bluuebunny/crossref_metadata_2025 huggingface dataset:
A stochastic epigenetic switch controls the dynamics of T-cell lineage commitment
Authors: Ng Kenneth K.H. , Yui Mary A. , Mehta Arnav , Siu Sharmayne , Irwin Blythe , Pease Shirley , Hirose Satoshi , Elowitz Michael B. , Rothenberg Ellen V. , Kueh Hao Yuan
Published: May 2018

Cell fate decisions occur through the switch-like, irreversible activation of fate-specifying genes. These activation events are often assumed to be tightly-coupled to changes in upstream transcription factors, but could also be constrained by cis-epigenetic mechanisms at individual gene loci. Here, we studied the activation of Bcl11b, which controls T-cell fate commitment. To disentangle cis and trans effects, we generated mice where two Bcl11b copies are tagged with distinguishable fluorescent proteins. Quantitative live microscopy of progenitors from these mice revealed that Bcl11b turned on after a stochastic delay averaging multiple days, which varied not only between cells but also between Bcl11b alleles within the same cell. Genetic perturbations, together with mathematical modeling, showed that a distal enhancer controls the rate of epigenetic activation, while a parallel Notch-dependent trans-acting step stimulates expression from activated loci. These results show that developmental fate transitions can be controlled by stochastic cis-acting events on individual loci.
Co-transcriptional loading of RNA export factors shapes the human transcriptome
Authors: Viphakone Nicolas , Sudbery Ian M , Heath Catherine G. , Sims David , Wilson Stuart A.
Published: May 2018

During gene expression, RNA export factors are mainly known for driving nucleocytoplasmic transport. Whilst early studies suggested that the Exon Junction Complex provides a binding platform for them, subsequent work proposed that they are only recruited by the Cap-Binding Complex to the 5’ end of RNAs, as part of TREX. Using iCLIP, we show that the export receptor Nxf1 and two TREX subunits, Alyref and Chtop, are actually recruited to the whole mRNA co-transcriptionally via splicing but before 3’-end processing. Consequently, Alyref alters splicing decisions and Chtop regulates alternative polyadenylation. Alyref is recruited to the 5’-end of RNAs by CBC and our data reveal subsequent binding to RNAs near EJCs. We demonstrate eIF4A3 stimulates Alyref deposition not only on spliced RNAs close to EJC sites, but also single exon transcripts. Our study reveals mechanistic insights into the co-transcriptional recruitment of mRNA export factors and how this shapes the human transcriptome.
How does the presence of neural probes affect extracellular potentials?
Authors: Buccino Alessio Paolo , Kuchta Miroslav , Jæger Karoline Horgmo , Ness Torbjørn Vefferstad , Berthet Pierre , Mardal Kent-Andre , Cauwenberghs Gert , Tveito Aslak
Published: May 2018

Objective

Mechanistic modeling of neurons is an essential component of computational neuroscience that enables scientists to simulate, explain, and explore neural activity. The conventional approach to simulation of extracellular neural recordings first computes transmembrane currents using the cable equation and then sums their contribution to model the extracellular potential. This two-step approach relies on the assumption that the extracellular space is an infinite and homogeneous conductive medium, while measurements are performed using neural probes. The main purpose of this paper is to assess to what extent the presence of the neural probes of varying shape and size impacts the extracellular field and how to correct for them.

Approach

We apply a detailed modeling framework allowing explicit representation of the neuron and the probe to study the effect of the probes and thereby estimate the effect of ignoring it. We use meshes with simplified neurons and different types of probe and compare the extracellular action potentials with and without the probe in the extracellular space. We then compare various solutions to account for the probes’ presence and introduce an efficient probe correction method to include theprobe effectin modeling of extracellular potentials.

Main results

Our computations show that microwires hardly influence the extracellular electric field and their effect can therefore be ignored. In contrast, Multi-Electrode Arrays (MEAs) significantly affect the extracellular field by magnifying the recorded potential. While MEAs behave similarly to infinite insulated planes, we find that their effect strongly depends on the neuron-probe alignment and probe orientation.

Significance

Ignoring theprobe effectmight be deleterious in some applications, such as neural localization and parameterization of neural models from extracellular recordings. Moreover, the presence of the probe can improve the interpretation of extracellular recordings, by providing a more accurate estimation of the extracellular potential generated by neuronal models.
Viewing one’s body during encoding boosts episodic memory
Authors: Bréchet Lucie , Mange Robin , Herbelin Bruno , Gauthier Baptiste , Serino Andrea , Blanke Olaf
Published: May 2018

