bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioproduction of single-stranded DNA from isogenic miniphage
Authors: Shepherd Tyson R. , Du Rebecca R. , Huang Hellen , Wamhoff Eike-Christian , Bathe Mark
Published: January 2019

Scalable production of gene-length single-stranded DNA (ssDNA) with sequence control has applications in homology directed repair templating, gene synthesis and sequencing, scaffolded DNA origami, and archival DNA memory storage. Biological production of circular single-stranded DNA (cssDNA) using bacteriophage M13 addresses these needs at low cost. A primary goal toward this end is to minimize the essential protein coding regions of the produced, exported sequence while maintaining its infectivity and production purity, with engineered regions of sequence control. Synthetic miniphage constitutes an ideal platform for bacterial production of isogenic cssDNA, using inserts of custom sequence and size to attain this goal, offering an inexpensive resource at milligram and higher synthesis scales. Here, we show that the Escherichia coli (E. coli) helper strain M13cp combined with a miniphage genome carrying only an f1 origin and a β-lactamase-encoding (bla) antibiotic resistance gene enables the production of pure cssDNA with a minimum sequence genomic length of 1,676 nt directly from bacteria, without the need for additional purification from contaminating dsDNA, genomic DNA, or fragmented DNAs. Low-cost scalability of isogenic, custom-length cssDNA is also demonstrated for a sequence of 2,520 nt using a commercial bioreactor. We apply this system to generate cssDNA for the programmed self-assembly of wireframe DNA origami objects with exonuclease-resistant, custom-designed circular scaffolds that are purified with low endotoxin levels (<5 E.U./ml) for therapeutic applications. We also encode digital information that is stored on the genome with application to write-once, read-many archival data storage.
Persistent effects of the orexin-1 receptor antagonist SB-334867 on motivation for the fast acting opioid remifentanil
Authors: Mohammadkhani Aida , James Morgan H. , Aston-Jones Gary
Published: January 2019

The orexin (hypocretin) system is important for reward-seeking behavior. The orexin-1 receptor (Ox1R) antagonist SB334867 (SB) reduces seeking of food and drug reward under conditions of high motivation. There is some evidence that the effects of systemic SB on reward seeking persist beyond the pharmacological availability of the drug, however the time course of these effects is not well characterized, nor is it known whether similar persistent effects are observed following intraparenchymal injections. Here, we used a behavioral economics paradigm, which allows for repeated testing of drug motivation across consecutive days, to examine the persistent effects of acute systemic and local treatment with SB on motivation for the short-acting opioid remifentanil. Systemic injections of SB immediately prior to behavioral testing reduced motivation for remifentanil; this effect was sustained on a subsequent test at 24h, but not on a third test at 48h. When injected locally into caudal ventral pallidum (cVP) the effects of SB were more persistent, with reduced motivation observed for up to 48h. We next made SB injections into cVP 24h prior to behavioral testing; this produced persistent effects that persisted for at least 72h post-treatment. Cued reinstatement of extinguished remifentanil seeking was also attenuated by pretreatment with SB 24h prior. These data indicate that the effects of SB on opioid seeking behavior persist beyond the bioavailability of the compound. These observations might have important ramifications for the future clinical use of orexin receptor antagonists for the treatment of addiction.
A language-familiarity effect on the recognition of computer-transformed vocal emotional cues
Authors: Nakai Tomoya , Rachman Laura , Arias Pablo , Okanoya Kazuo , Aucouturier Jean-Julien
Published: January 2019

People are more accurate in voice identification and emotion recognition in their native language than in other languages, a phenomenon known as the language familiarity effect (LFE). Previous work on cross-cultural inferences of emotional prosody has left it difficult to determine whether these native-language advantages arise from a true enhancement of the auditory capacity to extract socially relevant cues in familiar speech signals or, more simply, from cultural differences in how these emotions are expressed. In order to rule out such production differences, this work employed algorithmic voice transformations to create pairs of stimuli in the French and Japanese language which differed by exactly the same amount of prosodic expression. Even though the cues were strictly identical in both languages, they were better recognized when participants processed them in their native language. This advantage persisted in three types of stimulus degradation (jabberwocky, shuffled and reversed sentences). These results provide univocal evidence that production differences are not the sole drivers of LFEs in cross-cultural emotion perception, and suggest that it is the listeners’ lack of familiarity with the individual speech sounds of the other language, and not e.g. with their syntax or semantics, which impairs their processing of higher-level emotional cues.
phyloFlash – Rapid SSU rRNA profiling and targeted assembly from metagenomes
Authors: Gruber-Vodicka Harald R. , Seah Brandon K. B. , Pruesse Elmar
Published: January 2019

