid arises from nonlinear isotropic elasticity. A brief discussion is given in the conclusions of the possible extensions to other dissipative processes.
Honeybees possess a structurally diverse and functionally redundant set of queen pheromones
Authors: Princen Sarah A. , Oliveira Ricardo Caliari , Ernst Ulrich R. , Millar Jocelyn G. , van Zweden Jelle S. , Wenseleers Tom
Published: June 2019

Queen pheromones, which signal the presence of a fertile queen and induce workers to remain sterile, play a key role in regulating reproductive division of labour in insect societies. In the honeybee, volatiles produced by the queen's mandibular glands have been argued to act as the primary sterility-inducing pheromones. This contrasts with evidence from other groups of social insects, where specific queen-characteristic hydrocarbons present on the cuticle act as conserved queen signals. This led us to hypothesize that honeybee queens might also employ cuticular pheromones to stop workers from reproducing. Here, we support this hypothesis with the results of bioassays with synthetic blends of queen-characteristic alkenes, esters and carboxylic acids. We show that all these compound classes suppress worker ovary development, and that one of the blends of esters that we used was as effective as the queen mandibular pheromone (QMP) mix. Furthermore, we demonstrate that the two main QMP compounds 9-ODA and 9-HDA tested individually were as effective as the blend of all four major QMP compounds, suggesting considerable signal redundancy. Possible adaptive reasons for the observed complexity of the honeybee queen signal mix are discussed.
The effects of the neonicotinoid imidacloprid on gene expression and DNA methylation in the buff-tailed bumblebee
Bombus terrestris
Authors: Bebane P. S. A. , Hunt B. J. , Pegoraro M. , Jones A. R. C , Marshall H. , Rosato E. , Mallon E. B.
Published: June 2019

Neonicotinoids are effective insecticides used on many important arable and horticultural crops. They are nicotinic acetylcholine receptor agonists which disrupt the function of insect neurons and cause paralysis and death. In addition to direct mortality, there are numerous sublethal effects of low doses of neonicotinoids on bees. We hypothesize that some of these large array of effects could be a consequence of epigenetic changes in bees induced by neonicotinoids. We compared whole methylome (BS-seq) and RNA-seq libraries of the brains of buff-tailed bumblebee
Bombus terrestris
workers exposed to field-realistic doses of the neonicotinoid imidacloprid to libraries from control workers. We found numerous genes which show differential expression between neonicotinoid-treated bees and control bees, but no differentially methylated cytosines in any context. We found CpG methylation to be focused mainly in exons and associated with highly expressed genes. We discuss the implications of our results for future legislation.
Long-distance dispersal, ice sheet dynamics and mountaintop isolation underlie the genetic structure of glacier ice worms
Authors: Hotaling Scott , Shain Daniel H. , Lang Shirley A. , Bagley Robin K. , Tronstad Lusha M. , Weisrock David W. , Kelley Joanna L.
Published: June 2019

Disentangling the contemporary and historical factors underlying the spatial distributions of species is a central goal of biogeography. For species with broad distributions but little capacity to actively disperse, disconnected geographical distributions highlight the potential influence of passive, long-distance dispersal (LDD) on their evolutionary histories. However, dispersal alone cannot completely account for the biogeography of any species, and other factors—e.g. habitat suitability, life history—must also be considered. North American ice worms (Mesenchytraeus solifugus) are ice-obligate annelids that inhabit coastal glaciers from Oregon to Alaska. Previous studies identified a complex biogeographic history for ice worms, with evidence for genetic isolation, unexpectedly close relationships among geographically disjunct lineages, and contemporary migration across large (e.g. greater than 1500 km) areas of unsuitable habitat. In this study, we analysed genome-scale sequence data for individuals from most of the known ice worm range. We found clear support for divergence between populations along the Pacific Coast and the inland flanks of the Coast Mountains (meanFST= 0.60), likely precipitated by episodic ice sheet expansion and contraction during the Pleistocene. We also found support for LDD of ice worms from Alaska to Vancouver Island, perhaps mediated by migrating birds. Our results highlight the power of genomic data for disentangling complex biogeographic patterns, including the presence of LDD.
Honeybee dietary neonicotinoid exposure is associated with pollen collection from agricultural weeds
Authors: Wood T. J. , Kaplan I. , Zhang Y. , Szendrei Z.
Published: June 2019

