bluuebunny/crossref_metadata_2025 huggingface dataset:
In schizophrenia, the effects of the IL-6/IL-23/Th17 axis on health-related quality of life and disabilities are partly mediated by generalized cognitive decline and the symptomatome
Authors: Al-Musawi Ali Fattah , Al-Hakeim Hussein Kadhem , Al-Haboby Inas H. , Almulla Abbas F. , Maes Michael
Published: May 2022

Schizophrenia patients show increased disabilities and lower quality of life (DisQoL). Nevertheless, there are no data whether, in schizophrenia, activation of the interleukin (IL)-6, IL-23, T helper (Th)-17 axis and lowered magnesium and calcium levels impact DisQoL scores. This study recruited 90 patients with schizophrenia (including 40 with deficit schizophrenia) and 40 healthy controls and assessed the World Health Association QoL instrument-Abbreviated version and Sheehan Disability scale, Brief Assessment of Cognition in Schizophrenia (BACS), IL-6, IL-23, IL-17, IL-21, IL-22, tumor necrosis factor (TNF)-α, magnesium and calcium. Regression analyses showed that a large part of the first factor extracted from the physical, psychological, social and environmental HR-QoL and interference with school/work, social life, and home responsibilities was predicted by a generalized cognitive deterioration (G-CoDe) index (a latent vector extracted from BACs scores), and the first vector extracted from various symptom domains (“symptomatome”), whereas the biomarkers had no effects. Partial Least Squares analysis showed that the IL6IL23Th17 axis and magnesium/calcium had highly significant total (indirect + direct) effects on HR-QoL/disabilities which were mediated by G-CoDe and the symptomatome (a first factor extracted from negative and positive symptoms). The IL6IL23Th17 axis explained 63.1% of the variance in a single latent trait extracted from G-CoDe, symptomatome, HR-QoL and disability data. The latter features are manifestations of a common core, namely the behavioral-cognitive-psycho-social worsening index, which is caused by the neuroimmunotoxic effects of the IL6IL23Th17 axis in subjects with lowered antioxidant defenses (magnesium and calcium) thereby producing damage to neuronal circuits underpinning deficit schizophrenia.
Hypoxia-mediated regulation of DDX5 through decreased chromatin accessibility and post-translational targeting restricts R-loop accumulation
Authors: Leszczynska Katarzyna B. , Dzwigonska Monika , Estephan Hala , Moehlenbrink Jutta , Bowler Elizabeth , Giaccia Amato J. , Mieczkowski Jakub , Kaminska Bozena , Hammond Ester M.
Published: May 2022

Local hypoxia occurs in most solid tumors and is associated with aggressive disease and therapy resistance. Widespread changes in gene expression play a critical role in the biological response to hypoxia. However, most research has focused on hypoxia-inducible genes as opposed to those which are decreased in hypoxia. We demonstrate that chromatin accessibility is decreased in hypoxia, predominantly at gene promoters and specific pathways are impacted including DNA repair, splicing and the R-loop interactome. One of the genes with decreased chromatin accessibility in hypoxia wasDDX5, encoding the RNA helicase, DDX5, which showed reduced expression in various cancer cell lines in hypoxic conditions, tumor xenografts and in patient samples with hypoxic tumors. Most interestingly, we found that when DDX5 is rescued in hypoxia, replication stress and R-loop levels accumulate further, demonstrating that hypoxia-mediated repression of DDX5 restricts R-loop accumulation. Together these data support the hypothesis that a critical part of the biological response to hypoxia is the repression of multiple R-loop processing factors, however, as shown for DDX5, their role is specific and distinct.
HiCognition: a visual exploration and hypothesis testing tool for 3D genomics
Authors: Langer Christoph C. H. , Mitter Michael , Stocsits Roman R. , Gerlich Daniel W.
Published: May 2022

The 3D organization of the genome and epigenetic marks play important roles in gene expression, DNA repair, and chromosome segregation. Understanding how structure and composition of the chromatin fiber contribute to function requires integrated analysis of multiple genomics datasets from various techniques, experimental conditions, and cell states. Genome browsers facilitate such analysis, yet currently visualize only a few regions at a time and lack statistical functions that are often necessary to extract meaningful information. Here, we present HiCognition, a visual exploration and machine-learning tool based on a new genomic region set concept, which enables detection of patterns and associations between 3D chromosome conformation and collections of 1D genomics profiles of any type. By revealing how transcriptional activity and cohesin subunit isoforms contribute to chromosome conformation, we showcase how the flexible user interface and machine learning tools of HiCognition can help understand the relationship between structure and function of the genome.
Dynamic tripartite construct of interregional engram circuits underlies forgetting of extinction memory
Authors: Gu Xue , Wu Yan-Jiao , Zhu Jia-Jie , Wu Xin-Rong , Wang Qi , Yi Xin , Lin Ze-Jie , Jiao Zhi-Han , Xu Miao , Jiang Qin , Li Ying , Xu Nan-Jie , Zhu Michael Xi , Wang Lu-Yang , Xu Tian-Le , Li Wei-Guang
Published: May 2022

