bluuebunny/crossref_metadata_2025 huggingface dataset:
hudson: A User-Friendly R Package to Extend Manhattan Plots
Authors: Lucas Anastasia , Verma Anurag , Ritchie Marylyn D.
Published: January 2022

The Manhattan plot is one of the most widely used visualization techniques when plotting summary statistics from genome-wide or phenome-wide association studies. While there are a number of existing tools to create these plots, there is room for extending their utility to satisfy increasingly complex and comprehensive analyses as well as the need for comparisons between different sets of results or between discovery and replication datasets. The R package presented here, hudson, provides user-friendly plotting functions intended for use with genome, phenome, and exposome-wide association studies, but its flexible framework can be utilized for a wide variety genome-wide analyses. Further, we have extended these figures to allow for interactive elements to facilitate results exploration for the ever-increasing large-scale dimensionality of these data. hudson can be obtained from https://github.com/RitchieLab/hudson.
Divergent binding mode for a protozoan BRC repeat to RAD51
Authors: Pantelejevs Teodors , Hyvönen Marko
Published: January 2022

Interaction of BRCA2 through ca. 30 amino acid residue motifs, BRC repeats, with RAD51 is a conserved feature of the double-strand DNA break repair process in eukaryotes. In humans the binding of the eight BRC repeats is relatively well understood, with structure of BRC4 repeat bound to human RAD51 showing how two sequence motifs, FxxA and LFDE, in the BRC repeat interact with distinct sites on RAD51. Little is known however of the interaction of BRC repeats in other species, especially in protozoans where variable number of BRC repeats are found in BRCA2 proteins. Here we have studied in detail the interactions of the two BRC repeats in Leishmania infantum BRCA2 with RAD51. We show that the LiBRC1 is a high affinity repeat with a KD of 0.29 μM while LiBRC2 binds to RAD51 with a KD of 13.5 μM. A crystal structure of LiBRC1 complexed with LiRAD51 revels an extended β-hairpin compared to human BRC4 and shows that the equivalent of human LFDE motif is not interacting with LiRAD51. A truncation analysis of LiBRC1 confirms that a shorter repeat is sufficient for high affinity interaction and this minimal repeat is functional in inhibiting the formation of LiRAD51-ssDNA nucleofilament.
Toll Like Receptor 9 Pathway Mediates Schlafen+-MDSC Polarization During Helicobacter-Induced Gastric Metaplasias
Authors: Ding Lin , Chakrabarti Jayati , Sheriff Sulaiman , Li Qian , Thi Hong Hahn Nguyen , Sontz Ricky A , Mendoza Zoe E , Schreibeis Amanda , Helmrath Michael A. , Zavros Yana , Merchant Juanita L
Published: January 2022

Background and Aims

A subset of MDSCs that express murine Schlafen4 (SLFN4) or its human ortholog SLFN12L polarize in the Helicobacter-inflamed stomach coincident with intestinal or spasmolytic polypeptide-expressing metaplasia (SPEM). We propose that individuals with a more robust response to damage-activated molecular patterns (DAMPs) and increased Toll-like receptor (TLR9) expression are predisposed to the neoplastic complications of Helicobacter infection.

Methods

A mouse or human Transwell™ co-culture system comprised of dendritic cells (DCs), 2-dimensional gastric epithelial monolayers and Helicobacter were used to dissect the cellular source of interferon (IFNα) in the stomach by flow cytometry. Conditioned media from the cocultures polarized primary myeloid cells. Myeloid-derived suppressor cell (MDSC) activity was determined by T cell suppression assays. In human subjects with intestinal metaplasia or gastric cancer, the rs5743836 TLR9T>C variant was genotyped and linked to TLR9, IFNα and SLFN12L expression by immunohistochemistry. NFκB binding to the TLR9 C allele was determined by electrophoretic mobility shift assays.

Results

Helicobacter infection induced gastric epithelial and plasmacytoid DC expression of TLR9 and IFNα. Co-culturing primary mouse or human cells with DCs and Helicobacter induced TLR9, IFNα secretion and SLFN+-MDSC polarization. Neutralizing IFNα in vivo mitigated Helicobacter-induced SPEM. The TLR9 minor C allele creates an NFκb binding site associated with higher levels of TLR9, IFNα and SLFN12L in Helicobacter-infected stomachs that correlated with a greater incidence of metaplasias and cancer.

Conclusion

TLR9 plays an essential role in the production of IFNα and polarization of SLFN+-MDSCs upon Helicobacter infection. Subjects carrying the rs5743836 TLR9 minor C allele are predisposed to neoplastic complications if chronically infected.
Overexpression of UCP4 in astrocytic mitochondria prevents multilevel dysfunctions in a mouse model of Alzheimer’s disease
Authors: Rosenberg Nadia , Reva Maria , Restivo Leonardo , Briquet Marc , Bernardinelli Yann , Rocher Anne-Bérengère , Markram Henry , Chatton Jean-Yves
Published: January 2022

