bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitroandin vivoevaluation of the biofilm-degradingPseudomonasphage Motto, as a candidate for phage therapy
Authors: Manohar Prasanth , Loh Belinda , Turner Dann , Tamizhselvi Ramasamy , Mathankumar Marimuthu , Elangovan Namasivayam , Nachimuthu Ramesh , Leptihn Sebastian
Published: October 2022

Infections caused byPseudomonas aeruginosaare becoming increasingly difficult to treat due to the emergence of strains that have acquired multidrug resistance. Therefore, phage therapy has gained attention as an alternative to the treatment of pseudomonal infections. Phages are not only bactericidal but occasionally show activity against biofilm as well. Here, we describe thePseudomonasphage Motto which has the ability to clearP. aeruginosainfections in an animal model and also exhibited biofilm-degrading properties. The phage has substantial antibiofilm activity against strong biofilm-producing isolates (n = 10), with at least a 2-fold reduction within 24 hours. To demonstrate the safety of using phage Motto, we performed cytotoxicity studies with human cell lines (HEK 293 and RAW 264.7 macrophages). Using a previously establishedin vivomodel, we demonstrated the efficacy of Motto inC. elegans, with a 90% survival rate when treated with the phage at an MOI of 10.

Importance

Phages are often evaluated mainly on their ability to kill bacterial hosts. One important aspect, however, is often neglected: Their ability to degrade biofilms. Not all phages are able to disintegrate biofilms. While phages can kill planktonic cells, it also has often been observed that phages are not able to infect those that are embedded in biofilms. Phage Motto appears to have highly efficient enzymes that degrade biofilms, and might therefore be a highly valuable therapeutic candidate.
Molecular Profiling of the Hippocampus of Children with Autism Spectrum Disorder
Authors: Rexrode Lindsay , Hartley Joshua , Showmaker Kurt C , Challagundla Lavanya , Vandewege Michael W. , Martin Brigitte E. , Blair Estelle , Bollavarapu Ratna , Antonyraj Rhenius B. , Hilton Keauna , Gardiner Alex , Valeri Jake , Gisabella Barbara , Garrett Michael , Theoharides Theoharis C. , Pantazopoulos Harry
Published: October 2022

Several lines of evidence point to a key role of the hippocampus in Autism Spectrum Disorders (ASD). Altered hippocampal volume and deficits in memory for person and emotion related stimuli have been reported, along with enhanced ability for declarative memories. Mouse models have demonstrated a critical role of the hippocampus in social memory dysfunction, associated with ASD, together with decreased synaptic plasticity. Chondroitin sulphate proteoglycans (CSPGs), a family of extracellular matrix molecules, represent a potential key link between neurodevelopment, synaptic plasticity, and immune system signaling. There is a lack of information regarding the molecular pathology of the hippocampus in ASD. We conducted RNAseq profiling on postmortem human brain samples containing the hippocampus from male children with ASD (n=7) and normal male children (3-14 yrs old), (n=6) from the NIH NeuroBioBank. Gene expression profiling analysis implicated molecular pathways involved in extracellular matrix organization, neurodevelopment, synaptic regulation, and immune system signaling. qRT-PCR and Western blotting were used to confirm several of the top markers identified. The CSPG protein BCAN was examined with multiplex immunofluorescence to analyze cell-type specific expression of BCAN and astrocyte morphology. We observed decreased expression of synaptic proteins PSD95 (p<0.02) and SYN1 (p<0.02), increased expression of the extracellular matrix (ECM) protease MMP9 (p<0.03), and decreased expression of MEF2C (p<0.03). We also observed increased BCAN expression with astrocytes in children with ASD, together with altered astrocyte morphology. Our results point to alterations in immune system signaling, glia cell differentiation, and synaptic signaling in the hippocampus of children with ASD, together with alterations in extracellular matrix molecules. Furthermore, our results demonstrate altered expression of genes implicated in genetic studies of ASD including SYN1 and MEF2C.
Therapeutic modulation of the blood-brain barrier and ischemic stroke by a bioengineered FZD4-selective WNT surrogate
Authors: Ding Jie , Lee Sung-Jin , Vlahos Lukas , Yuki Kanako , Rada Cara C. , van Unen Vincent , Vuppalapaty Meghah , Chen Hui , Sura Asmiti , McCormick Aaron K. , Tomaske Madeline , Alwahabi Samira , Nguyen Huy , Nowatzke William , Kim Lily , Kelly Lisa , Vollrath Douglas , Califano Andrea J. , Yeh Wen-Chen , Li Yang , Kuo Calvin J.
Published: October 2022

