bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane Ca2+permeability and IP3R2 dependent Ca2+-induced Ca2+release are essential for astrocytic intracellular Ca2+elevation upon neuronal stimulation at the mouse hippocampal CA3 - CA1 excitatory synapses
Authors: Hjukse Jarand B. , Vindedal Gry Fluge , Sprengel Rolf , Jensen Vidar , Nagelhus Erlend A. , Tang Wannan 
Published: October 2020

AbstractAstrocytes are intricately involved in the activity of neural circuits, however, their basic physiology of interacting with neurons remains controversial. Using dual-indicator two-photon imaging of neurons and astrocytes during stimulations of hippocampal CA3 - CA1 Schaffer collateral (Scc) excitatory synapses, we report that under physiological conditions, the increased glutamate released from the higher frequency stimulation of neurons can accelerate local astrocytic Ca2+levels. As consequences of extracellular glutamate clearance and maintaining of astrocytic intracellular Na+homeostasis, the increase of astrocytic membrane Ca2+permeability via Na+/Ca2+exchanger (NCX) reverse mode is the primary reason of eliciting astrocytic intracellular Ca2+elevation upon neuronal stimulation. This Ca2+-induced Ca2+release is dependent on inositol triphosphate receptor type 2 (IP3R2). In addition, ATP released from Scc excitatory synapses can contribute to this molecular mechanism of Ca2+-induced Ca2+release in astrocytes.
Primed smooth muscle cells acting as first responder cells in disease
Authors: Worssam Matt D , Lambert Jordi , Oc Sebnem , Taylor Annabel L , Dobnikar Lina , Chappell Joel , Harman Jennifer L , Figg Nichola L , Finigan Alison , Foote Kirsty , Uryga Anna K , Bennett Martin R , Spivakov Mikhail , Jørgensen Helle F 
Published: October 2020

ABSTRACTRationaleVascular smooth muscle cell (VSMC) dysregulation is a hallmark of vascular disease, including atherosclerosis. In particular, the majority of cells within atherosclerotic lesions are generated from pre-existing VSMCs and a clonal nature has been documented for VSMC-derived cells in multiple disease models. However, the mechanisms underlying the generation of oligoclonal lesions and the phenotype of proliferating VSMCs are unknown.ObjectiveTo understand the cellular mechanisms underlying clonal VSMC expansion in disease.Methods and ResultsHere we analyse clonal dynamics in multi-color lineage-traced animals over time after vessel injury. We demonstrate that VSMC proliferation is initiated in a small fraction of VSMCs that initially expand clonally in the medial layer and then migrate to form the oligoclonal neointima. Selective activation of VSMC proliferation also occursin vitro, suggesting that this is a cell-autonomous feature. Mapping of VSMC trajectories using single-cell RNA-sequencing reveals a continuum of cellular states after injury and suggests that VSMC proliferation initiates in cells that have downregulated the contractile phenotype and show evidence of pronounced phenotypic switching. We show that proliferation is associated with induced expression of stem cell antigen 1 (SCA1) and the expression signature previously identified in SCA1+ VSMCs in healthy arteries. A remarkably increased proliferation of SCA1+ VSMCs, directly validated in functional assays, indicates that SCA1+ VSMCs act as “first responders” in vascular injury. Early atherosclerotic lesions also had clonal VSMC contribution and we show that the proliferation-associated injury response is conserved in plaque VSMCs, extending these findings to atherosclerosis. Finally, we identify VSMCs in healthy human arteries that correspond to the SCA1+ state in mouse VSMCs and show that genes identified as differentially expressed in this human VSMC subpopulation are enriched for genes showing genetic association with cardiovascular disease.ConclusionsWe show that cell-intrinsic, selective VSMC activation drives clonal proliferation after injury and in atherosclerosis. Our study suggests that healthy mouse and human arteries contain VSMCs characterised by expression of disease-associated genes that are predisposed for proliferation. Targeting such “first responder” cells in patients undergoing vascular surgery could effectively prevent injury-associated VSMC activation and neoatherosclerosis.
Parental CG and CHG methylation variation is associated with allelic-specific expression in elite hybrid rice
Authors: Ma Xuan , Xin Feng , Jia Qingxiao , Zhang Qinglu , Hu Tong , Wu Baoguo , Shao Lin , Zhao Yu , Zhang Qifa , Zhou Dao-Xiu 
Published: October 2020

