bluuebunny/crossref_metadata_2025 huggingface dataset:
IMPA1 dependent regulation of plasma membrane phosphatidylinositol 4,5-bisphosphate turnover and calcium signalling by lithium
Authors: Saha Sankhanil , Krishnan Harini , Padinjat Raghu
Published: October 2022

Lithium (Li) is a widely used as a mood stabilizer in the clinical management of Bipolar Affective Disorder (BPAD). However, the molecular targets of Li in neural cells that underpin its therapeutic effect remain unresolved. Inositol monophosphatase (IMPA1), is an enzyme involved in the resynthesis of phosphatidylinositol 4,5-bisphosphate (PIP2) following receptor-activated phospholipase C (PLC) signalling.In vitro, Li inhibits IMPA1, but the relevance of this inhibition within neural cells remains unknown. Here we report that in human cells, treatment with therapeutically relevant concentrations of Li reduces receptor activated calcium release from intracellular stores and delays the resynthesis of PIP2following receptor activated PLC signalling. Both these effects of Li are abrogated in cells where IMPA1 has been deleted. We also observed that in human forebrain cortical neurons, treatment with Li results in reduced neuronal excitability as well as reduced calcium signals following receptor activated PLC signalling. Following Li treatment of human forebrain cortical neurons, transcriptome analyses reveal downregulation of multiple components of the glutamate receptor signalling system. Glutamate is a key excitatory neurotransmitter in the human brain and thus our findings provide an insight into the mechanisms underlying the dampening of neuronal excitability following Li treatment. Collectively, our findings suggest that Li inhibits receptor activated PLC signalling leading to an altered transcriptional response and reduced neuronal excitability.
Biotic and abiotic stress distinctly drive the phyllosphere microbial community structure
Authors: Bhandari Rishi , Saez Alvaro Sanz , Leisner Courtney P. , Potnis Neha
Published: October 2022

While the physiological and transcriptional response of the host to biotic and abiotic stresses have been intensely studied, little is known about the resilience of associated microbiomes and their contribution towards tolerance to these stresses. We evaluated the impact of one such abiotic stress, elevated tropospheric ozone (O3), under open-top chamber field conditions on host susceptibility and phyllosphere microbiome associated with pepper cultivars resistant and susceptible toXanthomonas. Pathogen challenge resulted in distinct microbial community structures in both cultivars under an ambient environment. Elevated O3alone affected microbial community structure associated with resistant cultivar but not the susceptible cultivar, indicating the role of host genotypic background in response to abiotic stress. Elevated O3did not influence overall host susceptibility but did increase disease severity on the resistant cultivar, indicating a possible compromise in the resistance. Interestingly, combined stress resulted in a shift in microbial composition and structure like that observed with pathogen challenge alone. It indicates the possible prioritization of community response towards the most significant stress and pathogen being most influential regardless of the cultivar. Despite community composition differences, overall functional redundancy was observed in the phyllosphere community. To gain insights into community-level interactions, network topology assessment indicated a stable network with enhanced taxon connectedness upon pathogen challenge. However, an observation of destabilized random network with a shift in hub taxa in the presence of combined stress warrants future studies on the consequences of such unstable microbial communities on host response to pathogens in the face of climate change.
On a mechanistic impact of transmembrane tetramerization in pathological activation of RTKs
Authors: Polyansky Anton A. , Efremov Roman G.
Published: October 2022

Constitutive activation of receptor tyrosine kinases (RTKs) via different mutation has a strong impact into development of severe human disorders, including cancer. While pathological effect of such mutations can be common on the phenotypical level, mechanistic understanding of their contribution into the receptor activation depends on the exact molecular context. Mutations in transmembrane (TM) domains represent an interesting class of pathological modifications since they can directly affect a signal transduction pathway from the receptor to the kinase domains of RTKs. Here we propose a putative activation scenario of RTK, whereby TM mutations can also promote higher order oligomerization of the receptors that leads to the subsequent ligand-free activation. To illustrate this model with all-atom resolution for a previously characterized oncogenic TM mutation V536E in platelet-derived growth factor receptor alpha (PDGFRA), we use a computational modeling framework including sequence-based structure prediction and all-atom 1 µs molecular dynamics (MD) simulations in a model membrane for the predicted configuration of the PDGFRA TM tetramers. We show that in the course of MD simulations the mutant tetramer retains stable and compact configuration, which is strengthened by tight protein-protein interactions. In contrast, the wild type tetramer demonstrates looser packing and tendency to dissociate. Such a structural organization shapes the dynamics of TM helices in the oligomeric state. Specifically, the mutation affects the characteristic motions of mutated TM helical segments by introducing additional non-covalent crosslinks in the middle of the TM tetramer, which work as mechanical hinges. This leads to dynamic decoupling of the C-termini from the rigidified N-terminal parts and facilitates higher possible displacement between the C-termini of the mutant TM helical regions. This, in turn, can provide more freedom to downstream kinase domains in their mutual rearrangement. The observed structural and dynamic effects of the V536E mutations in the context of PDGFRA TM tetramer provide an interesting possibility that an effect of oncogenic TM mutations can go beyond alternating structure and dynamics of TM dimeric states and also promote formation of higher-order oligomers that may directly contribute into the ligand independent signaling of PDGFRA and other RTKs.
Re-evaluating homoploid reticulate evolution in the annual sunflowers
Authors: Owens Gregory L. , Huang Kaichi , Todesco Marco , Rieseberg Loren H.
Published: October 2022

