bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishment of a novel method for the production of chimeric mouse embryos using oil droplets
Authors: Imai Hiroyuki , Tsuda Soichiro , Iwamori Tokuko , Ono Etsuro
Published: December 2019

The production of chimeric animals is frequently necessary for the constructing genetically modified animals, and has gained popularity in regenerative medicine in the recent years for the reconstruction of xenogeneic organs. The aggregation method and the injection method are generally used for producing chimeric mice. In the aggregation method, the chimeras are produced by co-culturing embryos and stem cells, and keeping them physically adhered. In the injection method, the chimeras are produced by injecting stem cells into the zona pellucida using microcapillaries. These methods only focus on the generation of chimeric animals, and are not expected to produce reproducible results or allow quantitative evaluation.

This study aimed to establish a novel method for producing chimeric embryos via droplets for improving on the conventional methods that are used for producing chimeric embryos. In this study, the embryonic stem cells and embryos were successfully isolated in the droplets, and the emergence of chimeric embryos was confirmed by co-culture for 6 hours. By this method, the control and operability of stem cell numbers can be regulated, and the method allows better reproducibility and quantification during the production of chimeric embryos. In addition to the conventional methods for producing chimeric embryo, the novel method described herein could be employed for the efficient production of chimeric animals.
Influence of Strontium on the Physical, Mechanical and In-Vitro Bioactivity of Glass Ionomer Cements
Authors: Li Yiyu
Published: December 2019

In this work, we investigated the effects of strontium incorporation in the glass phase of glass ionomer cements (GIC). Three different glass compositions were synthesized with 0, 5, and 10 mol% of SrO addition. GICs were prepared by the addition of 50 wt% polyacrylic acid (PAA) at powder to liquid ratio of 1:1.5. Initial characterization on the cement series was to study their rheological behavior. Cements represented working times between 50-64 seconds and setting times of 356-452 seconds. Rheological results indicated that the addition of strontium decreases the working and setting times of the cements. To analyze the mechanical properties, compressive and flexural strength studies were performed after 1, 10, and 30 days incubation in simulated body fluid. The compressive strength of the cements increased as a function of incubation time, with the strontium containing compositions showing the highest strength at 34 MPa and after 30 days of incubation. Biaxial flexural strength of the cements was not significantly affected by the composition and maturation time and ranged between 13.4 to 16.3 MPa. In-vitro bioactivity of the cements was analyzed using SBF trials and after 1, 10, and 30 days incubation periods. Strontium containing cements, showed higher solubility with higher amounts of calcium phosphate surface depositions only after 10 days incubation. The elemental identifications of the surface depositions indicated high amounts of Ca, P and Zn are present on the surface of SBF incubated samples.
Allosteric feed-forward activation of AP-2viaFCHO-BMP2K axis promotes clathrin-mediated endocytosis
Authors: Ramesh Shikha T. , Navyasree Kolaparamba V. , Ashok Anjitha B. , Qathoon Nishada , Mohanty Suryasikha , Swain Rajeeb K. , Umasankar Perunthottathu K.
Published: December 2019

Spatio-temporal regulation of central adaptor complex, AP-2 is pivotal for clathrin-mediated endocytosis (CME). We recently discovered that FCHO proteins trigger clathrin-coated pit (CCP) formation by allosterically activating AP-2 on plasma membrane (Umasankaret al., 2014). Here, we demonstrate that this activation promotes AP-2 phosphorylationviarecruitment and stabilization of BMP-2 inducible kinase (BMP2K), abona fideAP-2 kinase leading to CCP maturation. Accordingly, BMP2K mislocalizes and degrades in FCHO knockout/ AP-2 depleted cells. Functional inactivation of kinase impairs AP-2 phosphorylation leading to altered lattice morphology and CME phenotypes reminiscent of CCP maturation defects. Reexpression of FCHO rescues AP-2 phosphorylation defects in FCHO knockout cells implying membrane activation of AP-2 is a prerequisite for kinase function. Furthermore, gain- and loss-of function phenotypes of FCHO and BMP2K are analogous and mirror altered AP-2 functions during zebrafish embryogenesis. Together, our findings reveal anin vivoallosteric feed-forward axis for operation of CME.
iASPP contributes to cortex rigidity, astral microtubule capture and mitotic spindle positioning
Authors: Mangon Aurélie , Salaün Danièle , Lala Bouali Mohamed , Quitard Sabine , Isnardon Daniel , Audebert Stéphane , Puech Pierre-Henri , Verdier-Pinard Pascal , Badache Ali
Published: December 2019

