bluuebunny/crossref_metadata_2025 huggingface dataset:
The active repertoire ofEscherichia colipeptidoglycan amidases varies with physiochemical environment
Authors: Mueller Elizabeth A. , Iken Abbygail G. , Öztürk Mehmet Ali , Schmitz Mirko , Di Ventura Barbara , Levin Petra Anne
Published: October 2020

Nearly all bacteria are encased in a peptidoglycan cell wall, an essential crosslinked matrix of polysaccharide strands and short peptide stems. In the Gram-negative model organismEscherichia coli, more than forty cell wall synthases and autolysins coordinate the growth and division of the peptidoglycan sacculus in the periplasm. The precise contribution of many of these enzymes to cell wall metabolism remains unclear due to significant apparent redundancy, particularly among the cell wall autolysins.E. coliproduces three major LytC-type-N-acetylmuramoyl-L-alanine amidases, which share a role in separating the newly formed daughter cells during cytokinesis. Here, we reveal two of the three amidases exhibit growth medium-dependent changes in activity. Specifically, we report acidic growth conditions stimulate AmiB—and to a lesser extent, AmiC—activity. Combining computational and genetic analysis, we demonstrate that low pH-dependent stimulation of AmiB requires three periplasmic amidase activators: EnvC, NlpD, and YgeR. Altogether, our findings support overlapping, but not redundant, roles for theE. coliamidases in cell separation and illuminate the physiochemical environment as an important mediator of cell wall enzyme activity.

IMPORTANCE

Penicillin and related β-lactam antibiotics targeting the bacterial cell wall synthesis are among the most commonly prescribed antimicrobials worldwide. However, rising rates of antibiotic resistance and tolerance jeopardize their continued clinical use. Development of new cell wall active therapeutics, including those targeting cell wall autolysins, has been stymied in part due to high levels of apparent enzymatic redundancy. In this study, we report a subset ofE. coliamidases involved in cell separation during cell division are not redundant and instead are preferentially active during growth in distinct pH environments. Specifically, we discoverE. coliamidases AmiB and AmiC are activated by acidic pH. Three semi-redundant periplasmic regulators—NlpD, EnvC, and YgeR—collectively mediate low pH-dependent stimulation of amidase activity. This discovery contributes to our understanding of how the cell wall remains robust across diverse environmental conditions and reveals opportunities for the development of condition-specific antimicrobial agents.
3D analysis of the synaptic organization in the Entorhinal cortex in Alzheimer’s disease
Authors: Domínguez-Álvaro M , Montero-Crespo M , Blazquez-Llorca L , Plaza-Alonso S , Cano-Astorga N , DeFelipe J , Alonso-Nanclares L
Published: October 2020

The entorhinal cortex (EC) is especially vulnerable in the early stages of Alzheimer’s disease (AD). In particular, cognitive deficits have been linked to alterations in the upper layers of EC. In the present report, we examined layers II and III from eight human brain autopsies (four subjects with no recorded neurological alterations and four AD cases). We used stereological methods to assess cortical atrophy of the EC, and possible changes in the volume occupied by different cortical elements (neuronal and glial cell bodies; blood vessels; and neuropil). We performed 3D ultrastructural analyses of synapses using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) to examine possible alterations related to AD.

At the light microscope level, we found a significantly lower volume fraction occupied by neuronal bodies in layer III and a higher volume fraction occupied by glial cell bodies in layer II in AD cases. At the ultrastructural level we observed that (i) there was a significantly lower synaptic density in both layers in AD cases; (ii) synapses were larger and more complex in layer II in AD cases; and (iii) there was a greater proportion of small and simple synapses in layer III in AD cases than in control individuals. These structural differences may play a role in the anatomical basis for the impairment of cognitive functions in AD.