Derangements of the blood-brain barrier (BBB) or blood-retinal barrier (BRB) occur in disorders ranging from stroke, cancer, diabetic retinopathy, and Alzheimer’s disease. The Norrin/FZD4/TSPAN12 pathway activates WNT/β-catenin signaling, which is essential for BBB and BRB function. However, systemic pharmacologic FZD4stimulation is hindered by obligate palmitoylation and insolubility of native WNTs and suboptimal properties of the FZD4-selective ligand Norrin. Here, we developed L6-F4-2, a non-lipidated, FZD4-specific surrogate with significantly improved sub-picomolar affinity versus native Norrin. In Norrin knockout (NdpKO) mice, L6-F4-2 not only potently reversed neonatal retinal angiogenesis deficits, but also restored BRB and BBB function. In adult C57Bl/6J mice, post-stroke systemic delivery of L6-F4-2 strongly reduced BBB permeability, infarction, and edema, while improving neurologic score and capillary pericyte coverage. Our findings reveal systemic efficacy of a bioengineered FZD4-selective WNT surrogate during ischemic BBB dysfunction, with general applicability to adult CNS disorders characterized by an aberrant blood-brain barrier.
Host association and intracellularity evolved multiple times independently in theRickettsiales
Authors: Castelli Michele , Nardi Tiago , Gammuto Leandro , Bellinzona Greta , Sabaneyeva Elena , Potekhin Alexey , Serra Valentina , Petroni Giulio , Sassera Davide
Published: October 2022

The order Rickettsiales (Alphaproteobacteria) encompasses multiple diverse lineages of host-associated bacteria, including pathogens, reproductive manipulators, and mutualists. In order to understand how intracellularity and host association originated in this order, and whether they are ancestral or convergently evolved characteristics, we built an unprecedentedly large and phylogenetically-balanced dataset that includesde novosequenced genomes and an accurate selection of published genomic and metagenomic assemblies. We performed detailed functional reconstructions that clearly indicated “late” and parallel evolution of obligate host-association and intracellularity in differentRickettsialeslineages. According to the depicted scenario, multiple independent series of horizontal acquisitions of transporters led to the progressive loss of biosynthesis of nucleotides, amino acids and other metabolites, producing distinct conditions of host-dependence. Coherently, each clade experienced a different pattern of evolution of the ancestral arsenal of interaction apparatuses, including development of specialised effectors involved in the lineage-specific mechanisms of host cell adhesion/invasion and intracellularity.
Kinase Inhibitor Pulldown Assay (KiP) for Clinical Proteomics
Authors: Saltzman Alexander B , Chan Doug W , Holt Matthew V , Wang Junkai , Jaehnig Eric J , Anurag Meenakshi , Singh Purba , Malovannaya Anna , Kim Beom-Jun , Ellis Matthew J
Published: October 2022

Protein kinases are frequently dysregulated and/or mutated in cancer and represent essential targets for therapy. Accurate quantification is essential, but current approaches are inadequate. For breast cancer treatment for example, the identification and quantification of the protein kinase ERBB2 is critical for therapeutic decisions. While immunohistochemistry (IHC) is the current clinical diagnostic approach, it is only semiquantitative. Mass spectrometry-based proteomics offers more quantitative assays that, unlike IHC, can be used to accurately evaluate hundreds of kinases simultaneously. The enrichment of less abundant kinase targets for quantification, along with depletion of interfering proteins, improves sensitivity and thus promotes more effective downstream analyses. Multiple kinase inhibitors were therefore deployed as a capture matrix for kinase inhibitor pulldown (KiP) assays designed to profile the human protein kinome as broadly as possible. Optimized assays were initially evaluated in 16 patient derived xenograft models (PDX) where KiP identified multiple differentially expressed and biologically relevant kinases. From these analyses, an optimized single-shot parallel reaction monitoring (PRM) method was developed to improve quantitative fidelity. The PRM KiP approach was then reapplied to low quantities of proteins typical of protein yields from core needle biopsies of human cancers. The initial prototype targeting 100 kinases recapitulated intrinsic subtyping of PDX models obtained from comprehensive proteomic and transcriptomic profiling. Luminal and HER2 enriched OCT-frozen patient biopsies subsequently analyzed through KiP-PRM also clustered by subtype. Finally, stable isotope labeled peptide standards were developed to define a prototype clinical method.
IbpAB small heat shock proteins are not host factors for bacteriophage ϕX174 replication
Authors: Zhu Hannah X , Wright Bradley W , Logel Dominic Y , Molloy Mark P , Jaschke Paul R
Published: October 2022

Bacteriophages exploit host proteins for successful infection. Small heat shock proteins are a universally conserved family of stress-induced molecular chaperones that prevent irreversible aggregation of proteins. Two small heat shock proteins, IbpA and IbpB, are a class of holding modulators or “holdases”, which bind partially folded proteins and await ATP-driven folding chaperones for refolding. Bacteriophage ϕX174 is a small, icosahedral, and non-tailed virus belonging to theMicroviridae. During ϕX174 infection ofEscherichia coliC122, IbpA and IbpB were previously found to be the most highly upregulated host proteins, with expression levels comparable to ϕX174 proteins. In this work, to understand the role of IbpA and IbpB during ϕX174 infection, we used a hybrid approach of CRISPR interference and genomic knockouts to disrupt theibpAandibpBgenes. We show that these two proteins do not appear to be necessary for efficient ϕX174 replication, and moreover, their absence has no effect on ϕX174 fecundity.

