bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep phylotaxonogenomic revision of the genus Xanthomonas within family Xanthomonadaceae and proposal of novel family Frateuriaceae within order Xanthomonadales
Authors: Bansal Kanika , Kumar Sanjeet , Singh Anu , Chaudhary Arushi , Patil Prabhu B.
Published: September 2022

Genus Xanthomonas is primarily comprise phytopathogenic species. In a recent study by carrying out deep phyto-taxonogenomics, we reported that even the genera Xylella, Stenotrophomonas and Pseudoxanthomonas are miss-classified and belong to genus Xanthomonas. Hence to understand the breadth of the genus, we carried out deep phylo-taxonogenomics of the order Xanthomonadales. Such investigation revealed that at least four more genera belong to genus Xanthomonas with prominent being Lysobacter. Further order level deep phylo-taxonogenomics revealed two major families. One being the original family Xanthomonadaceae and other is proposed as Frateuriaceae fam. nov. as synonym of family Rhodanobacteraceae with novel genus Frateuria gen. nov.
The cell envelope of Thermotogae suggests a mechanism for outer membrane biogenesis
Authors: Sexton Danielle L. , Hashimi Ameena , Sibanda Lloyd , Beskrovnaya Polina , Huan Tao , Tocheva Elitza I.
Published: September 2022

The presence of a cell membrane is one of the major structural components defining life. Recent phylogenomic analyses have supported the hypothesis that the last bacterial common ancestor was likely a diderm. Yet, the mechanisms that guided outer membrane (OM) biogenesis remain unknown. Thermotogae is an early-branching phylum with a unique OM, the toga, previously shown to form 2-dimensional arrays of β-barrel trimers. Here we use cryo-electron tomography to characterize the in situ cell envelope architecture of Thermotoga maritima, proteomics and lipidomics to identify the protein and lipid composition of the toga, and bioinformatics to assess the distribution of the major toga components across the phylum. We show that the toga is composed of multiple Ompα and β-barrel homologs that represent a highly diverse bipartite OM-tethering system. We further reveal the presence of membrane microdomains (∼200nm) in the toga that are enriched in phosphatidylethanolamine (PE) lipids required to support the type 4 pilus and the BamA transmembrane complexes. Together, our results highlight a toga-like structure as a possible intermediate between monoderm and diderm cell envelope transitions.
PbAP2-FG2 and AP2R-2 function together as a transcriptional repressor complex essential for Plasmodium female development
Authors: Nishi Tsubasa , Kaneko Izumi , Iwanaga Shiroh , Yuda Masao
Published: September 2022

Gametocyte development is a critical step in the life cycle of Plasmodium. Despite that numbers of studies in the gametocyte development have been conducted, the molecular mechanisms regulating this process remains to be fully understood. This study investigates the functional roles of two female-specific transcriptional regulators, PbAP2-FG2 and AP2R-2, in P. berghei. Knockout of pbp2-fg2 or ap2r-2 impairs female gametocyte development, resulting in developmental arrest during ookinete development. ChIP-seq analyses of these two factors indicated their colocalization on the genome, suggesting they function as a complex. These analyses also revealed that their target genes contained a variety of genes, including both male and female-enriched genes. Moreover, differential expression analyses showed that these target genes were upregulated through the disruption of pbp2-fg2 or ap2r-2, indicating that these two factors function as a transcriptional repressor complex in female gametocytes. Further target analysis demonstrated a significant overlap between the target genes of PbAP2-FG2 and AP2-G, suggesting that repression of early gametocyte genes activated by AP2-G is one of the key roles for this female transcriptional repressor complex. Our results indicate that the PbAP2-FG2-AP2-R2 complex-mediated repression of the target genes supports the female differentiation from early gametocytes.

Author Summary

Gametocyte development in Plasmodium parasites, a causative agent of malaria, is an essential step for their transmission from vertebrate hosts to mosquitoes. Gametocytes are sexual precursor cells produced from a subpopulation of asexual blood-stage parasites. Upon uptake by mosquitoes through blood feeding, the male and female gametocytes become microgametes and macrogametes, respectively, and then they fertilize and develop into the mosquito midgut invasive stage, called ookinete. Therefore, it is crucial to understand the underlying mechanisms regulating this developmental process. This study revealed that the two female transcriptional regulators, PbAP2-FG2 and AP2R-2, function together as an essential transcriptional repressor complex in P. berghei, the target genes of which include male, female, and early gametocyte genes activated by AP2-G. Our findings suggest that PbAP2-FG2 and AP2R-2 play multiple roles in supporting the development of female gametocytes from early gametocytes.
USP7 inactivation suppresses APC-mutant intestinal hyperproliferation and tumor development
Authors: Novellasdemunt Laura , Kucharska Anna , Baulies Anna , Vlachogiannis Georgios , Repana Dimitra , Rowan Andrew , Suárez-Bonnet A , Ciccarelli Francesca , Valeri Nicola , Li Vivian S. W.
Published: September 2022

