bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of Metabolic Network Disruption in Engineered Microbial Hosts due to Enzyme Promiscuity
Authors: Porokhin Vladimir , Amin Sara A. , Nicks Trevor B. , Gopinarayanan Venkatesh Endalur , Nair Nikhil U. , Hassoun Soha
Published: September 2020

Background

Increasing understanding of metabolic and regulatory networks underlying microbial physiology has enabled creation of progressively more complex synthetic biological systems for biochemical, biomedical, agricultural, and environmental applications. However, despite best efforts, confounding phenotypes still emerge from unforeseen interplay between biological parts, and the design of robust and modular biological systems remains elusive. Such interactions are difficult to predict when designing synthetic systems and may manifest during experimental testing as inefficiencies that need to be overcome. Despite advances in tools and methodologies for strain engineering, there remains a lack of tools that can systematically identify incompatibilities between the native metabolism of the host and its engineered modifications.

Results

Transforming organisms such asEscherichia coliinto microbial factories is achieved via a number of engineering strategies, used individually or in combination, with the goal of maximizing the production of chosen target compounds. One technique relies on suppressing or overexpressing selected genes; another involves on introducing heterologous enzymes into a microbial host. These modifications steer mass flux towards the set of desired metabolites but may create unexpected interactions. In this work, we develop a computational method, termedMetabolicDisruption Workflow(MDFlow), for discovering interactions and network disruption arising from enzyme promiscuity – the ability of enzymes to act on a wide range of molecules that are structurally similar to their native substrates. We applyMDFlowto two experimentally verified cases where strains with essential genes knocked out are rescued by interactions resulting from overexpression of one or more other genes. We then applyMDFlowto predict and evaluate a number of putative promiscuous reactions that can interfere with two heterologous pathways designed for 3-hydroxypropic acid (3-HP) production.

Conclusions

UsingMDFlow, we can identify putative enzyme promiscuity and the subsequent formation of unintended and undesirable byproducts that are not only disruptive to the host metabolism but also to the intended end-objective of high biosynthetic productivity and yield. In addition, we show how enzyme promiscuity can potentially be responsible for the adaptability of cells to the disruption of essential pathways in terms of biomass growth.
Myosin-gelsolin cooperativity in actin filament severing and actomyosin motor activity
Authors: Vemula Venukumar , Huber Tamas , Usaj Marko , Bugyi Beáta , Mansson Alf
Published: September 2020

Actin is a major intracellular protein with key functions in cellular motility, signalling and structural rearrangements. Its dynamic behavior with actin filaments (F-actin) polymerising and depolymerising in response to intracellular changes, is controlled by actin-binding proteins (ABPs). Gelsolin is one of the most potent filament severing ABPs. However, myosin motors that interact with actin in the presence of ATP also produce actin filament fragmentation through motor induced shearing forces. To test the idea that gelsolin and myosin cooperate in these processes we used the in vitro motility assay, where actin filaments are propelled by surface-adsorbed heavy meromyosin (HMM) motor fragments. This allows studies of both motility and filament dynamics using isolated proteins. Gelsolin (5 nM) at very low [Ca2+] (free [Ca2+] ∼6.8 nM) appreciably enhanced actin filament severing caused by HMM-induced forces at 1 mM [MgATP], an effect that was increased at increased HMM motor density. This finding is consistent with cooperativity between actin filament severing by myosin-induced forces and by gelsolin. As further support of myosin-gelsolin cooperativity we observed reduced sliding velocity of the HMM propelled filaments in the presence of gelsolin. Overall, the results corroborate ideas for cooperative effects between gelsolin-induced alterations in the actin filaments and changes due to myosin motor activity, leading among other effects to enhanced F-actin severing of possible physiological relevance.
Calorie Restriction Prevents Age-Related Changes in the Intestinal Microbiota
Authors: Kurup Kavitha , Matyi Stephanie , Giles Cory B. , Wren Jonathan D. , Jones Kenneth , Ericsson Aaron , Raftery Daniel , Wang Lu , Promislow Daniel , Richardson Arlan , Unnikrishnan Archana
Published: September 2020

The effect of calorie restriction (CR) on the microbiome, fecal metabolome, and colon transcriptome of adult and old male mice was compared. Life-long CR increased microbial diversity and theBacteriodetes/Fermicutesratio and prevented the age-related changes in the microbiota, shifting it to a younger microbial and fecal metabolite profile in both C57BL/6JN and B6D2F1 mice. Old mice fed CR were enriched in theRikenellaceae, S24-7andBacteroidesfamilies. The changes in the microbiome that occur with age and CR were initiated in the cecum and further modified in the colon. Short-term CR in adult mice had a minor effect on the microbiome but a major effect on the transcriptome of the colon mucosa. These data suggest that the primary impact of CR is on the physiological status of the gastrointestinal system, maintaining it in a more youthful state, which in turn results in a more diverse and youthful microbiome.
Kcns3Deficiency Disrupts Parvalbumin Neuron Physiology in Mouse Prefrontal Cortex: Implications for the pathophysiology of schizophrenia
Authors: Miyamae Takeaki , Hashimoto Takanori , Abraham Monica , Kawabata Rika , Koshikizawa Sho , Bian Yufan , Kikuchi Mitsuru , Ermentrout G Bard , Lewis David A , Gonzalez-Burgos Guillermo
Published: September 2020