Importance

The small heat shock proteins (sHsps) are universally conserved family of stress-induced molecular chaperones that prevent irreversible protein aggregation. InE. coli, the IbpA/B sHsps work together, and separately, to bind partially folded proteins and await ATP-driven folding chaperones for refolding. These proteins are highly upregulated during protein overexpression and bacteriophage infection, but their collective role in bacteriophage infection has not been investigated. Here, we show that theibpA/Bgenes are dispensable for bacteriophage ϕX174 infection, and are likely not essential host factors despite their abundance during diverse phage infections. Instead, this work points towards their role as cell wall integrity sensors, similar to the phage shock protein system, in addition to their canonical role as holdases of cytoplasmic protein.
Bows and swords: why bacteria carry short and long-range weapons
Authors: Booth Sean C. , Smith William P.J. , Foster Kevin R.
Published: October 2022

Bacteria possess a diverse range of mechanisms for inhibiting competitors, including bacteriocins, tailocins, the type VI secretion system, and contact-dependent inhibition. Why bacteria have evolved such a wide array of weapon systems remains a mystery. Here we develop an agent-based model to compare short-range weapons that require cell-cell contact, with long-range weapons that rely on diffusion. Our models predict that contact weapons are useful when an attacking strain is outnumbered, facilitating invasion and establishment. By contrast, ranged weapons tend to only be effective when attackers are abundant. We test our predictions with the opportunistic pathogenPseudomonas aeruginosa, which naturally carries multiple weapons, including contact-dependent inhibition (CDI) and diffusing tailocins. As predicted, short-range CDI functions better at low frequency, while long-range tailocins require high frequency and cell density to function effectively. Head-to-head competitions between the two weapon types further support our predictions: a tailocin attacker only defeats CDI when it is numerically dominant, but then we find it can be devastating. Finally, we show that the two weapons work well together when one strain employs both. We conclude that short and long-range weapons serve different functions and allow bacteria to fight both as individuals and as a group.
Water mass age structures the auxiliary metabolic gene content of free-living and particle-attached deep ocean viral communities
Authors: Coutinho Felipe H , Silveira Cynthia B , Sebastián Marta , Sánchez Pablo , Duarte Carlos M , Vaqué Dolors , Gasol Josep M , Acinas Silvia G
Published: October 2022

Viruses play important roles on the biogeochemical cycles that take place in the ocean.Yet, deep ocean viruses are one of the most under-explored fractions of the global biosphere. Little is known about the environmental factors that control the composition and functioning of their communities, or how they interact with their free-living or particle-attached microbial hosts. Thus, we analysed 58 viral communities associated to size fractionated free-living (0.2–0.8 μm) and particle-attached (0.8–20 μm) cellular metagenomes from bathypelagic (2,150-4,018 m deep) microbiomes obtained during the Malaspina expedition. These metagenomes yielded 6,631 viral sequences, 91% of which were novel, and 67 represented high-quality genomes. Taxonomic classification assigned 53% of the viral sequences to families of tailed viruses from the order Caudovirales. Computational host prediction associated 886 viral sequences to dominant members of the deep ocean microbiome, such as Alphaproteobacteria (284), Gammaproteobacteria (241), SAR324 (23), Marinisomatota (39), and Chloroflexota (61). Free-living and particle-attached viral communities had markedly distinct taxonomic composition, host prevalence, and auxiliary metabolic gene content, which led to the discovery of novel viral encoded metabolic genes involved in the folate and nucleotide metabolisms. Water mass age emerged as an important factor driving viral community composition. We postulated this was due to changes in quality and concentration of dissolved organic matter acting on the host communities, leading to an increase of viral auxiliary metabolic genes associated with energy metabolism among older water masses. These results shed light on the mechanisms by which environmental gradients of deep ocean ecosystems structure the composition and functioning of free-living and particle-attached viral communities.
Stress-Induced Mucin 13 Reductions Drive Intestinal Microbiome Shifts and Despair Behaviors
Authors: Rivet-Noor Courtney R. , Merchak Andrea R. , Render Caroline , Gay Naudia , Beiter Rebecca M. , Brown Ryan , Keeler Austin , Moreau G. Brett , Li Sihan , Olgun Deniz E. , Steigmeyer Alexandra D. , Ofer Rachel , Phan Tobey Mihn Huu , Vemuri Kiranmayi , Chen Lei , Mahoney Keira E. , Shin Jung-Bum , Malaker Stacy A. , Deppmann Chris , Verzi Michael , Gaultier Alban
Published: October 2022

Depression is a prevalent psychological condition with limited treatment options. While its etiology is multifactorial, both chronic stress and changes in the microbiome are associated with disease pathology. In depression, stress is known to induce microbiome dysbiosis, defined here as a change in microbial composition associated with a pathological condition. This state of dysbiosis is then known to feedback on depressive symptoms. While studies have demonstrated that targeted restoration of the microbiome can alleviate depressive-like symptoms in mice, translating these findings to human patients has proven challenging due to the complexity of the human microbiome. As such, there is an urgent need to identify factors upstream of microbial dysbiosis. Here we investigate the role of mucin 13 as an upstream mediator of microbiome composition changes. Using a model of chronic stress, we show that the mucosal protein, mucin 13, is selectively reduced after psychological stress exposure. We further demonstrate that the reduction ofMuc13is mediated by theHnf4transcription factor family. Finally, we determine that deletingMuc13is sufficient to drive microbiome shifts and despair behaviors. These findings shed light on the mechanisms behind stress-induced microbial changes and reveal a regulator of mucin 13 expression.