Fear extinction allows for adaptive control of learned fear responses but often fails, resulting in a renewal or spontaneous recovery of the extinguished fear, i.e., forgetting of the extinction memory readily occurs. Using an activity-dependent neuronal labeling strategy, we demonstrate that engram neurons for fear extinction memory are dynamically positioned in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral hippocampus (vHPC), which constitute an engram construct in the term of directional engram synaptic connectivity from the BLA or vHPC to mPFC, but not that in the opposite direction, for retrieval of extinction memory. Fear renewal or spontaneous recovery switches the extinction engram construct from an accessible to inaccessible state, whereas additional extinction learning or optogenetic induction of long-term potentiation restores the directional engram connectivity and prevents the return of fear. Thus, the plasticity of engram construct underlies forgetting of extinction memory.
Changes in protonation states of in-pathway residues can alter ligand binding pathways obtained from spontaneous binding molecular dynamics simulations
Authors: Girame Helena , Garcia-Borràs Marc , Feixas Ferran
Published: May 2022

Protein-ligand binding processes often involve changes in protonation states that can be key to recognize and orient the ligand in the binding site. The pathways through which (bio)molecules interplay to attain productively bound complexes are intricate and involve a series of interconnected intermediate and transition states. Molecular dynamics (MD) simulations and enhanced sampling techniques are commonly used to characterize the spontaneous binding of a ligand to its receptor. However, the effect of protonation state changes of in-pathway residues in spontaneous binding MD simulations remained mostly unexplored. Here, we used molecular dynamics simulations to reconstruct the trypsin-benzamidine binding pathway considering different protonation states of His57. This residue is part of the trypsin catalytic triad and is located more than 10 Å away from Asp189, which is responsible for benzamidine binding in the trypsin S1 pocket. Our MD simulations showed that the binding pathways that benzamidine follow to target the S1 binding site are critically dependent on the His57 protonation state. Binding of benzamidine frequently occurs when His57 is protonated in the delta nitrogen while the binding process is significantly less frequent when His57 is positively charged. Constant-pH MD simulations retrieved the equilibrium populations of His57 protonation states at trypsin active pH offering a clearer picture of benzamidine recognition and binding. These results indicate that properly accounting for protonation states of distal residues can be important in spontaneous binding MD simulations.
Imaging the structure and dynamic activity of retinal microglia and macrophage-like cells in the living human eye
Authors: Rui Yuhua , Lee Daniel M.W. , Zhang Min , Snyder Valerie C , Raghuraman Rashmi , Gofas-Salas Elena , Mecê Pedro , Yadav Sanya , Tiruveedhula Pavan , Grieve Kate , Sahel José-Alain , Errera Marie-Hélène , Rossi Ethan A.
Published: May 2022

Purpose

We recently showed how a refined sequential detection pattern and image processing pipeline for multi-offset adaptive optics scanning light ophthalmoscopy (AOSLO) can increase the contrast of weakly scattering inner retinal structures, including microglia. However, sequential detection was still time-consuming, preventing dynamics from being monitored over short intervals (< 3 mins). Here we show that simultaneous fiber-bundle (FB) detection can overcomes this limitation to reveal the structure and dynamic activity of microglia and macrophage-like cells in healthy and diseased retinae.

Methods

We designed and implemented a custom 7-fiber optical FB with one central confocal fiber and six larger fibers for multi-offset detection in AOSLO at a single focal plane. We imaged the ganglion cell layer at several locations at multiple timepoints (from minutes to weeks) in 8 healthy participants and in 4 patients with ocular infections or inflammation, including ocular syphilis and posterior uveitis. Microglia and immune cells were manually segmented to quantify cell morphometry and motility.

Results

Fiber-bundle detection reduced single acquisition time to 20-30 seconds, enabling imaging over larger areas and monitoring of dynamics over shorter intervals. Presumed microglia in healthy retinas had an average diameter of 12.8 μm and with a spectrum of morphologies including circular cells and elongated cells with visible processes. We also detected the somas of putative macroglia, potentially astrocytes, near the optic nerve head. Microglia moved slowly in normal eyes (0.02μm/sec, on average) but speed increased in patients with active infections or inflammation (up to 2.37μm/sec). Microglia activity was absent in a patient with chronic uveitis that was quiescent but apparent over short intervals in an active uveitis retina. In a patient with ocular syphilis imaged at multiple timepoints during treatment, macrophage-like cells containing granular internal structures were seen. Decreases in the quantity and motility of these immune cells were correlated with improvements to vision and other structural and systemic biomarkers.

Conclusions

FB-AOSLO enable simplified optical setup with easy alignment and implementation. We imaged the fine-scale structure and dynamics of microglia and macrophage-like cells during active infection and inflammation in the living eye for the first time. In healthy eyes we also detected putative glia cell near the optic nerve head. FB-AOSLO offers promise as a powerful tool for detecting and monitoring retinal inflammation and infection in the living eye over short response to treatment.
Exploratory Meta-Analysis of Hypoxic Transcriptomes Using Precise Transcript Reference Sequence Set
Authors: Ono Yoko , Bono Hidemasa
Published: May 2022

Gene expression studies are intrinsically biased, with many studies influenced by concomitant information such as gene-disease associations. This limitation can be overcome using a data-driven analysis approach without relying on ancillary information. The FANTOM CAGE Associated Transcriptome (FANTOM-CAT) project provides a comprehensive meta-assembly of the human transcriptome using coding and non-coding genes. Hypoxia strongly influences gene expression; additionally, non-coding RNA (ncRNA) metabolism is downregulated in response to hypoxic stimuli. We evaluated the differential response of various transcripts to hypoxia by determining their hypoxia responsiveness scores. Enrichment analysis revealed that several genes associated with ncRNA metabolism, particularly those involved in ribosomal RNA processing, were downregulated in response to hypoxia. Previously published information from the FANTOM-CAT project was suitable for meta-analysis of the transcriptome sequencing data from both coding and ncRNAs, and evaluate the hypoxia responsiveness of target transcripts and relationship between sense-antisense transcripts from the same locus. Our results may facilitate functional annotation of various transcripts including ncRNAs, allowing for both sense and antisense and coding and non-coding evaluations.