Truncating mutation of the tumor suppressor gene adenomatous polyposis coli (APC) is the hallmark of colorectal cancer (CRC), resulting in constitutive WNT activation. Despite decades of research, targeting WNT signaling in cancer remains challenging due to its essential role in normal stem cell maintenance. We have previously shown that the deubiquitinating enzyme USP7 is a tumor-specific WNT activator in APC-truncated cells by deubiquitinating and stabilizing β-catenin, but its role in gut tumorigenesis is unknown. Here we show in vivo that deletion of Usp7 in Apc-truncated mice inhibits crypt hyperproliferation and intestinal tumor development. Importantly, intestine-specific Usp7 mutation does not yield any phenotype in wildtype animals, indicating that its loss is well tolerated. Unexpectedly, prolonged deletion of Usp7 in Apc+/− intestine induces varying degrees of colitis. Treatment with a USP7 inhibitor suppresses growth of patient-derived cancer organoids in vitro and of xenografts carrying APC truncations. We propose that USP7 inhibition may be efficacious for tumor-specific therapy of sporadic APC-mutated CRC, while patients with germline APC mutations should not receive such treatment.

Highlights

Usp7 deletion in Apc-truncated mice reduces intestinal tumor development.

Intestine-specific Usp7 mutation mutation has no phenotype in wildtype animals.

Treatment with Usp7 inhibitor suppresses growth of patient-derived cancer organoids carrying Apc truncations in vitro and of xenografts.
UBA52 attunes VDAC1-mediated mitochondrial dysfunction and dopaminergic neuronal death
Authors: Tiwari Shubhangini , Singh Abhishek , Gupta Parul , K Amrutha , Singh Sarika
Published: September 2022

Mitochondrial homeostasis regulates energy metabolism, calcium buffering, cell function and apoptosis. The present study has been conducted to investigate the implications of ubiquitin-encoding gene UBA52 in mitochondrial physiology. Transient expression of Myc-UBA52 in neurons significantly inhibited the rotenone-induced increase in reactive oxygen species generation, nitrite level and depleted glutathione level. Mass spectrometric and co-immunoprecipitation data suggested the profound interaction of UBA52 with mitochondrial outer membrane channel protein, VDAC1 in both the wild-type and Myc-α-synuclein overexpressed neuronal cells and in the Parkinson’s disease (PD)-specific substantia nigra and striatal region of the rat brain. In vitro ubiquitylation assay revealed that UBA52 participates in the ubiquitylation of VDAC1 through E3 ligase CHIP. Myc-UBA52 overexpression in neurons further improved the mitochondrial functionality and cell viability by preventing the alteration in mitochondrial membrane potential, mitochondrial complex-I activity, translocation of cytochrome-c and p-Nrf2 along with effect on intracellular calcium uptake, thus collectively inhibiting the opening of mitochondrial permeability transition pore. Additionally, Myc-UBA52 expression in neuronal cells offered protection against apoptotic and autophagic cell death. Altogether, our findings delineate functional association between UBA52 and mitochondrial homeostasis, providing new insights into the deterrence of dopaminergic cell death during acute PD pathogenesis.
Strand-biased circularizing integrative elements spread tmexCD-toprJ gene clusters encoding RND-type multidrug efflux pumps by repeated transpositions
Authors: Dao Trung Duc , Yano Hirokazu , Takemura Taichiro , Hirabayashi Aki , Trang Le Thi , Tran Hoang Huy , Shibayama Keigo , Hasebe Futoshi , Kasuga Ikuro , Suzuki Masato
Published: September 2022

Antimicrobial resistance genes (ARGs) are associated with mobile genetic elements (MGEs) that conscript useful genes into the human–microbe and microbe–microbe battlefields. Thus, under intense selective pressure, ARGs have been constantly adapting and evolving, spreading among microbes. tmexCD-toprJ gene clusters, which encode resistance–nodulation–cell division (RND)-type efflux pumps, confer multidrug-resistance to clinically important antimicrobials, including tigecycline. Noteworthily, these gene clusters have emerged in gram-negative bacteria in humans, animals, and the environment worldwide by MGE-mediated transfer. Here we show a hidden MGE, strand-biased circularizing integrative element (SE), that is recently recognized to mediate transpositions of ARGs, associated with the spread of tmexCD-toprJ gene clusters. We identified multidrug-resistant isolates of Aeromonas species in a water environment in Vietnam that harbored multiple copies of tmexCD-toprJ in their chromosomes that were associated with SEs. In particular, Aeromonas hydrophila NUITM-VA1 was found to harbor two copies of a novel variant of tmexC3.3D3.3-topJ1 within cognate SEs, whereas Aeromonas caviae NUITM-VA2 harbored four copies of a novel variant of tmexC2D2.3-topJ2 within cognate SEs. Based on the nature of SE to incorporate a neighboring sequence into the circular form and reinsert it into target sites during transposition, we identified the order of intragenomic movements of tmexCD-toprJ gene clusters. Altogether, our findings suggest that most known subgroups of tmexCD-toprJ and their subvariants underwent transpositions among bacterial chromosomes and plasmids via SEs. Hence, a tmexCD-toprJ gene cluster ancestor may have been initially mobilized via SE, subsequently spreading among bacteria and evolving in new hosts.
Proteomics Characteristics Reveal the Risk of T1 Colorectal Cancer Metastasis to Lymph Nodes
Authors: Zhuang Aojia , Zhuang Aobo , Qin Zhaoyu , Zhu Dexiang , Ren Li , Wei Ye , Zhou Pengyang , Yue Xuetong , He Fuchu , Xu Jianming , Ding Chen
Published: September 2022

Background

The presence of lymph node metastasis (LNM) affects treatment strategy decisions in T1NxM0 colorectal cancer (CRC), but the currently used clinicopathological-based risk stratification cannot predict LNM accurately. In this study, we established a classifier for predicting LNM in T1 CRC.