Alzheimer’s disease (AD) is becoming increasingly prevalent worldwide. It represents one of the greatest medical challenge as no pharmacologic treatments are available to prevent disease progression. Astrocytes play crucial functions within neuronal circuits by providing metabolic and functional support, regulating interstitial solute composition, and modulating synaptic transmission. In addition to these physiological functions, growing evidence points to an essential role of astrocytes in neurodegenerative diseases like AD. Early stage AD is associated with hypometabolism and oxidative stress. Contrary to neurons that are vulnerable to oxydative stress, astrocytes are particularly resistant to mitochondrial dysfunction and are therefore more resilient cells. In our study, we leveraged astrocytic mitochondrial uncoupling and examined neuronal function in the 3xTg AD mouse model. We overexpressed the mitochondrial uncoupling protein 4 (UCP4), which has been shown to improve neuronal survival in vitro. We found that this treatment efficiently prevented alterations of hippocampal metabolite levels observed in AD mice, along with hippocampal atrophy and reduction of basal dendrite arborization of subicular neurons. This approach also averted aberrant neuronal excitability observed in AD subicular neurons and preserved episodic-like memory in AD mice assessed in a spatial recognition task. These findings show that targeting astrocytes and their mitochondria is an effective strategy to prevent the decline of neurons facing AD-related stress at the early stages of the disease.
A comprehensive evaluation of consensus spectrum generation methods in proteomics
Authors: Luo Xiyang , Bittremieux Wout , Griss Johannes , Deutsch Eric W , Sachsenberg Timo , Levitsky Lev I. , Ivanov Mark V. , Bubis Julia A. , Gabriels Ralf , Webel Henry , Sanchez Aniel , Bai Mingze , Kall Lukas , Perez-Riverol Yasset
Published: January 2022

Spectrum clustering is a powerful strategy to minimize redundant mass spectral data by grouping highly similar mass spectra corresponding to repeatedly measured analytes. Based on spectrum similarity, near-identical spectra are grouped in clusters, after which each cluster can be represented by its so-called consensus spectrum for downstream processing. Although several algorithms for spectrum clustering have been adequately benchmarked and tested, the influence of the consensus spectrum generation step is rarely evaluated. Here, we present an implementation and benchmark of common consensus spectrum algorithms, including spectrum averaging, spectrum binning, the most similar spectrum, and the best-identified spectrum. We have analyzed diverse public datasets using two different clustering algorithms (spectra-cluster and MaRaCluster) to evaluate how the consensus spectrum generation procedure influences downstream peptide identification. The BEST and BIN methods were found the most reliable methods for consensus spectrum generation, including for datasets with post-translational modifications (PTM) such as phosphorylation. All source code and data of the present study are freely available on GitHub at https://github.com/statisticalbiotechnology/representative-spectra-benchmark.
Slow-cycling cells in glioblastoma: a specific population in the cellular mosaic of cancer stem cells
Authors: Yang C , Tian G , Dajac M , Doty A , Wang S , Lee JH , Rahman M , Huang J , Reynolds BA , Sarkisian MR , Mitchell D , Deleyrolle LP
Published: January 2022

Abstract

Glioblastoma (GBM) exhibits populations of cells that drive tumorigenesis, treatment resistance, and disease progression. Cells with such properties have been described to express specific surface and intracellular markers or exhibit specific functional features including being slow-cycling or quiescent with the ability to generate proliferative progenies. In GBM, each of these cellular fractions was shown to harbor cardinal features of cancer stem cells 1-7. In this study we focus on the comparison of these cells and present evidence of great phenotypic and functional heterogeneity in brain cancer cell populations with stemness properties, especially between slow-cycling cells and cells phenotypically defined based on the expression of markers commonly used to enrich for cancer stem cells (CSCs). Our data support the cancer stem cell mosaicism model with slow-cycling cells representing critical tesserae.
Stimulus Whitening Improves the Efficiency of Reverse Correlation
Authors: Compton Alexis , Roop Benjamin W. , Parrell Benjamin , Lammert Adam C.
Published: January 2022

Human perception depends upon internal representations of the environment that help to organize the raw information available from the senses by acting as reference patterns. Internal representations are widely characterized using reverse correlation, a method capable of producing unconstrained estimates of the representation itself, all on the basis of simple responses to random stimuli. Despite its advantages, reverse correlation is often infeasible to apply because the number of stimulus-response trials needed to provide an accurate estimate is typically very large. Prior approaches have aimed to overcome this sampling inefficiency by incorporating prior knowledge of the representation, which biases the estimate and ultimately limits the essential power of reverse correlation. The present approach, however, improves efficiency via stimulus whitening, a statistical procedure that decorrelates stimuli, making them less redundant, and commensurately more favorable for efficient estimation of an arbitrary target. We provide a mathematical justification for whitening, and demonstrate in simulation that whitening provides greater than 85% improvement in efficiency for a given estimation accuracy, and also a two- to five-fold increase in accuracy for a given sample size. Improving the efficiency of reverse correlation may enable a broader scope of investigations into individual variability and potential universality of perceptual mechanisms.
Essential bromodomain TcBDF2 as a drug target against Chagas disease
Authors: Pezza Alejandro , Tavernelli Luis E , Alonso Victoria L , Perdomo Virginia , Gabarro Raquel , Prinjha Rab , Araya Elvio Rodríguez , Rioja Inmaculada , Docampo Roberto , Calderón Felix , Martin Julio , Serra Esteban
Published: January 2022