Episodic autobiographical memories (EAMs) are recollections of contextually rich and personally relevant past events. EAM has been linked to the sense of self, allowing one to mentally travel back in subjective time and re-experience past events. However, the sense of self has recently been linked to online multisensory processing and bodily self-consciousness (BSC). It is currently unknown whether EAM depends on BSC mechanisms. Here, we used a new immersive virtual reality (VR) system that maintained the perceptual richness of life episodes and fully controlled the experimental stimuli during encoding and retrieval, including the participant’s body. We report that the present VR setup permits to measure recognition memory for complex and embodied 3D scenes during encoding and retrieval, that recognition memory depends on delay and number of changed elements, and that viewing one’s body as part of the virtual scene (as found in BSC studies) enhances delayed retrieval. This body effect was not observed when no virtual body or a moving control object was shown. These data show that embodied views improve recognition memory for 3D life-like scenes, thereby linking the sense of self, and BSC in particular, to episodic memory and the re-experiencing of specific past events in EAM.
PARPi triggers STING-dependent immune response and enhances therapeutic efficacy of immune checkpoint blockade independent of BRCAness
Authors: Shen Jianfeng , Zhao Wei , Ju Zhenlin , Wang Lulu , Peng Yang , Labrie Marilyne , Yap Timothy , Mills Gordon B. , Peng Guang
Published: May 2018

Poly-(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have shown remarkable therapeutic efficacy against BRCA1/2 mutant cancers through a synthetic lethal interaction. PARPis are believed to exert their therapeutic effects mainly through the blockade of single-strand DNA damage repair, which leads to the accumulation of toxic DNA double strand breaks, specifically in cancer cells with DNA repair deficiency (BCRAness), including those harboring BRCA1/2 mutations. Here, we show that PARPis modulate immune reposes, which contribute to their therapeutic effects independent of BRCA1/2 mutations. The mechanism underlying this PARPi-induced reprogramming of anti-tumor microenvironment involves a promoted accumulation of cytosolic DNA fragments due to unresolved DNA lesions. This in turn activates the DNA sensing cGAS-STING pathway and stimulates production of type I interferons. Ultimately, these events promote PARPi-induced antitumor immunity independent of BRCAness, which can be further enhanced by immune checkpoint blockade. Our results may provide a mechanistic rationale for using PARPis as immunomodulatory agents to harness therapeutic efficacy of immune checkpoint blockade.
Alginate-regulating genes are identified in the clinical cystic fibrosis isolate ofPseudomonas aeruginosaPA2192
Authors: Colbert Brett , Kumari Hansi , Piñon Ana , Frey Lior , Pandey Sundar , Mathee Kalai
Published: May 2018

Cystic fibrosis (CF) is a genetic disorder that leads to a buildup of mucus in the lungs ideal for bacterial colonization. WhenPseudomonas aeruginosaenters the CF lung, it undergoes a conversion from nonmucoid to mucoid; colonization by a mucoid strain ofP. aeruginosagreatly increases mortality. The mucoid phenotype is due to the production of alginate. The regulator of alginate production is the AlgT/U sigma factor. The observed phenotypic conversion is due to a mutation in themucAgene coding for an anti-sigma factor, MucA, which sequesters AlgT/U. This mucoid phenotype is unstable when the strains are removed from the lung as they acquire second-site mutations. Thisin vitroreversion phenomenon is utilized to identify novel genes regulating alginate production. Previously, second-site mutations were mapped toalgT/U, algO,andmucP, demonstrating their role in alginate regulation. Most of these studies were performed using a non-CF isolate. It was hypothesized that second site mutations in a clinical strain would be mapped to the same genes. In this study, a clinical, hyper-mucoidP. aeruginosastrain PA2192 was used to study the reversion phenomenon. This study found that PA2192 has a novelmucAmutation which was named themmucA180allele. Twelve colonies were sub-cultured for two weeks without aeration at room temperature in order to obtain nonmucoidsuppressors ofalginateproduction(sap). Only 41sapmutants were stable for more than 48 hours — a reversion frequency of 3.9% as compared to ~90% in laboratory strains showing that PA2192 has a stable mucoid phenotype. This phenotype was restored in 28 of the 41sapmutants when complemented with plasmids harboringalgT/U. Four of thesapmutants are complemented byalgO. Sequence analyses of thealgT/Umutants have found no mutations in the coding region or promoter leading to the hypothesis that there is another, as yet unidentified mechanism of alginate regulation in this clinical strain.
The role of chromatin accessibility in cis-regulatory evolution
Authors: Peng Pei-Chen , Khoueiry Pierre , Girardot Charles , Reddington James P. , Garfield David A. , Furlong Eileen E.M. , Sinha Saurabh
Published: May 2018

Transcription factor (TF) binding is determined by sequence as well as chromatin accessibility. While the role of accessibility in shaping TF-binding landscapes is well recorded, its role in evolutionary divergence of TF binding, which in turn can alter cis-regulatory activities, is not well understood. In this work, we studied the evolution of genome-wide binding landscapes of five major transcription factors (TFs) in the core network of mesoderm specification, betweenD. melanogasterandD. virilis, and examined its relationship to accessibility and sequence-level changes. We generated chromatin accessibility data from three important stages of embryogenesis in bothD. melanogasterandD. virilis, and recorded conservation and divergence patterns. We then used multi-variable models to correlate accessibility and sequence changes to TF binding divergence. We found that accessibility changes can in some cases, e.g., for the master regulator Twist and for earlier developmental stages, more accurately predict binding change than is possible using TF binding motif changes between orthologous enhancers. Accessibility changes also explain a significant portion of the co-divergence of TF pairs. We noted that accessibility and motif changes offer complementary views of the evolution of TF binding, and developed a combined model that captures the evolutionary data much more accurately than either view alone. Finally, we trained machine learning models to predict enhancer activity from TF binding, and used these functional models to argue that motif and accessibility-based predictors of TF binding change can substitute for experimentally measured binding change, for the purpose of predicting evolutionary changes in enhancer activity.
Error-correcting dynamics in visual working memory
Authors: Panichello Matthew F. , DePasquale Brian , Pillow Jonathan W. , Buschman Timothy J.
Published: May 2018

