bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human cortical pyramidal neurons: From spines to spikes via models
Authors: Eyal Guy , Verhoog Matthias B. , Testa-Silva Guilherme , Deitcher Yair , Benavides-Piccione Ruth , DeFelipe Javier , de Kock Christiaan P.J. , Mansvelder Huibert D. , Segev Idan 
Published: February 2018

AbstractWe present the first-ever detailed models of pyramidal cells from human neocortex, including models on their excitatory synapses, dendritic spines, dendritic NMDA- and somatic/axonal- Na+ spikes that provided new insights into signal processing and computational capabilities of these principal cells. Six human layer 2 and layer 3 pyramidal cells (HL2/L3 PCs) were modeled, integrating detailed anatomical and physiological data from both fresh and post mortem tissues from human temporal cortex. The models predicted particularly large AMPA- and NMDA- conductances per synaptic contact (0.88 nS and 1.31nS, respectively) and a steep dependence of the NMDA-conductance on voltage. These estimates were based on intracellular recordings from synaptically-connected HL2/L3 pairs, combined with extra-cellular current injections and use of synaptic blockers. A large dataset of high-resolution reconstructed HL2/L3 dendritic spines provided estimates for the EPSPs at the spine head (12.7 ± 4.6 mV), spine base (9.7 ± 5.0 mV) and soma (0.3 ± 0.1 mV), and for the spine neck resistance (50 – 80 MΩ). Matching the shape and firing pattern of experimental somatic Na+-spikes provided estimates for the density of the somatic/axonal excitable membrane ion channels, predicting that 134 ± 28 simultaneously activated HL2/L3- HL2/L3 synapses are required for generating (with 50% probability) a somatic Na+ spike. Dendritic NMDA spikes were triggered in the model when 20 ± 10 excitatory spinous synapses were simultaneously activated on individual dendritic branches. The particularly large number of basal dendrites in HL2/L3 PCs and the distinctive cable elongation of their terminals imply that ~25 NMDA- spikes could be generated independently and simultaneously in these cells, as compared to ~14 in L2/3 PCs from the rat temporal cortex. These multi-sites nonlinear signals, together with the large (~30,000) excitatory synapses/cell, equip human L2/L3 PCs with enhanced computational capabilities. Our study provides the most comprehensive model of any human neuron to-date demonstrating the biophysical and computational distinctiveness of human cortical neurons.
STAG: Species Tree Inference from All Genes
Authors: Emms D.M. , Kelly S. 
Published: February 2018

AbstractSpecies tree inference is fundamental to our understanding of the evolution of life on earth. However, species tree inference from molecular sequence data is complicated by gene duplication events that limit the availably of suitable data for phylogenetic reconstruction. Here we propose a novel method for species tree inference called STAG that is specifically designed to leverage data from multi-copy gene families. By application to 12 real species datasets sampled from across the eukaryotic domain we demonstrate that species trees inferred from multi-copy gene families are comparable in accuracy to species trees inferred from single-copy orthologues. We further show that the ability to utilise data from multi-copy gene families increases the amount of data available for species tree inference by an average of 8 fold. We reveal that on real species datasets STAG has higher accuracy than other leading methods for species tree inference; including concatenated alignments of protein sequences, ASTRAL & NJst. Finally we show that STAG is fast, memory efficient and scalable and thus suitable for analysis of large multispecies datasets.
Evolution of subgenomic RNA shapes dengue virus adaptation and epidemiological fitness
Authors: Finol Esteban , Ooi Eng Eong 
Published: February 2018