ABSTRACTHeterosis refers to the superior performance of the hybrid over the inbred parental lines. Besides genetic variation, epigenetic difference between the parental lines has been suggested to be involved in heterosis. However, precise nature and extent of parental epigenome difference and reprograming in hybrids governing heterotic gene expression remain unclear. In this work, we analyzed DNA methylomes and transcriptomes of the widely cultivated and genetically studied elite hybrid rice SY63, the reciprocal hybrid, and the parental varieties ZS97 and MH63, of which the high-quality reference genomic sequences are available. We show that the parental varieties display important variation in genic methylation at CG and CHG (H=A, C, or T) sequences. Compared with the parents the hybrids display dynamic methylation variation during development. However, many parental differentially methylated regions (DMR) at CG and CHG sites are maintained in the hybrid. Only a small fraction of the DMRs display non-additive DNA methylation variation which, however, shows no overall correlation with gene expression variation. By contrast, most of the allelic-specific expression (ASE) genes in the hybrid are associated with DNA methylation and the ASE negatively correlates with allelic-specific methylation (ASM) at CHG but positively at CG sites. The results reveal a specific DNA methylation reprogramming pattern in the hybrid rice and point to a role of parental CG and CHG methylation divergence in allelic specific expression that has been associated with phenotype variation and hybrid vigor in several plant species.One sentence summaryParental CG and CHG methylation divergence is maintained in hybrid and is related to allelic specific expression associated with phenotype variation and hybrid vigor.
DROL1subunit of U5 snRNP in the spliceosome is specifically required to splice AT–AC-type introns inArabidopsis
Authors: Suzuki Takamasa , Shinagawa Tomomi , Niwa Tomoko , Akeda Hibiki , Hashimoto Satoki , Tanaka Hideki , Hiroaki Yoko , Yamasaki Fumiya , Mishima Hiroyuki , Kawai Tsutae , Higashiyama Tetsuya , Nakamura Kenzo 
Published: October 2020

SummaryAnArabidopsismutant nameddefective repression of OLE3::LUC 1(drol1) was originally isolated as a mutant with defects in the repression ofOLEOSIN3(OLE3) after seed germination. In this study, we show that DROL1 is anArabidopsishomolog of yeast DIB1, a subunit of U5 snRNP in the spliceosome. It is also part of a new subfamily that is specific to a certain class of eukaryotes. Comprehensive analysis of the intron splicing using RNA-Seq analysis of thedrol1mutants revealed that most of the minor introns with AT–AC dinucleotide termini had reduced levels of splicing. Only two nucleotide substitutions from AT–AC to GT–AG enabled AT–AC-type introns to be spliced indrol1mutants. Forty-eight genes, including those having important roles in abiotic stress responses and cell proliferation, exhibited reduced splicing of AT–AC-type introns in thedrol1mutants. Additionally,drol1mutant seedlings showed retarded growth, similar to that caused by the activation of abscisic acid signaling, possibly as a result of reduced AT–AC-type intron splicing in the endosomal Na+/H+antiporters and plant-specific histone deacetylases. These results indicate that DROL1 is specifically involved in the splicing of minor introns with AT–AC termini, and that this plays an important role in plant growth and development.Significance statementDefective Repression of OLE3::LUC 1(DROL1)is a homolog of yeast DIB1, which is a subunit of the U5 snRNP in the spliceosome, but is also part of a new subfamily that is specific to a certain class of eukaryotes. Using RNA-Seq we show that introns with AT–AC dinucleotide termini were specifically retained in the transcriptome ofdrol1mutants and that their splicing plays an important role in plant growth and development.
Identification of potential inhibitory analogs of metastasis tumor antigens (MTAs) using bioactive compounds: revealing therapeutic option to prevent malignancy
Authors: Banik Anik , Ahmed Sheikh Rashel , Sajib Emran Hossain , Deb Anamika , Sinha Shiuly , Azim Kazi Faizul 
Published: October 2020