In this paper, authors identified a pathway by which stress induces microbiome shifts. They found that psychological stress selectively alters a key mucosal protein, mucin 13, which in turn modifies the microbial niche to induce changes in bacterial composition.
STAMP-Based Digital CRISPR-Cas13a (STAMP-dCRISPR) for Amplification-Free Quantification of HIV-1 Plasma Viral Load
Authors: Nouri Reza , Jiang Yuqian , Politza Anthony J. , Liu Tianyi , Greene Wallace , Nunez Jonathan , Lian Xiaojun Lance , Guan Weihua
Published: October 2022

The development of new nucleic acid techniques to quantify HIV RNA in plasma is critical for identifying the disease progression and monitoring the effectiveness of antiretroviral therapy. While RT-qPCR has been the gold standard for HIV viral load quantification, digital assays could provide an alternative calibration-free absolute quantification method. Here, we report the development of aself-digitalizationthroughautomatedmembrane-basedpartitioning (STAMP) technique to digitalize the CRISPR-Cas13 assay (dCRISPR) for amplification-free and absolute quantification of HIV-1 viral RNAs. The analytical performances of STAMP-dCRISPR were evaluated with synthetic HIV-1 RNA, and it was found samples spanning 4 orders of dynamic range between 100 aM to 1 pM can be quantified as fast as 30 min. We also examined the overall assay from RNA extraction to STAMP-dCRISPR quantification with spiked plasma samples. The overall assay showed a resolution of 42 aM at a 90% confidence level. Finally, a total of 20 clinical plasma samples from patients were evaluated with STAMP-dCRISPR. The obtained results agreed well with the RT-qPCR. Our result demonstrates a new type of easy-to-use, scalable, and highly specific digital platform that would offer a simple and accessible platform for amplification-free quantification of viral RNAs, which could be exploited for the quantitative determination of viral load for an array of infectious diseases.
Human gut Actinobacteria boost drug absorption by secreting P-glycoprotein ATPase inhibitors
Authors: Kyaw Than S , Sandy Moriah , Trepka Kai , Goh Janice JN , Yu Kristie , Dimassa Vincent , Bess Elizabeth N. , Bisanz Jordan E , Turnbaugh Peter J
Published: October 2022

Drug efflux transporters are a major determinant of drug efficacy and toxicity. A canonical example is P-glycoprotein (P-gp), an efflux transporter that controls the intestinal absorption of diverse compounds. Despite reports that P-gp expression depends on the microbiome, the mechanisms responsible and their physiological relevance remain unclear. Surprisingly, we found that the cardiac drug-metabolizing gut ActinobacteriumEggerthella lentaincreases drug absorption in mice through post-translational inhibition of P-gp ATPase efflux activity. P-gp inhibition is conserved in theEggerthellaceaefamily but absent in other Actinobacteria. Comparative genomics identified genes associated with P-gp inhibition. Finally, activity-guided biochemical fractionation coupled to metabolomics identified a cluster of isoflavonoids produced byE. lentarelated to plant-derived P-gp inhibitors. These results highlight the unexpected overlap between diet- and microbiome-derived compounds, and the importance of considering the broader relevance of the gut microbiome for drug disposition beyond first-pass metabolism.

One Sentence Summary

The gut bacteriumEggerthella lentasecretes inhibitors of P-glycoprotein ATPase activity, accelerating drug absorption.
Sporodochia formed byFusarium oxysporumf. sp.fragariaeproduce airborne conidia and are ubiquitous on diseased strawberry plants in California
Authors: Henry Peter M. , Dilla-Ermita Christine J. , Goldman Polly , Jaime Jose , Ramos Gerardo
Published: October 2022