Neonicotinoid insecticides have been linked to bee declines. However, tracking the primary exposure route for bees in the field has proven to be a major logistical challenge, impeding efforts to restore pollinator health in agricultural landscapes. We quantified neonicotinoid concentrations and botanical species composition in 357 pollen samples collected from 114 commercial honeybee colonies placed along a gradient of agricultural intensity between June and September. Neonicotinoid concentrations increased through the season, peaking at the end of August. As a result, concentrations in pollen were negatively associated with collection from woody and crop plants that flower early-mid season, and positively associated with collection from herbaceous plants that flower mid-late season. Higher clothianidin and thiamethoxam residues were correlated with samples containing a greater proportion of pollen collected from agricultural weeds. The percentage of agricultural land within 1500 m was positively correlated with thiamethoxam concentration; however, this spatial relationship was far weaker than the relationship with the proportion of pollen collected from herbaceous plants. These results indicate that both plant species identity and agricultural dominance are important in determining honeybee neonicotinoid exposure through the pollen diet, but that uncultivated plants associated with agriculture are the source of the greatest acute exposure.
A Bayesian framework for identifying consistent patterns of microbial abundance between body sites
Authors: Meier Richard , Thompson Jeffrey A , Chung Mei , Zhao Naisi , Kelsey Karl T. , Michaud Dominique S. , Koestler Devin C.
Published: June 2019

Recent studies have found that the microbiome in both gut and mouth are associated with diseases of the gut, including cancer. If resident microbes could be found to exhibit consistent patterns between the mouth and gut, disease status could potentially be assessed non-invasively through profiling of oral samples. Currently, there exists no generally applicable method to test for such associations. Here we present a Bayesian framework to identify microbes that exhibit consistent patterns between body sites, with respect to a phenotypic variable. For a given operational taxonomic unit (OTU), a Bayesian regression model is used to obtain Markov-Chain Monte Carlo estimates of abundance among strata, calculate a correlation statistic, and conduct a formal test based on its posterior distribution. Extensive simulation studies demonstrate overall viability of the approach, and provide information on what factors affect its performance. Applying our method to a dataset containing oral and gut microbiome samples from 77 pancreatic cancer patients revealed several OTUs exhibiting consistent patterns between gut and mouth with respect to disease subtype. Our method is well powered for modest sample sizes and moderate strength of association and can be flexibly extended to other research settings using any currently established Bayesian analysis programs.
Network Topology Dynamics of Circulating Biomarkers and Cognitive Performance in Older Cytomegalovirus-seropositive or -seronegative Men and Women
Authors: Benedetto Svetlana Di , Müller Ludmila , Rauskolb Stefanie , Sendtner Michael , Fassnacht Martin , Pawelec Graham , Müller Viktor
Published: June 2019

Background

Cytokines are signaling molecules operating within complex cascade patterns and having exceptional modulatory functions. They impact various physiological processes such as neuroendocrine and metabolic interactions, neurotrophins’ metabolism, neuroplasticity, and may affect behavior and cognition. In our previous study, we found that sex and Cytomegalovirus (CMV)-serostatus may modulate levels of circulating pro- and anti-inflammatory cytokines, metabolic factors, immune cells, and cognitive performance, as well as associations between them.

Results

In the present study, we used a graph-theoretical approach to investigate the network topology dynamics of 22 circulating biomarkers and 11 measures of cognitive performance in 161 older participants recruited to undergo a six-months training intervention. For network construction, we applied coefficient of determination (R2) that was calculated for all possible pairs of variables (N = 33) in four groups (CMV− men and women; CMV+ men and women). Network topology has been evaluated by clustering coefficient (CC) and characteristic path length (CPL) as well as local (Elocal) and global (Eglobal) efficiency, showing the degree of network segregation (CC and Elocal) and integration (CPL and Eglobal). We found that networks under consideration showed small-world networks properties with more random characteristics. Mean CC, as well as local and global efficiency were highest and CPL shortest in CMV− males (having lowest inflammatory status and highest cognitive performance). CMV− and CMV+ females did not show any significant differences. Modularity analyses showed that the networks exhibit in all cases highly differentiated modular organization (with Q-value ranged between 0.397 and 0.453).

