bluuebunny/crossref_metadata_2025_split huggingface dataset:
Branching and extinction in evolutionary public goods games
Authors: Johnson Brian , Altrock Philipp M. , Kimmel Gregory J. 
Published: August 2020

AbstractPublic goods games (PGGs) describe situations in which individuals contribute to a good at a private cost, but others can free-ride by receiving their share of the public benefit at no cost. PGGs can be nonlinear, as often observed in nature, whereby either benefit, cost, or both are nonlinear functions of the available public good (PG): at low levels of PG there can be synergy whereas at high levels, the added benefit of additional PG diminishes. PGGs can be local such that the benefits and costs are relevant only in a local neighborhood or subset of the larger population in which producers (cooperators) and free-riders (defectors) co-evolve. Cooperation and defection can be seen as two extremes of a continuous spectrum of traits. The level of public good production, and similarly, the neighborhood size can vary across individuals. To better understand how distinct strategies in the nonlinear public goods game emerge and persist, we study the adaptive dynamics of production rate and neighborhood size. We explain how an initially monomorphic population, in which individuals have the same trait values, could evolve into a dimorphic population by evolutionary branching, in which we see distinct cooperators and defectors emerge, respectively characterized by high production and low neighborhood sizes, and low production and high neighborhood sizes. We find that population size plays a crucial role in determining the final state of the population, as smaller populations may not branch, or may observe extinction of a subpopulation after branching. Our work elucidates the evolutionary origins of cooperation and defection in nonlinear local public goods games, and highlights the importance of small population size effects on the process and outcome of evolutionary branching.
SARS-CoV-2 infects human pluripotent stem cell-derived cardiomyocytes, impairing electrical and mechanical function
Authors: Marchiano Silvia , Hsiang Tien-Ying , Higashi Ty , Khanna Akshita , Reinecke Hans , Yang Xiulan , Pabon Lil , Sniadecki Nathan J. , Bertero Alessandro , Gale Michael , Murry Charles E. 
Published: August 2020

AbstractGlobal health has been threatened by the COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2)1. Although considered primarily a respiratory infection, many COVID-19 patients also suffer severe cardiovascular disease2–4. Improving patient care critically relies on understanding if cardiovascular pathology is caused directly by viral infection of cardiac cells or indirectly via systemic inflammation and/or coagulation abnormalities3,5–9. Here we examine the cardiac tropism of SARS-CoV-2 using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and three-dimensional engineered heart tissues (3D-EHTs). We observe that hPSC-CMs express the viral receptor ACE2 and other viral processing factors, and that SARS-CoV-2 readily infects and replicates within hPSC-CMs, resulting in rapid cell death. Moreover, infected hPSC-CMs show a progressive impairment in both electrophysiological and contractile properties. Thus, COVID-19-related cardiac symptoms likely result from a direct cardiotoxic effect of SARS-CoV-2. Long-term cardiac complications might be possible sequelae in patients who recover from this illness.
Ribosome inhibition byC9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM
Authors: Loveland Anna B. , Svidritskiy Egor , Susorov Denis , Lee Soojin , Park Alexander , Demo Gabriel , Gao Fen-Biao , Korostelev Andrei A. 
Published: August 2020

AbstractToxic dipeptide repeat (DPR) proteins are produced from expanded G4C2hexanucleotide repeats in theC9ORF72gene, which cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two DPR proteins, poly-PR and poly-GR, repress cellular translation but the molecular mechanism remains unknown. Here we show that poly-PR and poly-GR of ≥ 20 repeats inhibit the ribosome’s peptidyl-transferase activity at nanomolar concentrations, comparable to specific translation inhibitors. High-resolution cryo-EM structures reveal that poly-PR and poly-GR block the polypeptide tunnel of the ribosome, extending into the peptidyl-transferase center. Consistent with these findings, the macrolide erythromycin, which binds in the tunnel, competes with the DPR proteins and restores peptidyl-transferase activity. Our results demonstrate that strong and specific binding of poly-PR and poly-GR in the ribosomal tunnel blocks translation, revealing the structural basis of their toxicity inC9ORF72-ALS/FTD.
Quantitative imaging of RNA polymerase II activity in plants reveals the single-cell basis of tissue-wide transcriptional dynamics
Authors: Alamos Simon , Reimer Armando , Niyogi Krishna K. , Garcia Hernan G. 
Published: August 2020