Methods

We detected proteins in formalin-fixed paraffin-embedded (FFPE) tumor samples from 143 LNM-negative and 78 LNM-positive patients with T1 CRC and revealed changes in molecular and biological pathways by label-free LC-MS/MS. An effective prediction model was built and validated in a training cohort (N=132) and two validation cohorts (VC1, N=42; VC2, N=47) by machine learning. We further built a simplified classifier with 9 proteins. The expression patterns of 13 proteins were confirmed by immunohistochemistry, and the IHC score of 5 proteins were used to build a IHC predict model.

Result

Patients with or without LNM have different molecular signatures. The 55-proteins prediction model achieved an impressive AUC of 1.00 in the training cohort, 0.96 in VC1 and 0.93 in VC2. The 9-protein classifier achieved an AUC of 0.824, and the calibration plot was excellent. We found that 5 biomarkers could predict LNM by the IHC score, with an AUC of 0.825. RHOT2 silence significantly enhanced migration and invasion of colon cancer cells.

Conclusions

Our study explored the mechanism of metastasis in T1 CRC and can be used to facilitate the individualized prediction of LNM in patients with T1 CRC, which may provide a guidance for clinical practice in T1 CRC.
Epigenetic mechanisms controlling human leukemia stem cells and therapy resistance
Authors: Takao Sumiko , Morell Victor , Uni Masahiro , Slavit Alicia , Rha Sophia , Cheng Shuyuan , Schmalbrock Laura K , Brown Fiona C , Beneyto-Calabuig Sergi , Koche Richard P , Velten Lars , Kentsis Alex
Published: September 2022

Many human cancers, including acute myeloid leukemia (AML), arise from mutations of stem and progenitor cells. Immunophenotypic profiling has shown that leukemias develop hierarchically, with mutations in leukemia stem cells associated with disease propagation and relapse1,2. Although leukemia initiating cells can be enriched using cell surface markers, their frequency tends to be variable and low, obscuring mechanisms and hindering effective therapies3,4. To define AML stem cells in human patients, we performed functional genomic profiling of diverse leukemias using label tracing techniques designed to preserve hematopoietic stem cell (HSC) function in vivo. We found that propagation of human AML is mediated by a rare but distinct quiescent label-retaining cell (LRC) population that evades detection by currently known immunophenotypic markers. We show that human AML LRC quiescence is reversible, sparing genetic clonal competition that maintains its epigenetic inheritance. LRC quiescence is defined by distinct promoter-centered chromatin and gene expression dynamics and controlled by a distinct AP-1/ETS transcription factor network, including JUN in particular, which is associated with disease persistence and chemotherapy resistance in diverse patients. These results enable prospective isolation and functional genetic manipulation of immunophenotypically-varied leukemia stem cells in human patient specimens, as well as establish key functions of epigenetic plasticity in leukemia development and therapy resistance. We anticipate that these findings will lead to the elucidation of essential properties of leukemia stem cell quiescence and the design of therapeutic strategies for their clinical identification and control.
The immune response to lumpy skin disease virus in cattle is influenced by inoculation route
Authors: Fay Petra C. , Wijesiriwardana Najith , Munyanduki Henry , Sanz-Bernardo Beatriz , Lewis Isabel , Haga Ismar R. , Moffat Katy , van Vliet Arnoud H. M. , Hope Jayne , Graham Simon , Beard Philippa M.
Published: September 2022

Lumpy skin disease virus (LSDV) causes severe disease in cattle and water buffalo and is transmitted by hematophagous arthropod vectors. Detailed information of the adaptive and innate immune response to LSDV is limited, hampering the development of tools to control the disease. This study provides an in-depth analysis of the immune responses of calves experimentally inoculated with LSDV via either needle-inoculation or arthropod-inoculation using virus-positive Stomoxys calcitrans and Aedes aegypti vectors. Seven out of seventeen needle-inoculated calves (41%) developed clinical disease characterised by multifocal necrotic cutaneous nodules. In comparison 8/10 (80%) of the arthropod-inoculated calves developed clinical disease. A variable LSDV-specific IFN-γ immune response was detected in the needle-inoculated calves from 5 days post inoculation (dpi) onwards, with no difference between clinical calves (developed cutaneous lesions) and nonclinical calves (did not develop cutaneous lesions). In contrast a robust and uniform cell-mediated immune response was detected in all eight clinical arthropod-inoculated calves, with little response detected in the two nonclinical arthropod-inoculated calves. Neutralising antibodies against LSDV were detected in all inoculated cattle from 5-7 dpi. Comparison of the production of anti-LSDV IgM and IgG antibodies revealed no difference between clinical and nonclinical needle-inoculated calves, however a strong IgM response was evident in the nonclinical arthropod-inoculated calves but absent in the clinical arthropod-inoculated calves. This suggests that early IgM production is a correlate of protection in LSD. This study presents the first evidence of differences in the immune response between clinical and nonclinical cattle and highlights the importance of using a relevant transmission model when studying LSD.
Integrated cardio-behavioural defensive states
Authors: Signoret-Genest Jérémy , Schukraft Nina , Reis Sara L. , Segebarth Dennis , Tovote Philip
Published: September 2022

