bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation of Genomic Deoxyxylulose Phosphate Reductoisomerase (DXR) Mutations Conferring Resistance to Fosmidomycin
Authors: Pines Gur , Bassalo Marcelo C. , Oh Eun Joong , Choudhury Alaksh , Garst Andrew D. , Gill Ryan T.
Published: April 2018

Sequence to activity mapping technologies are rapidly developing, enabling the isolation of mutations that confer novel phenotypes. Here we used the CRISPR EnAbled Trackable genome Engineering (CREATE) technology to investigate the inhibition of the essential IspC gene in Escherichia coli. IspC gene product, Deoxyxylulose Phosphate Reductoisomerase (DXR), converts 1-deoxy-D-xylulose 5-phosphate to 2-C-methyl-D-erythritol 4-phosphate in the DXP pathway. Since this pathway is shared with many pathogenic bacteria and protozoa and is missing in humans, it is an appealing target for inhibition. We created a full saturation library of 33 sites proximal to ligand binding and other sites and challenged it with the DXR-specific inhibitor, fosmidomycin. We identified several mutations that confer fosmidomycin resistance. All sites are highly conserved and also exist in pathogens including the malaria-inducing Plasmodium falciparum. These findings may have general implications on the isolation of resistance-conferring mutations and specifically, may affect the design of future generations of fosmidomycin-based drugs.

Significance

The emergence of acquired drug resistance is a natural process that is likely to occur under most circumstances. Recently-developed technologies allow to map relative fitness contribution of multiple mutations in parallel. Such approaches may be used to predict which mutations are most likely to confer resistance, instead of waiting for them to evolve spontaneously. In this study, a rationally-designed IspC mutant library was generated genomically in E. coli. Mutants resistant to fosmidomycin, an antimalarial drug were identified, and most were in the highly conserved proline at position 274. These results may have implications on next-generation fosmidomycin drug design, and more broadly, this approach may be used for predicting mutational acquired resistance.
Mechanisms of selection for the control of action inDrosophila melanogaster
Authors: Frighetto Giovanni , Zordan Mauro A. , Castiello Umberto , Megighian Aram
Published: April 2018

In the last few years several studies have investigated the neural mechanisms underlying spatial orientation inDrosophila melanogaster. Convergent results suggest that this mechanism is associated with specific neural circuits located within the Central Complex (CC). Furthermore such circuits appear to be associated with visual attention, specifically with selective attention processes implicated in the control of action. Our aim was to understand how wild-type flies react to the abrupt appearance of a visual distractor during an ongoing locomotor action. Thus, we adapted the well-known ‘Buridan paradigm’, used to study walking behaviour in flies, so we could specifically address the mechanisms involved in action selection. We found that flies tended to react in one of two ways when confronted with a visual distractor during ongoing locomotion. Flies either: (i) committed to a new path situated midway between the original target and the distractor, consistent with a novelty effect; or (ii) remained on the original trajectory with a slight deviation in direction of the distractor. We believe that these results provide the first indication of how flies react, from the motor point of view, in a bi-stable context requiring the presence of selection-for-action mechanisms. Some considerations on the neural circuits underlying such behavioural responses are advanced.
Sensory learning and inference is impaired in the non-clinical continuum of psychosis: a replication study
Authors: Dzafic Ilvana , Randeniya Roshini , Harris Clare D. , Bammel Moritz , Garrido Marta I.
Published: April 2018

Our perceptions result from the brain’s ability to make inferences, or predictive models, of sensory information. Recently, it has been proposed that psychotic traits may be linked to impaired predictive processes. Here, we examine the brain dynamics underlying sensory learning and inference in stable and volatile environments, in a population of healthy individuals (N=75) with a range of psychotic-like experiences. We measured prediction error responses to sound sequences with electroencephalography, gauged sensory inference explicitly by behaviourally recording sensory ‘regularity’ learning errors, and used dynamic causal modelling to tap into the underlying neural circuitry. We discuss the findings that were robust to replication across the two experiments (N=31 and N=44 for the discovery and the validation datasets, respectively). First, we found that during stable conditions, participants demonstrated a stronger predictive model, reflected in a larger prediction error response to unexpected sounds, and decreased regularity learning errors. Moreover, individuals with attenuated prediction errors in stable conditions were found to make greater incorrect predictions about sensory information. Critically, we show that greater errors in sensory learning and inference are related to increased psychotic-like experiences. These findings link neurophysiology to behaviour during sensory learning and prediction formation, as well as providing further evidence for the idea of a continuum of psychosis in the healthy, non-clinical population.