Sporodochia are dense masses of fungal hyphae bearing asexual conidia. ForFusarium oxysporum, sporodochia are known to produce airborne conidia and enhance the dissemination of this otherwise soilborne pathogen. Sporodochia are small and transient, and they are documented for only a fewformae specialesofFusarium oxysporum. This study reports airborne conidia and sporodochia produced byF. oxysporumf. sp.fragariae, the cause of Fusarium wilt of strawberry, in the Monterey Bay region of California. Sporodochia were consistently present in Fusarium wilt-afflicted strawberry fields and were discovered in 21 of 24 Fusarium wilt-diseased fields. Only necrotic tissues were observed bearing sporodochia, and they were most frequently observed on petioles and peduncles. Sporodochia grew significantly longer up peduncles than petioles, extending further away from the base of the plant and toward parts of the canopy more exposed to wind. A stolon hosted the longest stretch of sporodochial growth, found covering the stolon’s entire 35 cm length and also the base of the daughter plant. Macroconidia were produced by all sporodochia samples, and we did not find microconidia on any samples. An initial series of experiments confirmed the potential for conidia produced by sporodochia to disperse with wind over short distances. The prevalence of sporodochia producing airborne spores ofF. oxysporumf. sp.fragariaehas great importance for disease management and biosecurity.
Treatment of prostate cancer with CD46 targeted225Ac alpha particle radioimmunotherapy
Authors: Bidkar Anil P. , Wang Sinan , Bobba Kondapa Naidu , Chan Emily , Bidlingmaier Scott , Egusa Emily A. , Peter Robin , Ali Umama , Meher Niranjan , Wadhwa Anju , Dhrona Suchi , Beckford-Vera Denis , Su Yang , Tang Ryan , Zhang Li , He Jiang , Wilson David M. , Aggarwal Rahul , VanBrocklin Henry F. , Seo Youngho , Chou Jonathan , Liu Bin , Flavell Robert R.
Published: October 2022

Radiopharmaceutical therapy is changing the standard of care in prostate cancer (PCa) and other malignancies. We previously reported high CD46 expression in PCa and developed an antibody-drug conjugate and immunoPET agent based on the YS5 antibody, which targets a tumor-selective CD46 epitope. Here, we present the preparation, preclinical efficacy, and toxicity evaluation of [225Ac]DOTA-YS5, a radioimmunotherapy agent based on the YS5 antibody. Our radiolabeled antibody retains binding efficacy and shows a high tumor to background ratio in PCa xenografts. Furthermore, we show that radiolabeled antibody was able to suppress the growth of cell-derived and patient-derived xenografts, including PSMA-positive and deficient models. Nephrotoxicity, not seen at low radioactive doses, is evident at higher radioactivity dose levels, likely due to redistribution of daughter isotope213Bi. Overall, this preclinical study confirms that [225Ac]DOTA-YS5 is a highly effective treatment and suggests feasibility for clinical translation of CD46 targeted radioligand therapy in PCa.
Iron Inhibits Glioblastoma Cell Migration and Polarization
Authors: Shenoy Ganesh , Kheirabadi Sina , Ataie Zaman , Palsa Kondaiah , Wade Quinn , Khunsriraksakul Chachrit , Khristov Vladimir , Slagle-Webb Becky , Lathia Justin D. , Wang Hong-Gang , Sheikhi Amir , Connor James R.
Published: October 2022

Glioblastoma is one of the deadliest malignancies facing modern oncology today. The ability of glioblastoma cells to diffusely spread into neighboring healthy brain makes complete surgical resection nearly impossible and contributes to the recurrent disease faced by most patients. Although research into the impact of iron on glioblastoma has addressed proliferation, there has been little investigation into how cellular iron impacts the ability of glioblastoma cells to migrate - a key question especially in the context of the diffuse spread observed in these tumors. Herein, we show that increasing cellular iron content results in decreased migratory capacity of human glioblastoma cells. The decrease in migratory capacity was accompanied by a decrease in cellular polarization in the direction of movement. Expression of CDC42, a Rho GTPase that is essential for both cellular migration and establishment of polarity in the direction of cell movement, was reduced upon iron treatment. Bioinformatic analysis of CDC42 mRNA revealed a potential iron-responsive element that may contribute to the regulation of CDC42 by iron. We then analyzed a single-cell RNA-seq dataset of human glioblastoma samples and found that cells at the tumor periphery had a gene signature that is consistent with having lower levels of cellular iron. Altogether, our results suggest that cellular iron content is impacting glioblastoma cell migratory capacity and that cells with higher iron levels exhibit reduced motility.
A Transducing Bacteriophage InfectingStaphylococcus epidermidisContributes to the Expansion of a Novel Siphovirus Genus and Implies Genus is Inappropriate for Phage Therapy
Authors: Andrews Taylor , Hoyer Steen , Ficken Karolyn , Fey Paul , Duffy Siobain , Boyd Jeffrey
Published: October 2022

The effort to discover novel phages infectingStaphylococcus epidermidiscontributes to both the development of phage therapy and the expansion of genome-based phage phylogeny. Here, we report the genome of anS. epidermidis–infecting phage SEP1 and compare its genome with five other sequenced phages with high sequence identity. These phages represent a novel siphovirus genus, which was recently reported in the literature. The published member of this group was favorably evaluated as a phage therapeutic agent, but SEP1 is capable of transducing antibiotic resistance. Members of this genus may be maintained within their host as extrachromosomal plasmid prophages, through stable lysogeny or pseudolysogeny. Therefore, we conclude that SEP1 may be temperate and members of this novel genus are not suitable for phage therapy.
Muscle stem cell function is impaired in absence of Talpid3 - a gene required for primary cilia formation
Authors: Martinez-Heredia Victor , Blackwell Danielle , Sebastian Sujith , Pearson Timothy , Mok Gi Fay , Mincarelli Laura , Utting Charlotte , Folkes Leighton , Poeschl Ernst , Macaulay Iain , Mayer Ulrike , Münsterberg Andrea
Published: October 2022