Fear and anxiety are brain states that evolved to mediate defensive responses to threat. While it is clear that the defense reaction includes multiple interacting behavioural, autonomic and endocrine adjustments, their integrative nature is poorly understood. In particular, threat has been associated with various cardiac changes, yet a clear consensus on their relevance for the integrated defense reaction is missing. We here define rapid microstates associated with specific behaviours and heart rate dynamics, both affected by long-lasting macrostates and reflecting context-dependent threat levels. In addition, we demonstrate that one of the most commonly used defensive behavioural responses, freezing measured by immobility, is part of an integrated cardio-behavioural microstate mediated by specific midbrain circuit elements. Our work puts forth a framework for systematic integration of cardiac and behavioural readouts that presents the basis for a better understanding of complex neural defensive states and their associated systemic functions.
A dramatic impairment of the antitumor activity of human Vγ9Vδ2 T cells is induced by TGF-β through significant phenotype, transcriptomic and metabolic changes
Authors: Rafia Chirine , Loizeau Clément , Renoult Ophélie , Harly Christelle , Pecqueur Claire , Joalland Noémie , Scotet Emmanuel
Published: September 2022

Despite significant advances, the eradication of cancer remains a clinical challenge which justifies the urgent exploration of additional therapeutic strategies such as immunotherapies. Human peripheral Vγ9Vδ2 T cells represent an attractive candidate subset for designing safe, feasible and effective adoptive T cell transfer-based therapies. However, following their infiltration within tumors, γδ T cells are exposed to various regulating constituents and signals from the tumor microenvironment (TME), which severely alter their antitumor functions. Here, we show that TGF-β, whose elevated production in some solid tumors is linked to a poor prognosis, interferes with the antigenic activation of human Vγ9Vδ2 T cells in vitro. This regulatory cytokine strongly impairs their cytolytic activity, which is accompanied by the induction of particular phenotypic, transcriptomic and metabolic changes. Collectively, these observations provide informations for better understanding and targeting the impact of TME components to regulate the antitumor activity of human T cell effectors.
Aberrant cell state plasticity mediated by developmental reprogramming precedes colorectal cancer initiation
Authors: Bala Pratyusha , Rennhack Jonathan P. , Aitymbayev Daulet , Morris Clare , Moyer Sydney M. , Duronio Gina N. , Doan Paul , Li Zhixin , Liang Xiaoyan , Hornick Jason L. , Yurgelun Matthew B. , Hahn William C. , Sethi Nilay S.
Published: September 2022

Cell state (phenotypic) plasticity is a carefully regulated feature of adult epithelial cells that enables adaptive responses to injury, inflammation, and other forms of stress. Aberrant expansion of the normally restricted capability for cell state plasticity to escape terminal differentiation is a critical aspect of neoplasia. The nongenetic factors and specific programs that mediate aberrant cell state plasticity and impaired differentiation require deeper characterization to understand this elusive aspect of cancer pathogenesis. Using genetically engineered and carcinogen-induced murine models of intestinal neoplasia, we demonstrate that impaired differentiation is a conserved event preceding cancer development. Single cell RNA-sequencing (scRNA-seq) of neoplastic intestinal lesions from both mouse models and a patient with familial adenomatous polyposis revealed that cancer initiates by adopting an aberrant transcriptional state characterized by nonoverlapping expression of a regenerative pathway, marked byLy6a(Sca-1), and a fetal intestinal program, positive forTacstd2(Trop2). Genetic inactivation ofSox9prevented adenoma formation in ApcKOmice, obstructed emergence of aberrant regenerative and fetal intestinal programs, and restored multi-lineage differentiation by scRNA-seq. Expanded chromatin accessibility at regeneration and fetal genes upon Apc inactivation was reduced by concomitant Sox9 suppression. These studies indicate that aberrant cell state plasticity mediated by unabated regenerative activity and developmental reprogramming precedes cancer development.
Deep transfer learning provides aParetoimprovement for multi-ancestral clinico-genomic prediction of diseases
Authors: Gao Yan , Cui Yan
Published: September 2022

Accurate genomic predisposition assessment is essential for the prevention and early detection of diseases. Polygenic scores and machine learning models have been developed for disease prediction based on genetic variants and other risk factors. However, over 80% of existing genomic data were acquired from individuals of European descent. As a result, clinico-genomic risk prediction is less accurate for non-European populations. Here we employ a transfer learning strategy to improve the clinico-genomic prediction of disease occurrence for the data-disadvantaged populations. Our multi-ancestral machine learning experiments on clinico-genomic datasets of cancers and Alzheimer’s disease and synthetic datasets with built-in data inequality and subpopulation shift show that transfer learning can significantly improve disease prediction accuracy for data-disadvantaged populations. Under the transfer learning scheme, the prediction accuracy for the data-disadvantaged populations can be improved without compromising the prediction accuracy for other populations. Therefore, transfer learning provides aParetoimprovement toward equitable machine learning for genomic medicine.
Molecular Mechanisms of Holliday Junction Branch Migration Catalyzed by an Asymmetric RuvB Hexamer
Authors: Rish Anthony D. , Shen Zhangfei , Chen Zhenhang , Fu Tian-Min
Published: September 2022