Sunflowers of the genusHelianthusare models for hybridization research and contain three of the best studied examples of homoploid hybrid speciation. To understand the broader picture of hybridization within the annual sunflowers, we used whole genome resequencing to conduct a phylogenomic analysis and test for gene flow between lineages. We find that all annual sunflower species tested have evidence of admixture, suggesting hybridization was common during the radiation of the genus. Support for the major species tree decreases with recombination rate, consistent with hybridization and introgression contributing to discordant topologies. Admixture graphs found hybridization to be associated with the origins of the three putative hybrid species (H. anomalus, H. deserticola, andH. paradoxus). However, the hybridization events are more ancient than suggested by previous work. Furthermore,H. anomalusandH. deserticolaappear to have arisen from a single hybridization event involving an unexpected donor, rather than through multiple independent events as previously proposed. Using a broader data set that covers the wholeHelianthusgenus, including perennial species, we find that signals of introgression span the genus and beyond, suggesting highly divergent introgression and/or the sorting of ancient haplotypes. Thus,Helianthuscan be viewed as a syngameon in which largely reproductively isolated species are linked together by occasional or frequent gene flow.
Filtering microbial populations with a magnetic field
Authors: Nazareth Michelle , Kilinc Ece , Deamer David
Published: October 2022

Magnetic fields strongly affect currents of electrically charged particles such as electrons, protons and other ions in solution. Because ionic currents of protons or sodium drive the rotation of bacterial flagella, it is possible that the motion of motile bacterial species will be affected if they swim through a strong magnetic field. We tested this prediction in mixed cultures of soil bacteria and observed that a magnetic field does in fact exert a filtering effect that alters the composition of the mixed population of motile species. We then monitored motility and growth to see if magnetic fields affected individual bacterial species (Vibrio, Enterobacter sp. andPseudomonas sp.) The same magnetic field had no observable effect on motility or growth. Although magnetic fields may have served as a selective factor in the evolution of certain species such as magnetotactic motile bacteria, they do not appear to have a direct effect on the ionic current driving flagellar rotation.
Elucidation of Global Trends in the Effects of VX-661 and VX-445 on the Expression of Clinical CFTR Variants
Authors: McKee Andrew G. , McDonald Eli F. , Penn Wesley D. , Kuntz Charles P. , Noguera Karen , Chamness Laura M. , Roushar Francis J. , Meiler Jens , Oliver Kathryn E. , Plate Lars , Schlebach Jonathan P.
Published: October 2022

Cystic fibrosis (CF) is a chronic genetic disease caused by mutations that compromise the expression and/ or function of the cystic fibrosis transmembrane conductance regulator chloride channel (CFTR). Most people with CF harbor a common misfolded CFTR variant (ΔF508), which can be rescued by combination therapies containing “corrector” compounds that restore its expression. Nevertheless, there are over 400 other CF variants that differ in their sensitivity to correctors for reasons that remain unclear. In this work, we utilize deep mutational scanning to quantitatively compare the effects of two FDA-approved correctors on the plasma membrane expression of 129 known CF variants, including 45 that are currently unclassified. Across 67 variants with attenuated expression, we find that VX-661-sensitive variants generally exhibit intermediate expression and feature mutations near its binding pocket in transmembrane domains (TMDs) 1, 2, 3, and 6. VX-445 also primarily rescues variants with intermediate expression but is instead uniquely effective towards mutations near its binding pocket in TMDs 10 & 11. Structural calculations suggest corrector binding provides similar stabilization to both sensitive and insensitive variants. These findings collectively suggest the mutation-specific effects of these compounds depend on the degree of variant destabilization and/ or the timing of cotranslational folding defects. Combining these correctors synergistically rescues variants with deficient and intermediate expression alike, presumably by doubling the total binding energy and suppressing defects at different stages of translation. These results provide an unprecedented overview of the properties of rare CFTR variants and establish new tools for CF pharmacology.
A unified model for the dynamics of ATP-independent ultrafast contraction
Authors: Floyd Carlos , Molines Arthur T. , Lei Xiangting , Honts Jerry E. , Chang Fred , Elting Mary Williard , Vaikuntanathan Suriyanarayanan , Dinner Aaron R. , Bhamla M. Saad
Published: October 2022

In nature, several ciliated protists possess the remarkable ability to execute ultrafast motions using protein assemblies called myonemes, which contract in response to Ca2+ions. Existing theories, such as actomyosin contractility and macroscopic biomechanical latches, do not adequately describe these systems, necessitating new models to understand their mechanisms. In this study, we image and quantitatively analyze the contractile kinematics observed in two ciliated protists (Vorticella spandSpirostomum sp), and, based on the mechanochemistry of these organisms, we propose a minimal mathematical model that reproduces our observations as well as those published previously. Analyzing the model reveals three distinct dynamic regimes, differentiated by the rate of chemical driving and the importance of inertia. We characterize their unique scaling behaviors and kinematic signatures. Besides providing insights into Ca2+-powered myoneme contraction in protists, our work may also inform the rational design of ultrafast bioengineered systems such as active synthetic cells.
Non-viral gene editingin uterowith lipid nanoparticles complexed to mRNA
Authors: Gao Kewa , Li Jie , Song Hengyue , Han Hesong , Wang Yongheng , Yin Boyan , Farmer Diana L. , Murthy Niren , Wang Aijun
Published: October 2022