The microtubule plus-end binding protein EB1 is the core of a complex protein network which regulates microtubule dynamics during important biological processes such as cell motility and mitosis. We found that iASPP, an inhibitor of p53 and predicted regulatory subunit of the PP1 phosphatase, associates with EB1 at microtubule plus-ends via a SxIP motif. iASPP silencing or mutation of the SxIP motif led to defective microtubule capture at the leading edge of migrating cells, and at the cortex of mitotic cells leading to abnormal positioning of the mitotic spindle. These effects were recapitulated by the knockdown of Myosin-Ic (Myo1c), identified as a novel partner of iASPP. Moreover, iASPP or Myo1c knockdown cells failed to round up during mitosis because of defective cortical rigidity. We propose that iASPP, together with EB1 and Myo1c, contributes to mitotic cell cortex rigidity, allowing astral microtubule capture and appropriate positioning of the mitotic spindle.
AUTS2 regulation of synapses for proper synaptic inputs and social communication
Authors: Hori Kei , Yamashiro Kunihiko , Nagai Taku , Shan Wei , Egusa Saki F. , Shimaoka Kazumi , Go Yasuhiro , Tatsumoto Shoji , Yamada Mitsuyo , Shiraishi Reika , Kanno Kouta , Miyashita Satoshi , Sakamoto Asami , Abe Manabu , Sakimura Kenji , Sone Masaki , Sohya Kazuhiro , Kunugi Hiroshi , Yamada Kiyofumi , Hoshino Mikio
Published: December 2019

Impairments in synapse development are thought to cause numerous psychiatric disorders.Autism susceptibility candidate 2(AUTS2) gene has been associated with various psychiatric disorders, such as autism and intellectual disabilities. Although roles for AUTS2 in neuronal migration and neuritogenesis have been reported, its involvement in synapse regulation remains unclear. In this study, we found that excitatory synapses were specifically increased in theAuts2-deficient primary cultured neurons as well asAuts2mutant forebrains. Electrophysiological recordings and immunostaining showed increases in excitatory synaptic inputs as well as c-fos expression inAuts2mutant brains, suggesting that an altered balance of excitatory and inhibitory inputs enhances brain excitability.Auts2mutant mice exhibited autistic-like behaviors including impairments in social interaction and altered vocal communication. Together, these findings suggest that AUTS2 regulates excitatory synapse number to coordinate E/I balance in the brain, whose impairment may underlie the pathology of psychiatric disorders in individuals withAUTS2mutations.
Characterization of eyes, photoreceptors and opsins in developmental stages of the chaetognath Spadella cephaloptera
Authors: Wollesen Tim , Rodríguez Monje Sonia Victoria , Oel Adam Phillip , Arendt Detlev
Published: December 2019

The phylogenetic position of chaetognaths has been debated for decades, however recently they have been grouped into the Gnathifera, sister taxon to the Lophotrochozoa. Chaetognaths possess photoreceptor cells that are anatomically unique and arranged remarkably different in the eyes of the various species. Studies investigating eye development and underlying gene regulatory networks are so far missing.

In order to gain insights into the development and the molecular toolkit of chaetognath photoreceptors and eyes a new transcriptome of the epibenthic species Spadella cephaloptera was searched for opsins. Our screen revealed single-copies of xenopsin and peropsin and gene expression analyses demonstrated that only xenopsin is expressed in photoreceptor cells of the developing lateral eyes. Adults likewise exhibit two xenopsin+ photoreceptor cells in each of their lateral eyes. Beyond that, a single cryptochrome gene was uncovered and found co-expressed with xenopsin in some photoreceptor cells of the lateral developing eye. In addition, it is co-expressed with peropsin in the cerebral ganglia, a condition reminiscent of a non-visual photoreceptive zone in the apical nervous system of the annelid Platynereis dumerilii that performs circadian entrainment and melatonin release. Cryptochrome expression was also detected in cells of the corona ciliata, a circular organ in the posterior dorsal head region that has been attributed several functions arguing for an involvement of this organ in circadian entrainment. Our study demonstrates the importance to investigate representatives of the Gnathifera, a clade that has been neglected with respect to developmental studies and that might contribute to unravel the evolution of spiralian and bilaterian body plans.
On the use of calcium deconvolution algorithms in practical contexts
Authors: Evans Mathew H. , Petersen Rasmus S. , Humphries Mark D.
Published: December 2019

Calcium imaging is a powerful tool for capturing the simultaneous activity of large populations of neurons. Here we determine the extent to which our inferences of neural population activity, correlations, and coding depend on our choice of whether and how we deconvolve the calcium time-series into spike-driven events. To this end, we use a range of deconvolution algorithms to create nine versions of the same calcium imaging data obtained from barrel cortex during a pole-detection task. Seeking suitable values for the deconvolution algorithms’ parameters, we optimise them against ground-truth data, and find those parameters both vary by up to two orders of magnitude between neurons and are sensitive to small changes in their values. Applied to the barrel cortex data, we show that a substantial fraction of the processing methods fail to recover simple features of population activity in barrel cortex already established by electrophysiological recordings. Raw calcium time-series contain an order of magnitude more neurons tuned to features of the pole task; yet there is also qualitative disagreement between deconvolution methods on which neurons are tuned to the task. Finally, we show that raw and processed calcium time-series qualitatively disagree on the structure of correlations within the population and the dimensionality of its joint activity. Collectively, our results show that properties of neural activity, correlations, and coding inferred from calcium imaging are sensitive to the choice of if and how spike-evoked events are recovered. We suggest that quantitative results obtained from population calcium-imaging be verified across multiple processed forms of the calcium time-series.
A Nanomule Peptide-siRNA Conjugate that Traverses the Intact Blood Brain Barrier and Attenuates Stroke
Authors: Eyford Brett A. , Singh Chaahat S.B. , Abraham Thomas , Munro Lonna , Choi Kyung Bok , Hildebrandt Rhonda , Hill Tracy , Welch Ian , Okon Mark , Vitalis Timothy Z. , Gabathuler Reinhard , Gordon Jacob A. , Adomat Hans , Guns Emma S.T. , Lu Chieh-Ju , Pfeifer Cheryl G. , Tian Mei Mei , Jefferies Wilfred A.
Published: December 2019