The unique fast spiking (FS) phenotype of cortical parvalbumin-positive (PV) neurons depends on multiple subtypes of voltage-gated potassium channels (Kv). PV neurons selectively expressKcns3, the gene encoding Kv9.3 subunits, suggesting thatKcns3expression is critical for the FS phenotype.KCNS3expression is lower in PV neurons in schizophrenia, but the effects of this alteration are unclear, because Kv9.3 subunit function is poorly understood. We therefore assessed the role of Kv9.3 subunits in PV neuron function by combining gene expression analyses, computational modeling, and electrophysiology in acute slices from the cortex ofKcns3-deficient mice

Kcns3mRNA levels were ~50% lower in cortical PV neurons fromKcns3-deficient relative to wildtype mice. While silentper se, Kv9.3 subunits are believed to amplify the Kv2.1 current in Kv2.1-Kv9.3 channel complexes. Hence, to assess the consequences of reducing Kv9.3 levels, we simulated the effects of decreasing the Kv2.1-mediated current in a computational model. The FS cell model with reduced Kv2.1 produced spike trains with irregular inter-spike intervals, or stuttering, and greater Na+channel inactivation, possibly due to a smaller afterhyperpolarization. As in the computational model, PV basket cells (PVBCs) fromKcns3-deficient mice displayed spike trains with strong stuttering, which depressed PVBC firing, and smaller afterhyperpolarization. Moreover,Kcns3deficiency impaired the recruitment of PVBCs by stimuli mimicking synaptic input during cortical UP states, which elicited bursts of spikes at gamma frequency. Our data suggest that Kv9.3 subunits are critical for PVBC physiology, and thatKCNS3deficiency in schizophrenia may impair the substrate of gamma oscillations.

Significance statement

In the neocortex,Kcns3, the gene encoding voltage-dependent potassium (Kv) channel subunits Kv9.3, is selectively expressed by parvalbumin-positive (PV) neurons. Moreover,KCNS3expression is decreased in PV neurons in schizophrenia. Kv 9.3 subunits are believed to amplify the current mediated by Kv2.1 subunits, however Kv9.3 function has not been investigated in PV cells.

Here, simulations in a computational model and electrophysiological experiments withKcns3-deficient mice revealed thatKcns3deficiency disrupts repetitive firing in cortical PV neurons, possibly enhancing Na+channel inactivation, and particularly with stimuli eliciting firing at gamma frequency band (30-80Hz). Our results suggest that Kv9.3 subunits are essential for PV neuron electrophysiology and that KCNS3 deficiency likely contributes to PV neuron dysfunction and gamma oscillation impairments in schizophrenia.
Impaired labyrinth formation prevents the establishment of the maternal-fetal interface in conditional Hand1-deficient mice
Authors: Courtney Jennifer A. , Cnota James , Jones Helen
Published: September 2020

Introduction

Congenital heart defects (CHD) affect approximately 1% of all live births, and often require complex surgeries at birth. Placental development and function is vital to ensure normal fetal development. We have previously demonstrated abnormal placental development and vascularization in human CHD placentas, and placental expression changes in genes important for heart development. Hand1 has roles in both heart and placental development and is implicated in CHDs including double right outlet, hypoplastic left heart syndrome, and septal defects; however, Hand1 involvement in placental vascularization and development is under-investigated. We utilized the Hand1A126fs/+murine model to investigate Hand1 in placentation and vascularization.

Methods

Hand1A126fs/+female mice were time-mated with Nkx2.5cre(placenta- and heart-specific) males to produce either Nkx2.5cre;Hand1+/+or Nkx2.5cre;Hand1A126fs/+fetuses. Feto-placental units were harvested at timepoints from E8.5 to E14.5 for histological analysis; vascular assessment by immunohistochemistry for Hand1, CD-31, and CK-7; and angiogenesis by qPCR.

Results

Embryonic lethality occurs in Nkx2.5cre/Hand1A126fs/+by E14.5 due to a failure of placental labyrinth formation and vascularization. Chorionic trophoblasts did not form, although trophoblast giant cell subtypes were present. Fetal vessels failed to develop properly and were significantly lower in the labyrinth by day E12.5. Placental growth factor levels were significantly increased, and Angiopoietin2 expression trended higher in Nkx2.5cre/Hand1A126fs/+placental labyrinths compared to control littermates.