Summary blurb

Exploratory meta-analysis of hypoxic RNA-seq data using FANTOM-CAT as a reference transcriptome facilitates the evaluation of relationship between sense-antisense transcripts from the same locus.
Genomic, transcriptomic and proteomic depiction of iPSC-derived smooth muscle cells as emerging cellular models for arterial diseases
Authors: Liu Lu , Jouve Charlène , Henry Joséphine , Berrandou Takiy-Eddine , Hulot Jean-Sébastien , Georges Adrien , Bouatia-Naji Nabila
Published: May 2022

Background

Vascular smooth muscle cells (VSMCs) plasticity is a central mechanism in cardiovascular health and disease. We aimed at providing deep cellular phenotyping, epigenomic and proteomic depiction of SMCs derived from induced pluripotent stem cells (iPSCs) and evaluating their potential as cellular models in the context of complex genetic arterial diseases.

Methods

We differentiated 3 human iPSC lines using either RepSox (R-SMCs) or PDGF-BB and TGF-β (TP-SMCs), during the second half of a 24-days-long protocol. In addition to cellular assays, we performed RNA-Seq and assay for transposase accessible chromatin (ATAC)-Seq at 6 time-points of differentiation. The extracellular matrix content (matrisome) generated by iPSCs derived SMCs was analyzed using mass spectrometry.

Results

Both iPSCs differentiation protocols generated SMCs with positive expression of SMC markers. TP-SMCs exhibited greater capacity of proliferation, migration and lower calcium release in response to contractile stimuli compared to R-SMCs. RNA-Seq data showed that genes involved in the contractile function of arteries were highly expressed in R-SMCs compared to TP-SMCs or primary SMCs. Matrisome analyses supported an overexpression of proteins involved in wound repair in TP-SMCs and a higher secretion of basal membrane constituents by R-SMCs. Open chromatin regions of R-SMCs and TP-SMCs were significantly enriched for variants associated with coronary artery disease and blood pressure, while only TP-SMCs were enriched for variants associated with peripheral artery disease.

Conclusions

Our study portrayed two iPSCs derived SMCs models presenting complementary cellular phenotypes of high relevance to SMC plasticity. In combination with genome-editing tools, our data supports high relevance of the use of these cellular models to the study of complex regulatory mechanisms at genetic risk loci involved in several arterial diseases.

Graphical Abstract
Combined MD and QM/MM Calculations reveal Allostery Driven Promiscuity in Dipeptide Epimerases of Enolase Family
Authors: Tripathi Ankita , Dubey Kshatresh Dutta
Published: May 2022

The adaptability of the active site to amplify the secondary function is supposed to be the fundamental cause of the promiscuity and the evolution of new functions in the enzymes. In most cases, mutations occur close to the active site and/or in the catalytic site to change the active site plasticity to accommodate the non-native substrate. In the present study, using MD simulations and hybrid QM/MM calculations, we have shown a new way to enhance the promiscuity, i.e., the allostery-driven promiscuity. Using a case study of the AEE enzyme where the capping loop recognizes the substrate, herein, we show that a single site mutation (D321G) far from the capping loop can induce a large conformational change in the capping loop to recognize different substrates for different functions. The QM/MM calculations for the WT and mutated enzyme provide a first validation of the mechanism of 1,1-proton transfer and dehydration by the AEE enzyme. Since AEE epimerase possesses a highly conserved TIM-barrel fold, we believe that our study provides a crucial lead to understanding the mechanism of emergence of secondary function which can be useful to repurpose ancient enzymes for modern usage.
Qualification of Identity, Quality-Attribute Monitoring and New Peak Detection in An Improved Multi-Attribute Method with Lys-C Digestion for Characterization and Quality Control of Therapeutic Monoclonal Antibodies
Authors: Li Xuanwen , Pierson Nicholas A. , Hua Xiaoqing , Patel Bhumit A. , Olma Michael H. , Strulson Christopher A. , Letarte Simon , Richardson Douglas D.
Published: May 2022