Working memory is critical to cognition, decoupling behavior from the immediate world. Yet, it is imperfect; internal noise introduces errors into memory representations (1, 2). Such errors accumulate over time (3–5) and increase with the number of items simultaneously held in working memory (6–10). Here, we show that error-correcting attractor dynamics mitigate the impact of noise on working memory. These dynamics pull memories towards a few stable representations in mnemonic space, inducing a bias in memory representations but reducing the effect of noise. Model-based and model-free analyses show attractor dynamics account for the frequency, bias, and precision of working memory reports in both humans and monkeys. Furthermore, attractor dynamics were optimized to the context; they adapted to the statistics of the environment, such that memories drifted towards contextually-predicted values. Our results suggest attractor dynamics mediate errors in working memory by counteracting noise and integrating contextual information into memories.
Activity of Telavancin against S. aureus isolated from cystic fibrosis patients including those with decreased susceptibility to Ceftaroline
Authors: Roch Melanie , Varela Maria Celeste , Taglialegna Agustina , Rose Warren E. , Rosato Adriana E.
Published: May 2018

Methicillin-resistant Staphylococcus aureus (MRSA) acquisition in cystic fibrosis (CF) patients confers a worse clinical outcome with increased rate of declined lung function. Telavancin, an approved lipoglycopeptide used to treat infections due to S. aureus has a dual mode of action causing inhibition of the peptidoglycan synthesis and membrane depolarization. CF-associated MRSA infections remain an important problem with no foreseeable decline in prevalence rates. Although telavancin is currently in clinical use for complicated skin infections and hospital-acquired pneumonia, the activity against CF-associated S. aureus infections has not been investigated. In this work, we studied the activity of telavancin against CF S. aureus strains collected from diverse geographical CF centers in the USA. We found that telavancin-MIC90 was 0.06 μg/ml, 8-fold lower than ceftaroline or daptomycin and 25-fold lower than linezolid and vancomycin. We demonstrate that telavancin at serum-free concentrations has rapid bactericidal activity with a decrease of more than 3 log10 CFU/ml during the first 4 to 6 hours of treatment, performing better in this assay than vancomycin and ceftaroline, including S. aureus resistant to ceftaroline.

Telavancin resistance was infrequent (0.3%), although we found that it can occur in-vitro in both CF-and non-CF S. aureus strains by progressive passages with sub-inhibitory concentrations. Genetic analysis of telavancin in-vitro mutants showed gene polymorphisms in cell wall and virulence genes, and increased survival in a Galleria mellonella infection model. Thus, we conclude that telavancin represents a promising therapeutic option for CF infections with potent in-vitro activity and low resistance potential.
GABAergic malfunction underlying maternal immune activation-induced social deficits
Authors: Okamoto Kazuki , Hitora-Imamura Natsuko , Hioki Hiroyuki , Ikegaya Yuji
Published: May 2018

Social deficits are one of the major symptoms of psychiatric disorders, including autism spectrum disorders (ASDs) and schizophrenia. However, the underlying mechanism remains ill-defined. Here, we focused on the anterior cingulate cortex (ACC), a brain region that is related to social behaviors, of mice that received poly(I:C)-induced maternal immune activation. Using whole-cell patch clamp recordings, we found that layer 2/3 pyramidal cells were hyperactive in acute ACC slices prepared from poly(I:C)-treated mice compared to those from saline-treated mice. The hyperexcitation was associated with a reduction in inhibitory synapse activity. Local injection of the GABAA receptor enhancer clonazepam into the ACC of poly(I:C)-treated mice restored the social behaviors of the mice. These results suggest that the balanced excitability of ACC neurons is essential for social ability.
Harvesting information from ultra-short ancient DNA sequences
Authors: de Filippo Cesare , Meyer Matthias , Prüfer Kay
Published: May 2018