Conclusion

We demonstrate that Hand1 expression in placental chorion and trophoblast is necessary for proper patterning of the labyrinth and vascularization within the labyrinth. Multiple angiogenic factors known to be expressed in trophoblast were disrupted in Nkx2.5cre/Hand1A126fs/+placental labyrinths compared to control littermates. Alterations in Hand1 expression represent a potential mechanism for abnormal placentation and early miscarriage in cases of CHD.
Machine learning enables new insights into clinical significance of and genetic contributions to liver fat accumulation
Authors: Haas Mary E. , Pirruccello James P. , Friedman Samuel N. , Emdin Connor A. , Ajmera Veeral H. , Simon Tracey G. , Homburger Julian R. , Guo Xiuqing , Budoff Matthew , Corey Kathleen E. , Zhou Alicia Y. , Philippakis Anthony , Ellinor Patrick T. , Loomba Rohit , Batra Puneet , Khera Amit V.
Published: September 2020

Excess accumulation of liver fat – termed hepatic steatosis when fat accounts for > 5.5% of liver content – is a leading risk factor for end-stage liver disease and is strongly associated with important cardiometabolic disorders. Using a truth dataset of 4,511 UK Biobank participants with liver fat previously quantified via abdominal MRI imaging, we developed a machine learning algorithm to quantify liver fat with correlation coefficients of 0.97 and 0.99 in hold-out testing datasets and applied this algorithm to raw imaging data from an additional 32,192 participants. Among all 36,703 individuals with abdominal MRI imaging, median liver fat was 2.2%, with 6,250 (17%) meeting criteria for hepatic steatosis. Although individuals afflicted with hepatic steatosis were more likely to have been diagnosed with conditions such as obesity or diabetes, a prediction model based on clinical data alone without imaging could not reliably estimate liver fat content. To identify genetic drivers of variation in liver fat, we first conducted a common variant association study of 9.8 million variants, confirming three known associations for variants in theTM6SF2, APOE, andPNPLA3genes and identifying five new variants associated with increased hepatic fat in or near theMARC1, ADH1B, TRIB1, GPAMandMAST3genes. A polygenic score that integrated information from each of these eight variants was strongly associated with future clinical diagnosis of liver diseases. Next, we performed a rare variant association study in a subset of 11,021 participants with gene sequencing data available, identifying an association between inactivating variants in theAPOBgene and substantially lower LDL cholesterol, but more than 10-fold increased risk of steatosis. Taken together, these results provide proof of principle for the use of machine learning algorithms on raw imaging data to enable epidemiologic studies and genetic discovery.
Common abnormality of gray matter integrity in substance use disorder and obsessive-compulsive disorder: A comparative voxel-based meta-analysis
Authors: Klugah-Brown Benjamin , Jiang Chenyang , Agoalikum Elijah , Zhou Xinqi , Zou Liye , Yu Qian , Becker Benjamin , Biswal Bharat
Published: September 2020

Aim

To determine robust transdiagnostic brain structural markers for compulsivity by capitalizing on the increasing number of case-control studies examining gray matter alterations in substance use disorders (SUD) and obsessive-compulsive disorder (OCD).

Design

Pre-registered voxel-based meta-analysis of grey matter volume (GMV) changes through seed-based d Mapping (SDM), follow-up functional, and network-level characterization of the identified transdiagnostic regions by means of co-activation and Granger Causality (GCA) analysis.

Participants

Literature search resulted in 31 original VBM studies comparing SUD (n = 1191, mean-age = 40.03, SD = 10.87) and 30 original studies comparing OCD (n = 1293, mean-age = 29.18, SD = 10.34) patients with healthy controls (SUD: n = 1585, mean-age = 42.63, SD = 14.27, OCD: n = 1374, mean-age = 28.97, SD = 9.96).

Measurements

Voxel-based meta-analysis within the individual disorders as well as conjunction analysis were employed to reveal common GMV alterations between SUDs and OCD. Meta-analytic coordinates and signed brain volumetric maps determining directed (reduced or increased) brain volumetric alterations between the disorder groups and controls served as the primary outcome. Meta-analytic results employed statistical significance thresholding (FWE< 0.05).

Findings

Separate meta-analysis demonstrated that SUD (cocaine, alcohol, and nicotine) as well as OCD patients exhibited widespread GMV reductions in frontocortical regions including prefrontal, cingulate, and insular regions. Conjunction analysis revealed that the left inferior frontal gyrus (IFG) consistently exhibited decreased GMV across all disorders. Functional characterization suggests that the IFG represents a core hub in the cognitive control network and exhibits bidirectional (Granger) causal interactions with the striatum. Only OCD showed increased GMV in the dorsal striatum with higher changes being associated with more severe OCD symptomatology.

Conclusions

Findings demonstrate robustly decreased GMV across the disorders in the left IFG, suggesting a transdiagnostic brain structural marker. The functional characterization as a key hub in the cognitive control network and casual interactions with the striatum suggest that deficits in inhibitory control mechanisms may promote compulsivity and loss of control that characterize both disorders.
A novel microcosm for recruiting inherently competitive biofertilizer-candidate microorganisms from soil environments
Authors: Pittroff S , Olsson S , Doolette Ashlea , Greiner R. , Richardson A.E. , Nicolaisen M
Published: September 2020