Significance Statement

Whilst perceiving the world, we make inferences by learning the regularities present in the sensory environment. It has been argued that psychosis may emerge due to a failure to learn sensory regularities, resulting in an impaired representation of the world. Recently it has been proposed that psychosis exists on a continuum; however, there is conflicting evidence on whether sensory learning deficits align on the non-clinical end of the psychosis continuum. We found that sensory learning is associated with brain prediction errors, and critically, it is impaired in healthy people who report more psychotic-like experiences. We replicated these findings in an independent sample, demonstrating strengthened credibility to support that the continuum of psychosis extends into the non-clinical population.
The transcriptional and translational landscape of equine torovirus
Authors: Stewart Hazel , Brown Katherine , Dinan Adam M. , Irigoyen Nerea , Snijder Eric J. , Firth Andrew E.
Published: April 2018

The genusTorovirus(subfamilyTorovirinae, familyCoronaviridae, orderNidovirales) encompasses a range of species that infect domestic ungulates including cattle, sheep, goats, pigs and horses, causing an acute self-limiting gastroenteritis. Using the prototype species equine torovirus (EToV) we performed parallel RNA sequencing (RNA-seq) and ribosome profiling (Ribo-seq) to analyse the relative expression levels of the known torovirus proteins and transcripts, chimaeric sequences produced via discontinuous RNA synthesis (a characteristic of the nidovirus replication cycle) and changes in host transcription and translation as a result of EToV infection. RNA sequencing confirmed that EToV utilises a unique combination of discontinuous and non-discontinuous RNA synthesis to produce its subgenomic RNAs; indeed, we identified transcripts arising from both mechanisms that would result in sgRNAs encoding the nucleocapsid. Our ribosome profiling analysis revealed that ribosomes efficiently translate two novel CUG-initiated ORFs, located within the so-called 5’ UTR. We have termed the resulting proteins U1 and U2. Comparative genomic analysis confirmed that these ORFs are conserved across all available torovirus sequences and the inferred amino acid sequences are subject to purifying selection, indicating that U1 and U2 are functionally relevant. This study provides the first high-resolution analysis of transcription and translation in this neglected group of livestock pathogens.

Importance

Toroviruses infect cattle, goats, pigs and horses worldwide and can cause gastrointestinal disease. There is no treatment or vaccine and their ability to spill over into humans has not been assessed. These viruses are related to important human pathogens including severe acute respiratory syndrome (SARS) coronavirus and they share some common features, however the mechanism that they use to produce subgenomic RNA molecules differs. Here we performed deep sequencing to determine how equine torovirus produces subgenomic RNAs. In doing so, we also identified two previously unknown open reading frames “hidden” within the genome. Together these results highlight the similarities and differences between this domestic animal virus and related pathogens of humans and livestock.
Oxidative stress resistance and fitness-compensatory response in vancomycin-intermediate Staphylococcus aureus (VISA)
Authors: Tan Xin-Ee , Neoh Hui-min , Cui Longzhu , Hiramatsu Keiichi , Jamal Rahman
Published: April 2018

In this study, VISA cells carrying vraS and/or graR mutations were shown to be more resistant to oxidative stress. Caenorhabditis elegans infected with these strains in turn demonstrated lower survival. Altered regulation in oxidative stress response and virulence appears to be physiological adaptations associated with VISA phenotype in the Mu50 lineage.
Combination of tenofovir and emtricitabine with efavirenz does not moderate inhibitory effect of efavirenz on mitochondrial function and cholesterol biosynthesis in human T lymphoblastoid cell line
Authors: Li Min , Sopeyin Anuoluwapo , Paintsil Elijah
Published: April 2018

Efavirenz (EFV), the most popular non-nucleoside reverse transcriptase inhibitor, has been associated with mitochondrial dysfunction in most in vitro studies. However, in real life the prevalence of EFV-induced mitochondrial toxicity is relatively low. We hypothesized that the agents given in combination with EFV might moderate the effect of EFV on mitochondrial function. To test this hypothesis, we cultured human T lymphoblastoid cell line (CEM cells) with EFV alone and in combination with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) to investigate the effects on mitochondrial respiration and function and cholesterol biosynthesis.

There was a statistically significant concentration- and time-dependent apoptosis, reduction in mitochondrial membrane potential (ΔΨ), and increase production of reactive oxygen species (ROS) in cells treated with either EVF alone or in combination with TDF/FTC. EFV treated cells compared to DMSO treated cells had significant reduction in oxygen consumption rate (OCR) contributed by mitochondrial respiration, ATP production-linked respiration, and spare respiratory capacity (SRC). Treatment with EFV resulted in a decrease in mitochondrial DNA content, and perturbation of more coding genes (n=13); among these were 11 genes associated with lipid or cholesterol biosynthesis. Our findings support the growing body of knowledge on the effects of EFV on mitochondrial respiration and function and cholesterol biosynthesis.