The study of ancient DNA is hampered by degradation, resulting in short DNA fragments. Advances in laboratory methods have made it possible to retrieve short DNA fragments, thereby improving access to DNA preserved in highly degraded, ancient material. However, such material contains large amounts of microbial contamination in addition to DNA fragments from the ancient organism. The resulting mixture of sequences constitute a challenge for computational analysis, since microbial sequences are hard to distinguish from the ancient sequences of interest, especially when they are short. Here, we develop a method to quantify spurious alignments based on the presence or absence of rare variants. We find that spurious alignments are enriched for mismatches and insertion/deletion differences and lack substitution patterns typical of ancient DNA. The impact of spurious alignments can be reduced by filtering on these features and by imposing a sample-specific minimum length cutoff. We apply this approach to sequences from the ~430,000 year-old Sima de los Huesos hominin remains, which contain particularly short DNA fragments, and increase the amount of usable sequence data by 17-150%. This allows us to place a third specimen from the site on the Neandertal lineage. Our method maximizes the sequence data amenable to genetic analysis from highly degraded ancient material and avoids pitfalls that are associated with the analysis of ultra-short DNA sequences.
Contrasting effects of acute and chronic stress on the transcriptome, epigenome, and immune response of Atlantic salmon
Authors: Uren Webster Tamsyn M. , Rodriguez-Barreto Deiene , Martin Samuel A.M. , Oosterhout Cock van , Orozco-terWengel Pablo , Cable Joanne , Hamilton Alastair , de Leaniz Carlos Garcia , Consuegra Sofia
Published: May 2018

Early-life stress can have long-lasting effects on immunity, but the underlying molecular mechanisms are unclear. We examined the effects of acute stress (cold-shock during embryogenesis) and chronic stress (absence of tank enrichment during larval-stage) on the gill transcriptome and methylome of Atlantic salmon four months after hatching. While only chronic stress induced pronounced transcriptional effects, both acute and chronic stress caused lasting, and contrasting, changes in the methylome. Crucially, we found that acute stress enhanced immune response to a pathogenic challenge (lipopolysaccharide), while chronic stress suppressed it. We identified stress-induced changes in promoter or gene-body methylation that were associated with altered expression for a small proportion of genes, and also evidence of wider epigenetic regulation within signalling pathways involved in immune response. Our study suggests that early-life stress can affect immuno-competence through epigenetic mechanisms, a finding that could open the way for improved stress and disease management of farmed fish.
The variations of human miRNAs and Ising like base pairing models
Authors: Banerjee Jyoti Prasad , Das Jayanta Kumar , Pal Choudhury Pabitra , Mukherjee Sayak , Hassan Sk. Sarif , Basu Pallab
Published: May 2018

miRNAs are small about 22-base pair long, RNA molecules are of extreme biological importance. Like other longer RNA molecules, messages in miRNAs are encoded by the permutations of only four nucleotide bases represented by A, U, C and G. However, just like words in any language, not all combination of these alphabets make a meaningful word. In fact, we find that the distributions of nucleotides bases in human miRNAs show significant deviation from randomness. First, a miRNA sequence containing four bases are mapped into a binary string with three kinds of classifications according to their chemical properties. Then, we propose a simple nearest neighbor model (Ising model) to understand the statistical variations in human miRNAs.
Tissue-specific BMAL1 cistromes reveal that enhancer-enhancer interactions regulate rhythmic transcription
Authors: Beytebiere Joshua R , Trott Alexandra J , Greenwell Ben , Osborne Collin A , Vitet Helene , Spence Jessica , Yoo Seung-Hee , Chen Zheng , Takahashi Joseph S , Ghaffari Noushin , Menet Jerome S
Published: May 2018

Abtsract

The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of thousands of genes. Consistent with the various biological functions under clock control, rhythmic gene expression is tissue-specific despite an identical clockwork mechanism in every cell. Here we show that BMAL1 DNA binding is largely tissue-specific, due to differences in chromatin accessibility between tissues and co-binding of tissue-specific transcription factors. Our results also indicate that BMAL1 ability to drive tissue-specific rhythmic transcription not only relies on the activity of BMAL1 cis-regulatory elements (CREs), but also on the activity of neighboring CREs. Characterization of the physical interactions between BMAL1 CREs and other CREs in the mouse liver reveals that interactions are quite stable, and that BMAL1 controls rhythmic transcription by regulating the activity of other CREs. This supports that much of BMAL1 target gene transcription depends on BMAL1 capacity to rhythmically regulate a network of enhancers.
Group size effects in social evolution
Authors: Peña Jorge , Nöldeke Georg
Published: May 2018

How the size of social groups affects the evolution of cooperative behaviors is a classic question in evolutionary biology. Here we investigate group size effects in the evolutionary dynamics of games in which individuals choose whether to cooperate or defect and payoffs do not depend directly on the size of the group. We find that increasing the group size decreases the proportion of cooperators at both stable and unstable rest points of the replicator dynamics. This implies that larger group sizes can have negative effects (by reducing the amount of cooperation at stable polymorphisms) and positive effects (by enlarging the basin of attraction of more cooperative outcomes) on the evolution of cooperation. These two effects can be simultaneously present in games whose evolutionary dynamics feature both stable and unstable rest points, such as public goods games with participation thresholds. Our theory recovers and generalizes previous results and is applicable to a broad variety of social interactions that have been studied in the literature.
Determination of novel members in theDrosophila melanogasteranteriorposterior patterning system using natural variation
Authors: Jermusyk Ashley A. , Gharavi Sarah E. , Tingare Aslesha S. , Reeves Gregory T.
Published: May 2018

The anterior-posterior axis of the developingDrosophila melanogasterembryo is patterned by a well-studied gene regulatory network called the Gap Gene Network. This network acts to buffer the developing pattern against noise, thereby minimizing errors in gene expression and preventing patterning defects.

