bluuebunny/crossref_metadata_2025 huggingface dataset:
AncientYersinia pestisgenomes from across Western Europe reveal early diversification during the First Pandemic (541–750)
Authors: Keller Marcel , Spyrou Maria A. , Scheib Christiana L. , Kröpelin Andreas , Haas-Gebhard Brigitte , Päffgen Bernd , Haberstroh Jochen , i Lacomba Albert Ribera , Raynaud Claude , Cessford Craig , Stadler Peter , Nägele Kathrin , Neumann Gunnar U. , Bates Jessica S. , Trautmann Bernd , Inskip Sarah , Peters Joris , Robb John E. , Kivisild Toomas , McCormick Michael , Bos Kirsten I. , Harbeck Michaela , Herbig Alexander , Krause Johannes
Published: November 2018

The first historically documented pandemic caused byYersinia pestisstarted as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although palaeogenomic studies have previously identified the causative agent asY. pestis, little is known about the bacterium’s spread, diversity and genetic history over the course of the pandemic.

To elucidate the microevolution of the bacterium during this time period, we screened human remains from 20 sites in Austria, Britain, Germany, France and Spain forY. pestisDNA and reconstructed six new genomes. We present a novel methodological approach assessing SNPs in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis reveals the existence of previously undocumentedY. pestisdiversity during the 6th–7thcenturies, and provides evidence for the presence of multiple distinctY. pestisstrains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as southern France and Spain, and that southern Germany seems to have been affected by at least two distinctY. pestisstrains. Four of the reported strains form a polytomy similar to others seen across theY. pestisphylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45 kb genomic region in the most recent First Pandemic strain affecting two virulence factors, intriguingly overlapping with a deletion found in 17th–18th-century genomes of the Second Pandemic.

Significance Statement

The first historically reported pandemic attributed toYersinia pestisstarted with the Justinianic Plague (541–544) and continued for around 200 years as the so-called First Pandemic. To date, only oneY. pestisstrain from this pandemic has been reconstructed using ancient DNA. In this study, we present six new genomes from Britain, France, Germany and Spain, demonstrating the geographic range of plague during the First pandemic and showing microdiversity in the Early Medieval Period. Moreover, we detect similar genome decay during the First and Second Pandemic (17thto 18thcentury) that includes the same two virulence factors, thus providing an example of potential convergent evolution ofY. pestisduring large scale epidemics.
Intelligible speech synthesis from neural decoding of spoken sentences
Authors: Anumanchipalli Gopala K. , Chartier Josh , Chang Edward F.
Published: November 2018

The ability to read out, or decode, mental content from brain activity has significant practical and scientific implications1. For example, technology that translates cortical activity into speech would be transformative for people unable to communicate as a result of neurological impairment2,3,4. Decoding speech from neural activity is challenging because speaking requires extremely precise and dynamic control of multiple vocal tract articulators on the order of milliseconds. Here, we designed a neural decoder that explicitly leverages the continuous kinematic and sound representations encoded in cortical activity5,6to generate fluent and intelligible speech. A recurrent neural network first decoded vocal tract physiological signals from direct cortical recordings, and then transformed them to acoustic speech output. Robust decoding performance was achieved with as little as 25 minutes of training data. Naïve listeners were able to accurately identify these decoded sentences. Additionally, speech decoding was not only effective for audibly produced speech, but also when participants silently mimed speech. These results advance the development of speech neuroprosthetic technology to restore spoken communication in patients with disabling neurological disorders.
Epigenetics of floral homeotic genes in relation to sexual dimorphism in the dioecious plantMercurialis annua
Authors: Khadka Janardan , Yadav Narendra Singh , Guy Micha , Grafi Gideon , Golan-Goldhirsh Avi
Published: November 2018

In plants, dioecy characterizes species carrying male and female flowers on separate plants and occurs in about 6% of angiosperms. To date, the molecular mechanism(s) underlying sexual dimorphism is essentially unknown. The ability of gender-reversal by hormone application suggests that epigenetics might play an important role in sexual dimorphism. Proteome analysis of nuclei derived from flower buds of females, males and feminized males of the dioecious plantMercurialis annuarevealed differentially expressed proteins related to nucleic acid binding proteins, hydrolases and transcription factors, including floral homeotic genes. Further analysis showed that class B genes are mainly expressed in male flowers, while class D genes, as well asSUPERMAN-like genes, were mainly expressed in female flowers. Cytokinin-induced feminization of male plants was associated with down-regulation of male-specific genes concomitantly with up-regulation of female-specific genes. No correlation could be found between the expression of class B and D genes and their DNA methylation or chromatin conformation. Thus, our results ruled out epigenetic control over floral identity genes as the major determinants regulating sexual dimorphisms. Rather, determination of sex inM. annuamight be controlled upstream of floral identity genes by a gender-specific factor that affects hormonal homeostasis.