AbstractThe deeper understanding of metastasis phenomenon and detection of drug targets could be a potential approach to minimize cancer mortality. In this study, attempts were taken to unmask novel therapeutics to prevent metastasis and cancer progression. Initially, we explored the physiochemical, structural and functional insights of three metastasis tumor antigens (MTAs) and evaluated some plant based bioactive compounds as potent MTA inhibitors. From 50 plant metabolites screened, isoflavone, gingerol, citronellal and asiatic acid showed maximum binding affinity with all three MTA proteins. The ADME analysis detected no undesirable toxicity that could reduce the drug likeness properties of top plant metabolites. Moreover, molecular dynamics studies revealed that the complexes were stable and showed minimum fluctuation at molecular level. We further performed ligand based virtual screening to identify similar drug molecules using a large collection of 3,76,342 compounds from DrugBank. The results suggested that several structural analogs (e.g. Tramadol, Nabumetone, DGLA, Hydrocortisone) may act as agonist to block the MTA proteins and inhibit cancer progression at early stage. The study could be useful to develop effective medications against cancer metastasis in future. Due to encouraging results, we highly recommend furtherin vitroandin vivotrials for the experimental validation of the findings.
Reovirus RNA recombination is sequence directed and generates internally deleted defective genome segments during passage
Authors: Smith Sydni Caet , Gribble Jennifer , Diller Julia R. , Wiebe Michelle A. , Thoner Timothy W. , Denison Mark R. , Ogden Kristen M. 
Published: October 2020

ABSTRACTFor viruses with segmented genomes, genetic diversity is generated by genetic drift, reassortment, and recombination. Recombination produces RNA populations distinct from full-length gene segments and can influence viral population dynamics, persistence, and host immune responses. Viruses in theReoviridaefamily, including rotavirus and mammalian orthoreovirus (reovirus), have been reported to package segments containing rearrangements or internal deletions. Rotaviruses with RNA segments containing rearrangements have been isolated from immunocompromised and immunocompetent children andin vitrofollowing serial passage at high multiplicity. Reoviruses that package small, defective RNA segments have established chronic infections in cells and in mice. However, the mechanism and extent ofReoviridaeRNA recombination are undefined. Towards filling this gap in knowledge, we determined the titers and RNA segment profiles for reovirus and rotavirus following serial passage in cultured cells. The viruses exhibited occasional titer reductions characteristic of interference. Reovirus strains frequently accumulated segments that retained 5′ and 3′ terminal sequences and featured large internal deletions, while similar segments were rarely detected in rotavirus populations. Using next-generation RNA-sequencing to analyze RNA molecules packaged in purified reovirus particles, we identified distinct recombination sites within individual viral gene segments. Recombination junction sites were frequently associated with short regions of identical sequence. Taken together, these findings suggest that reovirus accumulates defective gene segments featuring internal deletions during passage and undergoes sequence-directed recombination at distinct sites.IMPORTANCEViruses in theReoviridaefamily include important pathogens of humans and other animals and have segmented RNA genomes. Recombination in RNA virus populations can facilitate novel host exploration and increased disease severity. The extent, patterns, and mechanisms ofReoviridaerecombination and the functions and effects of recombined RNA products are poorly understood. Here, we provide evidence that mammalian orthoreovirus regularly synthesizes RNA recombination products that retain terminal sequences but contain internal deletions, while rotavirus rarely synthesizes such products. Recombination occurs more frequently at specific sites in the mammalian orthoreovirus genome, and short regions of identical sequence are often detected at junction sites. These findings suggest that mammalian orthoreovirus recombination events are directed in part by RNA sequences. An improved understanding of recombined viral RNA synthesis may enhance our capacity to engineer improved vaccines and virotherapies in the future.
The genomic and transcriptomic foundations of viviparous seed development in mangroves
Authors: Qiao Hongmei , Zhou Xiaoxuan , Su Wenyue , Zhao Xing , Jin Pengfei , He Shanshan , Hu Wei , Fu Meiping , Yu Dingtian , Hao Saiqi , Zhang Yuan-Ye , Wang Wenqing , Ye Congting , Li Qingshun Quinn , Shen Yingjia 
Published: October 2020