Trypanosoma cruzi is a unicellular parasite that causes Chagas disease, which is endemic in the American continent but also worldwide distributed by migratory movements. A striking feature of trypanosomatids is the polycistronic transcription associated with post-transcriptional mechanisms that regulate the levels of translatable mRNA. In this context, epigenetic regulatory mechanisms have been revealed of great importance, since they are the only ones that would control the access of RNA polymerases to chromatin. Bromodomains are epigenetic protein readers that recognize and specifically bind to acetylated lysine residues, mostly at histone proteins. There are seven coding sequences for BD-containing proteins in trypanosomatids, named TcBDF1 to TcBDF7, and a putative new protein-containing a bromodomain that was recently described. Using the Tet regulated overexpression plasmid pTcINDEX-GW and CRISPR/Cas9 genome editing we were able to demonstrate the essentiality of TcBDF2 in T cruzi. This bromodomain is located in the nucleus, through a bipartite nuclear localization signal. TcBDF2 was shown to be important for host cell invasion, amastigote replication, and differentiation from amastigotes to trypomastigotes. Overexpression of TcBDF2 diminished epimastigote replication. Also, some processes involved in pathogenesis were altered in these parasites, such as infection of mammalian cells, replication of amastigotes, and the number of trypomastigotes released from host cells. In in vitro studies, TcBDF2 was also able to bind inhibitors showing a specificity profile different from that of the previously characterized TcBDF3. These results, point to TcBDF2 as a druggable target against T. cruzi.
Gut bacterial nutrient preferences quantified in vivo
Authors: Zeng Xianfeng , Xing Xi , Gupta Meera , Keber Felix C , Lopez Jaime G , Roichman Asael , Wang Lin , Neinast Michael D , Donia Mohamed S , Wühr Martin , Jang Cholsoon , Rabinowitz Joshua D
Published: January 2022

Great progress has been made in understanding gut microbiome’s products and their effects on health and disease. Less attention, however, has been given to the inputs that gut bacteria consume. Here we quantitatively examine inputs and outputs of the mouse gut microbiome, using isotope tracing. The main input to microbial carbohydrate fermentation is dietary fiber, and to branched-chain fatty acids and aromatic metabolites is dietary protein. In addition, circulating host lactate, 3-hydroxybutyrate and urea (but not glucose or amino acids) feed the gut microbiome. To determine nutrient preferences across bacteria, we traced into genus-specific bacterial protein sequences. We find systematic differences in nutrient use: Most genera in the phylum Firmicutes prefer dietary protein, Bacteroides dietary fiber, and Akkermansia circulating host lactate. Such preferences correlate with microbiome composition changes in response to dietary modifications. Thus, diet shapes the microbiome by promoting the growth of bacteria that preferentially use the ingested nutrients.
Physiological Responses to Caprine Coccidiosis During a 100-year Rain Event in Oklahoma: An Opportunistic Case Study with a implications for climate change and clinical diagnosis
Authors: McCallum Malcolm L. , Tilahun Yonathan , Pinango Jessica Quijada , Wang Zaisen
Published: January 2022

The interaction between inclement weather and disease acquisition is a long-recognized relationship. In the case of coccidiosis, a parasitic infestation of the intestines, wet weather is known to promote incidences in livestock. Our opportunistic investigation tracks blood chemistries of goats that were exposed to coccidian in a 100 year rain event in Oklahoma. Our results suggest a potentially patterned response of blood chemistries that may be developed into a clinical tool in the future and provide warnings for producers of the risks associated with growing incidences of excessively wet weather related to climate change.
Target-dependent siRNA suppression distinguishes self from non-self endogenous siRNAs in C. elegans germline
Authors: Gajic Zoran , Kaur Diljeet , Ni Julie , Zhu Zhaorong , Zhebrun Anna , Gajic Maria , Kim Matthew , Hong Julia , Priyadarshini Monika , Frøkjær-Jensen Christian , Gu Sam
Published: January 2022

Despite their prominent role in transposon silencing, expression of endo-siRNAs is not limited to the “non-self” DNA elements. Transcripts of protein-coding genes (“self” DNA) in some cases also produce endo-siRNAs in yeast, plants, and animals [1]. How cells distinguish these two populations of siRNAs to prevent unwanted silencing of self-genes in animals is not well understood. To address this question, we examined the expression of ectopic siRNAs from an LTR retrotransposon in C. elegans germline. We found that the abundance of ectopic siRNAs was dependent on their homologous target genes: ectopic siRNAs against genes expressed only in somatic cells can be abundantly expressed. In contrast, ectopic siRNAs against germline-expressed genes are often suppressed. This phenomenon, which we termed “target-directed siRNA suppression”, is dependent on the target mRNA and requires germline P-granule components. We found that siRNA suppression can also occur to naturally produced endo-siRNAs. We suggest that siRNA suppression plays an important role in regulating siRNA expression and preventing self-genes from aberrant epigenetic silencing.
A phenotype-based forward genetic screen identifiesDnajb6as a sick sinus syndrome gene
Authors: Ding Yonghe , Lang Di , Yan Jianhua , Bu Haisong , Li Hongsong , Jiao Kunli , Yang Jingchun , Le Tai , Clark Karl J. , Ekker Stephen C. , Cao Hung , Zhang Yuji , Li Yigang , Glukhov Alexey V. , Xu Xiaolei
Published: January 2022