The use of Multi-attribute method (MAM) for identity and purity testing of biopharmaceuticals offers the ability to complement and replace multiple conventional analytical technologies with a single mass spectrometry (MS) method. Method qualification and phase-appropriate validation is one major consideration for the implementation of MAM in a current Good Manufacturing Practice (cGMP) environment. We developed an improved MAM workflow with optimized sample preparation using Lys-C digestion for therapeutic monoclonal antibodies. In this study, we qualified the enhanced MAM workflow for mAb-1 identity, product quality attributes (PQAs) monitoring and new peak detection (NPD). The qualification results demonstrated the full potential of the MAM for its intended use in mAb-1 characterization and quality control in regulated labs. To the best of our knowledge, this is the first report of MAM qualification for mAb identity, PQA monitoring, and new peak detection (NPD) in a single assay, featuring 1) the first full qualification of MAM using Lys-C digestion without desalting using a high-resolution MS, 2) a new approach for mAb identity testing using MAM, and 3) the first qualification of NPD for MAM. The developed MAM workflow and the approaches for MAM qualification may serve as a reference for other labs in the industry.
Omicron infection induces low-level, narrow-range SARS-CoV-2 neutralizing activity
Authors: Turelli Priscilla , Zaballa María-Eugenia , Raclot Charlène , Fenwick Craig , Kaiser Laurent , Eckerle Isabella , Pantaleo Giuseppe , Guessous Idris , Stringhini Silvia , Trono Didier
Published: May 2022

Background

The rapid worldwide spread of the mildly pathogenic SARS-CoV-2 Omicron variant has led to the suggestion that it will induce levels of collective immunity that will help putting an end to the COVID19 pandemics.

Methods

Convalescent serums from non-hospitalized individuals previously infected with Alpha, Delta or Omicron BA.1 SARS-CoV-2 or subjected to a full mRNA vaccine regimen were evaluated for their ability to neutralize a broad panel of SARS-CoV-2 variants.

Findings

Prior vaccination or infection with the Alpha or to a lesser extent Delta strains conferred robust neutralizing titers against most variants, albeit more weakly against Beta and even more Omicron. In contrast, Omicron convalescent serums only displayed low level of neutralization activity against the cognate virus and were unable to neutralize other SARS-CoV-2 variants.

Interpretation

Moderately symptomatic Omicron infection is only poorly immunogenic and does not represent a substitute for vaccination.

Funding

EPFL COVID Fund; private foundation advised by CARIGEST SA; Private Foundation of the Geneva University Hospitals; General Directorate of Health of the canton of Geneva, the Swiss Federal Office of Public Health.
An Epitope-Focused Trypanosome-Derived Vaccine Platform Elicits High-Affinity Antibodies and Immunity Against Fentanyl Effects
Authors: Triller Gianna , Vlachou Evi P. , Hashemi Hamidreza , van Straaten Monique , Zeelen Johan , Kelemen Yosip , Baehr Carly , Marker Cheryl L. , Ruf Sandra , Svirina Anna , Kruse Sebastian , Baumann Andreas , Miller Aubry K. , Bartel Marc , Pravetoni Marco , Stebbins C. Erec , Papavasiliou F. Nina , Verdi Joseph P.
Published: May 2022

Poorly antigenic small molecules pose challenges for the production of clinically efficacious antibodies. To address this, we have developed an immunization platform derived from the antigenic surface coat of the African trypanosome. Through sortase-based conjugation of antigens to the trypanosome surface coat protein variant surface glycoprotein (VSG), we created the VAST (VSG-immunogen Array by Sortase Tagging). We used VAST to elicit protective immunity to the effects fentanyl. Immunizing mice with fentanyl-VAST generated serological memory and protection from fentanyl challenge. Employing single-cell RNAseq, we then developed a streamlined method that synergizes with the VAST to identify immunization-elicited memory B cells and the antibodies they encode. All antibodies selected by this method displayed picomolar affinities for fentanyl. Passive immunization protected animals from fentanyl, while crystallography revealed that the mAbs bind fentanyl in an unusually deep pocket suited to small molecules, demonstrating the ability of the VAST to elicit high-quality therapeutic antibodies.
Integrated viral elements suggest the dual lifestyle of Tetraselmis spp. polinton-like viruses
Authors: Chase Emily E. , Desnues Christelle , Blanc Guillaume
Published: May 2022

In this study, we aimed at exploring horizontal gene transfer between viruses and Chlorodendraceae green algae (Chlorophyta) using available genomic and transcriptomic sequences for 20 algal strains. We identified a significant number of genes sharing a higher sequence similarity with viral homologues, thus signaling their possible involvement in HGTs with viruses. Further characterization showed that many of these genes were clustered in DNA regions of several tens to hundreds of kilobases in size, originally belonging to viruses related to known Tetraselmis spp. viruses (TetV and TsV). In contrast, the remaining candidate HGT genes were randomly dispersed in the algal genomes, more frequently transcribed and belonged to large multigene families. The presence of homologs in Viridiplantae suggested that these latter were more likely of algal rather than viral origin. We found a remarkable diversity Polinton- like virus (PLV) elements inserted in Tetraselmis genomes, all of which were most similar to the Tetrasemis striata virus TsV. The genes of PLV elements are transcriptionally inactive with the notable exception of the homologue of the TVSG_00024 gene of TsV whose function is unknown. We suggest that this gene may be involved in a sentinel process to trigger virus reactivation and excision in response to an environmental stimulus. Altogether, these results provide evidence that TsV- related viruses have a dual lifestyle, alternating between a free viral phase (i.e., virion) and a phase integrated into host genomes.
Evaluating and mitigating clinical samples matrix effects on TX-TL cell-free performance
Authors: Voyvodic Peter L. , Conejero Ismael , Mesmoudi Khouloud , Renard Eric , Courtet Philippe , Cattoni Diego I. , Bonnet Jerome
Published: May 2022