The SSU rRNA gene is the key marker in molecular ecology for all domains of life, but is largely absent from metagenome-assembled genomes that often are the only resource available for environmental microbes. Here we present phyloFlash, a pipeline to overcome this gap with rapid, SSU rRNA-centered taxonomic classification, targeted assembly, and graph-based binning of full metagenomic assemblies. We show that a cleanup of artifacts is pivotal even with a curated reference database. With such a filtered database, the general-purpose mapper BBmap extracts SSU rRNA reads five times faster than the rRNA-specialized tool SortMeRNA with similar sensitivity and higher selectivity on simulated metagenomes. Reference-based targeted assemblers yielded either highly fragmented assemblies or high levels of chimerism, so we employ the general-purpose genomic assembler SPAdes. Our optimized implementation is independent of reference database composition and has satisfactory levels of chimera formation. Using the phyloFlash workflow we could recover the first complete genomes of several enigmatic taxa, including Marinamargulisbacteria from surface ocean seawater. phyloFlash quickly processes Illumina (meta)genomic data, is straightforward to use, even as part of high-throughput quality control, and has user-friendly output reports. The software is available at https://github.com/HRGV/phyloFlash (GPL3 license) and is documented with an online manual.
Bacteriophage to Combat Biofilms in Hospital Drains
Authors: Huang Jenny Yijian
Published: January 2019

Background

According to the World Health Organization, nearly 15% of all hospitalized patients worldwide acquire nosocomial infections. A particular area of concern for bacterial build up in hospitals is sink drains. The moist, microbiologically active environment of drains promotes the formation of biofilms that are difficult to target with standard chemical disinfectants. Bacteriophages, however, show potential to be used as disinfecting agents in hospital drains. Not only do bacteriophages increase in titer as they infect, spreading to hard-to-reach surfaces, phages have been shown to degrade the extracellular matrix of biofilms and gain access to underlying bacteria. This research explores the potential of bacteriophages to eradicate biofilms in an environment modeling a sink drain by comparing the efficacy, range, and durability of bacteriophage to a chemical disinfectant.

Methods

E. coli biofilms were grown in M9 minimal media placed in sink P-traps assigned one of three treatments: chemical disinfectant, bacteriophage, or deionized water (control). Biofilms were quantified at five time points -- 1, 12, 24, 36, and 48 hours -- using the crystal violet assay.

Results

Both chemical disinfectant and bacteriophage significantly decreased the optical densities of biofilms (p < 0.001***). P-traps treated with bacteriophages showed more uniform destruction of biofilm across P-trap compared to chemical disinfectant (p < 0.01**). A trend may suggest that over time bacteriophage became more effective at reducing biofilm than chemical disinfectant.

Conclusion

This work highlights the potential of bacteriophage as an alternative to conventional chemical disinfectants for biofilm control in settings such as hospital drains.

Importance

Nosocomial infections prolong hospital stay, costing the U.S. healthcare system $5-10 billion annually. An increasing number of reports demonstrate that sink drains -- reservoirs for multidrug resistant bacteria -- may be a source of hospital-related outbreaks. Recent studies have elucidated the mechanism of dispersal of bacteria from contaminated sinks to patients, but limited data are available identifying disinfecting methods for hospital drains. Not only did this study demonstrate that bacteriophages could reduce biofilms on sink drains just as effectively as a commercial disinfectant, it showed that phages tended to spread more thoroughly across P-traps and may work for longer. With hand-washing an imperative activity for disease prevention, hospital sinks should remain clean. This work explores an alternative disinfecting method for hospital sink drains.
EphA7 functions as a receptor for cell-to-cell transmission of Kaposi’s sarcoma-associated herpesvirus into BJAB B cells and for cell-free virus infection by the related rhesus monkey rhadinovirus
Authors: Großkopf Anna K. , Schlagowski Sarah , Hörnich Bojan F. , Fricke Thomas , Desrosiers Ronald C. , Hahn Alexander S.
Published: January 2019

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma and is associated with two B cell malignancies, primary effusion lymphoma and the plasmablastic variant of multicentric Castleman’s disease. EphA2 functions as a cellular receptor for the gH/gL glycoprotein complex of KSHV for several adherent cell types. KSHV gH/gL was previously shown to also weakly interact with other members of the Eph family of receptors. Whether these interactions are of functional consequence remained unclear so far, even if other A-type Ephs were shown to be able to compensate for absence of EphA2 in overexpression systems. Here, we demonstrate for the first time that endogenously expressed EphA7 in BJAB B cells is critical for the cell-to-cell transmission of KSHV from producer iSLK cells to BJAB target cells. The BJAB lymphoblastoid cell line often serves as a model for B cell infection and expresses only low levels of all Eph family receptors other than EphA7. Endogenous EphA7 could be precipitated from the cellular lysate of BJAB cells using recombinant gH/gL, and knockout of EphA7 significantly reduced transmission of KSHV into BJAB target cells by over 80%. Finally, we demonstrate that receptor function of EphA7 is conserved between cell-to-cell transmission of KSHV and cell-free infection by the related rhesus monkey rhadinovirus (RRV), which is relatively even more dependent on EphA7 for infection of BJAB cells.