Skeletal muscle stem cells (MuSC) are crucial for tissue homeostasis and repair after injury. Following activation, they proliferate to generate differentiating myoblasts. A proportion of cells selfrenew, re-enter the MuSC niche under the basal lamina outside the myofiber and become quiescent. Quiescent MuSC have a primary cilium, which is disassembled upon cell cycle entry.Ex vivoexperiments suggest cilia are important for MuSC self-renewal, however, their role in muscle regenerationin vivoremains poorly understood. Talpid3 (TA3) is essential for primary cilia formation and Hedgehog (Hh) signalling. Here we use tamoxifen-inducible conditional deletion of TA3in MuSC (iSC-KO) and show that regeneration is impaired in response to cytotoxic injury. Repeat injury exacerbates the regeneration phenotype in TA3iSC-KOmice, indicating depletion of MuSCs. Single cell transcriptomics of MuSC progeny isolated from myofibers identifies components of several signalling pathways, which are deregulated in absence of TA3, including Hh and Wnt. Pharmacological activation of Wnt restores muscle regeneration, while purmorphamine, an activator of the Smoothened (Smo) co-receptor in the Hh pathway, has no effect. Together, our data suggest that TA3and primary cilia are important for MuSC self-renewal, and that pharmacological treatment can efficiently restore muscle regeneration.
Flight testing verification of lateral-directional dynamic stability of gliding birds due to wing dihedral
Authors: Wei Chenhao , Lin Gang , Huang Jun , Song Lei , Smith Howard
Published: October 2022

Purpose

Unlike conventional aircraft, birds can glide without a vertical tail. The purpose of this paper is to analyse the influence of dihedral angle spanwise distribution on lateral-directional dynamic stability by the simulation, calculation in the development of the bird-inspired aircraft and the flight testing.

Design/methodology/approach

The gliding magnificent frigatebird (Fregata magnificens) was selected as the study object. The geometric and mass model of the study object were developed. Stability derivatives and moments of inertia were obtained. The lateral-directional stability was assessed under different spanwise distributions of dihedral angle. A bird-inspired aircraft was developed, and a flight test was carried out to verify the analysed results.

Findings

The results show that spanwise distribution changing of dihedral angle has influence on the lateral-directional mode stability. All of the analysed configurations have convergent Dutch roll mode and rolling mode. The key role of dihedral angle changing is to achieve a convergent spiral mode. Flight test results show that the bird-inspired aircraft has a well-convergent Dutch roll mode.

Practical implications

The theory that birds can achieve its lateral-directional stability by changing its dihedral angle spanwise distribution may explain the stability mechanism of gliding birds.

Originality/value

This paper helps to improve the understanding of bird gliding stability mechanism and provides bio-inspired solutions in aircraft designing.
A novel identification approach of Bouc–Wen model parameter for piezoelectric hysteresis characteristic based on a modified whale optimization algorithm
Authors: Wang Geng , Zhou Yongsheng
Published: October 2022

Purpose

Due to the non-linear nature of the hysteresis behavior, the accurate identification of the parameters of the Bouc–Wen hysteresis model is still a challenging problem. The purpose of this paper is to explore the potential of a heuristic improved whale optimization algorithm (IWOA) to accurately identify the model parameters, which has never been applied to the field of piezoelectric hysteresis identification.

Design/methodology/approach

Based on the analysis of the Bouc–Wen model structure and WOA optimization process, an approach that can fully exploit the potential of WOA is proposed. In this work, the position updating formula is improved by introducing non-linear weights, and the convergence factor formula is modified. And thus, the iteration speed, accuracy and stability of the classical WOA can be improved.

Findings

The experimental results show that the model output is in good agreement with the response of the real piezoelectric platform. Compared with the standard WOA and particle swarm optimization algorithms, the search performance of the proposed IWOA is better than those two competitors in terms of convergence speed and identification accuracy.

Originality/value

An IWOA is proposed according to the properties of the Bouc–Wen model and piezoelectric hysteresis. It has been approved that the algorithm has a good prospect in the identification of piezoelectric hysteresis systems. Furthermore, this method is easy to implement and is a good candidate algorithm to identify Bouc–Wen model parameters.
Pose estimation method for construction machine based on improved AlphaPose model
Authors: Zhao Jiayue , Cao Yunzhong , Xiang Yuanzhi
Published: October 2022

Purpose

The safety management of construction machines is of primary importance. Considering that traditional construction machine safety monitoring and evaluation methods cannot adapt to the complex construction environment, and the monitoring methods based on sensor equipment cost too much. This paper aims to introduce computer vision and deep learning technologies to propose the YOLOv5-FastPose (YFP) model to realize the pose estimation of construction machines by improving the AlphaPose human pose model.

Design/methodology/approach

This model introduced the object detection module YOLOv5m to improve the recognition accuracy for detecting construction machines. Meanwhile, to better capture the pose characteristics, the FastPose network optimized feature extraction was introduced into the Single-Machine Pose Estimation Module (SMPE) of AlphaPose. This study used Alberta Construction Image Dataset (ACID) and Construction Equipment Poses Dataset (CEPD) to establish the dataset of object detection and pose estimation of construction machines through data augmentation technology and Labelme image annotation software for training and testing the YFP model.