The blood-brain barrier (BBB), hinders the distribution of therapeutics, intended for treatment of diseases of the brain. A twelve-amino acid peptide, termed MTfp, was derived from MTf, and retains the ability to cross the BBB intact and ferry cargo into intacellular organelles within neurons, glia and microglia in the brain. A novel MTfp-siRNA peptide-oligonucleotide conjugate (POC), directed against NOX4, a gene known to potentiate ischemic stroke, was chemically synthesized. The MTfp-NOX4 siRNA POC traversed the BBB, resulting in the knockdown of NOX4 expression in the brain. Following induction of ischemic stroke, animals treated with the POC exhibited significantly smaller infarcts; accompanied by significant protection against neurological deterioration and improved recovery. The data demonstrates that the MTfp portion, of this novel POC, can facilitate BBB transcytosis; where the siRNA moiety can elicit effective therapeutic knockdown of a gene associated with a disease of the central nervous system (CNS). This is a general platform to transport therapeutics to the CNS and thereby, offers new avenues for potential treatments of neuropathologies that are currently refractory to existing therapies.
Insights into the ligand-free structure of cyclic diguanosine monophosphate I riboswitch of Vibrio cholerae using molecular dynamics simulation
Authors: Kumari Priyanka , Som Anup
Published: December 2019

Riboswitches are key cis regulatory elements present at 5’ UTRs of mRNAs. They play a critical role in gene expression regulation at transcriptional and translational level by binding selectively to specific ligands followed by conformational changes. Ligands bind to the aptamer of riboswitches and their complex structures have been solved, but ligand-free riboswitches structures are not available which is important to understand specific ligand binding mechanism. In this paper, an all atom 150 nano-second (ns) molecular dynamics (MD) simulations of cyclic diguanosine monophosphate (c-di-GMP I) riboswitch aptamer domain from Vibrio cholerae were carried out to study ligand-free c-di-GMP I riboswitch aptamer structure and the binding mechanism. The Principle component analysis, cross correlation dynamics analysis and trajectory analyses revealed that the ligand-free structure has stable conformation with folded P2, P3 and an open P1 helix which opens the ligand binding helix-join-helix while the ligand-bound structure shows less deviation and remains as closed structure compared to the ligand-free structure. The junction residues significantly showed anti-correlated motions with each other elucidating the open conformation of the ligand-free aptamer of riboswitch. The identified key residues involved in binding are A18, G20, C46, A47 and C92.

Highlights

The c-di-GMP I riboswitch regulates the essential genes involved in the virulence of human bacterial pathogen V. Cholera.

A 150 ns molecular dynamics run was performed to find a ligand-free stable structure of c-di-GMP I riboswitch aptamer.

The trajectory analysis resulted in stable conformation of ligand-free structure with folded P2, slightly open P3 and an unwind P1 helix.

The atomic level analyses through cross correlation dynamics and RMSF values showed the opening of catalytic pocket and unwinding P1 helix.

The identified key residues involved in binding are A18, G20, C46, A47 and C92 at the catalytic pocket.
Voluntary wheel running has no impact on brain and liver mitochondrial DNA copy number or mutation measures in the PolG mouse model of aging
Authors: Maclaine Kendra D. , Stebbings Kevin A. , Llano Daniel A. , Rhodes Justin S.
Published: December 2019

The mitochondrial theory of aging attributes much of the aging process to mitochondrial DNA damage. The PolGAD257A/D257A(PolG) mutant mouse was created to explore the mitochondrial theory of aging and carries a mutated proofreading region of polymerase gamma, which exclusively transcribes the mitochondrial genome. As a result, PolG mice accumulate mitochondrial DNA (mtDNA) mutations which leads to premature aging including hair loss, weight loss, kyphosis, increased rates of apoptosis, organ damage, and eventually, an early death at around 12 months. Exercise has been reported to decrease skeletal muscle mtDNA mutations and normalize protein levels in PolG mice. However, brain mtDNA changes with exercise in PolG mice have not been explored. We found no effects of exercise on mtDNA mutations or copy number in brain or liver in PolG mice, despite effects on body mass. Our results suggest that mitochondrial mutations play little role in exercise-brain interactions in the PolG model of accelerated aging. In addition to evaluating the effect of exercise on mtDNA outcomes, we also implemented novel methods for mtDNA extraction and measuring mtDNA mutations to improve efficiency and accuracy.
In Situ Processing and Efficient Environmental Detection iSPEED of pests and pathogens of trees using point-of-use real-time pcr
Authors: Capron Arnaud , Stewart Don , Hrywkiw Kelly , Allen Kiah , Feau Nicolas , Bilodeau Guillaume , Tanguay Philippe , Cusson Michel , Hamelin Richard C.
Published: December 2019