In this paper, we sought to discover novel regulatory regions and transcription factors acting in a subset of the Gap network using a selection of wild-caught fly lines derived from the Drosophila Genetic Reference Panel (DGRP). The fly lines in the DGRP contain subtle genomic differences due to natural variation; we quantified the differences in positioning of gene expression borders of two anterior-poster patterning genes,Krüppel(Kr) and Even-skipped in 13 of the DGRP lines. The differences in the positions ofKrüppeland Even-skipped were then correlated to specific single nucleotide polymorphisms and insertions/deletions within the select fly lines. Putative enhancers containing these genomic differences were validated for their ability to produce expression using reporter constructs and analyzed for possible transcription factor binding sites. The identified transcription factors were then perturbed and the resulting Eve andKrpositioning was determined. In this way, we foundmedea, ultraspiracle, glial cells missing, andorthopediaeffectKrand Eve positioning in subtle ways, while knock-down ofpangolinproduces significant shifts inKrand subsequent Eve expression patterns. Most importantly this study points to the existence of many additional novel members that have subtle effects on this system and the degree of complexity that is present in patterning the developing embryo.
Facility ownership and mortality among older adults residing in care homes
Authors: Damián Javier , Pastor-Barriuso Roberto , García-López Fernando José , Ruigómez Ana , Martínez-Martín Pablo , de Pedro-Cuesta Jesús
Published: May 2018

Background and Objectives

Nursing or care home characteristics may have a long-term impact on the residents’ mortality risks that has not been studied previously. The study’s main objective was to assess the association between facility ownership and long-term, all-cause mortality. Research Design and Methods. We conducted a mortality follow-up study on a cohort of 611 nursing-home residents in the city Madrid, Spain, from their 1998–1999 baseline interviews up to September 2013. Residents lived in three types of facilities: public, subsidized and private, which were also sub-classified according to size (number of beds). Residents’ information was collected by interviewing the residents themselves, their caregivers and facility physicians. We used time-to-event multivariable models and inverse probability weighting to estimate standardized mortality risk differences.

Results

After a 3728 person-year follow-up (median/maximum of 4.8/15.2 years), 519 participants had died. In fully-adjusted models, the standardized mortality risk difference at 5 years of follow-up between large-sized public facilities and medium-sized private facilities was 18.9% (95% confidence interval [CI]: −33.4 to −4.5%), with a median survival (95% CI) of 3.6 (0.5 to 6.8) additional years. The fully-standardized 5-year mortality difference (95% CIs) comparing for-profit private facilities with not-for-profit public institutions was −15.1% (−31.1% to 0.9%), and the fully-standardized median survival difference (95% CIs) was 3.0 (-1.7 to 7.7) years.

Discussion and Implications

These results are highly compatible with an effect on the long-term mortality risk for residents due to factors associated with the ownership of their facilities.
Single-cell heterogeneity in the chloroplast redox state mediates acclimation to stress in a marine diatom
Authors: Mizrachi Avia , van Creveld Shiri Graff , Shapiro Orr H. , Rosenwasser Shilo , Vardi Assaf
Published: May 2018

Diatoms are photosynthetic microorganisms of great ecological and biogeochemical importance, forming vast blooms in diverse aquatic ecosystems. Current understanding of phytoplankton acclimation to stress is based on population-level analysis, masking cell-to-cell variability. Here we investigated heterogeneity within Phaeodactylum tricornutum populations in response to oxidative stress, which is induced by environmental stress conditions. We combined flow cytometry and a microfluidics system for live imaging to measure redox dynamics at the single-cell level using the roGFP sensor. Chloroplast-targeted roGFP exhibited a light-dependent, bi-stable oxidation pattern in response to H2O2, revealing distinct subpopulations of sensitive oxidized cells and resilient reduced cells. Subpopulation proportions depended on growth phase, linking the bi-stable phenotype to proliferation. Oxidation of chloroplast-targeted roGFP preceded commitment to cell death and was used as a novel cell fate predictor. We propose that light-dependent metabolic heterogeneity results in differential stress responses that regulate cell fate within diatom populations.
Insights into the cooperative nature of ATP hydrolysis in actin filaments
Authors: Katkar Harshwardhan H. , Davtyan Aram , Durumeric Aleksander E. P. , Hocky Glen M. , Schramm Anthony C. , De La Cruz Enrique M. , Voth Gregory A.
Published: May 2018