AbstractThe responses of plants to their environment often hinge on the spatiotemporal dynamics of transcriptional regulation. While live-imaging tools have been used extensively to quantitatively capture rapid transcriptional dynamics in living animal cells, lack of implementation of these technologies in plants has limited concomitant quantitative studies. Here, we applied the PP7 and MS2 RNA-labeling technologies for the quantitative imaging of RNA polymerase II activity dynamics in single cells of living plants as they respond to experimental treatments. Using this technology, we count nascent RNA transcripts in real-time inNicotiana benthamiana(tobacco) andArabidopsis thaliana(Arabidopsis). Examination of heat shock reporters revealed that plant tissues respond to external signals by modulating the number of cells engaged in transcription rather than the transcription rate of active cells. This switch-like behavior, combined with cell-to-cell variability in transcription rate, results in mRNA production variability spanning three orders of magnitude. We determined that cellular heterogeneity stems mainly from the stochasticity intrinsic to individual alleles. Taken together, our results demonstrate that it is now possible to quantitatively study the dynamics of transcriptional programs in single cells of living plants.
Plant NLR targets P-type ATPase for executing plasma membrane depolarization leading to calcium influx and cell death
Authors: Lee Hye-Young , Seo Ye-Eun , Lee Joo Hyun , Lee So Eui , Oh Soohyun , Kim Jihyun , Jung Seungmee , Kim Haeun , Park Hyojeong , Kim Sejun , Mang Hyunggon , Choi Doil 
Published: August 2020

AbstractHypersensitive response (HR) is a robust immune response mediated by plant nucleotide-binding and leucine-rich repeat receptor (NLR). However, the early molecular event linking NLR to cell death is obscure. Here we demonstrate that NLR targets plasma membrane H+-ATPases (PMA) generating electrochemical potential across the membrane. CCA309, an autoactive N-terminal domain of pepper coiled-coil NLR (CNL), associates with PMAs and its autoactivity is affected by silencing or overexpression of PMA. CCA309-induced extracellular alkalization accompanied with membrane depolarization is followed by calcium influx and cell death. CCA309 interacts with C-terminal regulatory domain of PMA and 14-3-3 negatively affects CCA309-induced cell death. Moreover, pharmacological experiments with fusicoccin, an irreversible PMA activator, confirmed that CC- and CNL-mediated cell death occurred through inhibiting PMA. We propose PMAs as the primary target of plasma membrane-associated CNL to disrupt electrochemical homeostasis leading to HR cell death.
Murine intrarectal instillation of purified recombinantC. difficiletoxins enables mechanistic studies of pathogenesis
Authors: Markham Nicholas O. , Bloch Sarah C. , Shupe John A. , Laubacher Erin N. , Washington M. Kay , Coffey Robert J. , Lacy D. Borden 
Published: August 2020

AbstractClostridioides difficileis linked to nearly 225,000 antibiotic-associated diarrheal infections and almost 13,000 deaths per year in the United States. Pathogenic strains ofC. difficileproduce toxin A (TcdA) and toxin B (TcdB), which can directly kill cells and induce an inflammatory response in the colonic mucosa. Hirota,et al. first introduced the intrarectal instillation model of intoxication using TcdA and TcdB purified from VPI 10463 and 630C. difficilestrains. Here, we expand this technique by instilling purified, recombinant TcdA and TcdB, which allows for the interrogation of how specifically mutated toxins affect tissue. Mouse colons were processed and stained with hematoxylin and eosin (H&E) for blinded evaluation and scoring by a board-certified gastrointestinal pathologist. The amount of TcdA or TcdB needed to produce damage was lower than previously reportedin vivoandex vivo. Furthermore, TcdB mutants lacking either endosomal pore-formation or glucosyltransferase activity resemble sham negative controls. Immunofluorescent staining revealed how TcdB initially damages colonic tissue by altering the epithelial architecture closest to the lumen. Tissue sections were also immunostained for markers of acute inflammatory infiltration. These staining patterns were compared with slides from a humanC. difficileinfection (CDI). The intrarectal instillation mouse model with purified recombinant TcdA and/or TcdB provides the flexibility needed to better understand structure/function relationships across different stages of CDI pathogenesis.
Capitalizing on paradoxical activation of the MAPK pathway for treatment of Imatinib-resistant mast cell leukemia
Authors: Wilhelm Thomas , Toledo Marcelo A. S. , Simons Ilka , Stuth Christian , Mohta Vrinda , Mülfarth Ronja , Nitsche Marcus , Maschke-Neuß Karin , Schmitz Susanne , Kaiser Anne , Arock Michel , Zenke Martin , Huber Michael 
Published: August 2020