The increase in global trade is responsible for a surge in foreign invasive species introductions across the world. Early detection and surveillance activities are essential to prevent future invasions. Molecular diagnostics by DNA testing has become an integral part of this process. However, for environmental applications, there is a need for cost-effective and efficient point-of-use DNA testing that would allow for the collection of results in real-time away from laboratory facilities. To achieve this requires the development of simple and fast sample processing and DNA extraction, room-temperature stable reagents and a portable instrument. We conducted a series of tests using a crude buffer-based DNA extraction protocol and lyophilized, pre-made, reactions to address the first two requirements. We chose to demonstrate the use of this approach with organisms that cover a broad spectrum of known undesirable insects and pathogens: the ascomycete Sphaerulina musiva, the oomycete Phytophthora ramorum, the basidiomycetes Cronartium ribicola and Cronartium comandrae and the insect Lymantria dispar. Tests performed from either infected leaf material or spores (pathogens), or legs and antenna (insects). We were able to obtain positive amplification for the targeted species in all the samples tested. The shelf-life of the lyophilized reactions was assessed, confirming the stability of over a year at room temperature. Finally, successful tests conducted with portable thermocyclers and disposable plastics, demonstrating the suitability of the method, named in Situ Processing and Efficient Environment Detection (iSPEED), for field testing. This kit is ideally adapted to field testing as it fits in a backpack and can be carried to remote locations.
Regulation of heterotopic ossification through local inflammatory monocytes in a mouse model of aberrant wound healing
Authors: Sorkin Michael , Huber Amanda K. , Hwang Charles , Carson William F. , Menon Rajasree , Li John , Vasquez Kaetlin , Pagani Chase , Patel Nicole , Li Shuli , Visser Noelle D , Niknafs Yashar , Loder Shawn , Scola Melissa , Nycz Dylan , Gallagher Katherine , McCauley Laurie K. , Xu Jiajia , James Aaron W. , Agarwal Shailesh , Kunkel Stephen , Mishina Yuji , Levi Benjamin
Published: December 2019

Heterotopic ossification (HO) is an aberrant regenerative process with ectopic bone induction in response to musculoskeletal trauma, in which mesenchymal stem cells (MSC) differentiate into osteochondrogenic cells instead of myocytes or tenocytes. Despite frequent cases of hospitalized musculoskeletal trauma, the inflammatory responses and cell population dynamics that regulate subsequent wound healing and tissue regeneration are still unclear. Here we examine, using a mouse model of trauma-induced HO, the local microenvironment of the initial post-injury inflammatory response. Single cell transcriptome analyses identify distinct monocyte/macrophage populations at the injury site, with their dynamic changes over time elucidated using trajectory analyses. Mechanistically, transforming growth factor beta-1 (TGFβ1)-producing monocytes/macrophages are associated with HO and aberrant chondrogenic progenitor cell differentiation, while CD47-activating peptides that reduce systemic TGFβ levels help ameliorate HO. Our data thus implicate CD47 activation as a novel therapeutic approach for modulating monocyte/macrophage phenotypes, MSC differentiation and HO formation during wound healing.
The Euler Characteristic and Topological Phase Transitions in Complex Systems
Authors: de Amorim Filho Edgar C. , Moreira Rodrigo A. , Santos Fernando A N
Published: December 2019

In this work, we use methods and concepts of applied algebraic topology to comprehensively explore the recent idea of topological phase transitions (TPT) in complex systems. TPTs are characterized by the emergence of nontrivial homology groups as a function of a threshold parameter. Under certain conditions, one can identify TPT’s via the zeros of the Euler characteristic or by singularities of the Euler entropy. Recent works provide strong evidence that TPTs can be interpreted as a complex network’s intrinsic fingerprint. This work illustrates this possibility by investigating some classic network and empirical protein interaction networks under a topological perspective. We first investigate TPT in protein-protein interaction networks (PPIN) using methods of topological data analysis for two variants of the Duplication-Divergence model, namely, the totally asymmetric model and the heterodimerization model. We compare our theoretical and computational results to experimental data freely available for gene co-expression networks (GCN) of Saccharomyces cerevisiae, also known as baker’s yeast, as well as of the nematode Caenorhabditis elegans. Supporting our theoretical expectations, we can detect topological phase transitions in both networks obtained according to different similarity measures. Later, we perform numerical simulations of TPTs in four classical network models: the Erdős-Renyi model, the Watts-Strogatz model, the Random Geometric model, and the Barabasi-Albert. Finally, we discuss some perspectives and insights on the topic. Given the universality and wide use of those models across disciplines, our work indicates that TPT permeates a wide range of theoretical and empirical networks.
HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation
Authors: Bridoux Laure , Zarrineh Peyman , Mallen Joshua , Phuycharoen Mike , Latorre Victor , Ladam Frank , Losa Marta , Sagerstrom Charles , Mace Kimberley A. , Rattray Magnus , Bobola Nicoletta
Published: December 2019