Nanoparticle-based drug delivery systems have the potential to revolutionize medicine but their low vascular permeability and rapid clearance by phagocytic cells have limited their medical impact. Nanoparticles delivered at thein uterostage have the potential to overcome these key limitations, due to the high rate of angiogenesis and cell division in fetal tissue, and the under-developed immune system. However, very little is known about nanoparticle drug delivery at the fetal stage of development. In this report, using Ai9 CRE reporter mice, we demonstrate that lipid nanoparticle (LNP) mRNA complexes can deliver mRNA for gene editing enzymesin uteroafter an intrahepatic injection, and can access and edit major organs, such as the heart, the liver, kidneys, lungs and the gastrointestinal tract with remarkable efficiency and low toxicity. In addition, we show here that Cas9 mRNA and sgRNA complexed to LNPs were able to edit the fetal organsin uteroafter an intrahepatic injection. These experiments demonstrate the possibility of non-viral delivery of gene editing enzymesin uteroand nanoparticle drug delivery has great potential for delivering macromolecules to organs outside of the liverin utero, which provides a promising strategy for treating a wide variety of devastating genetic diseases before birth.
Innate immune cell-intrinsic ketogenesis is dispensable for organismal metabolism and age-related inflammation
Authors: Goldberg Emily L. , Letian Anudari , Dlugos Tamara , Leveau Claire , Dixit Vishwa Deep
Published: October 2022

Aging is accompanied by chronic low-grade inflammation, but the mechanisms that allow this to persist are not well understood. Ketone bodies are alternative fuels produced when glucose is limited and improve indicators of healthspan in aging mouse models. Moreover, the most abundant ketone body, β-hydroxybutyrate (BHB), inhibits the NLRP3 inflammasome in myeloid cells, a key potentiator of age-related inflammation. Given that myeloid cells express ketogenic machinery, we hypothesized this pathway may serve as a metabolic checkpoint of inflammation. To test this hypothesis, we conditionally ablated ketogenesis by disrupting expression of the terminal enzyme required for ketogenesis, 3-Hydroxy-3-Methylglutaryl-CoA Lyase (HMGCL). By deleting HMGCL in the liver, we validated the functional targeting and establish that the liver is the only organ that can produce the life-sustaining quantities of ketone bodies required for survival during fasting or ketogenic diet feeding. Conditional ablation of HMGCL in neutrophils and macrophages had modest effects on body weight and glucose tolerance in agin, but worsened glucose homeostasis in myeloid cell specific Hmgcl deficient mice fed a high-fat diet. Our results suggest that during aging, liver derived circulating ketone bodies might be more important for deactivating NLRP3 inflammasome and controlling organismal metabolism.
An expandable FLP-ON::TIR1 system for precise spatiotemporal protein degradation inC. elegans
Authors: Xiao Yutong , Yee Callista , Martinez Michael A. Q. , Zhao Chris Z. , Zhang Wan , Shen Kang , Matus David Q. , Hammell Christopher
Published: October 2022

The auxin-inducible degradation system has been widely adopted in theC. elegansresearch community for its ability to empirically control the spatiotemporal expression of target proteins. This system can efficiently degradeauxin-inducibledegron (AID)-tagged proteins via the expression of a ligand-activatableAtTIR1 protein derived fromA. thalianathat adapts target proteins to the endogenousC. elegansproteosome. While broad expression ofAtTIR1 using strong, ubiquitous promoters can lead to rapid degradation of AID-tagged proteins, cell type-specific expression ofAtTIR1 using spatially restricted promoters often results in less efficient target protein degradation. To circumvent this limitation, we have developed a FLP/FRT3-based system that functions to reanimate a dormant, high-powered promoter that can drive sufficientAtTIR1expression in a cell type-specific manner. We benchmark the utility of this system by generating a number of tissue specific FLP-ON::TIR1 drivers to reveal genetically separable cell type-specific phenotypes for several target proteins. We also demonstrate that the FLP-ON::TIR1 system is compatible with enhanced degron epitopes. Finally, we provide an expandable toolkit utilizing the basic FLP-ON::TIR1 system that can be adapted to drive optimizedAtTIR1expression in any tissue or cell type of interest.
Engineered SMCHD1 and D4Z4 mutations reveal roles of D4Z4 heterochromatin disruption and feedforward DUX4 network activation in FSHD
Authors: Kong Xiangduo , Nguyen Nam Viet , Li Yumeng , Sakr Jasmine Shaaban , Williams Kate , Sharifi Sheila , Chau Jonathan , Bayrakci Altay , Mizuno Seiya , Takahashi Satoru , Kiyono Tohru , Tawil Rabi , Mortazavi Ali , Yokomori Kyoko
Published: October 2022

Facioscapulohumeral dystrophy (FSHD) is commonly associated with contraction of D4Z4 repeats on chromosome 4q (FSHD1). Mutations in theSMCHD1gene are linked to both minor cases with no prominent repeat loss (FSHD2) and severe cases of FSHD1. Abnormal upregulation of the transcription factor DUX4, encoded in theD4Z4repeat, is believed to play a central role in FSHD. However, defining the disease mechanism has been hampered by the heterogeneity of patient-derived cells, difficulty to detect DUX4 in patient myocytes, and limited animal models because D4Z4 repeats are primate-specific. To overcome these limitations, we engineered isogenic human skeletal myoblast lines with D4Z4 and/orSMCHD1mutations. We found a highly synergistic effect of double mutations on triggering two key disease processes, D4Z4 heterochromatin disruption and cross-stimulation of DUX4 targets, such as histone H3.X/Y and LEUTX transcription factor. Thus, engineered human myocyte models provide unique insights into the molecular mechanisms underpinning FSHD.