The Holliday junction (HJ) is a universal DNA intermediate of homologous recombination that is involved in many fundamental physiological processes. In bacteria, RuvB, a motor protein of the AAA+ ATPase superfamily, drives branch migration of the Holliday junction with a mechanism that had yet to be elucidated. Here, we report two cryo-EM structures of RuvB in complex with DNA and nucleotides, providing a comprehecomplex, which was further purified nsive understanding of HJ branch migration. Six RuvB protomers assemble into a spiral staircase, in the shape of a ring, with DNA in the central pore. Four protomers of RuvB hexamer interact with the backbone of the DNA substrate, suggesting a pulling-and-revolving mechanism of DNA translocation with a basic step size of 2 nucleotides. Moreover, the variation of nucleotide-binding states in our RuvB hexamer supports a sequential model for ATP hydrolysis, ADP release, and ATP reloading, which occur at specific positions on the RuvB hexamer. Furthermore, the asymmetric assembly of RuvB also explains the 6:4 stoichiometry between RuvB and RuvA, which assembles into a complex to coordinate HJ migration in cells. Taken together, we provide a comprehensive framework for the mechanistic understanding of HJ branch migration facilitated by RuvB motor protein, which may be universally shared in both prokaryotic and eukaryotic organisms.
Cas9-mediated endogenous plasmid loss in Borrelia burgdorferi
Authors: Takacs Constantin N. , Nakajima Yuko , Haber James E. , Jacobs-Wagner Christine
Published: September 2022

The spirochete Borrelia burgdorferi, which causes Lyme disease, has the most segmented genome among known bacteria. In addition to a linear chromosome, the B. burgdorferi genome contains over 20 linear and circular endogenous plasmids. While many of these plasmids are dispensable under in vitro culture conditions, they are maintained during the natural life cycle of the pathogen. Plasmid-encoded functions are required for colonization of the tick vector, transmission to the vertebrate host, and evasion of host immune defenses. Different Borrelia strains can vary substantially in the type of plasmids they carry. The gene composition within the same type of plasmid can also differ from strain to strain, impeding the inference of plasmid function from one strain to another. To facilitate the investigation of the role of specific B. burgdorferi plasmids, we developed a Cas9-based approach that targets a plasmid for removal. As a proof-of-principle, we showed that targeting wild-type Cas9 to several loci on the endogenous plasmids lp25 or lp28-1 of the B. burgdorferi type strain B31 results in sgRNA-specific plasmid loss even when homologous sequences (i.e., potential sequence donors for DNA recombination) are present nearby. Cas9 nickase versions, Cas9D10A or Cas9H840A, also cause plasmid loss, though not as robustly. Thus, sgRNA-directed Cas9 DNA cleavage provides a highly efficient way to eliminate B. burgdorferi endogenous plasmids that are non-essential in axenic culture.
Actomyosin cables position cell cohorts during Drosophila germband retraction by entraining their morphodynamic and mechanical properties
Authors: Nandi Sudeepa , Balse Aanchal , Inamdar Mandar M. , Kumar K. Vijay , Narasimha Maithreyi
Published: September 2022

The unfolding and displacement of the germband during Drosophila germband retraction (GBR) accomplish the straightening of the embryonic anterior-posterior axis. The failure of GBR reduces embryonic viability and results in the mispositioning of the embryonic segments and the gastrointestinal tract. Despite its importance, the cellular, molecular and physical mechanisms that govern the unfolding of the germband and ensure the accurate positioning of cell fields within it remain poorly understood. Here, we uncover the requirement of planar polarized, supracellular, tensile actomyosin cables for entraining cellular morphodynamics, cell field positioning and retraction kinematics. Circumferential, non-constricting cables that form during early retraction ensure the coherence of ‘placode-like’ cell cohorts, pattern medio-lateral gradients in cell shape and sidedness within it, and dampen retraction speed. Linear, constricting cables that power displacement at the end of retraction enable sequential, multi-tissue, collective T1 transitions to reposition medial cell fields to more posterior locations. Together, our results reveal how the spatiotemporally regulated deployment of actomyosin structures, functioning either as barricades or as purse strings, modulate the speed of tissue unfolding and enable cell field positioning by influencing the morphodynamic and mechanical properties of cell cohorts during morphogenesis.
Plzf mediates a switch between Fgf signalling regimes in the developing hindbrain
Authors: Leino Sami A. , Constable Sean C. J. , Streit Andrea , Wilkinson David G.
Published: September 2022