AbstractGenetic changes in the dengue virus (DENV) genome affects viral fitness both clinically and epidemiologically. Even in the 3’ untranslated region (3’UTR), mutations could impact the formation of subgenomic flaviviral RNA (sfRNA) and the specificity of sfRNA in inhibiting host proteins necessary for successful viral replication. Indeed, we have recently shown that mutations in the 3’UTR of DENV2 affected its ability to inhibit TRIM25 E3 ligase activity to reduce interferon (IFN) expression, which potentially contributed to the emergence of a new viral clade during the 1994 dengue epidemic in Puerto Rico. However, whether differences in 3’UTRs shaped DENV evolution on a larger scale remains incompletely understood. Herein, we combined RNA phylogeny with phylogenetics to gain insights on sfRNA evolution. We found that sfRNA structures are under purifying selection and highly conserved despite sequence divergence. Interestingly, only the second flaviviral Nuclease-resistant RNA (fNR2) structure of DENV-2 has undergone strong positive selection. Epidemiological reports also suggest that nucleotide substitutions in fNR2 may drive DENV-2 epidemiological fitness, possibly through sfRNA-protein interactions. Collectively, our findings indicate that 3’UTRs are important determinants of DENV fitness in human-mosquito cycles.HighlightsDengue viruses (DENV) preserve RNA elements in their 3’ untranslated region (UTR).Site-specific quantification of natural selection revealed positive selection on DENV2 sfRNA.Flaviviral nuclease-resistant RNA (fNR) structures in DENV 3’UTRs contribute to DENV speciation.A highly evolving fNR structure appears to increase DENV-2 epidemiological fitness.
Exosomes and exosomal miRNAs from muscle-derived fibroblasts promote skeletal muscle fibrosis
Authors: Zanotti Simona , Gibertini Sara , Blasevich Flavia , Bragato Cinzia , Ruggieri Alessandra , Saredi Simona , Introna Clelia , Bernasconi Pia , Maggi Lorenzo , Mantegazza Renato , Mora Marina 
Published: February 2018

AbstractWe investigated in vitro and in vivo the pro-fibrotic role of exosomes released by muscle-derived fibroblasts of Duchenne muscular dystrophy (DMD) patients, and of miRNAs carried by exosomes. We found that exosomes from DMD fibroblasts, but not from myoblasts, had significantly higher levels of miR-199a-5p, a miRNA up-regulated in fibrotic conditions, compared to control exosomes. In control fibroblasts, exposure to DMD fibroblast-derived exosomes induced a myofibroblastic phenotype with increase in α-smooth actin, collagen and fibronectin transcript and protein expression, soluble collagen production and deposition, cell proliferation, and activation of Akt and ERK signalling, while exposure to control exosomes did not. These findings were related to transfer of high levels of miR-199a-5p and to reduction of its target caveolin-1. Finally, injection of DMD fibroblast-derived exosomes into mouse tibialis anterior muscle after cardiotoxin-induced necrosis, produced greater fibrosis than control exosomes.Our findings indicate that exosomes produced by local fibroblasts in the DMD muscle are able to induce phenotypic conversion of normal fibroblasts to myofibroblasts thereby increasing the fibrotic response; and suggest miR-199a-5p and caveolin-1as potential therapeutic targets.
Probing the limits of alpha power lateralization as a neural marker of selective attention in middle-aged and older listeners
Authors: Tune Sarah , Wöstmann Malte , Obleser Jonas 
Published: February 2018

AbstractIn recent years, hemispheric lateralization of alpha power has emerged as a neural mechanism thought to underpin spatial attention across sensory modalities. Yet, how healthy aging, beginning in middle adulthood, impacts the modulation of lateralized alpha power supporting auditory attention remains poorly understood. In the current electroencephalography (EEG) study, middle-aged and older adults (N= 29; ~40-70 years) performed a dichotic listening task that simulates a challenging, multi-talker scenario. We examined the extent to which the modulation of 8-12 Hz alpha power would serve as neural marker of listening success across age. With respect to the increase in inter-individual variability with age, we examined an extensive battery of behavioral, perceptual, and neural measures. Similar to findings on younger adults, middle-aged and older listeners′ auditory spatial attention induced robust lateralization of alpha power, which synchronized with the speech rate. Notably, the observed relationship between this alpha lateralization and task performance did not co-vary with age. Instead, task performance was strongly related to an individual’s attentional and working memory capacity. Multivariate analyses revealed a separation of neural and behavioral variables independent of age. Our results suggest that in age-varying samples as the present one, the lateralization of alpha power is neither a sufficient nor necessary neural strategy for an individual’s auditory spatial attention, as higher age might come with increased use of alternative, compensatory mechanisms. Our findings emphasize that explaining inter-individual variability will be key to understanding the role of alpha oscillations in auditory attention in the aging listener.
Population Turnover in Remote Oceania Shortly After Initial Settlement
Authors: Lipson Mark , Skoglund Pontus , Spriggs Matthew , Valentin Frederique , Bedford Stuart , Shing Richard , Buckley Hallie , Phillip Iarawai , Ward Graeme K. , Mallick Swapan , Rohland Nadin , Broomandkhoshbacht Nasreen , Cheronet Olivia , Ferry Matthew , Harper Thomas K. , Michel Megan , Oppenheimer Jonas , Sirak Kendra , Stewardson Kristin , Auckland Kathryn , Hill Adrian V.S. , Maitland Kathryn , Oppenheimer Stephen J. , Parks Tom , Robson Kathryn , Williams Thomas N. , Kennett Douglas J. , Mentzer Alexander J. , Pinhasi Ron , Reich David 
Published: February 2018