Fertilizer phosphorus (P) is both a necessary crop nutrient and finite resource, necessitating the development of innovative solutions for P fertilizer efficiency and recycling in agricultural systems.Myo-inositol hexakisphosphate (phytate) and its lower order derivatives constitute the majority of identified organic P in many soil types and has been shown to accumulate with increasing application of P fertilizer. Phytate is only poorly available to plants, and in alkaline soils it often precipitated as even more unavailable calcium (Ca)-phytate. Incorporating phytase-producing biofertilizers (i.e., microbial-based products with capacity to mineralize phytate) into soil presents a viable and environmentally acceptable way of utilizing P from phytate, whilst reducing the need for mineral P application. Here we present an in-soil microcosm that utilizes precipitated Ca-phytate to recruit microorganisms with degradation activity towards phytatein solum. Our results show both direct and indirect evidence for Ca-phytate mineralizationin vitroandin solum. Furthermore, the abundance of bacteria recruited was measured via 16S rRNA gene copy number, as was three genes relating to organic P degradation;phoXandphoDphosphatases and the BPP (β-propeller phytase) gene. Amplicon sequencing as well as BioLog catabolism studies show that microcosm treatments containing the ‘bait’ Ca-phytate, recruited a different set of microorganisms when compared to controls. These Ca-phytate microcosms recruited mainly Actinobacteria, Firmicutes, and Proteobacteria, and the genusStreptomyceswas specifically enriched. We conclude that our microcosm presents an innovative approach for isolating soil microorganisms with the potential to degrade precipitated phytatein solumand represents a new isolation method with the potential to isolate inherently robust biofertilizer candidates directly from target soils.
Environment and sex control lifespan and telomere length in wild-derived African killifish
Authors: Reichard Martin , Giannetti Kety , Ferreira Tania , Vrtílek Milan , Polačik Matej , Blažek Radim , Ferreira Miguel Godinho
Published: September 2020

Telomere length is correlated positively with longevity at the individual level, but negatively when compared across species. Here, we tested the association between lifespan and telomere length in African annual killifish. We analyzed telomere length in 18Nothobranchiusstrains derived from diverse habitats and measured the laboratory lifespan of 14 strains ofN. furzeriandN. kadleci. We found that males had shorter telomeres than females. The longest telomeres were recorded in strains derived from dry region where male lifespans were shortest. At the individual level, we detected a weak negative association between rapid juvenile growth and shorter telomeres in early adulthood. Overall, average telomere length was a good descriptor of telomere length distribution. However, within-individual telomere length spread was not related to any pattern. This substantial variation in telomere length between strains from different environments provides killifish as powerful tool to understand the evolutionarily adaptive value of telomere length.
Genomic insight into the biogeographic history, divergence, and adaptive potential ofG. purpurascens, a forgotten landrace ofG. hirsutum
Authors: Nazir Mian Faisal , He Shoupu , Ahmed Haris , Sarfraz Zareen , Jia Yinhua , Li Hongge , Sun Gaofei , Iqbal Muhammad Shahid , Pan Zhaoe , Du Xiongming
Published: September 2020

Continuous selection and adaptation to the local environment resulted in the loss of genetic variation inGossypium hirsutum, which is the most important source of natural fiber. Wild progenitors are an excellent source for strengthening the genetic base and accumulation of desirable traits in modern cultivars. Here we reevaluate a landrace ofGossypium hirsutum, formerly known asGossypium purpurascens. We seek to understand the genomic structure, variation, and the adaptive/breeding potential among largely neglected landraces ofGossypium hirsutum purpurascens, providing insights into the biogeographic history and genomic changes likely associated with domestication. Population fixation statistics suggested marked differentiation betweenG. purpurascensand current varieties, obsolete accessions, and geographical landraces of upland cotton, emphasizing the divergent behavior ofG. purpurascens. Phylogeny established the primitive nature ofG. purpurascens, the inclusion of which in upland cotton gene-pool can enhance the narrowed genetic base of upland cultivars. Genome-wide associations comprehend multiple loci associated with domestication regions corresponding to flowering and fiber quality. Moreover, the conserved nature ofG. purpurascenscan provide insight into understanding the evolutionary process ofG. hirsutum.
Rapid acting antidepressant (2R,6R)-hydroxynorketamine (HNK) targets glucocorticoid receptor signaling: a longitudinal cerebrospinal fluid proteome study
Authors: Herzog David P. , Perumal Natarajan , Manicam Caroline , Treccani Giulia , Nadig Jens , Rossmanith Milena , Engelmann Jan , Jene Tanja , Hasch Annika , van der Kooij Michael A. , Lieb Klaus , Gassen Nils C. , Grus Franz H. , Müller Marianne B.
Published: September 2020