Actin filaments continually assemble and disassemble within a cell. Assembled filaments “age” as a bound nucleotide ATP within each actin subunit quickly hydrolyzes, followed by a slower release of the phosphate Pi, leaving behind a bound ADP. This subtle change in nucleotide state of actin subunits affects filament rigidity as well as its interactions with binding partners. We present here a systematic multiscale ultra-coarse-graining (UCG) approach that provides a computationally efficient way to simulate a long actin filament undergoing ATP hydrolysis and phosphate release reactions, while systematically taking into account available atomistic details. The slower conformational changes and their dependence on the chemical reactions are simulated with the UCG model by assigning internal states to the coarse-grained sites. Each state is represented by a unique potential surface of a local heterogeneous elastic network. Internal states undergo stochastic transitions that are coupled to conformations of the underlying molecular system. The UCG model reproduces mechanical properties of the filament and allows us to study whether fluctuations in actin subunits produce cooperative aging in the filament. Our model predicts that nucleotide state of neighboring subunit significantly modulates the reaction kinetics, implying cooperativity in ATP hydrolysis and Pirelease. We further systematically coarse-grain the system into a Markov state model that incorporates assembly and disassembly, facilitating a direct comparison with previously published models. We find that cooperativity in ATP hydrolysis and Pirelease significantly affects the filament growth dynamics only near the critical G-actin monomer concentration, while both cooperative and random mechanisms show similar growth dynamics far from the critical concentration. In contrast, filament composition in terms of the bound nucleotide distribution varies significantly at all monomer concentrations studied. These results provide new insights into the cooperative nature of ATP hydrolysis and Pirelease and the implications it has for actin filament properties, providing novel predictions for future experimental studies.
A double dissociation in sensitivity to verb and noun semantics across cortical networks
Authors: Elli Giulia V. , Lane Connor , Bedny Marina
Published: May 2018

What is the neural organization of the mental lexicon? Previous research suggests that partially distinct cortical networks are active during verb and noun processing. Are these networks preferentially involved in representing the meanings of verbs as opposed to nouns? We used multivoxel pattern analysis (MVPA) to investigate whether brain regions that are more active during verb than noun processing are also more sensitive to distinctions among their preferred lexical class. Participants heard four types of verbs (light emission, sound emission, hand-related actions, mouth-related actions) and four types of nouns (birds, mammals, manmade places, natural places). As previously shown, the left posterior middle temporal gyrus (LMTG) and inferior frontal gyrus (LIFG) responded more to verbs, whereas areas in the inferior parietal lobule (LIP), precuneus (LPC), and inferior temporal (LIT) cortex responded more to nouns. MVPA revealed a double-dissociation in semantic sensitivity: classification was more accurate among verbs than nouns in the LMTG, and among nouns than verbs in the LIP, LPC, and LIT. However, classification was similar for verbs and nouns in the LIFG, and above chance for the non-preferred category in all regions. These results suggest that the meanings of verbs and nouns are represented in partially non-overlapping networks.
CRISPR/Cas9-targeted removal of unwanted sequences from small-RNA sequencing libraries
Authors: Hardigan Andrew A. , Roberts Brian S. , Moore Dianna E. , Ramaker Ryne C. , Jones Angela L. , Myers Richard M.
Published: May 2018

In small RNA (smRNAs) sequencing studies, highly abundant molecules such as adapter dimer products and tissue-specific microRNAs (miRNAs) inhibit accurate quantification of lowly expressed species. We previously developed a method to selectively deplete highly abundant miRNAs. However, this method does not deplete adapter dimer ligation products that, unless removed by gelseparation, comprise most of the library. Here, we have adapted and modified recently described methods for CRISPR/Cas9–based Depletion of Abundant Species by Hybridization (“DASH”) to smRNA-seq, which we have termed miRNA and Adapter Dimer - DASH (MAD-DASH). In MAD-DASH, Cas9 is complexed with sgRNAs targeting adapter dimer ligation products, alongside highly expressed tissue-specific smRNAs, for cleavage in vitro. This process dramatically reduces (>90%) adapter dimer and targeted smRNA sequences, is multiplexable, shows minimal off-target effects, improves the quantification of lowly expressed miRNAs from human plasma and tissue derived RNA, and obviates the need for gel-separation, greatly increasing sample throughput. Additionally, the method is fully customizable to other smRNA-seq preparation methods. Like depletion of ribosomal RNA for mRNA-seq and mitochondrial DNA for ATAC-seq, our method allows for greater proportional read-depth of nontargeted sequences.
1,1-Bis(diphenylphosphoryl)hydrazine
Authors: Höhne Martha , Aluri Bhaskar R. , Spannenberg Anke , Müller Bernd H. , Peulecke Normen , Rosenthal Uwe
Published: May 2018

The title compound, C24H22N2O2P2, contains a diphosphazane backbone, as well as a hydrazine entity. The P—N—P diphosphazane unit and the N-amine N atom are almost coplanar, and the O atoms of the Ph2P(O) units are oriented trans to each other with respect to the P...P axis. In the crystal, centrosymmetrically related molecules are linked into dimers by pairs of N—H...O hydrogen bonds, forming rings of graph-set motif R
2
2(10).
Multi-storey residential buildings and occupant’s behaviour during fire evacuation in the UK
Authors: Gerges Michael , Penn Sholto , Moore David , Boothman Chris , Liyanage Champika
Published: May 2018

Purpose

The purpose of this paper is to investigate human behaviour during fire evacuations in multi-storey residential buildings through a focus on the challenges and obstacles that occupants face. In addition, the paper aims to study all the various behaviours that are relevant to the evacuation strategies/plans in the UK of multi-storey buildings in large cities.