Cell-free biosensors are promising tools for medical diagnostics, yet their performance can be affected by matrix effects arising from the sample itself or from external components. Here we systematically evaluate the performance and robustness of cell-free systems in serum, plasma, urine, and saliva using two reporter systems, sGFP and luciferase. In all cases, clinical samples have a strong inhibitory effect. Of different inhibitors, only the RNase inhibitor mitigated matrix effects. However, we found that the recovery potential of RNase inhibitor was partially muted by interference from glycerol contained in the commercial buffer. We solved this issue by designing a strain producing an RNase inhibitor protein requiring no additional step in extract preparation. Furthermore, our new extract yielded higher reporter levels than previous conditions and tempered interpatient variability associated with matrix effects. This systematic evaluation and improvements of cell-free system robustness unified across many types of clinical samples is a significant step towards developing cell-free diagnostics for a wide range of conditions.
Quantitative spatial analysis of neuroligin-3 mRNA expression in the enteric nervous system reveals a potential role in neuronal-glial synapses and reduced expression inNlgn3R451Cmice
Authors: Herath Madushani , Cho Ellie , Franks Ashley E , Bornstein Joel C , Hill-Yardin Elisa L
Published: May 2022

Mutations in the Neuroligin-3 (Nlgn3) gene are implicated in autism spectrum disorder (ASD) and gastrointestinal (GI) dysfunction but its cellular expression in the GI tract remains to be characterised. Localisation of NLGN3 protein is challenging in intestinal tissue due to the lack of target-specific antibodies. Here, we combined RNAScopein situhybridization forNlgn3mRNA and immunofluorescence for markers of all enteric neurons, cholinergic submucosal neurons, non-cholinergic submucosal neurons, nitregic and calretinin-containing myenteric neurons as well as glial cells. We also developed a quantitative 3-dimensional image analysis method to measureNlgn3mRNA cellular expression levels in enteric neurons and glia. We show thatNlgn3mRNA is expressed in most submucosal and myenteric neurons as well as in enteric glia. The R451C mutation reducesNlgn3mRNA expression levels in cholinergic, nitrergic and calretinin enteric neuronal subpopulations but does not affectNlgn3mRNA expression in VIPergic submucosal neurons. In summary, we show that the autism-associated R451C mutation inNlgn3reducesNlgn3mRNA expression in the mouse ENS. These findings could shed light on the pathophysiology of GI dysfunction in ASD.
In situ structural analysis reveals membrane shape transitions during autophagosome formation
Authors: Bieber Anna , Capitanio Cristina , Erdmann Philipp S. , Fiedler Fabian , Beck Florian , Lee Chia-Wei , Li Delong , Hummer Gerhard , Schulman Brenda A. , Baumeister Wolfgang , Wilfling Florian
Published: May 2022

Autophagosomes are unique organelles which form de novo as double-membrane vesicles engulfing cytosolic material for destruction. Their biogenesis involves a series of membrane transformations with distinctly shaped intermediates whose ultrastructure is poorly understood. Here, we combine cell biology, correlative cryo-electron tomography (ET) and novel data analysis to reveal the step-by-step structural progression of autophagosome biogenesis at high resolution directly within yeast cells. By mapping individual structures onto a timeline based on geometric features, we uncover dynamic changes in membrane shape and curvature. Moreover, we reveal the organelle interactome of growing autophagosomes, highlighting a polar organization of contact sites between the phagophore and organelles such as the vacuole and the ER. Collectively, these findings have important implications for the contribution of different membrane sources during autophagy and for the forces shaping and driving phagophores towards closure without a templating cargo.
Heterologously secreted MbxA fromMoraxella bovisinduces a membrane blebbing response of the human host cell
Authors: Erenburg Isabelle N. , Hänsch Sebastian , Chacko Feby M. , Hamacher Anna , Wintgens Sebastian , Stuhldreier Fabian , Poschmann Gereon , Spitz Olivia , Stühler Kai , Wesselborg Sebastian , Hegemann Johannes , Smits Sander H. J. , Weidtkamp-Peters Stefanie , Schmitt Lutz
Published: May 2022

Many proteins of the Repeats in Toxins (RTX) protein family are toxins of Gram-negative pathogens including hemolysin A (HlyA) of uropathogenicE. coli. RTX proteins are secreted via Type I secretion systems (T1SS) and adopt their native conformation in the Ca2+-rich extracellular environment. Here we employed theE. coliHlyA T1SS as a heterologous surrogate system for the RTX toxin MbxA from the bovine pathogenMoraxella bovis. InE. colithe HlyA system successfully activates the heterologous MbxA substrate by acylation and secretes the precursor proMbxA and active MbxA allowing purification of both species in quantities sufficient for a variety of investigations. The activatingE. coliacyltransferase HlyC recognizes the acylation sites in MbxA, but unexpectedly in a different acylation pattern as for its endogenous substrate HlyA. HlyC-activated MbxA shows host species-independent activity including a so-far unknown toxicity against human lymphocytes and epithelial cells. Using live- cell imaging, we show an immediate MbxA-mediated permeabilization and a rapidly developing blebbing of the plasma membrane in epithelial cells, which is associated with immediate cell death.
Deep trans-omic network fusion reveals altered synaptic network in Alzheimer’s Disease
Authors: Xie Linhui , Raj Yash , Varathan Pradeep , He Bing , Nho Kwangsik , Risacher Shannon L. , Salama Paul , Saykin Andrew J. , Yan Jingwen
Published: May 2022