Significant Statement

Analysis of the synaptic characteristics provides critical data on synaptic organization. Using 3D electron microscopy, the present study shows the synaptic organization of the neuropil of the human entorhinal cortex (EC) at the ultrastructural level. The EC is especially vulnerable in the early stages of Alzheimer’s disease (AD). Our present results show structural differences that may contribute as anatomical basis for the impairment of cognitive functions in AD. Thus, these results may help to understand the relationship between alterations of the synaptic circuits and the cognitive deterioration in AD.
Dynein-dynactin segregate meiotic chromosomes inC. elegansspermatocytes
Authors: Barbosa Daniel J. , Teixeira Vanessa , Duro Joana , Carvalho Ana X. , Gassmann Reto
Published: October 2020

The dynactin complex is an essential co-factor of the microtubule-based motor dynein. Dynein-dynactin have well-documented roles in spindle assembly and positioning duringC. elegansfemale meiosis and embryonic mitosis, while dynein-dynactin’s contribution to male meiosis has not been investigated. Here, we characterize the G33S mutation in DNC-1’s N-terminal microtubule binding domain, which corresponds to G59S in the human dynactin subunit p150/Glued that causes motor neuron disease. In spermatocytes,dnc-1(G33S)delays spindle assembly and penetrantly inhibits anaphase spindle elongation in meiosis I, which prevents homologous chromosome segregation and generates aneuploid sperm with an extra centrosome. Consequently, embryos produced bydnc-1(G33S)hermaphrodites exhibit a high incidence of tetrapolar mitotic spindles, yetdnc-1(G33S)embryos with bipolar spindles proceed through early mitotic divisions without errors in chromosome segregation. Deletion of the DNC-1 N-terminus shows that defective meiosis indnc-1(G33S)spermatocytes is not due to DNC-1’s inability to interact with microtubules. Rather, our results suggest that the DNC-1(G33S) protein, which is aggregation-pronein vitro, is less stable in spermatocytes than the early embryo, resulting in different phenotypic severity in the two dividing tissues. Thus, the unusual hypomorphic nature of thednc-1(G33S)mutant reveals that dynein-dynactin drive meiotic chromosome segregation in spermatocytes and illustrates that the extent to which protein misfolding leads to loss of function can vary significantly between cell types.
Filopodia-based contact stimulated collective migration drives tissue morphogenesis
Authors: Bischoff Maik C. , Lieb Sebastian , Renkawitz-Pohl Renate , Bogdan Sven
Published: October 2020

Cells migrate collectively to form tissues and organs during morphogenesis. Contact inhibition of locomotion (CIL) drives collective migration by inhibiting lamellipodial protrusions at cell-cell contacts and promoting polarization at the leading edge. Here, we report on a CIL-related collective cell behavior of myotubes that lack lamellipodial protrusions, but instead use filopodia to move as a cohesive cluster in a formin-dependent manner. Genetic, pharmacological and mechanical perturbation analyses reveal essential roles of Rac2, Cdc42 and Rho1 in myotube migration. They differentially control not only protrusion dynamics but also cell-matrix adhesion formation. Here, active Rho1 GTPase localizes at retracting free edge filopodia. Rok-dependent actomyosin contractility does not mediate a contraction of protrusions at cell-cell contacts but likely plays an important role in the constriction of supracellular actin cables.

We propose that contact-dependent asymmetry of cell-matrix adhesion drives directional movement, whereas contractile actin cables contribute to the integrity of the migrating cell cluster.
COVID-19: Variant screening, an important step towards precision epidemiology
Authors: Chattopadhyay Amrita , Lu Tzu-Pin , Shih Ching-Yu , Lai Liang-Chuan , Tsai Mong-Hsun , Chuang Eric Y.
Published: October 2020

Precision epidemiology using genomic technologies allows for a more targeted approach to COVID-19 control and treatment at individual and population level, and is the urgent need of the day. It enables identification of patients who may be at higher risk than others to COVID-19-related mortality, due to their genetic architecture, or who might respond better to a COVID-19 treatment. The COVID-19 virus, similar to SARS-CoV, uses the ACE2 receptor for cell entry and employs the cellular serine protease TMPRSS2 for viral S protein priming. This study aspires to present a multi-omics view of how variations in theACE2andTMPRSS2genes affect COVID-19 infection and disease progression in affected individuals. It reports, for both genes, several variant and gene expression analysis findings, through (i) comparison analysis over single nucleotide polymorphisms (SNPs), that may account for the difference of COVID-19 manifestations among global sub-populations; (ii) calculating prevalence of structural variations (copy number variations (CNVs) / insertions), amongst populations; and (iii) studying expression patterns stratified by gender and age, over all human tissues. This work is a good first step to be followed by additional studies and functional assays towards informed treatment decisions and improved control of the infection rate.
Testing the Role of Δ9-Tetrahydrocannabinol During Adolescence as a Gateway Drug: Behavioural, Brain Imaging and Transcriptomic Studies
Authors: Orihuel Javier , Capellán Roberto , Roura-Martínez David , Ucha Marcos , Gómez-Rubio Laura , Valverde Claudia , Casquero-Veiga Marta , Soto-Montenegro María Luisa , Desco Manuel , Vives Marta Oteo , Moragues Marta Ibáñez , Calvo Natalia Magro , Morcillo Miguel Ángel , Ambrosio Emilio , Higuera-Matas Alejandro
Published: October 2020