Conclusions

In this work, we found that segregation and integration properties of the network were notably stronger in the group with balanced inflammatory status. We were also able to confirm our previous findings that CMV-infection and sex modulate multiple circulating biomarkers and cognitive performance and that balanced inflammatory and metabolic status in elderly contributes to better cognitive functioning. Thus, network analyses provide a useful strategy for visualization and quantitative description of multiple interactions between various circulating pro- and anti-inflammatory biomarkers, hormones, neurotrophic and metabolic factors, immune cells, and measures of cognitive performance and can be in general applied for analyzing interactions between different physiological systems.
Adiabatic invariants drive rhythmic human motion in variable gravity
Authors: Boulanger N. , Buisseret F. , Dehouck V. , Dierick F. , White O.
Published: June 2019

Natural human movements are stereotyped. They minimise cost functions that include energy, a natural candidate from mechanical and physiological points of view. In time-changing environments, however, motor strategies are modified since energy is no longer conserved. Adiabatic invariants are relevant observables in such cases, although they have not been investigated in human motor control so far. We fill this gap and show that the theory of adiabatic invariants explains how humans move when gravity varies.
Nucleus Basalis Stimulation Enhances Working Memory by Stabilizing Attractor Networks in Prefrontal Cortex
Authors: Qi Xue-Lian , Liu Ruifeng , Singh Balbir , Bestue David , Compte Albert , Vazdarjanova Almira I. , Blake David T. , Constantinidis Christos
Published: June 2019

Acetylcholine in the neocortex is critical for executive function. Degeneration of the basal forebrain cholinergic system is associated with cognitive decline in aging and Alzheimer’s disease. Cholinergic agonists and acetylcholinesterase inhibitors improve cognitive performance as does intermittent electrical stimulation of the cortical source of acetylcholine, the Nucleus Basalis (NB) of Meynert. Here we tested how NB stimulation improves working memory behavior and alters its neural code. NB stimulation increased dorsolateral prefrontal activity during the delay period of working memory tasks but did not strengthen phasic responses to the optimal visual stimulus of each neuron. Unexpectedly, improvement of behavioral performance was not the result of increased neural selectivity. Tuning of neuronal responses broadened, which rendered an attractor network more stable and filtered distracting visual stimuli more effectively. Thus, the effects of acetylcholine on prefrontal neural activity and selectivity in working memory contrast those of dopamine and stabilize neural ensembles based on neuromodulatory tone.
Neural Multi-Scale Self-Supervised Registration for Echocardiogram Dense Tracking
Authors: Zhu Wentao , Huang Yufang , Vannan Mani A , Liu Shizhen , Xu Daguang , Fan Wei , Qian Zhen , Xie Xiaohui
Published: June 2019

Echocardiography has become routinely used in the diagnosis of cardiomyopathy and abnormal cardiac blood flow. However, manually measuring myocardial motion and cardiac blood flow from echocar-diogram is time-consuming and error-prone. Computer algorithms that can automatically track and quantify myocardial motion and cardiac blood flow are highly sought after, but have not been very successful due to noise and high variability of echocardiography. In this work, we propose a neural multi-scale self-supervised registration (NMSR) method for automated myocardial and cardiac blood flow dense tracking. NMSR incorporates two novel components: 1) utilizing a deep neural net to parameterize the velocity field between two image frames, and 2) optimizing the parameters of the neural net in a sequential multi-scale fashion to account for large variations within the velocity field. Experiments demonstrate that NMSR yields significantly better registration accuracy than the state-of-the-art methods, such as advanced normalization tools (ANTs) and Voxel Morph, for both myocardial and cardiac blood flow dense tracking. Our approach promises to provide a fully automated method for fast and accurate analyses of echocardiograms.
Catabolism of alkylphenols inRhodococcusvia ameta-cleavage pathway associated with genomic islands
Authors: Levy-Booth David J. , Fetherolf Morgan M. , Stewart Gordon , Liu Jie , Eltis Lindsay D. , Mohn William W.
Published: June 2019