Multi-omic data spanning from genotype, gene expression to protein expression have been increasingly explored to interpret findings from genome wide association studies of Alzheimer’s disease (AD) and to gain more insight of the disease mechanism. However, each -omics data type is usually examined individually and the functional interactions between genetic variations, genes and proteins are only used after discovery to interpret the findings, but not beforehand. In this case, multi-omic findings are likely not functionally related and therefore give rise to challenges in interpretation. To address this problem, we propose a new interpretable deep neural network model MoFNet to jointly model the prior knowledge of functional interactions and multi-omic data set. It aims to identify a subnetwork of functional interactions predictive of AD evidenced by multi-omic measures. Particularly, prior functional interaction network was embedded into the architecture of MoFNet in a way that it resembles the information flow from DNA to gene and protein. The proposed model MoFNet significantly outperformed all other state-of-art classifiers when evaluated using multi-omic data from the ROS/MAP cohort. Instead of individual markers, MoFNet yielded multi-omic sub-networks related to innate immune system, clearance of misfolded proteins, and neurotransmitter release respectively. Around 50% of these findings were replicated in another independent cohort. Our identified gene/proteins are highly related to synaptic vesicle function. Altered regulation or expression of these genes/proteins could cause disruption in neuron-neuron or neuron-glia cross talk and further lead to neuronal and synapse loss in AD. Further investigation of these identified genes/proteins could possibly help decipher the mechanisms underlying synaptic dysfunction in AD, and ultimately inform therapeutic strategies to modify AD progression in the early stage.
Quantitative stable-isotope probing (qSIP) with metagenomics links microbial physiology and activity to soil moisture in Mediterranean-climate grassland ecosystems
Authors: Greenlon Alex , Sieradzki Ella , Zablocki Olivier , Koch Benjamin J. , Foley Megan M. , Kimbrel Jeffrey A. , Hungate Bruce A. , Blazewicz Steven J. , Nuccio Erin E. , Sun Christine L. , Chew Aaron , Mancilla Cynthia-Jeanette , Sullivan Matthew B. , Firestone Mary , Pett-Ridge Jennifer , Banfield Jillian F.
Published: May 2022

The growth and physiology of soil microorganisms, which play vital roles in biogeochemical cycling, are likely dependent on current and prior soil moisture levels. Here, we developed and applied a genome-resolved metagenomic implementation of quantitative stable isotope probing (qSIP) to an H218O labeling experiment to determine which microbial community members, and with what capacities, are growing under in situ conditions. qSIP enabled measurement of taxon-specific growth because isotopic incorporation into microbial DNA requires production of new genome copies. We studied three Mediterranean grassland soils across a rainfall gradient to evaluate the hypothesis that historic precipitation levels are an important factor controlling trait selection. We used qSIP-informed genome-resolved metagenomics to resolve an active subset of soil community members and identify the ecophysiological traits that characterize them. Higher year-round precipitation levels correlated with higher activity and growth rates of flagellar motile microorganisms. In addition to bacteria that were heavily isotopically labeled, we identified abundant isotope-labeled phages suggesting phage-induced cell lysis likely contributed to necromass production at all three sites. Further, there was a positive correlation between phage activity and the activity of putative phage hosts. Contrary to our expectations, the capabilities to decompose the diverse complex carbohydrates common in soil necromass or oxidize methanol and carbon monoxide were broadly distributed across active and inactive bacteria in all three soils, implying that these traits are not highly selected for by historical precipitation.
The impact of message framing on travellers’ behavioural intentions towards green hotels
Authors: Nimri Rawan , Patiar Anoop , Jin Xin
Published: May 2022

Purpose

Research in consumer behaviour in the pro-environmental hospitality domain is limited. Furthermore, the efficiency of interventions using pictorial elements, with positive and negative framing, to influence travellers' intentions (INTs) to book green accommodation remains scarcely investigated. The theory of planned behaviour (TPB) offers a platform for testing interventions that could impact consumer behaviour. This study aims to introduce a TPB pictorial intervention in green accommodation and to provide a robust assessment of the intervention targeted at the TPB's factors.

Design/methodology/approach

The data were collected from Australian travellers who were exposed to convincing messages through pictorial elements. These featured either positive or negative pro-environmental effects of hotel operations. A usable sample size of 771 respondents has been achieved. A multi-group analysis using structural equation modelling was performed to investigate the intervention effect.

Findings

The results highlighted the supremacy of positive framing to influence travellers’ INTs regarding patronage of green accommodation. A knowledge-based approach to promoting green practices might encourage travellers to book green accommodations.

Originality/value

This study advances theory building in environmental communication. Subsequently, hoteliers might enhance their marketing strategies to publicise their pro-environmental programs.
Becoming top global chef: what does it take to become a highly successful entrepreneurial careerist?
Authors: Elbasha Tamim , Baruch Yehuda
Published: May 2022

Purpose

This study aims to understand the career path to the pinnacle of professional life. What does it take for an entrepreneur to become a global celebrity in one’s profession? The authors explore the career motivation, trajectory and outcomes of a niche population who made it to the top of their careers.