Sick sinus syndrome (SSS) is a group of heart rhythm disorders caused by malfunction of the sinus node, the heart’s primary pacemaker. Partially owing to its aging-associated phenotypic manifestation and low expressivity, molecular mechanisms of SSS remain difficult to decipher. Here, we aim to develop a phenotype-based forward genetic approach in the zebrafish (Danio rerio) animal model for discovering essential genes which dysfunction could result in SSS-like phenotypes. Previously we showed the generation of protein trap library by using a revertible gene-breaking transposon (GBT)-based insertional mutagenesis system. Here, we reported the generation of a collection of 35 zebrafish insertional cardiac lines derived from this protein trap library, which was screened using electrocardiographic measurements. As a result, three mutants with SSS-like phenotypes were identified. We then focused on one of these 3 GBT mutants calledGBT411in whichdnajb6bgene was disrupted, and conducted expressional, genetic, transcriptome, and electrophysiological studies using both zebrafish and mouse models. These studies confirmed the identity ofDnajb6as a novel SSS causative gene with a unique expression pattern within the specialized population of sinus node pacemaker cardiomyocytes that lack the expression of HCN4 channels. Together, this study demonstrates the feasibility of a genetic screening approach in an adult vertebrate animal model for discovering new genetic factors for a heart rhythm disorder such as SSS.
Defining the Substrate Envelope of SARS-CoV-2 Main Protease to Predict and Avoid Drug Resistance
Authors: Shaqra Ala M. , Zvornicanin Sarah , Huang Qiu Yu , Lockbaum Gordon J. , Knapp Mark , Tandeske Laura , Barkan David T. , Flynn Julia , Bolon Daniel N.A. , Moquin Stephanie , Dovala Dustin , Kurt Yilmaz Nese , Schiffer Celia A.
Published: January 2022

Coronaviruses, as exemplified by SARS-CoV-2, can evolve and spread rapidly to cause severe disease morbidity and mortality. Direct acting antivirals (DAAs) are highly effective in decreasing disease burden especially when they target essential viral enzymes, such as proteases and polymerases, as demonstrated in HIV-1 and HCV and most recently SARS-CoV-2. Optimization of these DAAs through iterative structure-based drug design has been shown to be critical. Particularly, the evolutionarily conserved molecular mechanisms underlying viral replication can be leveraged to develop robust antivirals against rapidly evolving viral targets. The main protease (Mpro) of SARS-CoV-2, which is evolutionarily constrained to recognize and cleave 11 specific sites to promote viral maturation, exemplifies one such target. In this study we define the substrate envelope of Mpro by determining the molecular basis of substrate recognition, through nine high-resolution cocrystal structures of SARS-CoV-2 Mpro with the viral cleavage sites. These structures enable identification of evolutionarily vulnerable sites beyond the substrate envelope that may be susceptible to drug resistance and compromise binding of the newly developed Mpro inhibitors.
Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability
Authors: Shi Wei , Wang Lingshu , Zhou Tongqing , Sastry Mallika , Yang Eun Sung , Zhang Yi , Chen Man , Chen Xuejun , Choe Misook , Creanga Adrian , Leung Kwan , Olia Adam S. , Pegu Amarendra , Rawi Reda , Shen Chen-Hsiang , Stancofski Erik-Stephane D. , Talana Chloe Adrienna , Teng I-Ting , Wang Shuishu , Corbett Kizzmekia S. , Tsybovsky Yaroslav , Mascola John R. , Kwong Peter D.
Published: January 2022

Immunization with SARS-CoV-2 spike elicits diverse antibodies, but can any of these neutralize broadly? Here, we report the isolation and characterization of antibody WS6, from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, MERS-CoV, and hCoV-OC43. The crystal structure at 2-Å resolution of WS6 with its S2 epitope revealed recognition to center on a conserved helix, which was occluded in both prefusion and post-fusion spike conformations. Structural and neutralization analyses indicated WS6 to neutralize by inhibiting fusion, post-viral attachment. Comparison of WS6 to other antibodies recently identified from convalescent donors or mice immunized with diverse spikes indicated a stem-helical supersite – centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156 – to be a promising target for vaccine design.

Highlights

SARS-CoV-2 spike mRNA-immunized mouse elicited an antibody, WS6, that cross reacts with spikes of diverse human and bat beta-coronaviruses

WS6 neutralizes SARS-CoV-2 variants, SARS-CoV, and related viruses

Crystal structure at 2-Å resolution of WS6 in complex with a conserved S2 peptide reveals recognition of a helical epitope

WS6 neutralizes by inhibition of fusion, post-viral attachment

WS6 recognizes a supersite of vulnerability also recognized by other recently identified antibodies

Helical supersite of vulnerability comprises a hydrophobic cluster spanning three helical turns, with acid residues framing the center turn

Genetic and structural analysis indicate supersite recognition to be compatible with diverse antibody ontogenies
The Alternative Sigma Factor SigL Influences Clostridioides difficile Toxin Production, Sporulation, and Cell Surface Properties
Authors: Clark Andrew E. , Adamson Chelsea C. , Carothers Katelyn E. , Roxas Bryan Angelo P. , Viswanathan V.K. , Vedantam Gayatri
Published: January 2022