The bacterial catabolism of aromatic compounds has considerable promise to convert lignin depolymerization products to commercial chemicals. Alkylphenols are a key class of depolymerization products whose catabolism is not well elucidated. We isolatedRhodococcus rhodochrousEP4 on 4-ethylphenol and applied genomic and transcriptomic approaches to elucidate alkylphenol catabolism in EP4 andRhodococcus jostiiRHA1. RNA-Seq and RT-qPCR revealed a pathway encoded by theaphABCDEFGHIQRSgenes that degrades 4-ethylphenol via themeta-cleavage of 4-ethylcatechol. This process was initiated by a two-component alkylphenol hydroxylase, encoded by theaphABgenes, which were up-regulated ~3,000-fold. Purified AphAB from EP4 had highest specific activity for 4-ethylphenol and 4-propylphenol (~2000 U/mg) but did not detectably transform phenol. Nevertheless, a ΔaphAmutant in RHA1 grew on 4-ethylphenol by compensatory up-regulation of phenol hydroxylase genes (pheA1-3). Deletion ofaphC, encoding an extradiol dioxygenase, prevented growth on 4-alkylphenols but not phenol. Disruption ofpcaLin the β-ketoadipate pathway prevented growth on phenol but not 4-alkylphenols. Thus, 4-ethylphenol and 4-propylphenol are catabolized exclusively viameta-cleavage in rhodococci while phenol is subject toortho-cleavage. Putative genomic islands encodingaphgeneswere identified in EP4 and several other rhodococci. Overall, this study identifies a 4-alkylphenol pathway in rhodococci, demonstrates key enzymes involved, and presents evidence that the pathway is encoded in a genomic island. These advances are of particular importance for wide-ranging industrial applications of rhodococci, including upgrading of lignocellulose biomass.

Importance

Elucidation of bacterial alkylphenol catabolism is important for the development of biotechnologies to upgrade the lignin component of plant biomass. We isolated a new strain,Rhodococcus rhodochrousEP4, on 4-ethylphenol, an alkylphenol that occurs in lignin-derived streams, including reductive catalytic fractionation products of corn stover. We further demonstrated its degradation via ameta-cleavage pathway (Aph) with transcriptomics. A new class of Actinobacterial hydroxylase, AphAB, acts specifically on alkylphenols. Phylogenomic analysis indicated that theaphgenes occur on putative genomic islands in several rhodococcal strains. These genes were identified in the genetically-tractable strainRhodococcus jostiiRHA1. Strains missing this element cannot metabolise 4-ethylphenol and 4-propylphenol. Overall, we advanced the understanding of how aromatic compounds are degraded by environmental bacteria and identified enzymes that can be employed in the transition away from petro-chemicals towards renewable alternatives.
Protein function prediction in genomes: Critical assessment of coiled-coil predictions based on protein structure data
Authors: Simm Dominic , Hatje Klas , Waack Stephan , Kollmar Martin
Published: June 2019

Coiled-coil regions were among the first protein motifs described structurally and theoretically. The beauty and simplicity of the motif gives hope to detecting coiled-coil regions with reasonable accuracy and precision in any protein sequence. Here, we re-evaluated the most commonly used coiled-coil prediction tools with respect to the most comprehensive reference data set available, the entire Protein Data Base (PDB), down to each amino acid and its secondary structure. Apart from the thirtyfold difference in number of predicted coiled-coils the tools strongly vary in their predictions, across structures and within structures. The evaluation of the false discovery rate and Matthews correlation coefficient, a widely used performance metric for imbalanced data sets, suggests that the tested tools have only limited applicability for large data sets. Coiled-coil predictions strongly impact the functional characterization of proteins, are used for functional genome annotation, and should therefore be supported and validated by additional information.
Genetic dissection reveals the role of Ash1 domains in counteracting Polycomb repression
Authors: Dorafshan Eshagh , Kahn Tatyana G. , Glotov Alexander , Savitsky Mikhail , Schwartz Yuri B.
Published: June 2019

Antagonistic functions of Polycomb and Trithorax proteins are essential for proper development of all metazoans. While the Polycomb proteins maintain the repressed state of key developmental genes, the Trithorax proteins ensure that these genes stay active in cells where they have to be expressed. Ash1 is the Trithorax protein that was proposed to counteract Polycomb repression by methylating lysine 36 of histone H3. However, recently it was shown that genetic replacement ofDrosophilahistone H3 with the variant that carried Arginine instead of Lysine at position 36 did not impair the ability of Ash1 to counteract Polycomb repression. This argues that Ash1 counteracts Polycomb repression by methylating, yet unknown, non-histone proteins. To find these substrates, one may need to look beyond the function of the Ash1 histone methyltransferase SET domain at other evolutionary conserved parts of the protein that received little attention. Here we usedDrosophilagenetics to demonstrate that Ash1 requires each of the BAH, PHD and SET domains to counteract Polycomb repression, while AT hooks are dispensable. Our findings argue that,in vivo, Ash1 acts as a multimer. Thereby, it can combine the input of the SET domain and PHD-BAH cassette residing in different peptides. Finally, using new loss of function alleles, we show that zygotic Ash1 is required to prevent erroneous repression of homeotic genes.
Single-cell based elucidation of molecularly-distinct glioblastoma states and drug sensitivity
Authors: Ding Hongxu , Burgenske Danielle M. , Zhao Wenting , Subramaniam Prem S. , Bakken Katrina K. , He Lihong , Alvarez Mariano J. , Laise Pasquale , Paull Evan O. , Spinazzi Eleonora F. , Dovas Athanassios , Marie Tamara , Upadhyayula Pavan , Cruz Filemon Dela , Diolaiti Daniel , Kung Andrew , Bruce Jeffrey N. , Canoll Peter , Sims Peter A. , Sarkaria Jann N. , Califano Andrea
Published: June 2019