Teaser

FSHD mutations cause D4Z4 heterochromatin disruption and feedforward DUX4 network activation.
Manipulating Oxalate Decarboxylase Provides the Basis of Antilithic Therapy by Acting on the Gut Microbiota
Authors: Wu Fang , Cheng Yuanyuan , Zhou Jianfu , Ye Peisen , Liu Xuehua , Zhang Lin , Lin Rongwu , Xiang Songtao , Liu Zhongqiu , Wang Caiyan
Published: October 2022

A high concentration of oxalate is associated with an increased risk of kidney calcium oxalate (CaOx) stones, and the degradation of exogenous oxalate mainly depends on oxalate-degrading enzymes from the intestinal microbiome. We found that Zinc Gluconate supplement to patients with CaOx kidney stones could significantly improve the abundance of oxalate metabolizing bacteria in human body through clinical experiments on the premise of simultaneous antibiotic treatment and the imbalance ofLactobacillusand OxDC was involved in CaOx kidney stones through clinical sample analysis. Then, we identified that Zn2+could be used as an external factor to improve the activity of OxDC and protectLactobacillus, achieved the preventive effect on rats with stones aggravated by antibiotics. Finally, by analyzing the three-dimensional structure of OxDC and somein vitroexperiments, we propose a hypothesis Zn2+increases the metabolism of oxalate in humans through its positive effects onLactobacillusand OxDC to reduce CaOx kidney stone symptoms in rats.

IMPORTANCE

Urinary stone disease is one of the most common urological disorders, and 70%-80% of urinary stones are calcium oxalate (CaOx) stones. We found the structural basis and metabolic mechanism by which oxalate decarboxylase metabolizes oxalate were elucidated, and Zn2+was illustrated to have therapeutic effects on CaOx stones by improving the tolerance of Lactobacillus to antibiotics. According to that, proper Zn2+levels in the diet, the consumption of more probiotic food and avoidance of the antibiotic overuse might be desirable measures for the prevention and treatment of kidney stones.

Graphical Abstract
β-catenin-dependent endomesoderm specification appears to be a Bilateria-specific co-option
Authors: Lebedeva Tatiana , Boström Johan , Mörsdorf David , Niedermoser Isabell , Genikhovich Evgeny , Adameyko Igor , Genikhovich Grigory
Published: October 2022

Endomesoderm specification based on a maternal β-catenin signal and axial patterning by interpreting a gradient of zygotic Wnt/β-catenin signalling was suggested to predate the split between Bilateria and their evolutionary sister Cnidaria. However, in Cnidaria, the roles of β-catenin signalling in both these processes have not been proven directly. Here, by tagging the endogenous β-catenin protein in the sea anemoneNematostella vectensis, we show that the oral-aboral axis in a cnidarian is indeed patterned by a gradient of β-catenin signalling. Unexpectedly, in a striking contrast to Bilateria,Nematostellaendoderm specification takes place opposite to the part of the embryo, where β-catenin is translocated into the nuclei. This suggests that β-catenin-dependent endomesoderm specification is a Bilateria-specific co-option, which may have linked endomesoderm specification with the subsequent posterior-anterior patterning.
Daily turnover of active giant virus infection during algal blooms revealed by single-cell transcriptomics
Authors: Hevroni Gur , Vincent Flora , Ku Chuan , Sheyn Uri , Vardi Assaf
Published: October 2022

Viruses are the most abundant biological entity in the ocean and play a significant role in shaping the marine ecosystem. The past two decades have revealed an outstanding diversity of giant viruses infecting protists across the tree of life and, in particular, algae that form massive blooms in the ocean. Virus-induced bloom demise significantly impacts marine ecology and biogeochemistry, as well as the associated microbial community. Nevertheless, little is known about the infection dynamics of these giant viruses in the natural environment and their role in regulating algal blooms. Here, we provide evidence for a daily life cycle of giant viral infection in algal blooms by processing the transcriptome of over 12,000 single algal cells during different phases of interaction with their giant viruses. We revealed that viral infection occurs already at the exponential phase of the bloom and that the timing of infection can determine the magnitude of the bloom but not the fraction of infected cells. We further revealed that the same proportion of infected cells are in the early phase of the viral replication program (13.5%) throughout several consecutive days of the bloom, suggesting that a daily turnover of infection is at play during the bloom and demise phases of the algal population. This may imply that a continuous source of virocell-associated metabolites diffuses throughout the bloom succession and could fuel the microbial food webs. Finally, we link single cell infection state to host physiology and show that infected cells remained calcified even in the late stage of infection, contradicting common observation of bulk population in which viral infection is directly linked with decalcification. Together, these results highlight the importance of studying host-virus dynamics in natural populations at a single-cell resolution, which can provide a fresh view of the dynamics and propagation of viral infection. This approach will enable quantification of the impact of marine viruses on microbial food webs.
Exploration of the sensitivity to macrocyclic lactones in the canine heartworm (Dirofilaria immitis) in Australia using phenotypic and genotypic approaches
Authors: Power Rosemonde Isabella , Šlapeta Jan
Published: October 2022