SummaryAncient DNA analysis of three individuals dated to ~3000 years before present (BP) from Vanuatu and one ~2600 BP individual from Tonga has revealed that the first inhabitants of Remote Oceania (“First Remote Oceanians”) were almost entirely of East Asian ancestry, and thus their ancestors passed New Guinea, the Bismarck Archipelago, and the Solomon Islands with minimal admixture with the Papuan groups they encountered [1]. However, all present-day populations in Near and Remote Oceania harbor 25-100% Papuan ancestry, implying that there must have been at least one later stream of migration eastward from Near Oceania. We generated genome-wide data for 14 ancient individuals from Efate and Epi Islands in Vanuatu ranging from 3,000-150 BP, along with 185 present-day Vanuatu individuals from 18 islands. We show that people of almost entirely Papuan ancestry had arrived in Vanuatu by 2400 BP, an event that coincided with the end of the Lapita cultural period, changes in skeletal morphology, and the cessation of long-distance trade between Near and Remote Oceania [2]. First Remote Oceanian ancestry subsequently increased via admixture but remains at 10-20% in most islands. Through a fine-grained comparison of ancestry profiles in Vanuatu and Polynesia with diverse groups in Near Oceania, we find that Papuan ancestry in Vanuatu is consistent with deriving from the Bismarck Archipelago instead of the geographically closer Solomon Islands. Papuan ancestry in Polynesia also shows connections to the ancestry profiles present in the Bismarck Archipelago but is more similar to Tolai from New Britain and Tutuba from Vanuatu than to the ancient Vanuatu individuals and the great majority of present-day Vanuatu populations. This suggests a third eastward stream of migration from Near to Remote Oceania bringing a different type of Papuan ancestry.
Human noise blindness drives suboptimal cognitive inference
Authors: Castañón Santiago Herce , Bang Dan , Moran Rani , Ding Jacqueline , Egner Tobias , Summerfield Christopher 
Published: February 2018

AbstractHumans typically make near-optimal sensorimotor judgments but show systematic biases when making more cognitive judgments. Here we test the hypothesis that, while humans are sensitive to the noise present during early sensory processing, the “optimality gap” arises because they are blind to noise introduced by later cognitive integration of variable or discordant pieces of information. In six psychophysical experiments, human observers judged the average orientation of an array of contrast gratings. We varied the stimulus contrast (encoding noise) and orientation variability (integration noise) of the array. Participants adapted near-optimally to changes in encoding noise, but, under increased integration noise, displayed a range of suboptimal behaviours: they ignored stimulus base rates, reported excessive confidence in their choices, and refrained from opting out of objectively difficult trials. These overconfident behaviours were captured by a Bayesian model which is blind to integration noise. Our study provides a computationally grounded explanation of suboptimal cognitive inferences.
Shifting patterns of seasonal influenza epidemics
Authors: Coletti Pietro , Poletto Chiara , Turbelin Clément , Blanchon Thierry , Colizza Vittoria 
Published: February 2018