Interestingly, combining TDF/FTC with EFV did not alter the effects of EFV on mitochondrial respiration and function and cholesterol biosynthesis. The gap between the prevalence of EFV-induced mitochondrial toxicityin vitroandin vivostudies may be explained by individual differences in the pharmacokinetic of EFV.
Heterogeneous Viral Strategies Promote Coexistence in Virus-Microbe Systems
Authors: Gulbudak Hayriye , Weitz Joshua S.
Published: April 2018

Viruses of microbes, including bacterial viruses (phage), archaeal viruses, and eukaryotic viruses, can influence the fate of individual microbes and entire populations. Here, we model distinct modes of virus-host interactions and study their impact on the abundance and diversity of both viruses and their microbial hosts. We consider two distinct viral populations infecting the same microbial population via two different strategies: lytic and chronic. A lytic strategy corresponds to viruses that exclusively infect and lyse their hosts to release new virions. A chronic strategy corresponds to viruses that infect hosts and then continually release new viruses via a budding process without cell lysis. The chronic virus can also be passed on to daughter cells during cell division. The long-term association of virus and microbe in the chronic mode drives differences in selective pressures with respect to the lytic mode. We utilize invasion analysis of the corresponding nonlinear differential equation model to study the ecology and evolution of heterogenous viral strategies. We first investigate stability of equilibria, and characterize oscillatory and bistable dynamics in some parameter regions. Then, we derive fitness quantities for both virus types and investigate conditions for competitive exclusion and coexistence. In so doing we find unexpected results, including a regime in which the chronic virus requires the lytic virus for survival and invasion.
Born to run? Quantifying the balance of prior bias and new information in prey escape decisions
Authors: Sutton Nicholas M. , O’Dwyer James P.
Published: April 2018

Animal behaviors can often be challenging to model and predict, though optimality theory has improved our ability to do so. While many qualitative predictions of behavior exist, accurate quantitative models, tested by empirical data, are often lacking. This is likely due to variation in biases across individuals and variation in the way new information is gathered and used. We propose a modeling framework based on a novel interpretation of Bayes’ theorem to integrate optimization of energetic constraints with both prior biases and specific sources of new information gathered by individuals. We present methods for inferring distributions of prior biases within populations rather than assuming known priors, as is common in Bayesian approaches to modelling behavior, and for evaluating the goodness of fit of overall model descriptions. We apply this framework to predict optimal escape during predator-prey encounters, based on prior biases and variation in what information prey use. Using this approach we collected and analyzed data characterizing white-tailed deer (Odocoileus virginianus) escape behavior in response to human approaches. We found that distance to predator alone was not sufficient for predicting deer flight response, and have shown that the inclusion of additional information is necessary. Additionally, we compared differences in the inferred distributions of prior biases across different populations and discuss the possible role of human activity in influencing these distributions.
Flat-field illumination for quantitative fluorescence imaging
Authors: Khaw Ian , Croop Benjamin , Tang Jialei , Möhl Anna , Fuchs Ulrike , Han Kyu Young
Published: April 2018

The uneven illumination of a Gaussian profile makes quantitative analysis highly challenging in laser-based wide-field fluorescence microscopy. Here we present flat-field illumination (FFI) where the Gaussian beam is reshaped into a uniform flat-top profile using a high-precision refractive optical component. The long working distance and high spatial coherence of FFI allows us to accomplish uniform epi and TIRF illumination for multi-color single-molecule imaging. In addition, high-throughput borderless imaging is demonstrated with minimal image overlap.
Identifying progressive gene network perturbation from single-cell RNA-seq data
Authors: Mukherjee Sumit , Carignano Alberto , Seelig Georg , Lee Su-In
Published: April 2018

Identifying the gene regulatory networks that control development or disease is one of the most important problems in biology. Here, we introduce a computational approach, called PIPER (ProgressIve networkPERturbation), to identify theperturbed genesthat drive differences in the gene regulatory network across different points in a biological progression. PIPER employs algorithms tailor-made for single cell RNA sequencing (scRNA-seq) data to jointly identify gene networks for multiple progressive conditions. It then performs differential network analysis along the identified gene networks to identify master regulators. We demonstrate that PIPER outperforms state-of-the-art alternative methods on simulated data and is able to predict known key regulators of differentiation on real scRNA-Seq datasets.
A shared cis-regulatory module activates transcription in the suspensor of plant embryos
Authors: Henry Kelli F. , Bui Anhthu Q. , Kawashima Tomokazu , Goldberg Robert B.
Published: April 2018

The mechanisms controlling the transcription of gene sets in specific regions of a plant embryo shortly after fertilization remain unknown. Previously, we showed that G564 mRNA, encoding a protein of unknown function, accumulates to high levels in the giant suspensor of both Scarlet Runner Bean (SRB) and Common Bean embryos, and a cis-regulatory module containing three unique DNA sequences, designated as the 10-bp, Region 2, and Fifth motifs, is required for G564 suspensor-specific transcription [Henry, K. F. et al., Plant Mol. Biol. 88(3):207-217 (2015); Kawashima, T. et al., Proc. Natl. Acad. Sci USA 106(9):3627-3632 (2009)]. We tested the hypothesis that these motifs are also required for transcription of the SRB GA 20-oxidase gene, which encodes a gibberellic acid hormone biosynthesis enzyme and is co-expressed with G564 at a high level in giant bean suspensors. We used deletion and gain-of-function experiments in transgenic tobacco embryos to show that two GA 20-oxidase DNA regions are required for suspensor-specific transcription – one in the 5’ untranslated region (UTR) (+119 to +205) and another in the 5’ upstream region (−341 to −316). Mutagenesis of sequences in these two regions determined that the cis-regulatory motifs required for G564 suspensor transcription are also required for GA 20-oxidase transcription within the suspensor, although the motif arrangement differs. Our results demonstrate the flexibility of motif positioning within a cis-regulatory module that activates gene transcription within giant bean suspensors, and suggest that G564 and GA 20-oxidase comprise part of a suspensor gene regulatory network.