Highlights

Sex determination inMercurialis annuais not related to epigenetics of floral homeotic genes but appears to be modulated by an unknown gender-specific regulator(s) that affects hormonal homeostasis.
Protective low avidity anti-tumour CD8+ T cells are selectively attenuated by regulatory T cells
Authors: Sugiyarto G. , Prossor D. , Dadas O. , Elliott T. , James E.
Published: November 2018

Regulatory T cells (Treg) play a major role in the suppression of protective anti-tumour T cell responses. In the CT26 BALB/c murine model of colorectal carcinoma, Tregs differentially suppress responses to two characterised CD8+ T epitopes, AH1 and GSW11, which results in an absence of detectable IFN-γ producing GSW11- specific T cells in the spleen and lymph nodes of tumour challenged mice. Activation of GSW11-specific T cells correlates with protection against tumour growth. Here we show that GSW11-specific T cells are in fact induced in Treg-replete, CT26-bearing mice, where they make up the majority of tumour infiltrating CD8+ lymphocytes, but exhibit a dysfunctional ‘exhausted’ phenotype. This dysfunctional phenotype is induced early in the anti-tumour response in draining lymph nodes, spleens and tumours and is significantly more pronounced in GSW11-specific T cells compared to other tumour-specific T cell responses. Depletion of Tregs prior to tumour challenge significantly reduces the induction of exhaustion in GSW11-specific T cells and correlates with altered T cell receptor (TcR) usage. Moreover, the avidity of GSW11- specific TcRs that expanded in the absence of Tregs was significantly lower compared to TcRs of cytotoxic T lymphocyte (CTL) populations that were diminished in protective anti-tumour responses. This indicates that Tregs suppress the induction of protective anti-tumour T cell responses and may signify that the induction of low avidity T cells, while being more susceptible to exhaustion are the most efficacious in tumour rejection.
The repressive genome compartment is established early in the cell cycle before forming the lamina associated domains
Authors: Luperchio TR , Sauria MEG , Hoskins VE , Wong X , DeBoy E , Gaillard M-C , Tsang P , Pekrun K , Ach RA , Yamada NA , Taylor J , Reddy KL
Published: November 2018

Three-dimensional (3D) genome organization is thought to be important for regulation of gene expression. Chromosome conformation capture-based studies have uncovered ensemble organizational principles such as active (A) and inactive (B) compartmentalization. In addition, large inactive regions of the genome associate with the nuclear lamina, the Lamina Associated Domains (LADs). Here we investigate the dynamic relationship between A/B-compartment organization and the 3D organization of LADs. Using refined algorithms to identify active (A) and inactive (B) compartments from Hi-C data and to define LADs from DamID, we confirm that the LADs correspond to the B-compartment. Using specialized chromosome conformation paints, we show that LAD and A/B-compartment organization are dependent upon chromatin state and A-type lamins. By integrating single-cell Hi-C data with live cell imaging and chromosome conformation paints, we demonstrate that self-organization of the B-compartment within a chromosome is an early event post-mitosis and occurs prior to organization of these domains to the nuclear lamina.
Assessing the potential for assisted gene flow using past introduction of Norway spruce in Southern Sweden: Local adaptation and genetic basis of quantitative traits in trees
Authors: Milesi Pascal , Berlin Mats , Chen Jun , Orsucci Marion , Li Lili , Jansson Gunnar , Karlsson Bo , Lascoux Martin
Published: November 2018

Norway spruce (Picea abies) is a dominant conifer species of major economic importance in Northern Europe. Extensive breeding programs were established to improve phenotypic traits of interest. In southern Sweden seeds used to create progeny tests were collected on about 3000 trees of outstanding phenotype (“plus” trees) across the region. Some were of local origin but many were recent introductions from the rest of the natural range. The mixed origin of the trees together with partial sequencing of the exome of >1,500 of these trees and phenotypic data retrieved from the Swedish breeding program offered us a unique opportunity to dissect the genetic basis of local adaptation of three quantitative traits (height,diameterandbudburst). Through a combination of multivariate analyses and genome-wide association studies, we showed that there was a very strong effect of geographical origin on growth (height and diameter) and phenology (budburst) with trees from southern origins outperforming local provenances. Association studies also indicated that growth traits were highly polygenic and budburst somewhat less. Hence, our results suggest that assisted gene flow and genomic selection approaches could help alleviating the effect of climate change onP. abiesbreeding programs in Sweden.
The impact of ischemic stroke on connectivity gradients
Authors: Bayrak Şeyma , Khalil Ahmed A. , Villringer Kersten , Fiebach Jochen B. , Villringer Arno , Margulies Daniel S. , Ovadia-Caro Smadar
Published: November 2018

Understanding the relationship between localized anatomical damage, reorganization, and functional deficits is a major challenge in stroke research. Previous work has shown that localized lesions cause widespread functional connectivity alterations in structurally intact areas, thereby affecting a whole network of interconnected regions. Recent advances suggest an alternative to discrete functional networks by describing a connectivity space based on a low-dimensional embedding of the full connectivity matrix. The dimensions of this space, described as connectivity gradients, capture the similarity of areas’ connections along a continuous space. Here, we defined a three-dimensional connectivity space template based on functional connectivity data from healthy controls. By projecting lesion locations into this space, we demonstrate that ischemic strokes resulted in dimension-specific alterations in functional connectivity over the first week after symptoms onset. Specifically, changes in functional connectivity were captured along connectivity Gradients 1 and 3. The degree of change in functional connectivity was determined by the distance from the lesion along these connectivity gradients regardless of the anatomical distance from the lesion. Together, these results provide a novel framework to study reorganization after stroke and suggest that, rather than only impacting on anatomically proximate areas, the indirect effects of ischemic strokes spread along the brain relative to the space defined by its connectivity.
Rapid Whole Cell Imaging Reveals A Calcium-APPL1-Dynein Nexus That Regulates Cohort Trafficking of Stimulated EGF Receptors
Authors: York H M , Patil A , Moorthi U K , Kaur A , Bhowmik A , Hyde G J , Gandhi H , Gaus K , Arumugam S
Published: November 2018