Cannabis is widely consumed by adolescents, and is also a potential prior step leading to the use of other drugs later in life (Gateway Hypothesis); however, the evidence for this hypothesis is controversial. This work aimed to increase our understanding of the long-term consequences of adolescent exposure to Δ9-tetrahydrocannabinol (THC) and to test the Gateway Hypothesis, experimentally. We exposed rats of both sexes to THC and studied its effects on reward-related processes, brain morphology (MRI), metabolism (1H-MRS), function (PET) and the transcriptomic profiles of the nucleus accumbens (RNASeq). Lastly, we studied cocaine-induced cellular activation (c-Fos) and cocaine addiction-like behaviours. THC exposure increased Pavlovian to instrumental transfer in males, goal-tracking (regardless of the sex) and impulsivity, but did not affect habit formation. Adolescent THC reduced striatal volume (in females), commissural integrity and ventricular volume. Also, there were lower levels of choline compounds in the cortex of THC-exposed rats and cerebellar hypoactivation in THC-females. THC also modified some of the gene expression programs of the nucleus accumbens, which could contribute to the behavioural features observed. Lastly, THC exposure increased cocaine-induced c-Fos levels in cortical and hypothalamic areas and increased the motivation for cocaine, followed by a higher rebound of use in THC-females after reestablishing low-effort conditions. Critically, acquisition of cocaine self-administration, compulsive seeking, intake under extended access or the incubation of seeking were unaltered. These results suggest that adolescent THC exposure alters psychological and brain development and that the Gateway Hypothesis does not entirely pass the test of preclinical enquiry.
SARS-CoV and SARS-CoV-2 are transmitted through the air between ferrets over more than one meter distance
Authors: Kutter Jasmin S , de Meulder Dennis , Bestebroer Theo M , Lexmond Pascal , Mulders Ard , Fouchier Ron AM , Herfst Sander
Published: October 2020

SARS-CoV-2 emerged in late 2019 and caused a pandemic, whereas the closely related SARS-CoV was contained rapidly in 2003. Here, a newly developed experimental set-up was used to study transmission of SARS-CoV and SARS-CoV-2 through the air between ferrets over more than a meter distance. Both viruses caused a robust productive respiratory tract infection resulting in transmission of SARS-CoV-2 to two of four indirect recipient ferrets and SARS-CoV to all four. A control pandemic A/H1N1 influenza virus also transmitted efficiently. Serological assays confirmed all virus transmission events. Although the experiments did not discriminate between transmission via small aerosols, large droplets and fomites, these results demonstrate that SARS-CoV and SARS-CoV-2 can remain infectious while travelling through the air. Efficient virus transmission between ferrets is in agreement with frequent SARS-CoV-2 outbreaks in mink farms. Although the evidence for airborne virus transmission between humans under natural conditions is absent or weak for SARS-CoV and SARS-CoV-2, ferrets may represent a sensitive model to study interventions aimed at preventing virus transmission.
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

Astrocytes 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

Rationale

Vascular 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.

Objective

To understand the cellular mechanisms underlying clonal VSMC expansion in disease.

Methods and Results

Here 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.

Conclusions

We 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

Heterosis 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 summary

Parental 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

AnArabidopsismutant 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 statement

Defective 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

The 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

For 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.

IMPORTANCE

Viruses 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

Vivipary 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

The 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

Purpose

The 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/approach

The 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.

Findings

Empirical 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/value

This 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

Purpose

Drawing 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/approach

Using the Hayes (2013) approach, the authors tested the model by collecting a multi-wave data from banking sector employees.