Delayed onset of antidepressant action is a shortcoming in depression treatment. Ketamine and its metabolite (2R,6R)-hydroxynorketamine (HNK) have emerged as promising rapidacting antidepressants. However, their mechanism of action remains unknown. In this study, we first described the anxious and depression-prone inbred mouse strain, DBA/2J, as a animal model to assess the antidepressant-like effects of ketamine and HNKin vivo.To decode the molecular mechanisms mediating HNK’s rapid antidepressant effects, a longitudinal cerebrospinal fluid (CSF) proteome profiling of its acute and sustained effects was conducted using an unbiased, hypothesis-free mass spectrometry-based proteomics approach. A total of 387 proteins were identified, with a major implication of significantly differentially expressed proteins in the glucocorticoid receptor (GR) signaling pathway, providing evidence for a link between HNK and regulation of the stress hormone system. Mechanistically, we identified HNK to repress GR-mediated transcription and reduce hormonal sensitivity of GRin vitro.In addition, mammalian target of rapamycin (mTOR) and brain-derived neurotrophic factor (BDNF) were predicted to be important upstream regulators of HNK treatment. Our results contribute to precise understanding of the temporal dynamics and molecular targets underlying HNK’s rapid antidepressant-like effects, which can be used as a benchmark for improved treatment strategies for depression in future.
Migration without interbreeding: evolutionary history of a highly selfing Mediterranean grass inferred from whole genomes
Authors: Stritt Christoph , Gimmi Elena L. , Wyler Michele , Bakali Abdelmonaim H. , Skalska Aleksandra , Hasterok Robert , Mur Luis A. J. , Pecchioni Nicola , Roulin Anne C.
Published: September 2020

Wild plant populations show extensive genetic subdivision and are far from the ideal of panmixia which permeates population genetic theory. Understanding the spatial and temporal scale of population structure is therefore fundamental for empirical population genetics – and of interest in itself, as it yields insights into the history and biology of a species. In this study we extend the genomic resources for the wild Mediterranean grassBrachypodium distachyonto investigate the scale of population structure and its underlying history at whole-genome resolution. 86 accessions were sampled at local and regional scales in Italy and France, which closes a conspicuous gap in the collection for this model organism. The analysis of 196 accessions, spanning the Mediterranean from Spain to Iraq, suggests that the interplay of high selfing and seed dispersal rates has shaped genetic structure inB. distachyon. At the continental scale, the evolution inB. distachyonis characterized by the independent expansion of three lineages during the Upper Pleistocene. Today, these lineages may occur on the same meadow yet do not interbreed. At the regional scale, dispersal and selfing interact and maintain high genotypic diversity, thus challenging the textbook notion that selfing in finite populations implies reduced diversity. Our study extends the population genomic resources forB. distachyonand suggests that an important use of this wild plant model is to investigate how selfing and dispersal, two processes typically studied separately, interact in colonizing plant species.
Analysis of diffusion tensor imaging data from UK Biobank confirms dosage effect of 15q11.2 copy-number variation on white matter and shows association with cognition
Authors: Silva Ana I. , Kirov George , Kendall Kimberley M. , Bracher-Smith Mathew , Wilkinson Lawrence S. , Hall Jeremy , Ulfarsson Magnus O. , Walters G. Bragi , Stefansson Hreinn , Stefansson Kari , Linden David E. J. , Caseras Xavier
Published: September 2020

Background

Copy-number variations at the 15q11.2 BP1-BP2 locus are present in 0.5 to 1.0% of the population, and the deletion is associated with a range of neurodevelopmental disorders. Previously, we showed a reciprocal effect of 15q11.2 copy-number variation on fractional anisotropy, with widespread increases in deletion carriers. We aim to replicate and expand these findings, using a larger sample of participants (n=30,930), higher resolution imaging, and examining the implications for cognitive performance.

Methods

Diffusion tensor imaging measures from participants with no neurological/psychiatric diagnoses were obtained from the UK Biobank database. We compared 15q11.2 BP1-BP2 deletion (n=103) and duplication (n=119) carriers to a large cohort of control individuals with no neuropsychiatric copy-number variants (n=29,870). Additionally, we assessed how changes in white matter mediated the association between carrier status and cognitive performance.

Results

Deletion carriers showed increases in fractional anisotropy in the internal capsule and cingulum, and decreases in the posterior thalamic radiation, compared to both duplication carriers and controls (who had intermediate values). Deletion carriers had lower scores across cognitive tasks compared to controls, which were mildly influenced by white matter alterations. Reduced fractional anisotropy in the posterior thalamic radiation partially contributed to worse cognitive performance in deletion carriers.

Conclusions

This study, together with our previous findings, provides convergent evidence for a dosage-dependent effect of 15q11.2 BP1-BP2 on white matter microstructure. Additionally, changes in white matter were found to partially mediate cognitive ability in deletion carriers, providing a link between white matter changes in 15q11.2 BP1-BP2 carriers and cognitive function.
On demand MyD88 oligomerization is controlled by IRAK4 during Myddosome signaling
Authors: Deliz-Aguirre Rafael , Cao Fakun , Gerpott Fenja H. U. , Auevechanichkul Nichanok , Chupanova Mariam , Mun YeVin , Ziska Elke , Taylor Marcus J.
Published: September 2020