Gene expression programs determine cell fate in embryonic development and their dysregulation results in disease. Transcription factors (TFs) control gene expression by binding to enhancers, but how TFs select and activate their target enhancers is still unclear. HOX TFs share conserved homeodomains with highly similar sequence recognition properties, yet they impart the identity of different animal body parts. To understand how HOX TFs control their specific transcriptional programsin vivo, we compared HOXA2 and HOXA3 binding profiles in the mouse embryo. HOXA2 and HOXA3 directly cooperate with TALE TFs and selectively target different subsets of a broad TALE chromatin platform. Binding of HOX and tissue-specific TFs convert low affinity TALE binding into high confidence, tissue-specific binding events, which bear the mark of active enhancers. We propose that HOX paralogs, alone and in combination with tissue-specific TFs, generate tissue-specific transcriptional outputs by modulating the activity of TALE TFs at selected enhancers.
ExploringCryptococcus neoformanscapsule structure and assembly with a hydroxylamine-armed fluorescent probe
Authors: Crawford Conor J. , Cordero Radamés J.B. , Guazzelli Lorenzo , Wear Maggie P. , Bowen Anthony , Oscarson Stefan , Casadevall Arturo
Published: December 2019

Chemical biology is an emerging field that allows the study and manipulation of biological systems using probes that inform on structure based on their reactivity. We report the synthesis of a hydroxylamine-armed fluorescent probe that reacts with reducing glycans and its application to study the architecture of theCryptococcus neoformanscapsule under a variety of conditions. The probe signal localized intracellularly and at the cell wall-membrane interface, implying the presence of reducing end glycans at this location where the capsule attachment to the cell body occurs. In contrast, there was no fluorescence signal in the body of the capsule. We observed vesicle-like structures containing the reducing-end probe, both intra- and extracellularly, consistent with the importance of vesicles in capsular assembly. Disrupting the capsule with DMSO, ultrasound, or mechanical shear-stress resulted in capsule alterations that affected the binding of the probe as reducing ends were exposed, and cell membrane integrity was compromised. In contrast to the polysaccharides in the assembled capsule, isolated exopolysaccharides contained reducing ends. The reactivity of the hydroxylamine-armed fluorescent probe suggests a model for capsule assembly where reducing ends localize to the cell wall surface, supporting previous work suggesting that this is an initiation point for capsular assembly. Chemical biology is a promising approach for studying theC. neoformanscapsule and its associated polysaccharides.
ImmuCellAI: a unique method for comprehensive T-cell subsets abundance prediction and its application in cancer immunotherapy
Authors: Miao Ya-Ru , Zhang Qiong , Lei Qian , Luo Mei , Xie Gui-Yan , Wang Hongxiang , Guo An-Yuan
Published: December 2019

The distribution and abundance of immune cells, particularly T-cell subsets, play pivotal roles in cancer immunology and therapy. There are many T-cell subsets with specific function, however current methods are limited in estimating them, thus, a method for predicting comprehensive T-cell subsets is urgently needed in cancer immunology research. Here we introduce Immune Cell Abundance Identifier (ImmuCellAI), a novel gene set signature-based method, for precisely estimating the abundance of 24 immune cell types including 18 T-cell subsets, from gene expression data. Performance evaluation on both our sequencing data with flow cytometry results and public expression data indicated that ImmuCellAI can estimate immune cells with superior accuracy than other methods especially on many T-cell subsets. Application of ImmuCellAI to immunotherapy datasets revealed that the abundance of dendritic cells (DC), cytotoxic T, and gamma delta T cells was significantly higher both in comparisons of on-treatment vs. pre-treatment and responders vs. non-responders. Meanwhile, we built an ImmuCellAI result-based model for predicting the immunotherapy response with high accuracy (AUC 0.80~0.91). These results demonstrated the powerful and unique function of ImmuCellAI in tumor immune infiltration estimation and immunotherapy response prediction. The ImmuCellAI online server is freely available at http://bioinfo.life.hust.edu.cn/web/ImmuCellAI/.
Geometric regulation of histone state directs melanoma reprogramming
Authors: Lee Junmin , Molley Thomas G. , Seward Christopher H. , Abdeen Amr A. , Zhang Huimin , Wang Xiaochun , Gandhi Hetvi , Yang Jia-Lin , Gaus Katharina , Kilian Kristopher A.
Published: December 2019