Glioblastoma heterogeneity and plasticity remain controversial, with proposed subtypes representing the average of highly heterogeneous admixtures of independent transcriptional states. Single-cell, protein-activity-based analysis allowed full quantification of >6,000 regulatory and signaling proteins, thus providing a previously unattainable single-cell characterization level. This helped identify four novel, molecularly distinct subtypes that successfully harmonize across multiple GBM datasets, including previously published bulk and single-cell profiles and single cell profiles from seven orthotopic PDX models, representative of prior subtype diversity. GBM is thus characterized by the plastic coexistence of single cells in two mutually-exclusive developmental lineages, with additional stratification provided by their proliferative potential. Consistently, all previous subtypes could be recapitulated by single-cell mixtures drawn from newly identified states. Critically, drug sensitivity was predicted and validated as highly state-dependent, both in single-cell assays from patient-derived explants and in PDX models, suggesting that successful treatment requires combinations of multiple drugs targeting these distinct tumor states.

Significance

We propose a new, 4-subtype GBM classification, which harmonizes across bulk and single-cell datasets. Single-cell mixtures from these subtypes effectively recapitulate all prior classifications, suggesting that the latter are a byproduct of GBM heterogeneity. Finally, we predict single-cell level activity of three clinically-relevant drugs, and validate them in patient-derived explant.
NemaLife: A structured microfluidic culture device optimized for aging studies in crawlingC. elegans
Authors: Rahman Mizanur , Edwards Hunter , Birze Nikolajs , Gabrilska Rebecca , Rumbaugh Kendra P. , Blawzdziewicz Jerzy , Szewczyk Nathaniel J. , Driscoll Monica , Vanapalli Siva A.
Published: June 2019

Caenorhabditis elegansis a powerful animal model in aging research. Standard longevity assays on agar plates involve the tedious task of picking and transferring animals to prevent younger progeny from contaminating age-synchronized adult populations. Large-scale studies employ progeny-blocking drugs or sterile mutants to avoid progeny contamination, but such manipulations change adult physiology and alter the influence of reproduction on normal aging. Moreover, for some agar growth-based technology platforms, such as automated lifespan machines, reagents such as food or drugs cannot be readily added/removed after initiation of the study. Current microfluidic approaches are well-suited to address these limitations, but in their liquid-based environments animals swim rather than crawl, introducing swim-induced stress in the lifespan analysis. Here we report a simple microfluidic device that we call NemaLife that features: 1) an optimized micropillar arena in which animals can crawl, 2) sieve channels that separate progeny and prevent the loss of adults from the arena during culture maintenance, and 3) ports which allow rapid accessibility to feed the adult-only population and introduce reagents as needed. Culture maintenance and liquid manipulation are performed with simple hand-held syringes to facilitate integration of our technology into general laboratory protocols. Additionally, device geometry and feeding protocols were designed to emulate the body gait, locomotion, and lifespan of animals reared on agar. We validated our approach with longevity analyses of classical aging mutants (daf-2,age-1,eat-2, anddaf-16) and animals subjected to RNAi knockdown of age-related genes (age-1anddaf-16). We also showed that healthspan measures such as pharyngeal pumping and tap-induced stimulated reversals can be scored across the lifespan. Overall, the capacity to generate reliable lifespan and physiological data from the NemaLife chip underscores the potential of this device to accelerate healthspan and lifespan investigations inC. elegans.
Choice suppression is achieved through opponent but not independent function of the striatal indirect pathway in mice
Authors: Delevich Kristen , Hoshal Benjamin , Collins Anne GE , Wilbrecht Linda
Published: June 2019