Design/methodology/approach

A qualitative method was applied, using publicly available, prerecorded interviews of a documentary series on a unique sample of 30 top global chefs who gain Michelin-stars or equivalent. The authors used a qualitative approach to analyze the data alternating data and theory.

Findings

The authors identify a unique pattern, which the authors label as the “two-steps” trajectory, where these successful chefs went through a dual-hurdle process: first, delving into formal training and establishing themselves; then moving to a top chef status through innovation inspired by their history, chance events and treating their work as an artistic oeuvre and an experience.

Practical implications

The authors provide an observed pattern for what is required to be a top global chef.

Originality/value

This study advances career theory and entrepreneurship studies via integrating the two perspectives. The authors offer a theoretical contribution by identifying the relevance and importance of “new careers” for entrepreneurs, recognizing critical success factors and reinstating the balance between the agency of the entrepreneur and their context.
Re-examining oil price-stock market returns nexus in Nigeria using a two-stage Markov regime switching approach
Authors: Raifu Isiaka Akande , Oshota Sebil Olalekan
Published: May 2022

Purpose

It has been said that oil price shocks affect stock market returns. However, empirical studies remain inconclusive regarding the nexus between oil price shocks and stock market returns. Consequently, the purpose of this study is to investigate the asymmetric impact of oil price shocks on stock returns in Nigeria.

Design/methodology/approach

A two-stage Markov regime-switching approach is used to examine the asymmetric effects of three different structural oil shocks on stock returns. The oil shocks, which include oil supply shock, aggregate demand shock and oil-specific demand shock, are derived using structural vector autoregressive. Monthly data that spans the period between January 1990 and December 2018 are deployed for estimation.

Findings

The linear estimation results show that only oil demand shock negatively and significantly affects the stock market returns. The Markov-switching regime results reveal that oil supply shock has a significant positive impact on the stock returns in a low-volatility state, whereas oil-specific demand shock negatively impacts the stock returns in a high-volatility state.

Practical implications

There is a need for policymakers and investors to take cognizance of not only the positive outcomes of a relatively stable state of oil price but also the negative consequences of a high-volatility state when formulating policy and making investment decisions, respectively.

Originality/value

This study differs from other similar studies in Nigeria that have examined the asymmetric relationship between oil price shocks and stock market return by using a two-stage Markov regime-switching approach. To the best of the authors’ knowledge, this is the first attempt at using this methodology.
Transportation service level impact on aircraft availability
Authors: McLean Vincent , Reiman Adam D.
Published: May 2022

Purpose

Aircraft fail to meet mission capable rate goals due to a lack of supply of aircraft parts in inventory where the aircraft breaks. This triggers an order at the repair location. To maximize mission capable rate, the time from order to delivery needs to be minimized. The purpose of this research is to examine the case of three airfields for the order to delivery time of mission critical aircraft parts for a specific aircraft type.

Design/methodology/approach

This research captured data from three information systems to assess the order fulfillment process. The data were analyzed to determine the performance in fiscal year 2020. Using the model of that performance, the cost of reducing transportation times using publicly available commercial cost estimates was assessed against the impact on aircraft availability.

Findings

The results indicate that paying the costs for expedited shipping would have increased aircraft availability by 1.09 times the average annual aircraft flying hours for the three cases. The cost for the equivalent of an additional aircraft for the year was a third of the annual straight-line depreciation for that aircraft type.

Research limitations/implications

This research assumed that the transportation time service levels publicly posted could be achieved. The weight of each mission critical part was not available, so the weight was selected from a probability distribution of mission critical part weights that was retrieved from prior research. This research provides options to enhance aircraft availability and identifies the associated costs.

Practical implications

Adjusting the contract with transportation providers to reduce the transportation times of mission critical parts could have a large impact on aircraft availability at relatively little cost.

Social implications

This research could enhance aircraft readiness in service of the common defense.

Originality/value

This research provides an effective methodology for enhancing military readiness through contract adjustments with commercial partners. The value of this research is that it will serve to adjust the value proposition of mission critical parts inside the United States Transportation Command’s Next Generation Delivery Service contract.
In the evolving digital environment: is cataloging lagging behind?
Authors: Monyela Madireng
Published: May 2022

Purpose

The purpose of this paper is to suggest that cataloguing departments and agencies could benefit from Fourth Industrial Revolution and advanced technologies.

Design/methodology/approach

A desk research based on literature review extracted from different information sources. Literature was interpreted based on the search of the researcher on key concepts of the topic.

Findings

Literature indicates new trends in cataloguing and how technologies could be incorporated into cataloguing.

Practical implications

This study can inform policies on artificial intelligence adoption in cataloguing.

Originality/value

The 4IR and artificial intelligence does not often occur in cataloguing literature. Linking 4IR and advanced technologies, artificial intelligence and robotic science in cataloguing could inform policies and practice in cataloguing.
Effect of alloy particle size and stencil aperture shape on solder printing quality
Authors: Mohamed Sunar Mohamad Solehin , Abu Bakar Maria , Jalar Azman , Ramli Mohamad Riduwan , Che Ani Fakhrozi
Published: May 2022

Purpose

Reflow solder joint quality is significantly affected by the ability of the solder to perfectly fill pad space and retain good solder joint shape. This study aims to investigate solder joint quality by quantitatively analyzing the stencil printing-deposited solder volume, solder height and solder coverage area.