Design/methodology/approach

A literature review was conducted to identify the factors occupants face and also the decision making of occupants regarding the methods of egress. A mixed methods research was adopted using interviews and a questionnaire survey. The findings from the interviews and survey are benchmarked against the information gathered from the literature review.

Findings

The paper identifies various challenges that occupants face when evacuating a multi-storey residential building. In terms of the decision-making process, the research results evidence that occupants could be given more information on the evacuation procedures within their specific building. The paper also finds that occupants remain reluctant to use a lift during evacuation in fire event, irrespective of any signage clearly stating that is appropriate to do so in the context of modern lift technology.

Originality/value

This paper contributes to the body of knowledge available on the evacuation of multi-storey buildings located in large cities within the UK, outlining the potential areas for future research, focussed on providing an insight of the behavioural decisions made by the occupants make when evacuating a building in the event of a fire.
Fatigue crack growth of 42CrMo4 and 41Cr4 steels under different heat treatment conditions
Authors: Lesiuk Grzegorz , Duda Monika Maria , Correia José , de Jesus Abilio M.P. , Calçada Rui
Published: May 2018

Purpose

For nowadays construction purposes, it is necessary to define the life cycle of elements with defects. As steels 42CrMo4 and 41Cr4 are typical materials used for elements working under fatigue loading conditions, it is worth to know how they will behave after different heat treatment. Additionally, typical mechanical properties of material (hardness, tensile strength, etc.) are not defining material’s fatigue resistance. Therefore, it is worth to compare, except mechanical properties, microstructure of the samples after heat treatment as well. The paper aims to discuss these issues.

Design/methodology/approach

Samples of normalized 42CrMo4 (and 41Cr4) steel were heat treated under three different conditions. All heat treatments were designed in order to change microstructural properties of the material. Fatigue tests were carried out according to ASTM E647-15 standard using compact tension specimens. Later on, based on obtained results, coefficients C and m of Paris’ Law for all specimens were estimated. Similar procedure was performed for 41Cr4 steel after quenching and tempering in different temperatures.

Findings

The influence of heat treatment on the fatigue crack growth rates (42CrMo4, 41Cr4 steel) has been confirmed. The higher fatigue crack growth rates were observed for lower tempering temperatures.

Originality/value

This study is associated with influence of microstructural properties of the material on its’ fatigue fracture. The kinetic fatigue fracture diagrams have been constructed. For each type of material (and its heat treatment), the Paris law constants were determined.
Beneficiaries of gambling and moral disengagement
Authors: Marionneau Virve , Kankainen Veera
Published: May 2018

Purpose

Gambling is used to raise public funds through taxes, fees and direct contributions. The rent generated can be distributed through two basic models: absorbing the surplus into state budgets and institutions, or channeling funds to civil society organizations (CSOs). However, gambling also causes negative externalities. The purpose of this paper is to focus on how the beneficiaries of gambling in two societies representing these opposite models respond to the moral issue of accepting funds from a source that causes harm to some.

Design/methodology/approach

The analysis is conducted by applying the moral disengagement (MD) model to qualitative interviews conducted with beneficiaries of gambling in Finland and France. In Finland, the majority of gambling revenue is redistributed to CSOs, who also exercise a strong influence and are heavily involved in the system. In France, most gambling proceeds are directed to the central state, making other beneficiaries less powerful.

Findings

The results of this paper show that in France, where the state is a strong beneficiary, other actors express more political awareness and debate than in the Finnish model in which CSOs benefit and are tightly implicated in the system. On the other hand, the involvement of Finnish actors in the system encouraged them to accept moral responsibility for the harm caused by gambling.

Originality/value

The paper provides policymakers information on beneficiaries’ implication and position in different types of models of dividing the rent of gambling, and the academic audience with a comparative and sociological application of the MD model.
Formalizing women entrepreneurs in Kathmandu, Nepal
Authors: Thapa Karki Shova , Xheneti Mirela
Published: May 2018

Purpose

Women’s economic empowerment through entrepreneurship is increasingly being recognised as significant to achieving the Sustainable Development Goals (SDGs). However, women entrepreneurship in developing countries is characterised by an overrepresentation in the informal economy and exposure to high levels of gender disparities. The purpose of this paper is to explore whether formalisation of women’s entrepreneurial activities in the informal economy supports SDGs through ensuring empowerment and equality.

Design/methodology/approach

The research adopts a qualitative research design to explore the empowerment outcomes of the formalisation of women’s entrepreneurial activities in the informal economy of Kathmandu, Nepal. Data were collected through interviews with 30 women entrepreneurs engaged in a mix of formal and informal entrepreneurial activities.