Findings

The experimental results show that the improved model YFP achieves an average normalization error (NE) of 12.94 × 10–3, an average Percentage of Correct Keypoints (PCK) of 98.48% and an average Area Under the PCK Curve (AUC) of 37.50 × 10–3. Compared with existing methods, this model has higher accuracy in the pose estimation of the construction machine.

Originality/value

This study extends and optimizes the human pose estimation model AlphaPose to make it suitable for construction machines, improving the performance of pose estimation for construction machines.
Academic libraries and research data management: a case study of Dataverse global adoption
Authors: Chen Hsin-liang , Chiu Tzu-Heng , Cline Ellen
Published: October 2022

Purpose

The purpose of this study is to examine the development of Dataverse, a global research data management consortium. The authors examine specifically the institutional characteristics, the utilization of the associated data sets and the relevant research data management services at its participating university libraries. This evidence-based approach is essential for understanding the current state of research data management practices in the global context.

Design/methodology/approach

The data was collected from 67 participants’ data portals between December 1, 2020, and January 31, 2021.

Findings

Over 80% of its current participants joined the group in the past five years, 2016–2020. Thirty-three Dataverse portals have had less than 10,000 total downloads since their inception. Twenty-nine participating universities are included in three major global university ranking systems, and 18 of those university libraries offer research data services.

Originality/value

This project is an explorative study on Dataverse, an international research data management consortium. The findings contribute to the understanding of the current development of the Dataverse project as well as the practices at the participating institutions. Moreover, they offer insights to other global higher education institutions and research organizations regarding research data management. While this study is practical, its findings and observations could be of use to future researchers interested in developing a framework for data work in academic libraries.
Labour standards in the Ghanaian construction sector: an investigation of the governance landscape
Authors: Masino Serena , von Jacobi Nadia Laura , Akuffobea-Essilfie Mavis
Published: October 2022

Purpose

This paper aims to investigate the governance of labour standards in the less-studied yet rapidly globalising Ghanaian construction sector. While incorporation into international production networks generates several opportunities for workers, the drivers of adverse incorporation originate at multiple levels of analysis. The study offers an investigation into such drivers and their interconnections.

Design/methodology/approach

The authors utilise a multi-scalar framework and mixed methods of analysis. Both the qualitative and multi-level quantitative analyses rely on a primary dataset collected among 30 firms and 304 respondents, through semi-structured interviews.

Findings

A composite yet unbalanced labour standards governance configuration emerges, where the absence of social governance combined with a weak role of the State leaves labour standards subject to the variegated landscape of firms' embeddedness in the sector.

Originality/value

The construction industry is acquiring ever-increasing relevance in the economic trajectory of Ghana as well as that of several other African economies, not least for its large employment generation potential. Research on the governance of labour standards in the sector is, however, largely missing. The authors argue that labour incorporation dynamics represent a complex under-investigated regulatory challenge as well as a policy-making priority. The analysis is one of the first to offer a reconstruction of the governance landscape determining the challenges workers face in the Ghanaian construction sector, from both a qualitative and quantitative perspective.
Driving sustainability in supply chain management for a more inclusive and responsible future
Authors: El-Garaihy Wael Hassan , Farag Tamer , Al Shehri Khalid , Centobelli Piera , Cerchione Roberto
Published: October 2022

Purpose

Nowadays, a prominent research area is the development of competitive advantages in companies, due to their environmental commitment and orientation. Based on resource-based view (RBV) and institutional theory (InT), this paper aims to investigate the influence of internal and external orientation on businesses' sustainable performance while considering the effect of sustainable supply chain management (SSCM) practices.

Design/methodology/approach

Data from 351 manufacturing companies in the Kingdom of Saudi Arabia have been collected and analysed through structural equation modelling (SEM) using the partial least squares (PLS) method.

Findings

The results indicated that both internal and external environmental orientation have important effects on SSCM practices, which in turn have a considerable beneficial effect on environmental, social and economic performance.

Originality/value

Although SSCM is constantly gaining ground in the literature, most SSCM research and models examine its effects, antecedents or motivation, mainly adopting a qualitative approach. Research on the topic adopting a large-scale empirical approach is still limited. In this context, this study contributes to the SSCM management literature by exploring the role of environmental orientation in facilitating the adoption of SSCM practices and improving companies' performance.
The effects of job demands of enterprise social media on employees' outcomes: a curvilinear mediated model
Authors: Liu Shiqi , Shen Tao , Wu Yuliang , Chen Yang , Li Yifan , Tang Yumeng , Lu Lu
Published: October 2022

Purpose

Extant research has paid considerable attention to the effects of enterprise social media (ESM) on employees' work attitudes and outcomes, yet the authors know little about the influence of job demands arising from the implementation of ESM. Drawing on resource allocation theory, the purpose of this study is to unravel how ESM-related job demands influence employee outcomes.