Significance

Little is known about how genes are expressed in different plant embryo regions. We tested the hypothesis that shared cis-regulatory motifs control the transcription of genes specifically in the suspensor. We carried out functional studies with the Scarlet Runner Bean (SRB) GA 20-oxidase gene that encodes a gibberellic acid (GA) hormone biosynthesis enzyme, and is expressed specifically within the suspensor. We show that cis-regulatory motifs required for GA 20-oxidase transcription within the suspensor are the same as those required for suspensor-specific transcription of the SRB G564 gene, although motif number, spacing and order differ. These cis-elements constitute a control module that is required to activate genes in the SRB suspensor and may form part of a suspensor regulatory network.
Toxoplasma activates host hypoxia inducible factor-1 by cytoplasmic trapping and lamp1-dependent lysosomal degradation of prolyl-hydroxylase 2
Authors: Florimond Celia , Liu Tongi , Menendez Matthew , Lippl Kerstin , Schofield Christopher J. , Blader Ira J.
Published: April 2018

Hypoxia Inducible Factor-1 is a metazoan heterodimeric transcription factor that senses changes in O2levels. HIF-1α subunit abundance is post-translationally regulated by prolyl-hydroxylase domain enzymes (PHDs), which use molecular O2and α-ketoglutarate to hydroxylate two prolyl-residues in HIF-1α. Three PHDs have been identified and PHD2 is the most critical regulator of HIF-1α. HIF-1α can also be activated independently of hypoxia and in some cases this is due to changes in PHD2 abundance through poorly understood mechanisms. Previously, we reported that under O2-replete conditions that the intracellular parasiteToxoplasma gondiiactivates HIF-1 by reducing PHD2 protein abundance. Here, we demonstrate thatToxoplasmaregulates PHD2 through a multistep process. First, PHD2 is a nucleocytoplasmic protein andToxoplasmainduces PHD2 cytoplasmic accumulation to separate it from nuclear HIF-1α. PHD2 is then degraded by lysosomes independently of the major autophagic processes, macroautophagy or chaperone-mediated autophagy. Rather, PHD2 interacts with the major lysosomal membrane protein, LAMP1, which is required for HIF-1 activation. These data therefore highlight for the first time that cytoplasmic trapping and subsequent lysosomal degradation of a host nucleocytoplasmic protein is a mechanism used by a microbial pathogen to regulate host gene expression.
Higher order spherical harmonics reconstruction of fetal diffusion MRI with intensity correction
Authors: Deprez Maria , Price Anthony , Christiaens Daan , Estrin Georgia Lockwood , Cordero-Grande Lucilio , Hutter Jana , Daducci Alessandro , Tournier J-Donald , Rutherford Mary , Counsell Serena J. , Cuadra Merixtell Bach , Hajnal Joseph V.
Published: April 2018

We present a comprehensive method for reconstruction of fetal diffusion MRI signal using a higher order spherical harmonics representation, that includes motion, distortion and intensity correction. By applying constrained spherical deconvolution and whole brain tractography to reconstructed fetal diffusion MRI we are able to identify main WM tracts and anatomically plausible fiber crossings. The proposed methodology facilitates detailed investigation of developing brain connectivity and microstructure in-utero.
WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria
Authors: Abdallah Abdallah M. , Weerdenburg E.M. , Guan Qingtian , Ummels R. , Borggreve S. , Adroub S.A. , Malas Tareq B. , Naeem Raeece , Zhang Huoming , Otto T.D. , Bitter W. , Pain A.
Published: April 2018

The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages, suggesting an important role in ESX-1-mediated virulence during the early phase of infection. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.
Uncoupling DNA- and RNA-directed DNA methylation at Rasgrf1
Authors: Chu Erin T. , Taylor David H. , Hofstedt Margaret , Soloway Paul D.
Published: April 2018

Long noncoding RNAs (lncRNAs) have garnered much attention as possible links between DNA sequence and the protein factors that mediate DNA methylation. However, the mechanisms by which DNA methylation is directed to specific genomic locations remain poorly understood. We previously identified a lncRNA in mouse, the pitRNA, that was implicated in the control of DNA methylation at the imprinted Rasgrf1 locus. The pitRNA is transcribed in the developing male germline antisense to the differentially methylated region (DMR) that harbors paternal allele methylation, and is driven by a series of tandem repeats that are necessary for imprinted methylation.