The alternative sigma factor SigL (Sigma-54) facilitates bacterial adaptation to the extracellular environment by modulating the expression of defined gene subsets. A homolog of the gene encoding SigL is conserved in the diarrheagenic pathogen Clostridioides difficile. To explore the contribution of SigL to C. difficile biology, we generated sigL-disruption mutants (sigL::erm) in strains belonging to two phylogenetically distinct lineages – the human-relevant Ribotype 027 (strain BI-1) and the veterinary-relevant Ribotype 078 (strain CDC1). Comparative proteomics analyses of mutants and isogenic parental strains revealed lineage-specific SigL regulons. Concomitantly, loss of SigL resulted in pleotropic and distinct phenotypic alterations in the two strains. Sporulation kinetics, biofilm formation, and cell surface-associated phenotypes were altered in CDC1 sigL::erm relative to the isogenic parent strain, but remained unchanged in BI-1 sigL::erm. In contrast, secreted toxin levels were significantly elevated only in the BI-1 sigL::erm mutant relative to its isogenic parent. We also engineered SigL overexpressing strains and observed enhanced biofilm formation in the CDC1 background, and reduced spore titers as well as dampened sporulation kinetics in both strains. Thus, we contend that SigL is a key, pleiotropic regulator that dynamically influences C. difficile’s virulence factor landscape, and thereby, its interactions with host tissues and co-resident microbes.

Contribution to the Field

Alternative sigma factors modulate bacterial gene expression in response to environmental and metabolic cues. C. difficile encodes multiple alternative sigma factors which mediate critical cellular processes. A Sigma-54 ortholog, SigL, is conserved across all sequenced strains, yet its function remains to be elucidated. We demonstrate that SigL dynamically influences C. difficile biology in fundamental, but distinct, ways in two strains representing two clinically-relevant C. difficile phylogenetic lineages (ribotypes). Loss of SigL results in changes in sporulation kinetics, biofilm formation, alterations in cell surface properties, and secreted toxin levels in a strain-specific manner. SigL overexpression, however, uniformly impedes sporulation. Thus, SigL plays a fundamental role in regulating the expression of C. difficile virulence factors and likely profoundly impacts pathogenesis in a strain-specific manner.
Culture and genomic analysis of Arsenophonus apicola sp. nov. isolated from the honeybee Apis mellifera
Authors: Nadal-Jimenez Pol , Siozios Stefanos , Frost Crystal L. , Court Rebecca , Chrostek Ewa , Drew Georgia C. , Evans Jay D. , Hawthorne David J. , Burritt James B. , Hurst Gregory D.D.
Published: January 2022

The genus Arsenophonus has been traditionally considered to be comprised of heritable bacterial symbionts of arthropods. Recent work has reported a microbe related to the type species A. nasoniae as infecting the honey bee, Apis mellifera. The association was unusual for members of the genus in that the microbe-host interaction arose through environmental and social exposure rather than vertical transmission. In this study, we describe the in vitro culture of ArsBeeUS, a strain of this microbe isolated from A. mellifera in the USA. The 16S rRNA sequence of the isolated strain clearly indicates it falls within the genus Arsenophonus. Biolog analysis indicates the bacterium has a restricted range of nutrients that support growth. In vivo experiments demonstrate the strain proliferates rapidly on injection into A. mellifera hosts. We further report the closed genome sequence for the strain. The genome is 3.3 MB and 37.6% GC, which is smaller than A. nasoniae but larger than the genomes reported for non-culturable Arsenophonus symbionts. The genome is complex, with 6 plasmids and 11 predicted intact phage elements, but notably less complex than A. nasoniae. With 92% average nucleotide identity (ANI) to the type strain A. nasoniae, the ArsBeeUS strain isolated is clearly distinct from the type species, and we propose the name Arsenophonus apicola sp. nov. (CECT 30499; LMG 32504).
Zebrafish caudal fin amputation induces a metabolic switch necessary for cell identity transitions and cell cycle re-entry to support blastema formation and bone regeneration
Authors: Brandão Ana S. , Borbinha Jorge , Pereira Telmo , Brito Patrícia H. , Lourenço Raquel , Bensimon-Brito Anabela , Jacinto António
Published: January 2022

Regeneration depends on the ability of mature cells at the injury site to respond to injury, generating tissue-specific progenitors that incorporate the blastema and proliferate to reconstitute the original organ architecture. The metabolic microenvironment has been tightly connected to cell function and identity during development and tumorigenesis. Yet, the link between metabolism and cell identity at the mechanistic level in a regenerative context remains unclear. The adult zebrafish caudal fin, and bone cells specifically, have been crucial for the understanding of mature cell contribution to tissue regeneration. Here, we use this model to explore the relevance of glucose metabolism for the cell fate transitions preceding new osteoblast formation and blastema assembly. We show that injury triggers a shift in the metabolic profile at early stages of regeneration, enhancing glycolysis at the expense of mitochondrial oxidation. This metabolic switch mediates transcriptional changes that make mature osteoblast amenable to be reprogramed into pre-osteoblasts and induces cell cycle re-entry and progression. Manipulation of the metabolic profile led to severe reduction of the pre-osteoblast pool, diminishing their capacity to generate new osteoblasts, and to a complete abrogation of blastema formation. Overall, our data indicate that metabolic alterations have a powerful instructive role in regulating genetic programs that dictate fate decisions and stimulate proliferation, thereby providing a deeper understanding on the mechanisms regulating blastema formation and bone regeneration.
Syntheses, crystal structures and Hirshfeld surface analysis of (Z)-3-[(3-acetyl-2-hydroxyphenyl)amino]-2-bromoprop-2-enal and a novel ZnIIcomplex
Authors: Jiang Tan-Lin , Li Wei-Zhou , Gao Qi-Feng , Tan Deng-Feng , Pang Jin-Ying , Zhang Shu-Hua
Published: January 2022