Malignant melanoma displays a high degree of cellular plasticity during disease progression, making classification of the heterogeneous population and selection of an appropriate therapy challenging. Signals in the tumor microenvironment are believed to influence melanoma plasticity through changes in the epigenetic state to guide dynamic differentiation and de-differentiation events that underlie tumorigenicity and dissemination. Here we uncover a relationship between geometric features at perimeter regions of multicellular melanoma aggregates, and reprogramming to a stem cell-like melanoma initiating cell (MIC) through histone marks H3K4Me2 and H3K9Ac. Using an in vitro tumor microengineering approach, we find concurrent expression of molecular MIC markers and spatial enrichment of these histone modifications at perimeter features. Chromatin immunoprecipitation and sequencing analysis demonstrates broad regulation of genes associated with SOX-, ETS-, and USF-families. SOX10 and PRDM14, transcriptional regulators with a putative role in several cancers, overlap with H3K9Ac and show elevated expression in cells along regions of perimeter curvature. siRNA knockdown of the epigenetic modifier PRDM14 abolishes the MIC phenotype suggesting a role in regulating melanoma heterogeneity. Our results suggest mechanotransduction at the periphery of melanoma tumors may orchestrate the activity of epigenetic modifiers to regulate histone state, cellular plasticity, and tumorigenicity.
Causal role of L-glutamine in sickle cell disease painful crises: a Mendelian randomization analysis
Authors: Iboudo Yann , Garrett Melanie E. , Bartolucci Pablo , Brugnara Carlo , Clish Clary B. , Hirschhorn Joel N. , Galactéros Frédéric , Ashley-Koch Allison E. , Telen Marilyn J. , Lettre Guillaume
Published: December 2019

In a recent clinical trial, the metabolite L-glutamine was shown to reduce painful crises in sickle cell disease (SCD) patients. To confirm this observation and identify other metabolites implicated in SCD clinical heterogeneity, we profiled 129 metabolites in the plasma of 705 SCD patients. We tested correlations between metabolite levels and six SCD-related complications (painful crises, cholecystectomy, retinopathy, leg ulcer, priapism, aseptic necrosis) or estimated glomerular filtration rate (eGFR), and used Mendelian randomization (MR) to assess causality. We found a causal relationship between L-glutamine levels and painful crises (N=1,278, odds ratio (OR) [95% confidence interval] = 0.68 [0.52 – 0.89], P=0.0048). In two smaller SCD cohorts (N=299 and 406), the protective effect of L-glutamine was observed (OR=0.82 [0.50-1.34]), although the MR result was not significant (P=0.44). We identified 66 significant correlations between the levels of other metabolites and SCD-related complications or eGFR. We tested these correlations for causality using MR analyses and found no significant causal relationship. The baseline levels of quinolinic acid was associated with prospectively ascertained survival in SCD patients, and this effect was dependent on eGFR. Metabolomics provide a promising approach to prioritize small molecules that may serve as biomarkers or drug targets in SCD.
What kind of emotions do emoticons communicate?
Authors: Brito Pedro Quelhas , Torres Sandra , Fernandes Jéssica
Published: December 2019

Purpose

The purpose of this paper is to study the nature and concept of emoticons/emojis. Instead of taking for granted that these user-generated formats are necessarily emotional, we empirically assessed in what extent are they and the specificity of each one. Drawing on congruent mood state, valence core and emotion appraisal theories we expected a compatible statistical association between positive/negative/neutral emotional valence expressions and emoticons of similar valence. The positive emoticons were consistently associated with positive valence posts. Added to that analysis, 21 emotional categories were identified in posts and correlated with eight emoticons.

Design/methodology/approach

Two studies were used to address this question. The first study defined emoticon concept and interpreted their meaning highlighting their communication goals and anticipated effects. The link between emojis and emoticons was also obtained. Some emoticons types present more ambiguity than others. In the second study, three years of real and private (Facebook) posts from 82 adolescents were content analyzed and coded.

Findings

Only the neutral emoticons always matched neutral emotional categories found in the written interaction. Although the emoticon valence and emotional category congruence pattern was the rule, we also detected a combination of different valence emoticons types and emotion categories valence expressions. Apparently the connection between emoticon and emotion are not so obviously straightforward as the literature used to assume. The created objects designed to communicate emotions (emoticons) have their specific corresponding logic with the emotional tone of the message.

Originality/value

Theoretically, we discussed the emotional content of emoticons/emojis. Although this king of signals have an Asian origin and later borrowed from the western countries, their ambiguity and differing specificity have never been analyzed.
Ethical attribute and brand concept congruity enhances brand evaluations
Authors: Tofighi Maryam , Grohmann Bianca , Bodur H. Onur
Published: December 2019

Purpose

This paper aims to examine to what extent congruity between ethical attributes (i.e. product attributes with positive implications for the environment, human rights, social issues and animal welfare) and brand concept (i.e. the unique meaning associated with a brand in consumers’ minds) influences consumers’ evaluations of brands offering ethical attributes.

Design/methodology/approach

Four studies involving North American consumers empirically tested the moderation effect of brand concept on consumer evaluations of ethical attributes and the mediating role of perceived congruity.

Findings

This research finds an interactive effect of ethical attribute type and brand concept on brand evaluations, such that congruent ethical attribute–brand concept pairings (i.e. a utilitarian [symbolic] ethical attribute offered by a brand with a utilitarian [symbolic] brand concept) result in more favorable brand evaluations (Studies 1, 2, 3 and 4). Consumers’ perceptions of congruity between ethical attributes and brand concepts mediate this interactive effect (Studies 2 and 3). Moreover, a positive congruity effect of ethical attributes and brand concepts emerges at higher levels of conspicuous brand consumption (Study 4).

