bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFβ2 regulates human trabecular meshwork cell contractility via ERK and ROCK pathways with distinct signaling crosstalk dependent on the culture substrate
Authors: Li Haiyan , Henty-Ridilla Jessica L. , Ganapathy Preethi S. , Herberg Samuel 
Published: July 2021

AbstractTransforming growth factor beta 2 (TGFβ2) is a major contributor to the pathologic changes occurring in human trabecular meshwork (HTM) cells in primary open-angle glaucoma. Receptor binding of TGFβ2 activates non-canonical extracellular-signal-regulated kinase (ERK) and Rho-associated kinase (ROCK) signaling pathways, both broadly affecting HTM cell behavior. However, exactly how these signaling pathways converge to regulate pathologic HTM cell contractility associated with glaucomatous dysfunction is unclear. Here, we investigated the molecular mechanism underlying TGFβ2-induced pathologic HTM cell contractility, and the crosstalk between ERK and ROCK signaling pathways. We compared soft biomimetic hydrogels composed of collagen type I, elastin-like polypeptide, and hyaluronic acid with conventional stiff glass coverslips. Results show that HTM cell morphology and filamentous (F)-actin organization was affected by the underlying culture substrate: TGFβ2 increased HTM cell contractility via ERK and ROCK signaling pathways by differentially regulating F-actin, α-smooth muscle actin, fibronectin, and phospho-myosin light chain in cells grown on hydrogels compared to glass. Importantly, we showed that ERK inhibition further increased TGFβ2-induced phospho-myosin light chain levels in HTM cells on hydrogels, but not on glass, which translated into hypercontractility of three-dimensional (3D) HTM cell-laden hydrogels. ROCK inhibition had precisely the opposite effects and potently relaxed the TGFβ2-induced hydrogels. This suggests that ERK signaling negatively regulates ROCK-mediated HTM cell contractility, and that impairment of this crosstalk balance contributes to the pathologic contraction associated with the glaucomatous stressor TGFβ2. These findings emphasize the critical importance of using 3D tissue-mimetic extracellular matrix substrates for investigating HTM cell physiology and glaucomatous pathophysiologyin vitro.
The effects of introgression across thousands of quantitative traits revealed by gene expression in wild tomatoes
Authors: Hibbins Mark S. , Hahn Matthew W. 
Published: July 2021

AbstractIt is now understood that introgression can serve as powerful evolutionary force, providing genetic variation that can shape the course of trait evolution. Introgression also induces a shared evolutionary history that is not captured by the species phylogeny, potentially complicating evolutionary analyses that use a species tree. Such analyses are often carried out on gene expression data across species, where the measurement of thousands of trait values allows for powerful inferences while controlling for shared phylogeny. Here, we present a Brownian motion model for quantitative trait evolution under the multispecies network coalescent framework, demonstrating that introgression can generate apparently convergent patterns of evolution when averaged across thousands of quantitative traits. We test our theoretical predictions using whole-transcriptome expression data from ovules in the wild tomato genus Solanum. Examining two sub-clades that both have evidence for post-speciation introgression, but that differ substantially in its magnitude, we find patterns of evolution that are consistent with histories of introgression in both the sign and magnitude of ovule gene expression. Additionally, in the sub-clade with a higher rate of introgression, we observe a correlation between local gene tree topology and expression similarity, implicating a role for introgressed cis-regulatory variation in generating these broad-scale patterns. Our results have important implications for the study of gene expression evolution—and quantitative trait evolution more broadly—in systems with evidence of introgression.
CRISPR/Cas9 deletions induce adverse on-target genomic effects leading to functional DNA in human cells
Authors: Geng Keyi , Merino Lara G. , Wedemann Linda , Martens Aniek , Sobota Małgorzata , Sanchez Yerma P. , Søndergaard Jonas Nørskov , White Robert J. , Kutter Claudia 
Published: July 2021