MitoPLD, a factor necessary for piRNA biogenesis, both processes piRNAs from the pitRNA, and is necessary for complete methylation at the locus, along with piRNA binding proteins. Using two independent mouse systems where pitRNA transcription is driven by the doxycycline-inducible Tet Operator, we demonstrate that pitRNA transcription across the DMR is insufficient for imprinted methylation, and that the Rasgrf1 repeats have additional, critical cis-acting roles for imparting DNA methylation to Rasgrf1, independently of their control of pitRNA transcription. Furthermore, pitRNA overexpression and oocyte loading of pitRNA is insufficient to induce transallelic and transgenerational effects previously reported for Rasgrf1. Notably, manipulation of the pitRNA with the TetOFF system led to transcriptional perturbations over a broad chromosomal region surrounding the inserted Tet Operator, revealing that the effects of this regulatory tool are not localized to a single target gene.

AUTHOR SUMMARY

DNA methylation is a heritable genetic modification known to impact vital biological processes. While the proteins that establish, maintain, and remove DNA methylation are well characterized, the mechanisms by which these proteins are directed to specific genetic sequences are poorly understood. We have previously demonstrated that DNA methylation at the imprinted Rasgrf1 locus requires a DNA element with a series of tandem repeats. These repeats act as a promoter for a long noncoding RNA, the pitRNA, which is targeted by a small noncoding RNA pathway known to silence viral elements in the male germline via DNA methylation. We queried the sufficiency of the pitRNA to mediate DNA methylation at Rasgrf1. We show that, in the absence of the repeats, the pitRNA expression is insufficient to establish imprinted methylation. This work supports a pitRNA-independent mechanism for methylation at Rasgrf1, and a critical cis-acting role for the tandem repeats separate from their control of pitRNA transcription.
Predictive remapping of visual features beyond saccadic targets
Authors: He Tao , Fritsche Matthias , Lange Floris P. de
Published: April 2018

Visual stability is thought to be mediated by predictive remapping of the relevant object information from its current, pre-saccadic locations to its future, post-saccadic location on the retina. However, it is heavily debated whether and what feature information is predictively remapped during the pre-saccadic interval. Using an orientation adaptation paradigm, we investigated whether predictive remapping occurs for stimulus features and whether adaptation itself is remapped. We found strong evidence for predictive remapping of a stimulus presented shortly before saccade onset, but no remapping of adaptation. Furthermore, we establish that predictive remapping also occurs for stimuli that are not saccade targets, pointing toward a ‘forward remapping’ process operating across the whole visual field. Together, our findings suggest that predictive feature remapping of object information plays an important role in mediating visual stability.
Polypyrimidine Tract Binding Protein blocks microRNA-­124 biogenesis to enforce its neuronal specific expression
Authors: Yeom Kyu-Hyeon , Mitchell Simon , Linares Anthony J. , Zheng Sika , Lin Chia-Ho , Wang Xiao-Jun , Hoffmann Alexander , Black Douglas L.
Published: April 2018

MicroRNA-124 is expressed in neurons, where it represses genes inhibitory for neuronal differentiation, including the RNA binding protein PTBP1. PTBP1 maintains non-neuronal splicing patterns of mRNAs that switch to neuronal isoforms upon neuronal differentiation. We find that pri-miR-124-1 is expressed in mouse embryonic stem cells (mESCs) where mature miR-124 is absent. PTBP1 binds to this precursor RNA upstream of the miRNA stem-loop to inhibit mature miR-124 expression in vivo, and DROSHA cleavage of pri-miR-124-1 in vitro. This new function for PTBP1 in repressing miR-124 biogenesis adds an additional regulatory loop to the already intricate interplay between these two molecules. Applying mathematical modeling to examine the dynamics of this regulation, we find that the pool of pri-miR-124 whose maturation is blocked by PTBP1 creates a robust and self-reinforcing transition in gene expression as PTBP1 is depleted during early neuronal differentiation. While interlocking regulatory loops are often modeled between miRNAs and transcriptional regulators, our results indicate that miRNA targeting of posttranscriptional regulators also reinforces developmental decisions. Notably, induction of neuronal differentiation observed upon PTBP1 knockdown likely results from direct de-repression of miR-124, in addition to indirect effects previously described.
YggG is a Novel SPI-1 Effector Essential for Salmonella Virulence
Authors: Li Menghan , Gu Bing , Bomjan Rajdeep , Chitale Meghana , Kihar Daisuke , Zhou Daoguo
Published: April 2018