IMPORTANCE

Infection of B cells is biologically relevant for two KSHV-associated malignancies, the plasmablastic variant of multicentric Castleman’s disease (MCD) and primary effusion lymphoma (PEL). Elucidating the process of B cell infection is therefore important to understand the pathogenesis of these diseases. For various types of adherent cells, EphA2 has been shown by several groups to function as an entry receptor that is engaged by the gH/gL glycoprotein complex. Our previous findings indicate that KSHV does not only interact with EphA2, but can also bind to other members of the Eph family of receptor tyrosine kinases with comparatively lower avidity. We now analyzed the requirement of Eph interactions for infection of the BJAB B cell line, a model for infection of B cells by KSHV. We identify EphA7 as the principal Eph receptor for infection of this model B cell line by both KSHV and the related rhesus monkey rhadinovirus.
Early steps in the evolution of vertical transmission revealed by a plant-bacterium symbiosis
Authors: De Meyer Frédéric , Danneels Bram , Acar Tessa , Rasolomampianina Rado , Rajaonah Mamy Tiana , Jeannoda Vololoniaina , Carlier Aurelien
Published: January 2019

Various plant species establish intimate symbioses with bacteria within their aerial organs. The bacteria are contained within nodules or glands often present in distinctive patterns on the leaves in what is commonly referred to as leaf nodule symbiosis. We describe here a highly specific symbiosis between a wild yam species from Madagascar,Dioscorea sansibarensisand bacteria of the speciesOrrella dioscoreae. Using whole genome sequencing of plastid and bacteria from wild-collected samples, we show phylogenetic patterns consistent with a vertical transmission of the symbionts. Unique among leaf nodule symbioses, the bacteria can be cultured and are amenable to comparative transcriptomics and phenotypic characterization, revealing a potential role in complementing the host’s arsenal of secondary metabolites. We propose a very recent acquisition of the vertical mode of transmission in this symbiosis which, together with a large effective populations size explain the cultivability and remarkable lack of genome reductive evolution inO. dioscoreae. We leverage these unique features to reveal pathways and functions under positive selection in these specialized endophytes, highlighting the mechanisms enabling a permanent association in the phyllosphere.
The HCN Channel Voltage Sensor Undergoes A Large Downward Motion During Hyperpolarization
Authors: Dai Gucan , Aman Teresa K. , DiMaio Frank , Zagotta William N.
Published: January 2019

Voltage-gated ion channels (VGICs) underlie almost all electrical signaling in the body1. They change their open probability in response to changes in transmembrane voltage, allowing permeant ions to flow across the cell membrane. Ion flow through VGICs underlies numerous physiological processes in excitable cells1. In particular, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which operate at the threshold of excitability, are essential for pacemaking activity, resting membrane potential, and synaptic integration2. VGICs contain a series of positively-charged residues that are displaced in response to changes in transmembrane voltage, resulting in a conformational change that opens the pore3–6. These voltage-sensing charges, which reside in the S4 transmembrane helix of the voltage-sensor domain (VSD)3 and within the membrane’s electric field, are thought to move towards the inside of the cell (downwards) during membrane hyperpolarization7. HCN channels are unique among VGICs because their open probability is increased by membrane hyperpolarization rather than depolarization8–10. The mechanism underlying this “reverse gating” is still unclear. Moreover, although many X-ray crystal and cryo-EM structures have been solved for the depolarized state of the VSD, including that of HCN channels11, no structures have been solved at hyperpolarized voltages. Here we measure the precise movement of the charged S4 helix of an HCN channel using transition metal ion fluorescence resonance energy transfer (tmFRET). We show that the S4 undergoes a significant (~10 Å) downward movement in response to membrane hyperpolarization. Furthermore, by applying constraints determined from tmFRET experiments to Rosetta modeling, we reveal that the carboxyl-terminal part of the S4 helix exhibits an unexpected tilting motion during hyperpolarization activation. These data provide a long-sought glimpse of the hyperpolarized state of a functioning VSD and also a framework for understanding the dynamics of reverse gating in HCN channels. Our methods can be broadly applied to probe short-distance rearrangements in other ion channels and membrane proteins.
Cell Autonomous Neuroprotection by the Mitochondrial Uncoupling Protein 2 in a Mouse Model of Glaucoma
Authors: Hass Daniel T. , Barnstable Colin J.
Published: January 2019

Glaucoma is a group of disorders associated with retinal ganglion cell (RGC) degeneration and death. There is a clear contribution of mitochondrial dysfunction and oxidative stress toward glaucomatous RGC death. Mitochondrial uncoupling protein 2 (Ucp2) is a well-known regulator of oxidative stress that increases cell survival in acute models of oxidative damage. The impact of Ucp2 on cell survival during sub-acute and chronic neurodegenerative conditions however is not yet clear. Herein, we test the hypothesis that increased Ucp2 expression will improve retinal ganglion cell survival in a mouse model of glaucoma. We show that increasing retinal ganglion cell but not glial Ucp2 expression in transgenic animals decreases glaucomatous RGC death, but also that the PPAR-γ agonist rosiglitazone, an endogenous transcriptional activator of Ucp2, does not significantly alter RGC loss during glaucoma. Together, these data support a model whereby increased Ucp2 expression mediates neuroprotection during a long-term oxidative stressor, but that transcriptional activation alone is insufficient to elicit a neuroprotective effect, motivating further research in to the post-transcriptional regulation of Ucp2.
NWB:N 2.0: An Accessible Data Standard for Neurophysiology
Authors: Rübel Oliver , Tritt Andrew , Dichter Benjamin , Braun Thomas , Cain Nicholas , Clack Nathan , Davidson Thomas J. , Dougherty Max , Fillion-Robin Jean-Christophe , Graddis Nile , Grauer Michael , Kiggins Justin T. , Niu Lawrence , Ozturk Doruk , Schroeder William , Soltesz Ivan , Sommer Friedrich T. , Svoboda Karel , Lydia Ng , Frank Loren M. , Bouchard Kristofer
Published: January 2019