Findings

By using Mayoux’s (1998) framework of empowerment at the individual, household and community level, the findings show the variation in empowerment outcomes as a result of women’s diverse motivations for engaging in entrepreneurship. Whilst informal entrepreneurial activities improve women’s confidence and life aspirations, they have limited potential in lifting women out of poverty and enable them to significantly challenge gender relations in the society. Formalization does further empower women at the household and community level but this is primarily the case of younger and more educated women.

Originality/value

The research contributes to the debates on entrepreneurship as “emancipation” and more specifically, on whether formalization contributes to the SDGs by furthering gender equality and empowerment. Formalization policies need to acknowledge the heterogeneity of women entrepreneurs.
Using social media for competitive business outcomes
Authors: Cao Yingxia , Ajjan Haya , Hong Paul , Le Thuong
Published: May 2018

Purpose

The purpose of this paper is to examine the drivers, practices, and outcomes of social media use in the management of organizational supply chain.

Design/methodology/approach

Online questionnaire survey was used to collect data from 285 organizations representing different industries in China. The data then were analyzed with structure equation modeling using SmartPLS.

Findings

The results indicate that key antecedents such as external pressures, internal readiness, expected benefits, strategic goals, and perceived risks influence organizational social media use, which subsequently impact organizational performance outcomes in operation and marketing as well as the satisfaction level of both internal and external constituents, such as customers, employees, partners, and suppliers.

Research limitations/implications

The study obtained data about one organization from only one respondent and did not used random sampling.

Practical implications

This study provides insights on why and how companies should use social media for relationship building and business outcomes.

Originality/value

Drawing from the resources-based view, social networks, strategic choice theory, and technology organization and environment framework, a new social media utilization model for business outcome was established and testified using empirical data. This study is one of the first studies that adopts technology-organization-environment (TOE) framework of technology adoption theory to study organizational social media use. The findings in this study confirm the validity of the TOE framework for analyzing social media adoption and use in various organizations.
Organizational health management through metaphor: a mission-based approach
Authors: Woodside Joseph M.
Published: May 2018

Purpose

The purpose of this paper is to identify the underlying metaphors that hospitals use to establish their organizational mission. Metaphors impact the direction and managerial decision making of organizations, and provide a method to more easily communicate to a variety of stakeholders.

Design/methodology/approach

A text analytics process is run to evaluate the mission statements from the largest hospitals by revenue in each of the 50 states of the USA and District of Columbia to identify the types of metaphor-based organizational health management methods.

Findings

A cluster analysis is generated to evaluate primary mission-based metaphors, and metatriangulation is used to evaluate output, develop theory and provide practical implications for healthcare management.

Originality/value

Key contributions include a review of healthcare metaphors, an analysis for understanding commonly utilized metaphors, a theory building process for developing a new integrated value-based care management metaphor, and a value-based process is developed for providing healthcare managers an easy to follow and repeatable process for improving organizational communication.
Coming “home” to do glocal engaged scholarship? A reflexive account of managing competing commitments during an organizational ethnography
Authors: McAllum Kirstie
Published: May 2018

Purpose

The purpose of this paper is to focus on how the author’s status as an international academic wanting to maintain “local” research relationships in the author’s country of origin both improved and derailed the process of conducting an organizational ethnography.

Design/methodology/approach

Using visual representations of the research design process inspired by Maxwell’s (2013) model, the paper traces the evolution of a glocal engaged scholarship project and the personal, professional, and commitments that pulled the researcher and the research project in competing directions.

Findings

The first iteration of the project showed that, despite geographical nomadism, the author was firmly anchored to professional norms and methodological choices, with these attachments to values, principles, and practices constituting a global academic “home.” As the project unfolded, local organizational needs and desires that called into question the researcher’s local organizational knowledge and methodological choices destabilized the author’s sense of home, creating a situation of “away-ness” that acted as a catalyst for reflexivity about the project and relationships with organizational partners.

Originality/value

By overturning a view of home as being rooted in a particular locale and homelessness as being nomadic, this confessional tale problematizes the idea that some organizational ethnographers and projects are local while others are foreign.
“At-home ethnography”
Authors: Suarez Delucchi Adriana Angela
Published: May 2018

Purpose

The purpose of this paper is to problematise the idea of “at-home ethnography” and to expand knowledge about insider/outsider distinctions by using insights from institutional ethnography (IE). It also examines the strengths and challenges of “returning” researchers recognising their unique position in overcoming these binaries.

Design/methodology/approach

IE is the method the researcher used to explore community-based water management in rural Chile. The researcher is interested in learning from rural drinking water organisations to understand the way in which their knowledge is organised. The data presented derived from field notes of participant observation and the researcher’s diary.

Findings

The notion of “at-home ethnography” fell short when reflecting on the researcher’s positions and experiences in the field. This is especially true when researchers return to their countries to carry out fieldwork. The negotiation of boundaries, codes and feelings requires the researcher to appreciate the complex relationships surrounding ethnographic work, in order to explore how community-based water management is done in the local setting, without forgetting where the setting is embedded.

Originality/value

Unique insights are offered into the advantages and tensions of conducting fieldwork “at home” when the researcher has lived “abroad” for an extended time. A critique and contribution to “at-home ethnography” is offered from an IE perspective.