AbstractPrevention of fatal side effects during cancer therapy of cancer patients with high-dosed pharmacological inhibitors is to date a major challenge. Moreover, the development of drug resistance poses severe problems for the treatment of patients with leukemia or solid tumors. Particularly drug-mediated dimerization of RAF kinases can be the cause of acquired resistance, also called “paradoxical activation”. Here we re-analyzing the effects of different tyrosine kinase inhibitors (TKIs) on the proliferation, metabolic activity, and survival of the Imatinib-resistant, KITV560G,D816V-expressing human mast cell (MC) leukemia (MCL) cell line HMC-1.2. We observed that low concentrations of the TKIs Nilotinib and Ponatinib resulted in enhanced proliferation, suggesting paradoxical activation of the MAPK pathway. Indeed, these TKIs caused BRAF-CRAF dimerization, resulting in ERK1/2 activation. The combination of Ponatinib with the MEK inhibitor Trametinib, at nanomolar concentrations, effectively suppressed HMC-1.2 proliferation, metabolic activity, and induced apoptotic cell death. Effectiveness of this drug combination was recapitulated in the humanKITD816V MC line ROSA KITD816Vand inKITD816V hematopoietic progenitors obtained from in patient-derived induced pluripotent stem cells (iPS cells). In conclusion, mutated KIT-driven Imatinib resistance can be efficiently bypassed by a low concentration combination of the TKI Ponatinib and the MEK inhibitor Trametinib, potentially reducing the negative side effects associated to MCL therapy.
ZNF410 uniquely activates the NuRD component CHD4 to silence fetal hemoglobin expression
Authors: Lan Xianjiang , Ren Ren , Feng Ruopeng , Ly Lana C. , Lan Yemin , Zhang Zhe , Aboreden Nicholas , Qin Kunhua , Horton John R. , Grevet Jeremy D. , Mayuranathan Thiyagaraj , Abdulmalik Osheiza , Keller Cheryl A. , Giardine Belinda , Hardison Ross C. , Crossley Merlin , Weiss Mitchell J , Cheng Xiaodong , Shi Junwei , Blobel Gerd A. 
Published: August 2020

SummaryMetazoan transcription factors typically regulate large numbers of genes. Here we identify via a CRISPR-Cas9 genetic screen ZNF410, a pentadactyl DNA binding protein that in human erythroid cells directly and measurably activates only one gene, the NuRD component CHD4. Specificity is conveyed by two highly evolutionarily conserved clusters of ZNF410 binding sites near the CHD4 gene with no counterparts elsewhere in the genome. Loss of ZNF410 in adult-type human erythroid cell culture systems and xenotransplant settings diminishes CHD4 levels and derepresses the fetal hemoglobin genes. While previously known to be silenced by CHD4, the fetal globin genes are exposed here as among the most sensitive to reduced CHD4 levels. In vitro DNA binding assays and crystallographic studies reveal the ZNF410-DNA binding mode. ZNF410 is a remarkably selective transcriptional activator in erythroid cells whose perturbation might offer new therapeutic opportunities in the treatment of hemoglobinopathies.HighlightsA CRISPR screen implicates ZNF410 in fetal globin gene repressionThe CHD4 gene is the singular direct ZNF410 target in erythroid cellsThe fetal globin genes are exquisitely sensitive to CHD4 levelsFive C2H2 zinc fingers of ZNF410 recognize the major groove of a 14 base pair sequence
BAP1 and YY1 regulate expression of death receptors in malignant pleural mesothelioma
Authors: Ishii Y , Kolluri KK , Pennycuick A , Nigro E , Alrifai D , Borg E , Falzon M , Shah K , Kumar N , Janes SM 
Published: August 2020