Neurodata Without Borders: Neurophysiology (NWB:N) is a data standard for neurophysiology, providing neuroscientists with a common standard to share, archive, use, and build common analysis tools for neurophysiology data. With NWB:N version 2.0 (NWB:N 2.0) we made significant advances towards creating a usable standard, software ecosystem, and vibrant community for standardizing neurophysiology data. In this manuscript we focus in particular on the NWB:N data standard schema and present advances towards creating an accessible data standard for neurophysiology.
Consistency of SVDQuartets and Maximum Likelihood for Coalescent-based Species Tree Estimation
Authors: Wascher Matthew , Kubatko Laura
Published: January 2019

Abtract

Numerous methods for inferring species-level phylogenies under the coalescent model have been proposed within the last 20 years, and debates continue about the relative strengths and weaknesses of these methods. One desirable property of a phylogenetic estimator is that of statistical consistency, which means intuitively that as more data are collected, the probability that the estimated tree has the same topology as the true tree goes to 1. To date, consistency results for species tree inference under the multispecies coalescent have been derived only for summary statistics methods, such as ASTRAL and MP-EST. These methods have been found to be consistent given true gene trees, but may be inconsistent when gene trees are estimated from data for loci of finite length (Roch et al., 2019). Here we consider the question of statistical consistency for four taxa for SVDQuartets for general data types, as well as for the maximum likelihood (ML) method in the case in which the data are a collection of sites generated under the multispecies coalescent model such that the sites are conditionally independent given the species tree (we call these data Coalescent Independent Sites (CIS) data). We show that SVDQuartets is statistically consistent for all data types (i.e., for both CIS data and for multilocus data), and we derive its rate of convergence. We additionally show that ML is consistent for CIS data under the JC69 model, and discuss why a proof for the more general multilocus case is difficult. Finally, we compare the performance of maximum likelihood and SDVQuartets using simulation for both data types.
Genome rearrangements induce biofilm formation inEscherichia coliC – an old model organism with a new application in biofilm research
Authors: Król Jarosław E. , Hall Donald C. , Balashov Sergey , Pastor Steven , Siebert Justin , McCaffrey Jennifer , Lang Steven , Ehrlich Rachel L. , Earl Joshua , Mell Joshua C. , Xiao Ming , Ehrlich Garth D.
Published: January 2019

Escherichia coliC forms more robust biofilms than the other laboratory strains. Biofilm formation and cell aggregation under a high shear force depends on temperature and salt concentrations. It is the last of fiveE. colistrains (C, K12, B, W, Crooks) designated as safe for laboratory purposes whose genome has not been sequenced. Here we present the complete genomic sequence of this strain in which we utilized both long-read PacBio-based sequencing and high resolution optical mapping to confirm a large inversion in comparison to the other laboratory strains. Notably, DNA sequence comparison revealed the absence of several genes thought to be involved in biofilm formation, including antigen 43,waaSBOJYZULfor LPS synthesis, andcpsBfor curli synthesis. The first main difference we identified that likely affects biofilm formation is the presence of an IS3-like insertion sequence in front of the carbon storage regulatorcsrAgene. This insertion is located 86 bp upstream of thecsrAstart codon inside the −35 region of P4 promoter and blocks the transcription from the sigma32and sigma70promoters P1-P3 located further upstream. The second is the presence of an IS5/IS1182 in front of thecsgDgene, which may drive its overexpression in biofilm. And finally,E. coliC encodes an additional sigma70subunit overexpressed in biofilm and driven by the same IS3-like insertion sequence. Promoter analyses using GFP gene fusions and total expression profiles using RNA-seq analyses comparing planktonic and biofilm envirovars provided insights into understanding this regulatory pathway inE. coli.

IMPORTANCE

Biofilms are crucial for bacterial survival, adaptation, and dissemination in natural, industrial, and medical environments. Most laboratory strains ofE. coligrown for decadesin vitrohave evolved and lost their ability to form biofilm, while environmental isolates that can cause infections and diseases are not safe to work with. Here, we show that the historic laboratory strain ofE. coliC produces a robust biofilm and can be used as a model organism for multicellular bacterial research. Furthermore, we ascertained the full genomic sequence as well as gene expression profiles of both the biofilm and planktonic envirovars of this classic strain, which provide for a base level of characterization and make it useful for many biofilm-based applications.
Relating growth potential and biofilm formation of ShigatoxigenicEscherichia colitoin plantacolonisation and the metabolome of ready-to-eat crops
Authors: Merget Bernhard , Forbes Ken J. , Brennan Fiona , McAteer Sean , Shepherd Tom , Strachan Norval J.C. , Holden Nicola J.
Published: January 2019