AbstractVivipary in plants refers to a specific seed development and reproductive strategy where seeds minimize the dormancy stage and germinate while still attached to their maternal plants. It is one of the most unique adaptive genetic features used by many mangrove species where elongated hypocotyls aid in quick root emergence to anchor the seedling in coastal intertidal wetlands. The genetic mechanisms behind mangrove vivipary, however, remain elusive. Using comparative genomic and transcriptomic technologies to investigate viviparous mangroves and their close inland relatives, we found that a full array of gene expression profiles were altered, including key plant hormone metabolic pathways, high expression of embryonic signature genes, and reduced production of proanthocyanidins and storage proteins. Along with these changes, a major gene regulating seed dormancy,Delay of Germination-1(DOG1), is entirely missing or defunct within the entire linage of the four genera with true viviparous characteristics. These results suggest a systemic level change is required to warrant the genetic program of mangrove vivipary. Understanding of the molecular processes of vivipary could benefit the design of pregerminated propagules for forestation in harsh environments or prevent precocious germination of grain crops pre- and post-harvest.
Conserved cholesterol-related activities of Dispatched drive Sonic hedgehog shedding from the cell membrane
Authors: Ehring K. , Manikowski D. , Froese J. , Goretzko J. , Jakobs P. , Gude F. , Rescher U. , Grobe K. 
Published: October 2020

SummaryThe Sonic hedgehog (Shh) pathway controls embryonic development and tissue homeostasis after birth. Long-lasting questions about this pathway are how dual-lipidated, firmly plasma membrane-associated Shh ligand is released from producing cells to signal to distant target cells, and how the resistance-nodulation-division transporter Dispatched (Disp) regulates this process. Here we show that Disp inactivation in Shh expressing cells specifically impairs proteolytic Shh release from its lipidated terminal peptides, a process called ectodomain shedding. Shh shedding from Disp-deficient cells was restored by pharmacological membrane cholesterol extraction and by overexpressed transgenic Disp or structurally related Patched (Ptc, a putative cholesterol transporter). These data suggest that Disp regulates physiological Shh function via controlled cell surface shedding and that molecular mechanisms shared by Disp and Ptc exercise such sheddase control.
How the egocentric alliance network impacts firm ambidextrous innovation: a three-way interaction model
Authors: Zhang Guiyang , Tang Chaoying 
Published: October 2020

PurposeThe purpose of the paper is to advance a framework that can analyze the impact of the egocentric alliance network on firm ambidextrous innovation holistically. On this purpose, the framework involves and integrates structural holes (SH), alliance functional diversity (AFD) and alliance partner geographical diversity (APGD) that measure network characteristics from structural, relational and nodal perspectives, respectively.Design/methodology/approachThe authors collected multi-source matching panel data including alliance deals, technical patents and financial information during 2000–2017 of the 106 top high-tech firms in the computer, communications, electronics and biopharmaceutical industries and conducted a three-way interaction model to uncover the complex mechanisms from a contingency perspective.FindingsEmpirical results show that SH as structural capital is positive to both exploitative and exploratory innovation. Both AFD as relational capital and APGD as cognitive capital positively moderate the SH-exploitative innovation nexus rather than the SH-exploratory innovation nexus. APGD and AFD co-moderate the relationship between SH and firm ambidextrous innovation in the way that when APGD and AFD are both high, SH has the strongest positive impacts on firm exploitative and exploratory innovation.Originality/valueThis research provides new insights into the benefit-cost paradox of the structural brokerage position (SH) by uncovering relational (AFD) and nodal (APGD) network characteristics that impact the trade-off. Also, it contributes to social capital theory by differentiating three dimensions of network capital (structural, relational and cognitive capital) and integrating them into ambidextrous innovation research. Finally, the findings give firms enlightenment to configure their egocentric alliance network for innovation ambidexterity.
Say no to wrongdoing: the serial mediation model of responsible leadership and whistleblowing intentions
Authors: Akhtar Muhammad Waheed , Javed Muzhar , Syed Fauzia , Aslam Muhammad Kashif , Hussain Khalid 
Published: October 2020