Canine heartworm disease is a potentially deadly cardiopulmonary disease caused by the mosquito-borne filarial nematodeDirofilaria immitis. In Australia, the administration of macrocyclic lactone (ML) drugs has successfully reduced the prevalence ofD. immitisinfection. However, the recent re-emergence ofD. immitisin dogs in Queensland, Australia and the identification of ML-resistant isolates in the USA poses an important question of whether ML-resistance has emerged in this parasite in Australia. The aim of this study was to utilise phenotypic and genotypic approaches to examine the sensitivity to ML drugs inD. immitisin Australia. To do this, we surveyed 45 dogs from Queensland and New South Wales across 3 years (2019-2022) for the presence ofD. immitisinfection using an antigen test, quantitative Modified Knott’s test, and qPCR targeting bothD. immitisand theD. immitissymbiontWolbachia. A phenotype observed by utilising sequential quantification of microfilariae for 23/45 dogs was coupled with genetic testing of filtered microfilariae for SNPs previously associated with ML-resistance in isolates from the USA. Sixteen (16/45) dogs tested positive forD. immitisinfection despite reportedly receiving ‘rigorous’ heartworm prevention for 12 months prior to the study, according to the owners’ assessment. The phenotype and genotypic assays in this study did not unequivocally demonstrate the presence of ML-resistantD. immitisin Australia. Although the failure of 16 dogs to reduce microfilaremia by >90% after ML treatment was considered a suspect phenotype of ML-resistance, no genotypic evidence was discovered using the genetic SNP analysis. The traditional quantitative Modified Knott’s test can be substituted by qPCR targetingD. immitisor associatedWolbachiaendosymbiont DNA for a more rapid measurement of microfilariae levels. More definitive phenotypic evidence of resistance is critically needed before the usefulness of SNPs for the detection of ML-resistance in Australia can be properly assessed.
The Allosterically Modulated Free Fatty Acid Receptor 2 is Transactivated by an Increase in the Cytosolic Concentration of Calcium Ions
Authors: Lind Simon , Wu Yanling , Sundqvist Martina , Forsman Huamei , Dahlgren Claes
Published: October 2022

Allosterically modulated free fatty acid receptor 2 (FFA2R/GPR43) can be activated without the involvement of any orthosteric FFA2R agonist, by signals generated for example by P2Y2R, the G protein coupled receptor for ATP. An FFA2R specific positive allosteric modulator (PAM; Cmp58) was used to disclose the molecular mechanism by which signals generated by ATP/P2Y2R transactivates FFA2R. The P2Y2R induced signal that transactivates the allosterically modulated FFA2R was generated downstream of the Gαqcontaining G protein that couple to P2Y2R. A receptor induced rise in the cytosolic concentration of ionized calcium ([Ca2+]i) was hypothesized to be the receptor transactivation signal. The Gαqdependent transient rise in [Ca2+]iinduced by the ATP activated P2Y2Rs was not affected by Cmp58. The hypothesis gained, however, support from the finding that the modulator transferred FFA2R to a Ca2+sensitive state. The rise in [Ca2+]iinduced by the Ca2+specific ionophore ionomycin, activated the allosterically modulated FFA2R. The response induced by ionomycin was rapidly terminated and the FFA2Rs could then no longer be activated by the orthosteric FFA2R agonist propionate or be transactivated by the signal generated by the activated ATP receptor. The desensitized/non-responding state of FFA2R was, however, revoked by an earlier described cross-sensitizing/activating allosteric FFA2R modulator. The receptor transactivation of the allosterically modulated FFA2Rs, represent a unique regulatory receptor cross-talk mechanism by which the activity of a G protein coupled receptor is controlled by a signaling system operating from the cytosolic side of the plasma membrane.

One-sentence summary

A P2Y2receptor signal generated downstream of a Gαq containing G protein transactivates the allosterically modulated FFA2 receptor
SLICER: Seamless Loss of Integrated Cassettes Using Endonuclease Cleavage and Recombination inDeinococcus radiodurans
Authors: Brumwell Stephanie L. , Van Belois Katherine D. , Nucifora Daniel P. , Karas Bogumil J.
Published: October 2022

Methods for creating seamless genome modifications are an essential part of the microbial genetic toolkit that allows for strain engineering through the recycling of selectable markers. Here, we report the development of a method, termed SLICER, which can be used to create seamless genome modifications inD. radiodurans. We used SLICER to sequentially target four putative restriction-modification (R-M) system genes, recycling the same selective and screening markers for each subsequent deletion. A fifth R-M gene was replaced by a selectable marker to create a finalD. radioduransstrain with 5 of the 6 putative R-M systems deleted. While we observed no significant increase in transformation efficiency, SLICER is a promising method to obtain a fully restriction-minus strain and expand the synthetic biology applications ofD. radioduransincluding as anin vivoDNA assembly platform.