Salmonella is a leading cause of food borne illness and poses a major public health problem worldwide. Two type III secretion systems (TTSSs) are responsible for the delivery of a series of bacterial effectors into the infected cells to reprogram host cell functions to promote bacterial invasion and intracellular survival/replication. Nearly half of Salmonella genes encode proteins that are annotated as "hypothetical". We hypothesize that some of these hypothetical proteins might be TTSS effectors and participate in Salmonella virulence. In this study, we employed an in silico screen to identify putative TTSS effector proteins and performed a large scale screening of Salmonella effectors using a β-lactamase protein translocation reporter assay. We identified 22 novel effectors that have not been previously reported. One of the effector - YggG, is found to be cytotoxic to mammalian cells when overexpressed suggesting interference with mammalian cell functions and survival. Importantly, Salmonella strains lacking YggG has reduced virulence in the mouse infection model. Our study demonstrated that YggG and its protease activity are required for Salmonella virulence in the mouse infection model. Surprisingly, no detectable roles in invasion into epithelial cells and no effect on the survival and replication inside cultured macrophages. We speculate that YggG may be involved in altering some aspects of the host immune system to promote infection. Our finding significantly expands the number of known Salmonella effectors, and laid a solid foundation in further understanding Salmonella pathogenesis.
Energy research with neutrons (ErwiN) and installation of a fast neutron powder diffraction option at the MLZ, Germany
Authors: Heere Michael , Mühlbauer Martin J. , Schökel Alexander , Knapp Michael , Ehrenberg Helmut , Senyshyn Anatoliy
Published: April 2018

The need for rapid data collection and studies of small sample volumes in the range of cubic millimetres are the main driving forces for the concept of a new high-throughput monochromatic diffraction instrument at the Heinz Maier-Leibnitz Zentrum (MLZ), Germany. A large region of reciprocal space will be accessed by a detector with sufficient dynamic range and microsecond time resolution, while allowing for a variety of complementary sample environments. The medium-resolution neutron powder diffraction option for `energy research with neutrons' (ErwiN) at the high-flux FRM II neutron source at the MLZ is foreseen to meet future demand. ErwiN will address studies of energy-related systems and materials with respect to their structure and uniformity by means of bulk and spatially resolved neutron powder diffraction. A set of experimental options will be implemented, enabling time-resolved studies, rapid parametric measurements as a function of external parameters and studies of small samples using an adapted radial collimator. The proposed powder diffraction option ErwiN will bridge the gap in functionality between the high-resolution powder diffractometer SPODI and the time-of-flight diffractometers POWTEX and SAPHiR at the MLZ.
Artisan entrepreneurship: a question of personality structure?
Authors: Hoyte Cherisse
Published: April 2018

Purpose

The purpose of this paper is to examine the role of culture in artisan entrepreneurship. It is argued that culture plays a critical role in entrepreneurial behaviour as culture is a key determinant of what it means to be a person. The concept of culture is explored from a micro level of analysis therefore, conceptualising culture from the perspective of the individual entrepreneur’s personality. The main research question being investigated within this paper is: whether artisan entrepreneurs share common personality traits with other entrepreneur groups, using the five factor model (FFM) of personality as the basis of the conceptual model presented herein.

Design/methodology/approach

A literature review on the emerging field of artisan entrepreneurship, followed by a review of the literature on personality theory and entrepreneurship. Then, drawing upon the FFM of personality, a conceptual framework is introduced which proposes a relationship between the Big Five personality traits and four dimensions of artisan entrepreneurship such as cultural heritage, community entrepreneurship, craftsmanship and innovation, developed from concepts derived from extant literature.

Findings

The theoretical contribution is in the form of propositions. Four propositions have been formulated around the entrepreneurial personality of artisan business owners for each of the four dimensions: cultural heritage, community entrepreneurship, craftsmanship and innovation.

Originality/value

The paper is the first to propose a relationship between the Big Five personality dimensions and the likelihood of starting and/or running a business among an entrepreneur group rather than explaining personality differences among entrepreneur and non-entrepreneur groups. The focus of the paper is specifically on artisan entrepreneurs and it has been proposed that the personality trait of agreeableness is important in the decision to start a cultural-based business. It has also been proposed that artisan entrepreneurs possess personal characteristics of openness to newness and openness to innovation that are integral to regional development.
A device to monitor fatigue level in order-picking
Authors: Calzavara Martina , Persona Alessandro , Sgarbossa Fabio , Visentin Valentina
Published: April 2018

Purpose

In order-picking activities, the performance of the system can be influenced by different variables such as the order to be fulfilled, the distance to be covered or the experience of operators. Usually, this kind of activity is performed by operators rather than machines to assure flexibility. Consequently, their fatigue accumulation can decrease the performance of the overall system. The purpose of this paper is to define the kind of device to be used in an order-picking context, to obtain data which can be utilized for the evaluation of the level of fatigue and to improve the performance of the picking system.

Design/methodology/approach

The paper presents a comparison between existing fatigue methods which can be applied in a picking context. In addition, an analysis of the physiological literature for the evaluation of a new device for the monitoring of fatigue level is carried on and its practical use is shown.

Findings

The proposed research identifies in the heart rate monitor the device that, thanks to its advantages, can be the best one to be used in an industrial context for monitoring the physical fatigue of operators.