A recurring feature of innate immune receptor signaling is the self-assembly of signaling proteins into oligomeric complexes. The Myddosome is an oligomeric complex that is required to transmit inflammatory signals from TLR/IL1Rs and consists of MyD88 and IRAK family kinases. However, the molecular basis for how Myddosome proteins self-assemble and regulate intracellular signaling remains poorly understood. Here, we developed a novel assay to analyze the spatiotemporal dynamics of IL1R and Myddosome signaling in live cells. We found that MyD88 oligomerization is inducible and initially reversible. Moreover, the formation of larger, stable oligomers consisting of more than 4 MyD88s triggers the sequential recruitment of IRAK4 and IRAK1. Notably, genetic knockout of IRAK4 enhanced MyD88 oligomerization, indicating that IRAK4 controls MyD88 oligomer size and growth. MyD88 oligomer size thus functions as a physical threshold to trigger downstream signaling. These results provide a mechanistic basis for how protein oligomerization might function in cell signaling pathways.
The wheat cytosolic glutamine synthetaseGS1.1modulates N assimilation and spike development by characterizing CRISPR-edited mutants
Authors: Wang Yazhou , Teng Wan , Wang Yanpeng , Ouyang Xiang , Xue He , Zhao Xueqiang , Gao Caixia , Tong Yiping
Published: September 2020

Glutamine synthetase (GS) mediates the first step in the assimilation of inorganic nitrogen (N) into amino acids, however the function of GS encoding genes is not well understood in wheat (Triticum aestivum). We found that the cytosolicTaGS1.1was the major transcriptedGS1gene and was up-regulated by low-N availability. CRISPR/Cas9 mediated genome editing was employed to develop twogs1.1mutants with mutatedTaGS1.1-6A, −6B, and-6D. Both mutants had lower grains per spike and grain yield per plant than the wild type under both low-N and high-N conditions in field experiments. In a hydroponic culture treated with different N resources, the two mutants was more sensitive to low-N stress than the wild type, but showed similar sensitivity to high ammonium stress with the wild type. The growth deficiency and impaired spike development were associated with the imbalance of N metabolites in the mutant plants. During grain filling,TaGS1.1mutation reduced N translocation efficiency and delayed leaf N loss and grain N filling. Our results suggested thatTaGS1.1is important for N assimilation and remobilization, and required for wheat adaptation to N-limited conditions and spike development.

Highlight

The wheat cytosolic glutamine synthetaseTaGS1.1is important for N assimilation and remobilization, and is required for wheat adaptation to low-N stress and spike development.
Employees’ identification and management control systems: a case study of modern policing
Authors: Cuganesan Suresh , Free Clinton
Published: September 2020

Purpose

The authors examined how squad members within an Australian state police force perceived and attached enabling or coercive meanings to a suite of management control system (MCS) changes that were new public management (NPM) inspired.

Design/methodology/approach

The authors conducted a longitudinal case study of a large Australian state police department utilizing an abductive research design.

Findings

The authors found that identification processes strongly conditioned the reception of the MCS changes introduced. Initially, the authors observed mixed interpretations of controls as both enabling and coercive. Over time, these changes were seen to be coercive because they threatened interpersonal relationships and the importance and efficacy of squads in combating serious and organized crime.

Research limitations/implications

The authors contributed to MCSs literature by revealing the critical role that multifaceted relational and collective identification processes played in shaping interpretations of controls as enabling–coercive. The authors build on this to elaborate on the notion of employees’ centricity in the MCS design.

Practical implications

This study suggests that, in complex organizational settings, the MCS design and change should reckon with pre-existing patterns of employees’ identification.

Originality/value

The authors suggested shifting the starting point for contemplating the MCS change: from looking at how what employees do is controlled to how the change impacts and how employees feel about who they are. When applied to the MCS design, employee centricity highlights the value of collaborative co-design, attentiveness to relational identification between employees, feedback and interaction in place of inferred management expectations and traditional mechanistic approaches.
Research on the construction of the semantic model for Chinese ancient architectures based on architectural narratives
Authors: Chen Jinju , Ou Shiyan
Published: September 2020

Purpose

This paper aims to reorganize the relevant information of Chinese ancient architectures with the use of Semantic Web technologies and thus facilitate its deep discovery and usage.

Design/methodology/approach

This paper proposes an ontology model for Chinese ancient architectures based on architectural narratives theory. To verify the availability of the ancient architecture ontology, we designed and implemented three experiments, including semantic retrieval based on SPARQL query, semantic reasoning with the use of Jena reasoner and visual analysis based on the Chinese Online Digital Humanities Resources Platform.

Findings

The proposed ontology provided a solution for the semantic annotation of the unstructured information of Chinese ancient architectures. On this basis, deep knowledge services such as semantic retrieval, semantic reasoning and visual analysis can be provided.

Practical implications

The proposed semantic model of ancient architectures can effectively improve the organization and access quality of the semantic content of Chinese ancient architectures.

Originality/value

This paper focuses on the semantic modelling for the unstructured information of Chinese ancient architectures to semantically describe the related entities (e.g. persons, events, places and times) and uncover their relationships, and thus it made contribution to the deep semantic annotations on ancient architectures.
Friendly bureaucrats, formal rules and firms' investment decisions: evidence from a survey experiment in Russia
Authors: Yakovlev Andrei , Ivanov Denis
Published: September 2020

Purpose

The purpose of this paper is to investigate the links between investment activity and personal contacts for small- and medium-sized firms with public officials at the subnational level in Russia.