Contamination of fresh produce with pathogenicEscherichia coli,including ShigatoxigenicE. coli(STEC), represents a serious risk to human health. Colonisation is governed by multiple bacterial and plant factors that can impact on the probability and suitability of bacterial growth. Thus, we aimed to determine whether the growth potential of STEC for plants associated with foodborne outbreaks (two leafy vegetables and two sprouted seed species), is predictive for colonisation of living plants as assessed from growth kinetics and biofilm formation in plant extracts. Fitness of STEC was compared to environmentalE. coli, at temperatures relevant to plant growth. Growth kinetics in plant extracts varied in a plant-dependent and isolate-dependent manner for all isolates, with spinach leaf lysates supporting the fastest rates of growth. Spinach extracts also supported the highest levels of biofilm formation. Saccharides were identified as the major driver of bacterial growth, although no single metabolite could be correlated with growth kinetics. The highest level ofin plantacolonisation occurred on alfalfa sprouts, though internalisation was 10-times more prevalent in the leafy vegetables than in sprouted seeds. Marked differences inin plantagrowth meant that growth potential could only be inferred for STEC for sprouted seeds. In contrast, biofilm formation in extracts related to spinach colonisation. Overall, the capacity ofE. colito colonise, grow and internalise within plants or plant-derived matrices were influenced by the isolate type, plant species, plant tissue type and temperature, complicating any straight-forward relationship betweenin vitroandin plantabehaviours.

Importance

Fresh produce is an important vehicle for STEC transmission and experimental evidence shows that STEC can colonise plants as secondary hosts, but differences in the capacity to colonise occur between different plant species and tissues. Therefore, an understanding of the impact of these plant factors have on the ability of STEC to grow and establish is required for food safety considerations and risk assessment. Here, we determined whether growth and the ability of STEC to form biofilms in plants extracts could be related to specific plant metabolites or could predict the ability of the bacteria to colonise living plants. Growth rates for sprouted seeds (alfalfa and fenugreek) exhibited a positive relationship between plant extracts and living plants, but not for leafy vegetables (lettuce and spinach). Therefore, the detailed variations at the level of the bacterial isolate, plant species and tissue type all need to be considered in risk assessment.
Identification of regulatory genes through global gene expression analysis of aHelicobacter pylorico-culture system
Authors: Tubau-Juni Nuria , Bassaganya-Riera Josep , Leber Andrew , Zoccoli-Rodriguez Victoria , Kronsteiner Barbara , Viladomiu Monica , Abedi Vida , Hontecillas Raquel
Published: January 2019

Helicobacter pyloriis a gram-negative bacterium that establishes life-long infections by inducing immunoregulatory responses. We have developed a novelex vivo H. pylorico-culture system to identify new regulatory genes based on expression kinetics overlapping with that of genes with known regulatory functions. Using this novel experimental platform, in combination with global transcriptomic analysis, we have identified five lead candidates, validated them using mouse models ofH. pyloriinfection andin vitroco-cultures under pro-inflammatory conditions. Plexin domain containing 2(Plxdc2)was selected as the top lead immunoregulatory target. Gene silencing and ligand-induced activation studies confirmed its predicted regulatory function. Our integrated bioinformatics analyses and experimental validation platform has enabled the discovery of new immunoregulatory genes. This pipeline can be used for the identification of genes with therapeutic applications for treating infectious, inflammatory, and autoimmune diseases.
Epigenetic suppression of interferon lambda receptor expression leads to enhanced HuNoV replication in vitro
Authors: Arthur Sabastine E , Sorgeloos Frédéric , Hosmillo Myra , Goodfellow Ian
Published: January 2019

Human norovirus (HuNoV) is the main cause of gastroenteritis worldwide yet no therapeutics are currently available. Here, we utilize a human norovirus replicon in human gastric tumor (HGT) cells to identify host factors involved in promoting or inhibiting HuNoV replication. We observed that an IFN-cured population of replicon-harboring HGT cells (HGT-cured) was enhanced in their ability to replicate transfected HuNoV RNA compared to parental HGT cells, suggesting that differential gene expression in HGT-cured cells created an environment favouring norovirus replication. Microarray analysis was used to identify genes differentially regulated in HGT-NV and HGT-cured compared to parental HGT cells. We found that the IFN lambda receptor alpha (IFNLR1) expression was highly reduced in HGT-NV and HGT-cured cells. All three cell lines responded to exogenous IFN-β by inducing interferon stimulated genes (ISGs), however, HGT-NV and HGT-cured failed to respond to exogenous IFN-λ. Inhibition of DNA methyltransferase activity with 5-aza-2'-deoxycytidine partially reactivated IFNLR1 expression in HGT-NV and IFN-cured cells suggesting that host adaptation occurred via epigenetic reprogramming. In line with this, ectopic expression of the IFN-λ receptor alpha rescued HGT-NV and HGT-cured cells response to IFN-λ. We conclude that type III IFN is important in inhibiting HuNoV replication in vitro and that the loss of IFNLR1 enhances replication of HuNoV. This study unravels for the first time epigenetic reprogramming of the interferon lambda receptor as a new mechanism of cellular adaptation during long-term RNA virus replication and shows that an endogenous level of interferon lambda signalling is able to control human norovirus replication.
Disharmony of the world’s island floras
Authors: König Christian , Weigelt Patrick , Taylor Amanda , Stein Anke , Dawson Wayne , Essl Franz , Pergl Jan , Pyšek Petr , van Kleunen Mark , Winter Marten , Chatelain Cyrille , Wieringa Jan J. , Krestov Pavel , Kreft Holger
Published: January 2019