GRAPHICAL ABSTRACT
Intrinsically disordered protein regions are required for cell wall homeostasis inBacillus subtilis
Authors: Brunet Yannick R. , Habib Cameron , Brogan Anna P. , Artzi Lior , Rudner David Z.
Published: October 2022

Intrinsically disordered protein regions (IDRs) have been implicated in diverse nuclear and cytoplasmic functions in eukaryotes, but their roles in bacteria are less clear. Here, we report that extracytoplasmic IDRs inBacillus subtilisare required for cell wall homeostasis. TheB. subtilisσItranscription factor is activated in response to envelope stress through regulated intramembrane proteolysis (RIP) of its membrane-anchored anti-σ factor, RsgI. Unlike canonical RIP pathways, we show that ectodomain (site-1) cleavage of RsgI is constitutive, but the two cleavage products remain stably associated, preventing intramembrane (site-2) proteolysis. The regulated step in this pathway is their dissociation, which is triggered by impaired cell wall synthesis and requires RsgI's extracytoplasmic IDR. Intriguingly, the major peptidoglycan polymerase PBP1 also contains an extracytoplasmic IDR, and we show that this region is important for its function. Disparate IDRs can replace the native IDRs on both RsgI and PBP1, arguing that these unstructured regions function similarly. Our data support a model in which the RsgI–σIsignaling system and PBP1 represent complementary pathways to repair gaps in the PG meshwork. The IDR on RsgI senses these gaps and activates σI, while the IDR on PBP1 directs the synthase to these sites to fortify them.
Insights into the structural symmetry of YCrO3 from synchrotron X-ray diffraction
Authors: Zhao Qian , Sun Kaitong , Zhu Yinghao , Zhao Zirui , Li Hai-Feng
Published: October 2022

A high-resolution synchrotron X-ray diffraction study of a single-crystal YCrO3 compound was employed to obtain its crystallographic information, such as lattice parameters, atomic positions, bond lengths and angles, and local crystalline distortion size and mode. The measurements were taken at 120 K (below the antiferromagnetic transition temperature T
N ≃ 141.5 K), 300 K (between T
N and the ferroelectric transition temperature T
C ≃ 473 K) and 500 K (above T
C). Using the high intensity of synchrotron X-rays, it was possible to refine collected patterns with the previously proposed noncentrosymmetric monoclinic structural model (P1211, No. 4) and determine detailed structural parameters. Meanwhile, for a controlled study, the data were refined with the centrosymmetric orthorhombic space group (Pmnb, No. 62). The lattice constants a, b and c and the unit-cell volume increased nearly linearly upon heating. With the P1211 space group, the distributions of bond lengths and angles, as well as local distortion strengths, were observed to be more dispersed. This implies that (i) the local distortion mode of Cr2O6 at 120 K correlates with the formation of canted antiferromagnetic order by Cr1–Cr2 spin interactions, primarily via intermediate O3 and O4 ions; and (ii) the previously reported dielectric anomaly may have a microscopic origin in the strain-balanced Cr1—O3(O4) and Cr2—O5(O6) bonds as well as the local distortion modes of Cr1O6 and Cr2O6 octahedra at 300 K. Local crystalline distortion is shown to be an important factor in the formation of ferroelectric order. The comprehensive set of crystallographic information reported here allows for a complete understanding of the unique magnetic and ferroelectric properties of YCrO3.
The impact of social media technologies on organization cultural intelligence and new product development in international markets
Authors: Hazzam Joe , Wilkins Stephen , Strong Carolyn
Published: October 2022

Purpose

The study examines the role of social media technologies (SMTs) as a driver of organization cultural intelligence (OCI) and new product development (NPD) capabilities, and how the complementary effects of these capabilities contribute to multinational corporations (MNCs)’ performance. Further, the study investigates the capability–performance relationship under conditions of high and low market and technological turbulence.

Design/methodology/approach

A quantitative survey method was implemented, with the data provided by senior marketing managers employed in MNC regional offices. The proposed model was tested using structural equation modeling and multi-group moderation analysis, and fuzzy-set qualitative comparative analysis (fsQCA).

Findings

The results indicate that SMTs support the development of OCI and NPD capabilities, which in turn contribute to MNC regional performance. A high level of technological turbulence only weakens the relationship between OCI and performance.

Research limitations/implications

The results suggest that OCI contributes to MNCs’ performance, by deploying social media information and complementing the organization’s NPD capability under a specific environmental context.

Practical implications

The paper offers practical recommendations to MNCs on social media use when developing and launching new products in different regional markets. MNCs need to recruit culturally intelligent managers, who consider the level of market and technological turbulence when combining several types of capabilities.

Originality/value

Within the dynamic marketing capabilities literature, this is the first study to incorporate and reliably measure cultural intelligence capability. The research offers empirical evidence that OCI and NPD capabilities are necessary to achieve superior MNC performance and depend on the level of market and technological turbulence.
Dynamic brand positioning: a firm-customer synergistic strategy of brand meaning cocreation in a hyperconnected world
Authors: He Jiaxun , Zhang Fan
Published: October 2022

Purpose

This study aims to explore how cocreated brand meaning builds and affects dynamic brand positioning in a hyperconnected world.