The dorsomedial striatum (DMS) plays a key role in action selection, but little is known about how direct and indirect pathway spiny projection neurons (dSPNs and iSPNs) contribute to choice suppression in freely moving animals. Here, we used pathway-specific chemogenetic manipulation during a serial choice foraging task to test opposing predictions for iSPN function generated by two theories: 1) the ‘select/suppress’ heuristic which suggests iSPN activity is required to suppress alternate choices and 2) the network-inspired Opponent Actor Learning model (OpAL) which proposes that the weighted difference of dSPN and iSPN activity determines choice. We found that chemogenetic activation, but not inhibition, of iSPNs disrupted learned suppression of nonrewarded choices, consistent with the predictions of the OpAL model. Our findings suggest that iSPNs’ role in stopping and freezing does not extend in a simple fashion to choice suppression. These data may provide insights critical for the successful design of interventions for addiction or other conditions in which suppression of behavior is desirable.
Transcriptome Dynamics Reveals Progressive Transition from Effector to Memory in CD4+T cells
Authors: Soon Megan S. F. , Lee Hyun Jae , Engel Jessica A. , Straube Jasmin , Thomas Bryce S. , Clarke Lachlan S. , Laohamonthonkul Pawat , Pernold Clara P. S. , Haldar Rohit N. , Williams Cameron G. , Lansink Lianne I. M. , Koufariotis Ross , Lakis Vanessa , Wood Scott , Chen Xi , James Kylie R. , Lönnberg Tapio , Lane Steven W. , Davenport Miles P. , Khoury David S. , Svensson Valentine , Teichmann Sarah A. , Haque Ashraful
Published: June 2019

CD4+T cells are repositories of immune memory, conferring enhanced immunity to many infectious agents. Studies of acute viral and bacterial infection suggest that memory CD4+T cells develop directly from effectors. However, delineating these dynamic developmental pathways has been challenging. Here, we used high-resolution single-cell RNA-seq and temporal mixture modelling to examine the fate of Th1 and Tfh effector cells during non-lethalPlasmodiuminfection in mice. We observed linear Th1 and Tfh pathways towards memory, characterized by progressive halving in the numbers of genes expressed, and partial transcriptomic coalescence. Low-level persisting infection diverted but did not block these pathways. We observed in the Th1-pathway a linear transition from Th1 through a Tr1 state to TEMcells, which were then poised for Th1 re-call. The Tfh-pathway exhibited a modest Th1-signature throughout, with little evidence of Tr1 development, and co-expression of TCMand memory Tfh markers. Thus, we present a high-resolution atlas of transcriptome dynamics for naïve to memory transitions in CD4+T cells. We also defined a subset of memory-associated genes, including transcription factorsId2andMaf, whose expression increased progressively against the background of transcriptomic quiescence. Single-cell ATAC-seq revealed substantial heterogeneity in chromatin accessibility in single effectors, which was extensively, though incompletely reset and homogenized in memory. Our data reveal that linear transitions from effector to memory occur in a progressive manner over several weeks, suggesting opportunities for manipulating CD4+T cell memory after primary infection.

Highlights

scRNA-seq reveals progressive transition from effector to memory in CD4+T cells.

Transcriptome dynamics suggest linear not branching models for memory development.

A subset of genes associates with gradual onset of CD4+T cell memory.

Th1/Tfh predisposition varies among clonotypes with identical antigen-specificity.

scATAC-seq uncovers non-coding “memory” elements in the genome.
An epitranscriptomic switch at the 5′-UTR controls genome selection during HIV-1 genomic RNA packaging
Authors: Pereira-Montecinos Camila , Toro-Ascuy Daniela , Rojas-Fuentes Cecilia , Riquelme-Barrios Sebastián , Rojas-Araya Bárbara , García-de-Gracia Francisco , Aguilera-Cortés Paulina , Ananías-Sáez Catarina , de Bisschop Grégoire , Chaniderman Jonás , Acevedo Mónica L. , Sargueil Bruno , Valiente-Echeverría Fernando , Soto-Rifo Ricardo
Published: June 2019

During retroviral replication, the full-length RNA serves both as mRNA and genomic RNA (gRNA). While the simple retrovirus MLV segregates its full-length RNA into two functional populations, the HIV-1 full-length RNA was proposed to exist as a single population used indistinctly for protein synthesis or packaging. However, the mechanisms by which the HIV-1 Gag protein selects the two RNA molecules that will be packaged into nascent virions remain poorly understood. Here, we demonstrate that HIV-1 full-length RNA packaging is regulated through an epitranscriptomic switch requiring demethylation of two conserved adenosine residues present within the 5′-UTR. As such, while m6A deposition by METTL3/METTL14 onto the full-length RNA was associated with increased Gag synthesis and reduced packaging, FTO-mediated demethylation was required for the incorporation of the full-length RNA into viral particles. Interestingly, HIV-1 Gag associates with the RNA demethylase FTO in the nucleus and drives full-length RNA demethylation. Finally, the specific inhibition of the FTO RNA demethylase activity suppressed HIV-1 full-length RNA packaging. Together, our data propose a novel epitranscriptomic mechanism allowing the selection of the full-length RNA molecules that will be used as viral genomes.
Consumption in fast-food restaurants in Croatia and Serbia
Authors: Sapic Srdjan , Filipovic Jovana , Dlacic Jasmina
Published: June 2019