Originality/value

This study considers the importance of human factors in picking activities such as physical fatigue of operators and the need to have validated tools to monitor and to define the level of fatigue accumulation in each activity of different rate and duration.
A study of social media users’ perceptional typologies and relationships to self-identity and personality
Authors: Kim Jin-Young
Published: April 2018

Purpose

The purpose of this paper is to explore and describe different viewpoints on the use of social networking sites (SNSs). It analyzes perceptional typologies of SNS users and the characteristics of each type, which has similarities and differences. It also examined possible relationships among different perceptional types, users’ self-identities, and their personality.

Design/methodology/approach

This study utilized Q-methodology in order to identify diverse explanations of SNS users’ perspectives. Q-methodology requires participants (referred to as P sample) to sort a series of items (Q-statements). After completing a questionnaire including demographics, self-identity, etc., each respondent performed the Q-sorting work. This task involves sorting well-composed statements about SNSs (Q-sample). In all, 46 SNS users from a university in Korea were chosen as participants. Once the P sample had finished Q-sorting, participants had in-depth interviews. When all interviews were finalized, analysis of the Q-sorts was done with the help of QUNAL program.

Findings

Consequently, four types of SNS users were identified and given the following descriptive labels: Impression Management Type, Lurker Type, SNS Enjoyer and Relationship Focus Type, and Social Value Orientation Type. Further, there was a significant difference in “Relational Identity” among user types. Regarding personality, the extraversion of Type III appeared to be the highest, and the extraversion of Type II appeared to be the lowest.

Originality/value

Combining aspects of both qualitative and quantitative research to study the subjectivity, the findings of this study provide insight for further research regarding an audience study or an examination of the media behaviors of SNSs. It also suggests theoretical and practical implications.
Mobile internet and consumer happiness: the role of risk
Authors: Zhan Ge , Zhou Zhimin
Published: April 2018

Purpose

The purpose of this paper is to investigate the influence of mobile internet (MI) use and risk factors on MI happiness.

Design/methodology/approach

An online survey with 521 MI users was conducted to test the direct and moderating effects of risk factors on MI happiness.

Findings

The results provide evidence that there is a non-linear relationship between variety of use and MI happiness, and consumers become happier with increased frequency of use. The results also indicate that the privacy risk and task risk reduce MI happiness, and both types of risks moderate the inverted U-shaped relationship between variety of use and MI happiness.

Research limitations/implications

This study reconciles two opposing theories, stimulation vs displacement, on the impact of internet use on consumer well-being. The findings suggest that the stimulation effect of MI use is associated with an intermediate level of usage variety, while social displacement is more likely connected with higher- or lower-variety of use. Risk plays an important role in exploring the boundary conditions of both theories. The findings also have important implications to the debate over the role of privacy in consumer adoption of internet services or applications.

Originality/value

This study reconciles two opposing theories, stimulation vs displacement, on consumer happiness by elaborating the role of risk associated with MI use.
Gender digital divide in India: a case of inter-regional analysis of Uttar Pradesh
Authors: Bala Shashi , Singhal Puja
Published: April 2018

Purpose

This study aims to endeavor to explore the extent of gender digital divide(GDD) in Uttar Pradesh (U.P., IT-Hub of North India), a most populous state of India, with a particular focus on the first and second order of digital divide, including availability, access time and use of the internet.

Design/methodology/approach

The authors have adopted stratified multistage sampling procedure for this research and conducted an empirical study on the data set of 600 respondents of six districts of U.P. to perform the inter-regional analysis. Furthermore, χ2 method has been used to reveal the factors responsible for the GDD among selected districts of UP.

Findings

Statistical results clearly indicate that out of 12 sub-districts, most of the districts suffered from first order as well as second order of GDD, and this gender disparity within an increasing digitization environment is due to the existence of exclusion from basic technological skills, social norms and financial constraints.

Practical implications

The results have implications for the U.P. Government in general and policymakers behind digitization projects in particular as well as the promoters of gender equality including researchers and fellows.

Originality/value

This study is the first to illustrate the orders of the digital gender gap in a developing economy such as India and to gain an insight into the factors behind it. This research will also consider a promising avenue for future work.
Online or in-store: unravelling consumer’s channel choice motives
Authors: Haridasan Anu C. , Fernando Angeline Gautami
Published: April 2018

Purpose

The purpose of this study is to compare online and in-store shoppers motivations based on product type.

Design/methodology/approach

Means-end approach was used to extract motivational factors that drive shoppers channel choice for hedonic and utilitarian products. A total of 100 respondents were interviewed using laddering technique. Hierarchical virtual maps were constructed to determine values associated with attributes and consequences identified by the consumer.

Findings

Shopping motivations differed for online and in-store shoppers based on product type. Variety, value for money and delivery were important attributes for online shoppers. In-store shoppers looked for social interaction and personalized attention. Convenience, affordability and gratification were unique online consequences, while nostalgia and loyalty benefits were specific to in-store hedonic purchases. Self-confidence, availability of wider choices and in-store shopping experience were the values sought for hedonic products. Control of shopping experience was the desired value for utilitarian purchases irrespective of channels.