A novel zero-dimensional dinuclear zinc complex, di-μ-acetato-1:2κ4O:O′-(μ-2-acetyl-6-{[(Z)-2-bromo-3-oxoprop-1-en-1-yl]azanidyl}phenolato-1κ2O1,O2:2κ3O1,N,O6)(N,N-dimethylacetamide-1κO)dizinc(II), [Zn2(C11H8BrNO3)(CH3COO)2(C4H9NO)] or [Zn2(L)(CH3COO)2(DMA)],1, was synthesized using (Z)-3-[(3-acetyl-2-hydroxyphenyl)amino]-2-bromoprop-2-enal (H2L), which was synthesized from 1-(3-amino-2-hydroxyphenyl)ethanone and 2-bromomalonaldehyde. H2Land1were characterized by single-crystal X-ray diffraction, FT–IR spectroscopy and elemental analysis. Theoretical calculations of the bond orders and excited state of H2Lconfirmed that there is extensive electron delocalization in the H2Lmolecules. Single-crystal X-ray diffraction shows that the two Zn atoms are pentacoordinated in distorted trigonal bipyramidal configurations in the crystals of1. The thermogravimetric analysis of1shows that the main frame of the complex remains stable to about 190 °C. Powder X-ray diffraction (PXRD) analysis shows that1possesses high purity and acid and alkali resistance. The intermolecular interactions of H2Land1were analyzed using Hirshfeld surface analysis and the results indicate that the H...H and O...H interactions of H2Land1play a considerable role in stabilizing the self-assembly process.
Model of integrated reporting “concept in practice” in the light of pragmatic constructivist paradigm: case studies of life science companies
Authors: Dyczkowska Joanna , Fijałkowska Justyna
Published: January 2022

Purpose

This longitudinal research paper is based on a case study analysis of two Danish life science companies. The general purpose of the paper is to uncover changes in the reporting practices of experienced integrated reporting (IR) reporters. In order to meet that objective, a pragmatic constructivist paradigm was applied to make a better understanding of factors affecting disclosure decisions in the integrated reports.

Design/methodology/approach

The research uses a qualitative methodological approach. It is based on content and discourse analyses of the written documents, including the integrated reports, auditors' statements and independent assurance reports.

Findings

The model developed in this study reflects a real phenomenon related to the development of IR practices. The pragmatic constructivist paradigm explains how practitioners perceive business reality, act in the face of changing facts and values and make decisions regarding material disclosures.

Research limitations/implications

The investigation of only two companies may be perceived as a limitation of this study. However, a small number of life science companies have prepared integrated reports for a long time. The selected organisations are the pioneers in that field and have drawn up integrated reports since 2002 or 2004.

Originality/value

This paper develops an original model of IR “concept in practice”. It considers the regulatory framework regarding materiality in IR through the prism of facts that form a basis for practical work. It also emphasises an impact of a value system and social context on disclosure decisions in integrated reports. In that way, a link between the constructivist paradigm and IR is created.
The systems architecture ontology (SAO): an ontology-based design method for cyber–physical systems
Authors: Sales Diego Camara , Becker Leandro Buss , Koliver Cristian
Published: January 2022

Purpose

Managing components' resources plays a critical role in the success of systems' architectures designed for cyber–physical systems (CPS). Performing the selection of candidate components to pursue a specific application's needs also involves identifying the relationships among architectural components, the network and the physical process, as the system characteristics and properties are related.

Design/methodology/approach

Using a Model-Driven Engineering (MDE) approach is a valuable asset therefore. Within this context, the authors present the so-called Systems Architecture Ontology (SAO), which allows the representation of a system architecture (SA), as well as the relationships, characteristics and properties of a CPS application.

Findings

SAO uses a common vocabulary inspired by the Architecture Analysis and Design Language (AADL) standard. To demonstrate SAO's applicability, this paper presents its use as an MDE approach combined with ontology-based modeling through the Ontology Web Language (OWL). From OWL models based on SAO, the authors propose a model transformation tool to extract data related to architectural modeling in AADL code, allowing the creation of a components' library and a property set model. Besides saving design time by automatically generating many lines of code, such code is less error-prone, that is, without inconsistencies.

Originality/value

To illustrate the proposal, the authors present a case study in the aerospace domain with the application of SAO and its transformation tool. As result, a library containing 74 components and a related set of properties are automatically generated to support architectural design and evaluation.
Assessment of corrosivity of emulsions from a petroleum sample on X80 steel
Authors: Quej-Ake Luis Manuel , García Jiménez Sergio , Liu Hongbo , Alamilla J.L. , Angeles-Chavez Carlos
Published: January 2022

Purpose

The purpose of this paper is to study the corrosion process by examining the deterioration of X80 steel exposed to a real petroleum sample containing condensed hydrocarbon plus oilfield-produced water, which were subjected to stimulated emulsions in flowing media at 50°C.