Aim

Disharmony is a key concept in island biology that describes the imbalance in the representation of higher taxa on islands compared to their mainland source regions. Although there are strong theoretical arguments for the differential colonization success of different taxa on islands, the empirical evidence for disharmony remains largely anecdotal. Here, we develop a novel method for delineating island source regions and present the first global quantitative assessment of island disharmony.

Location

Global.

Time period

Recent.

Major taxa studied

Vascular plants.

Methods

We developed a generalizable method for estimating the source regions of an island flora based on statistical predictions of species turnover. We then designed two metrics to investigate disharmony from an island- and a taxon-centered perspective. First, we used linear mixed effects models to analyse the overall taxonomic bias of 305 island floras (compositional disharmony) as a function of geographical and climatic island features. Second, we applied linear models to examine the over- or under-representation of 450 vascular plant families on islands (representational disharmony) as a function of family size, age, higher taxonomic group and family-specific functional traits.

Results

We found that compositional disharmony scales positively with island isolation and negatively with island area, and is strongly modulated by climatic variables. In contrast, the relationship between representational disharmony and family-specific characteristics was weaker. We found significant effects of family species richness and pollination syndrome, whereas family age and all other tested functional traits remained without effect.

Conclusions

The taxonomic scope of the disharmony concept has historically limited its wider applicability, because higher taxa are inconsistent ecological proxies. However, our results provide a strong foundation for integrating disharmony with quantitative functional and phylogenetic approaches in order to gain a deeper understanding of assembly processes on islands.
Development of an ELISA-Based Method for Testing Aflatoxigenicity and Aflatoxigenic Variability among Aspergillus species in Culture
Authors: Micah Lagat Kipkemboi , Toroitich Faith Jebet , Obonyo Meshack Amos
Published: January 2019

Aflatoxins contaminate foodstuff posing a severe threat to human health because chronic exposure is linked to liver cancer while acute exposure may cause death. Therefore, it is of interest to reduce the contamination of crops by aflatoxins in the field and post-harvest. Among the current technologies being developed is the deployment of non-aflatoxigenic strains of Aspergillus species to competitively exclude aflatoxigenic conspecifics from crops in the field thereby curtailing aflatoxin production by the former. The success in this endeavor makes the non-aflatoxigenic fungi good candidates for biological control programs. However, the current techniques for segregating non-aflatoxigenic from aflatoxigenic fungi suffer two main drawbacks: they are based on morphological and chemical tests with a combination of visual color changes detected in a culture plate which suffer some degree of inaccuracy. Secondly, the existing methods are incapable of accurately quantifying aflatoxin production by fungi in culture. We developed a culture system for inducing aflatoxin production by Aspergillus using maize kernels as growth substrate followed by quantification using ELISA. The method was compared to the Dichlorvos-Ammonia (DV-AM) method for determining aflatoxigenicity. Our findings encapsulate a method more robust than the currently used DV-AM approach because, for the first time, we are able to assess aflatoxigenicity and aflatoxigenic variability among Aspergillus species earlier classified as non-aflatoxigenic by the DV-AM method. Furthermore, the new method presents an opportunity to attribute toxin production by actively growing fungal cultures. We believe this method when further developed presents a chance to study and predict fungal behavior prior to field trials for biological control programs.
Thiel Embalming Pre-Frozen Cadavers: A Mouse Model
Authors: AlShehry Murad , Kandil Mostafa , Alzahrani Raed , Soames Roger
Published: January 2019

Thiel embalming has been gaining a great deal of worldwide attention. Its long-lasting life-like quality enables multiple applications in surgical training programs. The standard process of Thiel embalming, which involves perfusion of embalming fluid in fresh cadavers through cannulation of the arterial and venous systems could be difficult in some areas of the world where fresh body donation rates are low or banned. This study will assess the ability to Thiel embalm fresh frozen mice as an animal model as a solution for the lack of fresh cadavers. The ability of Thiel embalming frozen tissue would enable areas in the world where they do not have access to recently diseased donated cadavers. The study was ethically approved King Fahad Medical City Institutional Review Board. The 20 Mice cadavers were ethically gained from the university of Dundee animal house. They were euthanized ethically by carbon dioxide. They were handled by following the university’s ethical code. The mice were split into 4 groups with 5 mice for each group, where group 1 is fresh unfixed. Group 2 standard Theil embalmed. Group 3 defrosted one-week frozen mice then standard embalmed. group 4 perfused with Theil fluid, frozen, defrosted then set in the embalming tank. The embalming validation tests were made by visual gross and histological changes in the gastric, renal and muscular tissue. These tissues were chosen to test the penetration of the embalming solution. The results show similarity in all groups with difference of internal gross changes in the pre-frozen cadavers. Histological changes were similar in all embalmed groups meaning that the embalming method has been successful from a histological point of view.
Aβ-Positivity Predicts Cognitive Decline but Cognition Also Predicts Progression to Aβ-Positivity
Authors: Elman Jeremy A. , Panizzon Matthew S. , Gustavson Daniel E. , Franz Carol E. , Sanderson Mark E. , Lyons Michael J. , Kremen William S.
Published: January 2019