Multicellular life processes such as proliferation and differentiation depend on cell surface signaling receptors that bind ligands generally referred to as growth factors. Recently, it has emerged that the endosomal system provides rich signal processing capabilities for responses elicited by these factors [1-3]. At the single cell level, endosomal trafficking becomes a critical component of signal processing, as exemplified by the epidermal growth factor (EGF) receptors of the receptor tyrosine kinase family. EGFRs, once activated by EGF, are robustly trafficked to the phosphatase-enriched peri-nuclear region (PNR), where they are dephosphorylated [4-8]. However, the details of the mechanisms regulating the movements of stimulated EGFR in time and space, i.e., towards the PNR, are not known. What endosomal regulators provide specificity to EGFR? Do modifications to the receptor upon stimulation regulate its trafficking? To understand the events leading to EGFR translocation, and especially the early endosomal dynamics that immediately follow EGFR internalization, requires the real-time, long-term, whole-cell imaging of multiple elements. Here, exploiting the advantages of lattice light-sheet microscopy [9], we show that the binding of EGF by its receptor, EGFR, triggers a transient calcium increase that peaks by 30 s, causing the desorption of APPL1 from pre-existing endosomes within one minute, the rebinding of liberated APPL1 to EGFR within three minutes, and the dynein-dependent translocation of APPL1-EGF-bearing endosomes to the PNR within five minutes. The novel, cell spanning, fast acting network that we reveal integrates a cascade of events dedicated to the cohort movement of activated EGFR receptors. Our findings support the intriguing proposal that certain endosomal pathways have shed some of the stochastic strategies of traditional trafficking, and have evolved behaviors whose predictability is better suited to signaling [10, 11]. Work presented here demonstrates that our whole cell imaging approach can be a powerful tool in revealing critical transient interactions in key cellular processes such as receptor trafficking.
A synthetic morphogenic membrane system that responds with self-organized shape changes to local light cues
Authors: Gavriljuk Konstantin , Scocozza Bruno , Ghasemalizadeh Farid , Nandan Akhilesh P. , Medina Manuel Campos , Seidel Hans , Schmick Malte , Koseska Aneta , Bastiaens Philippe I. H.
Published: November 2018

Reconstitution of artificial cells capable of transducing extracellular signals into cytoskeletal changes is a challenge in synthetic biology that will reveal fundamental principles of non-equilibrium phenomena of cellular morphogenesis and information processing. Here, we generated a ‘life-like’ Synthetic Morphogenic Membrane System (SynMMS) by encapsulating a dynamic microtubule (MT) aster and a light-inducible signaling system driven by GTP/ATP chemical potential into cell-sized vesicles. The biomimetic design of the light-induced signaling system embodies the operational principle of morphogen induced Rho-GTPase signal transduction in cells. Activation of synthetic signaling promotes membrane-deforming growth of MT-filaments by dynamically elevating the membrane-proximal concentration of tubulin. The resulting membrane deformations enable the recursive coupling of the MT-aster with the signaling system, creating global self-organized morphologies that reorganize towards external light cues in dependence on prior sensory experience that is stored in the dynamically maintained morphology. SynMMS thereby signifies a step towards bio-inspired engineering of self-organized cellular morphogenesis.
Hfq CLASH uncovers sRNA-target interaction networks involved in adaptation to nutrient availability
Authors: Iosub Ira A. , Marchioretto Marta , Sy Brandon , McKellar Stuart , Nieken Karen J. , van Nues Rob W. , Tree Jai J. , Viero Gabriella , Granneman Sander
Published: November 2018

By shaping gene expression profiles, small RNAs (sRNAs) enable bacteria to very efficiently adapt to constant changes in their environment. To better understand howEscherichia coliacclimatizes to changes in nutrient availability, we performed UV cross-linking, ligation and sequencing of hybrids (CLASH) to uncover sRNA-target interactions. Strikingly, we uncovered hundreds of novel Hfq-mediated sRNA-target interactions at specific growth stages, involving many novel 3’UTR-derived sRNAs and a plethora of sRNA-sRNA interactions. We discovered sRNA-target interaction networks that play a role in adaptation to changes in nutrient availability. We characterized a novel 3’UTR-derived sRNA (MdoR), which is part of a regulatory cascade that enhances maltose uptake by (a) inactivating repressive pathways that block the accumulation of maltose transporters and (b) by reducing the flux of general porins to the outer membrane. Our work provides striking examples of how bacteria utilize sRNAs to integrate multiple regulatory pathways to enhance nutrient stress adaptation.
FDA-ARGOS: A Public Quality-Controlled Genome Database Resource for Infectious Disease Sequencing Diagnostics and Regulatory Science Research
Authors: Sichtig Heike , Minogue Timothy , Yan Yi , Stefan Christopher , Hall Adrienne , Tallon Luke , Sadzewicz Lisa , Nadendla Suvarna , Klimke William , Hatcher Eneida , Shumway Martin , Aldea Dayanara Lebron , Allen Jonathan , Koehler Jeffrey , Slezak Tom , Lovell Stephen , Schoepp Randal , Scherf Uwe
Published: November 2018