Developing tissues are sequentially patterned by extracellular signals that are turned on and off at specific times. In the zebrafish hindbrain, fibroblast growth factor (Fgf) signalling has different roles at different developmental stages: in the early hindbrain, transient Fgf3 and Fgf8 signalling from rhombomere 4 is required for correct segmentation, whereas later, neuronal Fgf20 expression confines neurogenesis to specific spatial domains within each rhombomere. How the switch between these two signalling regimes is coordinated is not known. We present evidence that the promyelocytic leukaemia zinc finger (Plzf) transcription factor is required for this transition to happen in an orderly fashion. Plzf expression is high in the early anterior hindbrain, then gradually upregulated posteriorly and confined to neural progenitors. In mutants lacking functional Plzf, fgf3 expression fails to be downregulated and persists until a late stage, resulting in excess and more widespread Fgf signalling during neurogenesis. Accordingly, the spatial pattern of neurogenesis is disrupted in plzf mutants. Our results reveal how the distinct stage-specific roles of Fgf signalling are coordinated in the zebrafish hindbrain.
Statistical learning quantifies transposable element-mediated cis-regulation
Authors: Pulver Cyril , Grün Delphine , Duc Julien , Sheppard Shaoline , Planet Evarist , de Fondeville Raphaël , Pontis Julien , Trono Didier
Published: September 2022

Background

Transposable elements (TEs) have colonized the genomes of most metazoans, and many TE-embedded sequences function as cis-regulatory elements (CREs) for genes involved in a wide range of biological processes from early embryogenesis to innate immune responses. Because of their repetitive nature, TEs have the potential to form CRE platforms enabling the coordinated and genome-wide regulation of protein-coding genes by only a handful of trans-acting transcription factors (TFs).

Results

Here, we directly test this hypothesis through mathematical modeling and demonstrate that differences in expression at protein-coding genes alone are sufficient to estimate the magnitude and significance of TE-contributed cis-regulatory activities, even in contexts where TE-derived transcription fails to do so. We leverage hundreds of overexpression experiments and estimate that, overall, gene expression is influenced by TE-embedded CREs situated within approximately 200kb of promoters. Focusing on the cis-regulatory potential of TEs within the gene regulatory network of human embryonic stem cells, we find that pluripotency-specific and evolutionarily young TE subfamilies can be reactivated by TFs involved in post-implantation embryogenesis. Finally, we show that TE subfamilies can be split into truly regulatorily active versus inactive fractions based on additional information such as matched epigenomic data, observing that TF binding may better predict TE cis-regulatory activity than differences in histone marks.

Conclusion

Our results suggest that TE-embedded CREs contribute to gene regulation during and beyond gastrulation. On a methodological level, we provide a statistical tool that infers TE-dependent cis-regulation from RNA-seq data alone, thus facilitating the study of TEs in the next-generation sequencing era.
Time-dependent dynamical Bragg diffraction in deformed crystals by the beam propagation method
Authors: Krzywinski Jacek , Halavanau Aliaksei
Published: September 2022

This paper describes how to efficiently solve time-dependent X-ray dynamic diffraction problems in distorted crystals with a fast Fourier transform based beam propagation method. Examples are given of using the technique to simulate the propagation of X-ray beams in deformed crystals in space and time domains relevant to the cavity-based X-ray free-electron lasers and X-ray free-electron laser self-seeding systems.
On single-crystal total scattering data reduction and correction protocols for analysis in direct space. Corrigendum
Authors: Koch Robert J. , Roth Nikolaj , Liu Yu , Ivashko Oleh , Dippel Ann-Christin , Petrovic Cedomir , Iversen Bo B. , v. Zimmermann Martin , Bozin Emil S.
Published: September 2022

The name of the third author of the article by Koch et al. [Acta Cryst. (2021). A77, 611–636] is corrected.
Users’ attitude on perceived security of mobile cloud computing: empirical evidence from SME users in China
Authors: Palanisamy Ramaraj , Shi Yi
Published: September 2022

Purpose

The purpose of this paper is to rank the users’ attitude on major components of mobile cloud computing (MCC) security and investigate the degree of impact of these components on MCC security as a whole.

Design/methodology/approach

Hypotheses were evolved and tested by data collected through an online survey-questionnaire. The survey was administered to 363 users from Chinese organizations. Statistical analysis was carried out and structural equation model was built to validate the interactions.

Findings

The eight components of MCC security in the order of importance are as follows: mobile device related, user identity related, deployment model related, application-level security issues, data related, virtualization related, network related and service delivery related. The empirical analysis validates that these security issues are having significant impact on perceived security of MCC.

Practical implications

Constant vigilance on these eight issues and improving the level of user awareness on these issues enhance the overall security.

Social implications

These issues can be used for designing and developing secured MCC system.

Originality/value

While several previous research has studied various security factors in the MCC security domain, a consolidated understanding on the different components of MCC security is missing. This empirical research has identified and ranked the major components of MCC security. The degree of impact of each of these components on overall MCC security is identified. This provides a different perspective for managing MCC security by explaining what components are most important.
Open source SIEM solutions for an enterprise
Authors: Tariq Aamna , Manzoor Jawad , Aziz Muhammad Ammar , Tariq Zain Ul Abideen , Masood Ammar
Published: September 2022

Purpose

The security of applications, systems and networks has always been the source of great concern for both enterprises and common users. Different security tools like intrusion detection system/intrusion prevention system and firewalls are available that provide preventive security to the enterprise networks. However, security information and event management (SIEM) systems use these tools in combination to collect events from diverse data sources across the network. SIEM is a proactive tool that processes the events to present a unified security view of the whole network at one location. SIEM system has, therefore, become an essential component of an enterprise network security architecture. However, from various options available, the selection of a suitable and cost-effective open source SIEM solution that can effectively meet most of the security requirements of small-to-medium-sized enterprises (SMEs) is not simple because of the lack of strong analysis.