ABSTRACTThe CRISPR/Cas9 system is widely used to permanently delete genomic regions by inducing double-strand breaks via dual guide RNAs. However, on-target consequences of Cas9 deletion events have yet to be fully investigated. To characterize Cas9-induced genotypic abnormalities in human cells, we utilized an innovative droplet-based target enrichment approach followed by long-read sequencing and coupled it to a customized de novo sequence assembly. This approach enabled us to dissect the sequence content at kilobase scale within an on-target genomic locus. We here describe extensive genomic disruptions by Cas9, involving a genomic duplication and inversion of the target region as well as integrations of exogenous DNA and interchromosomal DNA fragment rearrangements at the double-strand break sites often at the same time. Although these events altered the genomic composition of the on-target region, we found that the aberrant DNA fragments are still functional, marked by active histones and bound by RNA polymerase III. In HAP1 cells, the integration of the target-derived fragments accelerated cell proliferation in deletion clones. Our findings broaden the consequential spectrum of the Cas9 deletion system, reinforce the necessity of meticulous genomic validations and rationalize extra caution when interpreting results from a deletion event.
Goldilocks and RNA: Where Mg2+ concentration is just right
Authors: Guth-Metzler Rebecca , Mohamed Ahmad Mohyeldin , Cowan Elizabeth T. , Henning Ashleigh , Ito Chieri , Frenkel-Pinter Moran , Wartell Roger M. , Glass Jennifer B. , Williams Loren Dean 
Published: July 2021

AbstractMagnesium, the most abundant divalent cation in cells, catalyzes RNA cleavage but also promotes RNA folding. Because folding can protect RNA from cleavage, we predicted a “Goldilocks peak”, which is a local maximum in RNA lifetime at the Mg2+ concentration required for folding. Here we use simulation and experiment to discover an innate yet sophisticated mechanism of control of RNA lifetime. By simulation we characterized the RNA Goldilocks peak and its dependence on cleavage parameters and extent of folding. Supporting experiments with yeast tRNAPhe and Tetrahymena ribozyme P4-P6 domains show that structured RNA can inhabit a Goldilocks peak in vitro. The Goldilocks peaks are tunable by differences in cleavage rate constants, Mg2+ binding cooperativity, and Mg2+ affinity. Broad ranges of those folding and cleavage parameters produce Goldilocks peaks of different intensities. Goldilocks behavior allows ultrafine control of RNA chemical lifetime, whereas non-folding RNAs do not display a Goldilocks peak. In sum, the effects of Mg2+ on RNA persistence are expected to be pleomorphic, both protecting and degrading RNA. In evolutionary context, Goldilocks behavior may have shaped RNA in an early Earth environment containing Mg2+ and other metals.
High throughput measurement of Arabidopsis thaliana fitness traits using deep learning
Authors: Wang Peipei , Meng Fanrui , Donaldson Paityn , Horan Sarah , Panchy Nicholas L. , Vischulis Elyse , Winship Eamon , Conner Jeffrey K. , Krysan Patrick J. , Shiu Shin-Han , Lehti-Shiu Melissa D. 
Published: July 2021

SummaryRevealing the contributions of genes to plant phenotype is frequently challenging because the effects of loss of gene function may be subtle or be masked by genetic redundancy. Such effects can potentially be detected by measuring plant fitness, which reflects the cumulative effects of genetic changes over the lifetime of a plant. However, fitness is challenging to measure accurately, particularly in species with high fecundity and relatively small propagule sizes such as Arabidopsis thaliana.An image segmentation-based (ImageJ) and a Faster Region Based Convolutional Neural Network (R-CNN) approach were used for measuring two Arabidopsis fitness traits: seed and fruit counts.Although straightforward to use, ImageJ was error-prone (correlation between true and predicted seed counts, r2=0.849) because seeds touching each other were undercounted. In contrast, Faster R-CNN yielded near perfect seed counts (r2=0.9996) and highly accurate fruit counts (r2=0.980).By examining seed counts, we were able to reveal fitness effects for genes that were previously reported to have no or condition-specific loss-of-function phenotypes.Our study provides models to facilitate the investigation of Arabidopsis fitness traits and demonstrates the importance of examining fitness traits in the study of gene functions.
CHROMOMETHYLTRANSFERASE3/ KRYPTONITE maintain the sulfurea paramutation in Solanum lycopersicum
Authors: Martinho Cláudia , Wang Zhengming , Ghigi Andrea , Buddle Sarah , Barbour Felix , Yarur Antonia , Gouil Quentin , Müller Sebastian , Stam Maike , Liu Chang , Baulcombe David C. 
Published: July 2021