Findings

Results 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/value

The 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

Purpose

This 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/approach

This 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.

Findings

Results 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/value

The 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.
Framework on strategic competence performance – a case study of a UK NHS organization
Authors: Darling Chris , Venkitachalam Krishna
Published: October 2020

Purpose

Extant literature on strategic environment analysis confirm broad evidence of studies on competences in the context of private sector organizations. Nevertheless, there is a growing interest and evidence of strategic competence in public sector organizations seeking to deliver improved performance. This paper attempts to determine the strategic competences of a National Health Service (NHS) unit for better organizational performance.

Design/methodology/approach

Based on the qualitative analysis of empirical evidence collected in a UK based NHS case study organization, we arrive at a strategic competence performance framework for the health unit using research carried out through interviews with employees and partner organization members.

Findings

By examining a UK-based qualitative case study, the proposed framework puts forward four strategic competence pillars vital for delivering organizational performance and effectively managing the environment of NHS unit's operations. The four strategic competences that are identified to foster NHS unit's performance are strategic leadership, staff engagement, knowledge transfer and partnership working.

Originality/value

The study examines the environment in which a UK based NHS health unit operates and identify the different strategic competences to deliver organizational performance.
A discussion on using quantitative or qualitative data for assessment of individual competencies
Authors: Macchi Silva Vítor Vasata , Ribeiro José Luis Duarte
Published: October 2020

Purpose

This article presents an investigation of the suitability of using quantitative or qualitative data for individual competencies assessment. Specifically, the primary purpose of this article is to identify if the results provided by quantitative and qualitative instruments focused on individual competencies are convergent.

Design/methodology/approach

In order to do the investigation proposed, a survey on individual competencies comprising a group of employees of the administrative area of a steel company was carried out. A total of 268 evaluations were collected and analyzed.

Findings

The analysis of the employee's performance appraisals provided by ratings and narrative comments indicates a low correlation between these assessments. The reasons for such low correlation include the qualitative assessments variability, the restricted list of competencies used in the quantitative assessments and the analytical format of quantitative assessments.

Originality/value

The study indicates that quantitative and qualitative assessments should be carried out jointly so that they can generate more comprehensive results. When the combined use is not possible, the quantitative approach is better suited for assessing performance, while the qualitative approach provides more valuable insights for boosting people development processes.
Effect of orexin‐A on mitochondrial biogenesis, mitophagy and structure in HEK293‐APPSWE cell model of Alzheimer's disease
Authors: Zhu Zhengyu , Xu LinLin , Cao DeYan , Song ChaoYuan , Wang YuZhen , Li Maoyu , Yan Jieke , Xie ZhaoHong
Published: October 2020

Mitochondrial dysfunction plays a key role in the pathogenesis and progression of Alzheimer's Disease (AD). Our previous studies showed that over expression of AD‐associated mutant β‐amyloid precursor protein (APP) led to abnormalities of mitochondrial biogenesis and mitophagy, leading to mitochondrial dysfunction. However, the mechanism remains unclear. In this study, we investigated the effect of orexin‐A on mitochondrial biogenesis, mitophagy and mitochondrial structure in overexpression of AD‐associated mutant APP cells. We used 20E2 cells as the AD cell model. 20E2 cells were treated with orexin‐A (50, 100 nmol/L). The effect of different concentrations of orexin‐A on cell activity was detected by MTT. As compared with the non‐treated 20E2 cells, orexin‐A‐treated 20E2 cells showed increased expression of APP, decreased cell viability and decreased adenosine triphosphate (ATP) level, decreased levels of regulatory proteins of mitochondrial biogenesis (peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha [PGC‐1α], nuclear respiratory factor 1/2 [NRF1/2], mitochondrial transcription factor A [TFAM]), increased levels of regulatory proteins of mitophagy (Parkin, PTEN‐induced putative kinase 1 [PINK1], microtubule‐associated protein light chain 3 II/I [LC3‐II/LC3‐I]) and decreased p62 level, with damaged mitochondrial structure. Orexin‐A may reduce mitochondrial biogenesis, enhance mitophagy and damage mitochondrial structure in AD.
Potential risks of Tithonia diversifolia in Yunnan Province under climate change
Authors: Dai Guanghui , Wang Shuai , Geng Yupeng , Dawazhaxi  , Ou Xiaokun , Zhang Zhiming
Published: October 2020