AbstractMalignant pleural mesothelioma (MPM) is a rare, aggressive, and incurable cancer arising from the mesothelial lining of the lungs with few treatment options. We recently reported loss of function of the nuclear deubiquitinase BRCA associated protein-1 (BAP1), a frequent event in MPM, is associated with sensitivity to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL). As a potential underlying mechanism, here we report that BAP1 negatively regulates the expression of TRAIL receptors: death receptors 4 (DR4) and 5 (DR5). Using tissue microarray (TMAs) of tumour samples from MPM patients, we found a strong inverse correlation between BAP1 and TRAIL receptors.BAP1knockdown increased DR4 and DR5 expression, whereas overexpression of BAP1 had the opposite effect. Reporter assays confirmed wild-typeBAP1, but not catalytically-inactive mutantBAP1, reduced promoter activities ofDR4andDR5, suggesting deubiquinase activity plays an important role in the regulation of gene expression. Co-IP studies demonstrated direct binding of BAP1 and the transcription factor Ying Yang 1 (YY1) and ChIP assays revealed BAP1 and YY1 to be enriched in the promoter regions ofDR4andDR5. Notably, shRNA knockdown ofYY1also increased DR4 and DR5 expression, and sensitivity to TRAIL. These results demonstrate that BAP1 and YY1 together negatively regulate transcriptional activity of TRAIL receptors. BAP1 and YY1 may both therefore be strong therapeutic targets to enhance the efficacy of TRAIL-induced apoptosis.Statement of significanceWe describe how the most-frequently mutated tumour suppressor gene in mesothelioma regulates the response to TNF-related apoptosis-inducing ligand (TRAIL). These findings will accelerate a biomarker-driven cancer therapy.
Perturbations of theAMI1IAM-amidohydrolase expression trigger plant stress responses inArabidopsis thaliana
Authors: Pérez-Alonso Marta-Marina , Ortiz-García Paloma , Moya-Cuevas José , Lehmann Thomas , Sánchez-Parra Beatriz , Björk Robert G. , Karim Sazzad , Amirjani Mohammad R. , Aronsson Henrik , Wilkinson Mark D. , Pollmann Stephan 
Published: August 2020

ABSTRACTThe evolutionary success of plants relies to a large extent on their extraordinary ability to adapt to changes in their environment. These adaptations require that plants balance their growth with their stress responses. Plant hormones are crucial mediators orchestrating the underlying adaptive processes. However, whether and how the growth-related hormone auxin and the stress-related hormones jasmonic acid (JA), salicylic acid, and abscisic acid (ABA) are coordinated remains largely elusive. Here, we analyze the physiological role of AMIDASE 1 (AMI1) in plant growth and its possible connection to plant adaptations to abiotic stresses. AMI1 contributes to cellular auxin homeostasis by catalyzing the conversion of indole-acetamide into the major plant auxin indole-3-acetic acid. Functional impairment of AMI1 increases the plants’ stress status rendering mutant plants more susceptible to abiotic stresses. Transcriptomic analysis ofami1mutants disclosed the reprogramming of a considerable number of stress-related genes, including JA and ABA biosynthesis genes. Theami1mutants exhibit only moderately repressed growth, but an enhanced ABA accumulation, which suggests a role for AMI1 in the crosstalk between auxin and ABA. Altogether, our results suggest that AMI1 is involved in coordinating the trade-off between plant growth and stress responses, balancing auxin with ABA homeostasis.HIGHLIGHTThe IAM amidohydrolase AMI1 catalyzes the conversion of IAM into IAAin vivo. Expression ofAMI1is specifically repressed by osmotic stress conditions, which triggers ABA biosynthesis through the induction ofNCED3, thereby linking auxin homeostasis with plant stress responses.
Dynamic reliability and variance-based global sensitivity analysis of pipes conveying fluid with both random and convex variables
Authors: Chen Bingqian , Wang Anqiang , Guo Qing , Dai Jiayin , Liu Yongshou 
Published: August 2020

Purpose
This paper aims to solve the problem that pipes conveying fluid are faced with severe reliability failures under the complicated working environment.

Design/methodology/approach
This paper proposes a dynamic reliability and variance-based global sensitivity analysis (GSA) strategy with non-probabilistic convex model for pipes conveying fluid based on the first passage principle failure mechanism. To illustrate the influence of input uncertainty on output uncertainty of non-probability, the main index and the total index of variance-based GSA analysis are used. Furthermore, considering the efficiency of traditional simulation method, an active learning Kriging surrogate model is introduced to estimate the dynamic reliability and GSA indices of the structure system under random vibration.

Findings
The variance-based GSA analysis can measure the effect of input variables of convex model on the dynamic reliability, which provides useful reference and guidance for the design and optimization of pipes conveying fluid. For designers, the rankings and values of main and total indices have essential guiding role in engineering practice.