AbstractParamutation involves the transfer of a repressive epigenetic mark from a silent allele to an active homologue and, consequently, non-Mendelian inheritance. In tomato the sulfurea (sulf) paramutation is associated with a high level of CHG hypermethylation in a region overlapping the transcription start site of the SlTAB2 gene that affects chlorophyll synthesis. The CCG sub-context hypermethylation is under-represented at this region relative to CTG or CAG implicating the CHROMOMETHYLTRANSFERASE3 (CMT3) in paramutation at this locus. Consistent with this interpretation, loss of CMT3 function leads to loss of the sulf chlorosis, the associated CHG hypermethylation and paramutation. Loss of KRYPTONITE (KYP) histone methyl transferase function has a similar effect linked to reduced H3K9me2 at the promoter region of SlTAB2 and a shift in higher order chromatin structure at this locus. Mutation of the largest subunit of RNA polymerase V (PolV) in contrast does not affect sulf paramutation. These findings indicate the involvement of a CMT3/KYP dependent feedback rather than the PolV-dependent pathway leading to RNA directed DNA methylation (RdDM) in the maintenance of paramutation.
Qualification of ELISA and neutralization methodologies to measure SARS-CoV-2 humoral immunity using human clinical samples
Authors: Larsen Sasha E. , Berube Bryan J. , Pecor Tiffany , Cross Evan , Brown Bryan P. , Williams Brittany , Johnson Emma , Qu Pingping , Carter Lauren , Wrenn Samuel , Kepl Elizabeth , Sydeman Claire , King Neil P. , Baldwin Susan L. , Coler Rhea N. 
Published: July 2021

AbstractIn response to the SARS-CoV-2 pandemic many vaccines have been developed and evaluated in human clinical trials. The humoral immune response magnitude, composition and efficacy of neutralizing SARS-CoV-2 are essential endpoints for these trials. Robust assays that are reproducibly precise, linear, and specific for SARS-CoV-2 antigens would be beneficial for the vaccine pipeline. In this work we describe the methodologies and clinical qualification of three SARS-CoV-2 endpoint assays. We developed and qualified Endpoint titer ELISAs for total IgG, IgG1, IgG3, IgG4, IgM and IgA to evaluate the magnitude of specific responses to the trimeric spike (S) antigen and total IgG specific to the spike receptor binding domain (RBD) of SARS-CoV-2. We also qualified a pseudovirus neutralization assay which evaluates functional antibody titers capable of inhibiting the entry and replication of a lentivirus containing the Spike antigen of SARS-CoV-2. To complete the suite of assays we qualified a plaque reduction neutralization test (PRNT) methodology using the 2019-nCoV/USA-WA1/2020 isolate of SARS-CoV-2 to assess neutralizing titers of antibodies in plasma from normal healthy donors and convalescent COVID-19 individuals.
Prioritizing the economic indicators of SSC: an integrative QFD approach of performance prism and BSC
Authors: Goharshenasan Ali , Sheikh Aboumasoudi Abbas , Shahin Arash , Ansari Azarnoush 
Published: July 2021