Design/methodology/approach

In this work, the authors first review the security challenges faced by different SME sectors and then consider a comprehensive comparative analysis of the capabilities of well-known open source SIEM solutions. Based on this, the authors provide requirements based recommendations of open source SIEM solutions for SMEs. This paper aims to provide a valuable resource that can be referred to by SMEs for the selection of a SIEM system best suited to their organization’s security posture.

Findings

Security requirements of SMEs vary according to their network infrastructure; therefore, every open source SIEM solution would not be suitable for an SME. Selection of a SIEM solution from available open source solutions based upon the security requirements of an SME network is a critical task. Therefore, in this work, a meaningful insight for the selection of an appropriate SIEM solution for SMEs is provided.

Originality/value

Major contribution of this work is the mapping of the security requirements of the SME sectors under consideration, against the open source SIEM options to provide meaningful insight for SMEs in the selection of an appropriate solution.
Determinants of students' perceived enjoyment towards online learning
Authors: Nguyen Hong Thi Thu
Published: September 2022

Purpose

The study aims to seek the factors affecting perceived online learning enjoyment among university students across Viet Nam.

Design/methodology/approach

Based on the concept of the technology acceptance model (TAM), this research adopts structural equation modelling (SEM) to analyse data collected from 795 undergraduate students who have gained the experience of online courses in the period of the COVID-19 pandemic.

Findings

The results of this study indicate that both perceived ease of use and perceived usefulness are significant predictors of students' perceived enjoyment in online courses while perceived obstacles are not its direct antecedents. The correlation between perceived ease of use and perceived usefulness is also affirmed in this study. Besides, differences are found based on students' characteristics including gender, grade and academic major.

Research limitations/implications

As online learning turns education to be learner-centred, it is crucial to have a better understanding of students' perceptions toward this advanced learning method. The insights found in this research may be of interest to educational administrators, aimed at achieving the digital transformation success in education which may adapt to the current trend of Industrial Revolution 4.0.

Originality/value

According to the best of the knowledge, this research is the first to explore the effect of the group of three predictors including perceived ease of use, perceived usefulness and perceived obstacles on the students' learning enjoyment toward the online learning method, especially in the context of Viet Nam.
Breaking down walls, building bridges: the importance of transformational leadership considering contextual and individual factors in resistance to change
Authors: Sánchez Iván D. , Sitú María , Murillo Laura
Published: September 2022

Purpose

This study aims to analyze the role of trust in the leader as a contextual factor and the personality of the employee as an individual factor in the relationship between transformational leadership (TFL) and resistance to change (RC).

Design/methodology/approach

A total of 170 surveys were applied to employees in two organizations that had recently implemented a change. Using hierarchical regression and Hayes’ PROCESS macro, both direct and indirect relationships were analyzed.

Findings

The results show that TFL is negatively related to RC. Nevertheless, such a relationship is partially mediated by trust in the leader and moderated by two employee personality traits (openness and neuroticism), both of which strengthen the relationship. Similarly, employee’s openness to experience is negatively related to RC.

Originality/value

This research contributes to understand the relationship between leadership and RC, incorporating both contextual and individual factors, as literature has debated over whether resistant to change obeys to factors surrounding the employees, or within them. While this research contributes to this approach, its contributions extend beyond the leadership–resistance relationship to include indirect (mediation and moderation) relationships. Consideration of the moderating role of the employee’s personality in the effect of the leader’s behavior on the employee’s resistance, for instance, contributes to the development of a theoretical logic that helps to explain the leader–follower interaction and its effect on the follower’s attitudes and behaviors.
The economic consequences of IFRS 16 adoption: the role of gearing restriction in debt covenants
Authors: Lau Chee Kwong
Published: September 2022

Purpose

This study aims to examine the economic consequences of, and managerial behaviour in response to, the introduction of IFRS 16 Leases. It extends the debt covenant hypothesis to explain why firms reduce the use of operating leases with the introduction.

Design/methodology/approach

This study develops a model, based on operating leases as an alternative financing source and the determinants of debt policy, to estimate the effects of gearing on operating lease intensity. High gearing is a proxy to probably closer to the violation of, or expected to violate, the gearing restriction in debt covenants given the retrospective capitalisation of operating leases, when IFRS 16 takes effect.

Findings

This study finds that operating lease intensity fell between 2011 (immediately after the first exposure draft leading to IFRS 16) and 2018 (immediately prior to the effective date of IFRS 16). It also finds that gearing affects changes in operating lease intensity over 2011 and 2018, consistent with the debt covenant hypothesis.

Research limitations/implications

The introduction of IFRS 16 is a natural experiment with unique characteristics (the active lobbying behaviour, ex ante evidence on adverse economic consequences, a prolonged standard-setting period, etc.) valuable for accounting research.