AbstractSeasonal waves of influenza display a complex spatiotemporal pattern resulting from the interplay of biological, socio-demographic, and environmental factors. At country level many studies characterized the robust properties of annual epidemics, depicting a typical season. Here we analyzed season-by-season variability, introducing a clustering approach to assess the deviations from typical spreading patterns. The classification is performed on the similarity of temporal configurations of onset and peak times of regional epidemics, based on influenza-like-illness time-series in France from 1984 to 2014. We observed a larger variability in the onset compared to the peak. Two relevant classes of clusters emerge: groups of seasons sharing similar recurrent spreading patterns (clustered seasons) and single seasons displaying unique patterns (monoids). Recurrent patterns exhibit a more pronounced spatial signature than unique patterns. We assessed how seasons shift between these classes from onset to peak depending on epidemiological, environmental, and socio-demographic variables. We found that the spatial dynamics of influenza and its association with commuting, previously observed as a general property of French influenza epidemics, applies only to seasons exhibiting recurrent patterns. The proposed methodology is successful in providing new insights on influenza spread and can be applied to incidence time-series of different countries and different diseases.
From spiral cleavage to bilateral symmetry: The developmental cell lineage of the annelid brain
Authors: Vopalensky Pavel , Tosches Maria Antonietta , Achim Kaia , Handberg-Thorsager Mette , Arendt Detlev 
Published: February 2018

AbstractThe spiral cleavage pattern is characteristic for Spiralia (Lophotrochozoa), a large assembly of marine invertebrates. In most cases, spiral cleavage produces freely swimming, trochophora-type larvae with a simple nervous system that controls ciliary locomotion. These larvae acquire bilateral symmetry, as manifested for example in the larval brain. The transition from the rotational symmetry of spiral cleavage into the bilateral adult body has not yet been understood. Here, we present the developmental cell lineage of the brain of the annelidPlatynereis dumeriliifrom the zygote until the mid-trochophore stage (~30 hpf), in combination with a gene expression atlas for several embryonic and larval stages. Comparison of multiple embryos reveals a highly stereotypical development and an invariant cell lineage of the differentiated cell types. In addition, we observe a fundamental subdivision of the larval brain into a highly proliferative dorsolateral region and an early differentiating ventromedial region that gives rise to the apical nervous system. The transition from rotational to bilateral symmetry progresses gradually from the lateral to the central regions. Strikingly, the spiral-to-bilateral transition does not involve extensive cell migration. Rather, corresponding cells in different spiral quadrants acquire highly divergent identities in line with their bilateral position.
Quandary of a social entrepreneur
Authors: Sharma Shalaghya , Singh Anjani K. 
Published: February 2018

Subject area
Social entrepreneurship

Study level/applicability
The case can be a learning resource for management students and budding entrepreneurs with aspirations for a career in the field of social entrepreneurship.

Case overview
This case examines the organizational change and dilemmas social entrepreneurs have to face when enterprises grow. The organization under study “Action for Children Today” (ACT) aimed to help under privileged children. The organization was the brain child of young, energetic, media professional Ananthi Subramanian. Ananthi had never dreamt of being a social entrepreneur, but her mission of inclusion for underprivileged orphans in mainstream society by educating and inculcating skills, took her towards a new life and career. The endeavour began as a shelter for homeless children, but Ananthi came across other issues faced by the children, so new ventures were added under the umbrella of ACT. Although it was never an easy journey, Ananthi’s commitment kept her motivated to work for the cause and the organization that started with just one child has been home to more than 300 children up to the present day. ACT had its share of ups and downs through its journey and the case is based on certain issues and challenges that the organization had to face and how it overcame those hurdles.