Design/methodology/approach

The impedance and polarization spectra were used to assess the aggressiveness of the petroleum sample and tried to find a washing process using condensed hydrocarbon with deionized water. Mössbauer technique was used to identify the phases in precipitated ions obtained during an oven-drying procedure of the oilfield produced water.

Findings

The emulsion, chloride, sulphur compounds, heavy metals and the use of a double hydrodynamic system were the most important factors affecting the corrosion of X80 steel. The corrosion rate of this steel increased when oilfield-produced water was stimulated by a double hydrodynamic system (4.56 mm/year). It was determined to be 7.66 mm/year and 4.01 mm/year when steel was exposed to a stimulated emulsion using the petroleum sample and condensed hydrocarbon with deionized water at 24 h, respectively, suggesting that a significant process of hydrocarbon washing could occur and a more corrosive solution was highlighted. Mössbauer results showed that the ions precipitates included the following phases at Wt.%: magnetite (20.0), greigeite (22.8), siderite (3.2), pyrite (2.9), marcasite (26.7) and mackinawite (24.4).

Originality/value

A stimulated hydrocarbon/water emulsions with a more homogeneous solution containing high concentrations of saline compounds and heavy metals were used to simulate the susceptibility to corrosion on the internal pipeline steels exposed to any type of immiscible liquids such as condensed hydrocarbon, or crude oil, containing water. A practical application of the presented research could provide a novel framework for understanding the internal corrosion in pipelines from the simulation of washed hydrocarbons after the stimulated emulsions that can be found in the field. Because more susceptibility to corrosion for pipeline steels would be expected at the end of the transportation of the fluid. It is possible to investigate the possible corrosion mechanisms by using a dried oilfield-produced water sample interacting with the pipeline steels.
“Iranian family caregivers of autistic children: the experience of stigma”
Authors: Poorkhorshidi Nastaran , Zohari Anboohi Sima , Mohtashami Jamile , Alavi Majd Hamid
Published: January 2022

Purpose

Autistic children and their family caregivers are impacted widely by the social arrangements, which bring up a variety of problems and make their caregiving duties even more difficult. One of the main troubles family caregivers struggle with is the “Autism stigma” that eventually leads to social exclusion. This study aims to identify shreds of evidence of Autism stigma experienced by family caregivers of autistic children. The study also aims to present some general comparison between the findings in Iran and a few other countries’ available respective data to the “Autism stigma.”

Design/methodology/approach

This study is an inductive qualitative content analysis. Twelve family caregivers were purposefully selected. Data were gathered exercising semi-structured, in-depth interviews and scrutinized using content analysis method.

Findings

In the interviews with the participants, a new category called “Autism stigma” was discerned. This category includes three subcategories: “Diagnosis process,” “Lack of awareness” and “Presence in the society.”

Originality/value

In Iran, Autism is considered a kind of social stigma. It mainly happens due to a lack of public awareness about this psychological disorder. The family caregivers in the community suffer from the stigma of autism, which leads them to distance themselves from society. This paper aims to improve the social awareness in regard to the negative impacts of Autism stigma.
When and how brands affect importance of product attributes in consumer decision process
Authors: Park Hyun Young , Chang Sue Ryung
Published: January 2022

Purpose

This research investigates when and how brands influence attribute importance weights. Most past studies modelling consumer decision processes treated the brand of a product as an attribute parallel to the price, color or size of a product, and as a result, those studies assigned an equal (i.e. non-contingent) importance weight across brands for each attribute. In contrast, this study introduces a brand-contingent attribute-weighting process, in which brand is a higher-order construct that influences attribute importance.

Design/methodology/approach

This study presents a multi-level choice model in which the importance weight of an attribute can vary across brands. This study then estimates the model using real purchase data and survey data from an airline industry.

Findings

This study finds that attribute importance weights are contingent upon two aspects of a brand – the perceived relative position of the brand and consumers’ brand usage experiences. Specifically, when consumers perceive a brand to be inferior to its competitors in a given attribute, they generally place greater weight on that attribute for that brand. In contrast, when consumers perceive a brand to be superior to its competitors in a given attribute, only consumers with extensive brand usage experiences place greater weight on that attribute for that brand.

Practical implications

The findings provide managerial insights on brand positioning and segmentation strategies using consumers’ brand usage experiences.

Originality/Value

This study advances the literature on consumer decision processes by modeling an attribute-weighting process that is contingent upon brands. The present study models this process based on consumer behavior theories and estimates the model using real market data.
Exploring the effects of learning abilities, technology and market changes on the need for future skills
Authors: Gouda Hanan
Published: January 2022

Purpose

The study investigates the effects of learning abilities, market changes and technological development in the field of the need for future skills.

Design/methodology/approach

This quantitative research is a descriptive study, as it describes the characteristics of variables. Non-probability sampling was applied. A survey was distributed online during May–July, 2021, using a cross-sectional timeframe, to managers (in three industries: FINTECH, FMCG and industrial/production field) who work with teams of Gen Z and Millennials. The data collected were analyzed using SPSS.

Findings

There is a significant positive relationship between learning abilities and future skills development, there is a significant positive relationship between technology development and future skills development, and there is a significant positive relationship between market changes and future skills development.

Research limitations/implications

Data were collected through online surveys, focusing on three industries. This study neglects the use of qualitative data in order to gain further explanations regarding the main factors influencing employees' future skills development in times of globalization, advanced technology, global crisis, and the need for sustainability, the model of qualification for future jobs seems dynamic and controversial. This study's empirical evidence illustrates that future skills need to be developed for employees in order to affect their methods with regard to performing their role in the company.