Purpose

The purpose of this paper is to explore the antecedents of product evaluations and behavioural intentions regarding fast-food restaurants. Research tests the moderating effects of tradition on selected relationships in Croatia and Serbia. Further, it tests consumer willingness to use services in domestic and foreign fast-food restaurants.

Design/methodology/approach

Samples were collected from 332 and 362 respondents from Croatia and Serbia, respectively. The validity of the model was tested with confirmatory factor analysis, and structural equation modelling was used to determine main and interaction effects.

Findings

For both foreign and domestic fast-food restaurants, variety seeking and cosmopolitanism had a positive impact on consumer evaluations and behavioural intentions, while the desire for unique products had a negative impact. Personal innovativeness had a positive impact on evaluations and intentions regarding foreign restaurants but a negative impact for domestic restaurants. A moderating effect of tradition was more present in the Serbian sample.

Originality/value

This study is the first to use the theory of planned behaviour and theory of social identity to investigate the impact of variety seeking, desire for unique products, cosmopolitanism and personal innovativeness on consumption in fast-food restaurants in two emerging countries in the country of origin context. Furthermore, it also provides information for researchers and marketers on fast-food consumption antecedents in different countries. New insights are provided for the moderating role of tradition.
Agility assessment in manufacturing companies
Authors: Rahiminezhad Galankashi Masoud , Helmi Syed Ahmad , Abdul Rahim Abd. Rahman , Rafiei Farimah Mokhatab
Published: June 2019

Purpose

The purpose of this paper is to propose a framework to assess the agility of manufacturing companies.

Design/methodology/approach

Particularly, three supply chain logistic drivers (facility, transportation and inventory) along with three cross-functional drivers (information, sourcing and pricing) are selected as the main sets to classify all required activities of agility. In addition, supply chain contracts, as an important indicator of supply chain agility, is also considered to categorize the activities. These activities are ranked using an (AHP) and then categorized based on the major perspectives of agility. Finally, using a cycle view of supply chain, the developed activities are categorized as the major policies of supply chain’s echelons.

Findings

This study developed a framework to evaluate the agility of manufacturing companies. Operational activities of agile supply chain strategy (ASCS) in addition to supply chain contracts are determined and categorized with regard to supply chain drivers.

Originality/value

This study contributes to recognizing, ranking and classifying the operational activities of ASCS with regard to logistics and cross-functional drivers of supply chain. In addition, this study considers the supply chain contracts in conjunction with supply chain drivers. From the theoretic and methodological features, to the best of authors’ knowledge, this study contributes to offer new insights to this area as no similar research has been conducted before.
Story-making as a method for business modelling
Authors: Haggège Meyer , Vernay Anne-Lorène
Published: June 2019

Purpose

Imagining a new business model is a creative process that requires entrepreneurs to define how a firm can create and capture value with a new activity. The literature emphasises various tools and approaches for prototyping business models. The purpose of this paper is to investigate the suitability of story-making as a means of designing new business models and to shed light on its potential for stimulating creative entrepreneurial thinking.

Design/methodology/approach

This paper tests the use of story-making for business modelling in a real-life case to show its usefulness and shed light on its potential for stimulating creative entrepreneurial thinking.

Findings

The authors argue that story-making should be recognised as an approach to business modelling that can foster creativity and empathy. Building on insights from design thinking literature, the paper shows that planning for a long exploratory phase is necessary to allow system thinking. It also shows that anchors can act as intermediary stopping rule and help manage complexity.

Originality/value

The paper introduces an original method for crafting business models during early stages of the innovation process and argues that this method could also be used to design business processes, especially when they are not already formalised.
Beyond national culture difference
Authors: Cui Zhipeng , Liu Junying , Xia Bo , Cheng Yaxiao
Published: June 2019

Purpose

International construction joint ventures (ICJVs) have been widely used as a temporary arrangement in many projects all over the world, especially in megaprojects. Within ICJVs, the national culture difference between partners affects their cooperation significantly. However, prior research has provided contradictory empirical evidence regarding these impacts. To address this problem, the purpose of this paper is to introduce cultural intelligence that judges an individual’s capability to function and manage effectively in culturally diverse settings as a moderating variable.