Design/methodology/approach

This study conducts a two-wave time-lagged survey of 223 employees from 53 teams in 14 financial service firms in China to test the conceptual model.

Findings

The findings of this paper indicate that ESM-related job demands have indirect effects on employee outcomes (i.e. job satisfaction and work–family conflict), and emotional exhaustion plays an intermediary role in these relationships. Specifically, ESM-related job demands have a U-shaped effect on emotional exhaustion.

Originality/value

This study combines job demands with ESM research and clarifies the mechanism behind how ESM-related job demands at different intensity affect employee outcomes from a new perspective. Moreover, this study’s findings suggest several beneficial courses of action for managers to take advantage of ESM.
Economic effects of green bond market development in Asian economies
Authors: Phung Thanh Quang
Published: October 2022

Purpose

In the recent decades, the green projects have suffered from serious lack of investment, highlighting the major role of green financing to attract private investors to these projects. The main purpose of this paper is to explore the economic impacts of green bond (GB) market in 37 Asian economies.

Design/methodology/approach

To empirically analyze the impacts of issued GBs on different macroeconomic variables of 37 Asian countries, the co-integration and causality approaches are employed to analyze the data for the period of 2002–2018.

Findings

The primary findings indicated the presence of a unidirectional causal direction running from inflation rate, inward FDI, governance indicator, and human development index to issued GBs for the sample of Asian economies that were analyzed. Regarding Group I (higher and upper-middle income Asian countries), there are bi-directional relationships between the GB and other variables, indicating that the policies of governments in each variable influence other variables, whereas for Group II (low and lower-middle income Asian countries), there are uni-directional relationships running from HDI, governance indicator, and inflation rate to GBs, but only bi-directional causal relationships.

Practical implications

In Asian economies with a lower per capita income, implementing policies to enhance the efficiency of issued GBs so that they have a positive impact on economic activities and human development may be an appropriate strategy with major policy implications. In this way, financial system improvement, financing rural electrification and the transition to electric vehicles through GBs are recommended, while for the case of high- and upper-middle-income economies in Asia, simplifying capital flows from abroad to the GB market can be considered a practical policy.

Originality/value

This study contributes to current green finance research by studying the effects of several variables on the GB market for the instance of Asian countries with low and lower-middle incomes, as well as high-upper middle incomes.
Risky combination: the role of managerial perceptions of social media use and entrepreneurial orientation on SME innovation
Authors: Brooks Stoney , Sahaym Arvin , Datta Avimanyu , Srivastava Smita
Published: October 2022

Purpose

This study examines the conditions when “managerial perception of the contribution of social media” (SMC) enhances and inhibits entrepreneurially oriented small and medium-size enterprises' (SMEs') ability for new product introductions (NPI) to the market. We also propose that while firm proactiveness enhances the rate of NPI, managers' risk-taking attitude hurts the process even when managerial perceptions of social media use are high.

Design/methodology/approach

This study uses the survey data collected from 322 SMEs in the US to examine the theoretical model. By adopting the partial least square (PLS-SEM) technique, the direct and moderating effects among the SMC, proactive behavior and risk-taking attitude on NPI are explored under dynamic and stable market conditions.

Findings

Empirical findings show that although SMC has a significant positive influence on the rate of NPI in case of SMEs', if the managers are risk-takers themselves, then social media use can distract them, make them overly adventurous trying to introduce too many products and hurt SMEs' innovation efforts with less NPI. We show that SMEs' entrepreneurial orientation (EO) has a differential impact on SMC-NPI relationship, especially in dynamic market conditions.

Practical implications

The findings provide practical evidence that SMEs get benefitted when their managers perceive that the contributions from social media are positive for their firm. Contrary to the prior understanding of high risk and high return, managers' risk-taking attitude hurts SMEs innovation efforts. SMEs being resource-constrained, it is practically vital for them to be taking less risk while developing new products.

Originality/value

This research synthesizes the insights of the new and emerging “Strategy-as-practice view” and “Behavioral theory of the firm” to empirically examine how managerial perceptions on social media use shape firms' key strategic activity, NPI. This research also highlights the dark side of firm characteristics, such as managerial risk-taking attitude for SMEs.
Police officers’ support for corruption: examining the impact of police culture
Authors: Amagnya Moses Agaawena
Published: October 2022

Purpose

This study examines the relationship between police culture and support for corruption among Ghanaian police officers.

Design/methodology/approach

The study draws on data from a survey of 616 police officers across three regions in Ghana. The research questions and hypotheses are addressed through a hierarchical regression analysis.

Findings

The results show that perception of corruption prevalence, lack of deterrence (i.e. perceived oversight measures) and the Upper East Region significantly predicted officers’ support for corruption. Particularly, lack of deterrence was a consistent predictor of support for corruption across different models compared to corruption prevalence. Contrary to previous studies, code of silence was found not to predict officers’ support for corruption.

Originality/value

This paper contributes to the police culture and corruption debate an African perspective, where little research has explored the relationship between police culture and corruption. The code of silence not predicting support for corruption contradicts previous studies and contributes to the debate, literature and theory development.