Design/methodology/approach

The authors conducted a qualitative study of Casarte, a high-end appliance brand, as an instrumental case for conceptualizing and theorizing. This study constructs a matrix of dynamic brand positioning as the key analysis framework using in-depth interview data, firm materials and user-generated content from online brand communities.

Findings

The matrix of dynamic brand positioning has two dimensions: brand core and peripheral meaning, and firm- and customer-led orientation. The interaction between the firm and its customers strengthens the understanding of a brand’s core meaning and consistency perception, expands the scope of brand peripheral meaning and improves the perception of brand meaning diversity. The mutual transformation of the ambidexterity of core and peripheral meanings facilitates the dynamic positioning of brands.

Research limitations/implications

This study is a qualitative case study; the relevant conclusions have not been tested empirically. If longitudinal data of actual tracking support the effect of dynamic brand positioning, the theory’s reliability can be more rigorously tested.

Practical implications

It provides managerial logic and a tool for firms to practice dynamic brand positioning in a hyperconnected world, which contributes to the implementation of the emerging firm-customer synergistic strategy.

Originality/value

This study proposes a construct of dynamic brand positioning supported by qualitative evidence. It disputes the traditional view that brand positioning is determined by the perception of core meaning consistency and creatively puts forward the view that brand positioning evolves dynamically with the mutual transformation of the ambidexterity of brand core meaning and peripheral meaning.
Launching the dynamic employee engagement framework: towards a better understanding of the phenomenon
Authors: Davis Amanda S. , Van der Heijden Beatrice I.J.M.
Published: October 2022

Purpose

The dynamic employee engagement framework visually delineates employee engagement from its antecedents and responds to the debates regarding how employee engagement is positioned within the academic literature.

Design/methodology/approach

A narrative literature review was conducted.

Findings

The new framework visually demonstrates the impact of contextual changes on employee engagement. Additionally, it positions employee engagement as a psychological state (psychological presence) and as a behaviour.

Research limitations/implications

The new framework promotes the study of behavioural engagement when the incorporation of context and/or multiple voices is required. Accordingly, studying behavioural engagement may help scholars understand more about the dynamics of employee engagement within and across different settings, reduce the reliance on self-reported studies and help bridge the employee engagement academic and practitioner discourses.

Practical implications

Human resource management/development practitioners and line managers may use the new structured framework in several ways to help them foster employee engagement.

Originality/value

The new framework extends five integrated employee engagement models by incorporating the macro and micro external context, and repositioning trust and feedback. In doing so, it more accurately conveys diagrammatically the dynamic nature of employee engagement following significant contextual changes. It also visually separates out the antecedents to employee engagement thus respecting construct boundaries and positions employee engagement as a multi-dimensional construct comprised of psychological state (psychological presence) and behavioural engagement. Building on this, we also argue that double-loop learning is an example of behavioural engagement.
Effect of the geometric parameter difference of multilayer structural transfer film on the wear of PTFE-based composites
Authors: Zhang Longxiao , Xie Ting
Published: October 2022

Purpose

The purpose of this paper is to explore the geometric parameter difference of the terrace-like structural transfer film under different working parameters [pressure and velocity (PV) values] and filled particle types (three fillers: SiO2, TiO2 and ZnO), and find the geometric parameter related to the wear of polytetrafluoroethylene (PTFE)-based composites.

Design/methodology/approach

PTFE composites were filled with SiO2, TiO2 and ZnO particles, and the morphology parameter of the PTFE composite transfer film under different PV values obtained from the rotary reciprocating pin-on-disk frictional tester was quantified by using a three-dimensional laser scanning microscope.

Findings

The results showed that the effective layer coverage rate and effective thickness of the transfer film had a good relationship with the wear of the three PTFE composites. On the whole, increasing the speed or load was helpful to increase the effective thickness of the three PTFE composite transfer films, but reduced the effective layer coverage rate. The greater the effective layer coverage rate and effective thickness of the transfer film, the better the wear resistance of the PTFE composites in the entire speed and load range.

Originality/value

This work will promote further understanding of the transfer film and lay a foundation for realizing its morphology regulation and improving the wear of the PTFE composites.
Spatial pattern of burglary in residential neighbourhoods: a case study of Abuja, Nigeria
Authors: Iliyasu Idris Isah , Abdullah Aldrin , Hedayati Marzbali Massoomeh
Published: October 2022

Purpose

Abuja, the capital city of Nigeria, is one of the fastest growing capital cities in sub-Saharan Africa. Recently, the city is experiencing an alarming rate of burglary and violent crimes, while the city planning management frameworks lacks adequate and effective crime mapping, monitoring and management techniques necessary for achieving liveable and safe environment for habitation despite its grandiose spatial planning and aesthetically appealing architectural design as a modern city. Based on police crime records (2007–2018) and geospatial analysis, this paper aims to provide adequate understanding on the interplay of land use configuration and burglary crime formation in residential neighbourhoods of Abuja, Nigeria.

Design/methodology/approach

The methods used for the purpose of data collection includes; field survey, Block Environmental Inventory, while inferential statistics and Geographic Information System tools was used for data analysis. The analysis established that Lagos, Nsukka and Enugu Streets are hotspots; while Chief Palace street, Ladoke Akintola and Oka-Akoko streets were found to be cold spots.