Design/methodology/approach

A list-experiment design, using a survey of 21,000 Russian firms in 2017, was used to evaluate the importance of personal connections with officials for conducting business.

Findings

A total of 27% of firms without investment and 37% with investment considered personal connections with officials an important factor for doing business. The importance of such contacts was lower in regions with a better investment climate. However, a higher proportion of firms were likely to invest in the regions where higher importance was placed on political connections. Therefore, in Russia in the mid-2010s, investment from politically connected firms did not crowd out investment from other firms.

Research limitations/implications

Although the available data did not allow causality to be defined, the research shows that political connections are important for investors in emerging markets and that the importance of political connections diminishes with improvement in the business climate.

Originality/value

This paper provides a quantitative estimate of the relationship between political connections and firm investment in Russia, an example of large emerging economy. This relationship is moderated by institutional quality at the subnational level. The results provide empirical support for the theory of limited access orders elaborated by North et al. (2009), and stress the importance of rents and their productive utilization for the development of emerging economies.
Digitally enabled advanced services: a socio-technical perspective on the role of the internet of things (IoT)
Authors: Schroeder Andreas , Naik Parikshit , Ziaee Bigdeli Ali , Baines Tim
Published: September 2020

Purpose

The purpose of this study is to investigate how the internet of things (IoT) contributes to manufacturers' advanced services development and delivery. To better understand the creation of these IoT contributions, the study adopts a socio-technical research perspective, which expands the scope of the investigation and integrates the technological, information and social factors that enable these IoT contributions.

Design/methodology/approach

A multiple-case research method was employed to investigate the IoT contribution scenarios of 15 manufacturers who offer advanced services and to examine their dependence on other non-IoT factors, using thematic analysis.

Findings

The analysis identified five advanced services value propositions, which are enabled by nine “IoT-enabled information systems (IS) artefacts” that specify the distinct interactions between the technological, information and social subsystems supporting the manufacturers' advanced services value propositions.

Originality/value

The study advances the servitisation research by demonstrating that IoT technology on its own is insufficient for the creation of the IoT contributions. It shows, instead, the need for close interactions with a diverse range of other factors, which are often not considered when developing an IoT strategy. The study also introduces the IS artefact notion as a unit of analysis that constitutes an alternative to the commonly adopted techno-centric perspective used to conceptualise IoT contributions. The study and its findings add to the development of a socio-technical perspective on the IoT in advanced services and thereby suggests a number of theoretical and practical implications.
Networking capability and firm performance: the mediating role of market orientation and business process agility
Authors: Kurniawan Randy , Budiastuti Dyah , Hamsal Mohammad , Kosasih Wibowo
Published: September 2020

Purpose

This study aims to examine the effect of networking capability through market orientation and business process agility on the firm performance of medium and large telecommunication technology providers in Indonesia.

Design/methodology/approach

Research data was collected from the executive management of telecommunication technology providers in Indonesia via a questionnaire survey to obtain 150 valid questionnaires for analysis. This study analysed the overall model fit and hypotheses through confirmatory factor analysis and structural equation modelling.

Findings

The results reveal that networking capability has a positive and significant effect on market orientation. However, networking capability does not have a significant direct effect on business process agility. The results also indicate that market orientation does not have a significant direct effect on firm performance but through the mediating role of business process agility.

Practical implications

The findings provide a practical foundation for the organisation’s networking capability to be framed by market orientation and business process agility to enhance firm performance.

Originality/value

The results indicate that market orientation mediates the relationship between networking capability and business process agility. The findings also reveal that business process agility mediates the relationship between market orientation and firm performance. This study also reconceptualises market orientation to embody the inter-partner coordination dimension and reconceptualise business process agility to embody business partner switching capability.
Adapting sales influence tactics in the information intensive era
Authors: Leach Mark P. , Epler Rhett T. , Wang Sijun
Published: September 2020

Purpose

This paper aims to explore the usage of selling influence tactics across prospective customers with differing information-related needs.

Design/methodology/approach

The research study uses an exploratory critical incident technique (CIT) methodology to identify and examine salesperson influence tactics.

Findings

This study identifies and explores the use of salesperson influence tactics across three information-based conditions often encountered by salespeople (i.e. information seeking customers, informed customers with information inaccuracies and informed customers making sub-optimal decisions). Regardless of condition, salespeople readily used non-coercive information exchange tactics. Whereas, recommendations and ingratiation tactics were applied by more effective salespeople when interacting with informed customers with information deficiencies. Furthermore, salespeople report executing less effectively with prospects with inaccurate preexisting information and with prospects making flawed or sub-optimal decisions.

Research limitations/implications

Findings illustrate the need for a renewed focus on salesperson influence tactics, the conditions under which they are effective, and how salespeople adapt their influence tactics to various situations. The exploratory nature of this study limits the generalizability of findings.