PurposeThis paper aims to propose an integrative economic model of the GRI (Global Reporting Initiative) and performance prism based on concurrent engineering and developed balanced scorecard (BSC).Design/methodology/approachIn this paper, the supplier aspect added to the basic BSC framework, a quality function deployment (QFD) developed in four phases and the economic GRI priorities were determined. Finally, the outcomes of QFD were used in Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) for ranking the economic indicators.FindingsThe indicators of financial interpretation, risks and opportunities had the first rank in learning and growth, internal processes, customer and financial BSC aspects, and they had the second rank only in the suppliers' BSC aspect.Research limitations/implicationsIn this paper, merely the economic indicators of the GRI standard was studied, and no comparison was made between the variables of the other standards and the GRI standard.Originality/valueThe most important contribution of this study is merging the supplier aspect and BSC based on the concept of suppliers, inputs, process, outputs and customers (SIPOC) in supply chain analysis. Achieving economic sustainability by a concurrent engineering approach is another novelty of this paper. The proposed model was examined in the tile and ceramic industry for the first time.
External sources of finance and value creation of Chinese mergers and acquisitions: does ownership type matter?
Authors: Bi Xiaogang , Boateng Agyenim 
Published: July 2021

Purpose
This paper aims to investigate the effects of external sources of finance and ownership type on the value creation of Chinese acquiring firms.

Design/methodology/approach
The data set consists of domestic-listed mainland Chinese firms engaged in domestic mergers and acquisitions during the period 2004–2012. Standard event study methodology and cross-sectional regression analysis are used to examine the relationship between external finance, ownership type and value creation of the acquiring firms.

Findings
This paper finds that whereas bank financing is positively related to the firm value of privately-owned enterprises (POEs), bank financing has a negative but insignificant influence on the firm value of state-owned enterprises (SOEs). Moreover, equity financing has a negative and significant effect on the value creation of SOE acquirers, however, this appears not to be the case of POEs.

Research limitations/implications
The results suggest that the capital markets in China take into consideration the discriminatory and cheap access to bank loans available to SOEs as negative signals to stock markets, which cause capital markets to punish SOEs through price depreciation. Conversely, capital markets reward POEs in respect of Chinese banks’ discrimination against POEs in bank financing.

Practical implications
The results suggest that the capital markets in China take into account the discriminatory and cheap access to bank loans available to SOEs as negative signals to stock markets, which cause capital markets to punish SOEs through price depreciation. Conversely, capital markets reward POEs in respect of Chinese banks’ discrimination against POEs in bank financing.

Originality/value
The results of this study show that external sources of finance and ownership type influence acquiring firm value in an environment where the corporate governance system is weak and the banking sector is dominated by state banks. Further reforms in the financial sector, particularly, in the corporate governance system appear warranted.
Social and ethical practices and firm value: the moderating effect of green innovation: evidence from international ESG data
Authors: Chouaibi Salim , Chouaibi Jamel 
Published: July 2021

Purpose
This study aims to examine the potential effect of integrating social and ethical practices into strategy on the market valuation of environmental, social and governance (ESG) businesses using the moderating effect of green innovation.

Design/methodology/approach
The sample used consisted of 523 international firms listed on the ESG index and headquartered in North America and Western Europe, forming an unbalanced panel of 7,845 observations spanning the period 2005–2019. The authors run a fixed-effects panel regression model using the Thomson Reuters ASSET4 to test the relationship between societal and ethical practices and the stock market value creation. Similarly, as an extension of the research, this paper exploits two robustness analyzes. The authors tested the dynamic dimension of the data set through the generalized moment method and the effect of the legal system.

Findings
Evidence reveals a significant positive relationship between societal and ethical practices and businesses’ market valuation. The empirical results indicate that societal and ethical strengths increase firm value with the moderating effect of green innovation and weaknesses reduce it. The results found with the dynamic dimension of the data set indicate the existence of continuity between firm values over time.

Research limitations/implications
Given the long study period, many firms with missing data were eliminated. To avoid the small sample size, countries with few observations were included, which led to an uneven distribution between observations per country.