Research limitations/implications

It is important to acknowledge that the current research did not specifically consider the case of utilitarian and symbolic ethical attribute offerings by luxury brands. This is a question that is left to future investigations.

Practical implications

For marketing managers, findings indicate that brands gain from ethical attribute introductions only when these attributes are congruent with the brand concept. In addition, brands benefit to a greater extent from offering congruent ethical attributes when brand consumption is conspicuous.

Originality/value

The findings of this research contribute to the literature on the effect of ethical attributes on consumers’ responses to brands and highlight the importance of brands’ choice of ethical attributes.
Woke-washing: “intersectional” femvertising and branding “woke” bravery
Authors: Sobande Francesca
Published: December 2019

Purpose

This paper aims to explore how and why ideas regarding “intersectional” approaches to feminism and Black activism are drawn on in marketing content related to the concept of being “woke” (invested in addressing social injustices). It considers which subject positions are represented as part of this and what they reveal about contemporary issues concerning advertising, gender, race and activism.

Design/methodology/approach

This study involves an interpretive and critical discursive analysis of so-called feminist advertising (“femvertising”) and marketing examples that make use of Black social justice activist ideas.

Findings

Findings illuminate how marketing simultaneously enables the visibility and erasure of “intersectional”, feminist and Black social justice activist issues, with the use of key racialised and gendered subject positions: White Saviour, Black Excellence, Strong Black Woman (and Mother) and “Woke” Change Agent.

Research limitations/implications

This research signals how brands (mis)use issues concerning commercialised notions of feminism, equality and Black social justice activism as part of marketing that flattens and reframes liberationist politics while upholding the neoliberal idea that achievement and social change requires individual ambition and consumption rather than structural shifts and resistance.

Practical implications

This work can aid the development of advertising standards regulatory approaches which account for nuances of stereotypical representations and marketing’s connection to intersecting issues regarding racism and sexism.

Originality/value

This research outlines a conceptualisation of the branding of “woke” bravery, which expands our understanding of the interdependency of issues related to race, gender, feminism, activism and marketing. It highlights marketing responses to recent socio-political times, which are influenced by public discourse concerning movements, including Black Lives Matter and Me Too.
Consumers gain equivalent levels of happiness from sharing about an experience and an object
Authors: Bastos Wilson
Published: December 2019

Purpose

This paper aims to examine how conversing about experiences and objects affects consumer happiness. In contrast to previous research focusing on conversation frequency, this paper explores how each conversation instance influences happiness.

Design/methodology/approach

Four experiments use three different methodologies, namely, actual talking behavior (Study 1), recalled and mental framing interventions and measurement of the focal variables (Studies 2 and 3) and manipulation of purchase conversationality (Study 4).

Findings

Consumers derive equivalent levels of happiness from each material or experiential conversation they have. When the object is highly conversational (when it generates as much conversation as experiences do), it advances as much happiness as experiences.

Research limitations/implications

The findings inform precisely how the purchase conversationality model unfolds; clarify previous claims made in the literature; establish the direction of causal effect; and reveal a novel boundary condition of happiness superiority of experiences.

Practical implications

The findings inform marketing managers how to optimally allocate their world-of-mouth (WOM) resources to advance consumer happiness. Additionally, this work shows a mental framing strategy able to increase WOM for objects – i.e. a tool for the manager.

Originality/value

This is the first investigation to disentangle the frequency of conversation from each conversation’s ability to advance happiness. It is also the first to engage participants in an actual conversation and measure changes in their happiness, and therefore, conclusively establish the direction of the effect. Additionally, by manipulating purchase conversationality, this work demonstrates a new boundary condition associated with conversationality.
How to improve organisational citizenship behaviour by combining ability, motivation and opportunity
Authors: Morales-Sánchez Rafael , Pasamar Susana
Published: December 2019

Purpose

The purpose of this paper is to explore the relationship between the ability, motivation and opportunity model, and organisational citizenship behaviour (OCB) as a result variable, using the perceived organisational support (POS) as a moderator of this relationship.

Design/methodology/approach

The hypotheses developed here are tested using data from a sample of Spanish firms belonging to two industries: finance and hotels. These sectors were selected due to the serious impact the recent financial crisis had on them, and because they may benefit from extra-role behaviours.

Findings

The results reveal that ability and motivation significantly influence the level of OCB. POS also has a notable direct effect on OCB, as well as moderating in the relationship between opportunity and OCB.

Originality/value

The study’s findings have some important lessons for practitioners and researchers with an interest in OCB, showing how to improve these extra-role behaviours, which can be so necessary in this post-crisis context.
Analysis of archives infrastructure in South Africa
Authors: Netshakhuma Nkholedzeni Sidney
Published: December 2019

Purpose

The purpose of this study is to assess the extent to which the Mpumalanga Provincial Archives (MPA) complies with the Mpumalanga Archives Act, 2008 legislative/policy provisions of archives building, capacity building and electronic records management and to suggest recommendations for effective archives and records management (ARM) programme in South Africa.