Findings

This study, however, established the applicability of crime pattern, opportunity theory and routine activity theory in understanding the rising burglary crime events in the study areas and the link between physical characteristics of street block typology and burglary crime pattern. The results of the analysis has in a way affirmed the positions of the theories, while disagreed with them in cases where the results indicated contrary outcome.

Originality/value

This paper concluded with inference drawn from the results that supported mixed-use development but with built-in crime prevention through environmental design strategies as effective burglary crime prevention mechanisms that contribute to crime rate reduction.
Open strategizing and accelerated internationalization process in different contexts
Authors: Bellucci Christiane , Lavarda Rosalia Aldraci Barbosa , Floriani Dinorá Eliete
Published: October 2022

Purpose

Due to the changes in organizational, social, cultural and technological factors, companies from different contexts are shifting towards open forms of strategy-making with more widened inclusion of internal and external actors and greater transparency regarding their strategic issues, including their internationalization processes. The purpose of this paper is to understand how Open Strategizing occurs in the accelerated process of internationalization considering different contexts.

Design/methodology/approach

The authors conducted a qualitative comparative case study in Brazilian and English technology-based small and medium-sized enterprises (SMEs) which rapidly internationalized. Furthermore, data was collected through semi-structured interviews, observations and documental analysis.

Findings

The authors suggest that openness contributes to the accelerated process of internationalization. Additionally, the authors show that the home-country and the national cultural contexts affect openness. The authors also disclose openness as crucial and inherent to the accelerated process of internationalization, while context is relevant but not determinant in the Open Strategizing.

Originality/value

The authors contribute to Open Strategy (OS) literature by presenting how Open Strategizing unfolds daily during the internationalization process and by evidencing the role of home-country and national cultural contexts in the configuration and dynamics of Open Strategizing. The authors also contribute to the international entrepreneurship (IE) literature by advancing the understanding of the strategies and drivers adopted by technology-based SMEs internationalizing in an accelerated way.
Impact of workplace bullying on knowledge hiding: The mediating role of emotional exhaustion and moderating role of workplace friendship
Authors: Islam Talat , Chaudhary Arooba
Published: October 2022

Purpose

Workplace bullying has become a major challenge across the globe as it is associated with negative outcomes. Therefore, this study was designed to assess the impact of workplace bullying on knowledge hiding through emotional exhaustion. The study further investigated the moderating role of workplace friendship to reduce the detrimental effect of workplace bullying on knowledge hiding.

Design/methodology/approach

The study collected data from 358 nurses working in three large cities (Karachi, Islamabad and Lahore) of Pakistan in two lags to tackle the issue of common method bias.

Findings

The study applied structural equation modeling with maximum likelihood method using AMOS to test the hypotheses. The study noted that workplace bullying elevates emotional exhaustion and knowledge hiding among nurses; whereas, workplace friendship was noted as an essential factor to control adverse effects of workplace bullying on knowledge hiding.

Research limitations/implications

The study used a cross-section design that restricts causality. However, the findings of this study add to the conservation of resources theory by providing insights into the role of workplace friendship in reducing the relationship between workplace stressors (bullying) and negative behaviors (knowledge hiding). The study also suggests healthcare administration foster workplace friendship to cope with the negative outcomes of workplace bullying.

Originality/value

Drawing upon conservation of resources, this study explored the moderating role of workplace friendship between workplace bullying and knowledge hiding.
Novel approaches to energize microbial biocatalysts
Authors: Durante‐Rodríguez Gonzalo , Carmona Manuel , Díaz Eduardo
Published: October 2022

An efficient and cheap energization of microbial biocatalysts is essential in current biotechnological processes. A promising alternative to the use of common organic or inorganic electron donors is the semiconductor nanoparticles (SNs) that absorb light and transfer electrons (photoelectrons) behaving as artificial photosynthetic systems (biohybrid systems). Excited photoelectrons generated by illuminated SNs are highly reductive and readily accepted by membrane‐bound proteins and electron shuttles to drive specific cell reduction processes and energy generation in microbes. However, the operational mechanisms of these hybrid systems are still poorly understood, especially at the material–microbe interface, and therefore the design and production of efficient biohybrids are challenging. Some major limitations/challenges and future prospects of SNs as microbial energization systems are discussed.
Case report: Successful treatment with tofacitinib and colchicine in a patient with Schnitzler syndrome
Authors: Li Man , Chen Yu‐Wen , Shen Amy , Xie Yong‐Xin , Wu Yonglan , Zeng Xianlin , Leong Pui‐Ying
Published: October 2022

We report a case of late‐onset Schnitzler syndrome successfully treated with Janus‐activated kinase (JAK) inhibitors and colchicine. Schnitzler syndrome should be considered for recurrent chronic urticaria when accompanied by fever, fatigue, rapid weight loss, and poor response to antihistamine treatment. Skin biopsy, bone marrow biopsy, and electrophoresis help confirm the diagnosis. Early diagnosis and treatment can lead to complete resolution of symptoms. Besides interleukin (IL)‐1 and IL‐6 inhibitors, JAK inhibitors and colchicine may be considered as other choices of treatment.