Design/methodology/approach

Multiple regression analysis and moderated multiple regression were undertaken to test proposed hypotheses. A questionnaire survey was conducted with international construction practitioners who had experiences of managing or participating in ICJVs.

Findings

The result of multiple regression analysis revealed that difference in national culture has significant negative effects on information exchange, shared problem solving and flexibility when asking for changes, thus effecting cooperation within ICJVs. Meanwhile, cultural intelligence of members can weaken these negative influences.

Practical implications

First, given that national culture difference affects negatively on the cooperation within ICJVs, it needs to be regarded as one of vital resources of risk which should be prevented and managed when attending ICJVs; Second, managers should build a series of mutually agreeable regulations and rules to lessen the negative effect of national culture difference; Third, it is recommended that ICJV management teams contain as many work-experienced members as possible and members within ICJVs, especially new staff, receive cross-cultural training termly to facilitate the cooperation between partners.

Originality/value

This research reveals the moderating effects of cultural intelligence on the relationship between national culture difference and cooperation in ICJVs as well as provides practical implications for ICJV managers to deal with national culture difference and reduce its negative impact on cooperation within ICJVs.
How financial systems and firm strategy impact the choice of innovation funding
Authors: Sierra Jaime
Published: June 2019

Purpose

The funding of innovation is explained by typical cost-based financial approaches. This paper breaks away from such tradition, and the purpose of this paper is to propose an alternative view where innovation funding decisions are strategic and concern interactions between actors – each with their own characteristics and strategic intentions – project features, and traits of the setting in which interactions take place.

Design/methodology/approach

This paper builds up an alternative framework to understand how innovation is financed by considering the interplay of innovation characteristics, the strategic reasons of project owners and funders, and the role of the matching environment and conditions. This proposal includes explanatory elements overlooked by extant theories. An illustrative case is presented to support the need for this proposal.

Findings

The framework proposed proves useful to better understand innovation funding cases where the traditional financial theory does not suffice.

Practical implications

Innovative companies may improve decision making about resource allocation to innovation; innovation funders may refine their decision-making criteria and implementation; and policy makers and practitioners need to devise better supporting strategies for innovative companies.

Originality/value

This proposal considers a continuum of funding options where supply/demand will match on the grounds of strategic decisions made during the interaction itself, under certain contextual conditions. Hence, it enriches the understanding of strategic decisions regarding firm capital structure and investment theory when it comes to funding innovation.
Consumer engagement in online brand communities: the moderating role of personal values
Authors: Marbach Julia , Lages Cristiana , Nunan Daniel , Ekinci Yuksel
Published: June 2019

Purpose

Despite growing recognition of the importance of consumer engagement with new technologies, a gap remains in terms of understanding the antecedents, consequences and moderators of online consumer engagement (OCE). This paper aims to address this gap by exploring the relationship between personality traits, OCE, perceived value and the moderating role of personal values.

Design/methodology/approach

A theoretical framework anchored in the extant OCE literature is tested through a study of 559 users of two distinct firm-hosted online brand communities (FHOBCs).

Findings

Findings suggest that three personality traits – extraversion, openness to experiences and altruism – are positively correlated with OCE. OCE is related to two types of perceived value, namely, social value and aesthetic value. The personal values of conservation and self-enhancement moderate the relationships between the three identified personality traits and OCE.

Research limitations/implications

Future research into OCE should consider the application of this study’s conceptual framework across different cultures to account for the fast-changing nature of online communities.

Practical implications

Understanding how personality traits drive OCE and what value consumers receive from engagement in online communities can help managers to better segment and evaluate consumers. Engagement and levels of activity within these online communities can be improved accordingly.

Originality/value

This study’s contribution to the OCE literature is threefold. First, the study provides new insights regarding personality traits as antecedents of consumer engagement with FHOBCs. Second, the study reveals the first insights into the role of personal values in the relationship between personality traits and OCE. Specifically, conservation and self-enhancement emerged as moderators of the relationship between three personality traits (extraversion, openness to experiences, altruism) and OCE. Third, the study yields support for perceived value types (social value and aesthetic value) that emerge as consequences of consumer engagement in FHOBCs.