Infectious disease next generation sequencing (ID-NGS) diagnostics are on the cusp of revolutionizing the clinical market. To facilitate this transition, FDA proactively invested in tools to support innovation of emerging technologies. FDA and collaborators established a publicly available database, FDA dAtabase for Regulatory-Grade micrObial Sequences (FDA-ARGOS), as a tool to fill reference database gaps with quality-controlled genomes. This manuscript discusses quality control metrics for the proposed FDA-ARGOS genomic resource and outlines the need for quality-controlled genome gap filling in the public domain. Here, we also present three case studies showcasing potential applications for FDA-ARGOS in infectious disease diagnostics, specifically: assay design, reference database and in silico sequence comparison in combination with representative microbial organism wet lab testing; a novel composite validation strategy for ID-NGS diagnostics. The use of FDA-ARGOS as an in silico comparator tool could reduce the burden for completing ID-NGS clinical trials. In addition, use cases identifying Enterococcus avium and Ebola virus (Zaire ebolavirus variant Makona) demonstrate the utility of FDA-ARGOS as a reference database for independent performance validation of new tests and for documenting how one would use this database as an in silico sequence target comparator tool for ID-NGS validation, respectively.
Using expert driven machine learning to enhance dynamic metabolomics data analysis
Authors: Beirnaert Charlie , Peeters Laura , Meysman Pieter , Bittremieux Wout , Foubert Kenn , Custers Deborah , Van der Auwera Anastasia , Cuykx Matthias , Pieters Luc , Covaci Adrian , Laukens Kris
Published: November 2018

Data analysis for metabolomics is undergoing rapid progress thanks to the proliferation of novel tools and the standardization of existing workflows. However, as datasets and experiments continue to increase in size and complexity, standardized workflows are often not sufficient. In addition, as the ground truth for metabolomics experiments is intrinsically unknown, there is no way to critically evaluate the performance of tools. Here, we investigate the problem of dynamic multi-class metabolomics experiments using a simulated dataset with a known ground truth and evaluate the performance of tinderesting, a new and intuitive tool based on gathering expert knowledge to be used in machine learning, and compare it to EDGE, a statistical method for sequence data. This paper presents three novel outcomes. First we present a way to simulate dynamic metabolomics data with a known ground truth based on ordinary differential equations. This method is made available through the MetaboLouise R package. Second, we show that the EDGE tool, originally developed for genomics data analysis, is highly performant in analyzing dynamic case vs control metabolomics data. Last, we introduce the tinderesting method to analyse more complex dynamic metabolomics experiments that performs on par with statistical methods. This tool consists of a Shiny app for collecting expert knowledge, which in turn is used to train a machine learning model to emulate the decision process of the expert. This approach does not replace traditional data analysis workflows for metabolomics, but can provide additional information, improved performance or easier interpretation of results. The advantage is that the tool is agnostic to the complexity of the experiment, and thus is easier to use in advanced setups. All code for the presented analysis, MetaboLouise and tinderesting are freely available.
Functional disease architectures reveal unique biological role of transposable elements
Authors: Hormozdiari Farhad , Geijn Bryce van de , Nasser Joseph , Weissbrod Omer , Gazal Steven , Ju Chelsea J.-T. , O’Connor Luke , Hujoel Margaux Louise Anna , Engreitz Jesse , Hormozdiari Fereydoun , Price Alkes L.
Published: November 2018

Transposable elements (TE) comprise roughly half of the human genome. Though initially derided as “junk DNA”, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases and complex traits remains unknown. Here, we analyze data from 41 independent diseases and complex traits (average N=320K) to draw three main conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39±2% of heritability; enrichment of 0.72±0.03; 0.38-1.23 enrichment across four main TE classes), TE explain substantially more heritability than expected based on their depletion for known functional annotations (expected enrichment of 0.35±0.03; 2.11x ratio of true vs. expected enrichment). This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring biological function; SNPs inside the oldest 20% of TE explain 2.45x more heritability than SNPs inside the youngest 20% of TE. Third, Short Interspersed Nuclear Elements (SINE; one of the four main TE classes) are far more enriched for blood traits (2.05±0.30) than for other traits (0.96±0.09); this difference is far greater than expected based on the weaker depletion of SINEs for regulatory annotations in blood compared to other tissues. Our results elucidate the biological roles that TE play in the genetic architecture of diseases and complex traits.
APOE4is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in AgedAPOEMice
Authors: Nuriel Tal , Larrea Delfina , Guilfoyle David N. , Pirhaji Leila , Shannon Kathleen , Arain Hirra , Ashok Archana , Pera Marta , Chen Qiuying , Dillman Allissa A. , Figueroa Helen Y. , Cookson Mark R. , Gross Steven S. , Fraenkel Ernest , Duff Karen E. , Area-Gomez Estela
Published: November 2018

The ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer’s disease (AD). However, the reason for the association betweenAPOE4and AD remains unclear. While much of the research has focused on the ability of the apoE4 protein to increase the aggregation and decrease the clearance of Aβ, there is also an abundance of data showing thatAPOE4negatively impacts many additional processes in the brain, including bioenergetics. In order to gain a more comprehensive understanding of theAPOE4’s role in AD pathogenesis, we performed a multi-omic analysis ofAPOE4vs.APOE3expression in the entorhinal cortex (EC) and primary visual cortex (PVC) of agedAPOEmice. These studies revealed region-specific alterations in several bioenergetic pathways, including oxidative phosphorylation (OxPhos), the TCA-cycle and fatty acid metabolism. Follow-up analysis utilizing the Seahorse platform revealed decreased mitochondrial respiration in the hippocampus and cortex of agedAPOE4vs.APOE3mice, but not in the EC of these mice. Additional studies, as well as the original multi-omic data suggest that bioernergetic pathways in the EC of agedAPOEmice may be differentially regulated byAPOE4expression. Given the importance of the EC as one of the first regions to be affected by AD pathology in humans, this differential bionenergetic regulation observed in the EC vs. other brain regions of agedAPOE4mice may play an important role in the pathogenesis of AD, particularly amongAPOE4carriers.
Meiotic effects ofMSH4copy number variation support an adaptive role for post-polyploidy gene loss
Authors: Gonzalo Adrián , Lucas Marie-Odile , Marquis Catherine , Lloyd Andrew , Jenczewski Eric
Published: November 2018

Many eukaryotes descend from polyploid ancestors that experienced massive duplicate gene loss. This genomic erosion is particularly strong for duplicated (meiotic) recombination genes that return to a single copy more rapidly than genome average following polyploidy. To better understand the evolutionary forces underlying duplicate loss, we analysed how varying copy numbers ofMSH4, an essential meiotic recombination gene, influences crossover formation in allotetraploidBrassica napus. We show that faithful chromosome segregation and crossover frequencies between homologous chromosomes are unchanged withMSH4duplicate loss; by contrast, crossovers between homoeologous chromosomes (which result in genomic rearrangements) decrease with reductions inMSH4copy number. We also found that inter-homoeologue crossovers originate almost exclusively from the MSH4-dependent crossover pathway. Limiting the efficiency of this pathway by decreasing the copy number of key meiotic recombination genes could therefore contribute to adaptation to polyploidy, by promoting regular chromosome segregation and genomic stability.
Genotype network intersections promote evolutionary innovation
Authors: Bendixsen Devin P. , Collet James , Østman Bjørn , Hayden Eric J.
Published: November 2018

Evolutionary innovations are qualitatively novel traits that emerge through evolution and increase biodiversity. The genetic mechanisms that lead to innovation remain poorly understood. A systems view of innovation requires the analysis of genotype networks – the vast networks of genetic variants that produce the same phenotype. Innovations can occur at the intersection of two different genotype networks. Here, we use high-throughput sequencing to study the fitness landscape at the intersection of the genotype networks of two catalytic RNA molecules (ribozymes). We determined the ability of numerous neighboring RNA sequences to catalyze two different chemical reactions. We find extensive functional overlap, and over half the genotypes can catalyze both functions to some extent. We demonstrate through evolutionary simulations that these numerous points of intersection facilitate the discovery of a new function. Our study reveals the properties of a fitness landscape where genotype networks intersect, and the consequences for evolutionary innovations.
Using subthreshold events to characterize the functional architecture of electrically coupled networks
Authors: Lefler Yaara , Amsalem Oren , Segev Idan , Yarom Yosef
Published: November 2018

The electrical connectivity in the inferior olive (IO) nucleus plays an important role in generating well-timed spiking activity. Here we combined electrophysiological and computational approaches to assess the functional organization of mice IO nucleus. Spontaneous fast and slow subthreshold events were commonly encountered during in vitro recordings. We show that the fast events represent a regenerative response in unique excitable spine-like structures in the axon hillock, whereas the slow events reflect the electrical connectivity between neurons (‘spikelets’). Recordings from cell pairs revealed the synchronized occurrence of distinct groups of spikelets; their rate and distribution enabled an accurate estimation of the number of connected cells and is suggestive of a clustered organization. This study thus provides a new perspective on the functional and structural organization of the olivary nucleus, insights into two different subthreshold non-synaptic events, and a novel experimental and theoretical approach to the study of electrically-coupled networks.
Flagellar stators stimulate c-di-GMP production by Pseudomonas aeruginosa
Authors: Baker Amy E. , Webster Shanice S. , Diepold Andreas , Kuchma Sherry L. , Bordeleau Eric , Armitage Judith P. , O’Toole George A.
Published: November 2018