Introduction

Biomarker positivity predicts cognitive decline and Alzheimer’s dementia. But what predicts biomarker positivity? We hypothesized that cognitive function and p-tau would predict progression from normal to abnormal levels of β-amyloid (Aβ).

Methods

Baseline cognition in 292 non-demented, Aβ-negative Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants was measured with two cognitive composites and compared between those that progressed to Aβ-positivity versus Aβ-stable. Follow-up analyses included continuous CSF Aβ and p-tau levels to examine subthreshold effects.

Results

Continuously measured baseline subthreshold Aβ and p-tau predicted progression to Aβ-positivity, but both baseline cognitive measures predicted progression to Aβ-positivity even after controlling for baseline biomarker levels.

Discussion

Current Aβ thresholds may be ignoring relevant subthreshold pathology. Importantly, cognitive function can be an important early predictor of future risk, even earlier than the key biomarkers as currently measured. Moreover, A-/T+ individuals may still be on the AD pathway because p-tau also predicted progression to positivity.
CTCF sites display cell cycle–dependent dynamics in factor binding and nucleosome positioning
Authors: Oomen Marlies E. , Hansen Anders S. , Liu Yu , Darzacq Xavier , Dekker Job
Published: January 2019

CCCTC-binding factor (CTCF) plays a key role in the formation of topologically associating domains (TADs) and loops in interphase. During mitosis TADs are absent, but how TAD formation is dynamically controlled during the cell cycle is not known. Several contradicting observations have been made regarding CTCF binding to mitotic chromatin using both genomics- and microscopy-based techniques. Here, we have used four different assays to address this debate. First, using 5C, we confirmed that TADs and CTCF loops are readily detected in interphase, but absent during prometaphase. Second, ATAC-seq analysis showed that CTCF sites display greatly reduced accessibility and lose the CTCF footprint in prometaphase, suggesting loss of CTCF binding and rearrangement of the nucleosomal array around the binding motif. In contrast, transcription start sites remain accessible in prometaphase, although adjacent nucleosomes can also become repositioned and occupy at least a subset of start sites during mitosis. Third, loss of site-specific CTCF binding was directly demonstrated using CUT&RUN. Histone modifications and histone variants are maintained in mitosis, suggesting a role in bookmarking of active CTCF sites. Finally, live-cell imaging, fluorescence recovery after photobleaching, and single molecule tracking showed that almost all CTCF chromatin binding is lost in prometaphase. Combined, our results demonstrate loss of CTCF binding to CTCF sites during prometaphase and rearrangement of the chromatin landscape around CTCF motifs. This, combined with loss of cohesin, would contribute to the observed loss of TADs and CTCF loops during mitosis and reveals that CTCF sites, key architectural cis-elements, display cell cycle stage–dependent dynamics in factor binding and nucleosome positioning.
Transcription factor activity and nucleosome organization in mitosis
Authors: Festuccia Nicola , Owens Nick , Papadopoulou Thaleia , Gonzalez Inma , Tachtsidi Alexandra , Vandoermel-Pournin Sandrine , Gallego Elena , Gutierrez Nancy , Dubois Agnès , Cohen-Tannoudji Michel , Navarro Pablo
Published: January 2019

Mitotic bookmarking transcription factors (BFs) maintain the capacity to bind to their targets during mitosis, despite major rearrangements of the chromatin. While they were thought to propagate gene regulatory information through mitosis by statically occupying their DNA targets, it has recently become clear that BFs are highly dynamic in mitotic cells. This represents both a technical and a conceptual challenge to study and understand the function of BFs: First, formaldehyde has been suggested to be unable to efficiently capture these transient interactions, leading to profound contradictions in the literature; and second, if BFs are not permanently bound to their targets during mitosis, it becomes unclear how they convey regulatory information to daughter cells. Here, comparing formaldehyde to alternative fixatives we clarify the nature of the chromosomal association of previously proposed BFs in embryonic stem cells: While ESRRB can be considered as a canonical BF that binds at selected regulatory regions in mitosis, SOX2 and POU5F1 (also known as OCT4) establish DNA sequence-independent interactions with the mitotic chromosomes, either throughout the chromosomal arms (SOX2) or at pericentromeric regions (POU5F1). Moreover, we show that ordered nucleosomal arrays are retained during mitosis at ESRRB bookmarked sites, whereas regions losing transcription factor binding display a profound loss of order. By maintaining nucleosome positioning during mitosis, ESRRB might ensure the rapid post-mitotic re-establishment of functional regulatory complexes at selected enhancers and promoters. Our results provide a mechanistic framework that reconciles dynamic mitotic binding with the transmission of gene regulatory information across cell division.
How far is too far?
Authors: Nenycz-Thiel Magda , Romaniuk Jenni
Published: January 2019

Purpose

Retailers are increasingly adding banks, gas stations, mobile services and even real estate agencies to their portfolio and branding these new ventures with the retailer name, such as Tesco Bank or Asda Money. The purpose of this paper is to test the ability of a retailer brand to stretch from traditional packaged goods categories to very different categories such as banking.