Practical implications

A framework of adaptive selling strategies is proposed to help tackle new challenges faced by B2B salespeople in today’s information intensive market. When interacting with more informed customers, pre-existing information is often inaccurate and incomplete. Thus, salespeople must assess and address these flaws and gaps and can adapt their influence strategies to do so effectively.

Originality/value

Industrial buyers today have virtually unlimited avenues to conduct extensive research and gain supplier information without the aid of interactions with salespeople. Thus, salespeople often enter sales interactions when their prospects have significantly more information than ever before. By examining salesperson influence techniques in selling situations that vary based on prospective customer preexisting knowledge, this research provides guidance on how selling may need to change in a more information intensive era.
The bright side of geopolitical risk: evidence from Chinese firms
Authors: Oanh Ha Kieu , Hoang Khanh
Published: September 2020

Purpose

The paper aims to investigate whether firms invest in corporate social responsibility (CSR) as a risk protection mechanism as the response to increased geopolitical risk (GPR).

Design/methodology/approach

The sample of this study includes non-financial listed firms on the Chinese stock market over 2000–2016. Several measures of CSR and GPR were used to examine the relationship between two factors. Further investigation is conducted to find out how increasing uncertainty in the business environment in both geopolitics and macroeconomic policy affects corporate decision-making regarding CSR.

Findings

GPR has a significant and positive effect on CSR, meaning that Chinese firms use CSR investment as an insurance mechanism against uncertainty arising from heightened geopolitical uncertainty. Further analysis indicates a negative joint effect of GPR and uncertainty in macroeconomic policy on CSR and shows that it can exhaust firms’ resources and offset their individual positive impacts on CSR at the extreme level of uncertainty. The findings are robust to the choices of proxies, model specifications and endogeneity concerns.

Originality/value

This study sheds light on the existing literature by providing empirical evidence on the positive relationship between GPR and CSR. The findings of this study support the risk management view, in which firms engage more in CSR as a form of insurance mechanism to react to geopolitical uncertainty. This is also the first empirical study investigating the joint effect of GPR and economic policy uncertainty on CSR.
Retirement saving behavior: evidence from UAE
Authors: Alkhawaja Sara Osama , Albaity Mohamed
Published: September 2020

Purpose

This study aims to examine the effect of future time perspective (FTP), financial risk tolerance (FRT) and knowledge of financial planning for retirement (KFPR) on retirement saving behavior (RSB).

Design/methodology/approach

Primary data were collected using a non-probability judgmental sampling technique. A questionnaire was distributed either manually (by hand) or through email where 370 United Arab Emirates (UAE) residents used in the higher education sector participated. The data analysis was obtained by using SPSS and Smart-PLS software. Structural equation modeling was used to evaluate the linear relationship between FTP, FRT, KFPR and RSB.

Findings

The findings from this study are consistent with previous research. FTP and KFPR had a significant positive effect, while FRT had an insignificant negative effect on RSB.

Research limitations/implications

This study examined the effect of a few psychological variables on RSB and was conducted on a sample of university employees in the UAE. Additional research should examine environmental influences, individual differences and other psychological process factors. Furthermore, future research could extend the current study into other industries and other the Middle East and North Africa countries.

Practical implications

A better understanding of the factors that influence RSB can help working individuals, financial advisors/financial planning professionals, financial institutions and government/policymakers strengthen their understanding and initiatives toward retirement planning.

Originality/value

To the best of the authors knowledge, none of the previous research papers studied RSB in the UAE. Additionally, it is important to note that the results of this study can be generalized to all Gulf Cooperation Council countries because of the similar economic, political, ethical, social and cultural factors.
Withholding effort in sharing knowledge in online space: differential effects of task characteristics
Authors: Wu Dongming
Published: September 2020

Purpose

Knowledge withholding is an important but under-studied topic, which refers to the phenomenon that individuals give less than full effort to contributing knowledge. This study aims to investigate the differential effects of task characteristics on individuals’ knowledge withholding behavior in online space, this study develops and empirically verifies a theoretical model that covers the five core task characteristics in job characteristics model (autonomy, identity, feedback, skill variety and significance), knowledge sharing self-inefficacy and withholding effort in sharing knowledge.

Design/methodology/approach

Using an online survey method, this study collected empirical data from 351 general internet users from 30 provincial administrative units in China. The data were analyzed using the structural equation modeling technique of partial least squares.

Findings

The analysis results indicate that autonomy negatively affects, while identity, skill variety and significance positively affect users’ knowledge withholding behavior in online space through the mediation of knowledge sharing self-inefficacy, and that three task characteristics (autonomy, identity and feedback) strengthen the relationship between knowledge sharing self-inefficacy and knowledge withholding.

Practical implications

This study provides valuable insights for reducing knowledge withholding behavior in online space. Operationally, different levels of task characteristics such as autonomy, identity and feedback can be set to prevent users from perceiving themselves as inefficacious, and to weaken the behavioral expression of knowledge sharing self-inefficacy.

Originality/value

This study provides a comprehensive understanding of the differential effects of task characteristics on knowledge withholding in online space, and improves the cognition of the boundaries of withholding effort in sharing knowledge in online space.