Flagellar motility is critical for surface attachment and biofilm formation in many bacteria. A key regulator of flagellar motility in Pseudomonas aeruginosa and other microbes is cyclic diguanylate (c-di-GMP). High levels of this second messenger repress motility and stimulate biofilm formation. C-di-GMP levels regulate motility in P. aeruginosa in part by influencing the localization of its two flagellar stator sets, MotAB and MotCD. Here we show that just as c-di-GMP can influence the stators, stators can impact c-di-GMP levels. We demonstrate that the swarming motility-driving stator MotC physically interacts with the transmembrane region of the diguanylate cyclase SadC. Furthermore, we demonstrate that this interaction is capable of stimulating SadC activity. We propose a model by which the MotCD stator set interacts with SadC to stimulate c-di-GMP production in conditions not permissive to motility. This regulation implies a positive feedback loop in which c-di-GMP signaling events cause MotCD stators to disengage from the motor; then disengaged stators stimulate c-di-GMP production to reinforce a biofilm mode of growth. Our studies help define the bidirectional interactions between c-di-GMP and the motility machinery.

Importance.

The ability of bacterial cells to control motility during early steps in biofilm formation is critical for the transition to a non-motile, biofilm lifestyle. Recent studies have clearly demonstrated the ability of c-di-GMP to control motility via a number of mechanisms, including through controlling transcription of motility-related genes and modulating motor function. Here we provide evidence that motor components can in turn impact c-di-GMP levels. We propose that communication between motor components and c-di-GMP synthesis machinery allows the cell to have a robust and sensitive switching mechanism to control motility during early events in biofilm formation.
Olfactory Spatial Attention: Neural Structural Connectivity Revealed
Authors: Elumalai Ganesh , Chatterjee Harshita , Syed Imran Shareef , Brown Valencia , Sober Lekesha Adele , Venkata Ghanta Nitya Akarsha Surya , Chandrasekhar Pradeep , Venkatesan Anbarasan , Sewram Nadira , Muthukumaran Nitesh Raj , Harkrishna Golla , Vamsi Nanduri Mojess , Team NeurON Nneoma Somtochukwu Osakwe , University Texila American
Published: November 2018

Different aspects of spatial neglect, the disability to locate the position of the source of an external stimulus, has been studied frequently especially with regards to lack of response to visual stimuli. A modicum of papers fails to elaborate on that of the auditory field and even less conducted on the extraction of spatial information from olfactory stimuli. In this study we attempted to find a structural connection between the Olfactory Cortex (OC) and Temporoparietal Junction (TPJ), in order to suggest that processed olfactory information is carried from OC to TPJ, where the spatial information of the odor maybe acquired. Positive results were attained in all subjects with a lateralization observed in the right hemisphere.

One Sentence Summary

Existence and hemispherical dominance.
Using EEG to characterise drowsiness during short duration exposure to elevated indoor Carbon Dioxide concentrations
Authors: Snow Stephen , Boyson Amy , Felipe-King Marco , Malik Obaid , Coutts Louise , Noakes Catherine J , Gough Hannah , Barlow Janet , schraefel m.c.
Published: November 2018

Drowsiness which can affect work performance, is often elicited through self- reporting. This paper demonstrates the potential to use EEG to objectively quantify changes to drowsiness due to poor indoor air quality. Continuous EEG data was recorded from 23 treatment group participants subject to artificially raised indoor CO2 concentrations (average 2,700 ± 300 ppm) for approximately 10 minutes and 13 control group participants subject to the same protocol without additional CO2 (average 830 ± 70 ppm). EEG data were analysed for markers of drowsiness according neurophysiological methods at three stages of the experiment, Baseline, High CO2 and Post-Ventilation. Treatment group participants’ EEG data yielded a closer approximation to drowsiness than that of control group participants during the High CO2 condition, despite no significant group differences in self-reported sleepiness. Future work is required to determine the persistence of these changes to EEG over longer exposures and to better isolate the specific effect of CO2 on drowsiness compared to other environmental or physiological factors.

Practical implications

This study introduces EEG as a potential objective indicator of the effect of indoor environmental conditions upon drowsiness

Participants exposed to 2,700 ppm for 10 minutes showed greater evidence of a progression towards drowsiness (as measured by EEG) than that of participants who received the same protocol without additional CO2 (mean 830 ± 70 ppm), despite similar ratings of subjective sleepiness.

Subjective and objectively measured indications of drowsiness were reduced following ventilation of the room. Future work could explore the potential of regular ventilation episodes in knowledge work spaces to retain alertness.
First genome-wide association study of non-severe malaria in two birth cohorts in Benin
Authors: Milet Jacqueline , Boland Anne , Luisi Pierre , Sabbagh Audrey , Sadissou Ibrahim , Sonon Paulin , Domingo Nadia , Palstra Friso , Gineau Laure , Courtin David , Massougbodji Achille , Garcia André , Deleuze Jean-François , Perdry Hervé
Published: November 2018