Originality/value
The effectiveness of the proposed method to calculate the dynamic reliability and sensitivity of pipes conveying fluid while ensuring the calculation accuracy and efficiency in the meantime.
Products labeled as “made in domestic country”: the brand matters
Authors: Bernard Yohan , Collange Véronique , Ingarao Aurore , Zarrouk-Karoui Sarra 
Published: August 2020

Purpose
The purpose of this paper is to better understand an increasingly widespread practice consisting, of a brand, in signaling the domestic origin of its products aimed at domestic consumers, that is, the “made in the domestic country” (MIDC) strategy. To this end, it is proposed to analyze the MIDC label as a cue interacting with the brand’s characteristics (brand equity and country of origin of the brand).

Design/methodology/approach
A between-subjects experiment is conducted among 293 French consumers on four different brands of pasta. The overall design is a 2 (with/without the MIDC label) × 2 (high/low brand equity) × 2 (domestic/foreign brand) mixed design.

Findings
The results show that intention to buy the product increases significantly with the presence of the MIDC label, but not so willing to pay. The positive effect on buying intention is greater when: the product has rather low brand equity, consumer ethnocentrism is high and/or consumers are strongly attached to their national identity.

Research limitations/implications
The present research extends the literature on country-of-origin effects by taking into account the role of the brand equity of the product. However, the study focused on only one low-involvement product category (pasta) and one country (France).

Practical implications
This study shows that adding an MIDC label to the product is empirically justified.

Originality/value
While moderate or high scores on “patriotic” variables reinforce the positive impact of the MIDC label, low scores reverse the trend, that is, cause rejection.
Liberal and vocational education: the Gordian encounter
Authors: Burns Caroline J. , Natale Samuel M. 
Published: August 2020

PurposeThe purpose of this paper is to discuss how liberal higher education can strengthen vocational higher education.Design/methodology/approachThe paper uses Shay's (2013) framework of curriculum differentiation to articulate how the strengths and shortcomings of liberal education differ from those of vocational education and to allow the differences highlighted to inform a resolution to each other's shortcomings.FindingsThere is nothing new in the findings that liberal education differs from vocational education and that both have shortcomings. What the paper presents is a viewpoint that the differences are not confirmation that these two approaches to education are in opposition but rather that they complement each other. The strength of one is the weakness of the other.Originality/valueThe perspective taken in this paper is developed using the language of semantic density (SD) and semantic gravity (SG). Using Shay's semantic field of recontextualized knowledge, this paper suggests that liberal and vocational education inhabit two sides of contexts and concepts continua. The paper further proposes that both are alike in a meaningful way because both have unsuccessfully managed the role of context in their curricula.
Readability of Korean-Language advertising disclosures moderates knowledge effects
Authors: Lee Taejun (David) , Huhmann Bruce A. , Yun TaiWoong 
Published: August 2020

PurposeGovernment policy mandates information disclosure in financial communications to protect consumer welfare. Unfortunately, low readability can hamper information disclosures’ meaningful benefits to financial decision making. Thus, this experiment tests the product evaluation and decision satisfaction of Korean consumers with less or more subjective knowledge and with or without personal finance education.Design/methodology/approachA between-subjects experiment examined responses of a nationally representative sample of 400 Korean consumers toward a Korean-language credit card advertisement.FindingsFinancial knowledge improves financial product evaluation and decision satisfaction. More readable disclosures improved evaluation and satisfaction among less knowledgeable consumers. Less readable disclosures did not. Consumers without financial education exhibited lower evaluations and decision satisfaction regardless of readability. More knowledgeable consumers and those with financial education performed equally well regardless of disclosure readability.Practical implicationsFinancial service providers seeking more accurate evaluations and better decision satisfaction among their customers should use easier-to-read disclosures when targeting consumers with less prior financial knowledge.Social implicationsOne-size-fits-all financial communications are unlikely to achieve public policy or consumer well-being goals. Government-mandated information should be complemented by augmenting financial knowledge and providing personal finance training.Originality/valueAlthough almost a quarter of the world’s population lives in East Asia, this is the first examination of readability in disclosures written in East Asian characters rather than a Western alphabet. Previous readability research on Asian-originating financial disclosures has been conducted on English-language texts. This study extends knowledge of readability effects to growing East Asian markets.