Research limitations/implications

This study contributes to shopping motivation research by comparing motives of online and in-store shoppers for hedonic and utilitarian products.

Practical implications

Retailers need to enhance online trust and strengthen in-store customer service for hedonic products. They should also work on the online delivery capabilities and in-store personalized services for utilitarian purchases.

Originality/value

Prior research on deconstructing channel choice motivations based on product type is sparse. This paper uses hierarchy of means-end elements to illustrate attributes and consequences that drive consumer motives and values.
Interactions between plant defence signalling pathways: Evidence from bioassays with insect herbivores and plant pathogens
Authors: Moreira Xoaquín , Abdala‐Roberts Luis , Castagneyrol Bastien
Published: April 2018

Sequential damage by attackers is hypothesized to result in reciprocal antagonism (crosstalk) between jasmonic acid (JA) and salicylic acid (SA) defence signalling pathways in plants. However, evidence for this crosstalk is not universal and several studies have found positive interactions (i.e. synergism) or no interaction whatsoever between JA and SA pathways.

Here we conducted a meta‐analysis of studies on plant‐mediated effects of initial attackers on performance of subsequent attackers to test the hypothesis of crosstalk between plant hormonal signalling pathways.

We found a significant negative mean effect size of JA‐inducing initial attackers on both JA‐ and SA‐inducing subsequent attackers, but a non‐significant effect of SA‐inducing initial attackers on both JA‐ and SA‐inducing subsequent attackers. Effects on subsequent herbivores were contingent on the biology of the initial attacker, with negative effects of JA‐inducing initial herbivores but no effect of SA‐inducing initial herbivores, whereas pathogens on average did not influence subsequent herbivores. Furthermore, negative effects of JA‐inducing initial herbivores on JA‐ and SA‐inducing subsequent herbivores held when both attacks occurred on the same plant part, but when attacks were on different plant parts the effect of JA‐inducing herbivores on SA‐inducing herbivores was non‐significant.

Synthesis. These results indicate that reciprocal antagonism between jasmonic acid and salicylic acid pathways is not universal, and suggest assymetries and specificity in the strength of plant‐mediated interactions.
Expanding the clinical spectrum of biallelic ZNF335 variants
Authors: Stouffs K. , Stergachis A.B. , Vanderhasselt T. , Dica A. , Janssens S. , Vandervore L. , Gheldof A. , Bodamer O. , Keymolen K. , Seneca S. , Liebaers I. , Jayaraman D. , Hill H.E. , Partlow J.N. , Walsh C.A. , Jansen A.C.
Published: April 2018

ZNF335 plays an essential role in neurogenesis and biallelic variants in ZNF335 have been identified as the cause of severe primary autosomal recessive microcephaly in 2 unrelated families. We describe, herein, 2 additional affected individuals with biallelic ZNF335 variants, 1 individual with a homozygous c.1399 T > C, p.(Cys467Arg) variant, and a second individual with compound heterozygous c.2171_2173delTCT, p.(Phe724del) and c.3998A > G, p.(Glu1333Gly) variants with the latter variant predicted to affect splicing. Whereas the first case presented with early death and a severe phenotype characterized by anterior agyria with prominent extra‐axial spaces, absent basal ganglia, and hypoplasia of the brainstem and cerebellum, the second case had a milder clinical presentation with hypomyelination and otherwise preserved brain structures on MRI. Our findings expand the clinical spectrum of ZNF335‐associated microcephaly.
The relationship between supplier control and competition in public sector outsourcing
Authors: Johansson Tobias , Siverbo Sven
Published: April 2018

The aim of this article is to develop theory and contribute to empirical studies about how the effectiveness of bureaucratic controls in public sector outsourcing is contingent upon supplier competition, and why and how this interaction plays out differently for hard and soft types of outsourced services. In previous inter‐organizational management control (IOMC) research there is a contradiction between theory and empirical results concerning how bureaucratic control and supplier competition interacts in aligning suppliers. While IOMC theory suggests competition reduces the need for bureaucratic control, empirical studies clearly indicate the opposite. We extend previous research and theorizing by differing between the outsourcing of hard and soft types of services and by testing the joint effect of bureaucratic control and competition on supplier alignment. The empirical case for testing theory is outsourcing by competitive tendering in the public sector. We use transaction level data from 166 local government suppliers in Sweden. In accordance with our prediction, the effect of bureaucratic control in aligning suppliers decreases with supplier competition when hard types of services are outsourced. For soft types of services, our results indicate that bureaucratic control is not contingent upon supplier competition. Furthermore, we show that when supplier competition is low the effect of bureaucratic control on supplier alignment is stronger for hard than for soft types of services. These results constitute an important contribution to the central notion of the interplay between bureaucratic control and competition in the IOMC literature.