Recent research efforts to identify genes involved in malaria susceptibility using genome-wide approaches have focused on severe malaria. Here we present the first GWAS on non-severe malaria designed to identify genetic variants involved in innate immunity or innate resistance mechanisms. Our study was performed on two cohorts of infants from southern Benin (525 and 250 individuals respectively) closely followed from birth to 18-24 months of age, with an assessment of a space-and time-dependent environmental risk of exposure. Both the recurrence of mild malaria attacks and the recurrence of malaria infections as a whole (symptomatic and asymptomatic) were considered. Our study highlights a role ofPTPRT, a tyrosine phosphatase receptor involved in STAT3 pathway and several other genes whose biological functions are relevant in malaria infection. Results shows that GWAS on non-severe malaria can successfully identify new candidate genes and inform physiological mechanisms underlying natural protection against malaria.
Crystal structure and Hirshfeld surface analysis and of 2-ammoniumylmethyl-1H-benzimidazol-3-ium chloride monohydrate. Corrigendum
Authors: Sen Pinar , Kansiz Sevgi , Dege Necmi , Yildiz S. Zeki , Tsapyuk Galyna G.
Published: November 2018

In the paper by Sen et al. [Acta Cryst. (2018), E74, 1517–1520], the address of the correspondence author is incorrect.
Structures of the hydrate and dihydrate forms of the DNA-binding radioprotector methylproamine
Authors: White Jonathan Michael , Brydon Samuel Charles , Fellowes Thomas
Published: November 2018

Methyl proamine {N,N,3-trimethyl-4-[6-(4-methylpiperazin-1-yl)-1H,3′H-[2,5′-bibenzo[d]imidazol]-2′-yl]aniline}, C28H35N7O2, crystallized as both a dihydrate, C28H31N7·2H2O, and monohydrate, C28H31N7·H2O, form from water in the presence of β-cyclodextrin, in the P21/c and P21/n space groups, respectively. The two structures adopt different conformations and tautomeric forms as a result of the differing crystal packing as dictated by hydrogen-bonding interactions. The dihydrate crystallizes as a three-dimensional hydrogen-bonded network, while the monohydrate crystallizes as a two-dimensional hydrogen-bonded network.
catena-Poly[[[bis(glycolato-κ2
O,O′)copper(II)]-μ-4,4′-bipyridine-κ2
N:N′] ethane-1,2-diol monosolvate]
Authors: Zhong Kai-Long
Published: November 2018

In the title compound, {[Cu(C2H3O3)2(C10H8N2)]·C2H6O2}
n
, the CuII cation is six-coordinated in a slightly distorted octahedral manner by two N atoms from two different bridging 4,4′-bipyridine (4,4′-bipy) ligands and four O atoms from two individual glycolate anions. The 4,4′-bipy ligand bridges adjacent CuII centres, generating linear chains running parallel to the [1\overline10] direction. In the crystal structure, adjacent chains are further connected by classical O—H...O hydrogen bonds, resulting in a two-dimensional supermolecular network structure parallel to (100). The C atom of one of the ethane-1,2-diol solvent molecules is disordered over two sets of sites with occupancies of 0.51 (2) and 0.49 (2).
The perceived influence of relationship quality on brand loyalty
Authors: Ledikwe Aobakwe , Roberts-Lombard Mornay , Klopper Hendrik Baltus
Published: November 2018

Purpose

The purpose of this paper is to investigate the extent to which the attitudinal loyalty of customers of small and medium apparel businesses is influenced by their perceptions of trust, commitment and satisfaction. In turn, the influence of their attitudinal loyalty on future behavioural loyalty is established.

Design/methodology/approach

A quantitative descriptive research approach was employed and questionnaires were administered to customers of three selected small and medium enterprise (SME) brands in the metropolitan city of Gaborone, Botswana. A total of 260 questionnaires were suitable for data analysis. The interrelationship of the constructs was analysed via structural equation modelling. In addition, the measurement and structural models were assessed.

Findings

Trust, commitment and satisfaction have a positive and significant influence on the attitudinal loyalty of SME customers, while attitudinal loyalty has a positive and significant influence on their behavioural loyalty.

Research limitations/implications

The tested model confirms the hypothesised relationships between SME customers’ trust, commitment, satisfaction, attitudinal loyalty and behavioural loyalty. Attitudinal loyalty is linked to its three antecedents (trust, commitment and satisfaction) and its outcome, behavioural loyalty.

Practical implications

The findings assist the management of SMEs in understanding how the cultivation of trust, commitment and satisfaction can foster attitudinal loyalty, ultimately leading to improved behavioural loyalty.

Originality/value

The current study contributes to new knowledge on the interrelationship of selected relationship quality dimensions, attitudinal loyalty and behavioural loyalty among SME customers in the apparel industry of Botswana. Few research studies have examined how attitudinal loyalty relates to its antecedents and outcome in Botswana, as an emerging African economy.
Managing noise in signalling effectiveness: an empirical test of listed companies in China
Authors: Yao Nengzhi (Chris) , Zhu Weiwei , Wei Jiuchang
Published: November 2018

Purpose

Signalling theory suggests how “strong” or “weak” the signal quality detected by a receiver (defined as signalling strength) is distorted by noisy factors (defined as noise). Although corporate cooperation signals are known to lead to receiver reaction, the effects of distortion factors on signal credibility are generally unexplored in signalling process. The paper aims to discuss this issue.