PurposeDrawing on the role theory, this study examines how responsible leadership invokes whistleblowing intentions in employees by intervening through “trust in leader” and “person-organization fit.”Design/methodology/approachUsing the Hayes (2013) approach, the authors tested the model by collecting a multi-wave data from banking sector employees.FindingsResults of the study show that responsible leadership kindles whistleblowing intentions in banks' employees. Further, the results reveal that both “trust in leader” and “person-organization fit” individually mediate the relationship between responsible leadership and whistleblowing intentions. Moreover, we found that the relationship between responsible leadership and whistleblowing intentions is serially mediated through “trust in leader” and “person-organization fit.”Originality/valueThe current study contributes to whistleblowing intentions and responsible leadership literature by suggesting “trust in leader” and “person-organization fit” as process through which responsible leaders kindle employee's outcomes.
The promotion of sustainable development in higher education institutions: top-down bottom-up or neither?
Authors: Mazon Gisele , Pereira Ribeiro João Marcelo , Montenegro de Lima Carlos Rogerio , Castro Brenda Caroline Geraldo , Guerra José Baltazar Salgueirinho Osório de Andrade 
Published: October 2020

PurposeThis paper aims to analyze the sustainability approach within higher education institutions. Universities, as institutions of knowledge, play an important and strategic role in maximizing social and economic benefits in a hands-on way. However, some studies on sustainable development and HEIs reveal a distancing between students and the application of sustainable initiatives in universities. This fact differs from the premises of the Talloires Declaration, which points to students as a community and as global leaders and ambassadors for sustainability.Design/methodology/approachThis paper mapped the approaches, present in the literature, used to develop sustainable campuses and in particular the apparent dichotomy between the changes indicated as top-down or bottom-up in HEIs. To that end, scientific articles focused on sustainable actions in HEIs were analyzed to identify implementation approaches for sustainable development and student involvement in the process.FindingsResults have shown that sustainability promotion models in universities generally occur in a top-down manner, where students are receptors and not sources of development for sustainable policies in universities. Thus, the authors highlight the importance of students becoming central players in sustainable initiatives.Originality/valueThe article becomes original when it identifies the dichotomy between top-down and bottom-up approaches. It does so through multidimensional scaling and exploratory factorial analysis in scientific articles on the topic Sustainability Funding in Higher Education. These findings show that, unlike what is discussed in the literature, sustainability promotion in universities generally occurs in a top-down manner, where students are receptors and not active agents in promoting sustainability. In response to this, the authors discussed the importance of the bottom-up approach, where they are key players.
Co-creating consistent brand identity with employees in the hotel industry
Authors: Chung Sung-Yun (Ashley) , Byrom John 
Published: October 2020

Purpose
This paper aims to investigate how brand identity is co-created, with a specific focus on how employees contributed to the process in a five-star hotel setting. The focus of this study is on understanding how two hotels planned and executed their brand identity strategy simultaneously, differentiating one from the other and how employees actively participated in this process.

Design/methodology/approach
A longitudinal case study approach was adopted, centred on building the identity of two luxury hotels owned by a single company in Seoul, Korea. Various organizational documents were collected and analyzed to understand the brand identity of the hotels and how brand co-creation has been implemented. In addition, semi-structured in-depth interviews were conducted with 42 employees to understand the brand co-creation process from their perspective.

Findings
The brand co-creation process of the hotels was conducted simultaneously and evolved over the following four phases, with employees’ roles varying in each phase, namely, establishing a clear brand identity strategy; designing and selecting sensory identity; aligning organizational identity; and delivering brand identity through external communication. Employees that participated in brand co-creation enhanced their brand knowledge, developed emotional bonds with the brand and were motivated to deliver the brand identity. Furthermore, those that immersed themselves in the new brand identities were able to enable positive guest perceptions towards the brand image, which consequently enhanced employees’ pride in their work.

Research limitations/implications
This research advances the brand management literature in defining branding and brand identity elements, as well as emphasizing the importance of consistent branding. In addition, the current study expands the scope of internal branding, highlighting the process of brand co-creation and the role of employees as active participants. Moreover, it reveals that employees’ participation enhances not only their brand knowledge but also their emotional bonds with the brand. The proposed conceptual framework demonstrates the flow of branding elements, brand identity elements and the “infinite loop” of employee participation in brand co-creation.

Originality/value
The case study approach adopted here enables an in-depth investigation of employee participation in brand co-creation, including their different roles and activities in the process; a phenomenon that has not been adequately explored in previous research.