Design/methodology/approach

This paper adopts a quantitative approach supplemented by qualitative data using document review to collect data and content analysis.

Findings

The results show that MPA enacted Mpumalanga Archives Act, 2008. However, the challenge is the implementation of such legislation. The findings of this paper would contribute towards the literature in archival legislation in South Africa and other parts of the world.

Research limitations/implications

Even though the paper was based in South Africa, it was limited to the MPA of South Africa.

Practical implications

The findings are expected to be instrumental in the implementation of Mpumalanga Archives Act, 2008.

Social implications

The findings and recommendations will help in guiding MPA on the implementation of an effective provincial archive and records to facilitate the effective management of records to determine those of archival value, to preserve them for posterity and to make them accessible to the public.

Originality/value

This is an original study using a document review to review the Mpumalanga Archives Act, 1998. The effective archives infrastructure will contribute to compliance with legislative components such as archives building, cooperation, ERMS, appraisal and disposal of records, archives advisory body and access to information.
Design teams management of conflict in reaching consensus
Authors: Kiernan Louise , Ledwith Ann , Lynch Raymond
Published: December 2019

Purpose

The purpose of this paper is to explore the conversation activities of design teams to negotiate task conflict and reach consensus.

Design/methodology/approach

Four case studies were conducted to analyse the conversation activities that teams use in the course of design projects.

Findings

The conversation activities that teams used to negotiate conflict and bring about consensus were identified. These conversation activities are associated with collaboration, communication and social skills enabling teams to engage in the high level of information exchange and negotiation that is required to manage task conflict. How they were used to negotiate conflict and help reach consensus is also discussed.

Research limitations/implications

The findings from this research are based on a small number of participants; hence, it cannot be generalised without further study with larger groups. However, the questions this paper has raised can be generalised to other design tasks and groups.

Practical implications

The findings have implications for the management of design teams and teams working on complex unstructured problems both in industry and education. They highlight how conflict can be constructively managed to bring about consensus that integrates the knowledge and perspective of all team members.

Originality/value

The benefits of task conflict have been disputed in the literature. This research has identified the conversation activities that facilitate the constructive management of task conflict to bring about consensus that integrates the perspectives and knowledge of a team.
Evaluating the working conditions of the dependent self-employed
Authors: Horodnic Ioana Alexandra , Williams Colin C.
Published: December 2019

Purpose

In recent years, there has been a concern that employers are falsely classifying employees as self-employed to evade collective agreements and labour laws (e.g. minimum wages, working time legislation and protection in case of redundancy), and the result is that these dependent self-employed suffer poorer working conditions. The purpose of this paper is to provide an extensive evaluation of the working conditions of those in dependent self-employment compared with the genuine self-employed.

Design/methodology/approach

To do so, data are reported from a 2015 European Working Conditions Survey of 35,765 workers in 28 European Union member states.

Findings

Of the 4.3 per cent of the working population found to be in dependent self-employment, the finding is that they have similar working conditions to the genuine self-employed in terms of their physical and social environment and intensity of work. However, they have poorer job prospects and less ability to use their skills and discretion than the genuine self-employed. In terms of the working time quality, meanwhile, the finding is that they have better conditions than the genuine self-employed. Therefore, this analysis uncovers the need for a more nuanced understanding of the relative working conditions of the dependent self-employed.

Research limitations/implications

If the working conditions of the dependent self-employed are to be tackled, evaluation is now required of whether the current policy approaches, such as developing a hybrid category of employment with legal rights attached, address the specific working conditions that are worse for the dependent self-employed.

Originality/value

This is one of the few papers which provides an extensive evaluation of the working conditions of those in dependent self-employment in the EU28.
The liability of newer than newness: aspiring entrepreneurs and legitimacy
Authors: O’Toole Jay , Ciuchta Michael P.
Published: December 2019

Purpose

The purpose of this paper is to return to Stinchcombe’s original emphasis on emerging vs existing organizations by examining the cognitive legitimacy challenges aspiring entrepreneurs face vis-à-vis entrepreneurs with existing businesses.

Design/methodology/approach

The data collection included content analysis of profiles of an online crowdfunding, peer-to-peer lending market leading to a sample of 507 business loan requests, 123 of which were requests to support new business ideas rather than existing businesses. Negative binomial regression was used to test hypotheses regarding whether aspiring entrepreneurs seeking convenience-based support for their new business ideas would be less successful than their counterpart entrepreneurs seeking support for their existing businesses.

Findings

The findings show that aspiring entrepreneurs received less convenience-based support for their new business ideas from key resource providers than their peer entrepreneurs asking for support for existing businesses. The findings also suggest that this liability of newer than newness may be able to be mitigated by reputational signals such as the creditworthiness of the entrepreneur making the request.

Originality/value

This study focuses on the original insights Stinchcombe introduced when he described the social conditions that produce the liability of newness. Moreover, this study offers explicit theory as to the key mechanisms that cause the liability of newness by focusing on an aspiring entrepreneur’s ability to secure convenience-based support and potential ways an aspiring entrepreneur may offset that liability.