Design/methodology/approach

After analysing 264 contract announcements in 2013–2015 that befall publicly listed firms in China, the authors explore the signalling impact of contract value. the authors also incorporate the signalling noises, namely, signalling environment, external referents and other signallers, into the contracting context and investigate their effects on distorting the relationship between signal strength and receiver reaction.

Findings

Results indicate that firms’ contract-signing announcement conveys an effective signal to investors: the larger the contract scale is, the more investor reaction the firms experience. The signalling effects of contract scale on investor reaction are moderated by the three distorting factors.

Originality/value

The findings contribute to the signalling theory literature on the effects of signalling noise on receivers’ perception of signal observability.
Why do some SMEs explore more while others exploit further? Evidence from Chinese SMEs
Authors: Hu Hong , Wang Qiang , Chen Jixiang
Published: November 2018

Purpose

Why do some small and medium-sized enterprises (SMEs) explore more while others exploit further? What are the driving forces of their exploratory and exploitative innovation? These are intriguing questions worthy of in-depth research. The purpose of this paper is to crack these problems from both objective (i.e. organizational slack) and subjective (i.e. market orientation) perspectives. Specifically, the paper examines the effects of unabsorbed and absorbed slack on exploratory and exploitative innovation and the mediating roles played by proactive and responsive market orientation.

Design/methodology/approach

The authors collected data from 214 SMEs in several industries of China. These businesses were located in the city of Shanghai and the provinces of Jiangsu and Zhejiang in the southeastern part of China. The survey method was used to test the hypotheses.

Findings

Results reveal that unabsorbed and absorbed slack could affect exploratory and exploitative innovation. Proactive and responsive market orientation are related to unabsorbed and absorbed slack, exploratory and exploitative innovation, and they play the roles of mediators in two sets of the relationships.

Research limitations/implications

This research presents several profound insights for venture capitalists regarding to making investment decisions and for the entrepreneurs of SMEs in terms of how much resource slack they should gain and retain to reach intended level of exploratory and exploitative innovation. Some of the limitations of this study relate to the single respondent in each firm, lack of examination on relevant contextual factors and potential moderators.

Originality/value

This study addresses the gaps in the literature by exploring the mechanisms underlying the effects of different kinds of organizational slack on the two elements of ambidextrous innovation in non-large-scale businesses in a non-Western cultural setting.
Building spaces for literacy in school: mapping the emergence of a literacy makerspace
Authors: Stornaiuolo Amy , Nichols T. Philip , Vasudevan Veena
Published: November 2018

Purpose

Building on the growing interest in school-based “making” and “makerspaces,” this paper aims to map the emergence of a literacy-oriented makerspace in a non-selective urban public high school. It examines how competing conceptions of literacy came to be negotiated as students and teachers shaped this new space for literacy practice, and it traces how the layered uses of the space, in turn, reworked understandings of literacy in the larger school community.

Design/methodology/approach

Part of a longitudinal design-research partnership with an urban public high school, the paper draws on two years of ethnographic data collection to follow the creation, development and uses of a school-based literacy-oriented makerspace.

Findings

Using notions of “re-territorialization,” the paper examines how the processes of designing, mapping and building a literacy lab offered space for layered and contested purposes that instantiated more expansive views of literacy in the school – even as it created new frictions. In presenting two analytic mappings, the paper illustrates how mapping can offers resources for people to make and remake the spaces they inhabit, a form of worldmaking that can open possibilities for reshaping the built world in more just and equitable ways.

Originality/value

The study offers insights into how mapping can serve as a research and pedagogical resource for making legible the emergent dimensions of literacy practice across time and spaces and the multiple perspectives that inform the design and use of educational spaces. Further, it contributes to a growing literature on “making” and literacy by examining how informal making practices are folded into formal school structures and considering how this reconfigures literacy learning.
Effect of mental construals on cooperative and competitive conflict management styles
Authors: Mukherjee Kanchan , Upadhyay Divya
Published: November 2018

Purpose

This paper aims to explore the psychological antecedents and processes that lead to competitive or cooperative attitudes in conflict management using the lens of construal level theory (CLT). CLT suggests that adopting a distal versus proximal psychological perspective changes the way people think and behave. This research explores the systematic effect of these abstract versus concrete mental construals on preferred conflict management styles.

Design/methodology/approach

First, theoretically grounded hypotheses linking different mental construals to cooperative and competitive conflict management styles were formulated. Subsequently, four empirical studies were conducted to test the hypotheses.

Findings

The studies provide support to the hypotheses showing that high construal abstract thinking is linked to preference for cooperation while low construal thinking is linked to preference for competition. Further, two different psychological processes mediate participants’ preferences for cooperative and competitive conflict management styles, the former mediated by perspective taking and empathic concern and the latter by impulsivity and aggression.

Research limitations/implications

The research measures conflict management styles rather than actual behavior. Also, focus is on trait mental construals rather than priming of high or low construal thinking.

Practical implications

Deeper understanding of the psychology of cooperative and competitive conflict management styles can help parties attain better outcomes and can potentially contribute to training and talent development by educating conflict management practitioners.

Social implications

The findings of this research can potentially inform effective interventions aimed at reducing intergroup conflicts.

Originality/value

Mental construals and related psychological processes are linked to conflict management styles for the first time.