Expected learning outcomes
Expected learning outcomes are as follows: a better understanding of different forms of social entrepreneurship; an understanding of problems and challenges faced by social entrepreneurs; and an understanding of how to implement new business models.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS: 3 Entrepreneurship
Risk interaction identification in international supply chain logistics
Authors: Kwak Dong-Wook , Rodrigues Vasco Sanchez , Mason Robert , Pettit Stephen , Beresford Anthony 
Published: February 2018

PurposeInternational supply chains can be severely disrupted by failures in international logistics processes. Therefore, an understanding of international logistics risks, or causes of failure, how these may interact with each other and how they can be mitigated are imperatives for the smooth operation of international supply chains. The purpose of this paper is to specifically investigate the interactions between international logistics risks within the prevailing structures of international supply chains and highlights how these risks may be inter-connected and amplified. A new dynamic supply chain logistics risk analysis model is proposed which is novel as it provides a holistic understanding of the risk event interactivity.Design/methodology/approachThe paper applies interpretive structural modelling to data collected from a survey of leading supply chain practitioners, in order to analyse their perspectives of risk elements and interactions. The risk elements and their contextual relationship were derived empirically through the use of focus groups and subsequent Delphi study. The two stages of the research rely on experts’ views on risk events and clusters and the level of interactions among those clusters.FindingsA key finding of this research is that supply chain practitioner’s perception of risk consists of inter-connected four levels: value streams risks; information and relationship risks; risks in international supply chain activities; and external environment. In particular, since level 2 risk creates feedback loops of risks, risk management at level 2 can dampen the amplification effect and the strength of the interactions.Practical implicationsSeveral managerial implications are drawn. First, the research guides managers in the identification and evaluation of risk events which can impact the performance of their international logistics supply chain operations. Second, evidence is presented that supports the proposition that the relationships with trading partners and LSPs, and the degree of logistics information exchange, are critical to prevent, or at least mitigate, logistics risks which can substantially affect the responsiveness of the international supply chain.Originality/valueThe main contribution to knowledge that this study offers to the literature on supply chain risk management is the development of a supply chain logistics risk analysis model which includes both risk elements and interactions. The research demonstrates the importance of taking into account risk interactions in the process of identification and evaluation of risk events.
Perceptions of growth-impeding constraints acting upon SMEs’ operations and the identification and use of transitionary paths to elevate them
Authors: Clegg Ben 
Published: February 2018

PurposeThe purpose of this paper is to know which growth-impeding constraints are perceived to act upon operations of small- to medium-sized (SME) companies by their owner-managers and to recommend transitionary paths to elevate constraints and increase contribution levels made by SMEs’ operations. To do so, this research has been primarily founded upon Hayeset al.’s (2005) operations contribution model for differentiating between different levels of operations’ contribution, and secondarily on the theory of constraints philosophy to explain the perceptions of constraints found at each level – current and future.Design/methodology/approachAn open-ended survey and a series of group workshops have gathered new empirical data about these perceptions, which were coded using the relational content analysis to identify a parsimonious set of perceptual growth-impeding constraint categories. The most popular transitions were identified and a correlation of frequency rank orders between “perceived current” and “perceived future” constraints categories was calculated, and likely transitionary paths for growth are discussed. Three SME case studies were documented in related action research to contextualise survey findings.FindingsThe most popular transition was from “neutral” to “leading”. A lack of people capability was perceived to be the most commonly reported growth-impeding constraint category, followed by a combined lack of process competence and product and service innovation, further followed by a lack of skills in information technology automation. In addition, a new conceptual model has been generated inductively to address shortcomings found in the original operations contribution model (Hayeset al., 2005) during its application to UK SMEs. The new model is referred to in this paper as the “Operations Growth Rocket”.Research limitations/implicationsThis research only used data from UK SMEs.Practical implicationsThis work should help SME owner-managers to overcome growth-impeding constraints that act upon their operations and assist them to develop more effective actions and paths to increase the contribution levels made by their operations. This in turn should support growth of their organisations. Findings will also inform teaching about more effective operations management in SMEs.Social implicationsThis work should help UK SMEs to grow, which in turn will strengthen the UK economy.Originality/valueA novel approach and new data from 208 SMEs modify a classical operations contribution model (Hayeset al., 2005). This is achieved by considering transitionary paths to be meta-categories continua abstracted from constraint categories combined with case data for moving towards higher levels of operations contribution, rather than using discrete growth-impeding and growth-constraining “levels”. This research has inductively generated a new version of the classical contribution model that should be more suitable for stimulating growth in (UK) SMEs.