Practical implications

A showcase about the relevance of financial reporting for contracting interests of firms and managers and a good reference for accounting standard setters in considering and managing the economic consequences of proposed accounting standards.

Originality/value

This study adds to the limited research on the consequences of accounting standards and documents the ex-post impact on firm leverage ratios and the behavioural aspects of reporting entities.
Toward a contextualized understanding of inside sales: the role of sales development in effective lead funnel management
Authors: Terho Harri , Salonen Anna , Yrjänen Meri
Published: September 2022

Purpose

The purpose of this study is to provide a contextualized understanding of how business-to-business (B2B) firms use the sales development function for efficient and effective lead funnel management.

Design/methodology/approach

The authors adopted a qualitative field-study approach and interviewed 13 people from eight firms. While software as a service (SaaS) firms are the most prevalent application context for the sales development function, the authors also included respondents from non-SaaS firms to develop an in-depth understanding of the contextualized nature of the sales development process.

Findings

Sales development processes can be applied in outbound prospect-focused, outbound account-based, inbound prospect-focused and inbound account-based lead management contexts. The sales development processes of lead research, engagement and handover vary depending on the nature of the lead management context. These processes are supported by the appropriate design of organizational, technological and people platforms.

Practical implications

The authors explain how sales development as a form of inside sales can support effective lead funnel management in B2B firms through technology-enabled lead research and nurture processes designed to prepare customers for meaningful conversations with field sales.

Originality/value

To the best of the authors’ knowledge, this study is the first to focus purely on the sales development function as a form of inside sales. They explain how the sales development processes relating to lead research, engagement and handover are conducted in four distinct application contexts to qualify leads for the outside salesforce.
Adaptive reuse for leftover urban landscape: ruins, remains, waste and monsters for an approaching genealogy of future
Authors: Metta Annalisa
Published: September 2022

Purpose

This paper aims to explore the topic of adaptive reuse referring to urban open spaces into a more-than-human perspective. It underlines that dealing with heritage means being part of an inherent and ongoing process of transformation and so that reuse is inextricably an adaptive practice, constantly facing mutations, and that adaptation is a coral practice that involves different kinds of users and makers, inclusive of human and not human livings.

Design/methodology/approach

This paper looks at the lexicon of abandonment, in search of the more essential and intense meanings of words, and at some pioneering practices in Europe to comprehend the aesthetic and ethical implications of adaptive reuse of neglected landscapes.

Findings

Processes of reuse involve many different communities of users who in turn continuously redesign the site, into a comprehensive, coral and conflicting collaboration, whose results are never given once for all and are both uncanny and beautiful, scaring and marvellous, like a monster.

Practical implications

Accepting the idea that humans are not the only users and makers of urban sites can widen the range of tools, methods and values involved in heritage adaptive reuse.

Originality/value

This paper tries to widen the meanings of adaptation into a multispecies perspective. It intends to broaden the range of agents that can be involved as users and makers, assuming a more-than-human point of view that is not yet commonly applied.
Wellness tourism scholarship: a research agenda
Authors: Polat Eray , Koseoglu Mehmet Ali
Published: September 2022

Purpose

The study aims to explore the intellectual structure of wellness tourism (WT) research by performing a two-phase methodological approach.

Design/methodology/approach

Citation and co-citation analysis were performed on 209 articles published up to October 2021 in Scopus, and the results were visualised with the VOSviewer software. Furthermore, to assess clusters in-depth, qualitative thematic content analysis was used.

Findings

The findings indicate that the main articles of WT research examine the demand side of WT. Five clusters were explored by co-citation analysis. Each cluster is discussed by presenting the main theme, key theoretical framework, and characteristic methodological perspective. Accordingly, no dominant theory stands out in research on wellness tourism. Most of the study has been done through cross-sectional surveys.

Practical implications

The authors anticipate that by the recommendations outlined in this study, WT research will progress and provide significant insights to WT practitioners in the coming years to meet tourist expectations.

Originality/value

Via this research, which shows the discovery of the intellectual structure of WT and its holistic picture, the deficiencies in the picture will be seen, and practitioners will be provided information based on evidence.
Virtual spaces as the future of consumption in tourism, hospitality and events
Authors: Filimonau Viachaslau , Ashton Mark , Stankov Ugljesa
Published: September 2022

Purpose

Virtual spaces, commonly referred to as the Metaverse, are predicted to disrupt consumption patterns in tourism, hospitality and events (THE) by shifting some user experiences to a virtual world. Scholarly investigations are necessitated to aid in an understanding of virtual spaces and the implications of their consumption for THE industries. This viewpoint outlines a provisional research agenda on virtual spaces.

Design/methodology/approach

To inform its arguments, this viewpoint draws upon academic and grey literature surrounding the emerging topic of the Metaverse in THE industries.

Findings

The research agenda should consider four perspectives representing different actors of THE value chain, i.e. developers/suppliers, THE business professionals, customers and policymakers. The research agenda should also incorporate the wider spillover effects of consumption of virtual spaces which may stretch well beyond THE industries.

Originality/value

This viewpoint outlines some research directions which may aid different actors of THE value chain alongside academics in better understanding the emerging phenomenon of virtual spaces and comprehend the opportunities and challenges associated with their uptake by THE industries.