Yunnan province is known for its extraordinarily rich biodiversity, but this is threatened by invasive species under climate change. In the present study, the current and future potential distribution of an invasive grass—Tithonia diversifolia A. Gray in Yunnan province were predicted by species distribution modeling, under two climate change conditions (RCP2.6 and RCP8.5) through to 2050s. In addition, the potential risk of T. diversifolia to the protected areas of Yunnan was examined. Our results showed that the potential distribution areas of T. diversifolia would increase by 12 and 93% by 2050s, under RCP2.6 and RCP8.5, respectively. Yunnan's protected areas are now susceptible to T. diversifolia, and the scope of this plant's effects would continue to expand under climate change. A total of 26 protected areas are currently impacted by T. diversifolia, in a total affected range area of 2,822 km2, but by 2050s, this is predicted to increase by 23 and 53%, and would lead to one and 13 protected areas newly threatened under RCP2.6 and RCP8.5, respectively. These results suggest that T. diversifolia would benefit from global warming, we should prevent further global warming. In addition, human disturbance should be reduced and prohibited to protect native plants and forest ecosystem in southern, southeastern and northwestern part of Yunnan.
Phytotoxic effect of invasive speciesAmorpha fruticosaL. on germination and the early growth of forage and agricultural crop plants
Authors: Krstin Ljiljana , Katanić Zorana , Žuna Pfeiffer Tanja , Špoljarić Maronić Dubravka , Marinčić Dragica , Martinović Ana , Štolfa Čamagajevac Ivna
Published: October 2020

Invasive plant species can inhibit the growth of native plants by competing for resources as well as by secreting allelochemicals. Indigobush (Amorpha fruticosaL.), a deciduous shrub adaptable to a wide range of environmental conditions, was introduced into Europe as a decorative and valuable honey plant. In this study, we assayed the phytotoxic effect of aqueous leaf extracts (1, 3 and 5%) obtained fromA.fruticosaleaves on seed germination and seedling growth of four important agricultural species (Trifolium pratenseL. [cultivar “VIVA”],Medicago sativaL. [cultivar OS‐100],Helianthus annuusL. [hybrid “Matej”] andTriticum aestivumL. [cultivar OS‐Olimpija]). Five parameters were analyzed: germination percentage, mean germination time, germination index, fresh weight of seedling root and shoot. The phytotoxicity ofA.fruticosaleaf extract was compared to that of juglone, a strong allelochemical that is known to inhibit growth of numerous plant species. The results demonstrate thatA.fruticosaphytotoxicity is dependent on both the plant species tested and leaf extract concentration, with higher concentration extracts having stronger phytotoxicity. The highest concentration (5%) leaf extract caused similar inhibition of seed germination and seedling growth to that of juglone. The results of this study suggest that the rapid invasion ofA.fruticosain agricultural areas may have a negative impact on growth and yield of valuable forage and agricultural crops.
Rock structure drives the taxonomic and functional diversity of endolithic microbial communities in extreme environments
Authors: Ertekin Emine , Meslier Victoria , Browning Alyssa , Treadgold John , DiRuggiero Jocelyne
Published: October 2020

Endolithic (rock‐dwelling) microbial communities are ubiquitous in hyper‐arid deserts around the world and the last resort for life under extreme aridity. These communities are excellent models to explore biotic and abiotic drivers of diversity because they are of low complexity. Using high‐throughput amplicon and metagenome sequencing, combined with X‐ray computed tomography, we investigated how water availability and substrate architecture modulated the taxonomic and functional composition of gypsum endolithic communities in the Atacama Desert, Chile. We found that communities inhabiting gypsum rocks with a more fragmented substrate architecture had higher taxonomic and functional diversity, despite having less water available. This effect was tightly linked with community connectedness and likely the result of niche differentiation. Gypsum communities were functionally similar, yet adapted to their unique micro‐habitats by modulating their carbon and energy acquisition strategies and their growth modalities. Reconstructed population genomes showed that these endolithic microbial populations encoded potential pathways for anoxygenic phototrophy and atmospheric hydrogen oxidation as supplemental energy sources.