Design/methodology/approach

The dispensability of different solder paste types on printed circuit board (PCB) pads using different stencil aperture shapes was evaluated. Lead-free Type 4 (20–38 µm particle size) and Type 5 (15–25 µm particle size) solder pastes were used to create solder joints according to standard reflow soldering.

Findings

The results show that the stencil aperture shape greatly affects the solder joint quality as compared with the type of solder paste. These investigations allow the development of new strategies for solving solder paste stencil printing issues and evaluating the quality of solder joints.

Originality/value

The reflow soldering process requires the appropriate selection of the stencil aperture shape according to the PCB and the solder paste according to the particle-size distribution of the solder alloy powder. However, there are scarce studies on the effects of stencil aperture shape and the solder alloy particle size on the solder paste space-filling ability.
Sustainable human resource management: practitioners’ perspectivesGestión de recursos humanos sustentable: perspectiva de los profesionalesGestão sustentável de recursos humanos: perspectivas dos profissionais
Authors: Madero Gómez Sergio , Olivas-Lujan Miguel R. , Rubio Leal Yanira Lizeth , Yusliza Mohd Yusoff
Published: May 2022

Purpose

Identifying and analyzing aspects related to sustainable human resources (HRs) in an emerging, Iberoamerican location (Monterrey, Mexico). Documenting employee experiences regarding sustainable practices of HR in their companies to understand the enacted meaning of sustainable HR management (HRM). This study aims to seek answers to understand the ways environmental sustainability is present in HR subprocesses and the ways companies regard HRs from a sustainability perspective.

Design/methodology/approach

This exploratory research has a qualitative approach. The authors collected and summarized semi-structured interviews with 31 key informants that work fully or partially in HRs in a large, industrialized city in an Iberoamerican, emerging economy (Monterrey, Mexico).

Findings

The main findings based on responses from HR professionals are as follows: HR activities may contribute to the sustainability of the business and its physical environment; HR can create a culture of care for the resources, but training and development activities are not currently used optimally; and in addition to the economic sustainability of the employers, social and environmental sustainability are also within HR’s influence sphere.

Originality/value

This study contributes to the emerging literature on sustainability in HRM, due the dearth of information related to “green” or environmental practices in HRM. This study reports specifically on the ways this perspective adds value within Mexican enterprises, but the authors are confident that these findings also generalize across industries, enterprises and regions.
Financial innovation and the stability of money demand in Nigeria
Authors: Ujunwa Augustine , Onah Emmanuel , Ujunwa Angela Ifeanyi , Okoyeuzu Chinwe R , Kalu Ebere Ume
Published: May 2022

Studies that explore the relationship between financial innovation and the stability of money demand in Africa use the indirect measure of financial innovation. Previous studies on Nigeria also ignored total monetary aggregates (M3), despite its importance to monetary policy formulation and liquidity management. This paper contributes to the existing literature in two ways; first, we expand the generic money demand function to include the direct measure of financial innovation. Second, we test the model on Nigeria using a broader definition of money demand—narrow money (M1), broad money (M2) and total monetary aggregates (M3). We employ the Pesaran et al. (2001) autoregressive distributed lag (ARDL) bounds test approach to cointegration in estimating the respective equations and find evidence of a long‐run relationship between money demand and financial innovation. The CUSUM and CUSUM‐of‐Squares tests reveal stable money demand across the three measures of money demand, which indicates that the inclusion of financial innovation has not altered the long‐run stability of money demand in Nigeria.
Refugees are a Valuable but Overlooked Economic Resource, and it is Time to Update Our Approach to Migration
Authors: Baker Sally , Cousins Stephanie , Higgins Claire , Tani Massimiliano
Published: May 2022

The view that welcoming refugees represents a cost to a country's welfare services has become anachronistic; nowadays refugees are increasingly recognised for their high levels of education and skills, and their ability to make an economic contribution to a host country. Yet, most states' approach to migration management prevents displaced people from migrating based on the human capital that they can supply. Australia is trialling a new approach that enables refugees to access skilled migration through employer sponsorship. This article describes the pilot project and suggests ways to encourage employers to view refugees as a valuable solution to workforce shortages.
Absence in technicolour: protesting enforced disappearances in northern Sri Lanka
Authors: Buthpitiya Vindhya
Published: May 2022

This essay examines the political uses of photography in the protests of the Tamil families of the disappeared in northern Sri Lanka. Enforced disappearances have long featured as an instrument of state terror. Their lingering effects have been noted as a significant challenge to transitional justice processes in the aftermath of the island's civil war. By examining how protesters make their political demands and grievances known through photography, I explore the tensions between visibility and surveillance. The competing photographies of the protests subvert conceptual understandings of the medium as an ideological tool, but also complicate claims of its capacities for enabling emancipation. Against a backdrop of ethno‐nationalist conflict, this mobilization of and through photography serves as a defiant articulation of post‐war ‘irreconciliation’. It is further tethered to a global visual vernacular of civilian resistance challenging state atrocity, as well as irreconcilable assertions of nation and state.