Practical implications
Findings from this paper can help ESG firms to consider their future growth opportunities in a context where the approach of business ethics occupies a central position in business valuation.

Originality/value
This study is the only study that provides ESG companies with seven different nationalities with evidence for the effect of social and ethical practices regarding market valuation. This paper is also relevant as it addresses the relationship between social effectiveness and financial efficiency, as well as the dynamic effect of this relationship.
Driving forces of repurchasing social enterprise products
Authors: Wu Hsueh Ling , Chen Tser Yieth , Chen Bo Heng 
Published: July 2021

PurposeThis paper aims to use utilitarian benefits, hedonic benefits and corporate social responsibility to influence the consumer’s sense of brand identity and brand trust in social enterprise products and, thus, favourably affect repurchase intention.Design/methodology/approachThis study dispatched 430 questionnaires in Taiwan. The top six social enterprises in the organic food industry in Taiwan that accounted for 84.0% of total green organic stores and they were selected for field investigation. This study used structural equation modelling.FindingsThe main path indicates that corporate social responsibility has a largely positive effect going through brand identity and brand trust, and then affecting the decision to repurchase. Therefore, the image of` corporate social responsibility was the greatest driving force. The secondary path indicated that utilitarian benefits positively affected brand identity and brand trust, which, in turn, positively affected repurchase intention. Therefore, utilitarian benefits were the secondary driving force of repurchasing social enterprise products.Practical implicationsThis study indicates that social enterprises need to carry out effective corporate social responsibility to create a sense of strong brand trust in consumers’ minds. Empirical results can benefit social marketers for their product launches and promotions. Social enterprises can realize consumer differentiation preferences. With the effective grasp the information of consumer perception, the social marketers can turn passive into active and catch the marketing opportunities by the brand identity and trust to the content of the marketing programs design.Originality/valueThe novelty of this study is to propose an identity-repurchase intention (IRI) model, based on consumer information processing lens and self-congruency theory, to investigate the social enterprise perspective.
Tree species mixing affects soil microbial functioning indirectly via root and litter traits and soil parameters in European forests
Authors: Gillespie Lauren M. , Hättenschwiler Stephan , Milcu Alexandru , Wambsganss Janna , Shihan Ammar , Fromin Nathalie 
Published: July 2021

Abstract

Plant community composition influences soil microbial communities through plant trait variations that lead to changes in nutrient and organic carbon inputs into the soil by root exudates and plant litter. Although plant litter and living roots are known to influence microbial functioning independently, their relative effects are rarely measured simultaneously in naturally occurring plant communities.

Here, we sought to evaluate how forest floor litter and absorptive roots affect broad functions of soil microbial communities, and how this may be influenced by tree species mixing. To do so, forest floor litter, absorptive roots and soil were sampled from mono‐specific and three‐species mixed stands in four mature, natural forest ecosystems across Europe. The direct effects of tree species mixing, its indirect effects via litter and root traits, and the effects of soil parameters on microbial biomass, catabolic activity and diversity, and denitrification were analysed.

Results did not show direct tree mixture effects on the soil microbial parameters we measured but did suggest indirect influences via tree mixture effects on traits of above‐ground litter and absorptive roots and soil parameters. Mixed forests composed of any three tree species modified soil microbial functioning by influencing nutrient availability in forest floor litter and root resource acquisition. Tree mixing also modified soil microbial functioning and catabolic diversity by influencing soil fertility and physicochemical properties.

Our findings suggest an indirect but present influence of tree species mixing on the activity of heterotrophic soil microbial communities across four different forest ecosystems ranging from Mediterranean to boreal forests. Our study contributes to a better mechanistic understanding of mixed tree species effects on soil microbial functioning via the modification of forest floor litter properties and traits of absorptive roots represented by the tree community beyond simple species number consideration, and potentially via soil properties.

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