Originality/value

New skills are necessarily emerging in the labor market. The maturity level of higher education institutions to promote these skills is questioned. Thus, this study develops empirical knowledge for educational institutions regarding the effects of learning abilities, market changes and technological development.
Multifractality during upside/downside trends in the MENA stock markets: the effects of the global financial crisis, oil crash and COVID-19 pandemic
Authors: Mensi Walid , Yousaf Imran , Vo Xuan Vinh , Kang Sang Hoon
Published: January 2022

Purpose

This paper examines asymmetric multifractality (A-MF) in the leading Middle East and North Africa (MENA) stock markets under different turbulent periods (global financial crisis [GFC] and European sovereign debt crisis [ESDC], oil price crash and COVID-19 pandemic).

Design/methodology/approach

This study applies the asymmetric multifractal detrended fluctuation analysis (A-MF-DFA) method of Cao et al. (2013) to identify A-MF and MENA stock market efficiency during the COVID-19 pandemic.

Findings

The results show strong evidence of different patterns of MF during upward and downward trends. Inefficiency is higher during upward trends than during downward trends in most of the stock markets in the whole sample period, and the opposite is true during financial crises. The Turkish stock market is the least inefficient during upward and downward trends. A-MF intensifies with an increase in scales. The evolution of excessive A-MF for MENA stock returns is heterogeneous. Most of the stock markets are more inefficient during a pandemic crisis than during an oil crash and other financial crises. However, the inefficiency of the Saudi Arabia and Qatar stock markets is highly sensitive to oil price crashes. Overall, the level of inefficiency varies across market trends, scales and stock markets and over time. The findings of this study provide investors and policymakers with valuable insights into efficient investment strategies, risk management and financial stability.

Originality/value

This paper first explores A-MF in the MENA emerging stock markets. The A-MF analysis provides useful information to investors regarding asset allocation, portfolio risk management and investment strategies during bullish and bearish market states. In addition, this paper examines A-MF under different turbulent periods, such as the GFC, the ESDC, the 2014–2016 oil crash and the COVID-19 pandemic.
How the sanitation dimensions impacts consumer perceptions and emotions in five-star hotels due to COVID-19 pandemic?
Authors: Gupta Vikas , Roy Hiran , Chhabra Meghna , Sanchez‐Canizares Sandra M. , Sahu Garima
Published: January 2022

Purpose

This study aims to evaluate the consumer perceptions related to sanitation in the five-star hotels due to the COVID-19 pandemic. It also identified the most significant sanitation dimensions and their influence on the pertinent emotions experienced by the hotel consumers.

Design/methodology/approach

It identified seven sanitation dimensions (i.e. exterior of the hotel, guestrooms, washrooms/restrooms, in-house restaurant dining, hotel employees, public areas and handling of food) which were assessed through 10 positive and negative consumer sanitation emotions. A structured online survey was conducted to collect data from the 763 five-star hotel consumers. Exploratory factor analysis was applied on the 35 parameters of the seven identified sanitation dimensions, and analysis of variance (ANOVA) was used to determine the most significant dimensions among the hotel consumers.

Findings

Results revealed that among the seven sanitation dimensions, “exterior of the hotel” and “public area” dimensions were found to be statistically less significant compared to the other sanitation dimensions. Findings related to consumer emotions showed that a significantly high percentage of consumers revealed strong negative emotions, i.e. disgust and discontent toward the poor standards of sanitation in the hotels.

Practical implications

The study results may be helpful for the hotel administrators and managers to adequately plan the training sessions for their employees based on the consumer perception and emotions toward the identified sanitation dimensions. Further, it may also help in the implementation of the COVID-19 awareness program based on the consumer inputs and perceptions.

Originality/value

Although a few studies have been performed to explore the sanitation dimensions in the hospitality sector before, but this will be a first attempt to identify and measure the sanitation dimensions and corresponding consumer emotions due to the COVID-19 pandemic.
Case Study Telecom industry and competitive landscape in India: will MTNL and BSNL successfully recover?
Authors: Kumar Rohit , Bose Pallav
Published: January 2022

Purpose

This case study aims to analyse the different factors that cause a decline in an organisation's performance. It projects data for the prospective case readers to explore the possible approaches for the Chairman-cum-Managing Director (CMD) of Mahanagar Telephone Nigam Limited (MTNL) and Bharat Sanchar Nigam Limited (BSNL) to turnaround both the organisations. Furthermore, the case compels the readers to study the Indian Telecom industry to analyse the competitive behaviour and the consequent actions necessary to survive and thrive amongst their peers. From the theoretical perspective, the case emphasises the recent change observed in the Telecom industry regarding the transition from value-chain to value-network.

Design/methodology/approach

The authors collected the case facts and data for the case study from secondary sources like the latest news articles, the CRISIL database, company annual statements, company press releases and government regulatory body web portals.

Findings

The case study has identified the issues pertinent in the public sector companies in India, especially in the telecom sector, concerning leadership, pending government financial commitments and a slow-moving attitude towards taking action.

Originality/value

The case study highlights the management problems faced by the CMD of the two public sector telecom companies i.e. BSNL and MTNL.