Design/methodology/approach

Using data from an online survey collected from 953 UK grocery buyers, this paper examines consumers’ behaviour towards UK retailer brands across four categories: soft drinks, chocolate, fuel and banking.

Findings

The results show that cross-category retailer brand purchasing is stronger between categories with similar buying behaviour (e.g. soft drinks and chocolate) than in categories with very different buying behaviour (e.g. soft drinks and banking). The behavioural spill over effects are stronger for retailer brands from the same chain and persist even for unrelated categories. However, apart from fuel, the strongest cross-purchasing occurs across competing retailer-branded offers within the same category.

Research limitations/implications

The main implication of this study is that behavioural spill overs for retailer brands are possible even between unrelated categories. The finding about the effects being strongest within a given chain implies that umbrella branded strategy is a key to take advantage of the effects.

Practical implications

These findings extend past literature about the cross-category buying of umbrella branded store brands to very different categories. This paper highlights the challenges retailers face regarding their ability to extend the retailer brand across categories. The findings also provide insights for cross-selling retailer brands in unrelated categories to current store brand buyers.

Originality/value

This is the first study to examine the use of retailer brands across a wide spectrum of categories from Soft Drinks to Fuel.
Reviewing the research on the internationalization of Chinese firms
Authors: Haasis Timon Immanuel , Liefner Ingo
Published: January 2019

Purpose

Supplementing a previous review article on the internationalization of Chinese firms (ICF) by Deng (2012) that covers the period 1991–2010, the purpose of this paper is to examine how research on this subject has thematically expanded in recent years, systematically investigating the literature concerning the ICF between 2011 and June 2017 and highlighting the research advancements. Furthermore, it provides impulses for future research and outlines potential avenues for the overall future development of the entire ICF field.

Design/methodology/approach

Based on a systematic literature review, this paper categorizes the surveys reviewed according to the organizational framework of the research on the ICF provided by Deng (2012).

Findings

The results indicate that the research on the ICF has become more widespread and mature during the time period investigated. First, there are more articles examining functional management processes of Chinese firms. Consequently, new knowledge exists regarding the role, control and organization of foreign subsidiaries of Chinese enterprises and their host country institutional integration. Second, the state of knowledge regarding the implications of the ICF has increased. It is argued that the future convergence or divergence of the Chinese economic system determines the overall future development of research on the ICF.

Originality/value

This is the first review paper in the emerging ICF field that consciously continues the work of a previous review article, enabling the tracing of the thematic expansion of research on the ICF.
Knowledge-based dynamic capabilities: a joint R&D project in the French semiconductor industry
Authors: Faccin Kadígia , Balestrin Alsones , Volkmer Martins Bibiana , Bitencourt Claudia Cristina
Published: January 2019

Purpose

The purpose of this study is to identify dynamic capabilities in joint R&D projects, that enable them to successfully achieve knowledge creation and discover how they behave throughout the life cycle of a collaborative project, although this understanding could enhance the interorganizational knowledge creation process.

Design/methodology/approach

The authors conducted 65 semi-structured interviews and utilized secondary data from a joint R&D project. The authors analyzed all data using the Gioia method.

Findings

The authors confirm that specific dynamic capabilities are needed to create interorganizational knowledge and discovered 11 knowledge-based dynamic capabilities (KBDCs) for successful innovation results in joint R&D projects. Gioia method allowed to discover that different KBDCs are necessary for the different phases of the project lifecycle. Additionally, the authors identify two microprocesses in which KBDCs are engaged in joint R&D projects, knowing that is a part of the sensing and seizing processes and synthetizing that is a part of the seizing process, and establish several KBDC microfoundations.

Research limitations/implications

We used retrospective interviews. This kind of interviews are impacted by the experiences of the respondents lived after they have participated in the joint R&D project.

Practical implications

Dynamic capabilities for collaborative knowledge creation and their specific microfoundations can help managers delineate their strategic practices and actions to achieve more sustainable, long-lasting results from joint R&D projects.

Originality/value

The authors improve Teece’s model and propose two microprocesses in which dynamic capabilities are engaged, that emerged in the context of a joint R&D project, knowing that is a part of the sensing and seizing processes and synthetizing that is a part of the seizing process, which supplement those already known: sensing, seizing and transforming. The authors tested the Gioia method, which is important for detecting dynamic capabilities; therefore, the authors propose a methodological advance that can contribute to future studies. The authors provide an interorganizational perspective on KBDC and a methodological view of the changes in KBDCs required for joint R&D projects.